Histologically but Not Clinically Defined Fibrosing Cholestatic Hepatitis C Is Predictive of Poor Patient Outcomes in the Liver Transplant Population
Z Meriden, R Wells, G Makar, R Reddy, EE Furth. University of Pennsylvania, Philadelphia, PA
Background: Fibrosing cholestatic hepatitis (FCH) is a specific form of liver disease with poor patient outcome following transplantation for hepatitis C. There is no standard definition of FCH, and both clinical and/or histologic ones are used. The goal of our study was to compare patient and liver allograft outcomes of clinically and histologically, prospectively defined FCH.
Design: FCH was diagnosed prospectively by histology (HFCH: pericellular fibrosis, cholestatic injury, minimal inflammation) and clinically (CFCH: total bilirubin >4 for >30 days with other etiologies excluded and high viral load (>6 log normal) from a total cohort of 314 liver transplants performed for hepatitis C (2003-2007). Portal and pericellular fibrosis in post- transplant biopsies were scored by METAVIR (0-4) and a tiered system (absent=0, mild=1, moderate=2, severe=3), respectively. Fibrosis progression and survival among the cohorts and subsets therein were compared by the Kaplan-Meier method.
Results: The total FCH (TFCH) cohort (n=28:13 HFCH, 17 CFCH, 2 had both) had a mean patient and donor age of 50 and 44 years, respectively, with no statistically significant demographic differences between HCFH and CFCH. Cirrhosis progression in TFCH approximated that of the total patient cohort (P=0.1316), with a median time to cirrhosis of 4.7 years. Progression to cirrhosis between HFCH and CFCH groups was not different (P=0.5438). However, in TFCH, the rate of severe pericellular fibrosis development exceeded that of the total cohort by a factor of 4 (P=0.0076, HR 4.444, 95% CI 1.487-13.28), with 36% of TFCH having severe pericellular fibrosis by the end of year 1 post-transplant. While cirrhosis progression between HFCH and CFCH was similar, the rate of severe pericellular fibrosis development was 10-fold greater in HFCH (P=0.0002; HR=10.41; 95% CI = 3.059-35.43). Patients with HFCH had poorer survival than CFCH, with a nearly 5-fold greater rate of deaths (P=0.0226; HR 4.819; 95% CI 1.247-18.62) and median survival of 1.9 years.
Conclusions: The development of cirrhosis in TFCH patients only mirrors that of the general transplanted population, with no difference in those with HCFH vs. FCFH. However, patients with TFCH develop pericellular fibrosis more rapidly than the general population, with the effect being more dramatic in the HFCH subtype. In contrast to patients with CFCH, those with HFCH experience not only greater pericellular fibrosis progression, but also poorer patient outcomes.
Category: Liver & Pancreas
Monday, March 22, 2010 2:15 PM
Platform Session: Section D, Monday Afternoon