HBV合并HEV感染导致慢加急性肝衰竭HBV-PC区变异及临床特征分析

Analysis of HBV PC mutations in ACLF patients infected with HBV combined HEV and their clinical characteristics

目的分析乙型肝炎病毒合并戊型肝炎病毒导致的慢加急性肝衰竭的HBV-PC区变异及临床特征。方法回顾性分析HBV感染的慢加急性肝衰竭(ACLF)患者69例,其中单独HBV感染患者39例,HBV合并HEV感染患者30例;比较2组患者肝功能、HBV DNA水平、凝血功能、MELD评分以及预后情况;PCR扩增HBV-PC区序列,测序与ACLF相关的变异位点A1762T、G1764A、C1766T、T1768A、G1896A、A1762T+G1764A、G1764A+C1766T+T1768A,比较两组患者之间的差异。分析HBV合并HEV感染存活与死亡患者,Logistic回归分析重叠感染患者预后相关因素。结果与单纯HBV感染组比较,合并HEV感染组患者的TBil[(216.4±12.1)μmol/L对(364.2±170.24)μmol/L]、肝性脑病发生率(17.9%对33.3%)、MELD评分(21.26±6.65对28.26±8.65)均呈不同程度的升高;PTA[(33.3±22.4)%对(24.5±20.1)%]明显降低,差异均有统计学意义(P<0.05);2组患者HBV-PC变异分析比较位点A1762T(66.7%对76.7%)、G1764A(69.2%对80.0%)、A1762T+G1764A(59.0%对70.0%)和G1764A+C1766T+T1768A(2.6%对10.0%)差异有统计学意义(P<0.05)。HBV合并HEV感染患者存活组与死亡组比较,MELD评分和肝性脑病发生率明显升高,PTA明显降低,差异均有统计学意义(P<0.05);HBV-PC变异分析比较G1764A+C1766T+T1768A三联变异差异有统计学意义(P<0.05);Logistic回归分析显示,TBil(P=0.006,OR=2.672)、PTA(P=0.036,OR=2.115)、MELD评分(P=0.003,OR=1.682)、肝性脑病并发症(P=0.001,OR=3.631)和G1764A+C1766T+T1768A三联变异(P=0.043,OR=2.081)因素与预后有关。结论单独HBV与合并HEB感染导致的ACLF患者病情更加严重,预后更差。TBil、MELD评分、肝性脑病并发症和HBV-PC区G1764A+C1766T+T1768A三联变异发生率越高。PTA越低,ACLF患者预后越差。

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,C1766 T,T1768A,G1896A,A1762T ＋ G1764A and G1764 A ＋ 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.