Genome-wide analysis of mRNA and miRNA expression of hepatitis B virus (HBV)-associated acute liver failure reveals a dominant B-cell disease signature

INTRODUCTION: Spontaneous reactivation of hepatitis B is common. Some may develop jaundice and hepatic decompensation [acute-on-chronic liver failure (ACLF-B)] and are at risk of renal dysfunction and high mortality. Tenofovir improves survival by >40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine with tenofovir may negate this risk and could boost rapid viral clearance, thereby improving clinical outcomes. METHODS: Consecutive patients with spontaneous reactivation of hepatitis B [(ALT >59 ULN/ >39 baseline) + HBV DNA >1.8 9 10 IU/mL] were randomized to tenofovir (300 mg/day) monotherapy [TM] or tenofovir plus telbivudine (600 mg/day) dual therapy [DT] along with standard medical therapy. Clinical, virological and lab parameters were evaluated at baseline, at week 2, 4 and at 3 month. None had an option for liver transplantation. Primary end point was HBsAg loss. Secondary end points were serial reduction in HBV DNA, liver related complications, therapy related adverse effects and Survival at 1 and 3 month in subgroup with ACLF-B. RESULTS: Of 69 patients (TM, n = 35 and DT, n = 34), 25 had ACLF-B (TM, n = 13 and DT, n = 12). Overall baseline parameters in two treatment groups were comparable with no significant differences in MELD score, bilirubin and INR at week 2, 4 and 3 month of therapy. Patients with non-ACLF had rapid decline in bilirubin and ALT at 2 week as compared to ACLF-B, in whom the reduction was gradual. In ACLF-B patients, mean MELD score was 26.23 5.57 (TM) and 27.42 8.20 (DT) (p-0.8) but those on DT had significant improvement in MELD and bilirubin at week 4 and 3 month in comparison to baseline. 6 patients had HBsAg loss at 12 weeks, all in non-ACLF group and these patients had lower HBV DNA at baseline. Only one had anti-HBs+ at 24–36 weeks. Patients with ACLF-B receiving DT showed improvement in AKI on follow up compared to those on TM (p-0.05). Among 10 deaths in ACLF-B, 8 had received TM (p-0.02). Predictors of mortality in ACLF-B were septic shock, TM, e Antibody positivity and high baseline MELD score. CONCLUSIONS: In spontaneous reactivation of hepatitis B presenting as liver failure, combination of telbivudine with tenofovir is potentially safe with less risk of tenofovir related nephrotoxicity and hence improved outcomes. HEPATITIS B PATHOGENESIS