Early high peak hepatitis C viral load levels independently predict hepatitis C-related liver failure post-liver transplantation

Abstract

The aim of this study was to examine the importance of the serum hepatitis C viral load within the first year post-liver transplant in determining posttransplant survival. A retrospective analysis of 118 consecutive hepatitis C virus-positive liver transplant recipients who received an allograft from January 1997 to September 2005 was undertaken with a median duration of follow-up of 32.4 months. Univariate and multivariate analyses were used to examine the effects of recipient, donor, surgical, and viral factors on posttransplant outcomes. A total of 620 viral load estimations were undertaken in the first 12 months following transplantation. Patient and graft survival rates at 1, 3, and 5 years were 87.8%, 79.9%, and 70.1% and 87.0%, 79.2%, and 68.2%, respectively. According to multivariate analysis, a peak viral load Ն 10 7 IU/mL (P ϭ 0.004; hazard ratio, 8.68; 95% confidence interval, 2.04-37.02) and exposure to antirejection therapy (P ϭ 0.05; hazard ratio, 2.26; 95% confidence interval, 1.01-5.38) were both independent predictors of diminished patient and graft survival and hepatitis C-related allograft failure. The only other independent predictor of hepatitis C virus-related outcome after transplant was azathioprine use, which was associated with improved outcomes (P ϭ 0.04; hazard ratio, 0.25; 95% confidence interval, 0.07-0.91). A peak viral load in the first year after transplant of Ͼ10 8 , 10 7 to 10 8 , and Ͻ10 7 IU/mL was associated with a mean survival of 11.8, 70.6, and 89.1 months respectively (P Յ 0. Cirrhosis related to chronic infection with hepatitis C virus (HCV) has emerged as the most frequent indication for orthotopic liver transplantation. Presently, approximately 50% of transplants performed in the United States and Europe are for patients infected with HCV.1 The health burden due to HCV is expected to increase to such a degree that by the year 2020, the proportion of untreated HCV patients developing cirrhosis will have increased by 30%.1 Furthermore, it is projected that the number of HCV patients with cirrhosis will double and the number of HCV patients with cirrhosis developing hepatocellular carcinoma (HCC) will increase by 80%.

Liver Transplantation for Hepatitis C: Disease Management

“…HCV antigen expression by hepatocytes can be detected by week 3 [12,13]. HCV RNA levels at this early time point may correlate with histologic severity and fibrosis progression [14][15][16].…”

Treatment of Liver Transplant Recipients Who Have Chronic Hepatitis C Virus Infection

“…16,17 Several reports suggested that viral load before or after transplant did not correlate with the severity of liver disease or predict the timing of HCV recurrence after transplant, but another study showed an association between increased viral titers and worse histologic activity, increased risk of fibrosis, and decreased survival. [17][18][19] Transplant-related factors that may be associated with progression of HCV disease include immunosuppressive treatment. Steroid maintenance therapy has no detrimental effect on graft or patient survival.…”

HCV-Recurrence After Liver Transplantation

“…Progression of graft hepatitis-C seems to be accelerated in patients with HCV-genotype-Ib, high pre-transplant HCV-RNA-load and early post-transplant peak of viremia [29,[35][36][37]. Interestingly, HCVcore protein has been demonstrated to promote inflammation by the release of oxidative stress and to reinforce apoptosis and steatosis.…”

“…In spite of low success rates, HCV-infection is treated by subcutaneous administration of 180μg of Peg-IFN-α2a once a week and oral intake of RBV up to three times per day [22,35,81]. The cumulative duration of antiviral treatment comprises 12-18 months.…”