RESUMEN
INTRODUCTION AND OBJECTIVES: Hepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB. PATIENTS AND METHODS: Patients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models. RESULTS: Sixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study. CONCLUSION: Although it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.
Asunto(s)
Hepatitis B Crónica , Metformina , Humanos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Antígenos e de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Metformina/efectos adversos , Antivirales/efectos adversos , ADN Viral , Virus de la Hepatitis B/genética , Resultado del TratamientoRESUMEN
BACKGROUND: The effectiveness of nucleoside analogue (NA) treatment in patients with chronic hepatitis B (CHB) -associated liver failure is still controversial. Severe lactic acidosis has been reported during entecavir (ETV) treatment in patients with impaired liver function. AIM: To investigate the rescuing efficacy and safety of ETV in patients with CHB-associated liver failure. MATERIAL AND METHODS: A literature search was carried out to collect articles dated up to December, 2013 on ETV therapy for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was used as the primary efficacy measure. The safety of ETV was assessed. RESULTS: Six randomized controlled trials were selected. The overall analysis revealed ETV significantly improved survival at 4 weeks (RR = 1.35; 95% CI [1.16, 1.57]; p < 0.0001), 8 weeks (RR = 1.33; 95% CI [1.07, 1.64]; p = 0.009), 12 weeks (RR = 1.68; 95% CI [1.24, 2.28]; p = 0.0008). Pooled data also showed beneficial effects of antiviral therapy compared with control for HBV DNA negative change (RR = 5.35; 95% CI [2.06, 13.88]; p = 0.0006), TBIL and PTA improvement (TBIL: MD = -69.36; 95% CI [-134.37, -4.36]; p = 0.04. PTA: MD = 16.26; 95% CI [8.59, 23.94]; p < 0.0001). No adverse effect was identified in the examined studies. CONCLUSION: Our results showed that antiviral therapy with ETV improved the short-term survival of patients with CHB-associated liver failure. In addition, ETV was well tolerated during the treatment period. Further studies are still needed to strengthen these results.