Abstract
Objective : To identify predictors influencing the response to interferon (IFN) therapy in children with chronic hepatitis C (CH-C) and to assess histological findings of the liver long after IFN therapy.
Patients and Methods : Twenty-six children with CH-C who received natural IFN alfa therapy for 6 months (total dose : 8MU/kg), were divided into two groups : 12 patients showing a complete response (CR) and 14 patients with a partial response (PR). “CR” was defined as normalization of serum alanine aminotransferase (s-ALT) and the disappearance of hepatitis C virus ribonucleic acid (HCV RNA) from serum within 6 months after the cessation of therapy and continuing for at least 6 months thereafter. “PR” was defined as any other pattern of s-ALT and serum HCV RNA. Liver biopsies were performed within 6 months before IFN therapy in all 26 children, and again 2 years after therapy in 9 of the children.
Liver histology was categorized according to the standard criteria and Knodell's index of histological activity with some modifications (Modified HAI). Moreover, the frequency of five histological features (bile duct damage, lymphoid follicles and/or aggregates, acidophil bodies, steatosis and iron deposition) were examined.
Results : There were no significant differences on conventional histological diagnosis or in modified HAI for total, necroinflammation and fibrosis between the CR group and the PR group. Bile duct damage, acidophil bodies and steatosis were frequently observed in the PR group, while lymphoid follicles and/or aggregates were frequently recognized in the CR group. However, there were no significant differences in each of the four histological features between the two groups. However, there was a significant difference (p=0.009) in the frequency of liver iron deposition between the CR group (8%) and the PR group (58%). Significantly fewer patients in the CR group showed more than three of these five histological features compared to those in the PR group (0% vs 36%, p=0.021). There were also significantly fewer children in the CR group showing more than two of these four histological features excluding lymphoid follicles and/or aggregates compared to those in the PR group (8% vs 71%, p=0.001). Of the 9 children (CR : 7 cases, PR : 2 cases) who underwent liver biopsies 2 years after the cessation of IFN therapy, 8 (CR : 7 cases, PR : 1 case) showed an improved histological diagnosis.
Conclusions : These results suggest that the response to IFN therapy in children with CH-C is influenced by hepatic iron deposition and a combination of several histological features. A period of more than 2 years after the cessation of therapy was necessary to determine histological remission in the CR group.
