Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis: a meta‐analysis

Abstract

Background: The role of interferon in the prevention of hepatocellular carcinoma remains controversial. Aim: In this meta‐analysis we evaluated the hepatocellular carcinoma incidence in interferon‐treated and ‐untreated patients with hepatitis C virus‐related cirrhosis. Methods: Eleven studies with 2178 patients were found to fulfil our inclusion criteria. The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated from the raw study data. Results: Hepatocellular carcinoma development was significantly more frequent in untreated (21.5%) than in interferon‐treated patients (8.2%; OR: 3.0, 95% CI: 2.3–3.9). In the five studies reporting hepatocellular carcinoma incidence in patients with and without sustained response to interferon, hepatocellular carcinoma was detected at a much higher rate in patients without (9%) than with a sustained response (0.9%; OR: 3.7, 95% CI: 1.7–7.8). Moreover, hepatocellular carcinoma developed significantly more frequently in the untreated patients than in the non‐sustained responders (OR: 2.7, 95% CI: 1.9–3.9). The benefit from interferon on hepatocellular carcinoma incidence was not influenced by the study type (prospective or retrospective), the follow‐up duration, or the study origin. Conclusions: Interferon therapy significantly reduces the hepatocellular carcinoma risk in patients with hepatitis C virus cirrhosis. Hepatocellular carcinoma development becomes almost negligible among sustained responders, but a reduction in hepatocellular carcinoma incidence is also achieved even in the non‐sustained responders.

Effect of hepatitis C virus and its treatment on survival†‡

“…2,3 Treatment for HCV is associated with a reduced risk of liver disease progression and a lower incidence of hepatocellular carcinoma, even when the treatment does not achieve viral eradication. [4][5][6] The impact of HCV infection on survival in the general population is controversial. Some studies have shown a significant increase in mortality in HCV-infected persons, 7,8 whereas others have shown relatively low mortality rate and liver disease progression in otherwise healthy persons.…”

Does chemotherapy prevent HCV-related hepatocellular carcinoma? Cons

“…-Does the preventive effect of IFN on HCC development start before the onset of severe fibrosis or cirrhosis? Three meta-analyses on aggregate data [28][29][30] were performed to evaluate whether IFN reduces the incidence of HCC in patients with HCV-related cirrhosis. In the last published [30], IFN seemingly decreased HCC rate in all but one of 20 studies included in the meta-analysis, a significant difference being observed in 13 studies.…”

“…All meta-analyses [28][29][30] clearly showed that the heterogeneity in HCC incidence in patients who received IFN is the most relevant feature of the studies. The inconsistency among these trials is not surprising if one considers all potential biases in the selection of patients with different demographic and clinical characteristics, different timing of referral and diagnostic criteria, true differences in case mix, risk factors for HCC development, severity of the underlying cirrhosis and dose and length of IFN treatment.…”

Viral hepatitis and hepatocellular carcinoma: etiology and management

“…The risk of HCC in HCV patients who achieve SVR is markedly reduced, but patients remain at risk for HCC, especially patients who have bridging fibrosis or cirrhosis (71). Although eradication of HCV virus in the serum 12 weeks after therapy is terminated serves as a surrogate to eradicating virus in the liver, studies have shown that HCV RNA persists in the liver and peripheral blood mononuclear cells in some sustained viral responder (72,73).…”

“…The risk of HCC was lowest in patients with normal ALT values with or without HCV-RNA clearance, HR =0.32, P=0.012. A meta-analysis of 11 studies involving 2,178 patients found that HCC was 3.7 times more common in non-responders compared to sustained viral responders, Odds ratio =3.7 (95% CI, 1.7-7.8) (71). Even in patients who did not achieve an SVR there seems to be a benefit from IFN because the risk of HCC in untreated patients was 2.7-fold higher.…”