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Cholestatic hepatitis C in liver allografts
S A Taga1, M K Washington, N Terrault
1Hilo Medical Center, Hilo, HI, USA.
Insights
Hepatitis C virus (HCV) infection can cause cholestasis in liver transplant recipients, leading to aggressive disease and allograft failure. This aggressive HCV variant shows distinct histological features and higher viral loads.
Area of Science:
- Hepatology
- Virology
- Transplant Immunology
Background:
- Hepatitis C virus (HCV) infection is a concern in liver transplant recipients.
- Some recipients develop hyperbilirubinemia, suggesting a cholestatic variant of HCV.
Purpose of the Study:
- To investigate the histological and virological characteristics of cholestatic hepatitis C in liver transplant recipients.
- To compare these features with non-cholestatic HCV hepatitis in a control group.
Main Methods:
- Evaluation of liver biopsy samples from 6 HCV-positive liver transplant recipients with jaundice.
- Comparison with biopsy samples from HCV hepatitis patients without jaundice.
- Exclusion of patients with known ductopenic rejection, biliary obstruction, or co-infections.
- Measurement of viral titers and genomic typing.
Main Results:
- Patients with cholestasis exhibited more severe histological damage, including interface hepatitis, confluent necrosis, bridging fibrosis, hepatocyte swelling, and ductular proliferation.
- All 6 patients with cholestasis experienced allograft failure, unlike the control group.
- Patients with cholestasis had significantly higher HCV RNA titers compared to the control group.
Conclusions:
- Cholestasis in post-transplant hepatitis C may be driven by an aggressive HCV infection.
- Histological features like confluent necrosis, hepatocyte swelling, and ductular proliferation are indicative of this aggressive form.
- Elevated viral titers are common in patients with cholestatic HCV post-transplantation.
Abstract:
Some liver allograft recipients with hepatitis C virus (HCV) infection develop hyperbilirubinemia, which might be the result of a cholestatic variant of hepatitis C. We evaluated all liver biopsy samples from 6 liver transplant recipients who had polymerase chain reaction-positive HCV infection and histologic evidence of hepatitis and jaundice and compared them with liver biopsy samples from a control group of transplant recipients with HCV hepatitis without jaundice. Patients with known ductopenic rejection, biliary obstruction, or co-infection with hepatitis A or B were excluded from the study. Measurement of viral titers and genomic typing were performed when possible. Six patients developed hepatitis and jaundice, with maximum bilirubin levels ranging from 5.8 to 47.6 mg/dL. In this group, 5 (83%) had moderate interface hepatitis (control group, 15%), 6 (100%) had confluent necrosis (control group, 12%), 5 (83%) had bridging fibrosis (control group, 18%), 4 (67%) had significant hepatocyte swelling (control group, 9%), 4 (67%) had prominent ductular proliferation (control group, 3%), and 6 (100%) had mild duct damage and inflammation (control group, 53%). All 6 of the patients with cholestasis had allograft failure. Of these, three allografts were available for review, which did not reveal occult obstruction, rejection, or duct loss. All patients in the control group have retained their allografts. In 4 patients with cholestasis, the median HCV RNA titer was 93.97 mEq/mL, with a mean of 54.19 mEq/mL (control mean = 5.2 mEq/mL). Five patients also underwent viral genomic typing: 2 with type 1a, 2 with type 1b, and 1 with mixed type 1a and 1b. Cholestasis in patients with posttransplantation hepatitis C may be caused by an aggressive HCV infection that exhibits histologic features of confluent necrosis, hepatocyte swelling, and/or ductular proliferation. Viral titers are often increased in such patients.