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Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials.

Kimer N, Dahl EK, Gluud LL, Krag A - BMJ Open (2012)

Bottom Line: Sequential analysis confirmed the overall result.There was clear statistical evidence of bias in the cohort studies (p=0.02).The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

ABSTRACT

Objectives: To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.

Design: Systematic review and meta-analyses of randomised controlled trials. Prospective cohort studies were included in sensitivity analyses.

Data sources: Eligible trials were identified through electronic and manual searches.

Study selection: Eight randomised controlled trials comparing antiviral therapy (interferon or pegylated interferon alone or with ribavirin) versus placebo or no intervention were included.

Data extraction and synthesis: Two independent reviewers assessed the methodological quality of studies and extracted data. Random effects meta-analyses were performed. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate sources of intertrial heterogeneity, the risk of bias and the robustness of the results after adjusting for multiple testing.

Results: Random effects meta-analysis showed that antiviral therapy reduced the risk of HCC (81/1156 vs 129/1174; risk ratio 0.53, 95% CI 0.34 to 0.81). In subgroup analyses, antiviral therapy was more beneficial (test for subgroup differences p=0.03) in virological responders (0.15, 0.05 to 0.45) than in non-responders (0.57; 0.37 to 0.85). No evidence of bias was seen in regression analyses. Sequential analysis confirmed the overall result. The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC. There was clear statistical evidence of bias in the cohort studies (p=0.02).

Conclusions: Antiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis. The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

No MeSH data available.


Related in: MedlinePlus

Random effects meta-analysis of randomised trials and cohort studies onantiviral therapy versus no intervention for development of hepatocellularcarcinoma (HCC) in hepatitis C-related cirrhosis or fibrosis.
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Related In: Results  -  Collection

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BMJOPEN2012001313F2: Random effects meta-analysis of randomised trials and cohort studies onantiviral therapy versus no intervention for development of hepatocellularcarcinoma (HCC) in hepatitis C-related cirrhosis or fibrosis.

Mentions: In total, 81 of 1156 patients randomised to antiviral therapy and 129 of 1074patients in the control group developed HCC. Random effects meta-analysis showed thatantiviral therapy reduced the risk of HCC (RR 0.53, 95% CI 0.34 to 0.81;I2 50%; figure2). The corresponding number needed to treat to prevent one case of HCC waseight patients. There was no evidence of bias or small study effects in regressionanalysis (Egger's test p=0.931). The sequential analysis revealed thatthe cumulative Z-curve crossed the monitoring boundary, which confirmed the overallresult after adjusting for multiple testing. Similar results were achieved afterexclusion of trials without adequate randomisation which confirmed the overall result(RR 0.58, 95% CI 0.37 to 0.95) and trials on patients with fibrosis (RR 0.51,95% CI 0.34 to 0.77). In subgroup analysis (figure 3), the effect of antiviral therapy wasmore pronounced (test for subgroup differences p=0.03) among patients with avirological response (RR 0.15, 95% CI 0.05 to 0.45, Egger's testp=0.543) compared with virological non-responders (RR 0.57; 95% 0.37 to0.85, Egger's test p=0.425).


Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C: systematic review and meta-analysis of randomised controlled trials.

Kimer N, Dahl EK, Gluud LL, Krag A - BMJ Open (2012)

Random effects meta-analysis of randomised trials and cohort studies onantiviral therapy versus no intervention for development of hepatocellularcarcinoma (HCC) in hepatitis C-related cirrhosis or fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4400677&req=5

BMJOPEN2012001313F2: Random effects meta-analysis of randomised trials and cohort studies onantiviral therapy versus no intervention for development of hepatocellularcarcinoma (HCC) in hepatitis C-related cirrhosis or fibrosis.
Mentions: In total, 81 of 1156 patients randomised to antiviral therapy and 129 of 1074patients in the control group developed HCC. Random effects meta-analysis showed thatantiviral therapy reduced the risk of HCC (RR 0.53, 95% CI 0.34 to 0.81;I2 50%; figure2). The corresponding number needed to treat to prevent one case of HCC waseight patients. There was no evidence of bias or small study effects in regressionanalysis (Egger's test p=0.931). The sequential analysis revealed thatthe cumulative Z-curve crossed the monitoring boundary, which confirmed the overallresult after adjusting for multiple testing. Similar results were achieved afterexclusion of trials without adequate randomisation which confirmed the overall result(RR 0.58, 95% CI 0.37 to 0.95) and trials on patients with fibrosis (RR 0.51,95% CI 0.34 to 0.77). In subgroup analysis (figure 3), the effect of antiviral therapy wasmore pronounced (test for subgroup differences p=0.03) among patients with avirological response (RR 0.15, 95% CI 0.05 to 0.45, Egger's testp=0.543) compared with virological non-responders (RR 0.57; 95% 0.37 to0.85, Egger's test p=0.425).

Bottom Line: Sequential analysis confirmed the overall result.There was clear statistical evidence of bias in the cohort studies (p=0.02).The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

ABSTRACT

Objectives: To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.

Design: Systematic review and meta-analyses of randomised controlled trials. Prospective cohort studies were included in sensitivity analyses.

Data sources: Eligible trials were identified through electronic and manual searches.

Study selection: Eight randomised controlled trials comparing antiviral therapy (interferon or pegylated interferon alone or with ribavirin) versus placebo or no intervention were included.

Data extraction and synthesis: Two independent reviewers assessed the methodological quality of studies and extracted data. Random effects meta-analyses were performed. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate sources of intertrial heterogeneity, the risk of bias and the robustness of the results after adjusting for multiple testing.

Results: Random effects meta-analysis showed that antiviral therapy reduced the risk of HCC (81/1156 vs 129/1174; risk ratio 0.53, 95% CI 0.34 to 0.81). In subgroup analyses, antiviral therapy was more beneficial (test for subgroup differences p=0.03) in virological responders (0.15, 0.05 to 0.45) than in non-responders (0.57; 0.37 to 0.85). No evidence of bias was seen in regression analyses. Sequential analysis confirmed the overall result. The sensitivity analyses showed that the cohort studies found that antiviral therapy reduced the risk of HCC. There was clear statistical evidence of bias in the cohort studies (p=0.02).

Conclusions: Antiviral therapy may reduce the risk of HCC in hepatitis C-related fibrosis and cirrhosis. The effect may be seen irrespective of the virological response, but is more pronounced among virological responders compared with non-responders.

No MeSH data available.


Related in: MedlinePlus