The Efficacy and Safety of Nucleos(t)ide Analogues in Patients with Spontaneous Acute Exacerbation of Chronic Hepatitis B: A Systematic Review and Meta-Analysis

BACKGROUND Spontaneous acute exacerbation (AE) of chronic hepatitis B (CHB) is often detrimental but sometimes leads to sustained immune control and disease remission. The efficacy and safety of nucleos(t)ide analogues (NAs) in patients with spontaneous AE of CHB remains unclear. METHODS We performed a systematic review and meta-analysis of NAs in patients with spontaneous AE of CHB. We calculated pooled effects of NAs in these patients of each study and conducted quantitative meta-analysis, displaying results using Forest plots. RESULTS 15 studies were included and substantial heterogeneity was noted in the inclusion/exclusion criteria and controls. Pooled data showed no benefit of lamivudine (LAM) vs. untreated controls for transplant-free survival in patients with spontaneous AE of CHB (OR = 0.98 (95% CI, 0.50-1.92; P = 0.956)), hepatic decompensation (OR = 0.94 (95% CI, 0.47-1.88; P = 0.862)) and liver failure owing to AE (OR = 2.30 (95% CI, 0.35-15.37; P = 0.387)) at 3 months. Entecavir achieved even higher short-term mortality than LAM. NAs led to rates of ALT normalization, undetectable HBV DNA, HBeAg loss, HBeAg seroconversion and drug resistance at 1 year in 88%, 61%, 46%, 35% and 5%. Pooled data also showed benefit favoring LAM vs. untreated controls for ALT normalization (OR = 1.98 (95% CI, 1.03-3.80; P = 0.039)) and undetectable HBV DNA (OR = 38.50 (95% CI, 7.68-192.99; P<0.001)) at 3 months. All NAs were relatively safe and well tolerated. CONCLUSION NAs had no obvious impact on short-term survival in patients with AE of CHB, despite of possible better antiviral responses. We suggest additional studies to evaluate the efficacy of other NAs and early introduction of immunosuppressant in combination with NAs. We highlight developing prognostic models to identify predictors of mortality and disease progression for AE of CHB.