抗病毒治疗对慢乙肝相关致癌因素的干预研究(英文)

目的:研究抗病毒治疗对原发性肝癌的慢性乙型肝炎相关危险因素的干预作用。方法:回顾性分析青岛市传染病医院2010年2月至2012年6月住院的原发性肝癌患者病例249例,经统一编制的调查表记录相关数据,分析比较抗病毒治疗组与无抗病毒治疗组两组间各因素的分布差异。结果:抗病毒治疗组与无抗病毒治疗组患者被诊断为HCC前的HBV感染时间、肝硬化史以及HBV DNA载量,P0.05,差异均有统计学意义;两组间的HBV感染模式、AFP、CEA差异无统计学意义;相关肝功能指标经统计学处理差异均有意义。结论:抗病毒治疗可以明显降低慢乙肝相关致癌因素在患者中的分布,有效抑制HBV DNA复制,进而或可降低乙肝相关性肝癌的发病率。     

循环DNA 和HBV-DNA 载量与原发性肝癌的相关性探讨

目的:探讨血浆DNA和HBV-DNA载量在病毒性肝炎肝硬化后原发性肝癌(PHC)的诊断价值。方法:用RT-PCR方法随访检测HBsAg阳性且经彩色B超诊断为肝硬化的患者,每6个月检测一次患者的血液循环DNA和HBV-DNA载量,直到经临床症状、彩色B超、CT诊断为原发性肝癌为止。结果:在PHC中,循环DNA 61.3±31.9ng/ml,健康对照组20.3±9.9ng/ml,两组差异显著(P<0.01);而HBV-DNA载量,在PHC确诊时多数处于较低水平,78%≤105copies/ml,与PHC确诊前有明显差异(P<0.01)。PHC未发生淋巴结转移者循环DNA 51.2±17.9ng/ml,淋巴结转移者循环DNA 73.9±23.7ng/ml,两者存在差异(P<0.05);而HBV-DNA载量有无淋巴结转移无明显差异。结论:联合检测血液循环DNA和HBV-DNA载量对PHC的预测、预后价值明显,且方法简单,易于开展。     

乙型病毒性肝炎患者血清HBV-LP与HBV-DNA水平表达的相关性及临床意义

目的:探讨乙型病毒性肝炎患者血清乙肝病毒外膜大蛋白(HBV-LP)与乙肝病毒脱氧核糖核酸(HBV-DNA)水平表达的相关性及临床意义。方法:选择2016年1月至2018年6月间我院收治的乙型病毒性肝炎患者148例,根据不同乙型肝炎血清标志物模式将患者分为A组18例、B组52例、C组41例、D组37例。根据不同HBV-DNA载量分为阴性组70例、低载量组21例、中载量组35例、高载量组22例。检测不同乙型肝炎血清标志物模式下HBV-LP、HBV-DNA阳性率及水平,比较不同HBV-DNA载量HBV-LP水平和肝功能指标,并分析其相关性。结果:C组、D组患者HBV-LP、HBV-DNA阳性率及水平均高于A组和B组(P<0.05),A组和B组、C组和D组患者HBV-LP、HBV-DNA阳性率及水平比较差异无统计学意义(P>0.05)。阴性组、低载量组、中载量组、高载量组天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、HBV-LP水平均呈逐渐升高的趋势,组间比较差异有统计学意义(P<0.05)。经Pearson相关性分析显示,乙型病毒性肝炎患者血清HBV-LP与HBV-DNA载量的对数值、ALT、AST呈正相关(P<0.05)。结论:乙型病毒性肝炎患者血清HBV-LP可以反映HBV复制情况,并于肝功能指标密切相关。     

循环DNA和HBV—DNA载量与原发性肝癌的相关性探讨

目的：探讨血浆DNA和HBV—DNA载量在病毒性肝炎肝硬化后原发性肝癌（PHC）的诊断价值。方法：用RT—PCR方法随访检测HBsAg阳性且经彩色B超诊断为肝硬化的患者,每6个月检测一次患者的血液循环DNA和HBV-DNA载量,直到经临床症状、彩色B超、CT诊断为原发性肝癌为止。结果：在PHC中,循环DNA61．3±31．9ng／ml,健康对照组20．3±9．9ng／ml,两组差异显著（P〈0．01）;而HBV—DNA载量,在PHC确诊时多数处于较低水平,78％≤105copies／ml,与PHC确诊前有明显差异（P〈0．01）。PHC未发生淋巴结转移者循环DNA51．2±17．9ng／ml,淋巴结转移者循环DNA73．9±23．7ng／ml,两者存在差异（P〈0．05）;而HBV-DNA载量有无淋巴结转移无明显差异。结论：联合检测血液循环DNA和HBV—DNA载量对PHC的预测、预后价值明显,且方法简单,易于开展。     

肝硬化患者乙肝表面抗原的定量检测及意义

目的:探讨HBsAg定量测定在乙肝相关性肝硬化病程中的变化和意义。方法:选择乙肝相关性肝硬化患者60例纳入实验对象,根据2000年9月(西安)第10次全国病毒性肝炎学术会议修订的《病毒性肝炎防治方案》中的诊断标准分为代偿期组和失代偿期组,其中代偿期组35例,失代偿期组25例。另选取20例乙型肝炎病毒携带者作为对照组。应用电化学发光免疫分析法测定患者血清中HBsAg和HBeAg滴度,免疫荧光定量PCR法检测HBVDNA载量。结果:对照组、肝硬化代偿期组和肝硬化失代偿期组HBsAg滴度分别为:2574.73±3252.27COI、5494.35±2129.84COI和6921.25±1957.60COI,三组之间差别均有统计学意义(P<0.05)。肝硬化代偿期组中,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性(P<0.05()r=-0.350;r=-0.514)。肝硬化失代偿期组中,HBsAg滴度与HBVDNA及HBeAg水平均无明显相关性(r=-0.020;r=0.154)。结论:肝硬化失代偿期HBsAg滴度明显高于肝硬化代偿期,代偿期HBsAg滴度高于HBV携带者组,即HBsAg滴度随肝脏疾病进展呈阶梯型递增。肝硬化代偿期,HBsAg滴度与HBVDNA、HBeAg水平呈负相关性,HBsAg水平可以作为评估病毒复制的参考指标。肝硬化失代偿期,HBsAg滴度与HBVDNA和HBeAg无相关性,不能反映病毒复制水平,不能作为评估病毒复制的参考指标。     

13039例乙型肝炎患者血清HBV DNA水平流行病学分析

目的了解本地区近四年乙型肝炎患者HBV DNA阳性率与病毒载量分布特点。方法采用荧光定量聚合酶链反应(PCR)检测2012年至2015年间13 039例HBsAg阳性患者HBV DNA载量,并进一步分析24例HBeAg阳性、31例HBeAg阴性初诊乙肝患者4年间接受正规治疗后HBV DNA变化趋势。结果本地区近4年间血清HBV DNA阳性率依次为48.6%、46.18%、38.69%、37.66%,呈逐年下降趋势,差异具有统计学意义(P0.01);各年度病毒载量均值的对数值分别为(5.48±1.56),(5.27±1.72),(5.29±1.68),(5.35±1.85)拷贝/mL。2013年、2014年、2015年分别与2012年相比,差异均有统计学意义(P0.01、P0.01、P0.05),而低病毒载量(即病毒拷贝数的对数值小于5拷贝/mL)患者比例2012年明显大于其他年份,2012年分别与2013年、2014年、2015年相比,差异具有统计学意义(P0.01,P0.01,P0.05);HBeAg阳性/阴性乙肝患者接受正规治疗后,其HBV DNA载量均呈逐年下降趋势,其中第一年下降显著(P0.01)。结论近4年本地区血清HBV DNA阳性率呈逐年下降趋势,且低病毒载量比例明显增加。     

慢性乙型肝炎抗病毒治疗的体会

大量的临床研究表明 ,HBV在体内持续复制 ,是引起肝脏病变的持续活动及发展的病因 ,甚至可进一步发展为肝硬化、重症肝炎和肝癌。因此 ,抗病毒治疗是病毒性肝炎治疗的最主要的关键治疗措施 ,用抗病毒治疗来清除 HBV是根本的治疗措施。抗 HBV药物有干扰素、核苷类似物及免疫调节剂。1　干扰素　　用于病毒性肝炎治疗的主要是干扰素α,是目前国内外公认的治疗病毒性肝炎的有效药物。我科自 1 994～ 1 997年应用较多 ,共 83例 ,均诊断为慢性乙型肝炎 ,ALT升高 (3～ 5倍常值上限 ) HBe Ag阳性 ,干扰素α 3～ 5mu肌注 ,每周 3次 ,疗程 3～6…     

肝癌乙型肝炎病毒感染患者术后恩替卡韦抗病毒治疗的临床疗效及安全性评价

目的:探讨肝癌乙型肝炎病毒(HBV)感染患者根治性切除术后采用恩替卡韦抗病毒治疗的临床疗效及安全性。方法:收集2015年1月-2017年8月在我院行根治性切除术的肝癌HBV感染患者279例为研究对象,以血清HBV-DNA载量10~5 copies/ml为界限,分为高病毒复制组128例,低病毒复制组151例,按照随机数字表法将高病毒复制组分为高-治疗组64例、高-对照组64例,将低病毒复制组分为低-治疗组76例、低-对照组75例。高-治疗组和低-治疗组术后给予恩替卡韦0.5 mg/d,高-对照组和低-对照组未行抗病毒治疗。比较手术前、术后7 d各组的血清HBV-DNA水平,血清白蛋白(ALB)、谷丙转氨酶(ALT)、前白蛋白(PA),以及术后并发症的发生情况。结果:高-治疗组、高-对照组、低-治疗组、低-对照组术后血清ALB、PA均较治疗前降低,血清ALT均较治疗前升高,且高-治疗组或低-治疗组术后血清ALB、PA均高于高-对照组或低-对照组,血清ALT水平均低于高-对照组或低-对照组,差异均有统计学意义(P0.05);高-治疗组或低-治疗组术后血清HBV-DNA水平均低于治疗前,且均低于同期高-对照组或低-对照组,差异均有统计学意义(P0.05)。高-治疗组与高-对照组、低-治疗组与低-对照组患者术后并发症发生率均无统计学差异(P0.05)。结论:恩替卡韦能显著改善肝癌HBV感染患者术后的血清HBV-DNA载量水平和肝功能,安全性高,值得临床推广。     

干扰素-α治疗慢性乙型肝炎的疗效及其影响因素的研究

目的:分析影响干扰素-α(IFN-α)治疗慢性乙型肝炎(CHB)疗效的因素。方法:选择2006年到2009年青岛市传染病医院住院的CHB患者46例,应用IFN-α治疗48周,根据IFN-α治疗的疗效将其分为应答组与无应答组,评价患者的宿主、病毒载量及生化指标等因素对疗效的影响。结果:两组间的性别比例、年龄和病程无显著差异(P>0.05),应答组治疗前HBV-DNA载量低于无应答组,ALT水平高于无应答组,HBeAg阳性患者的应答率高于HBeAg阴性患者,差异均具有统计学意义(P<0.05),应答组在治疗12周时HBV-DNA载量下降>2log的比例高于无应答组,差异具有统计学意义(P<0.05)。结论:治疗前HBVDNA载量低、ALT水平高和HBeAg阳性以及治疗12周时的HBVDNA应答可以作为干扰素-α治疗慢性乙型肝炎48周时应答的预测因素。     

抗病毒治疗艾滋病48例临床研究

目的探讨艾滋病抗病毒治疗的效果,为进一步开展有效的抗病毒治疗提供依据。方法应用抗病毒治疗药物对符合治疗条件的艾滋病患者进行规范的抗病毒治疗,并进行病毒载量检测。结果对接受抗病毒治疗的48例患者进行病毒载量测定,平均病毒载量为2.0log拷贝/ml,其中16例血浆中未检测到艾滋病病毒,占57.14%。30例患者的CD4细胞均有不同程度升高,从26个/μl升高至517个/μl,平均升高(193.27±51.91)个/μl;治疗2年以上者CD4细胞平均升高(221.08±87.65)个/μl。病人机会性感染得到明显控制,发病率和死亡率显著降低(死亡率从44.44%下降至2.50%)。病人能从事中、重度体力劳动的比例由治疗前的13.33%上升到治疗后的30.0%。结论艾滋病患者抗病毒治疗效果显著,病人生活质量得到明显改善,符合治疗条件的病人应及早进行规范抗病毒治疗。     

慢性病毒性肝炎研究进展

近年,慢性病毒性肝炎研究领域有较大进展,慢性乙型肝炎病毒（HBV）感染,虽然有了应用广泛、历史较久、且效果较好的疫苗,但迄今仍是世界范围肝硬化和肝癌的主要诱因。传染途径可经产道、性接触和非肠道途径（包括静脉吸毒、血制品等）。成年病人有少有变慢性,但一岁以下患儿90％变成慢性肝炎。慢性肝损伤的临床表现可以是轻微的炎症重到晚期肝硬化,程度不等。α干扰素（IFNα）是治疗活动性肝炎的产宰药物,单核苷酸类药物（lamivudine和adefovir）也具有同样的疗效。晚期肝病和肝癌患者可进行移植,但异常伴发移植物的感染。乙型肝炎免疫球蛋白和新型抗病毒药物联合应用,可降低移植物感染的严重性。丙型肝炎病毒（HCV）在20世纪后期感染了大约1％的世界人口。这中RNA病毒非经口传播,绝大多数病人变成慢性肝炎,约20％逐渐演变成肝硬化或肝癌。用IFNα和病毒唑（Ribavirin）联合治疗,约40％病人的病理表现有所改善。肝移植对某些病例是适宜的,但移植物感染仍是悬而未决的问题,新发现的庚型肝炎病毒（HGV）和TT病毒目前认为并不引起严重的肝损害。     

Hepatitis B viral factors and clinical outcomes of chronic hepatitis B

Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.     

Chronic hepatitis B--who should be treated?

Hepatitis B virus (HBV) can cause both acute and chronic infection and is an important human pathogen, with an estimated 350 million individuals chronically infected worldwide. HBV carriers are at risk for the development of cirrhosis and hepatocellular carcinoma (HCC), and patients with chronic infection require life-long monitoring. Effective hepatitis B antiviral treatment is important given the significant associated global morbidity and mortality from liver-related complications. The goals of treatment are to achieve sustained suppression of HBV replication and remission of liver disease. In the past decade, great progress has been made in the treatment of chronic HBV infection. Interferon alfa, longer-acting pegylated interferon, and nucleos(t)ide analogs such as lamivudine, adefovir dipivoxil, and entecavir are currently available for treatment of HBV infection. Effective treatment decisions require an understanding of the natural history of hepatitis B and the range of treatment options. This review includes criteria for determining when and how to most effectively intervene with antiviral therapy for chronically infected patients.     

四环素诱导的丙型肝炎病毒非结构蛋白5B稳定细胞株的构建和检测

丙型肝炎病毒(HCV)感染个体后在宿主细胞内长时间保持低水平复制,与慢性肝炎、肝硬化及肝细胞肝癌的发生密切相关.目前,HCV感染后肝细胞发生转化的具体机制还不清楚.非结构蛋白5B(NS5B)是HCV编码的非结构蛋白之一,具有RNA依赖的RNA聚合酶活性(RdRp),是病毒复制所需的关键酶.除参与病毒复制外,NS5B通过...     

S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑的临床效果研究

目的:研究S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑患者的临床效果。方法:选择2011年3月~2013年3月我院收治的51例不同病因的胆汁淤积性肝病(药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例)并抑郁/焦虑的患者,予S-腺苷蛋氨酸1.0 g治疗2周,应用SDS/SAS量表分别评估和比较治疗前后各组患者抑郁/焦虑程度的评分情况。结果:S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94.12%,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100.00%,肝癌的有效率为60.00%,胆管癌的有效率为50.00%,药物性肝损害患者临床疗效与其他各组有差异(P0.05);药物性肝病患者SDS和SAS评分均较治疗前显著降低(P0.05)。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异(P0.05)。结论:S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁/焦虑患者的肝功能,并有效减轻其抑郁/焦虑情绪。     

Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90

Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in the folding of cellular and viral proteins and also interacts with HCV proteins. In the present study, we knocked down the expression of the Hsp90 gene and inhibited viral replication using siRNA molecules. Reducing the expression of Hsp90 successfully decreased HCV replication. All siRNA molecules specific to the viral genome showed the efficient inhibition of viral replication, particularly siRNA targeted to the 5′UTR region. The combination of siRNAs targeting the viral genome and Hsp90 mRNA also successfully reduced HCV replication and reduced the occurrence of viral resistance. Moreover, these results suggest that an approach based on the combination of cellular and viral siRNAs can be used as an effective alternative for hepatitis C viral suppression.     

The Multifaceted Associations of Hepatobiliary Disease and Diabetes

ObjectiveTo investigate the association of diabetes and hepatobiliary disease.MethodsWe performed a MEDLINE search of the English-language literature published between January 1980 and January 2007 for studies in which diabetes was associated with liver diseases.ResultsThrough its association with the insulin resistance syndrome, type 2 diabetes is associated with nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), NASH-cirrhosis, and NASH-cirrhosis-related hepatocellular carcinoma. Because of the association with insulin resistance, insulin sensitizers may slow or even arrest the progress of these diseases. Type 2 but not type 1 diabetes is associated with hepatitis C virus but not hepatitis B viral infection. This association is likely due to hepatitis C viral infection of the pancreatic β-cells. Early detection and antiviral therapy can decelerate the development of diabetes. Type 1 diabetes is associated with hemochromatosis and autoimmune hepatitis. Because of the presence of autonomic neuropathy, cholelithiasis but not cholecystitis is more common in patients with diabetes than in the general population. Therefore, asymptomatic cholelithiasis in patients with diabetes no longer warrants a cholecystectomy. In patients with advanced liver disease of any cause, insulin resistance and diabetes have an increased frequency of occurrence and can be reversed with liver transplantation. Rarely, medications used to treat type 2 diabetes have been associated with drug-induced hepatitis.ConclusionThe prevalence of hepatobiliary diseases is increased in patients with diabetes. Early recognition and treatment of these conditions can prevent, stabilize, or even reverse hepatic damage and prevent the development of hepatic carcinoma and liver failure. (Endocr Pract. 2007;13:300-312)     

Review on chemogenomic approaches towards hepatitis C viral targets

Hepatitis C virus (HCV) is the most prevalent viral pathogen that infects more than 185 million people worldwide. HCV infection leads to chronic liver diseases such as liver cirrhosis and hepatocellular carcinoma. Direct-acting antivirals (DAAs) are the recent combination therapy for HCV infection with reduced side effects than prior therapies. Sustained virological response (SVR) acts as a gold standard marker to monitor the success of antiviral treatment. Older treatment therapies attain 50-55% of SVR compared with DAAs which attain around 90-95%. The current review emphasizes the recent chemogenomic updates that have been unfolded through structure-based drug design of HCV drug target proteins (NS3/4A, NS5A, and NS5B) and ligand-based drug design of DAAs in achieving a stable HCV viral treatment strategies.     

Prediction of Clinical Outcomes in Hepatitis B E Antigen Negative Chronic Hepatitis B Patients with Elevated Hepatitis B Virus DNA Levels

Objectives

We investigated whether long-term clinical outcomes such as disease progression or inactive hepatitis B virus (HBV) carrier state can be predicted by baseline factors in hepatitis B e antigen (HBeAg)-negative HBV infected patients with an elevated viral load.

Methods

A retrospective cohort of 527 HBeAg-negative chronic HBV infected patients with an elevated viral load (HBV DNA ≥ 2,000 IU/ml) was assessed for disease progression defined by the development of hepatocellular carcinoma (HCC) or cirrhotic complication, as well as becoming an inactive carrier.

Results

During a median 3.6 years of follow-up, disease progression was detected in 46 patients (40 with HCC, 6 with cirrhotic complication), and 31 of 309 non-cirrhotic patients became inactive carriers. Older age, male gender, cirrhosis, high HBV DNA levels at baseline, and short antiviral therapy duration were independent risk factors for HCC. Low HBV DNA and quantitative hepatitis B surface antigen (qHBsAg) levels were independent predictors for becoming inactive carriers in patients without cirrhosis. In non-cirrhotic patients with both low qHBsAg and HBV DNA levels, the 5-year cumulative incidence of an inactive carrier was 39.8%, while that of disease progression was 1.6%.

Conclusion

HBeAg negative patients without cirrhosis can be closely monitored for becoming an inactive carrier when both HBV DNA and qHBsAg levels are low, as the risk of disease progression is low while incidence of an inactive carrier is high.     

S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁／焦虑的临床效果研究

目的：研究s-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁／焦虑患者的临床效果。方法：选择2011年3月-2013年3月我院收治的51例不同病因的胆汁淤积性肝病（药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例）并抑郁／焦虑的患者,予s-腺苷蛋氨酸1．0g治疗2周,应用SDS／SAS量表分别评估和比较治疗前后各组患者抑郁／焦虑程度的评分情况。结果：S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94．12％,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100．00％,肝癌的有效率为60．00％,胆管癌的有效率为50．00％,药物性肝损害患者临床疗效与其他各组有差异（P〈0．05）;药物性肝病患者SDS和SAS评分均较治疗前显著降低（P〈0．05）。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异（P〉0．05）。结论：S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁／焦虑患者的肝功能,并有效减轻其抑郁／焦虑情绪。