Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta‐analysis

Abstract

Interferon (IFN) has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen/HBV DNA seroclearance have been documented. However, the effect of treatment on the prevention of cirrhosis and hepatocellular carcinoma (HCC) development remains controversial. We conducted a meta-analysis of available literature to evaluate whether IFN reduces the incidence of liver cirrhosis and HCC in patients with chronic hepatitis B. Twelve clinical controlled trials, including 2082 patients and comparing IFN with no treatment, were selected. Data on the incidence of liver cirrhosis and HCC in IFN treated and untreated patients were extracted from each study. The evaluation of preventive effectiveness was performed with an intention-to-treat method. The relative risk (RR) and 95% confidence interval (CI) of the main outcomes as a measure of efficacy were used. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with STATA version 9.0 and Review Manager Version 4.2. Five studies including the data on development of liver cirrhosis, and eleven studies including the data on development of HCC were analyzed. There was no evidence for publication bias on the funnel plot or by Egger's test, and the heterogeneity test indicated that the variation of trial-specific RR was not statistically significant. A different incidence of liver cirrhosis and HCC was observed between treated and untreated patients. The RR of liver cirrhosis and HCC was 0.65 (95% CI: 0.47, 0.91) and 0.59 (95% CI: 0.43, 0.81), respectively. In conclusion, the results of this meta-analysis indicate that IFN prevents or delays the development of liver cirrhosis and HCC in patients with chronic hepatitis B.

Regulatory Effects of Programmed Cell Death 4 (PDCD4) Protein in Interferon (IFN)-Stimulated Gene Expression and Generation of Type I IFN Responses

“…Because of these activities, IFNs have been examined extensively in clinical trials over the last 3 decades and have found applications in the management of various malignancies, viral syndromes, and autoimmune disorders (35,49,57,59). This broad spectrum of clinical applications for IFNs is a reflection of the diversity of their biological effects.…”

Hepatocyte Nuclear Factor 4α Suppresses the Development of Hepatocellular Carcinoma

“…Unfortunately, effective strategies for HCC prevention in patients remain scarce to date. Antiviral therapies with IFN and nucleotide analogues were reported to be effective in prevention of HCC associated with hepatitis virus infection (3,4); as for HCC patients independent of hepatitis, the effect still needs to be confirmed. A randomized controlled study indicated that acyclic retinoid was able to reduce the recurrence of HCC in patients who had undergone surgical treatment (5).…”

Evidence-based clinical practice guidelines for liver cirrhosis 2015

“…With regard to an HCC-preventing effect, contradictory results were reported both in randomized controlled trials (RCTs) [40,41] and in meta-analyses [42,43]. Serious adverse effects, such as bacterial infections and hepatic failure, should not be ignored in interferon therapy for advanced cirrhosis.…”