慢性乙型肝炎（CHB）是我国常见的传染病,随着乙型肝炎病毒（HBV）在体内持续活跃复制可进展为肝硬化甚至肝癌,严重威胁患者健康与生命,而高病毒载量CHB患者不仅进展为肝硬化、肝癌的风险和发生母婴垂直传播的风险增加,还存在抗病毒治疗病毒学应答率偏低等特点,目前对高病毒载量CHB患者的管理已引起国内外学者的关注,但尚缺乏系统的研究与阐述。本文将针对上述问题结合国内外相关文献进行综述,期望今后本领域学者对高病毒载量CHB这类特殊患者能有更深入的研究。

Chronic hepatitis B（CHB）is a common infectious disease in China．With the continuous active replication of hepatitis B virus（HBV）in the body,cirrhosis and even liver cancer can progress,seriously threatening the health and life of patients．However,CHB patients with high viral load not only have an increased risk of cirrhosis and liver cancer,mother-to-child vertical transmission,but also with a lower rate of virological response to antiviral therapy．At present,the management of CHB patients with high viral load has attracted the attention of scholars at home and abroad,but there is still a lack of systematic research and elaboration．This paper will focus on the above problems combined with relevant domestic and foreign literature review,hoping that scholars in this field can have more in-depth research on special patients with high viral load CHB in the future．

目的 探讨与研究白介素-33（IL-33）、白介素-37（IL-37）、亮氨酸富集的核苷酸结合寡聚结构域-3（NLRP-3）及自然杀伤（NK）细胞/树突状细胞（DC）比值与慢性乙型肝炎（CHB）患者病情的相关性。方法 研究时间为2020年2月—2022年9月,选择在本院诊治的86例CHB患者作为肝炎组,同期选择86名体格检查健康者作为对照组。检测2组血清IL-37、IL-33、NLRP3含量,并计算NK/DC比值。对所有入选者的血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）含量进行检测并实施相关性分析。结果 与对照组相比,肝炎组的血清ALT、TBIL、AST有的增高趋势（P<0.05）,肝炎组的血清IL-33、IL-37、NLRP3含量更高（P<0.05）,NK/DC比值下降（P<0.05）。在肝炎组中,Pearson分析显示IL-33、IL-37、NLRP3、NK/DC比值与ALT、TBIL、AST均存在相关性（P<0.05）。在肝炎组中,ROC曲线分析显示IL-33、IL-37、NLRP3、NK/DC比值预测CHB病情的曲线下面积为0.705（95%CI：0.404~1.123）、0.690（95%CI：0.372~1.057）、0.670（95%CI：0.378~1.043）、0.685（95%CI：0.415~1.107）,联合检测预测病情的曲线下面积为0.895（95%CI：0.532~1.216）,与单独检测相比,联合检测具有更高的特异度与灵敏度。结论 CHB患者多伴随有血清IL-33、IL-37、NLRP3的高表达,并且NK/DC比值会降低,IL-33、IL-37、NLRP3及NK/DC比值与CHB患者病情存在相关性,联合检测对患者病情具有一定的预测性。

Objective To explore and study the correlation between interleukin-33(IL-33),interleukin-37(IL-37),leucine-enriched nucleotide-binding oligomeric domain(NLRP)- 3,the ratio of natural killer(NK)cells/dendritic cells(DC)and the conditions of patients with chronic hepatitis B(CHB). Methods From February 2020 to September 2022,86 patients with CHB treated in our hospital were selected as hepatitis group,and 86 healthy patients were selected as control group during the same period. The contents of IL-37,IL-33 and NLRP3 in serum of the two groups were detected,and NK/DC ratio was calculated. Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBIL)of all the selected subjects were detected and correlation analysis was carried out. Results Compared with the control group,the serum ALT,TBIL and AST in hepatitis group were significantly increased(P<0. 05),the contents of IL-33,IL-37 and NLRP3 were higher(P<0. 05),and the NK/DC ratio was significantly decreased(P<0. 05). In the hepatitis group,Pearson analysis showed that IL-33,IL-37,NLRP3 and NK/DC ratios were correlated with ALT,TBIL and AST(P<0. 05). In the hepatitis group,ROC curve analysis showed that the maximum areas under the curve of IL-33,IL-37,NLRP3 and NK/DC ratios were 0. 705(95%CI：0. 404-1. 123),0. 690(95%CI：0. 372-1. 057),0. 670(95%CI：0. 378-1. 043)and 0. 685(95%CI：0. 415-1. 107),and the maximum area under the curve of combined detection was 0. 895(95%CI：0. 532-1. 216). Compared with single detection,combined detection had higher specificity and sensitivity. Conclusions The patients with CHB are often accompanied by the high expression of serum IL-33,IL-37 and NLRP3,and the NK/DC ratio will be significantly reduced. IL-33,IL-37,NLRP3 and NK/DC ratio are correlated with the condition of patients with CHB,and can also predict the condition of patients.

目的 分析单核细胞-淋巴细胞比率（MLR）联合游离三碘甲腺原氨酸（FT₃）对乙型肝炎病毒（HBV）相关慢加急性肝衰竭（ACLF）患者生存状况的预测效果。方法 纳入我院在2019年1月—2022年1月期间收治的HBV-ACLF患者共187例进行研究,随访患者90 d的生存状况,其中69例死亡患者设为死亡组,其余118存活患者设为存活组。对2组患者的各项资料进行单因素分析,对差异有统计学意义的因素行Logistic多因素分析,分析HBV-ACLF患者死亡的危险因素,并分析MLR联合FT3对HBV-ACLF死亡的预测效果。结果 死亡组患者的年龄、肝硬化发生率、原发性腹膜炎发生率、肝肾综合征发生率、电解质紊乱发生率、终末期肝病模型、MLR、中性粒细胞与淋巴细胞计数比值、国际标准化比值、肌酐、白细胞计数、总胆红素水平均高于B组,血钠、FT₃、总血清胆固醇水平均低于存活组,差异有统计学意义（P<0.05）。MLR≥0.60、FT₃≤2.50 pmol/L均为HBV-ACLF患者死亡的危险因素（P<0.05）。MLR、FT₃、MLR+FT₃对HBV-ACLF患者死亡均有一定的预测价值,但MLR+FT3的预测价值高于其他单项预测。结论 MLR≥0.60、FT₃≤2.50 pmol/L均为HBV-ACLF患者死亡的危险因素（P<0.05）,且二者联合应用对HBV-ACLF患者死亡有较佳的预测价值。

Objective To analyze the predictive effect of mononuclear-lymphocyte ratio（MLR）combined with free triiodothyronine（FT₃）on the survival of patients with hepatitis B virus-related acute-on-chronic liver failure（HBV-ACLF）．Methods In the study,187 patients with HBV-ACLF from January 2019 to January 2022 in our hospital were included,and the survival status of the patients was followed up for 90 days．Among them,69 patients were included in the death group and the rest 118 patients were included in the survival group．The data of the two groups of patients were analyzed by univariate analysis,and the statistically significant factors were analyzed by Logistic multifactor analysis．The risk factors of death in patients with HBV-ACLF were analyzed,and the predictive effect of MLR combined with FT₃ on the death of HBV-ACLF was analyzed．Results The age,incidence of cirrhosis,primary peritonitis,hepatorenal syndrome,electrolyte disturbance,ratio of neutrophil to lymphocyte count,international standardized ratio,model for end stage liver disease,MLR,creatinine,white blood cell count and total bilirubin of the patients in the death group were higher than those in survival group,and the levels of serum sodium,FT₃ and total cholesterol were lower than those in survival group,the differences were significant（P<0.05）．The results showed that MLR≥0.60,FT₃≤2.50 pmol/L were risk factors for death of HBV-ACLF patients（P<0.05）．MLR,FT₃,MLR+FT₃ had certain predictive value for the death of HBV-ACLF patients,but the predictive value of MLR+FT₃ was higher than other single prediction．Conclusions MLR≥0.60 and FT₃≤2.50 pmol/L are risk factors for death of patients with HBV-ACLF（P<0.05）,and the combination of the two has a better predictive value for death of patients with HBV-ACLF．

目的 探讨替诺福韦酯单药治疗在慢性乙型肝炎(CHB)后肝硬化失代偿期(DCC)治疗中的长期应用价值。方法 随机将84例CHB后DCC患者分为对照组及观察组,每组42例。对照组接受拉米夫定联合阿德福韦酯治疗,观察组接受替诺福韦酯治疗。对比两组12个月内治疗时间内的死亡率及肝癌发生率,并分析两组肝功能、肝硬化指标及Child-Pugh评分变化趋势,同时对比两组治疗过程中HBeAg转阴率、HBV-DNA转阴率及失代偿好转率。此外,对比两组治疗不良反应的发生率。结果 在12个月的治疗时间内,两组死亡率及肝癌发生率比较,差异无统计学意义(P>0.05)。而两组治疗过程中ALT、AST、HA、LN、PCⅢ及Child-Pugh评分呈降低趋势,ALB呈升高趋势(P<0.05);治疗6个月及12个月时,治疗组ALT、AST、HA、LN、PCⅢ及Child-Pugh评分低于对照组,ALB高于对照组(P<0.05)。而两组12个月治疗完成后,HBeAg转阴率比较差异无统计学意义,但观察组HBV-DNA转阴率高于对照组(P<0.05)。此外,两组治疗不良反应发生率比较差异无统计学意义(P>0.05)。结论 在CHB后DCC的治疗中,替诺福韦酯单药治疗方案具有良好的长期治疗效果。

Objective To evaluate the long-term value of tenofovir disoproxil monotherapy in the decompensated cirrhosis(DCC) after chronic hepatitis B(CHB). Methods Eighty-four patients with DCC after CHB were randomly divided into control group and observation group, 42 cases in each group. The control group received lamivudine combined with adefovir dipivoxil, and the observation group received tenofovir disoproxil. Mortality and incidence of liver cancer within 12 months of treatment between the two groups were compared, and the change trend of liver function, liver fibrosis index and child-pugh score in the two groups were analyzed. At the same time,we compared the conversion rate of HBeAg, HBV-DNA and decompensated positive rate between the two groups. In addition, the incidence of adverse reactions were compared between the two groups. Results Within 12 months of treatment, there were no statistically significant differences in mortality and liver cancer incidence between the two groups(P>0.05). And during the treatment, the ALT, AST, HA, LN, PC Ⅲ and Child-Pugh score showed a decrease trend, ALB showed a increase trend(P<0.05). After 6-month and 12-month treatment, ALT, AST, HA, LN, PC Ⅲ Child-Pugh score of treatment group were lower than that of control group, ALB was higher than that of control group(P<0.05). After 12 months of treatment, the negative conversion rate of HBV-DNA in the observation group was higher than that of control group(P<0.05). In addition, there was no statistically difference in the incidence of adverse reactions between the two groups(P>0.05). Conclusion Tenofovir disoproxil monotherapy has a good long-term therapeutic effect in the treatment of DCC after CHB.

目的 分析妊娠期慢性乙型肝炎病毒携带者病毒载量与孕妇肝功能、妊娠并发症的相关性。方法 将本院2015年1月—12月间在本院住院并于本院分娩的携带慢性乙型肝炎病毒(HBV)的86例孕妇作为本次研究对象,于住院期间分娩前测定孕妇HBV脱氧核糖核酸(HBV-DNA)定量,依据HBV-DNA定量测定结果将全部患者分为阴性组与阳性组,分别对比2组患者的临床资料、肝功能、妊娠并发症发生率及母婴结局;分析HBV-DNA载量与孕妇妊娠期肝功能及妊娠并发症的相关性。结果 2组孕妇的年龄、BMI、孕次与产次均无差异,P>0.05;阴性组患者妊娠期肝功能指标优于阳性组,P<0.01。阴性组中羊水量异常(偏多或偏少)发生率高于阳性组,P<0.05;其他妊娠期并发症发生率2组均未见差异,P>0.05。2组母婴结局均未见统计学差异,P>0.05。HBV载量与ALT肝功能指标均呈正相关,0<r<1,说明HBV-DNA越高则ALT越高,孕妇的肝功能越差。HBV载量与并发症发生间基本不相关,|r|<0.3,P>0.05。结论 慢性乙型肝炎病毒携带者妊娠期时随着病毒载量的升高,孕妇的肝功能有所下降仍可维持在正常标准,但与妊娠并发症的发生无相关性;提示对HBV-DNA阳性的孕妇给予密切监护,通过临床常规对症治疗能够保证母婴安全。

Objective To analyze the correlation between viral load of chronic hepatitis B virus infection and liver function and pregnancy complications. Methods We selected 86 cases of pregnant women with chronic hepatitis B virus(HBV)in our hospital from January 2015 to December 2015 as the research objects, and then during the hospitalization to test the quality of the HBV deoxyribonucleic acid (HBV-DNA)for them before delivery. According to the HBV-DNA quantitative results, all patients were divided into low dosage group and high dosage group, and then the clinical data, liver function, the incidence rate of pregnancy complications and the outcomes of the two groups were compared; at last we analyzed the correlation among the HBV-DNA load, liver function of pregnant women during pregnancy and pregnancy complications. Results There was no difference between the two groups of pregnant women in the age, BMI, pregnancy and birth time, P>0.05; the low dose group was better than the high dose group in the liver function index during the pregnancy, P<0.01. The incidence of abnormal amniotic fluid volume (more or less) in the low dose group was higher than that in the high dose group, P<0.05; there was no significant difference between the two groups in the incidence of other complications, P>0.05. There was no statistical difference between the two groups in maternal and neonatal outcomes, P>0.05. The HBV load was positively correlated with the two liver function indexes ALT, 0<r<1, indicating that the higher the HBV-DNA, the higher theALT, the worse the liver function of the pregnant women. There was no correlation between HBV load and complications, |r|<0.3, P>0.05. Conclusion Chronic hepatitis B virus carriers during pregnancy with increasing viral load, liver function of pregnant women declined to maintain in normal level, but not associated with pregnancy complications; that of HBV-DNA positive pregnant women given close monitoring of disease through clinical routine treatment can ensure the safety of mother and child.