Hepatitis C genotype influences post-liver transplant outcomes

Abstract

Background: In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.

Methods: Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.

Results: Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.

Conclusion: Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.

Fig. 1

Unadjusted Cumulative Rate of Advanced Fibrosis by HCV-genotype in HCV-infected liver transplant recipients. The unadjusted cumulative rates of advanced fibrosis at 1, 3 and 5 years post-LT were 8%, 31% and 46% for patients with HCV genotype 1; 0%, 19% and 19% for HCV genotype 2; and 2%, 19% and 32% for HCV genotype 3 (log rank=0.008).

Fig. 2

Causes of Death by HCV-genotype in HCV-infected liver transplant recipients. HCV-related deaths were 55 (48%), 2 (27%) and 3 (25%) for genotype 1, 2 and 3 respectively. HCC-related deaths were 10 (9%), 1 (9%) and 4 (33%) for genotypes 1, 2 and 3 respectively; (p=0.06).