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Effect of interferon therapy on bile duct inflammation in hepatitis C
1Department of Pathology, University of Massachusetts Medical Center, Worcester 01450-125, USA.
Insights
Bile duct inflammation is common in chronic hepatitis C and decreases with interferon therapy. This study in liver biopsies shows reduced inflammation after treatment, correlating with other histological improvements.
Area of Science:
- Hepatology
- Immunology
- Gastroenterology
Background:
- Bile duct inflammation is a feature of chronic hepatitis C.
- Its correlation with histological variables and treatment response is not fully understood.
Purpose of the Study:
- To investigate bile duct inflammation in chronic hepatitis C.
- To determine changes with interferon alpha 2B (IFN) therapy.
- To correlate inflammation with histological features and MHC antigen expression.
Main Methods:
- Liver biopsies from 20 chronic hepatitis C patients before and after IFN therapy were analyzed.
- Histological variables including inflamed bile ducts (%IBDs), piecemeal necrosis, and lymphoid aggregates were quantified.
- Immunostaining assessed class I and II MHC antigen expression on ductal epithelium.
Main Results:
- Bile duct inflammation (%IBD) was more frequent in cirrhotic patients before therapy.
- After IFN therapy, %IBD and alkaline phosphatase decreased in non-cirrhotic responders.
- Changes in %IBD paralleled other histological improvements; no correlation with MHC antigens was found.
Conclusions:
- Bile duct inflammation is frequent in chronic hepatitis C and linked to other inflammatory features.
- Interferon therapy reduces bile duct inflammation in responding patients.
- Bile duct inflammation does not correlate with class I and II MHC antigen expression.
Abstract:
Inflammation of the bile ducts was studied in liver biopsies from patients with chronic hepatitis C to determine whether the frequency of inflamed bile ducts changes with therapy and correlates with other histological variables and expression of class I and II MHC antigens on ductal epithelium. Twenty patients treated at UMMC between 1991 and 1994 underwent needle biopsies of the liver before and after therapy with interferon alpha 2B (IFN). A complete response to therapy was defined as a return to normal serum alanine aminotransferase levels occurring and persisting during therapy. The number of inflamed bile ducts/total ducts (%IBDs), presence of piecemeal necrosis and lymphoid aggregates, and grade of inflammation were assessed in each high-power field in all areas with bile ducts. The frequencies of these variables were compared in cirrhotics and non-cirrhotics and in patients with complete or incomplete responses to IFN. Frozen sections of biopsies from 5 patients were immunostained using antibodies to HLA-DR and B-2 microglobulin, and positive staining was noted on bile ducts. Before therapy, the %IBD was slightly greater in patients with cirrhosis. After IFN, both %IBD and serum alkaline phosphatase levels decreased in non-cirrhotics who responded to IFN. The change in frequency of IBD with IFN paralleled the changes in the other histological features. No correlation was noted between bile duct inflammation and expression of class I and II antigens. The conclusion is that inflammation of the bile ducts occurs frequently in chronic hepatitis C, correlates with other features of inflammation in the triads, and decreases in response to IFN therapy.
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