Abstract
BackgroundSpontaneous 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.MethodsWe 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.Results15 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.ConclusionNAs 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.
Highlights
Chronic hepatitis B virus (HBV) infection is a major global public health problem
Inclusion and Exclusion Criteria The inclusion criteria were included as following: (1) study population: adult chronic hepatitis B (CHB) patients with spontaneous acute exacerbation (AE) presented with elevation of serum ALT levels to greater than 5 6 upper limit of normal (ULN), studies in patients with Severe acute exacerbation (SAE) of CHB defined as elevation of ALT levels accompanied by jaundice and/or coagulopathy were included; (2) treatment regimen: oral nucleos(t)ide analogues (NAs) monotherapy or in combination; (3) study design: any design including retrospective or open-label prospective studies with or without a control group
Efficacy Measures and Definitions Efficacy measures were categorized as: (1) total liver transplant (LT)-free survival rate defined as proportion of patients with AE of CHB surviving without LT; (2) LT-free survival rate of patients with hepatic decompensation and liver failure owing to AE defined as proportion of patients experienced hepatic decompensation or developed liver failure at baseline or during therapy due to clinical deterioration surviving without LT; (3) worsening of liver disease rate defined as proportion of patients developed liver disease worsening manifested by occurrence of hepatic decompensation and liver failure; (4) biochemical, virological and serological: proportion of patients with ALT normalization, undetectable HBV DNA, hepatitis B e antigen (HBeAg) loss and HBeAg seroconversion
Summary
It is estimated that approximately over 350 million people worldwide have been chronically infected with HBV [1]. Severe acute exacerbation (SAE) presented with high ALT levels accompanied by jaundice can be seen in approximately 15%–37% of CHB patients in 4 years [4]. These exacerbations may progress to acute on chronic liver failure with high potential mortality [5]. 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
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