Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines

BACKGROUND: Interleukin-18 (IL-18), a pro-inflamma- tory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 ( Th1) response. This study was designed to explore the effect of IL-18 on peripheral blood mononuclear cells ( PBMCs) derived from chronic hepatitis B (CHB) and on hepatitis B virus (HBV) DNA released by HepG2.2.15 cell lines, which were transfected with hepatitis B virus gene in vitro. METHODS: PBMCs isolated from 25 healthy people and 25 patients with CHB were stimulated with HBcAg and IL-18 of various concentrations for 72 hours. The levels of IFN-γ in the supernatants of cultured PBMCs were determined by ELISA. After the stimulation of IL-18 of various concentra- tions, PBMCs derived from one patient were co-cultured for 96 hours with HepG2. 2. 15 cells which had been cul- tured for 24 hours, and then the supernatants were collected by centrifugation and used for HBV DNA quantitative as- say. RESULTS: When PBMCs were stimulated by HBcAg and IL-18 at various concentrations, the levels of IFN-γ in the supernatants of CHB groups were much higher than those in normal control groups, at 0.2 ng/ml: t =11.70, P< 0.01; at 1.0 ng/ml: t =16.19, P<0.01; and at5.0 ng/ml: t =20.12, P <0.01. In the CHB groups, the levels of IFN-γ in the supernatants of PBMCs stimulated by HBcAg alone were lower than both those stimulated by HBcAg and EL-18 at various concentrations and those stimulated by HBcAg and EL-18 (5.0 ng/ml) together with EL-12 (mild: t = 2.20, P<0.05; moderate; t=2.97, P<0.05; severe; t = 0.66, P >0.05). The content of HBV DNA in the superna- tant of co-cultivation of HepG2. 2. 15 cells and PBMCs without stimulated materials was higher than that stimula-ted by HBcAg and EL-18 at various concentrations of HBc- Ag and IL-18 together with IL-12/IFN-α1lb. CONCLUSION: DL-18 can induce IFN-γ secretion and pro- bably play a key role in the modulation of both innate and adaptive immunity. It has implications in improving im- munoregulatory effect and increasing the ability of immune cells to kill cells infected by virus.

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

慢性乙型肝炎患者血清HBsAg与单个核细胞乙型肝炎病毒RNA水平对聚乙二醇干扰素治疗效果的预测价值

目的探讨慢性乙型肝炎患者外周血清HBsAg、乙型肝炎病毒(HBV)DNA与血清HBV RNA及单个核细胞(PBMC)HBV RNA的关系。方法50例慢性乙型肝炎患者,给予Peg-IFNα-2b 180μg皮下注射,每周一次,分别在初始治疗、24周和48周,检测患者血清HBV五项、肝功能、HBV DNA、HBV RNA及PBMC中HBV RNA的变化。结果患者三个时间段的生化指标ALT、AST、TBIL、AKP及GGT比较差异无统计学意义(P>0.05);免疫学标志物HBsAg、HBsAb、HBeAg、HBeAb差异有统计学意义(P<0.05);血清HBV DNA及HBV RNA与PBMC HBV RNA差异有显著统计学意义(P<0.001)。结论Peg-IFNα-2b抗病毒治疗各时间段,肝功能转氨酶无显著变化;治疗24周,血HBsAg、HBV DNA与HBV RNA及PBMC HBV RNA快速下降,有显著相关性;治疗48周,血清HBsAg、HBV DNA与HBV RNA及PBMC HBV RNA相关性减弱。因此,24周HBV RNA下降幅度优于48周,更能预测临床治愈。

慢性乙型肝炎者外周血SAA/CRP、NLR水平与HBV-DNA载量、病情程度的相关性分析

目的探究慢性乙型肝炎(chronic hepatitis B,CHB)患者外周血淀粉样蛋白A(serum amyloid A,SAA)与C反应蛋白(C-reactive protein,CRP)比值(SAA/CRP)、中性粒细胞与淋巴细胞比值(neutrophils lymphocytes ratio,NLR)水平与乙型肝炎病毒-脱氧核糖核酸(HBV-DNA)载量及病情程度的相关性。方法选取2020年6月至2022年6月达州市中西医结合医院100例CHB患者作为研究组,根据病情程度分为轻度(单纯CHB,n=36)、中度(乙肝代偿期肝硬化,n=33)和重度(乙肝失代偿期肝硬化,n=31)。另选同期、同年龄段50例健康志愿者作为对照组,比较研究组不同病情程度、对照组一般资料、血清SAA/CRP、NLR水平,并比较研究组不同HBV-DNA载量患者血清SAA/CRP、NLR水平,分析CHB患者血清SAA/CRP、NLR水平与HBV-DNA载量、病情程度的相关性;所有患者均行抗病毒治疗,治疗24周,比较不同抗病毒疗效患者治疗前、治疗后12周、24周血清SAA/CRP、NLR水平及变化值,分析治疗前后血清SAA/CRP、NLR水平变化值预测疗效的价值。结果重度CHB患者血清SAA/CRP、NLR水平>中度CHB患者>轻度CHB患者>健康人群(P<0.05);高载量患者血清SAA/CRP、NLR水平>中载量患者>轻载量患者(P<0.05);CHB患者血清SAA/CRP、NLR水平与HBV-DNA载量(r=0.756、0.709)、病情程度(r=0.776、0.745)呈正相关(P<0.05);无应答患者治疗后12周、24周外周血SAA/CRP、NLR水平均高于应答患者,变化值均低于应答患者(P<0.05);SAA/CRP△1、NLR△1单独预测的AUC分别为0.752、0.773,联合预测△1的AUC为0.861;SAA/CRP△2、NLR△2单独预测的AUC分别为0.796、0.819,联合预测△2的AUC为0.967,大于联合预测△1的AUC(P<0.05)。结论CHB患者的SAA/CRP、NLR与CHB HBV-DNA载量及病情程度具有相关性,临床可通过其水平变化评估病情及预测预后。

HBV相关慢加急性肝衰竭前期进展预测模型构建

目的探讨HBV相关慢加急性肝衰竭前期(HBV-Pre.ACLF)进展的预测指标及预测模型建立。方法采用回顾性病例分析研究,筛选2018年1月至2022年6月我院收治的符合纳入标准的患者102例,以进展到ACLF为观察终点,分析患者各项临床指标;通过单因素及多因素分析寻找出HBV-Pre.ACLF进展的独立危险因素及建立预测模型。结果基线水平时临床指标ALB、血钠及MELD、MELD-Na评分、是否联合前列地尔治疗为HBV-Pre.ACLF进展的独立危险因素(P<0.05);根据二元logistic回归分析结果,构建出HBV-Pre.ACLF进展预测模型得Logit(P)=34.75-0.34*ALB-0.16*血钠-1.26*前列地尔治疗(联合前列地尔治疗为1,未联合治疗为0)。结论HBV-Pre.ACLF基线时ALB、血Na、FIB及MELD、MELD-Na评分系统对疾病进展有一定的预测价值,早期联合前列地尔治疗能够在一定程度上遏制HBV-Pre.ACLF进展。

慢性乙型肝炎患者外周血B淋巴细胞亚群的变化特征及临床意义

目的观察慢性乙型肝炎(CHB)患者外周血B淋巴细胞(B细胞)亚群的变化特征,并探讨其临床意义。方法收集2022年7-10月在解放军总医院第五医学中心就诊的37例CHB未治疗患者的外周血标本,同时收集18名接种过乙肝疫苗的健康人外周血标本作为健康对照(HC),并收集研究对象的年龄、HBV DNA病毒载量、HBsAg定量、HBeAg半定量、谷丙转氨酶(ALT)、谷草转氨酶(AST)及AST/ALT比值等临床指标。采用多色流式细胞术检测并比较两组外周血B细胞及各亚群的频率、表型及功能标志物的变化特征,并探究其与临床指标之间的相关性。结果B细胞各亚群频率分析显示,与HC组比较,CHB组整体B细胞、过渡B细胞及幼稚B细胞频率均降低(P<0.05),而成熟B细胞、记忆B细胞、非典型记忆B细胞及激活记忆B细胞频率均升高(P<0.01);两组静息记忆B细胞频率比较,差异无统计学意义(P>0.05)。B细胞各亚群功能分析显示,与HC组比较,CHB组整体B细胞、成熟B细胞、记忆B细胞、幼稚B细胞、激活记忆B细胞、非典型记忆B细胞及静息记忆B细胞的CD79b表达水平均升高(P<0.05);此外,CHB组非典型记忆B细胞的程序性死亡受体1(PD-1)表达水平也高于HC组(P<0.05)。相关性分析显示,CHB组整体B细胞频率与年龄呈负相关(r=-0.39,P<0.05),且整体B细胞、成熟B细胞、过渡B细胞、记忆B细胞、幼稚B细胞的PD-1表达水平与年龄均呈正相关(r>0.36,P<0.05)。结论慢性HBV感染导致CHB患者外周血部分B细胞的频率及功能发生耗竭,而年龄是导致CHB患者体液免疫功能下降的潜在危险因素。

丙氨酸氨基转移酶≤2倍正常上限值且HBeAg阴性乙型肝炎肝纤维化无创预测模型的建立

目的:分析丙氨酸氨基转移酶(ALT)≤2倍正常上限值(2ULN)且HBeAg阴性的慢性乙型肝炎(CHB)肝纤维化的影响因素,并构建无创预测模型,以评估肝纤维化的严重程度。方法:回顾性分析295例ALT≤2ULN且HBeAg阴性的CHB病人的临床资料。所有病人根据肝穿刺病理结果进行肝纤维化分期,以纤维化分期S≥2作为显著肝纤维化的判别标准。其中肝纤维化轻度组(S≤1)94例,显著组(S≥2)201例。通过多因素logistic回归分析,筛选影响肝纤维化的独立预测因素并构建无创模型,最后通过受试者工作特征曲线下对该模型进行验证,以识别肝纤维化的严重程度。结果:多因素logistic回归分析显示,天门冬氨酸氨基转移酶、乙肝核心抗体升高可能是肝纤维化的独立预测因素(P<0.01)。该模型的AUC为0.721(95%CI:0.660~0.782,P<0.01),诊断显著肝纤维化的敏感性为60.0%,特异性为74.5%。结论:基于天门冬氨酸氨基转移酶、乙肝核心抗体两项指标构建的无创预测模型对评估CHB肝纤维化的严重程度具有较高的诊断价值。

BiPAP无创呼吸机配合布地奈德在CPHD患者中的应用分析

目的:探讨BiPAP无创呼吸机配合常规治疗对慢性肺源性心脏病(CPHD)患者血清氨基末端B型脑钠肽前体(NT-proBNP)、肺功能及血气分析指标的影响。方法:选择2020年1月—2022年12月本院60例CPHD患者,随机数字表法分为对照组(30例)和观察组(30例),对照组实施常规治疗,观察组在对照组基础上采用BiPAP无创呼吸机配合治疗。治疗前、治疗7 d后测定两组血清NT-proBNP水平、肺功能指标[一秒用力呼气容积(FEV1)、用力肺活量(FVC)、并比较两者比值即FEV1/FVC]、血气分析指标[动脉二氧化碳分压(PaCO_(2))、动脉氧分压(PaO_(2))和pH]并比较。结果:治疗前两组NT-proBNP、FVC、FEV1、FEV1/FVC、PaCO_(2)、PaO_(2)和pH比较,差异无统计学意义(P>0.05);治疗7 d后,两组血清NT-proBNP水平和PaCO_(2)均降低,且观察组低于对照组(P<0.05);两组FVC、FEV1、FEV1/FVC、PaO_(2)和pH均升高,且观察组高于对照组,差异有统计学意义(P<0.05)。结论:BiPAP无创呼吸机配合常规治疗对CPHD患者的NT-proBNP水平、肺功能和血气分析指标具有显著的改善作用。

“Treat-all”Strategy for Patients with Chronic Hepatitis B Virus Infection in China:Are We There Yet?

Chronic hepatitis B remains the primary cause of liver-related events in China.The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030.However,achieving this goal appears challenging due to the current low rates of diagnosis and treatment.The“Treat-all”strategy,which proposes treating all patients with detectable hepatitis B virus(HBV)DNA or even all patients with positive HBsAg,has been suggested to simplify anti-HBV treatment.In 2022,the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China,expanding antiviral indications and simplifying the treatment algorithm.According to this latest guideline,nearly 95%of patients with detectable HBV DNA are eligible for antiviral treatment.This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B(version 2022)and to identify gaps in achieving the“Treat-all”strategy in China.

Upregulation of Toll-like Receptor 4 on T Cells in PBMCs Is Associated with Disease Aggravation of HBV-related Acute-on-chronic Liver Failure

Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.

Management of occult hepatitis B virus infection:An update for the clinician

Occult hepatitis B virus(HBV) infection(OBI) is defined by the presence of HBV DNA in the liver tissue of individuals who test negative for hepatitis B surface antigen(HBsAg).Patients who have recovered from acute hepatitis B can carry HBV genomes for a long time and show histological patterns of mild necro-inflammation,even fibrosis,years after the resolution of acute hepatitis,without showing any clinical or biochemical evidence of liver disease.At least in conditions of immunocompetence,OBI is inoffensive itself,but when other relevant causes of liver damage are present it might make the course of the liver disease worse.The risk of HBV transmission through transfusion is related to blood donations negative for HBsAg that have been collected during the pre-seroconversion period or during chronic OBI.Use of HBV nucleic acid amplification testing and multivalent anti-HBs antibodies in the HBsAg assays is recommended for detection of true and false OBI,respectively.It is not known if prior hepatitis B immunization with an optimal anti-HBs response in cases of HBV transmission through organ transplantation can effectively modulate or abort the infection.Use of anti-viral agents as prophylaxis in patients with serological evidence of past HBV infection prevents reactivation of OBI after transplantation in most cases.Reactivation of OBI has been observed in other conditions that cause immunosuppression,in which antiviral therapy could be delayed until the HBV DNA or HBsAg becomes detectable.OBI might contribute to the progression of liver fibrosis and hepatocellular carcinoma development in patients with chronic liver disease.

血小板计数及相关评分模型对HBV相关慢加急性肝衰竭预后的预测价值

目的 探究血小板(PLT)计数与HBV相关慢加急性肝衰竭(HBV-ACLF)预后的相关性,建立新的PLT相关评分模型并评估其在HBV-ACLF短期预后中的预测价值。方法 选取2018年1月—2022年1月于西部战区总医院消化内科住院治疗的HBV-ACLF患者作为回顾性研究队列。收集所有患者入院24 h内的临床资料,根据随访180天后的生存情况将患者分为生存组和死亡组。符合正态分布的计量资料组间比较采用成组t检验;不符合正态分布的计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ^(2)检验。采用Pearson相关系数分析各指标之间相关性。采用Logistic回归模型进行预后影响因素分析。采用受试者工作曲线评估预后模型预测价值。通过Kaplan-Meier曲线分析患者生存情况。结果 共纳入236例患者,180天生存率为75.85%(179/236)。死亡组年龄[(53.98±10.45)岁vs (47.44±12.46)岁,P=0.001]、INR[1.78(1.46~2.04) vs 1.47(1.23~1.68),P<0.001]、TBil[275.60(165.00~451.45)μmol/L vs 230.60(154.90~323.70)μmol/L,P=0.035]、MELD评分[21.47(18.14~24.76)分vs 18.67(15.70~21.62)分,P<0.001]、ALBI评分[-1.06(-1.64~-0.86)分vs-1.32(-1.73~-1.01)分,P=0.034]高于生存组,PLT水平[80.00(50.00~124.50)×109/L vs 115.00(82.00~143.00)×109/L,P=0.001]、PWR[13.40(9.54~20.70) vs 18.49(13.95~24.74),P=0.001]低于生存组,差异均有统计学意义。Pearson相关性分析显示,PLT与肝硬化的发生及INR呈负相关(r值分别为-0.332、-0.194,P值分别为<0.001、0.003)。多因素Logistic回归分析显示,年龄、PLT、INR为HBV-ACLF患者180天预后的独立影响因素(OR值分别为1.045、0.990、2.591,95%CI分别为1.015~1.076、0.983~0.998、1.363~4.925)。获得新的预测模型:AIP=0.006×年龄+0.187×INR-0.001×PLT。AIP评分模型对预测HBV-ACLF患者180天生存率曲线下面积(AUC)为0.718 (敏感度为81.1%,特异度为54.1%),而PLT、PWR、LPACLF评分、MELD评分、ALBI评分的AUC分别为0.673、0.659、0.588、0.647、0.578。AIP评分模型的cut-off值为0.48。Kaplan-Meier生存分析发现,高AIP评分组的生存率明显低于低AIP评分组(P<0.001)。结论 PLT相关评分模型对HBV-ACLF预后的预测价值优于其他模型,高PLT水平HBV-ACLF患者的整体生存率更高。

Correlation analysis of TCM syndrome types with T lymphocytes and biochemical indices in patients with HBV-related primary liver cancer

Objective:To investigate the correlation between T lymphocytes and biochemical indices in patients with Primary liver cancer(PLC)associated with hepatitis B virus(HBV)and TCM syndrome differentiation.Methods:263 HBV-related PLC patients who were admitted to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2018 to December 2019 were retrospectively collected.There were 127 cases of liver depression and spleen deficiency syndrome(48.3%),48 cases of spleen deficiency and dampness syndrome(18.3%),31 cases of liver and gallbladder dampness and heat syndrome(11.8%),35 cases of liver and blood stasis syndrome(13.3%),and 22 cases of liver and kidney Yin deficiency syndrome(8.4%).The general data,T cell subsets,oncology and virology indicators,oncology characteristics,biochemical indicators and other data were counted.Epidata and Excel were used to collect and summarize the data,and SPSS26.0 software was used for statistical analysis.Results:There was no significant difference in gender and age distribution among the five syndrome types(χ^(2)=5.462,F=1.979,ALL P>0.05).The differences among T lymphocyte count(χ^(2)=57.785,P<0.001),CD4(+)T cell count(χ^(2)=47.103,P<0.001)and CD8(+)T lymphocyte count(F=12.760,P<0.001)were statistically significant.The T lymphocyte count,CD4(+)T lymphocyte count and CD8(+)T lymphocyte explicit count in patients with liver and kidney Yin deficiency syndrome were significantly lower than those in the other four syndrome types.AFP(χ^(2)=89.986,P<0.001),CEA(χ^(2)=95.501,P<0.001),CA199(χ^(2)=30.044,P<0.001)of the five syndrome types increased successively from the syndrome of liver depression and spleen deficiency to the syndrome of liver and kidney Yin deficiency,and the difference was statistically significant.There were statistically significant differences in the inner diameter of main portal vein,portal vein cancer thrombin and extrahepatic metastasis among the five syndrome types(ALL P<0.001).The main symptoms of portal vein cancer thrombin and extrahepatic metastasis were liver-gallbladder dampness-heat syndrome and liver-blood stasis syndrome.The differences among PLT(χ^(2)=39.234,P<0.001),Alb(χ^(2)=75.171,P<0.001),TBil(χ^(2)=51.140,P<0.001),AST(χ^(2)=55.881,P<0.001),PT(χ^(2)=21.515,P<0.001)were statistically significant.PLT and Alb decreased successively from the syndrome of liver depression and spleen deficiency to the syndrome of liver and kidney Yin deficiency.PLT and Alb of the syndrome of liver depression and spleen deficiency were significantly higher than those of the other four groups,and TBil and AST of the syndrome of liver and gallbladder dampness and heat were significantly higher than those of the other four groups.PT of liver and kidney Yin deficiency was significantly higher than that of the other four groups.The lymphocyte count,CD4(+) lymphocyte count and CD8(+) lymphocyte count were negatively correlated with AFP,PT and TBil(ALL P<0.05),and positively correlated with PLT(P<0.05).T lymphocyte count was positively correlated with AIb(P<0.05).Conclusion:This study found that patients with liver depression and spleen deficiency syndrome have better cellular immune function,liver function and prognosis.Patients with liver and kidney Yin deficiency have lower cellular immunity,worse liver function,and worse prognosis.Portal vein carcinoma embolus and extrahepatic metastasis were mainly characterized by dampness and heat of liver and gallbladder and blood stasis of liver.Patients with lower lymphocyte counts have poorer blood clotting,worse the liver reserve,and the higher the risk of further cancer.

抗病毒治疗慢性乙型肝炎患者血清外泌体HBV-miR-3动态变化与病毒学指标的关系

目的探讨抗病毒治疗慢性乙型肝炎(CHB)患者血清外泌体HBV-miR-3动态变化与病毒学指标的关系。方法选取2020年6月至2021年6月收治的116例CHB患者,均接受抗病毒治疗12个月,比较发生病毒学应答组(VR+组)和未发生病毒学应答组(VR-组)一般资料及接受抗病毒治疗前后病毒学指标和外泌体HBV-miR-3的动态变化。采用Pearson相关分析外泌体HBV-miR-3水平与病毒学指标的关系,采用受试者工作特征曲线分析外泌体HBV-miR-3水平对病毒学应答的预测效能。结果经12个月抗病毒治疗后,VR+组54例,VR-组62例,病毒学应答率为46.55%;VR+组ALT水平高于VR-组,而HBsAg、HBV DNA和外泌体HBV-miR-3水平低于VR-组(P<0.05);VR+组HBsAg、HBV DNA和外泌体HBV-miR-3水平在接受抗病毒治疗后明显下降,而VR-组虽有下降但变化不明显,且一直高于VR+组(P<0.05);血清外泌体HBV-miR-3水平与ALT无明显相关性(r=0.049,P=0.241),与HBV DNA和HBsAg呈正相关(r=0.314、0.809,P<0.05)。治疗3个月时,以4.52lg拷贝/mL为最佳界值的AUC最大为0.857(95%CI:0.716~0.962),敏感度和特异度最高,分别为82.70%和78.10%。结论CHB患者血清外泌体HBV-miR-3水平随着抗病毒治疗时间的延长而下降,与病毒学指标HBV DNA和HBsAg呈正相关,抗病毒治疗3个月时HBV-miR-3的临界值可作为预测CHB患者抗病毒治疗12个月的病毒学应答的指标。

乙型肝炎不确定期与灰区的再认识

慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的防治依然任重而道远.即使我国新版指南扩大了抗病毒治疗适应证,依然有一定比例的HBV感染者不符合抗病毒治疗适应证,称之为不确定期或灰区(grey zone,GZ).但当前关于不确定期或GZ的解读与判断标准较为混乱,两者之间的联系与区别还不甚清晰,不同研究所指向的对象不尽相同.但无论如何认定不确定期或GZ,其目的是为了及时、准确判断慢性HBV感染的疾病进展与是否需要及时治疗.基于GZ对应于“治疗的适应证分类”和不确定期对应于“自然史分期”的理解,本文结合国内外的研究进展阐述对慢性HBV感染不确定期与GZ的再认识.GZ即为不治疗对象(不符合抗病毒治疗适应证),而不确定期仅为难以明确归于自然史分期(不符合自然史分期)的患者,GZ应包括不确定期,而不是等同关系.对应我国新版指南标准,属于GZ的不确定期患者,建议抗病毒治疗;对应欧洲肝病学会2017年指南标准,免疫控制期与属于GZ的不确定期患者,建议抗病毒治疗.

基于肝脏病理的慢性乙型肝炎患者危险因素分析及抗病毒治疗适应证探讨

目的分析慢性乙型肝炎(CHB)患者肝脏炎症及纤维化进展的危险因素,为年龄<30岁CHB患者决策是否抗病毒治疗提供依据。方法收集2017年2月至2021年10月浙江树人大学树兰国际医学院附属树兰(杭州)医院收治的285例未行抗病毒治疗的CHB患者,记录肝脏穿刺病理结果、血液学指标及其他临床资料。根据炎症程度(G)、纤维化程度(S)分期(合称GS分期)分组,G≤1和S≤1患者纳为A组(123例),G>1和(或)S>1患者纳为B组(162例),比较两组患者血液学指标及临床资料,采用二元logistic回归分析影响CHB患者GS分期进展的危险因素,绘制ROC曲线评估相关风险因素对CHB患者肝脏GS分期进展的诊断效能。结果降低ALT阈值后ALT诊断肝脏GS分期进展的灵敏度升高,而特异度下降。两组年龄、WBC、PLT、白蛋白、ALT、AST、ALP、γ-谷氨酰转肽酶(γ-GT)、DBil、PT、国际标准化比值、透明质酸(HA)、Ⅳ型胶原(ⅣC)、基于ALT、AST、PLT和患者年龄的纤维化指数(FIB-4)比较,差异均有统计学意义(均P<0.05),二元logistic回归分析结果显示白蛋白、DBil、HA、ⅣC是CHB患者肝脏GS分期进展的危险因素(均P<0.05);ROC曲线显示HA、ⅣC诊断肝脏GS分期进展的AUC分别为0.616、0.655,白蛋白和DBil诊断肝脏GS分期进展的AUC无统计学意义。结论降低ALT阈值可提高诊断肝脏GS分期进展的灵敏度;对年龄<30岁CHB患者定期监测肝功能、肝纤维化指标、凝血功能等血液学指标,可有效评估其肝脏GS分期进展,有助于及时开启抗病毒治疗。

恩替卡韦、富马酸替诺福韦二吡呋酯及富马酸丙酚替诺福韦治疗慢性乙型肝炎的疗效及安全性分析

目的观察恩替卡韦(entecavir,ETV)、富马酸替诺福韦二吡呋酯(tenofovir disoproxil fumarate,TDF)及富马酸丙酚替诺福韦(tenofovir alafenamide fumarate,TAF)抗病毒治疗慢性乙型病毒性肝炎(慢乙肝)的临床疗效及安全性。方法选择2021年3月—2023年6月我院收治的181例慢乙肝患者,依据抗病毒治疗用药不同分为3组,ETV组(n=66)、TDF组(n=64)及TAF组(n=51)。比较3组患者的血脂、肝功能、HBsAg、HBV DNA、血肌酐及估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)等指标在治疗前后及组间的差异。结果ETV组有效率为86.36%(57/66),TDF组有效率为90.63%(58/64),TAF组有效率为90.20%(46/51),3组比较差异无统计学意义(P>0.05)。治疗后,3组的HBsAg水平、HBV DNA载量均低于治疗前(P均<0.05),且3组间HBsAg水平、HBV DNA载量的变化幅度比较,差异具有统计学意义(P<0.05)。治疗后,3组的ALT、AST水平均低于治疗前(P均<0.05),且3组间ALT、AST水平的变化幅度比较,差异有统计学意义(P<0.05)。治疗后,ETV组的HDL-C、LDL-C均高于治疗前(P均<0.05),TC、TG较治疗前差异均无统计学意义(P均>0.05);TDF组的TC、HDL-C均低于治疗前(P均<0.05),TG、LDL-C较治疗前差异均无统计学意义(P均>0.05);TAF组的TC、TG、HDL-C、LDL-C较治疗前差异均无统计学意义(P均>0.05),但3组间TC、TG、HDL-C、LDL-C的变化幅度比较,差异均有统计学意义(P均<0.05)。治疗后,3组的血肌酐、eGFR较治疗前差异均无统计学意义(P均>0.05),但3组间血肌酐、eGFR的变化幅度比较,差异均有统计学意义(P均<0.05)。结论ETV、TDF、TAF治疗慢乙肝的临床疗效相近,服用TAF不会对血脂造成影响,但服用ETV会引起HDL-C、LDL-C水平升高,服用TDF可降低TC、HDL-C水平,并且均有较好的肾脏安全性。

基于肝活检比较肝硬度值和血清学模型对慢性乙型肝炎获得持续病毒学应答人群肝纤维化的诊断效能

目的 基于肝病理Scheuer评分比较肝硬度值(LSM)和血清学模型对获得持续病毒学应答(MVR)的慢性乙型肝炎(CHB)人群肝纤维化分期的诊断效能。方法 纳入86例符合MVR且丙氨酸转氨酶正常、Scheuer评分G<2的CHB患者,收集并计算患者LSM及天冬氨酸转氨酶/血小板计数、基于4因子的肝纤维化指数、天冬氨酸/丙氨酸转氨酶、γ-谷氨酰转移酶/血小板、S指数、AGAP评分、King's指数、Forns指数等。根据肝活检Scheuer评分分组:轻微纤维化组35例(1≤S<2)、显著纤维化组41例(2≤S≤3)、进展期纤维化组10例(3<S≤4),对3组患者进行Scheuer分期与LSM和血清学模型之间Spearman相关性研究;用受试者操作特征曲线下面积(AUC)比较LSM与各血清学模型对S≥2及S≥3的诊断效能,并进行亚组分析,探讨LSM和血清学模型对不同乙型肝炎e抗原状态的诊断效能。结果 3组患者无创纤维化指标基线数据差异有统计学意义(P<0.05)。除天冬氨酸/丙氨酸转氨酶外,LSM和血清学模型与Scheuer分期均呈正相关关系,LSM相关性最大(rs=0.615,P<0.001)。在Scheuer分期S≥2、S≥3时,LSM-AUC分别为0.818、0.887,均高于血清学模型,尤其S≥3时,差异有统计学意义(P<0.05);AGAP评分+Forns指数+LSM-AUC(0.905)较LSM-AUC(0.887)有所提高,但差异无统计学意义(P=0.313)。在Scheuer分期S≥2、S≥3时,LSM在乙型肝炎e抗原阴性组AUC均高于乙型肝炎e抗原阳性组。结论 LSM诊断CHB-MVR患者纤维化效能高于各血清模型,尤其对乙型肝炎e抗原阴性CHB-MVR患者评估作用更强。但LSM用于肝纤维化动态进展评估效能的稳定性需做更长期的队列研究验证。

慢性乙型肝炎患者外周血单个核细胞中HBV cccDNA预测拉米夫定的治疗效果

目的:探讨慢性乙型肝炎拉米夫定治疗结束时,外周血单个核细胞(PBMC)中HBV cccDNA(乙型肝炎病毒共价闭合环状DNA)检测对拉米夫定持续应答的预测作用. 方法:对慢性乙型肝炎患者17例进行拉米夫定治疗48 wk,获得完全或部分疗效(血清HBV DNA转阴, ALT复常,伴或不伴HBeAg血清转换),48 wk治疗结束时检测PBMC中HBV cccDNA,并对患者进行1 a的血清HBVDNA监测. 结果:治疗结束时PBMC中HBV cccDNA为阳性9例, 阴性8例.在PBMC中HBV cccDNA阳性者,停止治疗的1 a内所有患者的血清HBVDNA阳转.而PBMC中HBV cccDNA阴性者,1例血清HBVDNA阳转. 结论:拉米夫定治疗结束时PBMC中HBV cccDNA的检测可能对拉米夫定治疗能否获得持续应答具有预测价值.