EFFECT OF INTERFERON-ALPHA ON PROGRESSION OF CIRRHOSIS TO HEPATOCELLULAR-CARCINOMA - A RETROSPECTIVE COHORT STUDY

Background There is debate about whether interferon-alpha treatment lo wers the risk of progression to hepatocellular carcinoma in patients w ith chronic viral hepatitis and cirrhosis and whether any effect is li mited to certain subgroups. We investigated these issues by retrospect ive analysis of data for 913 patients from Italy and Argentina. Method s 21 centres reported patients from their records who had chronic vira l hepatitis and Child's A cirrhosis, were positive for HBsAg or hepati tis-C-virus antibodies (anti-HCV), and had been screened yearly for at least 3 years by ultrasonography and alpha-1-fetoprotein testing. Pro gnostic risk factors for hepatocellular carcinoma defined by multivari ate Cox regression analysis and individual observation time were used for group matching and conditional logistic regression analysis of the independent interferon-alpha treatment effect. Findings After group m atching, the number of patients was reduced to 637. Age, male sex, and portal hypertension were significant risk factors for hepatocellular carcinoma (each p<0.001); hepatic inflammation (p=0.21) and iron stora ge (p=0.18) were also included in the model. 66 (19%) of 356 untreated patients and 29 (10%) of 281 treated patients developed hepatocellula r carcinoma (relative risk 1.99 [95% CI 1.09-3.64]); the corresponding proportions for anti-HCV-positive patients were 48 (18.5%) of 259 ver sus 21 (9.1%) of 232 (3.14 [1.46-6.80]), and those for hepatitis-B-vir us-infected (HBV) patients were 18 (10%) of 97 and eight (16%) of 49 ( 0.98 [0.33-2.92]). Among anti-HCV patients without HBV markers, 29 (20 %) of 129 untreated and six (5%) of 116 treated patients developed hep atocellular carcinoma (6.28 [1.65-23.8]). Interpretation Interferon tr eatment lowered the rate of progression to hepatocellular carcinoma tw o ford. The risk reduction was apparently greater for patients with ch ronic hepatitis C and no evidence of HBV infection. Future studies sho uld stratify HCV-infected patients by HBV status.