Diagnosis of hepatitis C virus (HCV) infection: diagnostic value of the anti-HCV test]

Different groups of patients were analysed for antibody to hepatitis-C-virus (anti-HCV). A high prevalence was found in individuals with parenteral exposure (chronic Non-A, Non-B hepatitis, 77.5%, drug addicts 84.5%), while blood donors had a prevalence of 0.51%, this was significantly higher in patients with chronic type B hepatitis (30%), in homosexuals (22.5%) and in patients with different types of autoimmune hepatitis (57.2%). This indicates that differential diagnosis of chronic hepatitis and indications for alpha interferon therapy is not possible by simply anti-HCV testing. Further studies are required to establish the diagnostic value of the anti-HCV test.     

Antiviral treatment responses in patients with chronic hepatitis C virus infection evaluated by a third generation anti-hepatitis C virus assay

summary . Antibodies to hepatitis C virus (HCV) may decrease or disappear after viral clearance in treated or spontaneously resolved infection. We evaluated the usefulness of serial antibody assays in predicting the antiviral treatment responses. One hundred and four chronic hepatitis C patients who received 24 weeks of interferon and ribavirin combination therapy were assayed with a third generation enzyme immunoassay anti-HCV. The mean titre of anti-HCV decreased by more than 50% (from 89.5 ± 10.8 to 43.6 ± 17.5) at 48 weeks post-treatment in patients with a sustained virological response, while in nonsustained virological responders and nonresponders, the titres remained over 85% of the pretreatment level at 48 weeks post-treatment. There was a divergence of anti-HCV titres between sustained and nonsustained virological responders during 6–9 months. By using the ratio of 9-month to 6-month titres as an index and receiver operator characteristic curve analysis with the cut-off point set at 90%, we could differentiate sustained virological responders from nonsustained virological responders with a sensitivity and specificity of 91.7% and 90.9%, respectively, 3 months after treatment. The titre of this third generation anti-HCV decreased progressively in sustained virological responders and this assay may be used to monitor and predict antiviral treatment responses.     

Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy

BACKGROUND: The goal of the present study was to assess risk factors for perinatal hepatitis C virus (HCV) transmission and the natural history of infection among HCV-infected infants. METHODS: In a cohort study, 244 infants born to HCV-positive mothers were followed from birth until age > or =12 months. Maternal serum was collected at enrollment and delivery; infant serum was collected at birth and at 8 well-child visits. Testing included detection of antibody to HCV, detection of HCV RNA (qualitative and quantitative), and genotyping. HCV-infected infants were followed annually until age 5 years. RESULTS: Overall, 9 of 190 (4.7% [95% confidence interval (CI), 2.3%-9.1%]) infants born to mothers who were HCV RNA positive at delivery became infected, compared with 0 of 54 infants born to HCV RNA-negative mothers (P=.10). Among HCV RNA-positive mothers, the rate of transmission was 3.8% (95% CI, 1.7%-8.1%) from the 182 who were human immunodeficiency virus (HIV) negative, compared with 25.0% (95% CI, 4.5%-64.4%) from the 8 who were HIV positive (P<.05). Three infected infants resolved their infection (i.e., became HCV RNA negative). In multivariate analysis restricted to HCV RNA-positive mothers, membrane rupture > or =6 h (odds ratio [OR], 9.3 [95% CI, 1.5-179.7]) and internal fetal monitoring (OR, 6.7 [95% CI, 1.1-35.9]) were associated with transmission of HCV to infants. CONCLUSION: If duration of membrane rupture and internal fetal monitoring are confirmed to be associated with transmission, interventions may be possible to decrease the risk of transmission.     

Anti-envelope antibodies in anti-hepatitis C virus (HCV) positive patients with and without liver disease

Summary Our aim was to verify whether the presence of antibodies to HCV envelope protein might mark the occurrence of liver damage, as recently suggested in the literature. Sera from 104 patients (62 male, 42 female) were tested: 84 were positive and 20 were negative to a second generation enzyme immunoassay for anti-HCV antibodies; 51 patients had mild chronic liver disease (44 chronic hepatitis, seven steatosis), 43 had liver cirrhosis (superimposed by hepatocellular carcinoma in 18) and ten were asymptomatic anti-HCV positive subjects with normal liver function tests. Besides, all sera were tested by means of an enzyme immunoassay for the presence of serum antibodies to the synthetic peptide S24A (SIYPGHVSGH RMAWDMMMNW SPTA) derived from amino acids 307–330 of HCV polyprotein. Anti-S24A antibodies were detected in 40/84 sera positive and 1/20 negative at anti-HCV testing (Pearsonx ² 12.29; p=0.005). Among anti-HCV positive sera, no significant difference existed in anti-S24A status with regard to clinical evidence of liver disease, ALT concentration or HCV RNA positivity. Thus, anti-S24A antibodies are detectable in approximately half of HCV-positive sera, but they do not seem to add significant clinical information to existing tests or to be useful as putative markers of viraemia.

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Antikörper gegen Hüllprotein bei anti-HCV-positiven Patienten mit und ohne Lebererkrankung

Zusammenfassung Ziel der Stude war es, zu prüfen, ob die Anwesenheit von Antikörpern gegen das HCV-Hüllprotein ein Marker für das Auftreten einer Leberschädigung ist, wie jüngst vorgeschlagen wurde. Sera von 104 Patienten (62 Männer, 42 Frauen) wurden untersucht: in einem Enzymimmunoassay der zweiten Generation waren 84 Patienten positiv und 20 negativ für anti-HCV-Antikörper; 51 Patienten hatten eine leichte chronische Lebererkrankung (44 chronische Hepatitis, 7 Fettleber), 43 eine Leberzirrhose (davon 18 bei hepatozellulärem Karzinom) und 10 waren asymptomatisch anti-HCV-positiv bei normalen Leberfunktionstests. Zusätzlich wurden alle Sera auf Antikörper gegen das synthetische Peptid S24A (SIYPGHVSGH RMAWDMMMNW SPTA), das sich aus der Aminosäuresequenz (307–330) des HCV-Polyproteins ableitet, mit Hilfe eines Enzymimmunoassays getestet. Anti-S24A-Antikörper fanden sich im Serum von 39 der 84 anti-HCV-positiven und in einem der 20 anti-HCV-negativen Patienten (Pearsonx ² 11,71, p<0,001). Bei den anti-HCV-positiven Patienten ergab sich keine signifikante Differenz im anti-S24A-Status in Abhängigkeit von klinischen Anzeichen einer Lebererkrankung, von der ALT-Konzentration oder von der HCV-RNA-Positivität. Somit sind anti-S24A-Antikörper zwar in ungefähr der Hälfte der HCV-positiven Sera nachweisbar, aber sie scheinen weder zusätzliche, signifikante klinische Information gegenüber bekannten Tests zu liefern, noch scheinen sie sich als denkbarer Virämie-Marker zu eignen.

     

The extrahepatic manifestations in hepatitis C virus (HCV) infection

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.     

Prediction of viremia for cases of hepatitis C virus (HCV) infection using a third-generation anti-HCV enzyme immunoassay test

BACKGROUND/AIMS: Positive results for anti-hepatitis C virus (HCV) testing reveal subjects are infected by HCV, with presence of HCV RNA indicating persistent infection. In this study, we attempted to evaluate the validity of the HCV viremia using a commercially available, third-generation anti-HCV test. METHODOLOGY: Sample rate/cut-off rate (S/CO) ratios for 1,907 anti-HCV-positive tests (S/CO >1, AxSYM HCV 3.0; Abbott, IL, USA), which had been performed during the last three years, were retrospectively analyzed. Cases with S/CO values between 1 and 100 were divided into 20 groups according to S/CO range (in increments of 10) and ALT (normal or elevated). Ten random cases were obtained for each of the 20 groups. If cases in any group numbered < or =10, all were recruited. Totally, 193 cases were enrolled for HCV RNA detection (COBAS Amplicor; Roche Diagnostics, NJ, USA). RESULTS: The S/CO distribution was biphasic, with two S/CO peaks in the ranges 1-10 (10.7%) and 81-90 (24.2%). Regardless of the ALT level, all samples with S/COs < or =10 were negative for HCV RNA. Of the samples with S/CO values >10, the optimal cut-off was 40 with sensitivity and specificity for both of 81%. In conclusion, subjects with S/CO values < or =10 (10.7%) were more likely to be cases of past infection or of non-specific reaction. Most (90%, 108/120) of the subjects with S/COs >40 represent current or persistent infection. To predict viremia in subjects with S/COs between 10 and 40, 6.7% of all anti-HCV-positive subjects was invalid by a cross-sectional observation. CONCLUSIONS: Follow-up or further study is recommended. The third-generation EIA test plays a semiquantitative role for the prediction of viremia in HCV infection.     

Prevalence of hepatitis G virus (HGV) infection in an endemic area of hepatitis C virus (HCV) infection

BACKGROUND/AIMS: We investigated the prevalence of hepatitis G virus infection among inhabitants of a hepatitis C virus endemic area. METHODOLOGY: Two hundred and eighty-eight inhabitants, who underwent medical examinations for health screening, were enrolled in this epidemiological study. HGV RNA and HCV RNA were detected by polymerase chain reaction. We also examined anti-HGV envelope protein (E2) antibodies in all serum samples. RESULTS: In these 288 inhabitants, we found anti-HCV antibodies (HCV-Ab) and HCV RNA in 28.5% and 17.4%, respectively. HGV RNA and anti-HGV E2 were detected in 9 (3.1%) and 16 (5.5%), respectively. One patient was positive for both HGV RNA and anti-HGV E2. The exposure rate, expressed as the percentage of people with HGV RNA and/or anti-HGV E2, was 8.3%, which was significantly lower than the incidence of positive HCV-Ab. Of the 24 patients with HGV RNA and/or anti-HGV E2, 15 (62.5%) were positive for HCV-Ab, of those HCV RNA was detected in 9 (37.5%). Further, we found a higher prevalence of HGV exposure in patients with HCV-Ab than in those without (8.3% vs. 4.4%). CONCLUSIONS: HGV infection was not identical to the epidemic hepatitis C virus infection among inhabitants of this town, suggesting that hepatitis C virus might be less infectious than hepatitis C virus.     

慢性丙型肝炎病毒感染者外周血淋巴细胞增殖反应

目的　观察慢性丙型肝炎患者外周血淋巴细胞对丙型肝炎病毒（ＨＣＶ） 抗原刺激的增殖反应．方法　外周血单个核细胞（ＰＢＭＣ） 与ＨＣＶ 抗原ｃ２２ 、ｃ３３ 、ｃ１００ － ３ 、ＮＳ５ 和植物血凝素（ＰＨＡ） 分别共同孵育,加入胸腺嘧啶核苷（３ ＨＴｄＲ） ,然后收集细胞于液闪仪测定每分钟脉冲数（ｃｐｍ） ．结果　根据对不同ＨＣＶ 抗原的淋巴细胞增殖反应发现,以ｃ２２免疫原性最强,ｃ１００ － ３ 次之：淋巴细胞激活与ＨＣＶ 基因型关系不大;健康对照和慢性乙型肝炎患者对各ＨＣＶ 抗原未能显示有效的淋巴细胞增殖反应;与健康对照比较,慢性丙型肝炎和乙型肝炎患者对ＰＨＡ 刺激的淋巴细胞增殖反应降低．结论　ＨＣＶ 抗原ｃ２２ 免疫原性最强,丙型肝炎患者对ＨＣＶ 抗原的淋巴细胞增殖反应系特异性;慢性丙型肝炎和乙型肝炎患者存在抑制的细胞免疫应答．     

Hepatitis C virus infection in renal failure patients in the absence of anti-hepatitis C virus antibodies

The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti-HCV and HCV-RNA. In addition, HCV genotype and HCV viral load were determined in HCV-RNA-positive sera. Anti-HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV-RNA-positive. Among the 267 HCV-seronegative dialysis patients, 25 (9%) were found to be HCV-RNA-positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV-seropositives. In contrast, in the Liver Clinic patients, HCV-RNA was found exclusively in HCV-seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference.   Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.     

Management and treatment of injection drug users with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus coinfection

Injection drug use is the major mode of hepatitis C virus (HCV) transmission in developed countries. Despite this, relatively few current and recovering injection drug users (IDUs) have received HCV treatment. Studies among individuals with a recent history of injection drug use or those receiving drug dependency treatment have provided evidence that these groups can be successfully treated for chronic HCV infection. These studies have provided the impetus to change guidelines for treatment of current and recovering IDUs, with a move toward individualized HCV treatment assessment and the removal of defined periods of illicit drug use abstinence. Strategies to improve access to HCV treatment for current and recovering IDUs include drug dependency treatment education and training for hepatologists and other HCV treatment physicians, HCV treatment education and training for addiction medicine physicians, development of multidisciplinary clinics, and peer-based eduction and support for individuals considering and receiving HCV treatment.     

Acute hepatitis C virus (HCV) infection in chronic carriers of hepatitis B virus (HBV): the impact of underlying active HBV replication on persistence of HCV infection and antibody responses to HCV

BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.     

Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence

This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.     

Clinical significance of hepatitis C virus (HCV) infection in liver transplant recipients

Hepatitis C virus (HCV) infection was studied in 60 liver transplant recipients. Antibodies to HCV were tested by both a second-generation ELISA test and a four-recombinant immunoblot assay (4-RIBA) just before the transplant and every three months thereafter. HCV RNA detection was performed by polymerase chain reaction (PCR) at least three times after the transplant in all the patients. Thirty-nine patients tested negative by ELISA before LT (group A), 14 patients tested positive by both serological tests (group B), and seven tested positive only by ELISA (group C). Posttransplant hepatitis was diagnosed in 11/14 in group B in comparison with 3/39 in group A (P<0.001) and 1/7 in group C (P<0.05). HCV RNA was detected in the sera of 14/14 patients in group B but in only 1/7 in group C and 6/39 in group A. Only 2/15 patients developed posttransplant hepatitis in the absence of HCV RNA detection. These data suggest that HCV is the major cause of hepatitis after LT. Patients HCV seropositive by RIBA test before the transplant formed a group of high-risk patients for developing viremia and hepatitis afterwards.Part of this work was presented at the XIVth International Congress of the Transplantation Society. Paris. August 1992.This work was supported by a grant from Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS 92/0357).     

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics during HCV treatment in HCV/HIV coinfection

We studied hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics in 10 coinfected subjects in a trial of pegylated interferon-alpha2a (PEG-IFN) alone or combined with ribavirin (RBV), compared with IFN plus RBV for the treatment of HCV. Five subjects, 4 of whom were treated with PEG-IFN, achieved a sustained virological response, although it was delayed by >/=1 week in 3 subjects. The median treatment efficacy in blocking virion production was 99.7% in the PEG-IFN group and 60% with standard IFN. In 2 patients with detectable HIV loads before starting HCV study drugs, we observed a 1-log decrease in HIV RNA load. The estimated HCV virion half-life was longer in the HIV-coinfected subjects, which suggests that coinfection may contribute to a slower clearance of HCV. Although the early viral kinetics of coinfected subjects treated with PEG-IFN or IFN differ from those of singly infected subjects, the treatment response seems unaffected.     

Progress in the development of a detection test for parenteral non-A, non-B hepatitis--results of enzyme immunoassay for anti-hepatitis C virus]

After more than one decennium of international research work the doubtless identification of the causative agents of the non A-non B-hepatitis (NANBH) has not yet been successful. 1988, however, a viral genome of the parenteral NANBH could be isolated, on which basis an EIA was built up. By means of this anti-HCV-ELISA altogether 413 sera were tested. In 262 sera of 154 women of a NANBH-group with homogeneous source of infection (contaminated anti-D-immunoglobulin) in 74% positive reactions were the result. This and the extensive reproducibility of the test results in identical patients speak for the fact that the recombinant antigen underlying the test really belongs to the parenteral NANBH-group. In the group of the sporadic, however, only in one case a positive reaction was achieved, which supports the thesis of at least two parenteral causative agents of NANBH. The deep-freezing storage of patients' sera lasting up to 8 years did not lead to the failure of the test. The reasons for non-reactive tests were discussed.