A meta-analysis and systematic review: adjuvant interferon therapy for patients with viral hepatitis-related hepatocellular carcinoma

Abstract

ObjectiveTo evaluate the efficacy and safety of adjuvant IFN therapy for viral hepatitis-related hepatocellular carcinoma (HCC) after treatment with surgical resection or transarterial chemoembolization (TACE).MethodsControlled trials of adjuvant treatment with IFN for patients with HCC published between 2000 and 2012 were searched electronically in MEDLINE, PubMed, Cochrane Library, and EMBASE databases. According to the heterogeneity of the studies, two different models - the fixed-effect model and the random-effect model - were applied to analyze the results.ResultsTen trials were screened according to inclusion and exclusion standards. Eight randomized, controlled trials and two non-randomized, controlled trials were included. These ten trials with a total of 1,029 subjects were eventually involved in the meta-analysis; 528 HCC patients were treated with adjuvant treatment with IFN and 501 patients with placebo. Compared to the control group, the recurrence rates of HCC in IFN group were significantly lower (odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.50 to 0.86; P = 0.02), especially after TACE treatment according to subgroup analysis (OR = 0.73; 95% CI = 0.52 to 1.01; P = 0.06 for surgical resection; and OR = 0.54; 95% CI = 0.33 to 0.86, P = 0.01 for TACE). The death rates in the IFN group also significantly decreased according to not only total events analysis (OR = 0.42; 95% CI = 0.32 to 0.56; P < 0.00001) but also subgroup analysis (OR = 0.51; 95% CI = 0.36 to 0.72; P = 0.0002 for surgical resection; and OR = 0.33; 95% CI = 0.21 to 0.50; P < 0.00001 for TACE).ConclusionsAdjuvant IFN therapy may significantly reduce the recurrence rates of patients with viral hepatitis-related HCC and improve the survival of patients after surgical resection or TACE. The ideal dose mostly selected is 3 MIU/ml, three times per week, which can make patients tolerate the adverse reactions of IFN better and maintain effective concentrations for a long time.

Current management of hepatocellular carcinoma: An Eastern perspective

“…A Japanese group previously showed positive effects of acyclic retinoids and vitamin K analogues on recurrence-free survival, but overall survival was not improved and large-scale studies were not performed appropriately [128,129] . Interferon has been suggested as an adjuvant therapy after resection [130] . According to a large current database in Taiwan, antiviral therapies reduce the recurrence of HCC after surgery in patients with chronic hepatitis B or C [131,132] .…”

“…In agreement, a randomized controlled trial conducted in China showed better recurrence-free survival (RR = 0.651, 95%CI: 0.451-0.938) and overall survival (RR = 0.420, 95%CI: 0.271-0.651) in patients receiving antiviral therapy, especially in terms of prevention of late recurrence [133] . It would be reasonable to recommend nucleoside or nucleotide analogues or interferon therapy to patients with hepatitis B and pegylated interferonbased therapy to patients with hepatitis C after curative hepatic resection [130][131][132][133] .…”

Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate‐activated protein kinase‐related kinases and retinoid X receptor α

“…Therefore, it might be possible that tumors will develop in the future even after HCV elimination when only a DAA regimen is used. Much like the reports demonstrating that IFN treatment has the ability to suppress the growth of hepatocellular carcinoma,45, 46 our new finding that RBV has the ability to suppress lipogenesis in hepatic cells will shed light once again on the beneficial abilities of RBV not only for antiviral but also antipathogenic treatments of liver diseases, such as hepatic steatosis or hepatocellular carcinoma, in which aberrant lipogenesis is involved.…”

IFN-λ Cancer Immunotherapy: New Kid on the Block

“…Several studies have demonstrated the suppressive effect of IFN-α in the development of HCC in patients with chronic hepatitis [45][46][47][48]. Thus IFN-α therapy for hepatitis B (HBV) and C (HCV) viral infections suppresses carcinogenesis and improves liver function [49][50][51][52].…”