INCREASED HEPATITIS C VIREMIA IN CHOLESTATIC HEPATITIS C FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION. IS THE PATHOGENECITY OF THE SYNDROME RELATED TO VIRAL CYTOPATHIC MECHANISMS?

Abstract

410 Introduction: Progressive cholestatic jaundice in hepatitis C (HCV) patients (pts) following orthotopic liver transplantation (OLTx) is associated with significant morbidity and mortality. The pathogenesis of this syndrome is not known. The aim of this study was to retrospectively compare pts with HCV who developed jaundice post transplant to a matched group of controls who had an uneventful clinical course. Patient and Methods: Cholestatic jaundice was defined as having a serum bilirubin >5.0mg/dL for more than one month, except for three patients who died within one month and were included in the analysis. Other causes such as acute rejection, biliary obstruction, vascular compromise, and viral diseases other than HCV were excluded. Twenty one (10%) of 212 pts transplanted for HCV cirrhosis had cholestatic hepatitis (Grp I). These pts were matched with 21 HCV pts who underwent OLTx but did not develop cholestasis (Grp II). Matching was random and blinded without knowledge of viral load. The two groups were matched for: age, sex, crossmatch, and timing of transplantation. Grp I consisted of 21 pts (11 females/10 males) with median age of 44 years(33-63 years). Grp II consisted of 21 pts (11 females/10 males) with median age 47 years (37-61 years). The positive lymphocytic cytotoxic crossmatch was also similar between the two groups (Grp I n=2, Grp II n=3). Serum HCV-RNA levels were measured by signal amplification of Chiron (Emeryville, CA) and converted into log scale. HCV-RNA levels for Grp I were measured pre transplant, at onset of jaundice, monthly during jaundice, and at the end of jaundice or death. Grp II HCV-RNA levels were measured at similar times after transplant (in terms of post-op days). Results: The duration of jaundice ranged from 9 to 468 days (median 99 days). Follow-up is provided through December 1997 and is similar among the two groups. Grp I (median 281 days, range 44-1114 days) and Grp II (median 246 days, range 29-1212 days). There was a statistically significant difference in serum HCV-RNA levels at all time points (Grp I vs Grp II): pre-op 6.41±0.661 vs 5.79±0.557 (p=0.007), onset of jaundice 7.47±0.767 vs 6.64±0.888 (p=0.004), during jaundice 7.62±0.338 vs 6.92±0.717 (p=0.0007), and at end of the event of jaundice 7.43±0.685 vs 6.76±1.001 (p=0.04). Cirrhosis was evident in five pts in Grp 1 and in no pts in Grp II (p=0.02). Genotyping was available on 7 pts in Grp 1: 1a n = 5, 1b n = 1, and mixed n = 1. Grp I had an 86% mortality rate (18/21) and Grp II a 10% mortality (2/21),(p=0.00000002). The causes of death in Grp I were: recurrent HCV n = 13, chronic rejection n = 2, sepsis n = 3. The causes of death in Grp II were: chronic rejection n = 1, and cardiac tamponade n = 1. Conclusions: 1) Cholestatic jaundice post-OLTx occurred in (10%) of pts and was associated with significant mortality. 2) Hepatitis C viremia was significantly higher at various times in pts with cholestasis. 3) Pathogenetic mechanisms may involve virus related cytopathic effects.