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

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.

Development and validation of a scoring system to predict progression to acute‐on‐chronic liver failure in patients with acute exacerbation of chronic hepatitis B

“…High HBV‐DNA levels correlate with the development of HCC and LC in patients with chronic HBV infection . However, whether HBV‐DNA levels influence short‐term outcomes in patients with AE of chronic HBV infection remains unclear . Jeng et al .…”

Causes of Acute Exacerbation of Chronic Hepatitis B Infection: A Report of Case Series

“…In one of our patients, decompensated cirrhosis developed and she had to be sent to a transplant center with acute failure on chronic basis. Antiviral therapy is recommended in patients with acute exacerbation to prevent a higher degree of liver damage (23,24,25). In this study, antiviral therapy (lamivudine or tenofovir disoproxil fumarate) was given to all patients previously untreated and, except in one patient mentioned above, it seemed successful.…”

Relationship between hepatitis B virus genotype B and C and response to interferon therapy in HBeAg positive chronic hepatitis B patients: A meta‐analysis

“…Second, the inclusion criteria and patients number varied greatly among the studies included. The heterogeneity in patient populations may lead to a lower level of confidence in the accuracy of the pooled estimates . However, all the study patients had characteristics of HBeAg‐positive CHB, and we were able to extract the majority parameters of most studies.…”

“…The heterogeneity in patient populations may lead to a lower level of confidence in the accuracy of the pooled estimates. 34 However, all the study patients had characteristics of HBeAg-positive CHB, and we were able to extract the majority parameters of most studies. Lastly, significant heterogeneities were observed in most meta-analyses, so generalization and interpretation of the results should be done with consideration.…”