Rapid Fibrosis and Significant Histologic Recurrence of Hepatitis C After Liver Transplant Is Associated With Higher Tumor Recurrence Rates in Hepatocellular Carcinomas Associated With Hepatitis C Virus-Related Liver Disease DR.BHAVIN VASAVADA

INTRODUCTION Hepatitis C virus recurrence after transplant is universal and results in progressive fibrosis, cirrhosis, graft loss, retransplant, and mortality. The course of graft hepatitis usually is more progressive than that of primary HCV infection. Histologic recurrence is observed in > 50% HCV infected grafts within the first year and is responsible for allograft failure in 10% recipients within 5 years of transplant.

AIMS OF STUDY To evaluate factors responsible for hepatocellular carcinoma recurrence and mortality including histologic markers.

Materials and Methods All patients who underwent living-donor liver transplant at Kaohsiung Chang Gung Memorial Hospital, Taiwan for HCV-related HCC from July 2002 to June 2012 were analyzed retrospectively.

DEFINITIONS Rapid fibrosers were defined as patients who developed grade 2 or more Ishak grade fibrosis within 1 year after liver transplant. The Hepatitis Activity Index (HAI) according to the Ishak score also was noted. We defined posttransplant Ishak score ≥ 6 as significant for HCV recurrence. Berenguer M, Prieto M, Palau A, et al. Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus-related graft cirrhosis. Liver Transpl. 2003;9(3): Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):

Protocol biopsies We perform protocol biopsy at 4 months and 1 year after liver transplant for HCV. Additional biopsies were performed when HCV recurrence was suspected. The HAI was noted according to the Ishak HAI, and fibrosis was noted according to the Ishak fibrosis score.

Follow-up protocol We followed patients who had HCC with ultrasonography and computed tomography scanning every – 3 months for the first year – every 6 months for the second year – yearly after the second year.

Results 109 patients with HCC associated with HCV who underwent living-donor liver transplant from July 2002 to June Median follow-up was 31 months. 14 patients who had HCC recurrence, 4 patients had intrahepatic and 10 patients had metastatic recurrence. 19 patients who had fibrosis grade > 2 at the end of 1 year and were defined as rapid fibrosers. 36 patients who had HAI ≥ 6 at the end of 1 year and were defined as having significant histologic recurrence.

. Pa tient characteristics and univariate and multivariate analysis for overall recurrence and survival

Recurrence-Free Survival in Rapid and Nonrapid Fibrosers P =.008; odds ratio, 0.326; 95% confidence interval,

Recurrence-Free Survival With Hepatitis Activity Index (HAI) ≥ 6 or < 6 P =.008; Odds ratio 4.467; 95% confidence interval,

Survival Comparison Between Patients Who Received or Did Not Receive Post-transplant Interferon P=0.043

Survival Comparison Between Patients Who Received or Did Not Receive Pretransplant Interferon P=0.009

CONCLUSIONS HCV recurrence on biopsy (HAI and fibrosis stage) is a poor prognostic factor and associated with higher risk of HCC recurrence after liver transplant. Rapid fibrosis after liver transplant independently predicts HCC recurrence. Pre operative and post operative HCV treatment helps in improvement of over-all survival Effect of new regimes for HCV treatment on HCC recurrence needs to be studied.

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