Abstract: Objective To study hepatitis B virus (HBV) basic core promoter and pre-C (PC) nucleotides mutations in patients coinfected with hepatitis E virus (HEV) related acute on chronic liver failure (ACLF) , and to analyze the clinical characteristics.Methods Sixty-nine cases with ACLF caused by HBV infection were retrospectively analyzed, of which 39 patients suffered single HBV infection, and the other 30 patients suffered HBV and HEV coinfection. Liver function, HBV DNA level, blood coagulation function, model for end stage liver disease (MELD) score and prognosis of the two groups were compared respectively. Polymerase chain reaction (PCR) was used for assessing HBV PC region amplification. Sequencing analysis was applied to detect reported ACLF-related mutation sites A1762T, G1764A, C1766T, T1768A, G1896A, A1762T + G1764A and G1764A + C1766T + T1768A for comparative analysis between the two groups. The survival rates and mortality of patients with HBV and HEV coinfection were evaluated for related prognostic factors by logistic regression analysis. Results In the coinfection group, total bilirubin (TBiL), incidence of hepatic encephalopathy and levels of the MELD score were significantly increased (216.4 ± 12.1 vs 364.2 ± 170.24, 17.9% vs 33.3%, 21.26 ± 6.65 vs 28.26 ± 8.65, respectively) when compared with those in single infection group, while prothrombin time activity (PTA) was obviously decreased (33.3 ± 22.4 vs 24.5 ± 20.1) (P<0.05). The comparative analysis of HBV-PC mutation sites A1762T (66.7% vs 76.7%), G1764A (69.2% vs 80.0%), A1762T+G1764A (59.0% vs 70.0%) and G1764A+C1766T+T1768A (2.6% vs 10.0%) showed statistically differences between the two groups (P<0.05). Additionally, among HBV and HEV coinfection patients, the MELD score and incidence of hepatic encephalopathy in death group increased significantly when compared to those in survival group, but the PTA decreased obviously (P<0.05). The comparative analysis of HBV-PC mutation site G1764A + C1766T + T1768A triplet mutation also showed significant difference (P<0.05) between the two groups in patients with coinfection. The logistic regression analysis suggested that TBiL (P=0.006, OR=2.672), PTA (P=0.036, OR=2.115), MELD score (P=0.003, OR=1.682), hepatic encephalopathy incidence (P=0.001, OR=3.631) and G1764A + C1766T + T1768A triplet mutation (P=0.043, OR=0.043) were all related to the prognosis.Conclusion The prognosis is poor in ACLF patients caused by HBV and HEV coinfection, which could be indicated from high TBiL level, MELD score, incidence of hepatic encephalopathy and HBV-PC area G1764A+C1766T+T1768A triplet mutation rate. Furthermore, lower PTA level always predicts a worse prognosis.

Key words: Hepatitis B virus, Hepatitis E virus, Acute-on-chronic liver failure, HBV-PC nucleotides mutations