Diseases of the Liver and Biliary System - part 8 ppt

Abscess may follow therapeutic hepatic arterialcatheterization to treat colonic cancer metastases [15].Increase in liver abscesses may also be related to the trans-numbers of severely im

Pyogenic liver abscess

Over the past 30 years there has been a marked change in

the aetiology of pyogenic liver abscess (fig 29.1) [7]

Abscesses secondary to biliary disease, particularly

malignant, have continued to increase The

immuno-suppressive states have increased the number due to

opportunistic infections

Earlier diagnosis has followed increased use of

scan-ning and cholangiographic techniques

Aetiology

Underlying biliary disease is the most frequent cause.

Septic cholangitis can complicate any form of biliary

obstruction, especially if partial More cases are related

to surgical or invasive non-surgical treatment of

hepato-biliary disease, despite the use of prophylactic

anti-biotics Biliary stenting for malignant biliary and

pancreatic disease is a particular association Abscess

may follow sclerosing cholangitis and congenital biliary

anomalies, especially Caroli’s disease

Portal pyaemia may follow pelvic or gastrointestinal

infection resulting in portal pylephlebitis or septic

emboli It can follow appendicitis, empyema of the

gallbladder, diverticulitis, regional enteritis [14],

Yersinia ileitis [9], perforated gastric or colonic ulcers,

leaking anastomoses, pancreatitis [1] or infected haemorrhoids

Neonatal umbilical sepsis may spread to the portalvein with subsequent liver abscesses

Injury to the hepatic arterial system may lead to liver

abscesses This can follow cholecystectomy In liver plant patients, abscess may be diagnosed 2 weeks post-operatively associated with technical complications,particularly hepatic arterial thrombosis Abscesses mayfollow local treatment of liver tumours by trans-hepaticchemo-embolization or percutaneous tumour injections[5] Abscess may follow therapeutic hepatic arterialcatheterization to treat colonic cancer metastases [15].Increase in liver abscesses may also be related to the

trans-numbers of severely immunosuppressed patients These

include those post-transplant, with HIV infection orwith leukaemia receiving chemotherapy [3]

Traumatic causes include penetrating wounds or blunt

trauma from automobile accidents

A solitary liver abscess may follow direct spread from

an adjacent septic focus such as a perinephric abscess.Diabetics may develop a liver abscess with gas-forming

organisms (Klebsiella) [16].

495

Chapter 29 The Liver in Infections

1952–72 1973–93

Trauma Hepatic

artery

Benign Benign Malignant Malignant

*

*

Fig 29.1 Aetiology of pyogenic hepatic

abscesses from 1952 to 1993 (from [7]).

About one half of abscesses are cryptogenic This is

especially so in the elderly

Infecting agents

The commonest are Gram-negative Escherichia coli,

Strep-tococcus faecalis, Klebsiella and Proteus vulgaris Recurrent

pyogenic cholangitis may be due to Salmonella typhi.

Streptococcus milleri, which is neither a true anaerobe

nor a micro-anaerobe is a very common cause [13]

Anaerobes are particularly important Infections are

liable to be mixed and often antibiotic resistant

Super-infection is common

Liver abscesses associated with biliary stents are often

due to resistant Klebsiella, enterobacter and Pseudomonas,

Candida may be found in the bile Fungal infections may

be associated with underlying malignancy

Staphylo-cocci, usually resistant, are found especially in those

who have received chemotherapy Klebsiella pneumoniae,

Pseudomonas and Clostridium welchii may also be found.

Rare causes include Yersinia enterocolitica [9] and

septi-caemic melioidosis The abscess may be sterile, but this is

usually due to lack of adequate, particularly anaerobic,

culture techniques or to previous antibiotics

Pathology

The enlarged liver may contain multiple yellow

abscesses, 1 cm in diameter or a single abscess encased in

fibrous tissue and usually found in the right lobe With

pylephlebitis, the portal vein and its branches contain

pus and blood clots There may be peri-hepatitis or

adhe-sion formation A chronic liver abscess may persist for

as long as 2 years before death or diagnosis In

biliary-associated cases, multiple foci correspond to the bile

duct system

Small pyaemic abscesses may be found in lung,kidney, brain or spleen Direct extension may lead tosub-phrenic or pleuro-pulmonary suppuration Exten-sion to the peritoneum or rupture of a sinus pointingunder the skin are rare A small amount of ascites may bepresent

Histologically, areas remote from the abscess showportal zone infection and surrounding disintegratinghepatocytes being infiltrated by polymorphs

The onset may be insidious and diagnosis delayed for

at least 1 month A single abscess is often insidious andcryptogenic especially in the elderly Multiple abscessesare more acute and the cause is more often identified.Sub-diaphragmatic irritation or pleuro-pulmonaryspread leads to right shoulder pain and to an irritablecough The liver is enlarged and tender and the pain isaccentuated by percussion over the lower ribs

Jaundice is late unless there is biliary disease It ismore common than with amoebic abscess

Recovery may be followed by portal hypertension due

to thrombosis of the portal vein

Serum alkaline phosphatase is usually raised morph leukocytosis is usual

Poly-Blood cultures may show the causative organism ororganisms [2]

Localization of the abscess

Ultrasound (US) distinguishes a solid from a fluid-filled lesion (fig 29.2) CT scanning is particularly valuable

although false negatives can be due to lesions near thedome of the liver and to micro-abscesses (figs 29.3–29.5).Multiple small abscesses aggregate, suggesting thebeginning of coalescence into single larger abscesses

(cluster sign) [8].

Endoscopic or percutaneous cholangiography may be used

to diagnose cholangitic abscesses

MRI shows a raised lesion with sharp borders,

hypo-intense on T1-weighting, and hyper-intense on a T2weighted image Appearances are not specific ordiagnostic of biliary or haematogenous origin [11]

-Aspirated material is positive in 90% [2] It should be

cultured aerobically, anaerobically and in carbon

dioxide-enriched media for Streptococcus milleri.

Treatment

Management has been revolutionized by the

wide-A

B

Fig 29.2 US of a pyogenic liver abscess shows a low-density

lesion (A) containing echogenic material which is pus and

necrotic tissue Acoustic enhancement (B) beyond the lesion is

characteristic.

spread use of imaging, especially US, allowing tion and easy aspiration for both diagnostic and thera-peutic purposes (fig 29.4) The majority of abscesses can be managed by systemic antibiotics and aspiration,which may need to be repeated [4] Intravenous anti-biotics are rarely effective alone Drainage is indicated ifsigns of sepsis persist Open surgical drainage is rarelyindicated However, solitary left-sided abscess mayrequire surgical drainage, especially in children [12].With multiple abscesses, the largest is aspirated andthe smaller lesions usually resolve with antibiotics.Occasionally, percutaneous drainage of each is necessary.

localiza-If amoebiasis is suspected, metronidazole should begiven before aspiration [6]

Biliary obstruction must be relieved, usually by ERCP,papillotomy and stone removal If necessary, a biliarystent is inserted (Chapter 32) Even with eventual cure,fever may continue for 1–2 weeks [2]

Prognosis

Needle aspiration and antibiotic therapy have loweredthe mortality [3] The prognosis is better for a unilocularabscess in the right lobe where survival is 90% Theoutcome for multiple abscesses, especially if biliary, isvery poor The prognosis is worsened by delay in diag-nosis, associated disease, particularly malignant [17],hyperbilirubinaemia, hypo-albuminaemia, pleural effu-sion and old age [10]

Fig 29.3 Thalassaemic Greek patient post-splenectomy CT

scan shows a filling defect in the right lobe of the liver with

marker over it (labelled 1).

Fig 29.4 Same patient as in fig 29.3 with directed puncture of

the abscess which resolved without surgery.

Fig 29.5 CT shows a large pyogenic

abscess with thick shaggy walls in the

inferior part of the right lobe of the liver

(arrowhead) The abscess contains gas.

1 Ammann R, Münch R, Largiadèr F et al Pancreatic and

hepatic abscesses: a late complication in 10 patients with

chronic pancreatitis Gastroenterology 1992; 103: 560.

2 Barnes PF, DeCock KM, Reynolds TN et al A comparison

of amebic and pyogenic abscesses of the liver Medicine

(Baltimore) 1987; 66: 472.

3 Branum GD, Tyson GS, Branum MA et al Hepatic abscess.

Changes in aetiology, diagnosis, and management Ann.

Surg 1990; 212: 655.

4 Ch Yu S, Hg Lo R, Kan PS et al Pyogenic liver abscess:

treatment with needle aspiration Clin Radiol 1997; 52:

912.

5 De Baere T, Roche A, Amenabar JM et al Liver abscess

formation after local treatment of liver tumours Hepatology

1996; 23: 1436.

6 Giorgio A, Tarantino L, Mariniello N et al Pyogenic

liver abscesses: 13 years of experience in percutaneous

needle aspiration with US guidance Radiology 1995; 195:

122.

7 Huang CJ, Pitt HA, Lipsett PA et al Pyogenic hepatic

abscess Changing trends over 42 years Ann Surg 1996;

223: 600.

8 Jeffrey RB Jr, Tolentino CS, Chang FC et al CT of small

pyogenic hepatic abscesses: the cluster sign Am J.

Roentgenol 1988; 151: 487.

9 Khanna R, Levendoglu H Liver abscess due to Yersinia

enterocolitica: case report and review of the literature Dig.

Dis Sci 1989; 34: 636.

10 Lee K-T, Sheen P-C, Chen J-S et al Pyogenic liver abscess:

multivariate analysis of risk factors World J Surg 1991; 15:

372.

11 Méndez RJ, Schiebler ML, Outwater EK et al Hepatic

abscesses: MR imaging findings Radiology 1994; 190: 431.

12 Moore SW, Millar AJ, Cywes S Conservative initial

treatment for liver abscesses in children Br J Surg 1994; 81:

872.

13 Moore-Gillon JC, Eykyn SJ, Phillips I Microbiology of

pyogenic liver abscess Br Med J 1981; 283: 819.

14 Vakil N, Hayne G, Sharma A et al Liver abscess in Crohn’s

disease Am J Gastroenterol 1994; 89: 1090.

15 Wong E, Khadori N, Carrasco CH et al Infectious

com-plications of hepatic artery catheterization procedures in

patients with cancer Rev Infect Dis 1991; 13: 583.

16 Yang CC, Chen CY, Lin XZ et al Pyogenic liver abscess in

Taiwan: emphasis on gas-forming liver abscess in diabetics.

Am J Gastroenterol 1993; 88: 1911.

17 Yeh TS, Jan YY, Jeng LB et al Pyogenic liver abscesses in

patients with malignant disease: a report of 52 cases treated

at a single institution Arch Surg 1998; 133: 242.

Cat scratch disease is due to Bartonella henselae It causes

hepatic nodules, biopsy of which reveals necrotizing

granulomas containing the organism [4] CT shows

focal hepatic defects and mediastinal and peri-portallymphadenopathy

Listeria monocytogenes can cause hepatic abscesses [1].

References

1 Jenkins D, Richards JE, Rees Y et al Multiple listerial liver

abscesses Gut 1987: 28: 1661.

2 Reddy KR, Farnum JB, Thomas E Acute hepatitis

asso-ciated with Campylobacter colitis J Clin Gastroenterol 1983; 5:

259.

3 Roberts-Thomas JC, Anders RF, Bhathal PS Granulomatous

hepatitis and cholangitis associated with giardiasis

Gastroen-terology 1982; 83: 480.

4 Tompkins LS Of cats, humans and Bartonella N Engl J Med.

1997; 337: 1916.

Hepatic amoebiasis

Entamoeba histolytica exists in a vegetative form and as

cysts, which survive outside the body and are highlyinfectious The cystic form passes unharmed through thestomach and small intestine and changes into the vegeta-tive, trophozoite form in the colon Here, it invades themucosa, forming typical flask-shaped ulcers Amoebaeare carried to the liver in the portal venous system Occa-sionally, they pass through the hepatic sinusoids into thesystemic circulation with the production of abscesses inlungs and brain

Amoebae multiply and block small intra-hepaticportal radicles with consequent focal infarction of livercells They contain a proteolytic enzyme which destroysthe liver parenchyma The lesions produced are single ormultiple and of variable size

The amoebic abscess is usually about the size of anorange The most frequent site is in the right lobe, oftensupero-anteriorly, just below the diaphragm The centreconsists of a large necrotic area which has liquefied intothick, reddish-brown pus This has been likened toanchovy or chocolate sauce It is produced by lysis ofliver cells Fragments of liver tissue may be recognized

in it Initially, the abscess has no well-defined wall, butmerely shreds of shaggy, necrotic liver tissue Histologi-cally, the necrotic areas consist of degenerate liver cells,leucocytes, red blood cells, connective tissue strands anddebris Amoebae may be identified in scrapings Hepato-cyte death is by apoptosis, but not proceeding throughFas or tumour necrosis factor as pathways [6]

Small lesions heal with scars, but larger abscessesshow a chronic wall of connective tissue of varying age.The lesion is focal and liver away from the abscess ormicro-abscesses is normal

Only 10% of those harbouring the parasite developinvasive amoebiasis Two species of entamoebae arefound and one is non-pathogenic The pathogenic may

be distinguished from the non-pathogenic by DNAmarkers for antigens on the surface of the amoeba [4]

Secondary bacterial infection of the abscess occurs in

about 20% The pus then becomes green or yellow and

foul smelling

Epidemiology

Colonic amoebae have a worldwide distribution, but

hepatic amoebiasis is a disease of the tropics and

sub-tropics Endemic areas are Africa, south-east Asia,

Mexico, Venezuela and Colombia

In temperate climates, symptomless carriers of toxic

strains are found but colonic ulcers are not seen It is a

frequent commensal in homosexual men [3]

In the tropics a new arrival is heavily exposed,

espe-cially when sanitation is poor Locals are less prone,

presumably because of partial immunity induced by

repeated contact

The latent period between the intestinal infection and

hepatic involvement has not been explained

Clinical features

Residence in tropical or subtropical areas is noted

Amoebic dysentery is found in only 10% and cysts in the

stool in only 15% Past history of dysentery is rare

Hepatic amoebiasis has been recorded as long as 30

years after the primary infection It is most frequent in

young males Multiple abscesses are frequent in such

areas as Mexico and Taiwan

The onset is usually sub-acute with symptoms lasting

up to 6 months Rarely it may be acute with rigors and

sweating and a duration of less than 10 days Fever is

variously intermittent, remittent or even absent unless

an abscess becomes secondarily infected; it rarely

exceeds 40°C Deep abscesses may present simply as

fever without signs referable to the liver

Jaundice is unusual and, if present, mild Bile duct

compression is rare

The patient looks ill, with a peculiar sallowness of the

skin, like faded suntan

Pain in the liver area may commence as a dull ache,

later becoming sharp and stabbing If the abscess is near

the diaphragm, there may be referred shoulder pain

accentuated by deep breathing or coughing Alcohol

makes the pain worse, as do postural changes The

patient tends to lean to the left side; this opens up the

right intercostal spaces and diminishes the tension on

the liver capsule The pain increases at night

A swelling may be visible in the epigastrium or

bulging the intercostal spaces Hepatic tenderness is

vir-tually constant It may be elicited over a palpable liver

edge or by percussion over the lower right chest wall

The spleen is not enlarged

The lungs may show consolidation of the right lower

zone, pleurisy or an effusion Pleural fluid may be blood

possible using antibody responses to recombinant E histolytica antigens [8].

Biochemical tests

In chronic cases, serum alkaline phosphatase values areusually about twice normal Increases in transaminasesare found only in those who are acutely ill or with severecomplications A rise in serum bilirubin is unusualexcept in those with superinfection or rupture into theperitoneum

Radiological features

A chest X-ray may show a high right diaphragm, ation of the costophrenic and cardiophrenic angles byadhesions, pleural effusions or right basal pneumonia(fig 29.6) A right lateral abscess may cause widening ofthe intercostal spaces The liver shadow may be enlargedwith a raised immobile right diaphragm The abscesscommonly causes a bulge in the antero-medial part ofthe right diaphragm

obliter-Fig 29.6 Amoebic abscess of liver Note the elevated right

diaphragm with overlying reaction in the lung field.

An abscess in the left lobe of the liver may show a

crescentic deformity of the lesser curve of the stomach

US is the most useful (fig 29.7) CT shows the abscess

with a somewhat irregular edge and low attenuation It

is more sensitive than US for small abscesses It may

show extra-hepatic involvement, for instance in the lung

[5]

MRI can be used for diagnosis and to follow treatment

[2] Liquefaction of the cavity may be shown as early as 4

days after starting treatment [2]

Diagnostic criteria

• History of residence in an endemic area

• An enlarged tender liver in a young male

• Response to metronidazole

• Leucocytosis without anaemia in those with a short

history, and less marked leucocytosis and anaemia with

a long history

• Suggestive postero-anterior and lateral chest X-ray

• Scanning showing a filling defect

• A positive amoebic fluorescent antibody test

Complications

Rupture into the lungs or pleura causes empyema,hepato-bronchial fistula or pulmonary abscess Thepatient coughs up pus, develops pneumonitis or lungabscess or a pleural effusion

Rupture into the pericardium is a complication ofamoebic abscess in the left lobe

Intra-peritoneal rupture results in acute peritonitis Ifthe patient survives the initial effect, long-term resultsare good Abscesses of the left lobe may perforate intothe lesser sac

Rupture into the portal vein, bile ducts or testinal tract is rare

gastroin-Secondary infection is suspected if prostration is particularly great, and fever and leucocytosis high Aspiration reveals yellowish, often fetid, pus and culturereveals the causative organism

Treatment

Metronidazole, 750 mg three times a day for 5–10 days,has a 95% success rate An intravenous preparation isavailable The time to defervescence is 3–5 days [1] Failures may be related to the persistence of intestinalamoebiasis, drug resistance or inadequate absorption.The time taken for the abscess to disappear depends

on its size and varies from 10 to 300 days [7]

Aspiration is rarely necessary even with very largeabscesses It should be done under US or CT guidance Atense abscess in the left lobe that is likely to rupture intothe peritoneum demands aspiration The mortality fromamoebic liver abscess should be zero [1]

A course of oral amoebocide should be given to coveramoebae persisting in the gut

References

1 Barnes PF, De Cock KM, Reynolds TB et al A comparison of

amebic and pyogenic abscess of the liver Medicine 1987; 66:

472.

2 Elizondo G, Weissleder R, Stark DD et al Amebic liver

abscess: diagnosis and treatment evaluation with MR

imaging Radiology 1987; 165: 795.

3 Goldmeier D, Sargeaunt PG, Price AB et al Is Entamoeba

his-tolytica in homosexual men a pathogen? Lancet 1986; i: 641.

4 Katwinkel-Wladarsch S, Lascher T, Rinder H Direct cation and differentiation of pathogenic and nonpathogenic

amplifi-Entamoeba histolytica DNA from stool specimens Am J Trop.

Med Hyg 1994; 51: 115.

Fig 29.7 Amoebic liver abscess US demonstrates an amoebic

abscess (1) in the liver (2), lying posteriorly against the

diaphragm (3) The anterior abdominal wall (4) is also shown.

1

5 Radin DR, Ralls PW, Colletti PM et al CT of amebic liver

abscess Am J Roentgenol 1988; 150: 1297.

6 Seydel KB, Stanley SL Jr Entamoeba histolytica induces host

cell death in amoebic liver abscess by a non-Fas-dependent,

nontumour necrosis factor alpha-dependent pathway of

apoptosis Infect Immun 1998; 66: 2980.

7 Simjee AE, Patel A, Gathiram V et al Serial ultrasound in

amoebic liver abscess Clin Radiol 1985; 36: 61.

8 Stanley SL Jr, Jackson TF, Foster L et al Longitudinal study of

the antibody response to recombinant Entamoeba histolytica

antigens in patients with amoebic liver abscess Am J Trop.

Med Hyg 1998; 58: 414.

Tuberculosis of the liver

Abdominal tuberculosis is suspected in immigrants

from developing countries and also increasingly in

patients with AIDS [4]

The liver may be involved as part of miliary

tuber-culosis or as local tubertuber-culosis where evidence of

extra-hepatic disease is not obvious Rarely, hepatic

tuberculosis can cause fulminant liver failure [5]

The basic lesion is the granuloma which is very

fre-quent in the liver in both pulmonary and

extra-pulmonary tuberculosis (fig 29.8) (Chapter 28) The

lesions usually heal without scarring but sometimes

with focal fibrosis and calcification

Pseudo-tumoral hepatic tuberculomas are rare [1] There

may be no evidence of extra-hepatic tuberculosis [2] The

tuberculomas may be multiple, consisting of a white,

irregular, caseous abscess surrounded by a fibrous capsule

(fig 29.9) Their naked eye distinction from Hodgkin’s

disease, secondary carcinoma or actinomycosis may be

difficult Occasionally, the necrotic area calcifies

Tuberculous cholangitis is extremely rare, resulting from

spread of caseous material from the portal tracts into the

bile ducts

Biliary stricture is a rare complication [3].

Tuberculous pylephlebitis results from rupture of

caseous material It is usually rapidly fatal althoughchronic portal hypertension can result [8]

Tuberculous glands at the hilum may lead rarely to

biliary obstruction

Clinical features

These may be few or absent The condition may present

as a pyrexia of unknown origin Jaundice may appear inoverwhelming miliary tuberculosis, particularly in theracially susceptible Rarely, multiple caseating granulo-mas lead to massive hepatosplenomegaly and death inliver failure [5]

Biochemical tests

Serum globulin is increased so that the lin ratio is reduced Alkaline phosphatase is dispropor-tionately elevated [2]

acid-A plain X-ray of the abdomen may reveal hepatic

calci-fication This may be multiple and confluent in

tubercu-Fig 29.8 Miliary tuberculosis: a caseating granuloma

contains lymphocytes, epithelial cells and numerous giant cells

(arrow) There is central caseation.

Fig 29.9 Hepato-splenic tuberculosis CT scan showing

scattered filling defects in the liver and spleen Aspirate showed acid-fast bacilli and the culture was positive.

loma, discrete and scattered and of uniform size, or large

and chalky adjoining a stricture in the common bile duct

[6]

CT may show a lobulated mass or multiple filling

defects in liver and spleen (fig 29.9)

Extra-hepatic features of tuberculosis may not be

obvious

Treatment is that for haematogenous tuberculosis.

The effect on the liver of tuberculosis elsewhere

Amyloidosis may complicate chronic tuberculosis Fatty

change is due to wasting and toxaemia Drug jaundice

may follow therapy, especially with isoniazid,

rifam-picin and pyrazinamide

Other mycobacteria

Atypical mycobacteria can produce a granulomatous

hepatitis, particularly as part of the AIDS syndrome

(see p 26) Mycobacterium scrofulaceum can cause a

granu-lomatous hepatitis, characterized by a rise in alkaline

phosphatase, tiredness and low-grade fever Liver

biopsy culture produces the organism [7]

References

1 Achem SR, Kolts BE, Grisnik J et al Pseudotumoral hepatic

tuberculosis Atypical presentation and comprehensive

review of the literature J Clin Gastroenterol 1992; 14: 72.

2 Chien R-N, Lin P-Y, Liaw Y-F Hepatic tuberculosis:

compari-son of miliary and local form Infection 1995; 23: 5.

3 Fan ST, Ng IOL, Choi TK et al Tuberculosis of the bile duct: a

rare cause of biliary stricture Am J Gastroenterol 1989; 84:

413.

4 Guth AA, Kim U The reappearance of abdominal

tuberculo-sis Surg Gynecol Obstet 1991; 172; 432.

5 Hussain W, Mutimer D, Harrison R et al Fulminant hepatic

failure caused by tuberculosis Gut 1995; 36: 792.

6 Maglinte DDT, Alvarez SZ, Ng AC et al Patterns of

calcifica-tions and cholangiographic findings in hepatobiliary

tuber-culosis Gastrointest Radiol 1988; 13: 331.

7 Patel KM Granulomatous hepatitis due to Mycobacterium

scrofulaceum: report of a case Gastroenterology 1981; 81: 156.

8 Ruttenberg D, Graham S, Burns D et al Abdominal

tubercu-losis—a cause of portal vein thrombosis and portal

hyperten-sion Dig Dis Sci 1991; 36: 112.

Hepatic actinomycosis

Hepatic involvement due to Actinomyces israeli is a

sequel to intestinal actinomycosis, especially of the

caecum and appendix It spreads by direct extension or,

more often, by the portal vein, but can be primary Large

greyish-white masses, superficially resembling

malig-nant metastases, soften and form collections of pus,

sep-arated by fibrous tissue bands, simulating a honeycomb

The liver becomes adherent to adjacent viscera and to theabdominal wall, with the formation of sinuses Theselesions contain the characteristic ‘sulphur granules’,which consist of branching filaments with eosinophilic,clubbed ends

Clinical features

The patient is toxic, febrile, sweating, wasted andanaemic There is local, sometimes irregular, enlarge-ment of the liver with tenderness of one or both lobes.The overlying skin may have the livid, dusky hue seenover a taut abscess that is about to rupture Multipleirregular sinus tracks develop Similar sinuses maydevelop from the ileo-caecal site or from the chest wall ifthere is pleuro-pulmonary extension

Diagnosis

The diagnosis is obvious at the stage of sinus tracts,because the organism can be isolated from the pus Ifactinomycosis is suspected before this stage, percuta-neous liver biopsy may reveal sulphur granules withorganisms [1]

Early presentation is as pyrexia, hepatosplenomegalyand anaemia It may be months before multipleabscesses are detected, often by US, CT [3] or MRI [4].Anaerobic blood cultures may be positive

Treatment

Intravenous penicillin is given in massive doses Because

of the thick capsule, the penicillin may reach the abscesswith difficulty Surgical resection may be necessary [2]

References

1 Bhatt BD, Zuckerman MJ, Ho H et al Multiple actinomycotic

abscesses of the liver Am J Gastroenterol 1990; 85: 309.

2 Kasano Y, Tanimura H, Yamaue H et al Hepatic sis infiltrating the diaphragm and right lung Am J Gastroen-

actinomyco-terol 1996; 91: 2418.

3 Mongiardo N, De Rienzo B, Zanchetta G et al Primary

hepatic actinomycosis J Infect 1986; 12: 65.

4 Nazarian LN, Spencer JA, Mitchell DG Multiple cotic liver abscesses: MRI appearances with aetiology sug-

actinomy-gested by abdominal radiography Case report Clin Imaging

1994; 18: 119.

Other fungal infections

These usually affect the immunocompromised, ing sufferers from AIDS, acute leukaemia [6], cancer [10]and following liver transplant

includ-The liver is involved, together with other organs, particularly kidney, spleen, heart, lungs and brain Fever

with a raised serum transaminase or alkaline

phos-phatase indicates needle liver biopsy

US shows multiple hypoechoic areas throughout the

liver and spleen, often with a target (bull’s eye)

configu-ration [8] CT shows multiple, non-enhancing,

low-attenuation lesions [6] The scanning appearances are

not diagnostic

The histological picture is usually granulomatous and

the causative organism can be identified by appropriate

stains and cultures, so allowing selection of appropriate

antifungal treatment [4, 5]

Candidiasis The liver is affected in up to three-quarters

of those with disseminated Candida albicans infection

who come to autopsy [5] Hepatic granulomas and

micro-abscesses are the commonest histological lesions

Candida can be demonstrated in the liver [2] The

treat-ment is with fluconazole

Disseminated aspergillosis may attack the

immunocom-promised patients with respiratory, renal or hepatic

failure [7]

Hepatic cryptococcosis usually affects the

immunocom-promised but sometimes it may be seen in the otherwise

normal Liver biopsy shows granulomas with yeast-like

organisms

The picture may resemble sclerosing cholangitis when

bile is positive for the fungus (Chapter 15)

Disseminated coccidioidomycosis may involve the liver

and be diagnosed by liver biopsy [3]

Torulopsis glabrata hepatic abscesses and fungaemia

have developed in a severely diabetic patient with

biliary stricture due to chronic pancreatitis [1]

Blastomyces dermatitidis can cause cholangitis in the

elderly or immunocompromised [9]

References

1 Friedman E, Blahut RJ, Bender MD Hepatic abscesses

and fungemia from Torulopsis glabrata Successful treatment

with percutaneous drainage and amphotericin B J Clin.

Gastroenterol 1987; 9: 711.

2 Gordon SC, Watts JC, Veneri RJ et al Focal hepatic

candi-diasis with perihepatic adhesions: laparoscopic and

immunohistologic diagnosis Gastroenterology 1990; 98: 214.

3 Howard PF, Smith JW Diagnosis of disseminated

coccid-ioidomycosis Arch Intern Med 1983; 143: 1335.

4 Korinek JK, Guarda LA, Bolivar R et al Trichosporon

hepati-tis Gastroenterology 1983; 85: 732.

5 Lewis JH, Patel HR, Zimmerman HJ The spectrum of

hepatic candidiasis Hepatology 1982; 2: 479.

6 Maxwell AJ, Mamtora H Fungal liver abscesses in acute

leukaemia—a report of two cases Clin Radiol 1988; 39: 197.

7 Park GR, Drummond GB, Lamb D et al Disseminated

aspergillosis occurring in patients with respiratory, renal

and hepatic failure Lancet 1982; i: 179.

8 Pastakia B, Shawker TH, Thaler M et al Hepatosplenic

candidiasis: wheels within wheels Radiology 1988; 166:

417.

9 Ryan ME, Kirchner JP, Sell T et al Cholangitis due to

Blastomyces dermatitidis Gastroenterology 1989; 96: 1346.

10 Thaler M, Pastakia FB, Shawker TH et al Hepatic

candidia-sis in cancer patients: the evolving picture of the syndrome.

Ann Intern Med 1988; 108: 88.

Syphilis of the liver

Congenital

The liver is heavily infected by any trans-placental fection It is firm, enlarged and swarming withspirochaetes Initially, there is a diffuse hepatitis, butgradually fibrous tissue is laid down between the livercells and in the portal zones, and this leads to a true peri-cellular cirrhosis

in-Since hepatic involvement is but an incident in a spread spirochaetal septicaemia, the clinical features areseldom those of the liver disease The fetus may be still-born or die soon after birth If the infant survives, othermanifestations of congenital syphilis are obvious, apartfrom the hepatosplenomegaly and mild jaundice.Syphilis nowadays rarely causes neonatal jaundice

wide-In older children who have survived without thisflorid neonatal picture, the hepatic lesion may be agumma

Diagnosis can be confirmed by blood serology which

Serology is positive Serum alkaline phosphataselevels are high The M1 cardiolipin fluorescent anti-mitochondrial antibody is positive and becomes normalwith recovery [2]

Liver biopsy shows non-specific changes with ate infiltration with polymorphs and lymphocytes, andsome hepato-cellular disarray, but cholestasis is absent

moder-or mild except in the severely cholestatic patients [2].Portal-to-central zone necrosis can be seen (fig 29.10).Spirochaetes are sometimes detected in the liver biopsy

Tertiary

Gummas may be single or multiple They are usually inthe right lobe They consist of a caseous mass with afibrous capsule Healing is followed by deep scars and

coarse lobulation (hepar lobatum).

Hepatic gummas are usually diagnosed incidentally,

by US or CT, at surgery or at autopsy US-guided biopsy

of a nodule shows aseptic necrosis, granulomas and

spirochaetes [3] Serology is positive Antibiotic

treat-ment is successful

Jaundice complicating penicillin treatment

Rarely, the patient shows an idiosyncrasy to penicillin

Jaundice, chills and fever, often with a rash (erythema of

Milan), occur about 9 days after starting therapy This is

part of the Herxheimer reaction The mechanism of the

jaundice is unclear

References

1 Case Records of the Massachusetts General Hospital Case

27, 1983 N Engl J Med 1983; 309: 35.

2 Comer GM, Mukherjee S, Sachdev RK et al

Cardiolipin-fluorescent (M1) antimitochondrial antibody and

cholesta-tic hepatitis in secondary syphilis Dig Dis Sci 1989; 34:

1298.

3 Maincent G, Labadie H, Fabre M et al Tertiary hepatic

syphilis A treatable cause of multinodular liver Dig Dis Sci.

1997; 42: 447.

4 Schlossberg D Syphilitic hepatitis: a case report and review

of the literature Am J Gastroenterol 1987; 82: 552.

Leptospirosis

Pathogenic Leptospira related to human disease can be

classified by DNA typing into at least 200 serovarieties

belonging to 23 subtypes [9] The disease due to tospira icterohaemorrhagiae was described by Weil in 1886

Lep-[8] It is a severe infection spread by the urine of infectedrats The whole group of leptospiral infections should bedesignated leptospirosis

Weil’s disease

Mode of infection

Living Leptospira are continually excreted in the urine of

infected rats and survive for months in pools, canals,flood water or damp soil The patient is infected by cont-aminated water or by direct occupational contact withinfected rats Those affected include agricultural andsewer workers and fish cutters Deteriorating cities inEurope and Asia, where rat populations are expanding,provide a source of infection [6]

Pathology

Histopathological changes are slight in relation to themarked functional impairment of kidneys and liver Thedamage is at a subcellular level An endotoxin-like sub-stance in the wall of spirochaetes has been suggested.Plasma tumour necrosis factor-a (TNF-a) levels havebeen related to the severity of organ involvement [5]

Liver [2] necrosis is minimal and focal Zone 3 necrosis

is absent Active hepato-cellular regeneration, shown bymitoses and nuclear polyploidy, is out of proportion tocell damage Swollen Kupffer cells contain leptospiraldebris Leukocyte infiltration and bile thrombi areprominent in the deeply jaundiced Cirrhosis is not asequel

Fig 29.10 Liver in secondary syphilis Mononuclear cell

infiltration can be seen in portal zones and in the sinusoids

(H & E, ¥ 160.)

Kidney shows tubular necrosis Skeletal muscle shows

punctate haemorrhages and focal necrosis

Heart may show haemorrhages in all layers.

Haemorrhages into tissues, especially skin and lungs, is

due to papillary injury and thrombocytopenia

Jaundice is related to hepatocyte dysfunction

magni-fied by renal failure impairing urinary bilirubin

excre-tion Tissue haemorrhages and haemolysis increase the

bilirubin load on the liver Hypotension with diminished

hepatic blood flow contributes

Kidney failure is related to impaired renal perfusion.

Clinical features (fig 29.11)

The clinical picture is not pathognomonic and the

disease is heavily underdiagnosed It is more often

anicteric than icteric The disease is most prevalent in

late summer and autumn The incubation period is 6–15

days The course may be divided into three stages: the

first or septicaemic phase lasts for about 7 days, the

second or toxic stage for a similar period, and the third or

convalescent period begins in the third week

The first or septicaemic stage is marked by the presence

of the spirochaete in the circulating blood

The onset is abrupt, with prostration, high fever and

even rigors The temperature rises rapidly to 39.5–40.5°Cand falls by lysis within 3–10 days

Abdominal pain, nausea and vomiting may simulate

an acute abdominal emergency, and severe muscularpains, especially in the back or calves, are common.Central nervous system involvement is shown bysevere headache, mental confusion and sometimesmeningism The cerebrospinal fluid confirms themeningeal infection If jaundice is present, there is xanthochromia

The eyes show a characteristic suffusion

In those with a severe attack, bleeding may occur fromnose, gut or lung, with skin petechiae or ecchymoses.Pneumonitis with cough, sore throat and rhonchioccurs in 40% of sufferers

Jaundice appears between the fourth and seventh day

in 80% of patients It is a grave sign, for the disease isnever fatal in the absence of icterus The liver is enlarged,but not the spleen

The urine shows albumin and bile pigment The stoolsare well coloured

There is a leucocytosis of 10 000–30 000/mm3with arelative increase in polymorphs Thrombocytopeniamay be profound

The second or immune stage in the second week is

char-Blood organisms + + + + + + ± 0

Stage Septicaemia Day

September John Jones (farmer) age 28

Headache Chills Muscle cramps Photophobia Pink eye

Jaundice Haemorrhages Nephritis Meningitis

Relapse Muscular pains

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Localization Convalescence

101 102 103 104

Fig 29.11 The clinical course of a

patient with Weil’s disease.

acterized by a normal temperature but without clinical

improvement This is the stage of deepening jaundice,

with increasing renal and myocardial failure

Albumin-uria persists, there is a rising blood urea, and oligAlbumin-uria

may proceed to anuria Death may be due to renal

failure A markedly elevated creatinine phosphokinase

level reflects myositis

Severe prostration is accompanied by a low blood

pressure and a dilated heart There may be transient

cardiac dysrhythmias and electrocardiograms may

show a prolonged P–R or Q–T interval, with T-wave

changes Death may be due to circulatory failure

During this stage, the Leptospira can be found in the

urine, and rising antibody titres demonstrated in the

serum

The third or convalescent stage starts at the beginning of

the third week Clinical improvement is shown by a

brightening of the mental state, fading of the jaundice, a

rise in blood pressure and an increased urinary volume,

with a drop in the blood urea concentration

Albumin-uria is slow to disappear

Temperature may rise during the third week (fig

29.11), associated with muscle pains Such relapses occur

in 20% of cases

There is great variation in the clinical course ranging

from a mild illness, clinically indistinguishable from

influenza, to a prostrating, fatal disease with anuria

Diagnosis

Before the appearance of antibodies, PCR demonstration

of Leptospira is the best method of diagnosis [3].

Rising titres of antibodies are sought by Dot-ELISA [4]

or immunofluoroscence [1] The microscopic

agglutina-tion test is too complex for routine use

Leptospira may be cultured from blood during the first

10 days Urine cultures are positive during the second

week and persist for several months

Liver function tests are non-contributory

Differential diagnosis

In the early stages, Weil’s disease is confused with

septi-caemic bacterial infections or typhus fever When

jaun-dice is evident acute viral hepatitis must be excluded

(table 29.1) Important distinguishing points are the

sudden-onset increased polymorph count and

albumin-uria of Weil’s disease

Spirochaetal jaundice would be diagnosed more often

if blood samples for antibodies were taken from patients

with obscure icterus and fever

Prognosis

Mortality is about 5% This depends on the depth of

jaundice, renal and myocardial involvement, and theextent of haemorrhages Death is usually due to renalfailure The mortality is negligible in non-icteric patients,and is lower in those under 30 years old Since manymild infections are probably unrecognized, the overallmortality may be considerably less

Although transient relapses in the third and fourthweeks are common, final recovery is complete

Prevention

Protective clothing should be provided for workers inindustries with a high incidence of Weil’s disease, andadequate measures taken to control rodents Bathing instagnant water should be avoided

Treatment

Early, mild leptospirosis is treated by doxycycline (100 mg by mouth) twice daily for 1 week More seri-ously ill patients, particularly with vomiting, are given intravenous penicillin G 6 million units/day for 1week [7]

Prognosis is improving with earlier diagnosis, tion to fluid and electrolyte balance, renal dialysis,antibiotics and circulatory support

atten-Other types of leptospirosis

In general these infections are less severe than those due

to L icterohaemorrhagiae L canicola infection, for instance,

is characterized by headache, meningitis and val infection Albuminuria is only found in 40%, andjaundice in only 18% of patients The frequent presenta-tion is that of ‘benign aseptic meningitis’ The diseaseaffects young adults who have usually been in close

conjuncti-Table 29.1 The differential diagnosis of Weil’s disease from

viral hepatitis during the first week of illness

Weil’s disease Viral hepatitis

Headache Constant Occasional Muscle pains Severe Mild Conjunctival injection Present Absent

Disorientation Common Rare Haemorrhagic diathesis Common Rare Nausea and vomiting Present Present Abdominal discomfort Common Common

Albuminuria Present Absent Leucocyte count Polymorph Leucopenia with

leucocytosis lymphocytosis

contact with an infected dog Fatalities in man are

virtu-ally unknown

Diagnosis is confirmed in a similar way to Weil’s

disease A convenient method is rising antibody titres

The spinal fluid shows a lymphocytic picture in most

cases

References

1 Appassakij H, Silpapojakul K, Wansit R et al Evaluation of

the immunofluorescent antibody test for the diagnosis of

human leptospirosis Am J Trop Med Hyg 1995; 52; 340.

2 Arean VM The pathologic anatomy and pathogenesis of

fatal human leptospirosis (Weil’s disease) Am J Pathol 1962;

40: 393.

3 Brown PD, Gravekamp C, Carrington DG et al Evaluation of

the polymerase chain reaction for early diagnosis of

lep-tospirosis J Med Microbiol 1995; 43: 110.

4 Ribeiro MA, Souza CC, Almeida SH et al Dot-ELISA for

human leptospirosis employing immunodominant antigen.

J Trop Med Hyg 1995; 98: 452.

5 Tajiki H, Salomao R Association of plasma levels of tumour

necrosis factor alpha—with severity of disease and mortality

among patients with leptospirosis Clin Infect Dis 1996; 23:

1177.

6 Vinetz JM, Glass GE, Flexner CE et al Sporadic urban

lep-tospirosis Ann Intern Med 1996; 125: 794.

7 Watt G, Padre LP, Tuazon ML et al Placebo-controlled trial of

intravenous penicillin for severe and late leptospirosis.

Lancet 1988; i: 433.

8 Weil A Über eine eigenthumliche mit Milztumour, Icterus

and Nephritis einhergehene, acute Infektionskrankheit.

Dtsch Arch Klin Med 1886; 39: 209.

9 Zuerner RL, Alt D, Bolin CA IS1533-based PCR assay for

identification of Leptospira interrogans sensu lato serovars J.

Clin Microbiol 1995; 33: 3284.

Relapsing fever

This arthropod-borne infection is caused by spirochaetes

of the species Borrelia recurrentis It is encountered

throughout the world except in New Zealand, Australia

and some parts of the west Pacific

The Borrelia multiply in the liver, invading liver cells

and causing focal necrosis Just before the crisis the

Borre-lia roll up and are ingested by reticulo-endotheBorre-lial cells.

This effect is related to immunologically competent

lym-phocytes Surviving Borrelia remain in the liver, spleen,

brain and bone marrow until the next relapse [2]

Clinical features [1]

The incubation period is 3–15 days The onset is acute

with chills, a continuous high temperature, headache,

muscle pains and profound prostration The patient is

flushed, sometimes with injected conjunctivae, and

epi-staxes In severe attacks, tender hepatosplenomegaly

and jaundice develop The jaundice is similar to that of

Weil’s disease Sometimes a rash develops on the trunk.There may be bronchitis

These symptoms continue for 4–9 days and then thetemperature falls, often with collapse of the patient Thisperipheral collapse may be fatal, but more usually thesymptoms and signs then rapidly abate, the patientremains afebrile for about 1 week, when there is arelapse There may be a second or even a third milderrelapse before the disease ends

Diagnosis

Spirochaetes can rarely be found in thick blood films.Agglutination and complement fixation tests are avail-able [2] Organisms may be identified by lymph nodeaspiration, or from the insect bite site

Treatment

Tetracyclines and streptomycin are more effective thanpenicillin Mortality is 5%

References

1 Bryceson ADM, Parry EHO, Perine PL et al Louse-born

relapsing fever: a clinical and laboratory study of 62 cases in

Ethiopia and a reconsideration of the literature Q J Med.

1970; 39: 129.

2 Felsenfeld O, Wolf RH Immunoglobulins and antibodies in

Borrelia turicetae infections Acta Trop 1969; 26: 156.

References

1 Goellner MH, Agger WA, Burgess JH et al Hepatitis due to

recurrent Lyme disease Ann Intern Med 1988; 108: 707.

2 Horowitz HW, Dworkin B, Forseter G et al Liver function in

early Lyme disease Hepatology 1996; 23: 1412.

Q fever

This rickettsial disease has predominantly pulmonarymanifestations Occasionally hepatitis may be promi-nent and clinical features may mimic anicteric viralhepatitis [2, 3]

The liver shows a granulomatous hepatitis Portalareas contain abundant lymphocytes and the limitingplate is destroyed Kupffer cells are hypertrophied The

granulomas have a characteristic ring of fibrinoid

necro-sis surrounded by lymphocytes and histiocytes In the

centre of the granuloma is a clear space giving a

‘dough-nut’ appearance (fig 29.12) The diagnosis is made by

showing a rising titre of complement-fixing antibodies to

Coxiella burnetii 2–3 weeks after the infection.

Rocky mountain spotted fever

Jaundice and rises in serum enzymes sometimes occur

Liver histology shows portal zone inflammation with

large mononuclear cells Hepato-cellular necrosis is

inconspicuous but erythrophagocytosis is marked

Rick-ettsiae may be demonstrated in the portal zones by

immunofluorescence microscopy [1]

References

1 Adams JS, Walker DH The liver in rocky mountain spotted

fever Am J Clin Pathol 1981; 75: 156.

2 Dupont HL, Hornick RB, Levin HS et al Q fever hepatitis.

Ann Intern Med 1971; 74: 198.

3 Tissot-Dupont H, Raoult D, Brouquil P et al Epidemiologic

features and clinical presentation of acute Q fever in

hospital-ized patients: 323 French cases Am J Med 1992; 93: 427.

Schistosomiasis (bilharziasis)

Hepatic schistosomiasis is usually a complication of the

intestinal disease, since emboli of Schistosoma ova reach

the liver from the intestines via the mesenteric veins

S mansoni and S japonicum affect the liver S

haemato-bium can sometimes involve the liver.

Schistosomiasis affects more than 200 million people

in 74 countries S japonicum is prevalent in Japan, China,

Indonesia and the Philippines S mansoni is found in

Africa, the Middle East, the Caribbean and Brazil [4]

Pathogenesis

Eggs, excreted in the faeces, hatch out in water to releasefree-swimming embryos which enter appropriate snailsand develop into fork-tailed cercariae These re-enterhuman skin in contact with infected water They burrowdown to the capillary bed, whence there is widespreadhaematogenous dissemination Those reaching themesenteric capillaries enter the intra-hepatic portalsystem, where they grow rapidly

The extent and severity of chronic liver disease lates with the intensity and duration of egg productionand hence with the number of eggs excreted Adult maleand female worms can exist for about 5 years producing300–3000 eggs daily in portal venules If liver disease

corre-is advanced, faecal egg counts may fall because of senescence of adult worms or previous therapy

S japonicum is more pathogenic than S mansoni and

produces hepatosplenic schistosomiasis more often andfaster

In the liver, the ova penetrate and obstruct the portalbranches and are deposited either in the large radicles,producing the coarser type of bilharzial hepatic fibrosis,

or in the small portal tracts, producing the fine diffuseform

The granulomatous reaction to the Schistosoma ovum

is of delayed hypersensitivity type, related to antigenreleased by the egg TH0- and TH2-type helper lympho-cytes play an important role in granuloma formation[10]

Portal fibrosis is related to the adult worm load Theclassic, clay-pipestem cirrhosis is due to fibrotic bandsoriginating from the granulomas

Early on, cytokines, formed from granulomas aroundova, may play a central role in fibrogenesis [7] Fibrosismay be slowly reversible with treatment

Wide, irregular, thin-walled arteriolar spaces arefound in 85% of cases in the thickened portal tracts.These angiomatoids are useful in distinguishing the bil-harzial liver from other forms of hepatic fibrosis Rem-nants of ova are also diagnostic There is little or no bileduct proliferation Nodular regeneration and distur-bance of the hepatic architecture is not sufficient tojustify the term ‘cirrhosis’

In areas where schistosomiasis, hepatitis virus B and Ccoexist, a mixed picture of schistosomal fibrosis with cir-rhosis may be seen

Splenic enlargement is mainly due to portal venoushypertension and reticulo-endothelial hyperplasia Veryfew ova are found in the spleen Portal-systemic collat-eral channels are numerous

There are associated bilharzial lesions in the intestines

Fig 29.12 Liver biopsy in Q fever showing a granuloma with

fibrin rings having a clear centre (Martius scarlet blue, ¥ 350.)

and elsewhere Fifty per cent of patients with rectal

schistosomiasis have granulomas in the liver

Clinical features

Schistosomiasis shows three stages Itching follows the

entry of the cercariae through the skin This is followed

by a stage of fever, urticaria and eosinophilia Finally, the

third stage of deposition of ova results in intestinal,

urinary and hepatic involvement

Initially, the liver and spleen are firm, smooth and

easily palpable This is followed by hepatic fibrosis and

eventually portal hypertension which may appear years

after the original infection

Oesophageal varices develop Bleeding episodes are

recurrent but rarely fatal

The liver shrinks in size and the spleen becomes much

larger Dilated abdominal wall veins and a venous hum

over the liver are indications of the portal venous

obstruction Ascites and oedema may develop The

blood shows leucopenia and anaemia The faeces at this

stage contain few, if any, parasites

Patients tolerate blood loss well and hepatic

encephalopathy is unusual Hepato-cellular function

remains good although there is a large porto-systemic

collateral circulation

Aspiration liver biopsy (fig 29.13) Eggs or their

rem-nants are seen in 94% of livers from those with faecal

eggs

Remnants of ova may be seen but appearances are not

usually diagnostic and the liver biopsy mainly excludes

other types of liver disease

Diagnostic tests

Detection of ova in urine, stool or rectal mucosal biopsy

(rectal ‘snip’) is still the accepted method of diagnosingactive infection (fig 29.14) Bleeding may be a complica-tion of rectal biopsy in those with portal hypertension

Serological antibody tests indicate past exposure without

specifying the time

Detection of circulating schistosomal antigen cates active disease An ELISA for detecting circulatingsoluble egg antigens in serum correlates with eggoutput A reagent strip assay is based on glycoconjugatesfor adult schistosomes [9]

indi-CT shows dense bands following the portal vein to the

liver edge; these enhance with contrast [5]

US shows greatly thickened portal veins (fig 29.15) It

may be used to grade fibrosis [1] Liver, spleen, portal and pancreatic lymph nodes are diffuselyenlarged without evidence of portal hypertension.Colour Doppler shows an increase in blood flow

peri-Fig 29.13 Bilharzial liver An ovum of S mansoni has lodged

in a portal tract which shows a granulomatous reaction (H &

E, ¥ 64.)

Fig 29.14 Rectal (‘snip’) biopsy in schistosomiasis mansoni.

A ‘squash’ preparation in glycerol reveals the ova of S mansoni.

Fig 29.15 Schistosomiasis: US shows bright portal tracts and

a portal vein with greatly thickened walls (arrow).

velocity in the portal and superior mesenteric varices

and the development of collaterals [8]

Portal hypertension

This is pre-sinusoidal and related to the portal

granulo-mas As the portal venous blood flow falls, hepatic

arter-ial blood flow increases so that total hepatic blood flow is

not significantly reduced Retrograde flow develops in

the portal vein [2]

At the stage of haemorrhage from varices the

granulo-matous reaction may have subsided and the picture is

predominantly that of fibrosis

Biochemical changes

Serum alkaline phosphatase may be raised

Hypo-albuminaemia can be related to poor nutrition and to

the effects of repeated gastrointestinal haemorrhages

Serum transaminases are virtually normal

Disease association

The prognosis is worsened by concomitant hepatitis B or

hepatitis C infection

When associated with an immunosuppressed state,

granuloma formation is reduced and egg output

decreases sharply

Treatment

Chemotherapy aims to relieve symptoms and prevent

further deposition of the eggs which will produce

further fibrosis If egg excretion is stopped, the life cycle

of the parasite is blocked Chemotherapy reduces

community transmission of disease

Metriphonate is an organophosphate compound,

effec-tive only in S haematobium infection It is given orally

and has negligible toxicity It is cheap and useful

Oxamniquine 20 mg/kg/day for 3 days is effective only

against S mansoni South American strains are less

sensi-tive than North or South African and larger doses may be

required It is expensive and well tolerated Side-effects

include dizziness, drowsiness and headache

Praziquantel has high therapeutic activity against all

species of Schistosoma It is safe and non-toxic in a single

dose of 40–75 mg orally The drug paralyses the worm

which migrates in the blood stream to the liver where it

is attacked by phagocytes, granulocytes and

cell-medi-ated immune cells It decreases messenger RNA levels of

the major proteins associated with fibrosis [6]

Disease control

This is by health education and reducing contamination

of water Attacks on the snails are limited by cost, theneed to repeat over long periods and the effects on fish.Mass treatment by drugs such as metrifonate islimited by cost and poor compliance Praziquantelwould be the ideal drug but the cost is too high

Vaccines

Schistosomal antigens have been identified and used asthe basis of vaccines, but so far none has proved effective

in man [3]

Bleeding oesophageal varices

This is rarely fatal and is usually controlled by rotherapy or variceal banding (Chapter 10) Distalspleno-renal shunt preferred over total shunts Gastro-oesophageal devascularization with splenectomy may

scle-be the procedure of choice [6] as it has a low mortalityand encephalopathy rate TIPS may be a satisfactoryalternative, but post-shunt jaundice is enhanced

References

1 Abdel-Wahab MF, Esmat G, Farrag A et al Grading of hepatic schistosomiasis by the use of ultrasonography Am.

J Trop Med Hyg 1992; 46: 403.

2 Alves CAP, Alves AR, Abreu ION et al Hepatic artery

hypertrophy and sinusoidal hypertension in advanced

schistosomiasis Gastroenterology 1977; 72: 126.

3 Bergquist NR Controlling schistosomiasis by vaccination: a

realistic option Parasitol Today 1995; 11: 191.

4 El-Garem AA Schistosomiasis Digestion 1998; 59: 589.

5 Fataar S, Bassiony H, Satyanath S CT of hepatic

schistoso-miasis mansoni Am J Roentgenol 1985; 145: 63.

6 Kresina TF, Qing HE, Esposti SD et al Gene expression of

transferring growth factor b1 and extra-cellular matrix

pro-teins in murine Schistosoma mansoni infection

8 Salama ZA, El Dorry AK, Soliman MT et al Doppler

sonog-raphy of the portal circulation in cases with portal

hyperten-sion Med J Cairo Univ 1997; 65: 347.

9 Van Etten L, Folman CC, Eggeltte TA et al Rapid diagnosis

of schistosomiasis by antigen detection in urine with a

reagent strip J Clin Microbiol 1994; 32: 2404.

10 Zhu Y, Lukacs NW, Botos DL Cloning of TH0- and

TH2-type helper lymphocytes from liver granulomas of

Schisto-soma mansoni-infected mice Infect Immun 1994; 62: 994.

Malaria[1]

In the erythrocytic stage, the parasite is engulfed by

reti-culo-endothelial cells The liver suffers from the generaleffects of the toxaemia and pyrexia [2]

In the pre-erythrocytic (exo-erythrocytic) stage,

schizo-gony takes place in the liver without obvious effect on its

function The hepatocyte is invaded by the sporozoite

The nucleus divides many times and, at last (in about

6–12 days), a spherical or irregular body containing

thousands of ripe merozoites is formed This schizont

bursts and the merozoites are discharged into the

sinu-soids and invade erythrocytes In quartan or benign

tertian malaria, a few merozoites return to the liver cells

to initiate the exo-erythrocytic or relapse cycle In

malig-nant tertian this does not happen and there are no true

relapses So far only Plasmodium falciparum and P vivax

have been found in the liver of man The tissue stage of

human malaria is confined to the liver cells

Pathology

The liver shows reticulo-endothelial proliferation, both

of Kupffer cells and in zone 1 Focal, non-specific

granu-lomas may be seen in the sinusoids Brown ‘malarial’

pigment (iron and haemofuscin) is seen in Kupffer cells

Malarial parasites are not shown Hepatocyte damage is

slight with nuclei of variable size and shape and

increased mitoses

In P falciparum malaria sinusoids may contain

para-sitized, clumped erythrocytes

Reaction to the malarial parasite is

reticulo-endothe-lial, with minor effects on the liver cells and no fibrosis

The high incidence of cirrhosis in malarial areas is due to

other factors

Clinical features

There are usually no specific hepatic features

Occasion-ally, in acute malignant malaria, there may be mild

jaundice, hepatomegaly and tenderness over the liver

Hepatic function

Increases in serum bilirubin are rarely above 3 mg/dl

(50 mmol/l) Serum transaminases increase slightly and

serum globulin concentrations rise

References

1 Cook GC Malaria in the liver Postgrad Med J 1994; 70: 780.

2 Hollingdale MR Malaria and the liver Hepatology 1985; 5:

327.

Kala-azar (leishmaniasis)

Leishmaniasis is a reticulo-endothelial disease

Peri-portal cellular infiltrations and macrophage

accumula-tions are scattered throughout the liver and within them

the Leishman–Donovan bodies may be identified (fig

29.16) There is some portal zone fibrosis [1] The picture

is similar in the American, Mediterranean and Orientaltypes [1]

Kala-azar presents with fever, splenomegaly, a firm,tender liver, pancytopenia, anaemia and very highserum globulins Aspiration of the bone marrow isusually positive Treatment is with paromomycin [2]

References

1 Da Silva JR, De Paola D Hepatic lesions in American

kala-azar: a needle-biopsy study Ann Trop Med Parasitol 1961;

55: 249.

2 Jha TK, Olliaro P, Thakur CP et al Randomized controlled

trial of aminosidine (paromomycin) v sodium conate for treating visceral leishmaniasis in North Bihar,

stiboglu-India Br Med J 1998; 316: 1200.

Hydatid disease

Hydatid disease is due to the larval or cyst stage of

infec-tion by the tapeworm, Echinococcus granulosus, which

lives in dogs Man, sheep and cattle are intermediatehosts

Biology(fig 29.17)Man is infected by the excreta of dogs, often duringchildhood The dog is infected by eating the viscera ofsheep, which contain hydatid cysts Scolices, contained

in the cysts, adhere to the small intestine of the dog andbecome adult worms which attach to the intestinal wall.Each worm sheds 500 ova into the bowel The infectedfaeces of the dog contaminate grass and farmland, andthe contained ova are ingested by sheep, pigs, camels orman The ova adhere to the coats of dogs, so man is

Fig 29.16 Kala-azar Liver biopsy shows enlarged Kupffer

cells (arrow) distending the sinusoids These contain Leishman–Donovan bodies (H & E, ¥ 100.)

infected by handling dogs, as well as by eating

contami-nated vegetables

The ova have chitinous envelopes which are

dis-solved by gastric juice The liberated ovum burrows

through the intestinal mucosa and is carried by the

portal vein to the liver, where it develops into an adult

cyst Seventy per cent of hydatid cysts form in the liver A

few ova pass through the liver and heart, and are held up

in the lungs causing pulmonary cysts A few ova reach

the general circulation causing spleen, brain and bone

cysts

Development of the hepatic cyst (fig 29.18)

The adult cyst develops slowly from the ovum and

provokes a cellular response in which three zones can be

distinguished: a peripheral zone of fibroblasts, an mediate layer of endothelial cells and an inner zone ofround cells and eosinophils The peripheral zone,

inter-derived from the host tissues, becomes the adventitia or

ectocyst, a thick layer which may calcify The

intermedi-ate and inner zones become hyalinized (the laminintermedi-ated layer) Finally, the cyst becomes lined with the germinal layer, which gives rise to pedunculated nodes of multi-

plying cells which project into the lumen of the cyst as

brood capsules Scolices develop from the brood capsules

and eventually indent it The attachment of the broodcapsules to the germinal layer becomes progressivelythinner until the capsule bursts, releasing the scolicesinto the cyst fluid These fall to the bottom and are

termed hydatid sand.

All hydatid cysts start as purely cystic type I structures[10] When they develop daughter cysts or a gelatinousmatrix, they are termed type II When formed, elementsdeprive the type II lesion of its nourishing hydatid fluid,

it dies and becomes a calcified and biologically inert type

Sheep liver containing

hydatid cyst eaten by

dog

Scolices enter small intestine

of dog

Scolices adhere to mucosa and develop into adult

Taenia echinococcus

Ova of Taenia pass

into canine faeces

Adult hydatid cyst develops in liver

Ova pass via portal system from intestine

to liver Grass ingested by sheep

HCl + pepsin dissolve chitinous envelope

DEFINITE HOST – DOG

INTERMEDIATE HOST – SHEEP AND MAN

Fig 29.17 The life cycle of the hydatid parasite.

III lesion The course is modified by rupture, infection or

anaphylaxis

Daughter and even grand-daughter cysts develop by

fragmentation of the germinal layer The majority of

cysts in adult patients are thus multilocular The cyst

fluid is a transudate of serum It contains protein and is

antigenic If released into the circulation, eosinophilia or

anaphylaxis may result

Endemic regions

The disease is common in sheep-raising countries, where

dogs have access to infected offal These include South

Australia, New Zealand, Africa, South America,

south-ern Europe, especially Cyprus, Greece and Spain, and

the Middle and Far East The disease is rare in Britain,

apart from some areas in Wales

Clinical features

These depend on the site, the stage and whether the cyst

is alive or dead The rest of the liver hypertrophies and

hepatomegaly results

The uncomplicated hydatid cyst may be silent and found

incidentally It should be suspected if a rounded smooth

swelling, continuous with the liver, is found in a patient

who is not obviously ill The only complaints may be a

dull ache in the right upper quadrant and sometimes a

feeling of abdominal distension The tension in the cyst

is high and fluctuation is never marked

Complications

Rupture Intra-peritoneal rupture is frequent and leads

to multiple cysts throughout the peritoneal cavity withintestinal obstruction and gross abdominal distension.The pressure in the cyst greatly exceeds that in bile andrupture into bile ducts is frequent This may lead to cure

or to cholestatic jaundice with recurrent cholangitis.Colonic rupture leads to elimination per rectum and tosecondary infection

The cysts may adhere to the diaphragm, rupture intothe lungs and result in expectoration of daughter cysts.Pressure on and rupture into the hepatic veins leads tothe Budd–Chiari syndrome Secondary involvement ofthe lungs may follow

Infection Secondary invasion by pyogenic organisms

follows rupture into biliary passages, giving the ture of a pyogenic abscess; the parasite dies Occasion-ally, the entire cyst content undergoes aseptic necrosisand again the parasite dies This amorphous yellowdebris must be distinguished from the pus of secondaryinfection

pic-Other organs Cysts can occur in lung, kidney, spleen,

brain or bone, but mass infestation is rare; the liver isusually the only organ involved If a hydatid cyst isfound elsewhere, there is always concomitant infestation

of the liver

Hydatid allergy Cyst fluid contains a foreign protein

which sensitizes the host This may lead to severe phylactic shock but more commonly to recurrenturticaria or ‘hives’

ana-Membranous glomerulonephritis may be related to

glomerular deposits of hydatid antigen [7]

Diagnosis

Serological tests

Hydatid fluid contains specific antigens, leakage ofwhich sensitizes the patient with the production of antibodies

ELISA gives positive results in about 85% [2]

Results may be negative for all tests if the cyst hasnever leaked, if it contains no scolices or if the parasite isdead

Eosinophilia of greater than 7% is found in about 30% of

patients

Imaging

Radiology shows a raised, poorly moving rightdiaphragm and hepatomegaly Calcium is laid down inthe ectocyst as a distinct round or oval opacity (fig 29.19)

or merely as shreds

Brood capsule Scolices

Germinal layer Laminated layer

Adventitia

or ectocyst (may be calcified)

Hydatid sand

Fig 29.18 The basic constitution of a hydatid cyst.

Floating bodies indicate the presence of free-moving

daughter cysts Infected gas-containing cysts may show

a fluid level

Hepatic cysts may displace the stomach or hepatic

flexure of the colon Characteristic radiological changes

may be seen in the lungs, spleen, kidney or bone

US or CT scanning demonstrates single or multiple

cysts which may be uni- or multiloculated, and thin or

thick walled (figs 29.20, 29.21, 29.22) US and CT are

highly sensitive for diagnosis: 97.7% for US and 100% for

CT

US changes provide the basis for classification (table

29.2) [6] WHO classification is into active, transitional

and inactive cysts Infected cysts are poorly defined

[17]

MRI may show a characteristic intense rim, daughter

cysts and detachment of the membranes [12]

Intra-hepatic and extra-Intra-hepatic rupture can be defined

ERCP may show cysts in the bile ducts (figs 29.23,

29.24)

Prognosis

The uncomplicated hepatic hydatid cyst carries a

rea-sonably good prognosis The risk of complications

is, however, always present Intra-peritoneal or

intra-pleural rupture is grave, but rupture into the biliary

tree is not so serious because spontaneous cure

may follow the biliary colic Infection is controlled by

antibiotics

Fig 29.19 X-ray of the abdomen shows a calcified hydatid

cyst in the liver.

3

2

1

Fig 29.20 US shows a hydatid cyst (1) in the right lobe of the

liver (2) Daughter cysts (3) can be seen inside the larger cyst.

Fig 29.21 CT scan shows calcified hydatid cyst (arrowed) in a

quadrate lobe of the liver (contrast-enhanced scan).

Fig 29.22 CT scan Hydatid cyst in right lobe of liver

showing patchy calcification of the wall and containing

multiple septae produced by daughter cysts

(contrast-enhanced scan).

Fig 29.23 Endoscopic cholangiography showing hydatid

cysts in the common bile duct.

Fig 29.24 Four glistening hydatid cysts (arrow) were

removed surgically from the common bile duct of the patient shown in fig 29.23.

Table 29.2 Classification of ultrasound appearances in

IV Heterogenous complex mass (dead parasite)

Calcified mass (eggshell) (dead parasite)

Treatment

Dogs are denied access to infected offal and hands are

washed after handling dogs [5] Dogs in affected areas

must be regularly de-wormed

Medical treatment

Mebendazole perfuses through the cyst membrane and

interferes with microtubular function It is poorly

absorbed

Albendazole is better absorbed and cyst levels equal

that achieved in plasma It is more satisfactory than

mebendazole

Medical therapy cannot be regarded as definitive

Albendazole can be given in a 6 to 24-month course for

those unsuitable for surgery, with disseminated disease

or with rupture About 30% of cysts disappear, 30–50%

degenerate or become smaller and 20–40% of cysts are

unchanged [13]

Mebendazole is particularly useful if given 10–14 days

before and for several weeks after surgery or

percuta-neous puncture to prevent recurrence [9]

Percutaneous drainage

US-guided percutaneous drainage is as effective as

surgery [4, 9] The ‘PAIR’ routine is used (table 29.3) [4]

Care must be taken that sclerosing solutions such as

for-malin are not injected as these may induce sclerosing

cholangitis [15] The cyst fluid must not be bile stained as

a fall in pressure might prevent closure of a biliary

fistula

Surgery

The object is to remove the cyst completely, without

soiling and infecting the peritoneum and with complete

obliteration of the resulting dead space Complete

removal of the cyst with its adventitia is ideal to avoid

spillage The usual operation is cystectomy with

removal of the germinal and laminated layers and

preservation of the host-derived ectocyst [11] Surgical

pericystectomy includes removal of the pericyst and has

a high mortality The mortality for these operations is

2.2% and the morbidity rate is 23.7% [11] Cure rates are

up to 22%

Hemi-hepatectomy or segmentectomy are

occasion-ally performed Cholangitis is treated by biliary

drainage, usually by ERCP, papillotomy and cyst

removal Surgical biliary drainage may be necessary The

technical problem is great

Rupture into the peritoneal cavity

The cyst contents are removed from the peritoneal cavity

as far as possible by sucking and swabbing The scolices,

however, usually settle down in the peritoneal cavity

and form daughter cysts so that recurrence is almost

inevitable

Urgent surgery has a substantial morbidity and

mortality [14] Chemotherapy is essential

Echinococcus multilocularis (alveolar echinococcosis)

This is found in the northern hemisphere Rodents are

intermediate hosts and foxes are definitive hosts The

larvae grow indefinitely and produce liver necrosis and

a major granulomatous reaction It may be diagnosed byPCR [8] The disease behaves like a locally malignant

tumour The Echinococcus invades liver and biliary

tissue, hepatic veins, inferior vena cava and diaphragm.Chemotherapy is effective but not curative [1] It is fatalunless completely removed by surgery [16] Hepatictransplant may be necessary [3]

References

1 Ammann RW, Ilitsch N, Marincek B et al Effect of

chemotherapy on the larval mass and the long-term course

of alveolar echinococcosis Hepatology 1994; 19: 735.

2 Babba H, Messedi A, Masmoudi S et al Diagnosis of human

hydatidosis: comparison between imaging and six serologic

techniques Am J Trop Med Hyg 1994; 50: 64.

3 Bresson-Hadni S, Franza A, Miguet JP et al Orthotopic liver

transplantation for incurable alveolar echinococcosis of the

liver: report of 17 cases Hepatology 1991; 13: 1061.

4 Filice C, Pirola F, Brunetti E et al A new therapeutic

approach for hydatid liver cysts Aspiration and alcohol

injection under sonographic guidance Gastroenterology

1990; 98: 1366.

5 Gemmell MA, Lawson JR, Roberts MG Control of echinococcosis/hydatidosis: present status of worldwide

progress Bull WHO 1986; 64: 333.

6 Gharbi HA, Hassine W, Brauner MW et al Ultrasound

examination of the hydatic liver Radiology 1981; 139: 459.

7 Ibarrola AS, Sobrini B, Guisantes J et al Membranous glomerulonephritis secondary to hydatid disease Am J.

Med 1981; 70: 311.

8 Kern P, Frosch P, Helbig M et al Diagnosis of Echinococcus

multilocularis infection by reverse-transcription polymerase

chain reaction Gastroenterology 1995; 109: 596.

9 Khuroo MS, Wani NA, Javid G et al Percutaneous drainage compared with surgery for hepatic hydatid cysts N Engl J.

Med 1997; 337: 881.

10 Lewall DB Hydatid disease: biology, pathology, imaging

and classification Clin Radiol 1998; 53: 863.

11 Magistrelli P, Masetti R, Coppola R et al Surgical treatment

of hydatid disease of the liver A 20-year experience Arch.

Surg 1991; 126: 518.

12 Marani SA, Canossi GC, Nicoli FA et al Hydatid disease:

MR imaging study Radiology 1990; 175: 701.

13 Nahmias J, Goldsmith R, Soibalman M et al Three to 7 years

follow-up after albendazole treatment of 68 patients with

cystic echinococcosis (hydatid disease) Ann Trop Med

Parasitol 1994; 88: 295.

14 Schaefer JW, Khan MY Echinococcosis (hydatid disease):

lessons from experience with 59 patients Rev Infect Dis.

1991; 13: 243.

15 Teres J, Gomez-Moli J, Bruguera M et al Sclerosing

cholangi-tis after surgical treatment of hepatic echinococcal cysts:

report of three cases Am J Surg 1984; 148: 694.

16 Wilson JF, Rausch RL, Wilson FR et al Alveolar hydatid

disease Review of the surgical experience in 42 cases of

active disease among Alaskan Eskimos Ann Surg 1995;

221: 315.

17 WHO Informal Working Group on Echinococcosis lines for the treatment of cystic and alveolar echinococcosis

Guide-in humans Bull WHO 1996; 74: 231.

Table 29.3 Treatment of hydatid liver cysts [4]

Percutaneous puncture Aspirate

Inject 25% alcohol Re-aspirate

Ascaris infection is particularly common in the Far East, India and South Africa Ova of the roundworm Ascaris lumbricoides arrive in the liver by retrograde flow in the

bile ducts They exert an immunological reaction andeggs, giant cells and granulomas are surrounded by adense eosinophil infiltrate (fig 29.25) The adult worm is10–20 cm long but occasionally may lodge in thecommon bile duct producing partial bile duct obstruc-

tion, and secondary cholangitic abscesses [2] The Ascaris

may be a nucleus for intra-hepatic gallstones [4] Biliarycolic is a complication

A plain abdominal X-ray may show calcified worms Clinical presentation is as acute cholecystitis, acute

cholangitis, biliary colic, acute pancreatitis and, rarely,hepatic abscess [2]

US shows long linear echogenic structures or strips

which characteristically move It can be used to monitormigration of the worms It cannot diagnose duodenalascariasis

ERCP shows the Ascaris as a linear filling defect (fig.

29.26) Worms can be seen moving into and out of thebiliary tree from the duodenum [1]

Treatment is by ERCP with endoscopic worm

extrac-tion with or without sphincterotomy [3] Failures needsurgical treatment

Treatment with piperazine citrate, mebendazole or

albendazole will usually kill Ascaris but it remains in the

bile ducts Re-invasion is common

Fig 29.25 Section shows a dead Ascaris in an intra-hepatic

blood vessel in a portal zone There is surrounding fibrous

tissue reaction (H & E, ¥ 40.)

Fig 29.26 Ascariasis: endoscopic

cholangiography shows linear filling

defects in the bile ducts due to Ascaris

worms (arrowheads).

1 Kamath PS, Joseph DC, Chandran R et al Biliary ascariasis:

ultrasonography, endoscopic retrograde

cholangiopancre-atography, and biliary drainage Gastroenterology 1986; 91:

730.

2 Khuroo MS, Zargar SA, Mahajan R Hepatobiliary and

pancreatic ascariasis in India Lancet 1990; 335: 1503.

3 Manialawi MS, Khattar NY, Helmy MM et al Endoscopic

diagnosis and extraction of biliary Ascaris Endoscopy 1986;

18: 204.

4 Shulman A Non-Western patterns of biliary stones and the

role of ascariasis Radiology 1987; 162: 425.

Strongyloides stercoralis

This soil-transmitted intestinal nematode is common

in tropical countries It is usually asymptomatic but

can cause biliary obstruction due to biliary stenosis [1]

Thiabendazole is effective treatment

Reference

1 Delarocque Astagneau E, Hadengue A, Degottc C et al.

Biliary obstruction resulting from Strongyloides stercoralis

infection: report of a case Gut 1994; 35: 705.

Trichiniasis

This disease is caused by eating raw, infected pork with

subsequent dissemination of Trichinella larvae

through-out the body

Hepatic histology may show invasion of hepatic

sinu-soids by Trichinella larvae and fatty change [1].

Diagnosis is difficult unless in an epidemic

Eosinophilia is suggestive Muscle pain and tenderness

may warrant muscle biopsy

Treatment ERCP is indicated if the biliary tract is

obstructed Treatment is unsatisfactory Mebendazole

may be effective in the migratory stage but is of doubtful

value later

Reference

1 Guattery JM, Milne J, House RK Observations on hepatic

and renal dysfunction in trichinosis Anatomic changes in

these organs occurring in cases of trichinosis Am J Med.

1956; 21: 567.

Toxocara canis (visceral larva migrans)

This parasite is spread by cats and dogs The second

stage can infect the liver of man, forming granulomas [1]

Hepatomegaly, recurrent pneumonia, eosinophilia and

hypergammaglobulinaemia are associated findings The

serum fluorescent antibody test is positive

Treatment may be tried with diethyl carbamazine orthiabendazole

duo-Clonorchis sinensis

The Chinese liver fluke is found mainly in eastern Asia

It can present years after the patient has left their country

of origin as the biliary flukes persist for decades Cystsare ingested with improperly cooked or raw, fresh-waterfish The cyst wall is destroyed by trypsin in the duode-num and the larvae migrate from the duodenum into theperipheral intra-hepatic bile ducts where they mature toadult worms In uncomplicated cases, the changes areconfined to the bile duct walls with abundant adenoma-tous formation; fibrosis increases with time [4] Cholan-giocarcinoma is a serious complication [8]

Clinical manifestations depend on the number of flukes,

the period of infestation and the complications Withheavy infestation, the patient suffers weakness, epigas-tric discomfort, weight loss and diarrhoea Jaundice isdue to obstruction to the intra-hepatic biliary tree byworms or inflammation Infection leads to fever, chillsand abdominal pain Cholangiocarcinoma is marked byprogressive jaundice and pruritus

Diagnosis is based on finding ova in the stool or

aspi-rated bile Laboratory findings include eosinophilia and

an increased serum alkaline phosphatase

ERCP shows filamentous filling defects in the bile

ducts which have blunted tips [7] The defects are ofuniform size and change in position

US and CT changes are based on flukes within dilated

ducts and peri-ductal changes without evidence of extra-hepatic biliary obstruction [1, 7]

The therapeutic response to praziquantel is poor and

relapses may follow bithionol

The bile ducts must be cleared of stones by scopic or percutaneous cholangiography or surgery [5, 6]

endo-Fasciola hepatica

The common sheep fluke is found mostly in mid- and

western Europe and in the Caribbean The animal

infes-tation rate in Britain is high: 30–90% of all sheep and

cattle excrete the ova This increases in wet summers

when the intermediate host, the snail Lymnaea trunculata,

is also more numerous The encysted cercariae from

these snails survive on herbage and patients are usually

infected by eating contaminated watercress

The clinical picture in the acute stage is of

cholan-gitis with fever, right upper quadrant pain and

hepatomegaly Eosinophilia and a raised serum alkaline

phosphatase are noted The picture may simulate

choledocholithiasis

ERCP shows several irregular linear or rounded filling

defects in the bile ducts or segmental stenosis, with an

inflammatory pattern Worms can be aspirated

Liver biopsy shows infiltration of the portal zones

with histiocytes, eosinophils and polymorphs Hepatic

granulomas and ova in the liver may occasionally be

seen

Diagnosis is suspected by finding the clinical picture

of biliary tract disease with eosinophilia It is confirmed

by finding ova in the faeces These, however, may not

be detected until 12 weeks after the infection when

parasites have attained sexual maturity They disappear

later

The diagnosis may be confirmed by ELISA testing

of circulating antibodies to Fasciola hepatica

excretory-secretory antigens [2, 3]

CT shows peripheral filling defects, sometimes

cres-centic, in the liver due to the migrating fluke (fig 29.27)

[9]

Treatment of all liver flukes is by praziquantel,

bithionol or albendazole

Recurrent pyogenic cholangitis

This is a common disease in south-east Asia The initial

cause is uncertain, but may be Clonorchis or enteric

micro-organisms Biliary stone and stricture formation followrecurrent bacterial infections Treatment is by antibioticsfollowing biliary drainage either endoscopic or surgical

References

1 Choi BI, Kim HJ, Han MC et al CT findings of clonorchiasis.

Am J Roentgenol 1989; 152: 281.

2 Cordova M, Herrera P, Nopo L et al Fasciola hepatica cysteine

proteinases: immunodominant antigens in human

fasciolia-sis Am J Trop Med Hyg 1997; 57: 660.

3 Espino AM, Marcet R, Finlay CM Detection of circulating excretory secretory antigens in human fascioliasis by

sandwich enzyme-linked immunosorbent assay J Clin.

Microbiol 1990; 28: 2637.

4 Hou PC, Pang LSC Clonorchis sinensis infestation in man in

Hong Kong J Pathol Bact 1964; 87: 245.

5 Jan YY, Chen MF Percutaneous trans-hepatic scopic lithotomy for hepatolithiasis: long-term results

cholangio-Gastrointest Endosc 1995; 42: 1.

6 Jan YY, Chen MF, Wang CS et al Surgical treatment of

hepatolithiasis: long-term result Surgery 1996; 120: 509.

7 Lim JH Radiologic findings of clonorchiasis Am J.

Fig 29.27 Fasciola hepatica CT in the

migratory stage shows multiple,

sometimes linear, filling defects at the

periphery of the liver (Courtesy of P.A.

McCormick.)

This upper abdominal peritonitis is associated with

genital infections, particularly Chlamydia trachomatis and

less often with Neisseria gonorrhoeae [2] It affects young,

sexually active women and simulates biliary tract

disease Diagnosis is by laparoscopy The liver surface

shows white plaques, tiny haemorrhagic spots and

‘violin string’ adhesions

CT may also show ‘violin string’ adhesions (fig 29.28)

[1] Treatment is with tetracycline

References

1 Haight JB, Ockner SA Chlamydia trachomatis perihepatitis

with ascites Am J Gastroenterol 1988; 83: 323.

2 Simson JNL Chlamydial perihepatitis (Curtis–Fitz Hugh

syndrome) after hydrotubation Br Med J 1984; 289: 1146.

Hepato-biliary disease in HIV infection

HIV does not seem to exert any direct effect on the

liver Many diseases, however, affect the

immun-odeficient and provide a confusing picture [23, 31]

All parts of the hepato-biliary system can show changes

and may be involved in more than one process (table

29.4) Hepatomegaly is seen in at least two-thirds

and 50% of patients show abnormal liver function tests

A blood culture is usually more helpful than a liver

biopsy

Hepatic histology is seldom normal, showing

macro-vesicular fat and mild zone 1 lymphocytes [18]

The causes of hepato-biliary disease differ depending

on the extent of immunocompromise [32] In earlier

stages where the CD4 cell count exceeds 500 109/l,hepatic complications are largely liver-specific, such asdrug-related, primary neoplasm or infection withhepato-trophic viruses such as hepatitis B and C Withprogression of immunodeficiency to CD4 cell counts of less than 200, the liver is generally involved as part of

systemic opportunistic infections due to Mycobacterium avium intracellulare (MAI), fungi or cytomegalovirus

(CMV) The liver is only one site involved in AIDS; liverdisease is rarely the primary cause of death

A high serum alkaline phosphatase level is an tion for US or CT (fig 29.29) Those with dilated bileducts should proceed to ERCP to confirm biliaryobstruction Those with a focal lesion should have aguided liver biopsy In the absence of a focal or bile duct

indica-Fig 29.28 CT in chlamydial peri-hepatitis shows ‘violin

string’ adhesions between liver and anterior abdominal wall

(arrowed) and ascites.

Table 29.4 Hepato-biliary changes in AIDS

Non-specific

Hepatomegaly Abnormal biochemistry Histology

fatty change portal inflammation Kupffer cell iron diminished lymphocytes

Toxoplasmosis Bacillary peliosis Hepatitis B virus Impaired response to vaccine and antiviral therapy Fulminant (rare)

* Associated biliary tract disease.

lesion a liver biopsy should be performed to exclude

mycobacteria (fig 29.29)

Infections

These are largely opportunistic and part of generalized

infection Liver biopsy in patients with hepatomegaly,

fever and abnormal biochemical tests gives the cause in

about 25%

MAI infection is a late complication It presents with

fever, night sweats, weight loss and diarrhoea Hepatic

histology shows poorly formed granulomas without

lymphocyte cuffing, giant cells or central caseation

Acid-fast bacilli are present in large numbers in clusters

of foamy histiocytes or within Kupffer cells (figs 29.30,

29.31) If MAC is seen in liver biopsies, the mean survival

is only 69 days

Mycobacterium tuberculosis can occur at an earlier stage

and is more prevalent in injection drug users than in

other categories When the CD4 count exceeds 200,

in-fection is pulmonary whereas atypical presentations,

including hepatic involvement, are seen in patients with

more severe immunodeficiency

CMV is late and part of generalized disease It is

associated with fever and weight loss Diagnosis is made

by demonstrating nuclear and cytoplasmic inclusions inKupffer cells, bile duct epithelium and occasionallyhepatocytes

Fever, jaundice, hepatomegaly, abdominal pain

Routine LFTs Hepatitis B and C markers

High alkaline phosphatase

Guided liver biopsy

Lymphoma Kaposi Abscess

infections

Mycobacteria

Abnormal bile ducts

Liver biopsy

Fig 29.29 The management of the

patient with hepato-biliary AIDS.

Fig 29.30 An ill-defined poorly cellular granuloma in the

liver of a patient with AIDS (H & E, ¥ 220.)

Bacillary peliosis hepatitis The angioproliferative

lesions in the liver resemble Kaposi’s sarcoma It is due

to Bartonella henselae, a tiny Gram-negative organism

which is difficult to cultivate [16, 29] Systemic features

include fever, lymphadenopathy, hepatosplenomegaly

and cutaneous and bony lesions It is treated by

ery-thromycin

Fungal infections are usually part of late disseminated

disease They include Cryptococcus neoformans where

yeast can be shown in the liver (fig 29.32) [4] Similarly,

histoplasmosis (fig 29.33), coccidiomycosis [27] and

Candida albicans may involve the liver Those with low

CD4 counts exposed to Cryptosporidium are at risk of

biliary disease and death within 1 year [30] Pneumocystis

carinii can rarely cause hepatitis [20].

Hepatitis B, C and D co-infection

Markers of past or present HBV infection are found inapproximately 90% of homosexual men or drug abuserswith AIDS In late stage disease, the HBV may activatewith conversion to HBe antigen positivity and anincrease in HBV polymerase [15] However, the HBVseems to have little effect on liver histology or survival[24] Patients respond poorly to HBV vaccination, and tointerferon therapy [19, 33] Hepatitis delta virus (HDV)

is present, depending on the location [25]

In contrast, HIV accelerates the course and reduces thesurvival of HCV-infected patients The co-infection isparticularly frequent in drug absuers and in haemophili-acs where the liver disease is particularly severe [12, 21,28] Antibodies to HCV can disappear despite persistentHCV viraemia [26] Interferon therapy may be tried, butwill have the greatest benefit only in those with higherCD4 counts With the modern therapy of HIV, thenumber of doubly infected patients with good immunefunction will increase and combined ribavirin/inter-feron therapy can be tried

Neoplasms

Non-Hodgkin’s lymphoma is usually metastatic, but can

be primary (fig 29.34) It usually appears late, but mayappear at any stage of the disease and can be a primarypresentation It presents as fever, weight loss, nightsweats and abdominal pain, with a rise in serumtransaminases and especially serum alkaline phos-phatase Large hepatic lesions present with jaundice andpruritus

US and CT show large, usually multifocal solid

space-occupying lesions Guided liver biopsy is diagnostic.Survival is short and response to chemotherapy poor

Fig 29.31 Same patient as in fig 29.30 Liver stained for

acid-fast bacilli shows two granulomas containing many

red-staining bacilli (Mycobacterium avium intracellulare).

Fig 29.32 Cryptococcal hepatitis in a patient with AIDS.

Many yeast forms of Cryptococcus neoformans are stained black.

(Methenamine silver, ¥ 350.)

Fig 29.33 Histoplasmosis hepatitis in a patient with AIDS.

Many intracellular forms of Histoplasma capsulatum are stained

red (PAS diastase, ¥ 500.)

The prognosis depends on the degree of promise.

immunocom-Kaposi’s sarcoma largely affects homosexual men and

is decreasing in prevalence The patient is usuallyasymptomatic It frequently involves the liver aspurple–brown, soft nodules Histology shows multifocalareas of vascular endothelial proliferation with pleomor-phic spindle cells and extravasated erythrocytes (fig.29.35) US shows small hyperechoic nodules and dense

peripheral bands CT shows hypoattenuated lesions

enhancing after contrast

Drug-induced HIV-infected patients are exposed to

many potential hepato-toxins Any agent should be considered at fault Drug interactions must always beconsidered Drug reactions are the commonest cause

of jaundice in AIDS [8] Anti-mycobacterials are most

commonly at fault, especially isoniazid and rifampicin.Trimethoprim-sulfamethoxasole is a common of-fender, causing granulomatous hepatitis and jaundice[17]

Hepatomegaly and steatosis may be related to side-analogue retroviral therapy [14] Zidovudine anddideoxyinosine can cause severe, sometimes fatal, liverfailure The picture is of mitochondrial failure [3]

nucleo-Hepato-biliary disease

This includes intra- and extra-hepatic sclerosing gitis [6], papillary stenosis and acalculous cholecystitis

cholan-[31] It is termed AIDS cholangiopathy It is associated

with severe immunodeficiency with CD4 lymphocytescounts of less than 200

Cryptosporidia are the single most common

pathogens identified Cryptosporidium parvum is

cyto-pathic for cultured human biliary epithelia via an totic mechanism (fig 29.36) [9]

apop-Fig 29.34 B-cell lymphoma in a patient with AIDS Sinusoids

are infiltrated with large pleomorphic lymphoid cells (H & E,

¥ 350.)

Fig 29.35 Kaposi’s sarcoma in a patient with AIDS Portal

zones show expansion with spindle cell tumour cells which are

forming vascular clefts (H & E, ¥ 150.)

Fig 29.36 Cryptosporidiosis of the gallbladder in a

patient with AIDS (H & E, ¥ 160.)

Microsporidia or cytomegalovirus may be causative [5,

22] The agent can be found in biliary or gallbladder wall

and in bile The patient presents with intermittent right

upper abdominal pain and tenderness Serum alkaline

phosphatase may be strikingly high, but serum bilirubin

is usually normal Presentation may also be as painless

cholestasis or as acute bacterial cholangitis

US is the best initial diagnostic tool It shows bile duct

thickening or biliary dilatation or both (fig 29.37) A

hyperechoic nodule may be seen as the distal end of the

common bile duct and represent an oedematous papilla

[10]

Endoscopic US is useful in demonstrating papillary

stenosis [2]

ERCP is the diagnostic gold standard, but gives little

additional information if the US is normal [11] It shows

an irregularly dilated common bile duct with papillary

stenosis (fig 29.38) Better yield of the causative agent is

obtained if multiple (duodenal and papillary) biopsies

are taken and the bile sampled [5]

Prognosis and treatment

The outcome (mean survival 7.5 months) is similar to

that of matched AIDS controls [13] Only 14% survive

1 year [5] Prognosis depends on the stage of

immuno-suppression

Treatment is primarily endoscopic Sphincterotomy

gives striking relief of pain or cholangitis [7] Balloon

dilatation and stents may be necessary Medical

treat-ment of cryptosporidial or microsporidial infection has

failed to relieve biliary symptoms

Acalculous cholecystitis

This is primarily infectious and due to the same causes asAIDS cholangiopathy It can be gangrenous US shows athickened gallbladder wall, air in the gallbladder andpericholecystic fluid [1] Acute cholecystitis must betreated surgically Results for laparoscopic cholecystec-tomy are not encouraging

References

1 Aaron JS, Wynter CD, Kirton OC et al Cytomegalovirus

associated with acalculous cholecystitis in a patient with

acquired immune deficiency syndrome Am J Gastroenterol.

1988; 83: 879.

2 Benhamou Y, Caumes E, Gerosa Y et al AIDS-related

cholangiopathy Critical analysis of a prospective series of

26 patients Dig Dis Sci 1993; 38: 1113.

3 Bissuel F, Bruneel F, Habersetzer F et al Fulminant hepatitis

with severe lactate acidosis in HIV-infected patients on

didanosine therapy J Intern Med 1994; 235: 367.

4 Bonacini M, Nussbaum J, Ahluwalia C Gastrointestinal,

hepatic, and pancreatic involvement with Cryptococcus

neoformans in AIDS J Clin Gastroenterol 1990; 12: 295.

5 Bouche H, Housset C, Dumont J-L et al AIDS-related cholangitis: diagnostic features and course in 15 patients J.

Hepatol 1993; 17: 34.

6 Cello JP Acquired immunodeficiency syndrome

cholan-giopathy: spectrum of disease Am J Med 1989; 86: 539.

T

Fig 29.37 Cryptosporidial biliary infection in a patient with

AIDS US showing a greatly thickened gallbladder wall

(arrowed) and bile ducts.

Fig 29.38 Ampullary stenosis and sclerosing cholangitis due

to cytomegalovirus infection in a patient with AIDS.

7 Cello JP, Chan MF Long-term follow-up of endoscopic

retrograde cholangiopancreatography sphincterotomy for

patients with acquired immune deficiency syndrome

papillary stenosis Am J Med 1995; 99: 600.

8 Chalasani N, Wilcox CM Etiology, evaluation and outcome

of jaundice in patients with acquired immunodeficiency

syndrome Hepatology 1996; 23: 728.

9 Chen X-M, Levine SA, Tietz P et al Cryptosporidium parvum

is cytopathic for cultured human biliary epithelia via an

apoptotic mechanism Hepatology 1998; 28: 906.

10 Da Silva F, Boudghene F, Lecomte I et al Sonography in

AIDS-related cholangitis: prevalence and cause of an

echogenic nodule in the distal end of the common bile duct.

Am J Roentgenol 1993; 160: 1205.

11 Daly CA, Padley SP Sonographic prediction of a normal or

abnormal ERCP in suspected AIDS related sclerosing

cholangitis Clin Radiol 1996; 51: 618.

12 Eyster ME, Diamondstone LS Natural history of hepatitis C

virus infection in multitransfused haemophiliacs: effect of

coinfection with human immunodeficiency virus J AIDS

1993; 6: 602.

13 Forbes A, Blanshard C, Gazzard B Natural history of

AIDS-related sclerosing cholangitis: a study of 20 cases Gut 1993;

34: 116.

14 Fortgang IS, Belitsos PC, Chaisson RE et al Hepatomegaly

and steatosis in HIV-infected patients receiving

ana-logue antiretroviral therapy Am J Gastroenterol 1995; 90:

1433.

15 Housset C, Pol S, Carnot F et al Interactions between human

immunodeficiency virus-1, hepatitis delta virus and

hepati-tis B virus infections in 260 chronic carriers of hepatihepati-tis B

virus Hepatology 1992; 15: 578.

16 Koehler JE, Quinn FD, Berger TG et al Isolation of

Rocha-limaea species from cutaneous and osseous lesions of

bacillary angiomatosis N Engl J Med 1992; 327: 1625.

17 Kreisberg R Clinical problem-solving We blew it N Engl J.

Med 1995; 332: 945.

18 Lefkowitch JH Pathology of AIDS-related liver disease.

Dig Dis Sci 1994; 12: 321.

19 McDonald JA, Caruso L, Karayiannis P et al Diminished

responsiveness of male homosexual chronic hepatitis B

carriers with HTLV-III antibodies to recombinant alpha

interferon Hepatology 1987; 7: 719.

20 Poblete RB, Rodriguez K, Foust RT et al Pneumocystis carinii

hepatitis in the acquired immunodeficiency syndrome

(AIDS) Ann Intern Med 1989; 110: 737.

21 Pol S, Lamorthe B, Thi NT et al Retrospective analysis of the

impact of HIV infection and alcohol use on chronic hepatitis

C in a large cohort of drug users J Hepatol 1998; 28: 945.

22 Pol S, Romana CA, Richard S et al Microsporidia infection

in patients with the human immunodeficiency virus and

unexplained cholangitis N Engl J Med 1993; 328: 95.

23 Poles MA, Lew EA, Dieterich DT Diagnosis and treatment

of hepatic disease in patients with HIV Gastroenterol Clin.

North Am 1997; 26: 291.

24 Scharschmidt BF, Held MJ, Hollander HH et al Hepatitis B

in patients with HIV infection: relationship to AIDS and

patient survival Ann Intern Med 1992; 117: 837.

25 Soloman RE, Kaslow RA, Phair JP et al Human

immunode-ficiency virus and hepatitis delta virus in homosexual men.

A study of four cohorts Ann Intern Med 1988; 108: 51.

26 Spengler U, Rockstroh JK Hepatitis C in the patient with

human immunodeficiency virus infection J Hepatol 1998;

29: 1023.

27 Stevens DA Current concepts Coccidiomycosis N Engl J.

Med 1995; 332: 1077.

28 Telfer P, Sabin C, Devereux H et al The progression of

HCV-associated liver disease in a cohort of haemophilic patients.

Br J Haematol 1994; 87: 555.

29 Tomkins LS Of cats, humans and Bartonella N Engl J Med.

1997; 337: 1916.

30 Vakil NB, Schwartz SM, Buggy BP et al Biliary

cryp-tosporidiosis in HIV-infected people after the water borne

outbreak of cryptosporidiosis N Engl J Med 1996; 334: 19.

31 Wilcox CM, Monkemuller KE Hepatobiliary diseases in patients with AIDS: focus on AIDS cholangiopathy and

gallbladder disease Dig Dis 1998; 16: 205.

32 Wilcox CM, Rabeneck L, Friedman S AGA technical review: malnutrition and cachexia, chronic diarrhea, and hepatobil- iary disease in patients with human immunodeficiency

virus infection Gastroenterology 1996; 111: 1724.

33 Wong DK, Yim C, Naylor CD et al Interferon alfa treatment

of chronic hepatitis B: randomised trial in a predominantly

homosexual male population Gastroenterology 1995; 108:

Liver biopsy shows non-specific changes; electronmicroscopy shows cholestasis There is also evidence oftoxic liver injury Increased numbers of fat-storinglipocytes are seen during the acute stage

Septicaemia and septic shock

Liver function abnormalities, including modestincreases in serum alkaline phosphatase, transaminasesand bile salts, are not uncommon in patients with severeinfections, septicaemia, toxic shock and endotoxaemia[1, 4] In two-thirds, jaundice is a feature and, if it persists, carries a bad prognosis

Hepatic histology shows non-specific hepatitis ing mid-zonal and peripheral necrosis Cholestasis may

includ-be marked and in severe cases is shown as inspissatedbile within dilated and proliferated portal and peri-portal bile ductules [2] Cultures of the liver are sterile.The causes are multifactorial Hepatic hypoperfusionplays a part The cholangiolar lesions might be related tointerference with canalicular exchange of water and elec-trolytes, to endotoxaemia, to staphylococcal exotoxin [3]

or to interference with the peri-biliary vascular plexus as

a result of shock [1] TNF-a may mediate

endotoxin-induced cholestasis [6] Endotoxin interferes with bile

acid transport

The syndrome of jaundice associated with

extra-hepatic infection is functional and reversible upon

control of the infection

References

1 Gourley GR, Chesney PJ, Davis JP et al Acute cholestasis in

patients with toxic-shock syndrome Gastroenterology 1981;

81: 928.

2 Lefkowitch JH Bile ductular cholestasis: an ominous

histo-pathologic sign related to sepsis and ‘cholangitis lenta’ Hum.

Pathol 1982; 13: 19.

3 Quale JM, Mandel LJ, Bergasa NV et al Clinical significance

and pathogenesis of hyperbilirubinemia associated with

Staphylococcus aureus septicemia Am J Med 1988; 85: 615.

4 Sikuler E, Guetta V, Keynan A et al Abnormalities in bilirubin

and liver enzyme levels in adult patients with bacteremia.

Arch Intern Med 1989; 149: 2246.

5 Tugwell P, Williams AO Jaundice associated with lobar

pneumonia Q J Med 1977; 46: 97.

6 Whiting JF, Green RM, Rosenbluth AB et al Tumor necrosis

factor-alpha decreases hepatocyte bile salt uptake and

medi-ates endotoxin-induced cholestasis Hepatology 1995; 22:

1273.

The increased use of radiological imaging, particularly

ultrasound examination, has led to much more frequent

identification of nodules in the liver Patient

manage-ment is vastly different depending on the different

causes (figs 30.1, 30.2)

Diagnosis and management depend on whether the

patient has underlying liver disease, usually cirrhosis,

when hepato-cellular cancer (HCC) has to be excluded,

or whether the lesion is a benign nodule or metastasis

Hepatitis B and C markers should be sought and a

routine serum a-fetoprotein level determined

Small hepato-cellular cancer (Chapter 31)

The patient is well aware of the significance of the small

nodule Considerable anxiety is present in both patient

and physician and a definitive diagnosis should be made

if at all possible, particularly as the survival rate (of

resection or transplant) is much greater with tumours

only 1–2 cm in diameter (fig 30.3)

Cirrhosis may or may not have been diagnosed

previ-ously The tumour is usually asymptomatic and there are

no additional physical signs The serum a-fetoprotein

level is usually less than 200 ng/ml The level may be

normal or modestly raised due to non-malignant

regen-eration nodules Serial records showing an increasing

a-fetoprotein level over the last few months and years may

be particularly helpful as well as any records of past

ultrasound or other imaging results

Difficulty exists in distinguishing a dysplastic or

macro-regenerative nodule from a cancer (figs 30.4,30.5) Indeed all three may coexist Imaging and histo-logical characteristics may be inconclusive

The percentage of diagnostic success using imagingdepends on the size of the lesion, particularly if it islarger than 2 cm in diameter

Ultrasound usually detects lesions less than 2 cm The

lesion is hypoechoic with ill-defined margins

CT shows a hypodense lesion It frequently fails to

detect the size and number of lesions Intravenous trast enhancement is essential

con-Hepatic angiography is not reliable diagnostically and

has largely been replaced by MRI

MRI is better than CT for showing focal lesions T2weighted images show focal lesions, vascular invasionand satellites Contrast such as gadolinium or super-magnetic iron oxide are safe and useful

-Guided nodule biopsy This is done under ultrasound

control Success depends on the size of the lesion and its position It is important to sample tissue away fromthe nodule so that the underlying cirrhosis may be diag-nosed There is a possibility of needle-tract seeding oftumour [15] The specimen may be fully diagnostic ofHCC, but more often the appearances are suspicious andsuggestive The picture in nodules having a high risk forevolution to HCC include an increased number of hepa-

527

Chapter 30 Nodules and Benign Liver Lesions

Fig 30.1 Algorithm for the management of hepatic mass

lesion (nodule) in a patient with underlying chronic liver

disease.

Hepatic mass lesions

No chronic liver disease

US

CT (? MRI) Haemangioma

Cyst

Metastases

Search primary

Guided biopsy

Fig 30.2 Algorithm for the management of a hepatic mass

lesion (nodule) in a patient without underlying chronic liver disease.

tocyte nuclei compared with surrounding tissue, clear

cell change, small cell dysplasia and fatty change [18]

Features in a dysplastic nodule favouring HCC include

nuclear atypia, high nuclear/cytoplasm density, absence

of portal tracts, unaccompanied arteries and reduction of

reticulin and mitoses [7]

Conclusions Any focal lesion in a cirrhotic liver must

be regarded as suspicious of HCC or of its impending

development [14] Macro-regenerative nodules which

are at least 1 cm in diameter and are hypoechoic, are

par-ticularly precancerous [5,19] Screening of focal lesions

by ultrasound and a-fetoprotein at 6-monthly intervals

at least is mandatory

Nodules in the absence of underlying

liver disease(fig 30.2)

Discovery of the lesion is followed by the usual detailed

history and clinical examination, routine biochemical

tests, hepatitis B and C viral markers and an a-fetoprotein

level A family history is taken for cystic disease

Simple cysts(Chapter 33)

The hepatic cyst may be simple or multiple and may be

accompanied by renal or other cysts

On ultrasound, simple cysts have smooth walls and

echo-free contents with through transmission of the

sound waves The CT scan shows a low attenuation

value of the centre equivalent to water There is no

enhancement with contrast MRI with T2-weighted

images shows the cysts as fluid

Haemangioma

This is the commonest benign tumour of the liver, being

found in about 5% of autopsies Diagnosis is increasing

with the greater use of scanning It is usually single and

small, but occasionally may be multiple or very large.The tumour is commonly subcapsular, on the convexity

of the right lobe and is occasionally pedunculated Onsection it appears round or wedge shaped, dark red incolour and has a honeycomb pattern, with a fibrouscapsule which may be calcified Histologically, a com-municating network of spaces contains red corpuscles.Factor VIII may be expressed The tumour is lined by flatendothelial cells and contains scanty fibrous tissue.Occasionally, there is a marked fibrous component

Clinical features The majority are asymptomatic and

discovered incidentally Symptoms from giant tumours(> 4 cm diamater) include abdominal mass and pain due

to thrombosis Symptoms may be due to pressure onadjacent organs Rarely, a vascular hum is heard over thelesion

Radiology A plain X-ray may show a calcified capsule Ultrasound shows a solitary echogenic spot with

Fig 30.3 Cirrhosis and a very small hepato-cellular

carcinoma.

Fig 30.4 Explant liver of chronic hepatitis C virus cirrhosis:

note nodularity Larger nodules with green/tan appearance are dysplastic.

Fig 30.5 Same patient as in fig 30.4 Part of a dysplastic

nodule: the central nodule (nodule-in-nodule) shows thick trabeculae and focal cholestasis It is probably a minute hepato-cellular carcinoma (H & E, ¥ 10.) (Courtesy of Professor A.P Dhillon.)

smooth well-defined borders Posterior acoustic

enhancement, due to increased sound transmission

through the blood of cavernous sinuses, is characteristic

CT scan enhanced by contrast shows distinctive

pud-dling of contrast in venous channels (fig 30.6) The

con-trast fills in the lesion from the periphery to the centre,

until opacification is homogeneous after 30–60 min Foci

of globular enhancement are seen after dynamic bolus

CT Calcification may be seen due to previous bleeding

or thrombus formation

MRI shows the tumour as a markedly high intensity

area T2 is prolonged over 8 ms (fig 30.7) MRI is ofspecial value in diagnosing small haemangiomas

SPECT with 99mTc-labelled red blood cells shows persistent blood pool activity within the lesion

Arteriography is rarely necessary Large arterial

branches are displaced The hepatic arteries divide toform small vessels before filling the vascular space Prolonged, up to 18 s, opacification of the lesion may beshown

Fig 30.6 Haemangioma CT shows a

giant benign haemangioma in the right

lobe A few small lesions are seen in the

left lobe The lesions filled in completely

after intravenous contrast.

Fig 30.7 Haemangioma MRI using

long T2-weighting shows a very bright

lesion (arrow) This reflects a profuse and

very sluggish circulation usually due to a

haemangioma.