Clinical and epidemiologic characteristics of hepatitis C in a gastroenterology/hepatology practice in Ottawa.

OBJECTIVE: To examine the clinical and epidemiologic features of hepatitis C virus (HCV) infection in a gastroenterology/hepatology practice in Ottawa. DESIGN: Retrospective chart review. PATIENTS: Sixty-three consecutive patients found to be anti-HCV positive. Their charts were analysed with respect to risk factors, history of hepatitis, serum aspartate aminotransferase (AST) levels and the presence of hepatitis B markers. The long-term sexual partners of 29 patients agreed to undergo HCV antibody testing. RESULTS: Of the patients 48 (76%) had been exposed to HCV parenterally: 27 used intravenous drugs, and 21 had received blood or blood products. Eleven patients did not have any known risk factor (sporadic infection), but eight of them had lived in countries where hepatitis C may be more prevalent; the other three had locally acquired infection. The mean serum AST level at the first visit was 140 (normally less than 40) IU/L. At least one hepatitis B marker was identified in 33% of the patients. None of the sexual partners who were tested were anti-HCV positive. CONCLUSION: Most cases of hepatitis C in Ottawa are acquired through parenteral exposure; sexual transmission is rare. Sporadic infection in the Ottawa region is rare but may be more common in people from countries with a higher prevalence rate of hepatitis C. Most cases of hepatitis C are asymptomatic.     

乙型肝炎病人重叠感染丙型肝炎的评价

应用ＥＬＩＳＡ和ＰＣＲ法检测５０２例乙肝病人血清,４０１例ＨＢｓＡｇ阳性血清中,有１１４例（２８．４％）抗－ＨＣＶ和ＨＣＶＲＮＡ双项阳性,２５例（６．２％）ＨＣＶＲＮＡ单项阳性;２１例（５．２％）抗－ＨＣＶ单项阳性。将ＨＢｓＡｇ乙肝病人分成ＨＢＶＤＮＡ,ＨＢｅＡｇ阳性组和ＨＢＶＤＮＡ,ＨＢｅＡｇ阴性组。前者抗－ＨＣＶ阳性率为１１．６％～２０．５％,ＨＣＶＲＮＡ阳性率为１６．２％～２０．５％。后者抗－ＨＣＶ阳性率为２０．２％～５５．６％,ＨＣＶＲＮＡ阳性率为２３％～６０．３％。结果说明长期携带ＨＢＶ者和慢性乙肝病人均可重叠ＨＣＶ感染。ＨＢＶＤＮＡ阳性组抗－ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于ＨＢＶＤＮＡ阳性组     

Evaluation of an enzyme immunoassay for hepatitis C virus antibody detection using a recombinant protein derived from the core region of hepatitis C virus genome

This study was undertaken to evaluate an enzyme immunoassay (EIA) for hepatitis C virus antibody detection (anti-HCV), using just one antigen. Anti-HCV EIA was designed to detect anti-HCV IgG using on the solid-phase a recombinant C22 antigen localized at the N-terminal end of the core region of HCV genome, produced by BioMérieux. The serum samples diluted in phosphate buffer saline were added to wells coated with the C22, and incubated. After washings, the wells were loaded with conjugated anti-IgG, and read in a microtiter plate reader (492 nm). Serum samples of 145 patients were divided in two groups: a control group of 39 patients with non-C hepatitis (10 acute hepatitis A, 10 acute hepatitis B, 9 chronic hepatitis B, and 10 autoimmune hepatitis) and a study group consisting of 106 patients with chronic HCV hepatitis. In the study group all patients had anti-HCV detected by a commercially available EIA (Abbott), specific for HCV structural and nonstructural polypeptides, alanine aminotransferase elevation or positive serum HCV-RNA detected by nested-PCR. They also had a liver biopsy compatible with chronic hepatitis. The test was positive in 101 of the 106 (95%) sera from patients in the study group and negative in 38 of the 39 (97%) sera from those in the control group, showing an accuracy of 96%. According to these results, our EIA could be used to detect anti-HCV in the serum of patients infected with hepatitis C virus.     

HCV-RNA和抗-HCV的联合检测在丙型肝炎确诊中的临床意义

目的:探讨抗-HCV和HCV-RNA的联合检测在丙型肝炎确诊中的临床意义。方法:采用ELISA法检测抗-HCV及实时荧光定量PCR检测HCV-RNA。结果:在急性丙型肝炎组中抗-HCV和HCV-RNA同时阳性所占百分率(29.8%)显著低于慢性丙型肝炎患者(62.3%)(P<0.05);抗-HCV阴性和HCV-RNA阳性在急性丙型肝炎组所占百分率(58.3%)显著高于慢性丙型肝炎患者(24.6%)(P<0.05);经相关性分析,ALT含量与HCV-RNA含量呈正相关性(r=0.725,P<0.05)。结论:临床抗-HCV和HCV-RNA的联合检测有助于丙型肝炎的早期明确诊断。     

Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil

In order to investigate the hepatitis C virus (HCV) infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7) was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.     

Evidence for hepatitis C viral infection in patients with primary hepatocellular carcinoma.

In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.     

Mizoribine inhibits hepatitis C virus RNA replication: effect of combination with interferon-alpha

Interferon (IFN)-alpha monotherapy, as well as the more effective combination therapy of IFN-alpha and ribavirin, are currently used for patients with chronic hepatitis C caused by hepatitis C virus (HCV) infection, although the mechanisms of the antiviral effects of these reagents on HCV remain ambiguous, and side effects such as anemia due to the administration of ribavirin present a problem for patients who are advanced in years. Using a recently developed reporter assay system in which genome-length dicistronic HCV RNA encoding Renilla luciferase gene was found to replicate efficiently, we found that mizoribine, an imidazole nucleoside, inhibited HCV RNA replication. The anti-HCV activity of mizoribine (IC50: approximately 100 microM) was similar to that of ribavirin. Using this genome-length HCV RNA replication monitor system, we were the first to demonstrate that the combination of IFN-alpha and ribavirin exhibited more effective anti-HCV activity than the use of IFN-alpha alone. Moreover, we found that the anti-HCV activity of mizoribine in co-treatment with IFN-alpha was at least equivalent to that of ribavirin. This effect was apparent in the presence of at least 5 microM mizoribine. Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, mizoribine is considered to be of potential use as a new anti-HCV reagent in combination with IFN-alpha.     

Novel evolved immunoglobulin (Ig)-binding molecules enhance the detection of IgM against hepatitis C virus

Detection of specific antibodies against hepatitis C virus (HCV) is the most widely available test for viral diagnosis and monitoring of HCV infections. However, narrowing the serologic window of anti-HCV detection by enhancing anti-HCV IgM detection has remained to be a problem. Herein, we used LD5, a novel evolved immunoglobulin-binding molecule (NEIBM) with a high affinity for IgM, to develop a new anti-HCV enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase-labeled LD5 (HRP-LD5) as the conjugated enzyme complex. The HRP-LD5 assay showed detection efficacy that is comparable with two kinds of domestic diagnostic kits and the Abbott 3.0 kit when tested against the national reference panel. Moreover, the HRP-LD5 assay showed a higher detection rate (55.9%, 95% confidence intervals (95% CI) 0.489, 0.629) than that of a domestic diagnostic ELISA kit (Chang Zheng) (53.3%, 95% CI 0.463, 0.603) in 195 hemodialysis patient serum samples. Five serum samples that were positive using the HRP-LD5 assay and negative with the conventional anti-HCV diagnostic ELISA kits were all positive for HCV RNA, and 4 of them had detectable antibodies when tested with the established anti-HCV IgM assay. An IgM confirmation study revealed the IgM reaction nature of these five serum samples. These results demonstrate that HRP-LD5 improved anti-HCV detection by enhancing the detection of anti-HCV IgM, which may have potential value for the early diagnosis and screening of hepatitis C and other infectious diseases.     

Seroepidemiology of hepatitis C virus in Beijing, China

To investigate the seroprevalence of hepatitis C virus (HCV) in China we tested sera from healthy individuals without hepatitis and no history of parenteral blood exposure and from patients admitted to a hepatitis hospital in Beijing. Sera were tested for anti-HCV by first-generation enzyme immunoassay; selected positives were tested with two second-generation EIAs, one utilizing recombinant antigens and the other synthetic peptides. We found anti-HCV with the following frequencies: 10 of 164 (6%) individuals with no disease; 2 of 36 (5.5%) patients with acute non-A non-B hepatitis (NANBH); 26 of 39 (67%) patients with post-transfusion NANBH; 10 of 34 (29%) patients with chronic hepatitis negative for hepatitis B surface antigen (HBsAg); 3 of 30 (10%) patients with chronic HBsAg-positive hepatitis; 0 of 19 patients with acute HBsAg-positive hepatitis. Of 24 repeat-positive sera, 19 were positive by both and 4 by one second-generation tests. We conclude that hepatitis C infection is common in China, that it contributes substantially to the incidence of post-transfusion hepatitis, and that HCV plays a significant role in both acute and chronic hepatitis. Further studies are needed to extend these observations and to define the predominant routes of transmission of HCV in China.     

Hepatitis C virus and Epstein-Barr virus: dual infection or atypical antibody response

Positive serological reactions against hepatitis C virus (HCV) appeared in the course of Epstein-Barr virus (EBV) infectious mononucleosis. In 429 consecutive patients with high levels of transaminases, 28 patients with EBV primary infection were found. The presence of anti-HCV antibodies and HCV RNA was studied in these subjects. In seven patients anti-HCV antibodies (C33 and C22c RIBA bands) were detected, but all were polymerase chain reaction (PCR) negative. These results may have been due solely to a HCV infection or were an atypical response to HCV in the course of infectious mononucleosis.     

Synthesis and inhibitory activity on hepatitis C virus RNA replication of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analogs

Using our recently developed assay system for full-genome-length hepatitis C virus (HCV) RNA replication in human hepatoma-derived Li23 cells (ORL8), we identified 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)aniline analog 1a as a novel HCV inhibitor. Structural modifications of 1a provided a series of sulfonamides 7 with much more potent HCV RNA replication-inhibitory activity than ribavirin. Compound 7a showed an additive anti-HCV effect in combination with standard anti-HCV therapy (IFN-α plus ribavirin). Since 7a generated reactive oxygen species (ROS) in the ORL8 system and its anti-HCV activity was blocked by vitamin E, its anti-HCV activity may be mediated at least in part by ROS.     

Frequency of occurrence of Hepatitis C virus markers and risk factors among hospital personnel in the Novosibirsk region

The occurrence of markers, the genotypic variety of isolates and the profile of risk factors with respect to viral hepatitis C among 629 employees of the Regional Clinical Hospital (RCH) in Novosibirsk and 1,020 employees of the Central District Hospital (CDH) in Iskitim were studied in a cross-sectional investigation. The occurrence of hepatitis C virus (HCV) markers was 5.1% in RCH and 2.2% in CDH. Among the risk factors in the population under study were: the medical history of blood transfusions (TF) with 0 TF, anti-HCV = 2.3%; 1 TF, = 5.7% > 1 TF, = 13.5% (p < 0.001); general anesthesia (GA) with < or = 2 GA, anti-HCV = 2.8%; > 2 GA, = 7.8% (p = 0.002); surgical interventions (SU) with 0 SU, = 1.9%; > 0 SU, = 4.3% (p = 0.012); the intravenous use of drugs (OR = 31.8); age (< or = 25 years, anti-HCV IgG = 8.6% > 25 years, = 4.5%); the number of partners of the opposite sex < or = 4 partners, = 2.4%; > 4 partners, = 6.9%; p < 0.001). The probable risk factors at a working place (pricks and cuts, contamination of mucous membranes with blood and other biological fluids, etc.) proved to be faintly related with the status of HBV infection. HBV isolates detected in the examined persons (35 examinees) were distributed by genotypes as follows: 60% of subtype 1b, 28.6% of subtype 2a/2c, 11.4% of subtype 3a. HBV of genotype 1a was not detected in the examined specimens, while the detection rate of genotype 2a/2c was considerably greater than in specimens obtained in the European and Asian parts of Russia (according to the data reported earlier).     

Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors

To investigate whether exposure to atomic bomb radiation altered the prevalence of hepatitis C virus (HCV) infection or accelerated the progress toward chronic hepatitis after HCV infection, the seropositivity of antibody to hepatitis C virus (anti-HCV) was determined for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. The seropositivity of anti-HCV antibody was 2.5 times higher among those with a history of blood transfusion and 1.2 times higher among those with a family history of liver disease, whereas acupuncture showed no association with anti-HCV. Although the prevalence of anti-HCV was lower for survivors with positive dose estimates than for those with 0 dose (relative prevalence 0.84, P = 0.022), there was no evidence of a smooth dose-response relationship. However, these data suggested that the radiation dose response for chronic liver disease among HCV antibody-positive survivors may be greater than that among HCV antibody-negative survivors (slope ratio 20). In conclusion, no dose-response relationship was found between anti-HCV positivity and radiation dose; a possible increase in the radiation dose response of chronic liver disease among anti-HCV-positive individuals was found. Thus radiation exposure may accelerate the progress of chronic liver disease associated with hepatitis C virus infection.     

Hepatitis C virus-RNA, immunoglobulin M anti-HCV and risk factors in haemodialysis patients

In order to evaluate hepatitis C virus-RNA (HCV-RNA), immunoglobulin M (IgM) anti-HCV and risk factors in haemodialysis patients, 180 subjects (45 HCV negative and 135 HCV positive) were studied. Sex, age, duration of dialysis, number of transfusions and ALT were also considered. HCV-RNA was determined by the Amplicor HCV test, and IgM anti-HCV by the Abbott HCV IgM EIA. These markers were present in 40% and 30.4% of anti-HCV positive subjects. The agreement between the two tests employed was 77%. The results showed a close association between HCV-RNA and IgM anti-HCV with abnormal ALT levels and between HCV-RNA and the number of transfusions. Both of these markers were different when correlated with age and time on dialysis, respectively. Therefore, IgM anti-HCV may also serve as a serological marker of HCV infection and a complementary marker of virus replication.     

福州地区庚型肝炎病毒重叠感染

为研究庚型肝炎病毒在福州地区的重叠感染,采用ＥＬＩＳＡ法检测本院住院的２８６例病毒性肝炎（ＨＶ）患者和５００名供血员的抗－ＨＧＶ。结果表明,甲、乙、丙、戊型肝炎患者和供血员的抗－ＨＧＶ检出率分别为２．０％、２．２％、４．０％、１０．０％和０．２％。急性肝炎、慢性肝炎、慢性重型肝炎、肝硬化、原发性肝癌和抗－ＨＣＶ阳性供血员的检出率分别为７．９％、４．３％、３３．３％、０％、７．１％和６．３％,慢性重型肝炎检出率较慢性肝炎显著升高（Ｐ＜０．０５）。各型肝炎患者和供血员均存在庚型肝炎病毒重叠感染,以慢性重型肝炎为著。     

Determining immunoassay cutoff value using Western blot results to predict hepatitis C infection in blood donors with low-titer anti-HCV reactivity

Since the 1990s, blood donors have been scanned for anti-hepatitis C virus (anti-HCV) antibodies, which can be defined by enzyme immunoassay as a screening test. In this population, false-reactive ratios have been high. Recently, some authors have aimed to find a cutoff value for anti-HCV different from those established by test manufacturers to predict HCV infection. In this study, 321 patients, after two repeating tests, had reactive results in s/co <10 titers on anti-HCV test. The patients were 29.6 % (n?=?95) in women and 70.4 % (n?=?226) in men. The patients were classified into three groups by Western blot (WB) results (PS, positive; NG, negative; and ID, indeterminate). The average anti-HCV titer of the whole group was 2.61?±?1.96. Anti-HCV titers of subgroups were 2.43?±?1.95 in NG, 4.93?±?2.53 in PS, and 2.50?±?1.65 in ID (p?<?0.001). There was a significant difference between NG and PS and between PS and ID subgroups (p?<?0.001). There was a positive correlation between WB and anti-HCV titers in all patients (r?=?0.298, p?<?0.001), in women (r?=?0.282, p?<?0.001), and in men (r?=?0.337, p?=?0.002). According to receiver operator characteristic curve analysis, the cutoff value of anti-HCV titer to predict hepatitis C infection was >2.61 s/co, with 74.1 % sensitivity and 71.6 % specificity (area under the curve, 0.820; 95 % confidence interval, 0.753 to 0.887). We suggest that an effective cutoff value for anti-HCV other than that established by the manufacturer cannot be assigned to predict hepatitis C infection for blood donors in low-prevalence areas.     

Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men.

OBJECTIVE--To determine the prevalence, incidence, and persistence of positivity for antibodies to hepatitis C virus (anti-HCV) and the potential for sexual transmission of the virus. DESIGN--A cohort analysis covering 1981-9 comparing estimated cumulative incidences of and seroconversion rates for anti-HCV with those of hepatitis B core antibody (anti-HBc) and antibodies to the human immunodeficiency virus (anti-HIV). SETTING--Copenhagen and Aarhus, Denmark. SUBJECTS--259 Male members of a Danish homosexual organisation. MAIN OUTCOME MEASURES--Correlations of prevalence and incidence with a wide range of sexual lifestyle variables. RESULTS--Only four (1.6%) subjects were positive for anti-HCV in 1981. The estimated cumulative incidence of positivity for anti-HCV was 4.1% in 1984 (seroconversion rate during 1981-4 (2.5%)) and remained at 4.1% in 1989 (seroconversion rate nil during 1984-9). In contrast, positivity for anti-HBC rose from 44.0% in 1981 to 52.7% in 1984 (seroconversion rate 15.5%) and 58.8% in 1989 (seroconversion rate 12.9%), and that for anti-HIV rose from 8.8% to 24.0% (seroconversion rate 16.7%) and 30.1% (seroconversion rate 8.0%) respectively. Three anti-HCV positive patients seroreverted three to five years later. None of the anti-HCV positive subjects had had a transfusion and only one gave a past history of intravenous drug use. Variables in sexual lifestyle correlated with the presence of anti-HBc but not with that of anti-HCV. CONCLUSIONS--In contrast with hepatitis B virus and HIV, sexual transmission of hepatitis C virus seems to be a rare event. Furthermore, antibodies to the virus may become undetectable after several years.     

Anti-hepatitic C virus antibodies hidden in circulating antibody/antigen aggregates in HCV-RNA positive patients

The aim of this study was to determine whether antibodies to HCV can be hidden in immunocomplex aggregates in anti-hepatitis C virus (HCV) negative, HCV-RNA positive patients and whether their presence could be related to HCV viral load or HCV genotype. Sera (23 in toto) from patients with elevated alanine aminotransferase (ALT) levels and negative for anti-HCV but positive for HCV-RNA and the immunocomplex aggregates (precipitate with PEG 6000 and glycine 1 M) were studied. The sera were treated using a rapid, simple new ELISA which disrupted the immunocomplex aggregates. Sera from ten patients were tested anti-HCV positive after immunocomplex disruption. No correlation with age, sex, ALT level, viral load or HCV genotype was observed. In some patients anti-HCV antibodies were hidden in circulating antibody/antigen complexes which could be dissociated with a simple, inexpensive and rapid protocol; therefore it can provide a valuable addition to the diagnosis of HCV infection and it may prevent some cases of post-transfusion hepatitis.