Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis☆,☆☆
Introduction
Chronic hepatitis C affects at least 3.2 million Americans and is the major cause of chronic liver disease, cirrhosis and liver cancer in the United States [1], [2]. Chronic viral hepatitis is typically silent; symptoms and signs are present only in those with severe or advanced disease. Importantly, symptoms and poor health-related quality of life (HRQOL) are not reliable in separating patients with mild from those with moderate or advanced disease [3]. In some patients, symptoms do not develop until the onset of advanced cirrhosis or hepatocellular carcinoma. Other patients have marked fatigue and weakness, despite having histologically mild or early disease.
Chronic hepatitis C therapies are available and effective in approximately half of selected patients [4]. Because of its expense and many side effects, therapy is usually reserved for patients who have evidence of progressive disease [5], [6]. The poor correlation of symptoms, signs, and liver test abnormalities with severity and stage of disease has led to the use of liver biopsy and staging of fibrosis as the major criterion for therapy. Furthermore, eradication of hepatitis C virus (HCV) and prevention of disease progression, rather than amelioration of symptoms or improvement in HRQOL, have been used as the major determinants of successful therapy. Indeed, in most trials of therapy of hepatitis C, symptoms and HRQOL are not mentioned as even secondary endpoints [7], [8], [9], [10]. Nevertheless, a few prospective studies have shown that a sustained virological response (SVR) to therapy of chronic hepatitis C can be associated with significant improvements in HRQOL [11], [12], [13], [14], [15]. The role of contemporary therapy of chronic hepatitis C in ameliorating symptoms and improving HRQOL, especially in advanced liver disease, is not well defined [16], [17], [18].
We evaluated HRQOL and sexual health prospectively in a cohort of patients with advanced chronic hepatitis C who had failed to respond to a previous course of interferon-α (with or without ribavirin) enrolled in the lead-in phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. Patients were re-treated with a 24-week “lead-in” course of peginterferon α-2a and ribavirin [19], [20]. Patients who responded continued treatment for a full 48 weeks and were followed for another 24 weeks to assess whether they achieved SVR [19], [20]. The aim of the current analysis was to identify correlates of impaired HRQOL at enrollment. Secondary aims included evaluation of changes in HRQOL and sexual health in the subset of patients who achieved an SVR and those who had a transient response (relapsers).
Section snippets
Patients
HALT-C trial patients had chronic hepatitis C with detectable HCV RNA in serum and, within 12 months of enrollment, had undergone liver biopsy that demonstrated bridging fibrosis or cirrhosis (Ishak fibrosis scores of 3–6) [21]. Reasons for exclusion included evidence of hepatic decompensation, other co-existent liver disorder, serious medical disorders that would preclude treatment with interferon, interferon intolerance, active use of illicit drugs, active alcohol abuse, a suicide attempt or
Baseline characteristics of cohort
As shown in Fig. 1, among the 1145 patients enrolled in the lead-in phase of the HALT-C Trial, 1144 completed the baseline HRQOL questionnaire. Selected demographic and clinical features of the patients are provided in Table 1. Average age was 50 years, 28% were women, approximately three-quarters were non-Hispanic whites, and 15% were blacks. According to self-reports, 17% of patients had diabetes mellitus, 14% had heart disease, and 8% had depression. One-third of patients (31%) were taking
Discussion
Despite the availability and efficacy of peginterferon and ribavirin, therapy of chronic hepatitis C remains problematic. Shortcomings of current therapy include the protracted and complicated nature of treatment and unpleasant side effects. In addition, SVR rates are only 50–60% in published clinical trials and are appreciably lower in community practice [44], [45]. Therapy is usually recommended only for patients with evidence of fibrosis or substantial necroinflammatory disease on liver
Acknowledgements
This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). Additional
References (50)
- et al.
The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity
J Hepatol
(2001) - et al.
Comorbid illness is an important determinant of health-related quality of life in patients with chronic hepatitis C
Am J Gastroenterol
(2001) - et al.
Comorbidities and quality of life in patients with interferon-refractory chronic hepatitis C
Am J Gastroenterol
(2001) - et al.
Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment
Gastroenterology
(2004) - et al.
Histological grading and staging of chronic hepatitis
J Hepatol
(1995) - et al.
Interpretation of change scores in ordinal clinical scales and health status measures: the whole may not equal the sum of the parts
J Clin Epidemiol
(1996) - et al.
Emotional distress in chronic hepatitis C patients not receiving antiviral therapy
J Hepatol
(2002) - et al.
Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study
Gastroenterology
(2004) - et al.
Pathogenesis, natural history, treatment, and prevention of hepatitis C
Ann Intern Med
(2000) - et al.
The prevalence of hepatitis C virus infection in the United States, 1999 through 2002
Ann Intern Med
(2006)
Hepatitis C: the clinical spectrum of disease
Hepatology
Optimal therapy of hepatitis C
Hepatology
Diagnosis, management, and treatment of hepatitis C
Hepatology
Health assessment for chronic HCV infection: results of quality of life
Dig Dis Sci
Autoimmune hepatitis
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection
N Engl J Med
Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose
Ann Intern Med
Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. The Consensus Interferon Study Group
Hepatology
Sustained virologic response is associated with improved health-related quality of life in relapsed chronic hepatitis C patients
Semin Liver Dis
Peginterferon alpha-2a (40 kDa) [Pegasys] improves HR-QOL outcomes compared with unmodified interferon alpha-2a [Roferon-A]: in patients with chronic hepatitis C
Pharmacoeconomics
Assessing health-related quality of life in chronic hepatitis C using the Sickness Impact Profile
Clin Ther
Screening for hepatitis C virus infection: a review of the evidence for the U.S. Preventive Services Task Force
Ann Intern Med
Evolution of the HALT-C Trial: pegylated interferon as maintenance therapy for chronic hepatitis C in previous interferon nonresponders
Control Clin Trials
Cited by (0)
- ☆
This is publication number 14 from the HALT-C Trial Group.
- ☆☆
Financial support: Financial relationships of the authors with Hoffmann-La Roche, Inc., are as follows: H.L. Bonkovsky is a consultant, is on the speakers’ bureau, and receives research support; P.F. Malet receives research support; R.K. Sterling is a consultant, on the speakers’ bureau, and receives research support; R.J. Fontana is a consultant and on the speakers’ bureau; A.M. Di Bisceglie is a consultant, on the speakers’ bureau, and receives research support; and T.R. Morgan is on the speaker’s bureau and receives research support. Other financial relationships related to this project are: H.L. Bonkovsky receives research support from Bayer Diagnostics; P.F. Malet receives research support from Bayer Diagnostics; R.K. Sterling is a consultant and receives research support from Wako Diagnostics; T.R. Morgan receives research support from Metabolic Solutions; and D.R. Gretch receives research support from Bayer Diagnostics. Authors with no financial relationships related to this project are K.K. Snow, C. Back-Madruga, C.C Kulig, J.L. Dienstag, and M.G. Ghany.