How reversible is hepatic functional impairment in autoimmune hepatitis?

BACKGROUND AND AIMS: We quantifed the short-term effects of immunosuppressive therapy on hepatic metabolic function in autoimmune hepatitis to establish how long it takes to achieve maximum functional improvement. METHODS: We studied 14 newly diagnosed patients with autoimmune hepatitis (12 type 1, two type 2) by antipyrine clearance and conventional liver tests, then repeated studies at 3-6 month intervals during the first 18 months of immunosuppressive therapy. RESULTS: Low values for antipyrine clearance were found in 13 of 14 cases; serum albumin concentration was low in four, bilirubin raised in eight and prothrombin time prolonged in four. Following immunosuppressive treatment for 3 months, antipyrine clearance improved by 98% (standard error of the mean 24%), which was proportionally greater than for serum albumin, bilirubin or prothrombin time. Antipyrine clearance and serum albumin continued to improve after 6-12 months of immunosuppressive treatment in several cases, whereas there were no further improvements in alanine aminotransferase (ALT), bilirubin and prothrombin time. CONCLUSIONS: In the short term, immunosuppressive therapy for autoimmune hepatitis markedly improves hepatic metabolic function, which is particularly striking for the sensitive metabolic test antipyrine clearance, but may also be seen with serum albumin. However, it may take up to 12 months to achieve maximal functional recovery. Management guidelines on autoimmune hepatitis should be extended to emphasize that changes in hepatic metabolic function, as well as ALT and gamma-globulin levels, be taken into consideration in the definition of remission.

Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C: value for predicting fibrotic progression.

OBJECTIVE: We tested whether fibrotic progression in chronic hepatitis C could be predicted by liver tests, antipyrine clearance, or platelet count. METHODS: In 58 patients (6 untreated, 52 interferon-treated), a second liver biopsy was taken median 4.5 yr after first histologic diagnosis. We used receiver operating characteristic curves to determine whether changes in conventional liver tests, antipyrine clearance, or platelet count were predictive of altered hepatic fibrosis score. RESULTS: Apart from a weak association with change in ALT, conventional liver tests (albumin, bilirubin, prothrombin time) failed to correlate with changes (Delta) in hepatic fibrosis, but there were significant correlations between deltaantipyrine clearance or deltaplatelet count and deltafibrosis score (p < 0.01). As indicated by areas under the receiver operating characteristic curves, the diagnostic accuracy of deltaantipyrine clearance for fibrotic progression was 68%; for Deltaplatelet count it was 80%. With defined cut-off values (-0.05 ml/min/kg for deltaantipyrine clearance; -41 x 10(9)/L for deltaplatelet count), the negative predictive values for fibrotic progression were 85% with antipyrine clearance and 89% with platelet count. Corresponding positive predictive values were 48% and 91%, respectively. CONCLUSIONS: Changes in antipyrine clearance and platelet count are more sensitive than conventional tests for indicating fibrotic change in chronic hepatitis C. Both could be used to reliably identify those who do not have fibrotic progression, and platelet count also has a high positive predictive value for disease progression.

Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study.

OBJECTIVES: Fibrotic severity, biochemical indices of poor liver function, and sporadic transmission are independent predictors of liver complications among people with chronic hepatitis C. After accounting for these factors, we tested whether interferon treatment or the treatment response reduces the rate of liver cancer, liver-related death or transplantation, and other liver complications during extended follow-up. METHODS: Liver clinic cohort of 455 patients with histologically proven chronic hepatitis C was followed prospectively for median 9 yr (IQ 6, 11 yr); 384 received interferon, 343 completed a treatment course. Liver complications were assessed in relation to treatment and treatment response in univariate and multivariate models, and survival to onset of liver-related complications was determined. RESULTS: The annual incidence of total liver complications was 1.5% in treated and 2.9% in untreated patients and appeared quasilinear throughout 9-yr follow-up. Interferon treatment did not influence the rate of liver complications. However, the rate of complications increased exponentially with transition of the treatment response from sustained viral response (SVR), through response-relapse to nonresponse (or no treatment). By univariate analysis, response to interferon treatment was a significant predictor of complications. After adjustment for fibrosis score, serum albumin concentration and mode of transmission in a multivariate model, treatment response just failed to reach significance (p= 0.058) as a predictor of outcome. CONCLUSIONS: Response to antiviral therapy, and particularly SVR, appears to reduce liver complications in chronic hepatitis C. However, in the absence of an antiviral treatment response, a course of interferon does not reduce risks of liver cancer or liver failure.