A randomized open label trial of tenofovir monotherapy versus tenofovir plus telbivudine in spontaneous reactivation of hepatitis B.

ABSTRACT: Background/Aim:Acute-on-chronic liver failure (ACLF-B) in spontaneous reactivation of chronic hepatitis B (SR-CHB) has high mortality. Tenofovir disoproxil fumarate (TDF) improves survival by ~40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine (LDT) with TDF may negate this risk and could boost rapid viral clearance and improve clinical outcomes. Patients and Methods:Seventy consecutive patients with SR-CHB were randomized to TDF (300 mg/day, n = 35) or TDF plus LDT (600 mg/day; n = 35). In all, 25 had ACLF-B and none had option for liver transplantation. Primary endpoint was survival at 3 months. Secondary endpoints were survival at 3 months in ACLF-B, serial reduction in hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) loss and liver-related complications. Results:Overall baseline clinical and laboratory parameters in the two groups were comparable. Reduction in HBV DNA at weeks 2, 4 and 12 was independent of treatment groups and presence of ACLF-B (P < 0.01). All six patients with HBsAg loss at 12 weeks had lower HBV DNA at baseline and none had ACLF-B. Patients with no ACLF-B had more rapid decline in bilirubin and alanine aminotraminase at week 2 compared with ACLF-B. Patients on TDF plus LDT showed significant improvement in AKI on follow-up (five of six patients) compared with TDF monotherapy (none of six patients) and had less reduction in estimated glomerular filtration rate at week 12. Eight of 10 patients with liver-related deaths received TDF monotherapy (P = 0.02). New-onset septic shock, TDF monotherapy, e-antibody positivity, and higher baseline model for end-stage liver disease score were predictors of mortality in ACLF-B. None had treatment-related severe adverse effects. Conclusion:Addition of LDT to tenofovir is safe and may be renoprotective in spontaneous reactivation of hepatitis B. Combination therapy improves survival in ACLF-B despite comparable HBV DNA suppression to tenofovir monotherapy.

SUBMITTER: Jindal A 

PROVIDER: S-EPMC6784432 | biostudies-literature | 2019 Sep-Oct

REPOSITORIES: biostudies-literature