new onset severe hypercholesterolemia in a patient with cholestatic liver disease should we treat the lipids

New-onset severe hypercholesterolemia in a patient with cholestatic liver disease.Should we treat the lipids?. M ANIP T Case Report New-onset severe hypercholesterolemia in a patient w

New-onset severe hypercholesterolemia in a patient with cholestatic liver disease.

Should we treat the lipids?

Panteleimon E Papakonstantinou, Eirini Theodoraki, Mairi Koulentaki, John A.

Papadakis

PII: S1109-9666(16)30239-1

DOI: 10.1016/j.hjc.2016.12.009

Reference: HJC 107

To appear in: Hellenic Journal of Cardiology

Received Date: 12 October 2016

Revised Date: 12 December 2016

Accepted Date: 23 December 2016

Please cite this article as: Papakonstantinou PE, Theodoraki E, Koulentaki M, Papadakis JA, New-onset severe hypercholesterolemia in a patient with cholestatic liver disease Should we treat the lipids?,

Hellenic Journal of Cardiology (2017), doi: 10.1016/j.hjc.2016.12.009.

This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo

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Case Report

New-onset severe hypercholesterolemia in a patient with cholestatic liver disease Should we treat the lipids?

Panteleimon E Papakonstantinoua, Eirini Theodorakib, Mairi Koulentakib,

John A Papadakisa

a

Hypertension Unit (ESH Excellence Centre), Department of Internal Medicine, University Hospital of Heraklion, 71500 Voutes, Heraklion, Crete, Greece

b

Department of Gastroenterology, University Hospital of Heraklion, 71500 Voutes, Heraklion, Crete, Greece

Panteleimon E Papakonstantinou e-mail: pantelispapakon@gmail.com

Eirini Theodoraki e-mail: eirinith25@yahoo.gr

Mairi Koulentaki e-mail: mkoulentaki@yahoo.gr

Corresponding author:

John A Papadakis MD, PhD

Internist - Clinical Hypertension Specialist EHS R

Director in the Department of Internal Medicine

Head of Hypertension Unit of the Dept of Internal Medicine(ESH Excellence Centre) University Hospital of Heraklion, 71500 Voutes, Heraklion, Crete ,GREECE

Phone: +302810392688

Fax: +302810392359

e-mail: papadakisja@hotmail.com

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Key words: cholestasis; cholestatic liver disease; dyslipidemia; ERCP;

hypercholesterolemia

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Dyslipidemia is one of the major factors of atherosclerotic artery disease1-3 In the presence of high serum cholesterol levels, secondary

causes of dyslipidemia should always be excluded4 The most common

causes are type 2 diabetes mellitus, obesity, chronic renal failure, nephrotic syndrome, drugs, hypothyroidism and cholestatic liver diseases5 More

specifically, hypercholesterolemia is a common feature of cholestatic syndromes4,6,7 However, cholesterol levels beyond 500 mg/dl rarely occur in

patients with cholestasis We report a case of new-onset severe hypercholesterolemia in a 39-year-old patient with cholestasis due to inflammation and stenosis of the common bile duct

A 39-year-old male was referred to our outpatient clinic due to severe new-onset of intermittent right hypochondriac pain, jaundice and hypercholesterolemia (total cholesterol of 958 mg/dl, LDL cholesterol of 871 mg/dl) His medical history included alcohol abuse (8 units of alcohol per day) during the last ten years He was an active smoker (20 pack years), his body mass index (BMI) was 23.8 kg/m2 and his family history was unremarkable

He was not receiving any medication, while he was under fat-free diet

Two years previously he suffered an episode of acute pancreatitis

He had undergone an Endoscopic retrograde cholangiopancreatography (ERCP), due to a bile duct stenosis, that was negative for dysplasia or malignancy in the cytological examination and a stent was placed which was replaced with a new one three months later The patient’s lipid levels during this (first) hospitalization are presented in table 1 (January 2014)

On the second admission, the patient complained of intermittent pain

in the right hypochondria for the last seven months On physical examination,

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there was jaundice, with no xanthomas or xanthelasmas Τhe thyroid hormones were within normal limits, while there was no evidence for nephrotic syndrome The fasting plasma glucose level was 83mg/dl (reference range: 70-115mg/dl) The laboratory examinations revealed elevated liver enzymes and hyperbilirubinemia (Table 1, March 2016) The abdominal ultrasound showed sludge in the gallbladder and a dilatation of the common bile duct (1.5cm) due to the presence of two gallstones Anti-mitochondrial antibodies (AMA), anti-M2, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were negative for primary biliary cirrhosis The patient underwent a new ERCP, removal of the ductal gallstones and new stenting due to inflammation and stenosis at the lower part of the common bile duct The liver enzymes and the cholesterol level decreased gradually (Table 1, April-June 2016) After a follow-up period of three months, the patient remained symptom-free without evidence of jaundice recurrence Liver enzymes decreased remarkably, while there was a subsequent improvement

in patient’s lipid profile

Hyperlipidemia is one of the most common complications of cholestatic liver disease Primary biliary cirrhosis (PBC) and similar disorders may be accompanied by marked hypercholesterolemia However, cholesterol levels in cholestatic liver diseases above 900 mg/dl are extremely rare in the literature with only few reports The range of serum cholesterol concentrations is wide, from 120mg/dl to 1775 mg/dl in one report of 284 patients, while the mean cholesterol level was 369.5 mg/dl8

The pathophysiology of dyslipidemia in cholestasis is not well established and is still under investigation The mechanism of

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hypercholesterolemia in cholestasis is different from that in other disorders as unusual lipoproteins are present In patients with cholestatic liver disease, the increase in serum cholesterol levels is largely due to an increased level of lipoprotein-X (LP-X) , an abnormal lipoprotein particle within the LDL density region that is rich in free cholesterol and phospholipids6 Although elevated

levels of lipoprotein X has been associated with hyperviscosity syndrome9, the

association between lipoprotein X and coronary heart diseases is unclear The available data suggest that, despite hypercholesterolemia , patients with PBC are not at increased risk of atherosclerosis6,8,10 LP-X has been shown

to have anti-atherogenic properties as it inhibits the oxidation of normal LDL particles and prevents oxidized LDL from disrupting survival mechanisms in vascular endothelial cells11 Consequently, the increased cholesterol levels

due to LP-X may actually reduce atherosclerotic risk

Most of studies for cholestatic liver diseases and hyperlipidemia are available for PBC The data for other specific types of cholestatic syndromes except for PBC is sparse in the literature The efficacy of drug therapy in lowering cardiovascular morbidity and mortality in PBC and cholestatic liver diseases is uncertain6 The administration of lipid-lowering agents (LLA) in

these syndromes is still controversial6,12 Further studies are required to be

performed to estimate the lipid treatment in cholestatic disease In our case,

we did not administrate LLA for two reasons Firstly, we thought that the hyperlipidemia in our patient was reversible by treating the primary cause of the cholestasis and also, we wanted to avoid a possible drug toxicity in this patient with impaired liver enzymes12 Moreover we disputed the necessity of

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treating the hyperlipidemia in cholestatic liver disease, as most of the studies have shown that these patients are not at high risk for CAD

In conclusion, this was a rare case of a new-onset, rapid, and extreme hyperlipidemia due to cholestatic liver syndrome In such cases, treatment of the primary disorder is associated with normalization of the lipid levels The administrations of LLA should be personalized according to the physician’s and patient’s preferences

Conflict of interest: none

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References

therapy: Unanswered questions Hellenic J Cardiol 2016;57:86-91

disease: a critical review of the evidence Jama 2003;290:932-940

characteristics, management and early outcomes of acute coronary syndromes

in Greece: The PHAETHON study Hellenic J Cardiol 2016;57:157-166

lipoprotein X in a patient with cholestasis Annals of hepatology 2015;14:924-928

J Cardiol 2012;110:823-825

hyperlipidemia, and atherosclerotic risk: a systematic review Atherosclerosis 2007;194:293-299

Rapid normalization of severe hypercholesterolemia mediated by lipoprotein

X after liver transplantation in a patient with cholestasis - a case report Acta biochimica Polonica 2015;62:621-623

atherosclerosis in primary biliary cirrhosis: what is the risk? Hepatology 1992;15:858-862

hypercholesterolemic patient with primary biliary cirrhosis Gastroenterology 1990;98:1351-1357

cardiovascular risk in primary biliary cirrhosis Gut 2002;51:265-269

primary biliary cirrhosis by preventing LDL oxidation Journal of lipid research 2004;45:2116-2122

dyslipidemic patients affected by liver diseases: a subtle balance between risks and benefits Nutrition, Metabolism and Cardiovascular Diseases 2004;14:215-224

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Table 1 Patient’s blood tests January 2014: patient’s first hospitalization; March 2016: patient’s second hospitalization; April 2016: one month

follow-up after his second hospitalization; May 2016: two months follow-follow-up after his second hospitalization; June 2016: three months follow-up after his second

hospitalization

January

2014

March

2016

April

2016

May

2016

June

2016

TC: Total cholesterol; LDL-C: Low-density lipoprotein - Cholesterol; HDL-C: High-density lipoprotein - Cholesterol; TG: Triglycerides; AST: Aspartate transaminase; ALT: Alanine transaminase; GGT: gamma-glutamyl transpeptidase; ALP: Alkaline phosphatase