Source
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
Abstract
OBJECTIVES:
The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV.
DESIGN:
Random-effects pairwise meta-analysis of randomised trials and observational studies.
SETTING:
Electronic and manual searches were combined. Randomised controlled trials (RCTs) were included in the primary analyses. Observational studies were included in sensitivity analyses.
PRIMARY AND SECONDARY OUTCOME MEASURES:
The primary outcome measures were HCC incidence and mortality. The secondary outcome measure was HCC mortality.
RESULTS:
We included 8 RCTs, 8 prospective cohort studies and 19 case-control studies with a total of 3433 patients allocated to antiviral therapy and 4625 controls. The maximum duration of follow-up was 23 years. Randomised trials found no effect of antiviral therapy on HCC or mortality. Cohort studies found that antiviral therapy increased the risk of HCC (risk ratio 1.43; 95% CI 1.06 to 1.95), whereas case-control studies found a decreased risk of HCC in the intervention group (risk ratio 0.69; 95% CI 0.54 to 0.88). There was a clear difference between the results of RCTs and observational studies (test for subgroup differences, p<0.001). Antiviral therapy did not affect mortality in cohort studies, but reduced mortality in case-control studies (relative risk 0.71; 95% CI 0.54 to 0.93; test for subgroup differences, p=0.406).
CONCLUSIONS:
The effect of antiviral therapy on clinical outcomes in HBV remains to be established. Although there was a positive effect in the sensitivity analyses, the strength of the evidence does not allow for extrapolation to clinical practice as research design plays an essential role in the overall assessment.