Hepatitis viral markers in patients undergoing primary liver transplants

The purpose of the study was to determine the prevalence in liver transplant (OLTx) patients of the hepatitis markers (anti-A, anti-B, anti-C, anti-D and HB_sAg) and the interrelationships between markers and patients' sexes, ages, dates of transplant, clinicopathological diagnoses, and short-term survivals. Slightly more than half of the patients were male. Anti-A and anti-B were about evenly distributed between male and female. Anti-C, anti-D, and HB_sAg were far more common in males. Age and year of transplant showed only a moderate increase in anti-A with increasing age. Anti-A was found in 57% of all patients, anti-B in 18%, anti-C in 17%, and HB_sAg in 17%. Anti-D was tested only in patients who were positive for anti-B or HB_sAg and occurred in 21 (11%) of 185. The poorest short-term survival occurred in males who showed both anti-A and HB_sAg.Supported by a grant from the Blood Science Foundation, Pittsburgh, Pennsylvania 15213. Dr. El-Ashmawy held a Peace Fellowship from USAID.     

HCV infection and its clinical features in recipients of blood screened for HCV (C100-3) antibody

Abstract After adoption of the anti-hepatitis C virus (C100-3) test, the incidences of definite and suspected cases of post-transfusional hepatitis (PTH) were 3.3% (7/209) and 7.2% (15/209), respectively. Four patients with definite PTH and seven patients with suspected PTH became positive for hepatitis C virus (HCV)-related antibodies or HCV-RNA after transfusion. These cases that became positive for anti-HCV or HCV-RNA showed a peak of alanine aminotransferase (ALT) more than 4 weeks after operation. Only rare cases that showed ALT peaks within 4 weeks after operation became positive for HCV-related antibodies or HCV-RNA. The peak ALT levels in cases showing positive conversion tended to be higher than those in cases showing no conversion. Judging from these results, cases of suspected PTH include those of transient liver disease attributable to surgery as well as clear cases of HCV infection. Thus new diagnostic criteria are required including data on HCV antibodies or HCV-RNA.     

Prevalence of non-A non-B hepatitis and anti-HCV antibodies in a Portuguese dialysis population.

Non-A Non-B hepatitis (NANBH) is nowadays one of the most common causes of hepatic dysfunction in dialysis patients. We reviewed the records of 231 HBsAg-negative patients in our unit and found 119 patients with biochemical criteria of NANBH (51.5%), 88 of them (68.9%) with circulating antibodies against HCV (chi 2 P less than 0.0001). Such high prevalence of NANBH was due to an outbreak of NANBH in the late 70s and early 80s. Time on haemodialysis (HD) was the major risk factor of NANBH in this population, and no other risk factors were identified. Prevalence of anti-HCV was similar to reports from non-uraemic populations. Anti-HCV seems to be a reliable test to confirm NANBH, but not better than using common biochemical criteria of NANBH to manage these patients in dialysis units.     

Hepatitis C virus and liver diseases

Hepatitis C virus (HCV) was identified molecularly and a procedure for its diagnosis was developed. In Japan, 70–80% of all cases of chronic liver disease, including hepatocellular carcinoma, are associated with HCV infection. Hepatitis C virus is a typical RNA virus with a high mutation rate. At least six variants of HCV have been identified by their nucleotide sequences. These variants are still classified into three types each containing at least two subtypes; that is, 1a (type I) and 1 b (type II), 2a (type III) and 2b (type IV), and 3a (type V) and 3b (type VI). Type 1 b (type II) is the predominant HCV in Japan. Even HCV cDNA clones isolated from a single patient showed mutations of HCV, especially in envelopecoding regions. Thus HCV may change during the course of chronic hepatitis due to the high mutation rate of HCV itself and elimination of some clones by immune reactions or interferon therapy. These findings explain the higher rate of chronic HCV infection and indicate that production of an effective vaccine is difficult.     

Intrafamilial transmission of hepatitis C virus

Abstract The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease. Thus, the intrafamilial transmission of HCV seems to be quite rare and much less common than that of HBV.     

Emerging roles of interferon-stimulated genes in the innate immune response to hepatitis C virus infection

Infection with hepatitis C virus (HCV), a major viral cause of chronic liver disease, frequently progresses to steatosis and cirrhosis, which can lead to hepatocellular carcinoma. HCV infection strongly induces host responses, such as the activation of the unfolded protein response, autophagy and the innate immune response. Upon HCV infection, the host induces the interferon (IFN)-mediated frontline defense to limit virus replication. Conversely, HCV employs diverse strategies to escape host innate immune surveillance. Type I IFN elicits its antiviral actions by inducing a wide array of IFN-stimulated genes (ISGs). Nevertheless, the mechanisms by which these ISGs participate in IFN-mediated anti-HCV actions remain largely unknown. In this review, we first outline the signaling pathways known to be involved in the production of type I IFN and ISGs and the tactics that HCV uses to subvert innate immunity. Then, we summarize the effector mechanisms of scaffold ISGs known to modulate IFN function in HCV replication. We also highlight the potential functions of emerging ISGs, which were identified from genome-wide siRNA screens, in HCV replication. Finally, we discuss the functions of several cellular determinants critical for regulating host immunity in HCV replication. This review will provide a basis for understanding the complexity and functionality of the pleiotropic IFN system in HCV infection. Elucidation of the specificity and the mode of action of these emerging ISGs will also help to identify novel cellular targets against which effective HCV therapeutics can be developed.     

国产抗HCV EIA试剂漏检原因分析

分析第三代丙型肝炎病毒抗体酶联免疫诊断试剂检测抗体情况，分析国产抗HCV EIA试剂漏检原因。对100批通过国家第三代第二批参考品检定合格的第三代丙型肝炎病毒抗体酶联免疫诊断试剂检定结果进行分析，结合RIBA结果进行综合评价。目前的第三代丙型肝炎病毒抗体酶联免疫诊断试剂在通过国家第三代第二批参考品的基础上仍有漏检，尤以NS3区及核心区抗体弱阳性血清漏检为严重，进口试剂的特异度优于国产试剂。第三代丙型肝炎病毒抗体酶联免疫诊断试剂对NS3区及核心区抗体弱阳性血清检测灵敏度需进一步加强，同时国产试剂应降低非特异性反应。     

ELISA法抗-HCV阳性献血者分片段试剂和RT-PCR法检测结果分析

目的观察无偿献血者标本中ELISA法抗-HCV检测的假阳性问题以及ELISA法对HCV不同抗原片段的反应性。方法留取本站无偿献血者中抗-HCV阳性（两种试剂检测阳性）样本56份和可疑样本（单试剂检测阳性）90份,分别使用抗-HCV分片段试剂和RT-PCR试剂进行检测,对使用分片段抗-HCV试剂检测单片段和两个以上片段（≥2个片段）阳性的样本再进行RT-PCR的确证检测。结果56份抗-HCV阳性的样本中分片段试剂两个片段以上阳性45份（80.4%）,RT-PCR阳性19份（42.2%）;单试剂抗-HCV检测阳性样本90份中分片段抗-HCV双片段以上阳性12份（13.3%）,RT-PCR阳性0份（0%）;单试剂抗-HCV检测阳性样本90份中分片段抗-HCV单片段阳性20份（22.2%）,RT-PCR阳性1份（1.1%）;154份阴性样本分片段抗-HCV试剂单片段阳性3份,RT-PCR检测全部阴性。结论目前采用两种抗-HCV试剂对献血者进行抗-HCV筛选,能够保证血液安全;抗-HCV试剂检测的假阳性率偏高,导致一些献血者的检测结果被误判;单试剂抗-HCV检测存在一定的漏检率,对献血者进行抗-HCV进行检测时应选择恰当的配伍试剂。     

北京地区不同人群HCV感染状况及其基因调查

为了解北京地区不同人群HCV感染状况及其基因型．对来自北京地区不同人群1072份血清分别进行了抗HCVELISA和HCVRNA基因型检测。结果显示．该地区自然人群、急性肝炎、慢性迁延性肝炎、慢性活动性肝炎、肝硬化和肝细胞癌患者中抗-HCV阳性率分别为1．7％、8．3％、12．4％、27．6％、38．1％及20．7％，HCV感染者中有56．4％具有输血、献血及使用血制品史．提示经血传播是该地区HCV的主要感染途径.该地区人群HCV基因型分布以Ⅱ型为主（77．4％）．其次为Ⅲ型（17．8％）．并有少量ⅡⅢ混合型（4．8％）。