Xueyuan Nian1, Zhihui Xu2, Yan Liu2, Jianhong Chen3, Xiaodong Li2, Dongping Xu4,5. 1. Institute of Infectious Diseases, 302 Teaching Hospital of Peking University, Beijing, 100039, China. 2. Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, 100039, China. 3. Department of Infectious Disease, Peking University First Hospital, Beijing, 100034, China. 4. Institute of Infectious Diseases, 302 Teaching Hospital of Peking University, Beijing, 100039, China. xudongping302@sina.com. 5. Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, 100039, China. xudongping302@sina.com.
Abstract
BACKGROUND: The relationship between hepatitis B virus (HBV) mutations in basal core promoter (BCP) and precore (PC) regions and the risk of hepatitis B-related acute-on-chronic liver failure (HB-ACLF) remains uncertain. METHODS: Databases were searched for papers that were published in English or Chinese until April 31, 2015. The odds ratios (ORs) of HBV mutation were pooled by using a fixed or random-effects model according to heterogeneity. RESULTS: Data for 13 studies with a total of 1,149 HB-ACLF and 1,867 chronic hepatitis B (CHB) cases were retrieved. Statistically significant summary ORs for HB-ACLF were obtained for T1753V (1.99; 95 % confidence interval 1.30-3.02) and A1762T/G1764A (2.11; 95 %, 1.75-2.54) in the BCP region and for A1846T (3.33; 95 %, 2.23-4.97), G1896A (2.78; 95 %, 2.07-3.74), and G1899A (3.09; 95 %, 1.82-5.25) in the PC region. In subgroup analysis, BCP mutations were found to have higher ORs in age-matched studies, but PC mutations were found to have higher ORs in age-unmatched studies; patients with the mutations in HBV genotype C were more susceptible to HB-ACLF; patients with pre-existing liver cirrhosis had a higher risk of HB-ACLF occurrence. In sensitivity, specificity, and accuracy analysis, A1762T/G1764A had the highest sensitivity (67.43 %); A1762T/G1764A + G1896A triple mutations had the highest specificity (93.70 %); and T1753V + A1762T + G1764A mutation had the highest accuracy (65.42 %). CONCLUSIONS: HBV T1753V, A1762T/G1764A, A1846T, G1896A, and G1899A mutations are correlated with an increase in the risk of HB-ACLF. These mutations alone and in combination may be predictive of the susceptibility of patients with CHB to developing HB-ACLF.
BACKGROUND: The relationship between hepatitis B virus (HBV) mutations in basal core promoter (BCP) and precore (PC) regions and the risk of hepatitis B-related acute-on-chronic liver failure (HB-ACLF) remains uncertain. METHODS: Databases were searched for papers that were published in English or Chinese until April 31, 2015. The odds ratios (ORs) of HBV mutation were pooled by using a fixed or random-effects model according to heterogeneity. RESULTS: Data for 13 studies with a total of 1,149 HB-ACLF and 1,867 chronic hepatitis B (CHB) cases were retrieved. Statistically significant summary ORs for HB-ACLF were obtained for T1753V (1.99; 95 % confidence interval 1.30-3.02) and A1762T/G1764A (2.11; 95 %, 1.75-2.54) in the BCP region and for A1846T (3.33; 95 %, 2.23-4.97), G1896A (2.78; 95 %, 2.07-3.74), and G1899A (3.09; 95 %, 1.82-5.25) in the PC region. In subgroup analysis, BCP mutations were found to have higher ORs in age-matched studies, but PC mutations were found to have higher ORs in age-unmatched studies; patients with the mutations in HBV genotype C were more susceptible to HB-ACLF; patients with pre-existing liver cirrhosis had a higher risk of HB-ACLF occurrence. In sensitivity, specificity, and accuracy analysis, A1762T/G1764A had the highest sensitivity (67.43 %); A1762T/G1764A + G1896A triple mutations had the highest specificity (93.70 %); and T1753V + A1762T + G1764A mutation had the highest accuracy (65.42 %). CONCLUSIONS:HBVT1753V, A1762T/G1764A, A1846T, G1896A, and G1899A mutations are correlated with an increase in the risk of HB-ACLF. These mutations alone and in combination may be predictive of the susceptibility of patients with CHB to developing HB-ACLF.
Entities:
Keywords:
Acute-on-chronic liver failure; Hepatitis B virus; Meta-analysis; Mutation
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