Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: A meta‐analysis of randomized controlled trials

Abstract

Available literature on the effects of interferon (IFN) treatment on development and progression of hepatocellular carcinoma (HCC) in patients with chronic virus infection reports controversial results. The primary objective of this meta-analysis was to evaluate the effect of IFN on HCC risk in patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; IFN's efficacy on local tumor progression and survival of advanced HCC patients was also assessed. All randomized controlled trials (RCTs) comparing IFN with no antiviral treatment were selected. Finally, we identified 11 RCTs including 1,772 patients, who met our inclusion criteria to perform this meta-analysis. Our analysis results showed that IFN significantly decreased the overall HCC incidence in HCV-infected patients [relative risk (RR) 5 0.39; 95% confidence interval (CI) 5 0.26-0.59; p 5 0.000], subgroup analysis indicated that IFN decreased HCC incidence in HCV-related cirrhotic patients evidently (RR 5 0.44; 95% CI 5 0.28-0.68; p 5 0.000); but HCC incidence in nonresponders to initial antiviral therapy did not reduce by maintenance IFN therapy (RR 5 0.96; 95% CI 5 0.59-1.56; p 5 0.864). Analysis results also demonstrated that IFN did not significantly affect the overall rate of HCC in HBV-infected patients although there was a trend favoring IFN therapy (RR 5 0.23; 95% CI 5 0.05-1.04; p 5 0.056). Besides, IFN did not improve one-year overall survival of advanced HCC patients significantly (RR 5 1.61; 95% CI 5 0.96-2.69; p 5 0.072); however, a quantitative analysis on local tumor progression could not be performed owing to lack of unified definitions among trials included in our study. By this meta-analysis, we conclude that IFN therapy is effective in reducing overall HCC risk in chronic HCV-infected patients; using it in this subpopulation seems promising, but its administration in other subpopulations still requires further exploration.Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors and is the third most common cause of death from cancer in the world.1 Despite extensive efforts to improve its prognosis, the overall survival rate of HCC patients remains very low to date. Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are the most common etiologies of HCC, and they are estimated to be causally associated with 53 and 25% of HCC worldwide, respectively.2 Thus, HCC prevention and treatment have become an important issue in patients with chronic HCV or HBV infection.Studies show that interferon (IFN) can not only suppress the replication of HCV and HBV, but also has a tumoricidal effect on a number of tumors including HCC. 3 In the past few years, several clinical studies have reported the preventive effect of IFN treatment on HCC occurrence in patients with HCV or HBV infection, especially in sustained virologic responders. [4][5][6][7] However, in those with advanced hepatitis C who did not achieve a sustained virologic response (SVR) to initial IFN-based antiviral therapy, m...

Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma

“…Several meta-analyses have examined the relationship between achievement of SVR and subsequent development of HCC (18,(22)(23)(24)(25)(26). Although these studies universally agree that SVR is strongly associated with a reduction in HCC, especially among persons who have progressed to advanced liver disease, the degree to which this association is true remains uncertain.…”

Hepatitis B virus-related hepatocellular carcinoma

“…Finally, since there is definitely no agreement on the efficacy and cost/effectiveness of antiviral treatment, whether IFN or NA, in HCC prevention (Asia-Pacific Working Party, 2010;Colombo, 2010;Liaw, 2010;Zhang et al, 2011), there is a need of well-constructed, large size, randomized prospective trials to confirm what is still based more on experts' opinions than on a sound scientific evidence, despite the number of studies published on the topic.…”

National Antiviral Treatment Program and the Incidence of Hepatocellular Carcinoma and Associated Mortality in Taiwan

“…8 Another report showed that the relative risk reduction of overall HCC incidence associated with interferon therapy was 77% in HBV-infected patients and 61% in HCV-infected patients. 16 From Taiwan Cancer Registry, 15 we know that there were about 300 incident HCC cases among men aged 30-39 in 2003. If the trend remained unchanged, there should have been 1500 new HCC cases from 2003 to 2007.…”