Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection, and its relation to disease severity. METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%) and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them (12%; occult HBV infection). CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.     

Detection of hepatitis C virus core antigen for early diagnosis of hepatitis C virus infection in plasma donor in China

AIM: To evaluate the effi cacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from 11 regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS: Among all of the sequential samples, the original 13 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples (75%) were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples (93.1%) were found HCV RNA-positive in HCV core antigen-positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION: This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period (PWP) plasma donations.     

Serodiagnosis of hepatitis B virus infection by antibody to core antigen

In a military population antibody to hepatitis B core antigen (anti-HBc) was found in 39% of acute hepatitis cases negative for hepatitis B surface antigen (HBS Ag) and in 96% of HBs Ag-positive cases. Persistence of antibody to HBs Ag (anti-HBs) in convalescent-phase sera was significantly greater (P less than 0.001) in individuals with acute HBs Ag-positive hepatitis B than in patients with clinical HBs Ag-negative hepatitis B. The prevalence of anti-HBc in the absence of HBs Ag, anti-HBs, and clinical disease was 3.2% in this military population. In longitudinal studies of hepatitis B infection, the presence of anti-HBc preceded anti-HBs and improved the ability to determine the onset of sublicnical infection. Anti-HBc is a useful serologic marker for the study of the epidemiology of hepatitis B and improves the efficiency of detection of hepatitis B virus infection.     

丙型肝炎病毒核心蛋白人源单链可变区抗体的筛选与鉴定

目的 筛选、鉴定抗丙型肝炎病毒（HCV）核心蛋白的人源单链可变区抗体（ScFv)。方法 采用噬菌体表面展示技术,以重组的HCV核心蛋白为包被抗原,从噬菌体单链可变区抗体库中经过3轮“吸附－洗脱－扩增”筛选过程,获得抗原结合活性较强的HCV核心蛋白特异性人源单链可变区抗体片段阳性克隆,并对其进行免疫学及核苷酸序列测定。结果 筛选得到的ScFv片段具有抗HCV核心蛋白的特异性,基因序列分析结果表明符合人源单链可变区抗体基因序列的结构特征。结论 利用噬菌体抗体库技术,成功获得HCV核心蛋白的特异性人源单可变区抗体的编码基因。     

合并乙型肝炎病毒感染对丙型肝炎病毒核心抗原检测的影响

目的 探讨合并HBV感染对慢性HCV感染者血清丙型肝炎病毒核心抗原(HCVcAg)检出情况的影响. 方法 收集2005年12月-2009年10月慢性丙型肝炎患者和HBV/HCV合并感染者资料,检测血清HCVcAg和HCV RNA,对后者血清进行HBV DNA、HBeAg检测,分析HCVcAg检出率与HBeAg、HBV DNA定量检测的关系.用独立两组多分类的X2检验方法进行统计学分析. 结果 共收集88例慢性丙型肝炎患者和62例HBV/HCV合并感染者资料,血清HCVcAg的检出率分别为72.7％(64/88)和38.7％ (24/62),两者比较,x2= 17.358,P＜0.01,差异有统计学意义.HCV RNA检出率分别为81.8％ (72/88)和53.2％ (33/62),两者比较,x2=20.110,P＜0.01,差异有统计学意义.62例HBV/HCV合并感染者血清中,HBeAg阳性和HBeAg阴性感染者HCVcAg检出率分别为28.6％ (12/42)和60.0％ (12/20),两者比较,x2=5.641,P=0.011,差异有统计学意义.HCV RNA阳性率分别为42.9％ (18/42)和80.0％ (16/20),两者比较,X2=7.547,P＜ 0.01,差异有统计学意义.HBV DNA阳性和阴性时HCVcAg检出率分别为39.1％ (18/46)和37.5％ (6/16),两者比较,P＞0.05,差异无统计学意义.与单纯HCV感染者血清HCVcAg检出率72.7％ (64/88)比较,HBeAg阴性合并感染者为60.0％ (12/20),x2=1.266,P=0.261,差异无统计学意义;HBV DNA阴性合并感染者为37.5％ (6/16),x2=7.635,P＜0.01,差异有统计学意义.结论 HBV/HCV合并感染时HCVcAg检出率较低,可能是由于HBeAg抑制HCV的复制,从而减少HCVcAg的表达所致.     

A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.     

Immunoglobulin A antibody against hepatitis B core antigen in the acute and persistent infection with hepatitis B virus

Antibody to hepatitis B core antigen of immunoglobulin A class was determined in the serum of patients infected with hepatitis B virus by a sandwich-type solid-phase radioimmunoassay with monoclonal antibodies. The antibody, as defined by a sample to normal ratio greater than 2.1, was detected in all of 39 patients with acute hepatitis, with titers varying widely depending on the time of blood sampling. In persons with persistent infection, the antibody was detected in only 2 (4%) of 46 asymptomatic carriers of the virus, contrasting with the positivity in as many as 15 (41%) of 37 patients with chronic persistent hepatitis, in 45 (94%) of 48 patients with chronic active hepatitis, and in 40 (87%) of 46 patients with liver cirrhosis with or without hepatocellular carcinoma. The mean +/- SE titer of antibody in chronic persistent hepatitis (3.8 +/- 0.9) was significantly lower than those in chronic active hepatitis (13.8 +/- 3.2) and cirrhosis with or without carcinoma (25.6 +/- 6.1) (p less than 0.001). Based on the results obtained, the antibody may reflect hepatic injury in the persistent hepatitis B virus infection.     

A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years.

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.     

Significance of IgM antibody to hepatitis B core antigen in a Greek population with chronic hepatitis B virus infection

IgM antibody to hepatitis B core antigen (IgM anti-HBc) may indicate an active immune response to persistent infection with hepatitis B virus (HBV). We studied 186 Greek HBsAg carriers for IgM anti-HBc and attempted to correlate it with other HBV and hepatitis delta virus (HDV) markers. Overall, IgM anti-HBc was detected more frequently than HBV DNA in this population (50% vs 34, p less than 0.001); this was also true for the 149 of the 186 HBsAg carriers with antibody to hepatitis B e antigen (anti-HBe) (48% vs 22%, p less than 0.001). The opposite was found in the carriers positive for hepatitis B e antigen (HBeAg): HBV DNA was observed in 93% and IgM anti-HBc in 64% of the cases (p less than 0.05). The detection of these markers was independent of sex. Serum alanine aminotransferase (ALT) levels were significantly more elevated in patients with positive tests for IgM anti-HBc and HBV DNA than in patients positive only for HBV DNA (p less than 0.001) irrespective of their HBeAg or anti-HBe status. Moreover, the detection of elevated ALT was independent of the intensity of the HBV DNA hybridization signal. Antibodies to hepatitis delta antigen (HDAg) were only found in 4 (2.4%) of 167 patients tested.     

HBsAg阴性或抗-HBc阳性者肺癌术后辅助化学治疗中乙型肝炎病毒的再激活

目的 探讨HBsAg阴性或抗-HBc阳性者肺癌术后辅助化学治疗中HBV的再激活及其相关危险因素.方法 回顾性分析2003年1月到2011年12月接受辅助化学治疗的3280例肺癌术后患者,所有入组患者进行HBV血清学标志物和生物化学检测,并接受以顺铂为基础的辅助化学治疗方案.数据比较行x2检验.结果 367例HBsAg阴性或抗-HBc阳性肺癌术后患者中,14例(3.81％)进展为乙型肝炎.单因素分析表明,患者年龄≥70岁(x2=13.003,P=0.019)、肝脏CT检查为脂肪肝或早期肝硬化(x2=11.225,P=0.026)和使用糖皮质激素累计剂量超过150mg(x2=7.008,P=0.033)是辅助化学治疗中HBV再激活的相关因素;而性别、基础辅助化学治疗方案与HBV的再激活无关联.结论 肺癌术后的辅助化学治疗中,HBsAg阴性或抗-HBc阳性者有一定比例可以发生HBV的再激活.     

Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P<0.05) and one (5.3%) of 19 patients with mild (P<0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.     

Detection of antibody to envelope (E2) antigen of hepatitis C virus

One hundred and four clinical specimens from provincial public health laboratories were tested for antibody to hepatitis C virus (HCV) envelope protein (anti-E2). To evaluate the effect of hypervariability of E2 region on anti-E2 assay, 49 recombinant immunoblot assay (RIBA) 3.0 positive samples were genotyped. All 49 genotyped samples were positive for anti-E2. Eight of 12 (67%) indeterminate, HCV RNA positive samples were anti-E2 reactive. Nine of 30 (30%) indeterminate, HCV RNA negative samples were also positive for anti-E2. Anti-E2 was detected in two of 13 (15%) RIBA-negative and enzyme immunoassays-positive samples. Although small number of samples were tested, the results showed that it may be possible to resolve indeterminate samples with the anti-E2 assay.     

Improved serodiagnosis of non-A, non-B hepatitis by an assay detecting antibody to hepatitis C virus core antigen.

We examined sequential serum samples from 12 patients with well-characterized posttransfusion non-A, non-B hepatitis who had an acute, resolving self-limited type of clinical course for the presence of antibody to the hepatitis C virus nucleocapsid (core) protein (p22) expressed by a recombinant baculovirus. These sera were simultaneously examined for antibody to the hepatitis C virus nonstructural protein (C100-3) that is presently used for blood screening worldwide. In three patients, both anti-p22 and anti-C100-3 antibodies were detected, but anti-p22 was detected much earlier. In four patients, only anti-p22 was detected. Two other patients were considered to be hepatitis C virus carriers who had been already infected with hepatitis C virus. In one patient, only anti-C100-3 was detected, and it was transient. In two patients, neither antibody was detected. Anti-p22 was detected in at least one of eight samples of transfused blood. Of the nine samples of donated blood that were positive for anti-p22, only four were positive for anti-C100-3. This new assay detecting the antibody to the p22 protein is thus useful for the serodiagnosis of non-A, non-B hepatitis in the acute phase and for blood screening.     

丙型肝炎病毒感染的检测

丙型肝炎病毒（HCV）感染的检测包括血清学检测和核酸检测（NAT）,前者包括HCV抗体（抗-HCV）、核心抗原检测,后者包括定性/定量RNA检测和基因型/亚型检测。抗-HCV检测是应用最广的HCV感染筛查试验,操作简便、耗时短、成本低,但其缺点是窗口期较长,不能判别是活动性感染还是病毒已被清除,不适用于免疫缺陷人群。HCV RNA是病毒感染的直接证据,既往定性RNA检测灵敏度较高,但随着实时定量PCR技术的成熟,定量检测灵敏度不断提高,线性范围不断拓宽,适用于临床抗病毒治疗应答的监测,也正逐步取代定性检测用于血液制品的筛查。近年HCV抗原检测和抗原抗体联合检测试剂盒已用于HCV感染的筛查及治疗监测,但其灵敏度尚不及NAT。目前主流的HCV基因分型试剂检测基因型有较高的符合率,而检测亚型的结果存在较大差异,需要方法学上的改进。     

Performance characteristics of a combined hepatitis C virus core antigen and anti-hepatitis C virus antibody test in different patient groups

We evaluated the performance of a hepatitis C virus (HCV) antigen/antibody combination test [Murex HCV Antigen/Antibody Combination Test (Murex Ag/Ab test)] by comparing it with the current third-generation HCV antibody enzyme immunoassay (anti-HCV). A total of 403 serum samples were consecutively collected from four patient groups: healthy controls (n=100); HCV-infected patients (HCV?group, n=102); Human immunodeficiency virus (HIV)/HCV-infected patients (HIV/HCV group, n=100); and patients with uremia (uremia group, n=101). Performances were evaluated for the Murex Ag/Ab, anti-HCV, and HCV RNA in the HIV/HCV and uremia patient groups. In the HCV group, all 102 samples showed concordant positive and negative results for anti-HCV, Murex Ag/Ab, and HCV RNA tests. In the HIV/HCV group, all 100 samples were positive for both anti-HCV and Murex Ag/Ab tests, whereas 88 patients (88%) were HCV RNA positive. In the uremia group, 14 (69.0%) of the 23 anti-HCV-positive patients were HCV RNA positive, whereas 14 (77.8%) of the 18 Murex Ag/Ab-positive patients were HCV RNA positive. None of anti-HCV-negative or Murex Ag/Ab-negative patients were HCV RNA positive. Based on the HCV RNA assay, the sensitivities for both anti-HCV and Murex Ag/Ab assays were 100%, whereas the specificities of these two assays were 89.7% and 95.4%, respectively. With good sensitivity and specificity, the Murex Ag/Ab assay could be a useful alternative diagnostic tool, especially in immunocompromised populations, such as patients with uremia or those infected with HIV.