Serological and histological aspects of hepatitis C virus infection in alcoholic patients

The recent cloning of the genome of hepatitis C virus (HCV) has allowed the detection of antibodies to HCV (anti-HCV) in human serum. The presence of serum antibodies to HCV often indicates active infection with HCV. We have assessed the serological and histological features in a group of alcoholic patients with chronic liver disease and have evaluated the possible etiologic role of HCV infection in the development of liver damage. Serum samples and liver biopsy specimens were obtained from 41 consecutive patients, all having a definite history of alcohol abuse and evidence of chronic hypertransaminasemia. Fifteen patients (37%) were positive for anti-HCV by ELISA, and 13 (86.6%) of them were also positive by RIBA. Eleven of these patients had histologic features of chronic active hepatitis (CAH), a lesion which is not known to be induced by excessive alcohol intake. No other possible causes of CAH were found, and CAH was not present in any of the anti-HCV negative patients. In patients with CAH, mean AST to ALT ratio was less than 1 (0.6), a finding which is characteristic of viral rather than alcoholic chronic liver disease. In conclusion, our study suggests that sporadic hepatitis C virus infection plays an etiologic role in the development of chronic active liver disease in a subgroup of alcoholic patients.     

Serological and molecular characterization of hepatitis B virus infection in chronic kidney disease patients from Rio de Janeiro,Brazil

Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) are more vulnerable to blood-borne viral infections due to frequent invasive procedures. Hepatitis B virus (HBV) infection in this cohort of patients has been a matter of concern worldwide. The objective of this cross-sectional study was to evaluate the frequency of serological markers for hepatitis B, and the occurrence of overt and occult HBV infection (OBI) and its molecular characterization in serum samples from 644 CKD patients in HD units located in Rio de Janeiro, Brazil, from 2013 to 2017. HBV DNA was investigated in HBsAg reactive and “anti-HBc alone” samples to determine infecting genotypes and genetic relatedness between sequences. The prevalence of serological markers HBsAg+, anti-HBc alone, anti-HBc+/anti-HBs+, anti-HBs+, anti-HBc/anti-HBs/HBsAg were 5.9%, 2.8%, 30.7%, 26.6%, 34.0%, respectively. HBV DNA was detected in 39.5% (15/38) of the HBsAg+ and in 5/18 (27.8%) of the “anti-HBc alone” individuals, indicating a high prevalence of OBI within this group. We found a higher prevalence of HBV/A1 (65%), followed by HBV/D3 (20%), and HBV/A2 (15%). Bayesian MCC tree with a highly supported clade, genetic distance comparison, and identical nucleotide sequences suggested a nosocomial spread of HBV in some units. The high prevalence of HBV infection and low number of individuals immune to infection reinforces the need for vaccination in this group. The presence of closely related strains in the same HD unit reinforces the importance of continuous improvement of safety control measures and laboratory surveillance of serological markers to prevent the risk of infection and transmission of HBV.     

Acute hepatitis C virus infection, 1986-2001: a rare cause of fulminant hepatitis in Chiba, Japan

BACKGROUND/AIMS: Hepatitis C virus (HCV) is the most common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It is controversial whether HCV causes fulminant hepatitis. METHODOLOGY: To determine the clinical features and etiology of acute hepatitis and fulminant hepatitis in Japan, an endemic area of hepatitis C, between 1986 and 2001 inclusively, a retrospective study of consecutively referred patients was performed. Two hundred and sixty-three patients admitted to a liver clinic after diagnosis of acute hepatitis or fulminant hepatitis, were evaluated. RESULTS: We found 181 cases of acute hepatitis and 82 cases of fulminant hepatitis/late onset hepatic failure. No cases of fulminant hepatitis were positive for HCV RNA. Only three cases had positive anti-HCV antibody, and they were thought to indicate past HCV infection. The main cause of infection in these three patients was hepatitis A virus in one,hepatitis B virus in one, and drugs in the remaining one. HCV did not seem to be the major cause. The three cases died without receiving liver transplantation. CONCLUSIONS: It was revealed that fulminant hepatitis C rarely occurs in Japan, as well as in the USA and European countries. Investigators should search for other causes in fulminant cases presenting an HCV marker.     

Epidemiological aspects of hepatitis C virus infection among HIV-infected individuals in Mato Grosso State, Central Brazil

The present study has been carried out to estimate the prevalence of HCV among HIV-positive individuals in the state of Mato Grosso, Central Brazil, as well as to identify the associated epidemiological factors. One thousand and eight individuals over 18 years of age bearing HIV/aids and being attended in the reference public health network of the state of Mato Grosso participated in this research. HIV-positive subjects were interviewed and blood samples were taken to be tested for anti-HCV antibodies by enzyme immunoassay (EIA). The anti-HCV antibodies were investigated in all the individuals by immunoenzymatic assay. The reactive samples in duplicate were submitted to a polymerase chain reaction (PCR) to detect HCV-RNA. The positive tests were submitted for genotyping by the LIA method. One hundred and ten (10.9%; CI 95%: 9.1-13.0) HIV-positive individuals presented anti-HCV by EIA. The PCR was positive in 60 (6.0%; CI 95%: 4.6-7.6) individuals. The 1a genotype was the most frequent, followed by the 3a and 1b. The genotype 2 was found in only one individual. There were more male and intravenous drug users among HIV-HCV coinfected individuals when compared to only HIV-infected individuals. Multivariate analysis revealed an association between the HIV-HCV coinfection, regarding either EIA or PCR results, and the use of intravenous drugs, the presence of tattoos, and having received blood transfusions before 1994. There was no association of the coinfection with the variables related to sexual transmission. The relatively low prevalence of HCV infection in the HIV-positive population in that region may be a consequence of a small number of intravenous drug users in the sample, despite a strong association between HCV infection and use of intravenous drugs.     

Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation

Hepatitis B virus, hepatitis C virus and human immunodeficiency virus share a similar transmission pathway and are often diagnosed in the same patient. These patients tend to have a faster progression of hepatic fibrosis. This cross-sectional study describes the demographic features and clinical profile of human immunodeficiency virus/hepatitis co-infected patients in Paraná, Southern Brazil. A total of 93 human immunodeficiency virus-infected patients attending a tertiary care academic hospital in Southern Brazil were included. Clinical, demographic and epidemiological data were evaluated. Hepatitis B virus and/or hepatitis C virus positive serology was found in 6.6% of patients. The anti-hepatitis C virus serum test was positive in 85% (79/93) of patients, and the infection was confirmed in 72% of the cases. Eighteen patients (19%) were human immunodeficiency virus/hepatitis B virus positive (detectable HBsAg). Among co-infected patients, there was a high frequency of drug use, and investigations for the detection of co-infection were conducted late. A low number of patients were eligible for treatment and, although the response to antiretroviral therapy was good, there was a very poor response to hepatitis therapy. Our preliminary findings indicate the need for protocols aimed at systematic investigation of hepatitis B virus and hepatitis C virus in human immunodeficiency virus-infected patients, thus allowing for early detection and treatment of co-infected patients.     

Incident hepatitis C virus infection in a community-based population in Japan

Hepatitis C virus (HCV) is an important cause of liver disease throughout the world. However, the natural history and pathogenesis of this infection is still not completely understood. The aim of this study was to characterize the evolution of incident, asymptomatic HCV infection in a community-based population in Japan. The Miyazaki Cohort Study is a prospective study of adult residents in two villages, one of which has a very high prevalence of HCV. Nine hundred and seventy-three people from this village were enrolled in the cohort between 1984 and 1995, with antibodies to HCV (anti-HCV) found in 23%. During subsequent visits to annual health screens, new HCV seroconverters were identified among susceptible individuals, and their sequential samples were tested for anti-HCV, HCV-RNA, and HCV core antigen. Fourteen participants (six males, eight females) acquired anti-HCV during the first 11 years of study follow-up, at an incidence rate of 362 per 100 000 person-years. Detectable HCV-RNA and high anti-HCV titres (> 1:2048) were observed for more than 5 years following seroconversion in 80% (8/10) of seroconverters with sufficient information, indicating the development of persistent infection in these subjects. Three (37.5%) of the eight sero converters with persistent infection had fairly consistent, albeit mild, alanine aminotransferase elevations (30–130 IU/L) during the study. Anti-HCV seroconversions occurred at a very high rate in this community-based population in Japan, in which this infection is endemic. Persistence also developed at a high frequency among the cases of newly acquired infection, although the associated liver enzyme abnormalities were mild.     

特殊人群丙型肝炎病毒感染特征分析

目的 了解近年来就诊我院各科患者丙型肝炎病毒（HCV）的感染情况,以及抗-HCV阳性者一般临床特征。方法对2007年1月至12月我院门诊、急诊、病房等就诊患者抗-HCV检测的结果和阳性分布状况进行分析。同时,对2006年1月至2007年12月的全部抗-HCV阳性者分析其临床及病毒学特征。结果在2007年22146例无重复检测人群中,498人（2．25％）抗-HCV阳性。其中,手术前筛查人群的阳性率为0．72％,感染科和肾脏疾病相关科室阳性率分别为8．80％和7．43％。0～20岁组及21～40岁组中男性的阳性率显著高于女性。此外,抗-HCV阳性人群中近30％伴抗-HBc阳性,14％伴HBsAg阳性。HCV1b型是最主要的基因型（60．98％）,其次是2a（19．51％）和3a型（9．76％）。结论近年来因非肝功能异常而就诊我院的患者HCV感染率处于较低水平,现阶段通过输血传播HCV的概率已较低,可能存在其他感染途径。     

Serological response to infection with different isolates of hepatitis C virus

Different isolates of hepatitis C virus (HCV) show nucleotide sequence variability throughout the genome. Detection of antibodies to recombinant proteins derived from hepatitis C virus genotype 1, the prototype HCV clone HCV-PT, constitutes the main method for screening HCV infection. The influence of the genomic variability on the serological diagnosis of HCV by enzyme immunoassay remains poorly defined. The aim of this study was to assess the serological reactivity of a panel of well characterized French HCV isolates typed by sequence analysis from patients with chronic hepatitis. The 73 sera samples were tested in three third generation EIA tests and three confirmatory assays. HCV isolates were determined by RT-PCR and sequencing in NS5B region of the genome. The 73 sera were positive in the three EIA tests. The three confirmatory tests showed a weaker reactivity with NS5 protein whatever the genotype, and a lower reactivity in NS4 antigens of non-type 1 sequences, particularly for genotype 3. Even though the reactivity of the antigens differed among the HCV isolates, the 73 isolates from genotype 1-6 were reactive with the three commercial screening assays. These results demonstrate that using a single test is adequate in the routine diagnosis of HCV infection in clinical laboratory, as recommended by the last French and European consensus conference.     

Serological response and detection of viraemia in acute hepatitis C virus infection.

The serological response during acute hepatitis C virus (HCV) infection was examined by enzyme-linked immunosorbent assay (ELISA) in sequential serum samples from 13 haemophiliacs following their first exposure to factor VIII concentrates contaminated with HCV. The commercially available C100-3 peptide and a new 22 kDa recombinant protein (p22) encoded by the nucleocapsid region of the viral genome were used for antibody detection, whilst a nested polymerase chain reaction (PCR) method was used for the detection of viraemia. In addition, eight sporadic cases of acute HCV infection were studied. The results in haemophiliacs demonstrated that seroconversion to the C100-3 antigen occurred in only one-third of the patients within 12 weeks of disease onset, but all of the patients had a diagnostic serological response to p22 during this phase of the disease. The new test was positive in all the sporadic cases at a time when the commercially available test was negative. Although PCR offers a sensitive method for the detection of recent HCV infection, the complex methodology makes it unsuitable for diagnostic laboratories. The new ELISA test with p22 may therefore have a useful diagnostic role in acute disease.     

齐齐哈尔市某高校人群血清乙型肝炎病毒流行病学调查*

目的了解齐齐哈尔市某高校各类人群乙型肝炎病毒血清流行病学感染状况。方法在2000名学生、200名教师、100名教辅人员、100名后勤人员和100名机关人员取血清,采用ELISA法检测HBsAg、抗-HBs、HBeAg、抗-HBe和抗-HBc。结果在2500人中,检出HBV标记物阳性232人（9.3%）;后勤人员血清HBsAg携带率为13%,显著高于其他各类人群 （x²=32.6, P<0.05）;其他各类人群血清HBsAg阳性率在7.0%~9.5%之间,无显著性差别（P>0.05）;所有被检测人员血清抗-HBs阳性率为50.3%,各组之间无明显统计学差别（x²=5.62,P>0.05）。结论高校各类人群乙型肝炎血清学指标检出率因群体不同而不同,需加强乙型肝炎防治教育,加强疫苗接种和卫生保健意识教育。     

Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects

Abstract: The epidemological and clinical features of hepatitis C virus infection have been evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence treatment center in the Veneto area in 1992–1993 and followed periodically. Hepatitis C virus infection was detected using second-generation anti-HCV ELISA in 171 (75%) subjects at enrollment. Anti-HCV seropositivity correlated with: a) the duration of drug abuse: 91% of intravenous drug users injecting for more than 8 years were seropositive as compared to 40% of those with a history of abuse lasting 4 years or less, p<0.001; b) sharing of injection equipment: 85% anti-HCV positive intravenous drug users had shared at some time as compared to 64% seronegative subjects, p<0.001; c) seropositivity for immunodeficiency virus infection: 25% anti-HCV positive intravenous drug users were coinfected as compared to 3.5% anti-HCV negative, p<0.001; d) markers of ongoing (two cases) or previous hepatitis B virus infection were detected in 62% of anti-HCV positive but in 21% of anti-HCV negative cases, p<0.01. Two initially anti-HCV negative intravenous drug users seroconverted during follow up giving an incidence rate of hepatitis C virus infection of 6.2 per 100 person-years. During the survey abnormal alanine aminotransferase levels were detected in 75% anti-HCV positive but in 24% anti-HCV negative cases (p<0.001), with significantly higher levels in the former. These findings suggest that the circulation of hepatitis C virus among intravenous drug users has been decreasing in recent years, although new infections still occur. In agreement with the high rate of chronicization of parenterally transmitted hepatitis C, the majority of anti-HCV positive subjects had biochemical features of associated liver disease.     

Transmission, natural history, and treatment of hepatitis C virus infection in the pediatric population

Compared with the adult population, hepatitis C virus infection may differ in the pediatric age group with respect to transmission, course, and response to treatment. The prevalence of hepatitis C in children is between 0.05% and 0.4%. The major mode of acquisition has shifted from parenteral transmission to maternal-infant transmission. However, the actual rate of maternal-infant transmission is low. The natural history of hepatitis C in children is not well characterized, although the available information suggests a milder disease than in adults. In the eight studies of treatment with interferon for hepatitis C in children, the incidence of a complete sustained response varied from 0 to 45%. No pediatric studies have evaluated quality of life or the effect of treatment on the development of cirrhosis and hepatocellular carcinoma. Children may respond better to treatment than adults. We recommend that children with hepatitis C are considered for treatment only as part of a controlled clinical trial.     

北京市吸毒人群丙型肝炎病毒感染的流行病学监测

目的探讨吸毒人群丙型肝炎病毒(HCV)感染的流行率,并分析HCV感染的可能危险因素。方法 2006-2009年于在押吸毒人群中,采用标准化问卷收集人口学、危险行为等信息,采用酶联免疫吸附试验(ELISA)检测HCV抗体。结果 1 253名吸毒者中,总的HCV抗体阳性率为25.3%,注射吸毒者HCV抗体阳性率为66.6%。多因素Logistic回归分析提示,注射吸毒(调整OR=18.988,95%CI:13.860～26.013)为吸毒人群感染HCV的最主要危险因素;其次是共用注射器(调整OR=1.025,95%CI:0.604～1.739)。注射吸毒时间≥5年者感染HCV的危险性较<5年者高(调整OR=0.669,95%CI:0.084～1.089);没有职业的吸毒者感染HCV的危险性较有职业者高(调整OR=1.280,95%CI:0.866～1.893)。结论吸毒人群HCV流行水平较高,注射吸毒是流行的最主要原因。应采取有效措施预防该人群HCV的二代传播,为阳性患者提供治疗刻不容缓。     

Outcomes and treatment of acute hepatitis C virus infection in a United States population.

BACKGROUND & AIMS: Acute hepatitis C infection progresses to chronic infection in up to 80% of infected persons. Reports from Europe indicate that early treatment of acute hepatitis C infection produces sustained virologic response rates as high as 80%-98%. However, the outcome of acute hepatitis C infection in United States cohorts is not well-characterized. METHODS: We describe the clinical course of 28 episodes of acute hepatitis C infection in 24 persons at our institution. RESULTS: Of the 28 infections, 7 episodes resolved spontaneously. Of the remaining 21 episodes, 16 were treated, and 5 did not receive treatment. Of the 16 treated episodes, 4 received interferon and ribavirin, 11 received pegylated interferon and ribavirin, and 1 was treated initially with interferon monotherapy followed by pegylated interferon monotherapy. Among those episodes treated with interferon, 3 of 4 experienced sustained virologic response. Among those episodes treated with pegylated interferon, all 12 achieved SVR. In total, 15 of 16 treated patients (94%) experienced SVR. In all, 18 of the 24 patients (75%) experienced spontaneous or treatment-induced sustained virologic clearance. CONCLUSIONS: Our experience with treated and untreated acute HCV infection is comparable to that observed in Europe. Patients treated with antiviral therapy had an excellent response. Randomized trials to investigate immediate versus delayed treatment of acute hepatitis C infection are warranted. In view of these strongly positive outcomes, increased vigilance for acute hepatitis C becomes essential.     

Two years' prospective collection of molecular and epidemiological data shows limited spread of hepatitis A virus outside risk groups in Amsterdam, 2000-2002

We performed a viral sequencing study on samples representing all reported primary cases of acute hepatitis A virus (HAV) infection reported for 2 years in Amsterdam. Two regions of HAV RNA were amplified, sequenced, and used for phylogenetic analysis. Of 156 cases, strains of 104 isolates (66.6%) clustered into 3 genotypes: 1A, 1B, and 3. Two separate transmission circles occurred, without mutual interrelation. In genotype 1A, 4 clusters occurred in men having sex with men (MSM), and the fifth cluster was related to a virus from Morocco. In genotype 1B, 6 small clusters were directly related to the Moroccan virus. In genotype 3, strains were related to a virus from Pakistan. Our analysis indicates that, to stop transmission of HAV in Amsterdam, the entire MSM population and travelers to countries where HAV is endemic, especially children, should be vaccinated. Prevention strategies need not include the vaccination of all children living in Amsterdam.     

Prevalence of hepatitis C virus infection among thalassemia patients: a perspective from a multi-ethnic population of Pakistan

ObjectiveTo evaluate current situation regarding the prevalence of hepatitis C virus (HCV) in thalassemic patients visiting a thalassemia centre in Rawalpindi District, Pakistan for supportive therapy.MethodsSerum samples were screened for hepatitis B surface antigen and anti-HCV by using commercially available ELISA kit. Micro-plate reader was used to perform analysis based on the absorbance/cut-off ratios. Samples were considered positive or negative. Results from ELISA were analyzed statistically.ResultsA total of 95 subjects were observed to have β-thalassemia major (96%) and β-thalassemia intermedia (4%). Among these, 47 (49%) were detected positive for anti-HCV antibodies and three for hepatitis B surface antigen. All recruited subjects were observed for therapy/medication behavior and clinical complications. About 83 (87%) patients were on chelation therapy, and overall complications (hepatomegaly, splenomegaly and splenectomy) were observed in 81% individuals. The distribution of disease status (thalassemia and hepatitis) was not significantly associated with gender, age, origin, province, socio-economic status and parental marriage type (P>0.05). The distributions of ferritin levels, therapy/medication and complications were assessed across demographic variables. Thalassemic subjects were distributed with respect to their sporadic and familial presentations. Among the familial cases (n=35), a total of 93 subjects were found to be affected. Parity was scored for the index cases, and majority belonged to second parity (29%), followed by first and third parities (25% and 15%, respectively). The sibship size was increasing with increasing parity level.ConclusionsAlthough standardized blood screening procedures are supposed to be implemented, higher prevalence of HCV in thalassemic patients requires greater attention in Pakistan. Furthermore, a poor compliance regarding iron chelation therapy has been observed in this study.