TIME-COURSE OF HISTOLOGICAL-CHANGES IN PATIENTS WITH A SUSTAINED BIOCHEMICAL AND VIROLOGICAL RESPONSE TO INTERFERON-ALPHA THERAPY FOR CHRONIC HEPATITIS-C VIRUS-INFECTION

Background/Aims: Although biochemical and virological responses to int erferon-alpha therapy for chronic hepatitis virus infection have been extensively studied, long-term changes in liver histology have not bee n well documented. Methods: We retrospectively analyzed 105 paired liv er biopsy specimens taken before and after treatment from 93 patients who persistently showed biochemical remission and an absence of viremi a for up to 68 months. Results: The grading scores for necroinflammato ry and fibrotic activity in the liver biopsy specimens decreased signi ficantly after interferon-alpha therapy. Histological scores graded ac cording to Knodell's components improved significantly in every catego ry after interferon-alpha therapy, However, inflammatory cell infiltra tes remained within the portal tracts for long periods; necroinflammat ion in the periportal and lobular regions were absent in most of the p ost-therapy specimens. The cumulative disappearance rate, calculated u sing the Kaplan-Meier method, was significantly lower for portal infla mmation than for periportal or lobular necroinflammation but was equiv alent to that for histological disease activity. On univariate analysi s, age and fibrosis at the onset of treatment were significant factors influencing the response of histological disease activity to interfer on-alpha therapy (p=0.025 and 0.049, respectively). Using Cox's propor tional hazard analysis, age was the only significant independent predi ctor of histological response to treatment (p=0.035). Conclusions: Cli nical remission of chronic hepatitis C virus infection is associated w ith histological resolution of necroinflammatory in the periportal and lobular regions. Host-related factors are likely to influence whether early remission of inflammation after interferon-alpha therapy occurs .