Long-Term Effects of Interferon-Based Therapy for Chronic Hepatitis C

Abstract

Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.

Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus

“…Failure to achieve an SVR to IFN-based therapies, and preexisting advanced hepatic fibrosis and/or cirrhosis, are major predictors of HCC [6,23,25,39,40]. In the present study, SVR emerged as an independent risk factor for the development of HCC, while non-SVR was not.…”

Interferon-Based Therapy Decreases Risks of Hepatocellular Carcinoma and Complications of Cirrhosis in Chronic Hepatitis C Patients

“…SVR is usually considered synonymous with cure and associated with decreasing cirrhosis complications [16], [26], [33], [34], though the data supporting this assumption remain inconclusive. To date, no randomized, controlled trials of IBT have demonstrated a beneficial impact on overall mortality, liver specific mortality or development of HCC, and most of the evidence in favor of IBT is inferred from data of highly selected patients, clinical trials, or cirrhotic patients in tertiary medical centers [7], [9], [11], [12], [14]–[16], [18], [19], [22]–[24], [26], [33], [35].…”

Adjuvant interferon therapy after curative therapy for hepatocellular carcinoma (HCC): A meta-regression approach

“…HCC occurrence/recurrence is not an endpoint (101) Study mistype (not RCT or cohort study) (31) No anti-viral therapy (9) Use of unapproved anti-viral agent ( our review criteria used conventional interferon (natural or recombinant) and the cumulative evidence indicated benefit of adjuvant interferon therapy in terms of improved RFS. The meta-regression analysis indicated that a lower percentage of patients with multiple tumors and the use of ablation therapy were the most important independent predictors for better treatment efficacy.…”

“…Newer anti-viral regimens, including nucleoside analogs, pegylated interferon and interferon-nucleoside combination therapy, can produce higher virological and biochemical responses [29,30]. The improved virological responses have been found to be associated with reduced HCC development in patients with chronic HCV infection, but data on long-term efficacy of these new regimens for the prevention of HCC recurrence after curative HCC therapy is lacking [31,32].…”