Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.
OBJECTIVE
To evaluate by meta-analysis of available literature whether interferon (IFN) reduces the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV)-related Child A cirrhosis.


METHODS
Three randomized controlled trials and 15 nonrandomized controlled trials, including 4614 patients and comparing IFN to no treatment, were selected. Data on the incidence of HCC in IFN treated and untreated patients were extracted from each study. Meta-analysis by the DerSimonian and Laird risk difference (RD) method was used to pool observations.


RESULTS
A different incidence of HCC between treated and untreated cirrhotic patients was observed for HCV (overall RD -12.8%; 95% CI -8.3 to -17.2%, P < 0.0001) and HBV (overall RD -6.4%; 95% CI -2.8 to -10%, P < 0.001). In HCV-related cirrhosis, the rate of HCC development was lower in sustained responders to IFN than in untreated patients (overall RD -19.1%; 95% CI -13.1 to -25.2%, P < 0.00001), with low heterogeneity among trials (P=0.053), and also in nonresponders vs. untreated patients (overall RD -11.8%; 95% CI -6.4 to -19.1%, P < 0.0001), although with significant heterogeneity. Inconsistency among the studies was a major problem, both for HCV (chi2 = 58.16 with 13 DF; P < 0.0001) and HBV (chi2 = 26.4 with 6 DF; P = 0.0001) related cirrhosis, and also when follow-up was shorter than 60 months. Consistent results were only observed when assessing data from European reports: in this subgroup no preventive effect of HCC was shown for HBV (overall RD -4.8%; 95% CI -11.1-1.5%, P, not significant), and only a weak effect for HCV (overall RD -10%; 95% CI -5.9 to -14.2%; P < 0.0001).


CONCLUSIONS
Literature data pooling suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to IFN. IFN does not seem to affect the rate of HCC in HBV-related cirrhosis.
Cammà
C
C
Istituto Metodologie Diagnostichie Avanzate, Consiglio Nazionale delle Ricerche, Palermo, Italy. camma@ismeda.pa.cnr.it
Giunta
M
M
Andreone
P
P
Craxì
A
A
D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology*; D008113:Liver Neoplasms / Q000517:prevention & control*
D000998:Antiviral Agents; D007372:Interferons