One study observed HBeAg positive patients, 233 treated with IFN and 233 untreated for 6.8 years, with cancers detected in 2% of treated patients and 7%

of untreated controls, showing carcinogenesis significantly reduced in the IFN therapy group (P < 0.025).[90] On the other hand, the other study of HBeAg positive patients, 208 treated with IFN and 203 untreated, found no significant difference in the rate INCB018424 order of carcinogenesis (2.9% vs 0%).[260] Although many other studies have evaluated the relationship between IFN therapy and carcinogenesis,[261-266] they have all been cohort studies and their results do not consistently demonstrate a carcinogenesis suppressor effect for IFN. In these cohort studies, the carcinogenesis rate in the control group (untreated patients) varies greatly from 0% to 30.8%, and the rate including patients with cirrhosis also varies from 0% to 100%, with considerable differences in subject clinical backgrounds. These differences

in the clinical background of applicable cases may be related to the variations in the reported carcinogenesis suppression effect of IFN. check details A number of meta-analyses have examined the relationship between IFN therapy and carcinogenesis. One analysis of 11 studies comprising 1006 patients treated with IFN and 1076 untreated controls found IFN therapy significantly reduced the carcinogenesis risk ratio to 0.59.[267] Another meta-analysis of 8 studies found that, although carcinogenesis was suppressed in IFN treated patients compared to untreated controls BCKDHA (risk difference 5.0%), the carcinogenesis suppression

effect was found in a subgroup of ethnic Asians, where the carcinogenesis rate in the untreated controls was ≥10%, and ≥70% of subjects were HBeAg positive.[268] A third meta-analysis of 7 studies evaluated the therapeutic effect of IFN in patients with cirrhosis, 122 cases of HCC developed in 1505 patients with liver cirrhosis, and a carcinogenesis risk difference of 6.4% in IFN treated patients compared to untreated controls.[269] The authors discussed that, although all 7 studies indicated a tendency for IFN therapy to suppress carcinogenesis, only 3 studies showed a significant difference, of which 2 studies were results from Asia. Then they concluded that the overall significant difference disappeared with elimination of the last 2 Asian studies, and no firm conclusion was made concerning carcinogenesis suppression by IFN therapy. Another meta-analysis of 12 studies examining 1292 IFN treated patients and 1450 untreated controls, IFN therapy significantly reduced the carcinogenesis risk ratio to 0.66.[270] A sub-analysis indicated that carcinogenesis was suppressed by IFN therapy in liver cirrhosis patients (11.6% vs 21.5%, risk ratio 0.53, 95% CI: 0.36–0.78), whereas for non-cirrhosis patients the cancer rate was low, 0.9% in treated patients and 1.1% in untreated controls, showing no significant difference.