Factors associated with the quality of life of patients with chronic hepatitis c in viet tiep hospital, hai phong city, viet nam

Table 7: Association between the total score of Chronic Liver Disease Questionnaire and independent variables .... 28 Table 7: Association between the total score of Chronic Liver Diseas

Master in Tropical Medicine and International Health

17th Promotion 2015 – 2017

Master thesis

Author: Duong Xuan TRAN

Supervisor: Vinh HAI VU M.D., Ph.D

Co-supervisor: Prof Daniel REINHARZ Rapporteur: Prof Virak KHIEU

Vientiane, 2017

Institut de la Francophonie pour la MédecineTropicale

(IFMT) Vientiane, RDP LAO

Factors associated with the Quality of Life of patients with chronic hepatitis C in Viet Tiep Hospital, Hai Phong City, Viet Nam

BIOGRAPHY

First and last name: Duong Xuan TRAN

Date of birth: 15 December 1985

Place of birth: Thai Binh province, Viet Nam

Nationality: Vietnamese

Bachelor's degree: Medicine, Thai Binh University of Medical and Pharmacy

Personal interest: Infectious diseases and quality of life

TITLE OF RESEARCH

TITRE DE MÉMOIRE

Presented by: Duong Xuan TRAN

24 August 2017, Vientiane, Lao PDR

Under the supervision of Vinh HAI VU M.D., Ph.D

The president of the jury: Prof Duangdao SOUK ALOUN, of the University of Health

Sciences, Lao PDR

Members of the Jury Prof Boungnong

BOUPHA University of Health Sciences, Lao PDR

Prof Virak KHIEU National Center for Entomology, Parasitology, and Malaria Control,

Cambodia

Prof Khue MINH

PHAM University of Medicine and Pharmacy of Hai Phong, Viet Nam

Prof Mayfong

MAYXAY University of Health Sciences, Lao PDR

Prof Paul NEWTON Lao-Oxford Medical Research Wellcome Trust Unit, Lao PDR

Prof Niranh

POUMINDR University of Health Sciences, Lao PDR

Rapporter: Prof Virak KHIEU

Factors associated with the Quality of Life of patients with chronic

hepatitis C in Viet Tiep Hospital, Hai Phong City, Viet Nam

Facteurs associés à la qualité de vie des patients atteints d'hépatite

chronique C au Viet Tiep Hôpital, Hai Phong, Viet Nam

ACKNOWLEDGEMENT

First of all, I would like to express my sincere feelings to my parents who have supported me all through my life

I am also very thankful to:

Prof Daniel REINHARZ, Director of IFMT, Professor of the University of Laval and supervisor

of my thesis Being his student was very fortunate for me and a great honor With him, my brain was free, my interesting ideas came out and my quality of life increased I am deeply grateful for his remarkable efforts, patience, conscientiousness and especially his love for me and IFMT

Dr VU Hai Vinh, vice chief of the Infectious Diseases Department and infectious diseases ward- Viet Tiep Hospital, co-supervisor I thank him for his help, experience and concern Without him, I do not know how I would have conducted this study

Department of Infectious Diseases, Viet Tiep Hospital and all the staffs there They helped me enthusiastically in collecting data

Prof Michel STROBEL, Professor of Pathology and Infectious Diseases, for his passion for teaching and his medical professionalism

Dr Phetsavanh CHANTHAVILAY who helped me analyze complicated data Without him, I do not know what I would have done

Percy AARON, English teacher, who I got many benefits in learning English and for his intelligent questions I thank him for his patience and efforts in revising my huge mistakes Aline SEBIE, French teacher, who helped me improve my French with enthusiasm

My family, especially my wife and my daughter, who were burdened and greatly inconvenienced

by my not being there for them

Thai Binh University of Medicine and Pharmacy, and the Department of Infectious Diseases for giving me permission to join and finish this course and those who took over my responsibilities there during my absence

I would also like to thank deeply the Agence Universitaire de la Francophonie (AUF) and all the IFMT staff who warmly supported all my activities

Last but not least, I would also like to express my thanks and appreciation to all the terrific friends I made in P17 They helped me overcome difficulties during my study with so much kindness, patience and fun They will forever be part of my family

Contents

I INTRODUCTION 13

II REVIEW OF LITERATURE 13

2.1 Hepatitis C virus: characteristics 13

Figure 1: Global distribution of genotypes of HCV 14

2.2 HIV co-infected with HCV 14

2.2 Epidemiology and burden of disease 15

Figure 2: Best estimates of prevalence of hepatitis C virus (HCV) co-infection in four population samples 16

2.3 Prevention of hepatitis C and HIV 16

2.3 Clinical evolution of a hepatitis infection 16

2.4 Treatment of hepatitis C 16

2.5 Quality of Life 16

2.5.1 Generalities regarding QoL 16

2.5.2 QoL in hepatitis patients 17

2.6 Hepatitis C in Viet Nam 18

III RESEARCH QUESTION AND OBJECTIVES OF STUDY 19

3.1 Research question 19

3.2 Objectives of research 19

3.3 Conceptual framework 19

Figure 3: Conceptual framework of the determinants of the QoL of patients with chronic hepatitis C 20

IV METHODOLOGY 20

4.1 Study design 20

4.2 Study location 20

4.3 Data collection period 21

4.4 Population of study 21

4.5 Sample size 21

4.6 Sources of information 21

4.7 Procedure 22

4.7.1 Translation of the specific QoL instrument 22

4.7.2 Data collection 22

4.8 Data analyses 23

4.9 Ethical considerations 24

V RESULTS 24

5.1 Descriptive analyses 24

Table 1: Socio-demographic characteristics of the participants 25

Table 2: Health-related factor characteristics 26

Table 3: Treatment-related factors 27

Table 4: Social support and lowest CD4 in HIV group 27

Table 5: Score of Chronic Hepatitis Disease Questionnaire 27

Table 6: Score of the 36-Item Short Form Health Survey (SF-36) 28

5.2 Bivariate analyses 28

5.2.1 Chronic Liver Disease Questionnaire (CLDQ) 28

Table 7: Association between the total score of Chronic Liver Disease Questionnaire and

independent variables 29

5.2.2 SF-36 Physical Component Summary (PCS) 30

Table 8: Association between the SF-36 PCS score and potential independent variables 30

5.2.3 SF-36 Mental Component Summary (MCS) 31

Table 9: Association between the total SF-36 MCS score and independent variables 31

5.2.4 SF-36 General Health (GH) Dimension 32

Table 10: Association between the SF-36 GH score and potential independent variables 33

5.2.5 SF-36 Physical Functioning (PF) Dimension 33

Table 11: Association between the SF-36 PF score and independent variables 34

5.2.6 SF-36 Role Physical (RP) Dimension 35

Table 12: Association between the SF-36 RP score and independent variables 35

5.2.7 SF-36 Bodily Pain Dimension (BP) 37

Table 13: Association between the SF-36 BP score and independent variables 37

5.2.8 SF-36 Vitality Dimension (VT) 38

Table 14: Association between the SF-36 VT score and potential independent variables 39

5.2.9 SF-36 Social Functioning Dimension (SF) 39

Table 15: Association between the SF-36 SF score and independent variables 40

5.2.10 SF-36 Role Emotional Dimension (RE) 41

Table 16: Association between SF-36 RE and independent variables 42

5.2.11 SF-36 Mental Health Dimension (MH) 43

Table 17: Association between the SF-36 MH score and independent variables 43

5.3 Multivariate analyses 45

5.3.1 Chronic Liver Disease Questionnaire (CLDQ) 45

Table 18: Multivariate analysis of factors associated with CLDQ 45

Logistic regression 45

5.3.2 SF-36 Physical Component Summary (PCS) 46

Table 19: Multivariate analysis of factors associated with PCS 46

Linear regression 46

5.3.3 SF-36 Mental Component Summary (MCS) 47

Table 20: Multivariate analysis of factors associated with MCS 47

5.3.4 SF-36 General Health Dimension (GH) 48

Table 21: Multivariate analysis of factors associated with GH 48

5.3.5 SF-36 Physical Function Dimension (PF) 49

Table 22: Multivariate analysis of factors associated with PF 49

5.3.6 SF-36 Role Physical Dimension (RP) 49

Table 23: Multivariate analysis of factors associated with RP 50

5.3.7 SF-36 Bodily Pain Dimension (BP) 50

Table 24: Multivariate analysis of factors associated with BP 51

5.3.8 SF-36 Vitality Dimension (VT) 51

Table 28: Multivariate analysis of factors associated with MH 55

Table 29: Summary of association between factors and QoL in final models 56

VI DISCUSSION 57

VII LIMITATIONS 59

VIII RECOMMENDATIONS 59

ANNEXES 64

Annexe 1: non-commercial license agreement of SF-36 64

Annex 2: English version informed consent form 65

Annex 3: Vietnamese version informed consent form 66

Annex 4: total english version of questions 67

Annex 5: Vietnameses version of total questions 80

LIST OF TABLES Table 1: Socio-demographic characteristics of the participants 25

Table 2: Health-related factor characteristics 26

Table 3: Treatment-related factors 27

Table 4: Social support and lowest CD4 in HIV group 27

Table 5: Score of Chronic Hepatitis Disease Questionnaire 27

Table 6: Score of the 36-Item Short Form Health Survey (SF-36) 28

Table 7: Association between the total score of Chronic Liver Disease Questionnaire and independent variables 29

Table 8: Association between the SF-36 PCS score and potential independent variables 30

Table 9: Association between the total SF-36 MCS score and independent variables 31

Table 10: Association between the SF-36 GH score and potential independent variables 33

Table 11: Association between the SF-36 PF score and independent variables 34

Table 12: Association between the SF-36 RP score and independent variables 35

Table 13: Association between the SF-36 BP score and independent variables 37

Table 14: Association between the SF-36 VT score and potential independent variables 39

Table 15: Association between the SF-36 SF score and independent variables 40

Table 16: Association between SF-36 RE and independent variables 42

Table 17: Association between the SF-36 MH score and independent variables 43

Table 18: Multivariate analysis of factors associated with CLDQ 45

Table 19: Multivariate analysis of factors associated with PCS 46

Table 20: Multivariate analysis of factors associated with MCS 47

Table 21: Multivariate analysis of factors associated with GH 48

Table 22: Multivariate analysis of factors associated with PF 49

Table 23: Multivariate analysis of factors associated with RP 50

Table 24: Multivariate analysis of factors associated with BP 51

Table 25: Multivariate analysis of factors associated with VT 52

Table 26: Multivariate analysis of factors associated with SF 53

Table 27: Multivariate analysis of factors associated with RE 54

Table 28: Multivariate analysis of factors associated with MH 55

Table 29: Summary of association between factors and QoL in final models 56

LIST OF FIGURES

Figure 1: Global distribution of genotypes of HCV 14Figure 2:Best estimates of prevalence of hepatitis C virus (HCV) co-infection in four population samples 16Figure 3: Conceptual framework of the determinants of the QoL of patients with chronic

hepatitis C 20

ABBREVIATIONS

QoL: Quality of life

HCV: Hepatitis C virus

CLDQ: Chronic Liver Disease Questionnaire

SF-36: Medical Outcome Study Short Form 36-Item Health Survey

HIV: Human Immunodeficiency Virus

CD4: Cluster Difference 4

RNA: ribonucleic acid

ALT: alanine aminotransferase

ART: antiretroviral therapies

PWID: people who inject drugs

WHO: World Health Organization

HQLQ: Hepatitis Quality of Life Questionnaire

LDQOL: The liver disease Quality of Life Questionnaire

LDSI: Liver Disease Symptom Index

IDUs: injecting drug users

DAAs: Direct-acting antivirals

MoH: Ministry of Health

TM: trademark

PCS: Physical Component Summary

MCS: Mental Component Summary

Factors associated with the Quality of Life of patients with chronic hepatitis C in Viet Tiep

Hospital, Hai Phong City, Viet Nam

Abstract

Problem: improving the quality of life (QoL) of patients with chronic hepatitis C is a

fundamental objective of healthcare Nothing is known about this topic in Viet Nam

Objective: The aim of this research is to evaluate the QoL of patients with chronic hepatitis C,

and some of its determinants

Material and Methods: A cross-sectional study was conducted on a sample of 128 HCV

patients Two questionnaires were used to measure QoL: SF-36 and the Chronic Liver Disease Questionnaire Multiple regressions were performed to identify potential determinants of the QoL

Results: Liver condition; gender; age; and a diagnosis done more than 3 years ago were found to

negatively affect QoL In contrast, having enough financial resources; having a higher level of education; being aware of the possible outcomes of the disease; being treated for hepatitis and receiving new generation drugs affect positively the QoL

Conclusion: improving QoL of patients with chronic hepatitis C is feasible Making patients

more knowledgeable about hepatitis C and prioritizing access to new generation anti-HCV drugs are key means for this improvement

Keywords: quality of life, hepatitis C virus, SF-36, Chronic Liver Disease Questionnaire (CLDQ), Viet Nam

Facteurs associés à la qualité de vie des patients atteints d'hépatite chronique C au Viet

Tiep Hôpital, Hai Phong, Viet Nam

Résumé

Problématiques: L’amélioration de la qualité de vie (QV) des patients atteints d'hépatite virale

chronique C (HVC) représente un objectif fondamental des soins dispensés à ces patients Peu de données sont disponibles sur ce sujet au Viet Nam

Objectif: Cette étude vise à évaluer la qualité de vie des patients atteints d'hépatite C chronique,

et de ses déterminants

Matériel et méthodes: Une étude transversale a été réalisée sur un échantillon de 128 patients

atteints de HVC Deux questionnaires ont été utilisés pour la mesure de la qualité de vie: le

SF-36 et le questionnaire sur les maladies hépatiques chronique Des analyses de régression multiple ont été réalisées pour identifier les déterminants potentiels de la qualité de vie

Résultats: L’état du foie; le sexe; l'âge et un diagnostic connu depuis plus de 3 ans ont

négativement affectés la QV des patients En revanche, avoir suffisamment de ressources financières; ayant un niveau d'éducation élevé; être au courant des conséquences possibles de la maladie; être traités et recevant des médicaments de nouvelle génération contre l’hépatite C ont

eu un effet positif sur la qualité de vie

Conclusion: l'amélioration de la qualité de vie des patients atteints d'hépatite chronique C est

possible Une amélioration de la connaissance sur l'hépatite C et à l'accès aux médicaments anti-VHC de nouvelle génération représentent des moyens clés pour améliorer leur qualité de vie

Mots-clés: qualité de vie, virus de l'hépatite C, SF-36, Questionnaire sur les maladies hépatiques chroniques (CLDQ), Viet Nam

Những yếu tố liên quan đến chất lượng cuộc sống của bệnh nhân viêm gan C mạn tính ở

bệnh viện Việt Tiệp, Hải Phòng, Việt Nam

Tóm tắt

Vấn đề: cải thiện chất lượng cuộc sống của bệnh nhân viêm gan C mạn tính là mục tiêu cơ bản

của điều trị Chưa có thông tin cụ thể về chủ đề này ở Việt Nam

Mục tiêu: Mục tiêu của nghiên cứu này là lượng giá chất lượng cuộc sống của bệnh nhân viêm

gan C mạn tính và những yếu tố của nó

Phương pháp và công cụ: Nghiên cứu cắt ngang đã được tiến hành trên mẫu 128 bệnh nhân

viêm gan C Hai bảng câu hỏi đã được sử dụng để tính chất lượng cuộc sống: SF-36 và bảng câu hỏi bệnh viêm gan mạn Hồi quy đa biến được sử dụng để xác định các yếu tố có khả năng quyết định chất lượng cuộc sống

Kết quả: Tình trạng lá gan; giới tính; tuổi và được chẩn đoán hơn 3 năm đã được xác định tác

động âm tính tới chất lượng cuộc sống Ngược lại, có đủ nguồn lực tài chính; giáo dục tốt hơn; biết về các hậu quả của bệnh; điều trị và điều trị bằng thế hệ thuốc mới tác động dương tính lên chất lượng cuộc sống

Kết luận: cải thiện chất lượng cuộc sống của bệnh nhân viêm gan C mạn tính là khả thi Làm

tăng sự hiểu biết của bệnh nhân về viêm gan C và ưu tiên tiếp cận với thuốc điều trị mới là chìa khóa

Từ khóa: Chất lượng cuộc sống, viêm gan virus C, SF-36, bảng câu hỏi viêm gan mạn, Viet Nam

No study has been done in Viet Nam on the QoL in hepatitis C patients Therefore, we do not know how to complement medical treatment with interventions that might improve the QoL

of HCV affected patients

II REVIEW OF LITERATURE

2.1 Hepatitis C virus: characteristics

HCV is a small enveloped RNA virus belonging to the family Flaviviridae and genus hepacivirus HCV genomic RNA is single-stranded with positive polarity, which is

packaged by core protein and enveloped by a lipid bilayer containing two viral glycoproteins (E1 and E2) to form the virion (1) Despite the nucleotide sequence divergence among genotypes, all currently recognized HCV genotypes are hepatotropic and pathogenic

The distribution of HCV genotypes and sub genotypes varies substantially in different parts

of the world (Figure 1) According to a recent review, genotype 1 is the most common, accounting for 46.2% of all HCV infections, followed by genotype 3 (30.1%) The diversity of genotypes also varies; the highest diversity is observed in China and Southeast Asia, while in some countries, such as Egypt and Mongolia, almost all HCV infections are due to a single genotype (2)

Figure 1: Global distribution of genotypes of HCV

The purpose of diagnosis of viral infection is to allow infected persons to be identified and treated Thus, diagnosis of viral infection is important to prevent disease progression and viral spread The majority of primary HCV-infected patients are asymptomatic Thus, symptoms cannot be used as specific indicators of HCV infection HCV viremia can still exist despite a normal serum alanine aminotransferase (ALT) level Therefore, virological methods, rather than ALT levels are used to diagnose HCV infection(3)

2.2 HIV co-infected with HCV

HIV is a member of the genus Lentivirus, part of the family Retroviridae There are two types: HIV-1 and HIV-2 HIV-1 is the virus that was initially discovered It is more virulent, more infective(4), and is the cause of the majority of HIV infections globally The lower infectivity of HIV-2 implies that fewer of those exposed to HIV-2 will be infected per exposure Due to its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa (5)

It is roughly spherical with a diameter of about 120 nm, around 60 times smaller than a red blood cell It is composed of two copies of positive single-stranded RNA that codes for the virus's nine genes enclosed by a conical capsid composed of 2 000 copies of the viral protein p24 (6) The single-stranded RNA is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease

living with HIV without treatment are less likely to spontaneously clear HCV infection, have higher HCV viral loads, and experience more rapid HCV disease progression than those without HIV infection (9) Although ART improves outcomes in HCV co-infected patients, with decreased HCV-related mortality(10), HCV co-infection might also complicate HIV treatment, with some evidence suggesting an increased risk of drug related hepatoxicity in those receiving ART.12 There is an absence of consistent data regarding the effect of HCV co-infection on HIV progression (8,10,11)

2.2 Epidemiology and burden of disease

HIV and hepatitis C virus (HCV) infection are major global public health concerns, with overlapping modes of transmission and affected populations Globally, the HIV population is estimated at about 36.7 million, with 2.1 million new cases every year, and 1.6 million deaths (12) Despite the fact that these cases have decreased since 2001 as a result of improved antiretroviral therapies (ART), there are more people living with HIV than before (13) HCV patients were calculated at more than 3 times HIV individuals at around 115 million worldwide

in 2014 (14) HCV treatment has developed rapidly recently with the appearance of direct-acting antivirals, which provide better treatment with higher cure rates for chronic HCV patients (15) However, the number of patients who can access this therapy is tiny due to its costs, particularly

in developing countries such as Viet Nam

Globally, HCV co-infected with HIV population is estimated at 2 278 400 cases (10) This gives a global prevalence of HCV co-infection in HIV-infected individuals of 6.2% (3.4–11.9) Eastern Europe and central Asia has the largest burden, representing 27% of the total There are 5.8 times (95% CI 4.5–7.5) increased odds of HCV antibody positivity in HIV-positive people compared with HIV-negative people, but with high heterogeneity (I² 95·7%, p<0·001) Hepatitis

C virus (HCV) infection, which is a major public health problem globally(16) is frequently observed in HIV-infected individuals and has emerged as a leading cause of morbidity and mortality in this population (17)

HCV co-infected with HIV affects 6.4% of the population of men who have sex with men Prevalence was highest in North America and lowest in East Asia and South and Southeast Asia (figure 1) (10) HCV co-infected with HIV constitutes 4% of HIV heterosexual exposure among pregnant women Highest prevalence is in West and Central Africa and lowest in Southern Africa (Figure 1) (10)

Figure 2: Best estimates of prevalence of hepatitis C virus (HCV) co-infection in four

population samples

Around 60% of HCV co-infected with HIV individuals are PWID, equal to 1.36 million cases It affected 82·4% (55·2–88·5) of people who inject drugs The highest prevalence was in North Africa and the Middle East and lowest was in Western and Central Europe (Figure 2) There was a clear association between the prevalence of self-reported injected drug use and HIV/HCV co-infection prevalence (correlation coefficient 0·89, p<0.01) (10)

2.3 Prevention of hepatitis C and HIV

2.3 Clinical evolution of a hepatitis infection

2.4 Treatment of hepatitis C

2.5 Quality of Life

2.5.1 Generalities regarding QoL

Definition by WHO: Quality of life is defined as the individuals' perceptions of their

position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns

Health-related QoL, or QoL, is a multi-dimensional concept The general basis of the concept is the definition of health by WHO There are physical, mental and social dimensions to the concept of QoL People are considered to have a good QoL if they have no physical, mental

problem, that for example, affects the capacity to have a sexual relationship, such as diabetes, will probably have an additional dimension to this aspect

Societies might consider differently some items For example, home chores for men might

be considered as a physical activity in some societies were males and females share equally home tasks, while it might be a societal item where men have a tendency to contribute little to housework

QoL if children can be strongly influenced by how a child is able to attend a regular school and be accepted by other children A dimension in school integration might be then considered in

a QoL instrument specific for children

The nature of QoL is therefore subjective and multidimensional It refers to a subjective evaluation of a state of well-being which is embedded in a cultural, social and environmental context Because it focuses of the perception of a state of well-being, it cannot be described simply through health status, symptoms or mental status It requires a multidimensional assessment, which incorporates the individual’s perception of his/her health status and the mental-social condition that affects his/her life

2.5.2 QoL in hepatitis patients

Several instruments have been used to estimate the QoL of patients with hepatitis Instruments can be generic or specific Generic QoL questionnaires as a rule can be applied to various conditions and various populations This has some advantages: scoring can be compared with scoring of other patient populations or with a healthy reference population A potential weakness of using a generic instrument is that they are not designed to identify disease-specific domains that may be important to establish and track clinical changes (18) Among the most common generic instruments used around the world, we can cite the Medical Outcome Study Short Form 36 (SF36) (19) SF-36 has a multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions

Disease – specific questionnaires have the advantage of offering greater sensitivity and specificity Four disease-specific QoL questionnaires have been proposed for chronic hepatitis patients: the Hepatitis Quality of Life Questionnaire (HQLQ) (20), the Chronic Liver Disease Questionnaire (CLDQ) (21), the Liver Disease Quality Of Life Questionnaire (LDQOL) (22) and the Liver Disease Symptom Index 2.0 (LDSI 2.0) (23)

QoL in acute hepatitis

The literature shows that HCV positive individuals have a reduced QoL in comparison to healthy controls or the general population (24) In a meta-analysis of 15 studies using SF36 to assess the QoL of patients with chronic Hepatitis C, patients with chronic HCV infection had a

median decrease of 9-20 points (weighted mean decrease: 7-16 points) compared to controls (25) HCV infection significantly impacted the mental health dimension, with a decrease of 10–

12 points in the mental health scores (mean decrease: 7–13 points) (25)

The deterioration in QoL in patients with HCV has been shown to be even or more severe than the decrease in the physical and general health dimensions of patients suffering from other chronic diseases such as hypertension, diabetes, arthritis or depression (20,26,27) HCV has been shown to have more impact on the physical dimension than hepatitis B mono-infection HCV has been shown to reduce the QoL on mental health more than other chronic conditions (28)

These results have been attributed to a complex multifactorial cause (24) Foster et al (1998) reported that the reduced QoL in patients with HCV could not be attributed to either the degree

of liver disease, or the association with a history of injected drug use They concluded that it was due mainly to HCV itself (29) Bronkovsky et al (1999) subsequently reported data from a large multi-centre drug trial which supported this hypothesis They showed that HCV infection reduces the QoL independently of the presence of comorbidities One of the factors found was the viral replication within the central nervous system (30)

Other factors found to affect the QoL of HCV patients are related to the host Illicit substance use has an important role in QoL, giving the high incidence of current or former substance users within this patient population (31) Injecting drug users have a lower QoL irrespective of their HCV status (32) Indeed, it has been shown that patients who acquired HCV through injected drug have lower QoL than patients who acquired it by another route such as sex

or mother-to-child route (29,33) Awareness of patient’s HCV status also seems to reduce the QoL of HCV population (34,35) In addition to these factors, other comorbidities, psychiatric or physical, have been implicated in the reduction of the QoL among HCV patients

Stigma could also be an important factor, which affects the QoL of HCV patients probably because it affects negatively their social status and self- image (35)

The decrease of QoL in HCV patients occurs even without cirrhosis or significant liver disease, and it is not associated with Alanine Aminotransferase (ALT) levels (29,36) Without treatment, the QoL of the HCV patient is significantly reduced This has been related, among others, to additional factors, as the sense of economic costs to the society, through a loss of productivity, increased absenteeism from work and increased use of healthcare resources (37)

2.6 Hepatitis C in Viet Nam

Viet Nam has one of the highest prevalence of HCV in the world HCV prevalence is estimated

HCV infection is a major public health problem in Viet Nam Despite efforts to control HCV infection, the access to anti-HCV treatment is still a huge challenge in the country The first national recommendations for HCV care were issued in 2014 and an updated version was published in September 2016 In this new version, oral short-duration regimens using direct acting antivirals (DAAs) were suggested Peg-Interferon based treatments are only mentioned as

an alternative Currently, generic treatment with Sofosbuvir, Sofosbuvir/Ledipasvir and Daclatasvir from India and Elbasvir/Grazoprevir from the United States, are available in Viet Nam

Above all, only a small proportion of the population benefits from national health insurance And for those, the cost of drugs remains generally high Effectively, although the Ministry of Health (MoH) added HCV to the list of diseases covered by the national health insurance scheme, there

is still limited reimbursement for the drugs (below 30% for Peg-Interferon/Ribavirine and no reimbursement for DAAs) As a result, only a few thousand wealthy people have access to treatment in private or public facilities

III RESEARCH QUESTION AND OBJECTIVES OF STUDY

b) Specific objective

More specifically, we wanted:

 To determine the QoL of chronic hepatitis C patients, with the use of 2 questionnaires; one specific in order to have a global score on QoL, and one generic with which we could analyze specific basic dimensions

 To determine factors associated with the QoL of the patients

3.3 Conceptual framework

Based on a review of literature, we built a conceptual framework for the questionnaire that was used in this study (annex 3,4) It is proposed that QoL is associated with four main factors: health-related, socio-demographic, treatment-related and environmental factor (figure 3)

IV METHODOLOGY

4.1 Study design

A cross-sectional study was performed

4.2 Study location

Hai Phong is situated 102 km east of Hanoi and 20 km from the sea It is one of the major

ports of the country and is well connected, not only to the rest of the country, but also

internationally thanks to its widespread and effective national, regional and international

QoL

Health-related factors

Co-morbidity with

non-infectious chronic disease

Age Sex Marital status Occupation Income Education level

Environmental factors

Data collection took place at the HIV Outpatient Clinic and the Hepatitis Outpatient Clinic

in the Department of Infectious Diseases of Viet Tiep Hospital, in Hai Phong, Viet Nam

4.3 Data collection period

Data collection took place from 20 March – 02 June 2017

4.4 Population of study

All consecutive chronic HCV patients who went to Viet Tiep Hospital for examination, treatment or follow-up treatment during the period of collection of data were requested to participate in the study Sample size was increased until the target sample size was reached

To be enrolled in the study, patients had to be more than 18 years of age and be anti-HCV positive for more than six months (42) The positivity was assessed by third-generation enzyme-linked immune sorbent assay Moreover, the diagnosis had to be confirmed and a viral load measurement had to be performed

To be enrolled, patients had to be literate and able to understand the questions and answer them They also had to be willing to participate in the study

4.5 Sample size

The calculation of the sample size was based on the planned final analyses, which are multiple regressions We used a rule of thumb for logistic regression which states that the sample size is n = 5 k/p, where k is the number of covariates to be introduced in the initial model and p

is the smallest proportion of one of the two dependent variables categories (43)

The conceptual framework (figure 3) allowed us to predict that 8 independent variables (age, sex, marital status, perception of economic status, liver condition, receiving HCV treatment, lowest CD4 count, duration with HCV) would be included in the initial model As the dependent variables (scores of QoL and CLDQ) would be transformed into a dichotomous variable based

on the mean, p will 0.5 With these parameters (p=0.4 and k=8), the calculated minimum sample size is n=98

4.6 Sources of information

Four questionnaires were used:

1 A generic instrument to measure the QoL is the 36-item Short-Form Health Survey (SF36) The SF36 is a widely used instrument to measure QoL It cannot produce a global QoL score, but allows assessing the QoL in 8 areas: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain dimensions; 5) general mental health; 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general

health perceptions The SF-36 has been validated in Vietnamese (44) RAND HEALTH gave us a free Student Academic Research License to use this instrument

2 A specific QoL instrument for hepatitis was used: the Chronic Liver Disease Questionnaire (CLDQ) This questionnaire was developed in 1999 by Boparai It includes 29 items in the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry It is short, easy to administer, produces both summary score and domain scores, and correlates with the severity of liver diseases CLDQ has not been validated into Vietnamese In our study, due to limitation in time, we only considered the total score produced with this instrument

3 A questionnaire to collect basic social demographic data

4 A questionnaire whose questions are based on the conceptual framework of the study, to collect data on potential factors associated with the QoL in patients with chronic hepatitis C

4.7 Procedure

4.7.1 Translation of the specific QoL instrument

The English version of the Chronic Liver Disease Questionnaire (CLDQ) was translated independently into Vietnamese by two persons who were not involved in the study Thereafter, the two translators compared their translations Any discrepancy was discussed and a consensus was reached This consensual version was then translated back into English by a third person This last version was compared with the original Each question that appeared to have been incorrectly translated was revised A working version of the questionnaire in Vietnamese was then produced This version was then presented to 5 patients with HCV, who did not participate

in the study, to get their feedback regarding the comprehensiveness of the questions, their clarity and absence of ambiguity

4.7.2 Data collection

Two researchers collected data in the HIV Outpatient Department and Hepatitis Outpatient Department simultaneously All consecutive patients who came to these clinics for a follow-up and treatment were asked to participate in the study

The researcher explained to the patients why this research was being conducted and gave them information sheets He answered all their questions regarding the study If the patients agreed to participate, they were asked to sign an informed consent form Patients then had to fill

We noted that at the analyses of the SF-36 data by the QualiMetric Health Outcome (TM) Scoring Software 5.0 that was performed always immediately after the questionnaires had been completed, 8 individuals had provided inconsistent answers These patients were dropped from the research

All information was collected on the same day that patients were enrolled The sample size was increased until the sample size was reached

4.8 Data analyses

The data of the SF-36 questionnaire were entered into the QualityMetric Health Outcomes (TM) Scoring Software 5.0 which was provided by Quality Metric Health Outcomes(tm) under a free license agreement (Annexe 1) The results were transferred to STATA version 12 for further analyses The other questionnaires were entered into Epi Data 3.1 The data were then transferred

to STATA version 12 Chronic Liver Disease Questionnaire, Social Support and Alcohol Dependency scores were calculated

Descriptive analyses were conducted to describe the study population’s characteristics, health-related factor characteristics, treatment-related factors, social support, duration of disease, biological outcome and the quality of life profile We described categorical variables by numbers and percentages, and continuous variables by means, standard deviations, minimum and maximum

The outcomes of interest in our analyses were: the total score of Chronic Liver Disease Questionnaire, and the scores of the following SF-36 dimensions: Physical Component Summary, Mental Component Summary, Physical Function, Role Physical, Bodily Pain, Social Functioning, Role Emotional, Mental Health, General Health and Vitality The scores of three dimensions Physical Component Summery, General Health, and Vitality that was used were the continuous score, because their distributions were normal The other SF-36 dimensions had non-normal distributions Their score was therefore dichotomized using the mean as a cut-off point with one exception For the Role Emotional dimensions, the score of 100 was used as the cut-off point because patients mostly had scores of 100

Bivariate analyses were conducted in order to identify the potential independent variables that would be introduced in initial model of multivariate analyses The independent variables are all potential factors related to quality of life in these patients These variables were initially examined using bivariate analyses Logistic regression or linear regression were used Odd ratio, 95% confidence interval and p-value were presented in the table Only variables with p-value less than 0.25 were included in the multivariate model

Multivariate analyses were conducted in order to determine the factors associated with quality of life in chronic hepatitis C patients (Score of quality of life and low or high quality of life if the score was dichotomized) To determine factors influencing the score of overall quality

of life, linear regressions were used Logistic regressions were used for factors influencing the level of quality of life (dichotomized score) Following the initial model, which included eligible

independent variables from bivariate analyses, the collinearity of independent variables was checked out Then, a stepwise backward process was conducted in removing one by one variables with p-values less than 0.05 The final model included only independent variables with p-value less than 0.05 The results of the final model were presented in table with OR or

coefficients, 95% confident intervals and p-values We also summarized the output of the final

model of each scale of quality of life in order to compare which factor was related to which scale

4.9 Ethical considerations

The protocol was accepted by Ethics Committee of Viet Tiep Hospital

The questionnaire was explained to participants, who were asked to sign a consent form (annex 2) indicating voluntary participation in the research project They could withdraw from the study at any time without penalty, without affecting the healthcare they would receive, or impairing their relationship with healthcare team All study data was collected and stored in a secure place and not shared with any other person without their permission

V RESULTS

5.1 Descriptive analyses

Table 1 presents the socio-demographic characteristics of the participants It shows that males constituted the vast majority of the sample The table also shows that the majority of participants were rather young, under the age of 45 years (mean 45.7, with a 25-82 range) Nearly two-thirds lived with a partner Half had a rather low level of education and half a steady occupation Half also considered themselves as not having enough financial resources to pay for their healthcare needs

Table 1: Socio-demographic characteristics of the participants

Perception of economic status

Table 2 presents the health-related factors of the participants It shows the sample is equally distributed over the different stages of liver damage

Table 2: Health-related factor characteristics

Co-morbidity with a non-infectious chronic

Table 3: Treatment-related factors

Sustained virologic response (SVR) after

Table 4: Social support and lowest CD4 in HIV group

Table 5 presents the scores (total and by dimension) of the specific chronic hepatitis quality

of life instrument It shows an average total score of 149.5±30.4 with the range from 59 to 195, denoting variability in the sample, which is also found in the dimensions of the quality of life

Table 5: Score of Chronic Hepatitis Disease Questionnaire

Table 6 shows the scores of the SF-36 dimensions, the generic quality of life instrument Here too, a variability of scores can be seen for all the dimensions

Table 6: Score of the 36-Item Short Form Health Survey (SF-36)

5.2 Bivariate analyses

5.2.1 Chronic Liver Disease Questionnaire (CLDQ)

The association between potential independent variables and the Chronic Liver Disease Questionnaire score was analyzed with the use of the Likelihood-ratio test Table 7 shows that six variables had a statistically significant association with the dependent variable: age, gender, education, perception of economic status, awareness of HCV outcomes, time of HCV diagnosis and liver condition

Feelings of having enough money and having a higher education level were positively correlated with the CLDQ QoL score, while age, gender, time of HCV diagnosis and having a liver condition were negatively correlated

Table 7: Association between the total score of Chronic Liver Disease Questionnaire and independent variables

Variables

Dichotomized total score of CLDQ

N (%)

Higher QoL (> mean score) (%)

Illiterate to secondary school 73 (57%) 35 (50%)

High school to university 55 (43%) 35 (50%) 1.9 0.92-3.88 0.079

Profession

Stable, retired, housewife or at school 70 (55%) 41 (59%)

Unstable/ unemployed 58 (45%) 29 (41%) 0.7 0.35-1.4 0.333

Perception of economic status

Not enough for my healthcare needs 66 (52%) 22 (31%)

Enough or more for my healthcare

Other drug (>12weeks) 11 (22%) 6 (19%)

Direct-acting antivirals (<12 weeks) 40 (78%) 26 (81%) 1.5 0.4-5.9 0.527

Lowest CD4 (500-1200)

Equal or less than 125.7 45 (35%) 26 (37%)

5.2.2 SF-36 Physical Component Summary (PCS)

The association between potential independent variables and the Physical Component Summary score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 8 shows that five variables had a statistically significant association with the dependent variable: age, perception of economic status, co-morbidity with a non-infectious chronic disease and liver condition

Feelings of having enough money were positively correlated with the QoL in the physical dimension, while age, having a comorbidity and having a liver condition was negatively correlated

Table 8: Association between the SF-36 PCS score and potential independent variables

Awareness of HCV outcomes : Cirrhosis or

5.2.3 SF-36 Mental Component Summary (MCS)

The association between potential independent variables and the Mental Component Summary score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 9 shows that five variables had a statistically significant association with the dependent variable: age, gender, perception of economic status, liver condition and time of HCV diagnosis

Feelings of having enough money was positively correlated with the Mental Component Summary dimension of QOL, while age, being female, having a liver in an advanced diseased condition and more than 3 years since HCV diagnosis were negatively correlated

Table 9: Association between the total SF-36 MCS score and independent variables

Variables

Dichotomized total score of MCS

N (%)

Higher QoL (> mean score) (%)

Illiterate to secondary school 73 (57%) 39 (51%)

High school to university 55 (43%) 37 (49%) 1.8 0.86-3.7 0.116

Profession

Stable, retired, housewife or at school 70 (55%) 44 (58%)

Unstable/ unemployed 58 (45%) 32 (42%) 0.72 0.36-1.48 0.379

Perception of economic status

Not enough for my healthcare needs 66 (52%) 28 (37%)

Enough or more for my healthcare

Other drug (>12weeks) 11 (22%) 6 (18%)

Direct-acting antivirals (<12 weeks) 40 (78%) 28 (82%) 1.9 0.5-7.6 0.34

Lowest CD4 (500-1200)

Equal or less than 125.7 45 (35%) 27 (36%)

5.2.4 SF-36 General Health (GH) Dimension

The association between potential independent variables and the General Health score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 10 shows that five variables

Table 10: Association between the SF-36 GH score and potential independent variables

Co-morbidity with a non-infectious chronic

5.2.5 SF-36 Physical Functioning (PF) Dimension

The association between potential independent variables and the Physical Functioning score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 11 shows that five variables had a statistically significant association with the dependent variable: age, gender, perception of economic status, co-morbidity with a non-infectious chronic disease and liver condition

Feelings of having enough money were positively correlated with QoL on the Physical Functioning dimension, while age, being female, having a co-morbidity with a non-infectious chronic disease, having a liver in advanced diseased condition were negatively correlated

Table 11: Association between the SF-36 PF score and independent variables

Variables

Dichotomized total score of PF

N (%)

Higher QoL (> mean score) (%)

Illiterate to secondary school 73 (57%) 48 (55%)

High school to university 55 (43%) 40 (45%) 1.3 0.6-2.9 0.4

Perception of economic status

Not enough for my healthcare

Enough or more for my

Co-morbidity with a

non-infectious chronic disease

5.2.6 SF-36 Role Physical (RP) Dimension

The association between potential independent variables and the Role Physical score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 12 shows that five variables had a statistically significant association with the dependent variable: age, gender, perception of economic status, co-morbidity with a non-infectious chronic disease and liver condition

Feelings of having enough money was positively correlated with the QoL on the Role Physical dimension, while age, being female, having a co-morbidity with a non-infectious chronic disease, having a liver in advanced diseased condition were negatively correlated

Table 12: Association between the SF-36 RP score and independent variables

Variables

Dichotomized total score of RP

N (%)

Higher QoL (> mean score) (%)

Secondary school and higher 119 (93%) 48 (91%) 0.54 0.13-2.1 0.377

Profession

Stable, retired, housewife or at

Perception of economic status

Not enough for my health care

Enough or more for my

Co-morbidity with a

non-infectious chronic disease

5.2.7 SF-36 Bodily Pain Dimension (BP)

The association between potential independent variables and the Bodily Pain score of

SF-36 was analyzed with the use of the Likelihood-ratio test Table 13 shows that five variables had

a statistically significant association with the dependent variable: age, perception of economic status, liver condition, awareness of HCV outcome and time of HCV diagnosis

Feelings of having enough money and knowing HCV outcomes were positively correlated with the QoL on the Bodily Pain dimension, while age, having a liver in advanced diseased condition and having been diagnosed more than 3 years earlier were negatively correlated

Table 13: Association between the SF-36 BP score and independent variables

Variables

Dichotomized total score of BP

N (%)

Higher QoL (> mean score) (%)

Illiterate to secondary school 73 (57%) 31 (54%)

High school to university 55 (43%) 27 (46%) 1.3 0.6-2.6 0.45

Perception of economic status

Not enough for my healthcare needs 66 (52%) 14 (24%)

Enough or more for my healthcare needs 62 (48%) 44 (76%) 9 4-20 0.000

Co-morbidity with a non-infectious

chronic disease

Other drug (>12weeks) 11 (22%) 6 (22%)

Direct-acting antivirals (<12 weeks) 40 (78%) 21 (78%) 0.9 0.24-3.5 0.9

Feelings of having enough money was positively correlated with the QoL on the VT score, while age, having a comorbidity and a liver condition were negatively correlated

Table 14: Association between the SF-36 VT score and potential independent variables

Co-morbidity with a non-infectious chronic

5.2.9 SF-36 Social Functioning Dimension (SF)

The association between potential independent variables and the SF score of SF-36 was analyzed with the use of the Likelihood-ratio test Table 15 shows that five variables had a statistically significant association with the dependent variable: age, gender, perception of economic status, liver condition and time of HCV diagnosis

Feelings of having enough money were positively correlated with the QoL on the Social Functioning dimension, while age, being female, having a liver in advanced diseased condition and having had a diagnosis more than 3 years earlier were negatively correlated

Table 15: Association between the SF-36 SF score and independent variables

Variables

Dichotomized total score of SF

N (%)

Higher QoL (> mean score) (%)

Illiterate to secondary school 73 (57%) 45 (55%)

High school to university 55 (43%) 37 (45%) 1.27 0.6-2.6 0.51

Perception of economic status

Not enough for my healthcare

Co-morbidity with a

non-infectious chronic disease

Liver condition