隐匿性乙型肝炎:免疫组织化学和S基因序列分析

目的　了解不明原因慢性肝病中隐匿性乙型肝炎所占比例 ,隐匿性乙型肝炎的发病机制及临床、病理特点。方法　给予 2 0例不明原因慢性肝病患者肝穿刺病理检查 ,应用免疫组织化学方法检测肝组织内的乙型肝炎病毒表面抗原 (HBsAg)、核心抗原 (HBcAg) ,丙型肝炎病毒NS3、NS4抗原。采用荧光定量PCR方法对血清HBVDNA进行定量 ,用套式PCR方法扩增HBVS基因 ,对PCR产物进行直接测序 ,比较S基因的核苷酸和推导出的氨基酸序列的差异。结果　 5例患者经肝脏病理检查表现为慢性炎症 ,3例在肝组织内HBsAg、HBcAg同时阳性 ,2例仅HBcAg阳性。S基因的氨基酸序列分析显示 ,1例患者S基因的 74位密码子发生终止变异 ,另 1例在HBsAg的“a”决定簇内有 2个氨基酸发生变异 (T13 1N ,M 13 3S) ,其他 3例患者HBsAg的“a”决定簇内未发现变异。 结论　在我国隐匿性乙型肝炎是不明原因肝病的主要原因之一 ,低水平的血清HBVDNA可以引起慢性肝炎。部分隐匿性乙型肝炎HBsAg阴性的原因是S基因变异引起的 ,而有些患者则可能因为血清HBsAg水平过低 ,导致HBsAg检测阴性。     

不明原因肝病患者中隐匿性HBV感染情况观察

目的观察不明原因肝病患者中隐匿性HBV感染情况。方法病因不明的肝病患者79例,应用PCR法检测血清HBV DNA。结果 79例病因不明肝病患者中,HBV DNA阳性15例(18.98%);其中,抗HBc阳性者中,HBV DNA阳性12例(37.5%);与不明原因肝炎相比,隐匿性HBV感染者年龄大、失代偿性肝硬化患者比例高,血透明质酸、ALT升高,白蛋白降低,P均<0.05。结论不明原因肝炎患者中存在一定的隐匿性HBV感染,与肝硬化密切相关。     

肝炎患者重度黄疸原因分析

目的观察重度黄疸肝炎病人的原因及转归。方法采用7170A血清生化仪进行检测肝功能,采用SPECTRA酶标仪检测肝炎病毒血清标志物,对281例深度黄疸病人的临床资料进行分析。结果单纯感染肝炎病毒的患者187例,未感染肝炎病毒的患者24例,肝炎病毒重叠感染患者58例,病因未明12例;急性重症肝炎16例,亚急性重症肝炎21例,慢性重症肝炎198例,瘀胆型肝炎43例,其它3例;存活159例,死亡122例。结论嗜肝病毒感染是引发本组病人发病的主要原因,其中感染乙型肝炎病毒者占多数,慢性重症肝炎占70.5%,深度黄疸的患者死亡率高达43.4%。     

肝炎肝硬化患者电解质紊乱原因分析

近年来 ,我们经常发现部分肝炎肝硬化患者因电解质紊乱而诱发或加重肝性脑病 ,其不仅治疗困难 ,而且易致死亡。现对引起电解质紊乱的主要原因分析如下。低钠血症 :1肝硬化患者多有腹水 ,加之长期低盐或无盐饮食 ,钠摄入减少 ,故易致低钠血症。 2肝硬化时肝脏合成功能降低 ,患者多有不同程度的低蛋白血症 ,白蛋白降低可致细胞内呈低渗状态 ,由于渗透压的作用 ,细胞外钠进入细胞内 ,故出现原发性低血钠。 3肝硬化患者长期输入无钠液及原有抗利尿激素活性增强 ,水潴留超过钠潴留 ,导致稀释性低血钠。 4肝硬化时 ,由于长期门脉高压 ,致胃肠道充…     

肝炎后糖尿病5例分析

2000年至2003年4月。我们在临床发现5例肝炎后糖尿病人，其中慢性活动性乙肝3例，急性乙型肝炎1例，急性黄疸型肝炎1例。以上5例肝炎病人．随后在不同时间内并发糖尿病。现分述如下：     

799例重型肝炎患者的临床病原学与实验室分析

目的探讨乙型重型肝炎患者乙型肝炎病毒(HBV)DNA定量、e抗原表达与病死率的相关性,为重型肝炎临床治疗提供参考。方法统计我院2000-2004年各型重型肝炎的发病率,进一步应用荧光定量多聚酶链反应方法检测乙型重型肝炎患者血清HBV DNA,应用微粒子方法检测乙型肝炎e抗原表达情况,并分析其与病死率及抗病毒治疗的临床疗效间的关系。结果(1)重型肝炎中乙型肝炎占83．50％,慢性重型肝炎中乙型肝炎占96．77％;(2)5年间慢性乙型重型肝炎患者HBV DNA定量大于1×10,拷贝／ml组,总病死率为53．25%,小于1×105拷贝／ml组,病死率为34．50％,差异有统计学意义(P<0．01);e抗原表达对病死率无影响;(3)2004年,慢性乙型重型肝炎患者HBV DNA定量大于1×105拷贝／ml病例加用拉米夫定抗病毒治疗,病死率由2000年的54．64%下降至2004年的30．38%,差异有统计学意义(P<0．01)。结论重型肝炎以慢性乙型重型肝炎为主,病毒载量高是高病死率关键因素之一,抗病毒治疗可以降低患者的病死率。     

40例肝炎患者血清抗HBc-IgM测定结果分析

血清抗HBc-IgM含量测定,对乙型肝炎活动期诊断具有较高的敏感性,是评价乙型肝炎的一项有意义的指标。本文就40例肝炎患者抗HBc-IgM含量进行了测定,现报导如下。 一、检测对象 40例肝炎患者,年龄12～73岁,平均24.8岁。急性肝炎34例,重症肝炎5例,肝硬化1例。诊断标准按1990年全国病毒性肝炎防治方案。     

不明原因性肝炎118例

目前甲、乙、丙、丁和戊型肝炎均能明确诊断 ,少数学者认为庚型肝炎病毒 (ＨＧＶ)和输血传播病毒 (ＴＴＶ)也能导致肝炎 ,但临床上仍有较多病情、病程类似的病毒性肝炎 ,却无明确的致病因子。我们统计了 118例无明确致病因子的肝炎 ,并暂命名为“不明原因性肝炎”。现报道如下。材料与方法一、病例与诊断方法118例不明原因性肝炎病例来自我院 1997年 1月至2 0 0 0年 5月住院患者 ,诊断方法为排除法。入院后用酶联免疫吸附试验 (ＥＬＩＳＡ)检测甲～戊型肝炎血清标志物 2次以上 ,均为阴性。并检测ＨＧＶＲＮＡ (Ｎｅｓｔｅｄ ＰＣＲ )、抗 …     

Role of occult hepatitis B virus in chronic hepatitis C patients with flare of liver enzymes

Background

Occult HBV infection is defined by detection of HBV DNA in the serum or liver tissue of patients who test negative for HBsAg. The prevalence of occult HBV is higher in hepatitis C virus (HCV) positive patients than HCV negative patients and may have an impact on their clinical outcome. In this study, we evaluated the role of occult hepatitis B virus infection in chronic hepatitis C patients with ALT flare.

Methods

Sixty HBsAg negative patients with chronic hepatitis C virus infection were included. Patients were divided into 2 groups according to their ALT level: 30 patients with normal or slightly high ALT and 30 patients with ALT flare (≥ 5 times normal values). Patients in both groups were examined for the detection of anti-HBs, anti-HBc IgM, and anti-HBc IgG. HBV DNA was detected using semi-nested PCR technique.

Results

In patients with normal or slightly high ALT, HBV DNA was detected in 4 (13.3%) patients, while in those with ALT flare, HBV DNA was detected in 19 (63.3%) patients (p < 0.001). No association was found between the presence of HBV DNA and various serology markers of HBV infection.

Conclusion

Presence of occult hepatitis B, with its added deleterious effect, must always be considered in chronic hepatitis C patients especially those with flare in liver enzymes; HBsAg should not be used alone for the diagnosis of HBV infection.     

Histopathological evaluation of liver biopsy specimens in children with chronic hepatitis B.

INTRODUCTION: Histopathological evaluation of the liver remains important diagnostic tool. OBJECTIVE: The aim of this study was to assess inflammatory activity, fibrosis and their correlation to the expression of viral antigens in the liver of children with chronic hepatitis B (CHB) before antiviral treatment. MATERIAL AND METHODS: The study included 190 liver biopsies of children aged 1.5-18 (mean 7.46+/-4.05 years) with CHB. The histopathological examination was based on the modified Knodell system. Additionally, immunomorphological analysis was performed in 125 specimens to detect HBsAg and HBcAg. RESULTS: Necroinflammatory activity was scored for mild in 109 children and moderate in 49. Fibrosis was scored for S1 in 90, S2 in 58 and S3-S4 in seven cases. Positive correlation between grading and staging was observed (chi(2)=77.65, p=0.000002). HBsAg was detected in 62 specimens, while HBcAg was found in the nuclei of 108 samples with cytoplasmic expression in 35-28% cases. No correlation of HBsAg expression to histopathological lesions was established whereas partial correlation of HBcAg expression with inflammatory infiltrate was confirmed. CONCLUSIONS: Progression of liver injury in children with CHB varies in severity. Necroinflammatory activity correlates with fibrosis. Expression of viral antigens is independent of histological changes, however confirms the etiology of liver disease.     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

Clinical significance of liver biopsy in chronic hepatitis B patients with persistently normal transaminase

OBJECTIVE: The aim of this study was to study the clinical significance of liver biopsy for individuals who had chronic hepatitis B virus infection and persistently normal serum transaminases for more than 6 months. METHODS: A total of 452 patients with positive hepatitis B surface antigen for over 6 months underwent percutaneous liver biopsy. All liver biopsy specimens were assessed by experienced liver pathologists blinded to the liver biochemistry, and were scored according to the modified criteria of grade and stage of chronic hepatitis. Patients were divided into four groups: group A and group C patients had normal transaminases, and were hepatitis B e antigen (HBeAg) positive and HBeAg negative, respectively; group B and group D patients had elevated transaminases, and were HBeAg positive and HBeAg negative, respectively. RESULTS: All patients had necrosis and inflammation in the liver. Patients with increased serum transaminases had a significantly higher grade (G) of hepatic necrosis and inflammation and more severe (S) fibrosis compared with patients with normal transaminases (P < 0.05). However, in the latter patients, G3 was seen in 10 (5.5%) and 13 cases (9.1%), S3 in seven (3.8%) and 16 cases (11.1%), and S4 in three (1.6%) and seven cases (4.9%) in Group A and Group C, respectively. Moreover, in patients with normal transaminases, the HBeAg‐negative group had more severe fibrosis than the HBeAg‐positive group (P < 0.05). CONCLUSION: Although more severe pathological changes were more frequent in patients with elevated transaminases, significant hepatic pathology could still be found in cases with persistently normal transaminases. Liver biopsy in cases of chronic hepatitis B virus infection is helpful to accurately assess both the activity of the disease and the degree of fibrosis, and to estimate if antiviral therapy is justifiable. Patients with normal transaminases and serious hepatic necrosis, inflammation and fibrosis need proper management.     

不明病因感染性疾病DNA病毒性病原检测方法的建立

目的建立不明病因感染性疾病DNA病毒性病原的检测方法。方法应用DNaseI-非序列依赖的单引物扩增技术,将患者血清过滤后,经DNase I处理去除血清中内源DNA。Csp6.I酶切病原DNA,加接头分子,并以接头分子为引物非特异扩增病原DNA,测序并进行序列分析。结果DNaseI处理血清中内源DNA不会降解病毒DNA;非序列依赖的单引物扩增血清中外源DNA得到多个DNA片段;将所有PCR产物测序,序列与已知病原DNA序列完全一致。结论应用DNaseI处理及非序列依赖的单引物扩增方法可以检测DNA病毒性病原。     

Dilemma of HBsAg seroconversion in chronic hepatitis B infection: Dilemma of HBsAg in chronic HBV

Patients with chronic hepatitis B infection should be followed up to identify possible changes in disease status, such as HBsAg seronversion. There are little data on the outcome of such cases, and the response rate to HBV vaccine has not been discussed extensively.     

An overview of occult hepatitis B virus infection

Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors...     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevale...