Significance of hepatitis B virus genotype in liver transplantation for chronic hepatitis B

Abstract

Hepatitis B virus (HBV) genotype influences the disease profile in chronic hepatitis B but its significance in patients who undergo liver transplantation (LTx) is not known. One hundred and nineteen patients with chronic HBV infection who underwent LTx using lamivudine prophylaxis had HBV genotype identifiable from the pre-transplant sera by direct sequencing technique (genotype A, 1; B, 43; C, 74; D, 1). The baseline characteristics and outcome after LTx of patients with genotype B (M:F, 38:5; median [range] age, 45 [17-66] years) were compared to those with genotype C (M:F, 68:6; median [range] age, 49 [21-61] years). More genotype B patients underwent LTx for acute decompensation with flare of HBV ( 15 of 43 Vs 9 of 74; p= 0.003) than genotype C, resulting in a higher serum alanine aminotransferase (58 U/L Vs 40 U/L; p=0.003), serum total bilirubin (426 μmol/L Vs 71 μmol/L); p=0.012), international normalized ratio (2.2 Vs 1.6; p=0.001), and MELD score (34 Vs 18; p=0.004). There were more patients seronegative for HBeAg on listing in genotype B (36 of 41 Vs 41 of 73; p=0.001) than genotype C but the difference in seropositivity for HBVDNA was not significant (26 of 40 Vs 34 of 69; p=0.112). The graft survival at 1, 2, and 3 years after LTx were 93%, 83%, and 83% for genotype B and 100%, 93%, and 89% for genotype C (p=0.2), respectively. Two patients of genotype B and 12 patients of genotype C developed mutants with resistance to lamivudine. The mutant-free survival at 1, 2, and 3 years after LTx were 100%, 100%, and 96% for genotype B and 88%, 82%, and 79% for genotype C (p=0.017), respectively. Liver biopsy taken after the development of mutants showed recurrent hepatitis B in 7 of 10 patients of genotype C, including 2 with fibrosing cholestatic hepatitis and no histologic evidence of hepatitis B in both patients of genotype B. Our data suggest that HBV genotypes B and C are associated with different patterns of end-stage liver disease that required transplantation and genotype C carries a higher risk of recurrence with lamivudine prophylaxis.