Introduction
The two most common viruses capable of causing chronic infection in the liver and associated complications are hepatitis B virus (HBV) and hepatitis C virus (HCV) (1). These are also the most important causes of chronic hepatitis in Turkey and other regions of the world. According to the World Health Organization, approximately 350-400 million people worldwide carry the virus and 1-2 million people a year die of HBV infection or complications (2). HCV infection is a widespread and severe health problem worldwide. The global prevalence of HCV infection is 3%, and 210 million people are infected (3). Quality of life is a subjective concept, and difficult to define and measure. Chronic liver disease is generally asymptomatic, but may exhibit systemic symptoms such as fatigue, nausea, pruritus, lack of appetite and psychological disorders. A significant impairment in health-related quality of life (HRQoL) may occur in this patient group (4). The majority of studies of HRQoL in chronic viral hepatitis have been concerned with HCV infection, while the number of studies concerning HBV infection is limited. Several studies of patients infected with HCV have determined a significant decrease in HRQoL compared to controls (5,6). Interferon alpha (IFN-α) is the first cytokine produced by recombinant DNA technology and is used in the treatment of numerous malignant and non-malignant diseases. Diseases treated using IFN-a include hepatitis B and C. Quality of life of patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC) under IFN therapy is known to be adversely affected (4). The purpose of this study was to evaluate HRQoL scores of naive CHB and CHC patients in the infectious diseases and clinical microbiology clinic before pegylated IFN (PEG-IFN) therapy and at the 3rd and 6th months of treatment and to investigate the effect of IFN therapy on quality of life by comparing these with the scores of healthy controls.
Materials and Methods
Research Type and Sample
Twenty-eight treatment-naive patients with HBV infection with alanine aminotransferase (ALT) levels twice as high as normal for 6 months, hepatitis B surface antigen (HBsAg)+, hepatitis B e antigen (HBeAg)+/-, with HBV-DNA ≥104 copies/mL and no clinical findings of cirrhosis, and 23 non-cirrhotic CHC patients, anti-HCV+, with determinable HCV-RNA levels, presenting to and treated in the infectious diseases and clinical microbiology clinic between June 2008 and June 2010 were included in this prospective clinical study. Fifty-one subjects with no underlying chronic disease were enrolled as the control group. All cases were selected from among individuals aged 17-69 years.
The participants were informed about the study at interviews before commencement, and informed consent was received from all. The study was approved by Atatürk University Faculty of Medicine Ethics Committee (approval number: 65/2008). A socio-demographic data questionnaire was used in order to determine subjects’ socio-demographic and disease characteristics, and the 36-Item Short Form-36 (SF-36) Health Survey was administered in order to measure quality of life. The face-to-face interview technique was used for data collection. The forms were administered verbally by a researcher, and the subjects were asked to indicate the option best matching their own circumstances.
Definitions Used in the Research
Patient group: Treatment-naive non-cirrhotic patients with HBV infection, with an at least 2-fold increase in ALT levels in the previous 6 months, HBsAg+, HBeAg+/-, HBV-DNA ≥104 copies/mL with polymerase chain reaction (PCR) and with necroinflammatory activity ≥4 and/or fibrosis ≥2 in liver biopsy, and naive patients diagnosed with chronic non-cirrhotic HCV infection, anti-HCV+ and with HCV-RNA capable of determination with PCR were included in the study. Patients with chronic HBV and HCV infection were started on PEG-IFN α-2a therapy.
Control group: Subjects with no underlying chronic disease.
Socio-demographic Data Form
A socio-demographic form consisting of nine questions was employed to determine subjects’ sex, marital status, number of children, place of residence, education level, and occupation.
The 36-Item Short Form Health Survey
The SF-36 was developed by the Rand Corporation for assessing HRQoL (7). The form has been translated into Turkish and its validity and reliability have been confirmed (8,9). The scale is a generic, self-report outcome measure. It consists of 36 items measuring eight domains-physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, energy/vitality, bodily pain and general health perception. It can evaluate the positive aspects of health status, as well as negative aspects (10). The SF-36 scoring requires a separate guideline. Subdomain score calculation can be performed with a series of procedures (10). Scores range from 0 (worst possible health) to 100 (best possible health), with higher scores indicating a better quality of life. All sections are scored independently (7).
Application Procedure
Patients presenting to the Atatürk University Faculty of Medicine Infectious Diseases and Clinical Microbiology Clinic between June, 2008 and June, 2010 and meeting the inclusion criteria were enrolled. All subjects enrolled were administered a socio-demographic data questionnaire and the SF-36 before IFN therapy and on the 3rd and 6th months of treatment.
Statistical Analysis
All the study data were coded numerically and subjected to the One-Way Analysis of Variance and the Mann-Whitney U test in a computer environment using the Statistical Package for Social Sciences (SPSS) v.18.0. A p value of less than 0.05 was considered statistically significant.
Results
Socio-demographic Characteristics
Socio-demographic characteristics of the patients are presented in Table 1.
Quality of Life Scores
Physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, energy/vitality, bodily pain and general health perception scores based on responses to the questions in the SF-36 were obtained for the patient group consisting of patients with HBV and HCV and receiving PEG-IFN therapy and for the control group consisting of healthy adults. Physical functioning (p=0.007), physical role limitations (p=0.008), emotional role limitations (p=0.007), vitality/energy (p=0.001), and general health (p=0.001) scores before treatment in the patient group were statistically significantly lower than in the control group. On the 3rd month of treatment, a statistically significant decrease was observed in the physical role limitations (p=0.03), emotional role limitations (p=0.01) and vitality/energy (p=0.002) scores in the patient group. On the 6th month of treatment, a statistically significant decrease was determined in the physical functioning (p=0.001), physical role limitations (p=0.004), emotional role limitations (p=0.004), mental health (p=0.004) and vitality/energy (p=0.0003) scores. When quality of life scores of patients with CHB and CHC were compared with pre-treatment values, a statistically significant decrease was determined in the emotional role limitations scores (p=0.027) in patients with CHC. A statistically significant decrease was also observed in the physical functioning (p=0.042) and social functioning (p=0.042) scores in patients with CHC on the 6th month of treatment. When we compared the pre-treatment HRQoL scores of patients with CHB and controls, we determined statistically significantly lower vitality/energy (p=0.01) and general health (p=0.01) scores in the patient group than in controls. On the 6th month of treatment, statistically significant differences were determined in the physical functioning (p=0.03), physical role limitations (p=0.011), emotional role limitations (p=0.003) and vitality/energy (p=0.006) scores in patients with CHB. When we compared the pre-treatment HRQoL scores of patients with CHC and controls, we determined statistically significantly lower physical functioning (p=0.006), physical role limitations (p=0.006), emotional role limitations (p=0.001), vitality/energy (p=0.000005), and general health (p=0.003) scores in patients with chronic hepatitis. A statistically significant decrease was determined in physical functioning (p=0.006), physical role limitations (p=0.013), emotional role limitations (p=0.001), mental health (p=0.041) and vitality/energy (p=0.000005) scores in patients with hepatitis C on the 3rd month of treatment. On the 6th month of treatment, statistically significant decreases were observed in physical functioning (p=0.000008), social functioning (p=0.005), physical role limitations (p=0.0000008), emotional role limitations (p=0.000007), mental health (p=0.001) and vitality/energy (p=0.000005) scores. Mean values, standard deviation and p values obtained for all groups in the study before and after 3 and 6 months of treatment are shown in Table 2. Distribution of SF-36 scores by socio-demographic properties of patients is summarized in Table 3. Distribution of SF-36 scores by socio-demographic properties of CHB patients in treatment periods is summarized in Table 4. Distribution of SF-36 scores by socio-demographic properties of CHC patients in treatment periods is summarized in Table 5.
Discussion
Patients with chronic hepatitis are generally asymptomatic, but may also exhibit systemic symptoms, such as fatigue, nausea, pruritus, lack of appetite and psychological disorders. A significant impairment in HRQoL may occur in this patient group. The majority of studies of HRQoL in chronic viral hepatitis have been concerned with HCV infection, while the number of studies concerning HBV infection is limited (4). HRQoL of patients with chronic hepatitis may vary depending on their socio-demographic characteristics. Numerous studies have shown that sex, marital status, education level, occupation and place of residence affect HRQoL of HBV- and HCV-infected patients. In agreement with the previous literature, we determined a significant decrease in female patients with chronic hepatitis (11,12,13,14,15,16,17,18,19,20). Women with chronic disease are known to receive less social support than men in many parts of the world. In addition, they generally receive medical care later than males; they either have to work, or else have to resume their responsibilities without being fully recovered (21). These may all account for the decrease in HRQoL of female patients with chronic hepatitis. In agreement with previous studies, we determined lower HRQoL scores in individuals infected with HCV (22,23). Being married and having social and individual responsibilities may affect HRQoL. No significant change in HRQoL and only a weak correlation between marital status and HRQoL was observed in married patients with chronic viral hepatitis B in previous studies. In the present study also, no significant changes in HRQoL were determined in this patient group. A low education level is another demographic characteristic that affects HRQoL. As also shown in several studies, HRQoL was statistically significantly affected before and during treatment in our chronic hepatitis patients with a low level of education (13,16). Housewives have been determined to have the lowest scores and clerical workers the highest in all areas of HRQoL (17). Low physical functioning, physical role limitations, general health and emotional role limitations scores have been determined among unemployed patients with CHB and CHC (13). In our study, pre-treatment physical functioning and 3rd month physical role limitations scores in patients with CHB were lower among housewives. Among the patients with CHC, a significant decrease was observed only in the mental health scores in agricultural workers at the 6th month of treatment. The effect of IFN therapy in terms of occupations of patients with chronic viral hepatitis is unclear, and no benchmark has been determined. However, the numerous side-effects of IFN and ribavirin may be described as an adverse physical impact. Lam et al. (11) showed a significant level of variation in HRQol scores in patients with CHB in the categories of physical role limitations, bodily pain, energy/vitality, social functioning and emotional role limitations. In a similar study of patients with hepatitis B and C and healthy controls, Ozkan et al. (13) observed a particularly significant decrease in the physical functioning and mental health domains in patients with HBV infection compared to controls. Several studies have reported lower HRQoL scores in patients with HBV and HCV infection compared to healthy controls (11,12,13,24,25). In the present study, we determined lower HRQoL scores in patients with HBV infection compared to healthy controls. Patients with CHC have more severe and more frequent symptoms of musculoskeletal pain, malaise and fatigue compared with other forms of chronic liver disease (14,26). Several studies have shown a decrease in HRQoL scores in all categories in patients with hepatitis C compared to controls (12,13,22,24). In this study, we also determined, in agreement with previous studies, lower HRQoL scores in patients with CHC compared to healthy controls. We observed statistically significant differences in physical functioning, physical role limitations, energy/vitality and general health scores in these patients compared to controls. Pojoga et al. (27) reported that patients with CHB had better general health, social functioning and mental health scores than patients with CHC. Another study showed a significant decrease in HRQoL scores in patients with hepatitis C compared to that in patients with CHB (12). In our study, although HRQoL scores in patients with CHC were lower than those in patients with CHB, the difference was only statistically significant in emotional role limitations scores. Lower HRQoL scores observed in patients with CHC compared to those with CHB may be attributed to symptoms such as lethargy and fatigue being more pronounced in the former and to this then affecting their emotional scores. When we compared the HQRoL scores of patients with CHC during the treatment period with those of the control group, we determined a significant difference. This difference consisted of significantly low physical functioning, physical role limitations, emotional role limitations, mental health and vitality/energy scores in patients with hepatitis C at the 3rd month of treatment and also a significantly lower social functioning score in addition to the other parameters at the 6th. HRQoL in chronic hepatitis is adversely affected during treatment. This may be due to drug side-effects such as fatigue, flu-like findings, such as myalgia, and changes in psychological state, concentration impairment and loss of libido adversely impacting patients’ energy and social functioning (28,29). Marcellin et al. (30) investigated HRQoL in patients with CHB and CHC receiving PEG-IFN α-2a therapy and reported better HRQoL scores, particularly in the physical component, in patients with hepatitis B compared to those with hepatitis C. In our study, HRQoL scores during treatment were better in patients with CHB than in those with CHC. The decrease in physical functioning and social functioning scores in patients with CHC at the 6th month was statistically significant. HRQoL during treatment being lower in patients with CHC than in patients with CHB may be associated with the side-effects of combined IFN and ribavirin therapy. We also determined a significant decrease in HRQoL scores during treatment in our patients with CHB compared with the control group. This decrease was statistically significant at the 6th month in physical, physical role limitations, emotional role limitations and energy/vitality scores.
Conclusion
Chronic viral hepatitis is a social health problem in Turkey. Chronic diseases can adversely affect quality of life in various ways. Patients with chronic hepatitis are exposed not only to the chronic effects of the disease, but also to undesirable effects of IFN treatment and antiviral drugs. Measuring and evaluating quality of life is even more important in this patient group, in which severe decreases may be anticipated. Patients’ quality of life is adversely affected by side-effects of treatment. This discomfort caused by treatment may also impair patients’ compliance and willingness to continue with therapy. Emotional changes during treatment must be monitored and treatment should be provided when required. Considering the changes occurring in emotional and psychological states, psychiatric evaluation at least once during follow-up may be useful. Provision of counseling and guidance services can improve quality of life of patients with chronic viral hepatitis. Good standardization of HRQoL measures and application to patients with chronic diseases will identify negativities emerging and perhaps also be of assistance in coping with them.
Ethics
Ethic Committee Approval: The study was approved by Ataturk University Faculty of Medicine Ethics Committee (approval number: 65/2008).
Informed Consent: Informed consent was received from all.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: H.A., K.Ö., E.P., Concept: N.Ç., S.E., M.P., Design: S.E., H.A., K.Ö., E.P., Data Collection or Processing: H.A., E.P., Analysis or Interpretation: H.A., K.Ö., M.P., S.E., Literature Search: H.A., K.Ö., E.P., Writing: H.A., K.Ö.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.