Time course of histological changes in patients with a sustained biochemical and virological response to interferon-α therapy for chronic hepatitis C virus infection

Background/Aims: Although biochemical and virological responses to interferon-α therapy for chronic hepatitis C virus infection have been extensively studied, long-term changes in liver histology have not been well documented. Methods: We retrospectively analyzed 105 paired liver biopsy specimens taken before and after treatment from 93 patients who persistently showed biochemical remission and an absence of viremia for up to 68 months. Results: The grading scores for necroinflammatory and fibrotic activity in the liver biopsy specimens decreased significantly after interferon-α therapy. Histological scores graded according to Knodellʹs components improved significantly in every category after interferon-α therapy. However, inflammatory cell infiltrates remained within the portal tracts for long periods: necroinflammation in the periportal lobular regions were absent in most of the post-therapy specimens. The cumulative disappearance rate, calculated using the Kaplan-Meier method, was significantly lower for portal inflammation than for periportal or lobular necroinflammation but was equivalent to that for histological disease activity. On univariate analysis, age and fibrosis at the onset of treatment were significant factors influencing the response of histological disease activity to interferon-α therapy (p=0.025 and 0.49, respectively). Using Coxʹs proportional hazard analysis, age was the only significant independent predictor of histological response to treatment (p=0.035). Conclusions: Clinical remission of chronic hepatitis C virus infection is associated with histological resolution of necroinflammation in the periportal and lobular regions. Host-related factors are likely to influence whether early remission of inflammation after interferon-α therapy occurs.