**2.2.3 Screening for HCC**

As defined in the published guideline (Bruix, Sherman, & Practice Guidelines Committee, 2005), "screening refers to an application of diagnostic tests in patients at risk for HCC, but in whom there is no prior reason to suspect that HCC is present". It states clearly that screening is to detect the presence of HCC among the asymptomatic hepatitis B carriers. The ultimate goal of screening for HCC is to reduce morbidity and mortality (Bruix et al., 2005; Ying, 2009; Yuen & Lai, 2003). That means to detect early preclinical and early HCC that can be cured (resection).

Screening for disease should fulfill certain criteria to be medically and economically acceptable. Wilson's criteria are widely used to judge whether a disease should be screened for and they are shown as follows (Wilson & Jungner, 1968):-


Although there are several published guidelines for HCC screening, there is no consensus regarding screening for HCC (Bruix et al., 2005; Keeffe et al., 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009; Omata et al., 2010). A recent AASLD practice guideline has been published and recommended that HBV carriers at high risk should be screened with ultrasound (US) every 6-12 months and alpha-fetoprotein (AFP) alone if US is not available (A S Lok & McMahon, 2009). Ultrasound and AFP are currently two commonly used screening tests for HCC (A S Lok & McMahon, 2009). High risk group is defined as Asian men aged >40 years old, Asian women aged >50 years old, those with cirrhosis or family history of severe liver disease, with persistent or intermittent ALT elevation and/or high HBV DNA level >2000 IU/mL (A S Lok & McMahon, 2009). On the other hand, the latest Asia-Pacific consensus suggested that only male HBV carriers aged 40 or above with cirrhosis or family history of serious liver disease should be screened with US and AFP every 3-6 months (Y F Liaw et al., 2008). In general, HCC screening should be considered for patients with cirrhosis. However, it remains unclear whether screening for HCC in an asymptomatic population has beneficial outcomes, what is the best screening strategy and whether screening is cost-effective.

#### **2.2.4 Health services for CHB in Hong Kong**

380 Hepatocellular Carcinoma – Basic Research

2009). Increase in creatine kinase levels (a level of >7 times upper limit of normal (ULN)) was more commonly found in patients receiving LdT than LVD (7.5% vs. 3.1%) (Leung, 2008; Y F Liaw et al., 2008). However, it improved spontaneously with continued drug therapy. Cases of reversible myopathy and peripheral neuropathy have been reported (Leung, 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009). Although LdT is more potent than LVD, its high resistance rate and cost limit its use as the first line treatment for CHB (Keeffe et al., 2008;

Tenofovir (TDF) is an oral anti-viral drug and has been approved for the treatment of CHB in 2008 (Ayoub & Keeffe, 2008; A S Lok & McMahon, 2009). It belongs to the same family of nucleotide analogs as ADV (Ayoub & Keeffe, 2008; Keeffe et al., 2008; A S Lok & McMahon, 2009; Zoulim & Perrillo, 2008). It has been shown to be more potent than ADV particularly in early suppression of HBV (Ayoub & Keeffe, 2008; Keeffe et al., 2008; Lai & Yuen, 2008; Leung, 2008; Marcellin et al., 2008). In a phase III clinical trial in HBeAg positive patients, TDF resulted in a significantly higher percentage of patients with undetectable HBV DNA levels compared with ADV (76% vs. 13%) after 48 weeks (Ayoub & Keeffe, 2008; Y F Liaw et al., 2008; Marcellin et al., 2008). No resistance mutations associated with TDF were found at week 48 and 72 (Ayoub & Keeffe, 2008; Keeffe et al., 2008; Lai & Yuen, 2008; Leung, 2008). The incidence of adverse events was similar in TDF and ADV (Ayoub & Keeffe, 2008; Keeffe et al., 2008). The incidence of ALT flares (>2 times baseline values) was higher in patients receiving TDF than those with ADV (11% vs. 4%) (Keeffe et al., 2008). Studies are still

As defined in the published guideline (Bruix, Sherman, & Practice Guidelines Committee, 2005), "screening refers to an application of diagnostic tests in patients at risk for HCC, but in whom there is no prior reason to suspect that HCC is present". It states clearly that screening is to detect the presence of HCC among the asymptomatic hepatitis B carriers. The ultimate goal of screening for HCC is to reduce morbidity and mortality (Bruix et al., 2005; Ying, 2009; Yuen & Lai, 2003). That means to detect early preclinical and early HCC that can

Screening for disease should fulfill certain criteria to be medically and economically acceptable. Wilson's criteria are widely used to judge whether a disease should be screened

ix. The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole;

ii. There should be an accepted treatment for patients with the recognized disease;

x. Case-finding should be a continuing process and not a once and for all project.

vii. The natural history of the condition should be adequately understood; viii. There should be an agreed policy on whom to treat as patients;

for and they are shown as follows (Wilson & Jungner, 1968):-

iii. Facilities for diagnosis and treatment should be available; iv. There should be a latent or early symptomatic stage; v. There should be a suitable test or examination; vi. The test should be acceptable to the population;

i. The condition sought should be an important health problem;

Leung, 2008; Y F Liaw et al., 2008; Zoulim & Perrillo, 2008).

ongoing for long-term efficacy and safety.

**2.2.3 Screening for HCC** 

be cured (resection).

The Hong Kong Government provides healthcare service to patients with HBV infection, but resources are limited and management has to be prioritized according to the severity of the illness. For patients found to be CHB carriers, the frequency of monitoring and types of laboratory tests differed by the severity of their diseases.

In Hong Kong, lamivudine (LVD), adefovir (ADV) and entecavir (ETV) are the standard antiviral drugs used for the treatment of CHB (Fung et al., 2008). Interferons are of doubtful use for Chinese patients (Fung et al., 2008). Telbivudine (LdT) is seldom used because of its cost and high resistance rate (Fung et al., 2008; Zoulim & Perrillo, 2008). The long-term effect of tenofovir (TDF) is unknown (Keeffe et al., 2008; Lai & Yuen, 2008; Y F Liaw et al., 2008).

Anti-viral drugs are expensive and the government provides subsidy for patients with cirrhosis and HCC only in public service. Most CHB patients with impaired liver function (ILF) need to pay for their full drug cost and HBV DNA assay. The costs of anti-viral treatment range from HKD 1,000 to HKD 3,000 per month depending on the drug choice (Yeo B, 2008). Patients' willingness to pay may influence treatment options which also affects the duration of treatment, effectiveness, drug resistance and side effects. Many patients cannot afford or are not willing to pay for treatment even though it is recommended by physicians. There is no policy on hepatitis B screening (Hong Kong (China). Dept. of Health., 1998), which is not routinely provided by the public service.

Free printed information on hepatitis is available from the Department of Health to educate the public about the prevention of spread of the disease, indication for treatment and treatment options (Department of Health). Primary care doctors or specialists can easily distribute these printed information to their patients during the consultation but this not often done because time is limited and the evaluation of disease pathology and its complication take top priority.

Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB) 383

that physical functioning and mental health were important indicators of both outpatient visits and hospitalization for patients with chronic disease after controlling for confounding variables (Nelson 1998). Another study by Mulunpalo et al showed that a significant linear relationship between HRQOL and outpatient physician visits for working-age population in Finland (Mulunpalo 1997). Furthermore, Dominick et al pointed out that HRQOL can be valuable tools for predicting future health care for older patients with osteoarthritis (Dominick 2004). Poorer general health was correlated with increased likelihood of analgesic or anti-inflammatory use (Dominick 2004). Poor mental health was associated with

There were several studies on the association between HRQOL and service utilization for Asian population (T. Chen & Li, 2009; C. L. K. Lam & Fong, 2002; Matsumura, 2000). A study by Matsumura in Japan found that subjects with Short Form-36 (SF-36) physical component summary (PCS) score below 40 were more likely to use outpatient services and to be hospitalized than those who had scores greater than 50 (Matsumura 2000). Subjects with both SF-36 physical and mental component summary scores below 40 were more likely to have taken sick leave than those who had scores greater than 50 (Matsumura, 2000). A large study in Hong Kong showed that a linear relationship between HRQOL and service utilization in the local Chinese population (C. L. K. Lam & Fong, 2002). Five out of eight SF-36 scores were independent determinants of consultation rates (C. L. K. Lam & Fong, 2002). Role limitation due to physical problem and bodily pain were associated with

A recent study assessing the effect of HRQOL on service utilization was conducted in 737 primary care patients in Mainland China (Chen 20009). Lower HRQOL scores were correlated with higher service utilization rates (Chen 20009). Three out of eight SF-36 scales

Numerous studies reported on the relationship between HRQOL and service utilization for Western and Asian populations (T. Chen & Li, 2009; Dominick & Ahern, 2004; Ethgen & Kahler, 2002; C. L. K. Lam & Fong, 2002; Matsumura, 2000; Nelson & McHorney, 1998; Parkerson & Gutman, 2000; Singh & Nelson, 2005), but no data were available for CHB patients. More studies are needed to explore the effect of HRQOL on service utilization in

**2.3 Health-related Quality of Life (HRQOL) as a health outcome measure for Chronic** 

The goal of healthcare is to maintain, restore and improve health of patients. Traditionally, clinicians have focused primarily on 'hard' clinical outcomes, for instance, patient's mortality and morbidity (Eisen, Locke, & Provenzale, 1999). Clinicians are more likely to judge the effectiveness or efficacy of a therapy in terms of survival rate, biochemical parameters such as liver function, viral markers, and symptoms (Eisen et al., 1999). Traditional clinical outcomes (i.e. morbidity and mortality) are important but they do not adequately reflect patients' perceived health, feelings and the impact of illness on life. Health-related quality of life (HRQOL) can provide additional information on the

were associated with both inpatient and outpatient consultation (Chen 20009).

increased likelihood of analgesic or anti-inflammatory use (Dominick 2004).

hospitalization (C. L. K. Lam & Fong, 2002).

patients with CHB.

**Hepatitis B (CHB) patients** 

effectiveness and quality of care.

#### a. Management of Asymptomatic Hepatitis B (AHB) carriers

Most infected individuals are asymptomatic and CHB is usually diagnosed incidentally during blood donation, health assessment or when they develop liver complications such as cirrhosis or HCC. Asymptomatic hepatitis B (AHB) carriers may be followed-up yearly at General Outpatient Clinic (GOPC) or private primary care doctors with liver function test (LFT) and alpha fetoprotein (AFP) but many are not. According to a local study in a primary care setting, most of HBV carriers did not attend GOPC for following up of their disease (Kung, Lam, & Li, 2004). Furthermore, there were large variations in follow-up period and test intervals (Kung et al., 2004). It ranges from 1 to 14 months for follow-up, 2 to 36 for blood tests, and 6 to 60 months for ultrasound (Kung et al., 2004). One month follow-up may be given to those who were very anxious about their condition (Kung et al., 2004). Since they are asymptomatic population, they do not need to take anti-viral treatment unless liver-related complications developed (European Association For the study of the liver, 2008; Keeffe et al., 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009). Both HCC screening and HBV DNA assay are not available for AHB carriers. AHB carriers are at risk of developing cirrhosis or HCC but screening is rarely done for these patients (Yuen et al., 2005).

b. Management of patients with Impaired Liver Function (ILF)

Patients with ILF usually have close monitoring and follow-up at Specialist Outpatient Clinics (SOPC) with LFT and AFP tests regularly. The frequency of follow-up contact may vary. It is determined by a combination of variables: results of LFT, degree of viral replication, and need of anti-viral drug. Patients with ILF who receive drug treatment often need to pay for their drug costs and HBV DNA assay. Screening for HCC is not available for patients with ILF.

c. Management of patients with cirrhosis or HCC

Patients with cirrhosis or HCC have close monitoring and follow-up at Specialist Outpatient Clinics (SOPC) with LFT and AFP tests regularly. Patients may receive anti-viral drug free of charge. Screening for HCC and HBV DNA assay are available for patients with cirrhosis.

Clinical guidelines have been established to provide guidance to healthcare providers and physicians for diagnosis and management of CHB infection to reduce the development of complications (Keeffe et al., 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009). However, the following issues remain unresolved. Firstly, not the majority of infected individuals are identified. Secondly, many CHB patients do not receive adequate management and follow-up, in particular, for those who initially do not consider anti-viral drug treatment. Despite numerous studies on the epidemiology, natural history and management of CHB, little has been done on the gap in healthcare services and patients' willingness to pay for their CHB treatment. Understanding patients' perceived needs can help to make service more patient-centered and improve the quality of life to CHB patients.

#### **2.2.5 HRQOL and service utilization**

Studies have shown a significant inverse relationship between HRQOL and service utilization in Western population (Dominick & Ahern, 2004; Ethgen & Kahler, 2002; Nelson & McHorney, 1998; Parkerson & Gutman, 2000; Singh & Nelson, 2005). Nelson et al found

Most infected individuals are asymptomatic and CHB is usually diagnosed incidentally during blood donation, health assessment or when they develop liver complications such as cirrhosis or HCC. Asymptomatic hepatitis B (AHB) carriers may be followed-up yearly at General Outpatient Clinic (GOPC) or private primary care doctors with liver function test (LFT) and alpha fetoprotein (AFP) but many are not. According to a local study in a primary care setting, most of HBV carriers did not attend GOPC for following up of their disease (Kung, Lam, & Li, 2004). Furthermore, there were large variations in follow-up period and test intervals (Kung et al., 2004). It ranges from 1 to 14 months for follow-up, 2 to 36 for blood tests, and 6 to 60 months for ultrasound (Kung et al., 2004). One month follow-up may be given to those who were very anxious about their condition (Kung et al., 2004). Since they are asymptomatic population, they do not need to take anti-viral treatment unless liver-related complications developed (European Association For the study of the liver, 2008; Keeffe et al., 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009). Both HCC screening and HBV DNA assay are not available for AHB carriers. AHB carriers are at risk of developing cirrhosis or HCC but screening is rarely done for these

Patients with ILF usually have close monitoring and follow-up at Specialist Outpatient Clinics (SOPC) with LFT and AFP tests regularly. The frequency of follow-up contact may vary. It is determined by a combination of variables: results of LFT, degree of viral replication, and need of anti-viral drug. Patients with ILF who receive drug treatment often need to pay for their drug costs and HBV DNA assay. Screening for HCC is not available for

Patients with cirrhosis or HCC have close monitoring and follow-up at Specialist Outpatient Clinics (SOPC) with LFT and AFP tests regularly. Patients may receive anti-viral drug free of charge. Screening for HCC and HBV DNA assay are available for patients with cirrhosis. Clinical guidelines have been established to provide guidance to healthcare providers and physicians for diagnosis and management of CHB infection to reduce the development of complications (Keeffe et al., 2008; Y F Liaw et al., 2008; A S Lok & McMahon, 2009). However, the following issues remain unresolved. Firstly, not the majority of infected individuals are identified. Secondly, many CHB patients do not receive adequate management and follow-up, in particular, for those who initially do not consider anti-viral drug treatment. Despite numerous studies on the epidemiology, natural history and management of CHB, little has been done on the gap in healthcare services and patients' willingness to pay for their CHB treatment. Understanding patients' perceived needs can help to make service more patient-centered and improve the quality of life to CHB patients.

Studies have shown a significant inverse relationship between HRQOL and service utilization in Western population (Dominick & Ahern, 2004; Ethgen & Kahler, 2002; Nelson & McHorney, 1998; Parkerson & Gutman, 2000; Singh & Nelson, 2005). Nelson et al found

a. Management of Asymptomatic Hepatitis B (AHB) carriers

b. Management of patients with Impaired Liver Function (ILF)

c. Management of patients with cirrhosis or HCC

**2.2.5 HRQOL and service utilization** 

patients (Yuen et al., 2005).

patients with ILF.

that physical functioning and mental health were important indicators of both outpatient visits and hospitalization for patients with chronic disease after controlling for confounding variables (Nelson 1998). Another study by Mulunpalo et al showed that a significant linear relationship between HRQOL and outpatient physician visits for working-age population in Finland (Mulunpalo 1997). Furthermore, Dominick et al pointed out that HRQOL can be valuable tools for predicting future health care for older patients with osteoarthritis (Dominick 2004). Poorer general health was correlated with increased likelihood of analgesic or anti-inflammatory use (Dominick 2004). Poor mental health was associated with increased likelihood of analgesic or anti-inflammatory use (Dominick 2004).

There were several studies on the association between HRQOL and service utilization for Asian population (T. Chen & Li, 2009; C. L. K. Lam & Fong, 2002; Matsumura, 2000). A study by Matsumura in Japan found that subjects with Short Form-36 (SF-36) physical component summary (PCS) score below 40 were more likely to use outpatient services and to be hospitalized than those who had scores greater than 50 (Matsumura 2000). Subjects with both SF-36 physical and mental component summary scores below 40 were more likely to have taken sick leave than those who had scores greater than 50 (Matsumura, 2000). A large study in Hong Kong showed that a linear relationship between HRQOL and service utilization in the local Chinese population (C. L. K. Lam & Fong, 2002). Five out of eight SF-36 scores were independent determinants of consultation rates (C. L. K. Lam & Fong, 2002). Role limitation due to physical problem and bodily pain were associated with hospitalization (C. L. K. Lam & Fong, 2002).

A recent study assessing the effect of HRQOL on service utilization was conducted in 737 primary care patients in Mainland China (Chen 20009). Lower HRQOL scores were correlated with higher service utilization rates (Chen 20009). Three out of eight SF-36 scales were associated with both inpatient and outpatient consultation (Chen 20009).

Numerous studies reported on the relationship between HRQOL and service utilization for Western and Asian populations (T. Chen & Li, 2009; Dominick & Ahern, 2004; Ethgen & Kahler, 2002; C. L. K. Lam & Fong, 2002; Matsumura, 2000; Nelson & McHorney, 1998; Parkerson & Gutman, 2000; Singh & Nelson, 2005), but no data were available for CHB patients. More studies are needed to explore the effect of HRQOL on service utilization in patients with CHB.

#### **2.3 Health-related Quality of Life (HRQOL) as a health outcome measure for Chronic Hepatitis B (CHB) patients**

The goal of healthcare is to maintain, restore and improve health of patients. Traditionally, clinicians have focused primarily on 'hard' clinical outcomes, for instance, patient's mortality and morbidity (Eisen, Locke, & Provenzale, 1999). Clinicians are more likely to judge the effectiveness or efficacy of a therapy in terms of survival rate, biochemical parameters such as liver function, viral markers, and symptoms (Eisen et al., 1999). Traditional clinical outcomes (i.e. morbidity and mortality) are important but they do not adequately reflect patients' perceived health, feelings and the impact of illness on life. Health-related quality of life (HRQOL) can provide additional information on the effectiveness and quality of care.

Reviews on the Epidemiology, Quality of Life, and Management of Chronic Hepatitis B (CHB) 385

Although numerous studies have shown significant lower health-related quality of life (HRQOL) scores in patients with chronic liver diseases (CLD), there is relatively little attention on the impact of HRQOL in patients with hepatitis B virus (HBV) because most data come from western populations where CHB is uncommon (J. J. Gutteling et al., 2007; L. M. Martin et al., 2002). In general, studies showed a significant decline in HRQOL in patients with hepatitis C virus (HCV) (Foster et al., 1998; Heitkemper, Jarrett, Kurashige, & Carithers, 2001; Koff, 1999; Kwan et al., 2008; Miller, Hiller, & Shaw, 2001; Spiegel et al., 2005; Strauss & Dias Teixeira, 2006). Only a few papers explored the effect of CHB on HRQOL (Bondini et al., 2007; Levy et al., 2008; Nokhodian et al., 2009; S C Ong et al., 2008; Tan et al., 2008). The first paper on HRQOL of CHB was published by Foster et al in 1998, which evaluated the impact of chronic hepatitis C (CHC) and CHB by a generic measure of HRQOL, the Medical Outcomes Study Short Form-36 (SF-36) Health Survey (Foster et al., 1998). Patients with CHB had significant lower HRQOL scores in mental health and general health perception aspects, but their physical related HRQOL scores were comparable to the healthy control (Foster et al., 1998). The results indicated patients with CHB infection did not have significant lower scores in physical functions but the results were limited by a very

Studies with a larger sample size and patients with different stages of CHB are needed in order to provide more precise measures of HRQOL. One study found that CHB patients had similar HRQOL scores to the healthy control group, as measured by both generic (Short Form-36 Health Survey, SF-36) and disease-specific (Chronic Liver Disease Questionnaire, CLDQ) questionnaires (Bondini et al., 2007). CHB patients had lower HRQOL scores in only two (fatigue and worry) out of six CLDQ scales and two (physical functioning and vitality) out of eight SF-36 scales compared to the norm (Bondini et al., 2007). However, health preference values (utility) of CHB patients were lower than the

Recently, two large studies showed that CHB infection had a negative impact on HRQOL (Levy et al., 2008; S C Ong et al., 2008). Asymptomatic hepatitis B (AHB) carriers, CHB patients with impaired liver function (ILF), and compensated cirrhosis (CC) patients had a small to moderate but significant effect on HRQOL, and decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC) patients had the lowest HRQOL scores (S C Ong et al., 2008). Ong et al demonstrated that HRQOL measured by the generic HRQOL measures, the SF-36 Health Survey and EQ-5D, in Chinese AHB carriers was comparable to healthy controls, although those with ILF and CC patients showed a significant reduction in general health and mental health dimensions (S C Ong et al., 2008). Patients with more advanced stages of CHB (DC and HCC) had the lowest HRQOL scores in all dimensions (S C Ong et al., 2008). The results indicated deterioration in physical health while the disease progresses

Another study by Tan et al showed that hepatitis B carriers in Singapore had good physical and mental health measured by both generic (SF-36 Health Survey) and disease-specific (Hepatitis Quality of Life Questionnaire) HRQOL measures (Tan et al., 2008). There was no significant difference in HRQOL between the 108 hepatitis B carriers in the study and

general population, except in social functioning (Tan et al., 2008).

**2.3.1 Impact of CHB on HRQOL** 

small sample of CHB patients (Foster et al., 1998).

population norm (Bondini et al., 2007).

(S C Ong et al., 2008).

Chronic hepatitis B (CHB) is a chronic debilitating condition that can lead to progressive impairment of physical and mental health as the disease progresses. Improvements in medical and surgical therapies in liver diseases have led to more people living with CHB. HRQOL should be considered an important outcome measures for assessing the impact of CHB and the effectiveness of treatment. The expansion from traditional clinical outcomes to include HRQOL outcomes will enable us to measure modern health care more sensitively (Younossi, 2001). HRQOL is more sensitive in capturing the effect of illness and interventions for those with uncomplicated disease (Bondini et al., 2007; Levy et al., 2008; Nokhodian, Ataei, Kassaian, Adibi, & Farajzadegan, 2009; S C Ong et al., 2008; Tan, Cheah, Teo, & Yang, 2008; Yi, 2006). Furthermore, HRQOL provides additional information for the prioritization of needs among patients with similar clinical severity defined by traditional clinical outcomes. The effect of an intervention on HRQOL has become a very important topic for both consumers and providers of health services (R. C. Martin, Eid, Scoggins, & McMasters, 2007; Poon et al., 2001; Yi, 2006).

The applications of HRQOL measures can be categorized as evaluative, discriminative and predictive (Preedy, Watson, & Lam, 2010; Yacavone, Locke, Provenzale, & Eisen, 2001). Evaluative measures are the most widely used in different populations or patients groups (Preedy et al., 2010). It is used to assess the impact of an illness, effectiveness or side effect of treatment, and quality of healthcare delivery (Preedy et al., 2010; Yacavone et al., 2001). Discriminative measures can be used to differentiate between groups in terms of HRQOL (Preedy et al., 2010; Yacavone et al., 2001). Predictive measures are used to identify people who are at risk or predict service needs for different populations or patient groups (Preedy et al., 2010). HRQOL measures can apply in economic evaluation in relation to treatment (Kanwal et al., 2005; Sun, Qin, Li, & Jiang, 2007; Takeda, Jones, Shepherd, Davidson, & Price, 2007; Veenstra, Spackman, Bisceglie, Kowdley, & Gish, 2008; Yuan, Iloeje, Li, Hay, & Yao, 2008).

The World Health Organization (WHO) states that 'health is a state of complete physical, mental and social well-being' (WHO, 1947). Well-being is the subjective perception of an individual's state of living, which has a similar concept as quality of life. It is noted that health is only one of many determinants of a person's quality of life, others include social environment, economy, religion etc. In the context of health services, the focus is on healthrelated quality of life (HRQOL) in an attempt to quantify the net consequence of a disease and its treatment on the patient's perception of his/her ability to live a useful and fulfilling life (Schipper, Clinch, & Olweny, 1996).

In the last few decades, there has been an increasing interest in the evaluation of HRQOL in patient groups, including those with chronic liver disease (Foster, Goldin, & Thomas, 1998; J. J. Gutteling, de Man, Busschbach, & Darlington, 2007; Younossi, 2001). The number of articles in gastroenterology on quality of life (QOL) or HRQOL has increased significantly in recent decades (Foster et al., 1998; L. M. Martin et al., 2006; L. M. Martin, Sheridan, & Younossi, 2002; L. M. Martin & Younossi, 2005; Younossi et al., 2001; Younossi, Kiwi, Boparai, Price, & Guyatt, 2000). HRQOL has become standard outcome measure in patients with chronic liver diseases in western countries especially in patients with chronic hepatitis C (CHC) (Chong et al., 2003; Foster, 1999; Foster et al., 1998; Kwan et al., 2008; Spiegel et al., 2005). It should also become an important outcome measure in CHB patients.
