ALT≤40U/L的HBeAg阴性慢性HBV感染者抗病毒治疗指征的无创指标分析

目的在肝组织病理的指导下探索ALT≤40 U/L的HBeAg阴性慢性HBV感染者抗病毒指征的无创指标。方法回顾性纳入2013年10月—2018年8月延安大学附属医院收治的已行肝活检的377例ALT≤40 U/L的HBeAg阴性慢性HBV感染者,入组患者中炎症活动度相似文献   

扩大慢性乙型肝炎抗病毒治疗应重视ALT正常、年龄≤30岁的HBeAg阴性慢性HBV感染者

目的 拟对2022年2月发布的《扩大慢性乙型肝炎抗病毒治疗的专家意见》的推荐意见进行分析验证和完善。方法 本研究为单中心回顾性研究,连续纳入2014年1月—2020年10月于中国人民解放军总医院第五医学中心接受肝穿刺活组织病理检查且ALT正常的成人慢性HBV感染者,并分析≤30岁和>30岁亚组中不同HBeAg状态人群存在中、重度肝损伤人群比例。结果 共纳入慢性HBV感染者290例,HBeAg阳性者121例(41.7%),HBeAg阴性者169例(58.3%)。进一步按年龄分组,在HBeAg阳性中,≤30岁37例,>30岁84例;在HBeAg阴性感染者中,≤30岁24例,>30岁145例。4组比较,年龄(H=151.539)、性别(χ²=9.959)、ALT(H=29.041)、AST(H=11.127)、Alb(H=23.538)、HBV DNA(H=187.982)、HBsAg(H=132.520)组间比较差异均有统计学意义(P值均<0.05)。年龄>30岁和≤30岁组均有近50%的患者存在中度及以上肝损伤(50.22%vs 47....     

ALT持续正常的慢性HBV感染者的肝组织病理特征及临床意义

目的探讨ALT正常的慢性HBV感染者的肝组织病理特征,并分析性别、年龄、ALT、血清HBV DNA及HBeAg对肝组织病理改变的影响。方法选取123例肝功能正常的慢性HBV感染者进行肝组织病理检查,根据性别、年龄、ALT、血清HBV DNA及HBeAg进行分组,并分别比较各组患者肝组织炎症分级和纤维化分期之间的差异。统计学处理采用方差分析。结果 HBV携带者性别、HBV DNA水平对肝脏损害程度的影响差异无统计学意义(P>0.05);随年龄增加、ALT水平升高,肝组织炎症及纤维化呈加重的趋势(P<0.01);血清HBeAg阳性与阴性对纤维化程度的影响差异有统计学意义(P<0.05)。结论对于年龄>40岁、ALT水平接近正常值上限的HBV携带者,应尽早进行肝脏活组织检查,根据不同病理结果决定是否进行抗病毒治疗。     

ALT持续正常的慢性HBV感染者诊疗专家共识

正本共识基于我国《慢性乙型肝炎防治指南(2019版)》~(~([1])),对ALT持续正常的慢性乙型肝炎的最新进展进行补充,旨在帮助临床医师在ALT持续正常慢性乙型肝炎患者的诊治中做出合理的诊疗决策。本共识中的证据分为A、B和C 3个等级,推荐等级分为1和2级(表1)。2014年全国流行病学调查结果显示,我国人群HBs Ag阳性率为5.0%～6.0%,慢性HBV感染者约7000万例,其中慢性乙型肝炎患者2000万～3000万例,4岁以下儿童HBs Ag阳性率为0.3%,5～15岁为0.9%,16～29岁为4.4%。全世界病死于HBV感染相关疾病的患者约88.7万例/年,     

80例慢性HBV感染者临床与肝组织病理学分析

目的探讨血清丙氨酸氨基转移酶（ALT）低于2倍正常值上限（ULN）的慢性乙型肝炎病毒（HBV）感染者临床特征和肝组织病理学的变化。方法在2010年7月至2013年11月住院行肝活检的80例慢性HBV感染者,常规检测血清HBeAg和HBV DNA水平,回顾性分析其临床资料和肝组织学改变。结果 50例HBeAg阳性和30例HBeAg阴性患者年龄分别为（28.52±9.10）岁和（39.37±10.14）岁,HBV DNA载量分别为（7.79±0.73）lg拷贝/毫升和（4.52±1.67）lg拷贝/毫升,差异均有统计学意义（P〈0.01）;两组肝组织炎症活动度分别为（1.00±0.57）和（1.27±0.45）,纤维化程度分别为（0.38±0.57）和（1.07±1.11）,差异均有统计学意义（P〈0.05）;两组肝组织HBsAg表达强度免疫染色评分（ISS）分别为（0.93±0.92）和（0.77±0.93）,HBcAg分别为（1.58±0.88）和（1.63±0.92）,差异均无统计学意义（P〉0.05）;22例患者年龄≥40岁和35例年龄〈30岁患者肝组织炎症活动度分别为（1.32±0.48）和（0.69±0.58）,纤维化程度分别为（1.00±1.27）和（0.40±0.50）,差异均有统计学意义（P〈0.05）;52例男性和28例女性患者肝组织炎症活动度分别为（1.12±0.55）和（1.07±0.54）,纤维化程度分别为（0.71±0.82）和（0.50±0.96）,肝组织HBsAg表达强度（ISS）分别为（0.89±0.89）和（0.82±1.00）,HBcAg分别为（1.44±0.94）和（1.24±1.09）,差异均无统计学意义。结论对年龄≥40岁且HBeAg阴性的血清ALT低于2×ULN的慢性HBV感染者,应及早行肝组织病理学检查,以进行正确的病情评估。     

ALT持续正常的慢性HBV感染者肝组织病理学检查分析

目的了解ALT持续正常的乙型肝炎病毒感染者肝组织变化情况。方法对118例ALT持续正常的乙型肝炎病毒感染者行肝穿活检。结果在118例慢性乙型肝炎病毒感染者中,病理学诊断慢性乙型肝炎60例,肝硬化58例;两组患者血清ALT、白蛋白、胆碱脂酶、有无肝硬化或肝癌家族史及HBV DNA载量之间存在明显差异（P〈0.05）;Logistic多因素回归分析显示白蛋白及A/G比值与肝硬化的发生存在因果关系。结论 ALT正常的HBV感染者其实肝内已存在严重的病变。     

慢性乙型肝炎病毒感染免疫耐受期患者的临床病理特征

目的:了解HBV慢性感染免疫耐受期患者的临床及病理学特征．方法:分析HBV感染不同时期380例患者的年龄、母婴垂直传播感染途径、乙肝家族史、肝细胞内HBsAg、HBcAg表达状况及肝组织病理学特征．结果:HBV慢性感染免疫耐受期患者年龄 16岁以下占61．8％,母婴垂直传播感染者占 55．0％,有乙肝家族史患者占46．6％,免疫耐受期患者89例肝组织内HBcAg阳性表达率 78．7％,均明显高于免疫活动期及感染非活动状态患者(x2=38．73,49．08,17．2,31．69, P<0．01)．免疫耐受期16岁以下的患者肝组织内HBsAg及HBcAg阳性表达率最高,分别占64．3％(45／75)和72．9％(51／79),显著高于免疫活动期和非活动HBV携带状态患者(x2= 17．51,31．17,P<0．001)．免疫耐受期16岁以上的患者肝组织内HBsAg及HBcAg阳性表达率最低,分别占35．7％(25／75)和27．1％(19／70),显著低于免疫活动期和非活动HBV携带状态患者(x2=17．51,x2=31．17,P<0．001)．结论:HBV慢性感染免疫耐受期患者中16岁以下者,母婴垂直传播感染者及乙肝家族史者所占比例明显高;HBV在肝组织复制表达以免疫耐受期患者最多,且16岁以下的患者占多数．     

HBeAg血清转换延迟患者的临床病理特征

目的探讨HBV感染者延迟HBeAg血清转换与肝脏病理变化的相关性。方法分析148例慢性HBV感染者的血清HBeAg表达与肝脏病理改变和HBcAg的关系。结果本组病例中HBeAg阳性78例,肝脏病理炎症分级G≥2者,53例（67.9%）,肝脏病理纤维化分期S≥2者,29例（37.2%）,HBeAg阴性70例,G≥2者,36例（51.4%）,S≥2者,25例（35.7%）,HBeAg阳性与阴性组肝脏炎症损害差异有统计学意义,χ2=4.20,P〈0.05,纤维化程度差异无统计学意义,χ2=0.532,P〉0.05。HBeAg阳性组肝脏HBcAg阳性者有60例（76.9%）明显高于HBeAg阴性组26例（37.1%）,χ2=23.98,P〈0.01。两组均以胞浆型为主分别为58.3%,65.4%。结论免疫活动期,HBV感染者延迟HBeAg血清转换组与HBeAg阴性组比较有更明显的炎症程度,血清HBeAg表达与肝脏HBcAg表达有明显相关性。     

Therapeutic strategies in the management of patients with chronic hepatitis B virus infection

Currently available options for the treatment of chronic hepatitis B virus (HBV) infection include standard and pegylated interferon alfa and four oral antiviral agents (lamivudine, adefovir, entecavir, and telbivudine). These treatment strategies are either therapies of finite duration that aim to achieve sustained off-therapy responses, or long-term treatments that aim to maintain on-therapy remission. Pegylated interferon alfa may offer higher sustained off-therapy responses after 1 year, but most patients do not respond. Oral antivirals are the only candidates for long-term treatment of patients with chronic HBV infection. Viral suppression has favourable effects on patients' outcome and modifies the natural history of the disease. Viral resistance is the main drawback of long-term antiviral therapy. Lamivudine monotherapy is associated with higher resistance (year 1, 10-27%; year 2, 37-48%; year 4, 60-65%) than adefovir (year 1, 0%; year 2, 3%; year 5, 29%) or telbivudine (year 1, 3-4%; year 2, 9-22%). Entecavir resistance is rare in naive individuals (year 4, <1%), but increases over time in lamivudine-resistant patients (year 4, 43%). The best strategy for long-term therapy in chronic HBV infection has yet to be established.     

Experimental duck hepatitis B virus infection: pathology and evolution of hepatic and extrahepatic infection

Seventy, 1-day-old ducklings inoculated intraperitoneally with duck hepatitis B virus and 30 controls have been studied over a 2-year period. Infection with duck hepatitis B virus occurred in all inoculated ducks, although this was not associated with clinical morbidity. Duck hepatitis B virus DNA was first detected in liver on Day 3, in pancreatic acinar cells on Day 4, serum on Day 6, splenic red and white pulp on Day 7 and in the renal glomurulus on Day 14, using a combination of dot, Southern blot and in situ hybridization techniques. Peak levels of circulating virus, as determined by DNA polymerase levels, occurred 1 to 4 weeks postinoculation. Mild degrees of portal inflammation were seen in sections of liver tissue in both infected and control ducks. However, moderately severe inflammatory changes were present in 8 of 22 infected birds compared with 0 of 18 controls (p less than 0.025). Appearance of this inflammatory infiltrate 6 weeks postinoculation coincided with a decrease in levels of duck hepatitis B virus DNA in hepatocytes and within the pancreatic acinar cells. At the same time, duck hepatitis B virus DNA became increasingly localized to the splenic germinal centers, and viral DNA was first detected in pancreatic islet cells. No histological changes accompanied the extra-hepatic tissue infection. The sequence and significance of duck hepatitis B virus infection in liver and extra-hepatic tissues is discussed in relation to the pathogenesis of hepatitis B virus infection in man.     

Customizing the management of chronic hepatitis B virus infection

As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.     

与直接抗病毒药物应用相关的HCV/HBV双重感染的特点及其诊治管理

HCV和HBV的双重感染(DI)具有不同于单一HCV或HBV感染的特殊临床、免疫学和病毒学特点,为临床诊治和管理带来了诸多挑战。在应用直接抗病毒药物(DAA)有效控制HCV感染的同时,可能导致HBV的激活和乙型肝炎的发作甚至肝衰竭。在抗HCV治疗的同时,根据不同的HCV/HBV-DI状态选用合适的抗HBV治疗和随访管理策略至关重要。     

经病理诊断的慢性乙型肝炎病毒携带者与慢性肝炎的临床分析

目的 比较病理学诊断为慢性HBV携带者与慢性肝炎患者的临床资料,为不同ALT水平的慢性HBV感染者的处理提供病理学依据.方法 对292例慢性HBV感染者进行肝活组织检查,按病理学诊断符合慢性HBV携带者标准(G0～G1且S0～S1)与慢性肝炎标准[G＞1和(或)S＞1]分为携带组和肝炎组,比较不同年龄分层及ALT水平分层与病理诊断的关系,同时比较其他可能与病理诊断相关的临床、生物化学及影像学指标,Logistic回归方程(后退法,极大似然法)进行多因素分析,确定病理学符合慢性HBV携带者诊断的独立影响因素.结果 292例患者中,病理诊断为慢性HBV携带者有140例,占47.9％;慢性肝炎152例,占52.1％.HBV携带组与慢性肝炎组在≤35岁与36～40岁、＞40岁比较,差异有统计学意义(x2=3.936,8.534;P=0.047,0.003); ALT水平在＜0.5×正常值上限(ULN)、(0.5～1.0)×ULN、(1.1～1.5)×ULN、(1.6～2.0)×ULN、＞2.0×ULN间比较差异有统计学意义(x2=55.314,P＜0.01),但ALT在(1.1～1.5)×ULN与＞2.0×ULN比较,差异无统计学意义(x2=3.810,P=0.051).多因素分析显示,病程、饮酒史、ALT分层、HBV DNA水平及超声检查肝表面是否光滑是病理学符合慢性HBV携带者诊断的独立影响因素(OR=0.995、0.224、0.516、1.308、0.270,P=0.005、0.007、0.000、0.025、0.001).结论 年龄35岁以上且ALT水平介于(1～2)×ULN的患者行肝活组织检查的临床意义更大.     

Sarcoidosis in patients with chronic hepatitis C virus infection: analysis of 68 cases

We describe the clinical characteristics, the patterns of association, and the role of antiviral therapies in patients with sarcoidosis associated with chronic hepatitis C virus (HCV) infection. Sixty-eight patients were included in the current study, 56 cases identified in the literature search plus 12 unpublished cases from our department. In 50 HCV patients, sarcoidosis appeared after starting antiviral therapy. Antiviral therapy associated with triggered sarcoidosis consisted of alpha-interferon monotherapy in 20 cases and combined therapy with alpha-interferon and ribavirin in 30. Sarcoidosis appeared during the first 6 months after starting therapy in 66% of patients. The clinical picture of sarcoidosis included predominantly pulmonary disease in 38 (76%) patients and cutaneous sarcoidosis in 30 (60%). Antiviral therapy was discontinued in 60% of patients and continued or adjusted in 14%, while sarcoidosis appeared after completed therapy in the remaining cases. Specific therapy for sarcoidosis was started in only 21 patients, mainly with oral corticosteroids. The outcome of patients was detailed in 46 cases: remission or improvement was observed in 38/46 (83%) patients, stabilization of sarcoidosis in 5/46 (11%), and reactivation of sarcoidosis after an initial improvement in 3/46 (6%). Finally, 18 treatment-naive HCV patients presented sarcoidosis, with 14/18 (87%) patients presenting with pulmonary involvement and 8/18 (44%) with cutaneous involvement.In summary, sarcoidosis may be observed in HCV patients in 2 different situations: triggered by antiviral therapy (in 75% of cases) and unrelated to treatment. Sarcoidosis during antiviral therapy may present mainly as cutaneous or pulmonary disease, with a benign, uncomplicated evolution in more than 85% of cases. However, more complicated cases are observed, especially in HCV patients with preexisting sarcoidosis and/or with previous antiviral treatment. Clinicians should be aware of the possibility that sarcoidosis may initially manifest or be reactivated during or shortly after treatment with antiviral therapy in patients with chronic HCV infection.     

132例家族聚集性慢性乙型肝炎病毒感染者影响自然病程进展的相关因素分析

目的探讨慢性乙型肝炎病毒感染者自然病程进展规律及其与感染持续时间、血清HBV DNA载量、HBe Ag状态和脾脏厚度的关系。方法 2007年1月至2010年8月就诊于中国医科大学附属盛京医院感染病科的家族聚集性慢性乙型肝炎病毒感染者132例,常规行肝组织活检病理学检查,采用化学发光法检测血清HBV标记物;采用荧光定量PCR法检测血清HBV DNA;使用西门子S200二维彩超诊断仪测量脾脏厚度。结果在132例慢性乙型肝炎患者中,年龄≥30岁患者肝组织炎症评分≥5分和纤维化评分≥3分发生率分别为33.3%和38.4%,显著高于年龄30岁组(14.9%和14.8%,P0.05);肝功能正常组肝组织炎症评分≤4分和纤维化评分≤2分发生率分别为92.0%和92.0%,肝功能异常组为53.6%和16.74%(P0.05);肝功能反复异常1年的患者肝组织炎症评分≥5分和纤维化评分≥3分发生率分别为42.8%和51.5%,显著高于肝功能异常≤1年组(31.9%和31.9%,P0.05);血清HBV DNA载量为3~5 lg copies/ml组肝组织炎症评分为≤4分和纤维化评分为≤2分发生率分别为50.0%和27.8%,显著高于病毒载量3 lg copies/ml组(P0.05);血清HBe Ag阴性组纤维化评分在3~4分和≥5分发生率分别为23.1%和20.5%,显著高于HBe Ag阳性组的11.8%和9.7%(P0.05);血清HBe Ag阳性与否与肝组织炎症无显著相关性(P0.05);脾脏厚度≥4 cm组肝组织炎症≥5分和纤维化评分≥5分发生率分别为76.9%、7.7%和76.9%,显著高于脾脏厚度4 cm组的16.0%、3.4%和5.9%(P0.05);多因素分析发现脾脏厚度与肝组织炎症(t=2.153)和纤维化程度(t=4.654)呈显著独立正相关(P=0.033);血清HBV DNA载量与肝组织纤维化程度(t=-2.826)也呈独立相关(P=0.005)。结论家族聚集性的慢性乙型肝炎病毒感染者肝组织炎症和纤维化程度与感染持续时间成正相关,年龄大于30岁时更易出现肝脏疾病的进展。肝功能异常时间越长肝脏炎症和纤维化改变越显著。脾脏厚度与肝组织炎症和纤维化程度具有独立正相关。血清HBV DNA载量为1×103~105copies/ml时肝组织炎症和纤维化改变更显著。