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[Clinical evaluation of RT-PCR method for detection of HCV-RNA--with special reference to Amplicor HCV].

Detection of the viral genome in serum is the most reliable way to analyze HCV viremia. In the present study, we evaluated the availability of a new detection kit for HCV-RNA, Amplicor HCV, which is based on the RT-PCR microplate hybridization protocol. The procedure of Amplicor HCV is simple, unlike the conventional RT-nested-PCR method. Although Amplicor HCV assay exhibited the lower sensitivity than the the conventional RT-nested-PCR method (10 x for HCV type 1a, 1b and 2b; 10(3) x for type 2a), Amplicor HCV assay could detect the HCV-RNA in all HCV-RNA positive cases by conventional RT-nested PCR method, except for one case who contained low concentration of HCV-RNA (10 copies/ml). The coincidence rate was 99.2% in 120 clinical samples between two assays. Amplicor HCV assay, moreover, could efficiently evaluate the viremia regardless of anti-HCV-2 antibody titer. This assay was useful for monitoring the effect of interferon therapy during and after administration. These results suggest that Amplicor HCV has an excellent availability for the clinical laboratories.

Hepacivirus↗

Molecular epidemiology of an outbreak of HCV in a hemodialysis unit: direct sequencing of HCV-HVR1 as an appropriate tool for phylogenetic analysis.

Infection with hepatitis C virus (HCV) is still a serious problem in hemodialysis patients, despite screening of blood products for anti-HCV antibodies. The prevalence of HCV in HD patients is between 15% and 30% in Germany. We report the molecular epidemiology of an HCV outbreak in a hemodialysis unit in 1997 is determined. HCV hypervariable region 1 (HVR1) was amplified from serum samples of 19 patients by polymerase chain reaction (PCR) and sequenced directly. In addition, HCV isolates from 3 of these 19 patients were cloned and sequenced. 14 newly infected patients and two patients, who had been infected for several years had very closely related HCV isolates. Unrelated HCV isolates as well as sequences obtained from an HCV outbreak in a plasmapheresis center were found in different, distantly related branches. These findings provide strong evidence for nosocomial transmission of the virus, despite following strict general hygiene precautions. The production of anti-HCV antibody was delayed significantly or seroconversion did not occur at all during the period of observation in 8 out of 14 newly infected HCV RNA positive patients. Close-meshed reverse transcription-polymerase chain reaction (RT-PCR) analyses on apparently non infected patients within hemodialysis units and upon admission of new patients is strongly recommended for the early detection and prevention of outbreaks of HCV.

Adult↗

Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women.

The prevalence and natural course of chronic hepatitis C virus (HCV) infection was evaluated in 15,250 consecutive pregnant women. The rate of HCV vertical and perinatal transmission was also assessed. The presence of anti-HCV was tested by means of EIA III and confirmed by recombinant immunoblot assay III. Alanine transaminase (ALT), anti-human immunodeficiency virus (HIV), and HCV-RNA were tested during the first month and third trimester of pregnancy, and 6 months after delivery; the same tests were made in all of the newborns of anti-HCV-positive mothers at birth (on cord blood samples) and then at 4-month intervals. Anti-HCV positivity was found in 370 cases (2.4%), 72% of whom were also HCV-RNA-positive. The proportion of women with hypertransaminases decreased from 56.4% at the first examination during the first month of pregnancy to 7.4% in the last trimester, and then increased again after delivery (54. 5%), without any concomitant changes in the proportion of those with viremia. The proportion of anti-HCV- and HCV-RNA-positive newborns was 5.1% after 1 year (8 of 155), all of whom had the same genotype as their mother. The rate of HCV transmission was not affected by the type of delivery or feeding, or the HIV status of the mother. The results of this large-scale study confirm previous data in smaller series concerning the prevalence of HCV infection in pregnant women, and strongly support the hypothesis of a favorable (possibly immunomediated) effect of pregnancy on liver cell necrosis in anti-HCV-positive women.

Adult↗

Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes.

Ribozymes are catalytic RNA molecules that can be designed to cleave specific RNA sequences. To investigate the potential use of synthetic stabilized ribozymes for the treatment of chronic hepatitis C virus (HCV) infection, we designed and synthesized hammerhead ribozymes targeting 15 conserved sites in the 5' untranslated region (UTR) of HCV RNA. This region forms an internal ribosome entry site that allows for efficient translation of the HCV polyprotein. The 15 synthetic ribozymes contained modified nucleotides and linkages that stabilize the molecules against nuclease degradation. All 15 ribozymes were tested for their ability to reduce expression in an HCV 5' UTR/luciferase reporter system and for their ability to inhibit replication of an HCV-poliovirus (HCV-PV) chimera. Treatment with several ribozymes resulted in significant down-regulation of HCV 5' UTR/luciferase reporter expression (range 40% to 80% inhibition, P <.05). Moreover, several ribozymes showed significant inhibition (>90%, P <.001) of chimeric HCV-PV replication. We further show that the inhibitory activity of ribozymes targeting site 195 of HCV RNA exhibits a sequence-specific dose response, requires an active catalytic ribozyme core, and is dependent on the presence of the HCV 5' UTR. Treatment with synthetic stabilized anti-HCV ribozymes has the potential to aid patients who are infected with HCV by reducing the viral burden through specific targeting and cleavage of the viral genome.

Antiviral Agents↗

Evaluation of hepatitis C antibody testing in saliva specimens collected by two different systems in comparison with HCV antibody and HCV RNA in serum.

Two different ELISA assays, the Ortho HCV 3.0 ELISA (Ortho Diagnostics Systems) and the Mono-Lisa anti-HCV Plus (Sanofi Diagnostics Pasteur) were evaluated for the detection of hepatitis C virus (HCV) antibody in saliva samples. Specimens were collected from 152 individuals who participated in a longitudinal cohort study on HIV infection, and who used illicit drugs. Saliva specimens were collected using two different systems: Salivette (Sarstedt) and Omni-Sal (Saliva Diagnostic Systems). Saliva specimens were tested following modified protocols by both ELISAs, and the results were compared with serum specimens that were tested according to the instructions of the manufacturer. Serum samples of 102 (67%) participants were positive by both assays, and 50 persons were negative for HCV antibody. A total of 99 of the 102 serum specimens were confirmed as positive using Ortho Riba HCV 3.0 (Ortho Diagnostics System) and Deciscan HCV (Sanofi Diagnostics Pasteur), and 3 yielded discrepant results. As no cut-off level is known for testing saliva samples by ELISA, 3 different levels were chosen: mean (M) + 1 standard deviation (SD), M + 2 SD, and M + 3 SD of the optical densities of saliva tests of the 50 HCV serum antibody negative persons. At a level of M + 1 SD and M + 2 SD the Salivette/Mono-Lisa combination gave the greatest proportion of HCV antibody positive saliva specimens obtained from the 102 HCV serum antibody positive participants, 88% and 79%, respectively. Differences between the various collection systems and assay combinations were not significant statistically. In 76 of the 102 persons with HCV antibodies in serum, HCV RNA was detected in serum. Salivary presence of HCV RNA, however, could not be demonstrated. The results show that the assays compared are unsuitable for diagnostic use, but the sensitivities of the assays are acceptable for use in epidemiological studies.

Adult↗

Direct detection of hepatitis C virus (HCV) RNA from whole blood, and comparison with HCV RNA in plasma and peripheral blood mononuclear cells.

Hepatitis C virus (HCV) requires reverse transcriptase-polymerase chain reaction (RT-PCR) or branched DNA signal amplification assays to be detected in patient samples. Although conventional methods of RNA isolation are employed for samples of serum, plasma, and peripheral blood mononuclear cells (PBMCs), whole blood is generally considered an unsuitable source of RNA because of abundant RNases and polymerase inhibitors. Using a cationic surfactant, Catrimox-14, we adapted a procedure for RNA isolation from whole blood, plasma, and PBMCs that yields RNA template suitable for HCV RT-PCR. RNA isolation required less than 2 hr, and HCV sequences were easily detected in sample volumes of 50 microliters whole blood or plasma, and in less than 1 x 10(4) PBMC. Following the addition of blood to Catrimox, HCV RNA was stable in the mixture when incubated for at least 7 days at room temperature prior to RNA extraction. Comparison of whole blood HCV RNA and plasma HCV RNA from individuals with chronic hepatitis suggests that HDV RNA can be more reliably detected in whole blood. Three of 15 HCV antibody positive patients (20%) had HCV RNA present in whole blood but simultaneously obtained plasma samples were negative. Two of the HCV antibody negative individuals with chronic hepatitis contained HCV RNA in whole blood, yet one of these patient's plasma was negative for viral RNA. The Catrimox-14 method of RNA purification is useful for detecting HCV RNA in whole blood and blood subfractions, and provides a practical method of measuring plasma and PBMC HCV RNA from clinical specimens.

Base Sequence↗

Evaluation of a total hepatitis C virus (HCV) core antigen assay for the detection of antigenaemia in anti-HCV positive individuals.

A new, sensitive enzyme immunoassay has been developed for detecting and quantifying total hepatitis C virus (HCV) core antigen in anti-HCV positive or negative sera ("trak-C", Ortho Clinical Diagnostics, Raritan, NJ). The purpose of this study was to evaluate the performance of trak-C as an additional laboratory diagnostic marker of viraemia. The performance was compared to HCV-RNA detection in the "screening" of sera from a large heterogeneous population of hospitalised patients and outpatients. Six hundred and eighteen anti-HCV negative sera, 405 anti-HCV positive/HCV-RNA negative sera, 604 anti-HCV positive/HCV-RNA positive sera and 67 anti-HCV negative sera containing antigens or antibodies potentially interfering with the performance of the assay were analysed. Supplemental HCV antibody testing was performed using a commercial strip immunoblot assay. HCV-RNA was investigated using a qualitative commercial assay. A quantitative commercial RT-PCR was used for the analysis of selected samples. Sensitivity and specificity values were 94.7 and 100%, respectively. The latter was also confirmed when anti-HCV negative samples containing potentially interfering antigens/antibodies were examined. Sensitivity below 100% was probably due to an antigenaemia below the detection limit of trak-C. Besides, because 65.6% of HCV-RNA positive/trak-C negative samples presented specific antibodies against all four RIBA antigens, the hypothesis was raised that, in some cases, the dissociation step efficiency could be sub-optimal. In conclusion, trak-C seems suitable for identifying HCV infection on large based populations. It is a rapid to perform, reliable and specific assay that can be adapted to any laboratory setting.

Enzyme-Linked Immunosorbent Assay↗

Influence of the dynamics of the hypervariable region 1 of hepatitis C virus (HCV) on the histological severity of HCV recurrence after liver transplantation.

Recurrence of hepatitis C virus (HCV) infection after liver transplantation is almost universal and usually leads to chronic hepatitis with different degrees of severity. The pathogenic mechanisms underlying the variable outcome of HCV infection recurrence are not well defined, but recent data suggest that the dynamics of HCV quasispecies may be involved. HCV quasispecies evolution was traced by longitudinal single strand conformation polymorphism, direct sequencing, and cloning analyses of pre- and post-transplant HCV-1b isolates from patients with histologically severe (seven cases) or mild or moderate (nine cases) HCV infection recurrence. Differences between the two groups of patients that concerned the level of viremia or the degree of HCV quasispecies complexity and diversity were not observed at any of the three time points analyzed. However, emergence of nucleotide and amino acid changes during the 12 months follow-up was significantly more frequent in patients with mild or moderate than in those with severe HCV infection recurrence. The ratio of non-synonymous to synonymous nucleotide substitutions 12 months after transplantation was also greater in the former, suggesting that the HVR1 of HCV is under stronger selective pressure in these subjects. These findings suggest that the degree of amino acid diversification in the HVR1 of HCV, which probably reflects the strength of immune pressure on HCV, is inversely related to the histological severity of HCV infection recurrence.

Amino Acid Sequence↗

Prevalence of HCV coinfection in HIV-infected individuals in Nigeria and characterization of HCV genotypes.

BACKGROUND: Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury, hepatic decompensation, and decreased survival time than that seen in an HIV-monoinfected population. While prevalence studies on HIV/HCV coinfection have been performed in the U.S. and in some European countries, little is known about coinfection rates in Africa. DESIGN: Retrospectively collected specimens from 146 confirmed HIV-positive individuals in Nigeria who had access to antiretroviral therapy (ART) were tested for HCV RNA, using the VERSANT HCV RNA qualitative assay (TMA), and, if HCV RNA-positive, for HCV genotype using the VERSANT HCV genotype assay (LiPA). RESULTS: Twelve out of the 146 individuals tested (8.2%) were HCV positive. Nine of the 12 HCV-positive individuals were infected with HCV genotype 1 (five 1a, three 1b, one non-subtypable) and three were infected with HCV genotype 2 (all non-subtypable). Coinfected individuals were more likely to be male, older, and have lower CD4+ cell counts than HIV-monoinfected individuals, although none of the differences reached statistical significance. CONCLUSION: The results highlight the potential public health impact of HCV infection in Nigeria, where anti-HCV testing is generally not performed in HIV-infected populations or in most blood transfusion centers.

Adult↗

Application of the trak-C HCV core assay for monitoring antiviral activity in HCV replication systems.

The Ortho trak-C immunoassay has recently established detection of the HCV core antigen as a viable indirect marker of HCV replication in clinical samples. In this study, trak-C is used to monitor HCV replication in three pre-clinical models: the cellular HCV replicon system, transient transfection of HCV genomes, and the murine Alb-uPa/SCID HCV infection model. All of these systems utilize full-length HCV genomes that direct the expression of core, facilitating its detection with monoclonal antibodies. When performed with purified protein, the assay detects HCV core with a lower limit of detection at 1.5pg, and exhibits linear detection up to 100pg. When assaying extracts prepared from Huh-7 clone 21-5 cells harboring a full-length HCV replicon, core is detectable from as few as 63 cell equivalents. The assay was used to determine the sensitivity of Huh 21-5 cells to the antiviral effects of interferon (IFN). Inhibition by IFN-alpha using core detection was comparable to that observed using branched-DNA (bDNA 3.0) detection of HCV RNA. Replication of transfected full-length HCV 1a Con1 genomes in Huh-7 cells was also detectable using the trak-C assay. Finally, in the transgenic murine HCV infection model, the course of viral amplification was detected from serum using trak-C with kinetics similar to those observed with RNA detection. Given its ease of use and the lack of requirement for RNA purification, the trak-C assay has several advantages over RNA-based methods of viral monitoring.

Animals↗

Usefulness of HCV-RNA assays in efficacy evaluation of interferon treatment for chronic hepatitis C: Amplicor HCV assay and branched DNA probe assay.

We investigated the usefulness of Amplicor HCV assay and branched DNA probe assay in efficacy evaluation of interferon therapies for chronic hepatitis C. Subjects were 164 HCV-RNA positive chronic hepatitis C patients who received interferon-alpha (IFN-alpha, HLBI) 3-6 MU per day for 14-24 weeks. Their HCV-RNA levels were examined five times by using reverse transcription-polymerase chain reaction (RT-PCR) assay, Amplicor HCV assay, and branched DNA probe assay. Complete response rate in the low virus level patients was significantly higher than in the high virus level patients (P < 0.001). In complete responders, the rate of HCV-RNA disappearance 2 weeks after the initiation of IFN therapy was higher than in non-responders (P < 0.001). The HCV-RNA positive rates in RT-PCR assay and Amplicor HCV assay agreed by 98% or more. The HCV-RNA negative patients 6 months later were still negative 12 months later by Amplicor HCV assay. Before starting interferon therapy for chronic hepatitis C, it is advisable to make a prediction of treatment efficacy by using branched DNA probe assay. In addition, disappearance of HCV-RNA after 2 weeks of treatment could be a useful predictor of the therapeutic efficacy of IFN. Amplicor HCV assay is useful in detecting HCV-RNA and for efficacy evaluation during and after a given interferon therapy.

Adult↗

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.

Adult↗

Diagnosis of acute hepatitis C: anti-HCV or HCV-RNA?

BACKGROUND: In theory, the optimal method for diagnosing acute hepatitis C is nucleotide amplification. This is because of the significant delay in the emergence of hepatitis C virus (HCV) antibodies. We studied whether the use of HCV polymerase chain reaction (PCR) screening for acute HCV infection in a clinical setting would identify otherwise undetected cases. METHODS: Patients clinically suspected of having acute viral hepatitis were tested over a 32-month period (n = 2023). RESULTS: Sixty-four patients were found HCV ribonucleic acid (RNA) positive. Of these, 13 were suffering from an acute infection and 12 of these 13 patients were concomitantly anti-HCV (and HCV-RNA) positive at the time of diagnosis. One patient was HCV-RNA positive and anti-HCV negative. This symptom-free patient was tested because of known exposure to HCV 2 weeks previously. CONCLUSION: Anti-HCV is reliable in screening for acute hepatitis C. In cases of known/possible HCV exposure, we find that HCV PCR is the diagnostic of choice.

Acute Disease↗

The hepatitis C virus (HCV)-Trimera mouse: a model for evaluation of agents against HCV.

The lack of small-animal models that are suitable for evaluation of agents used to treat infection with hepatitis C virus (HCV) severely hinders the assessment of potential new therapies for the disease. This study created such a model, termed the "HCV-Trimera" model. The HCV-Trimera model was developed by using lethally irradiated mice, reconstituted with SCID mouse bone marrow cells, in which human liver fragments infected ex vivo with HCV had been transplanted. Viremia (positive-strand HCV RNA levels) in HCV-Trimera mice peaked at approximately day 18 after liver transplantation, and an infection rate of 85% was reached. Viral replication in liver grafts was evidenced by the presence of specific negative-strand HCV RNA. The usefulness of this model for evaluation of anti-HCV agents was demonstrated by the ability of a small molecule (an HCV internal ribosomal entry site inhibitor) and an anti-HCV human monoclonal antibody (HCV AB(XTL)68) to reduce virus loads in HCV-Trimera mice in a dose-dependent manner.

Animals↗

Liver injury and changes in hepatitis C Virus (HCV) RNA load associated with protease inhibitor-based antiretroviral therapy for treatment-naive HCV-HIV-coinfected patients: lopinavir-ritonavir versus nelfinavir.

BACKGROUND: Highly active antiretroviral therapy (HAART) initiation in patients coinfected with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) has been associated with transaminase and HCV viral load flares. Previous studies have included highly variable antiretroviral regimens. We compared effects of 2 protease inhibitor-based regimens on alanine aminotransferase (ALT) levels and HCV loads in HCV-HIV-coinfected patients initiating HAART. METHODS: Seventy HIV-infected patients with positive baseline results of HCV enzyme-linked immunosorbant assay from a treatment trial comparing lopinavir-ritonavir with nelfinavir were evaluated during a 48-week period. HCV and HIV titers were analyzed at baseline, at weeks 24 and 48 of treatment, and during flares in the ALT level of >5 times the upper limit of normal. RESULTS: A total of 57 of 70 patients tested positive for HCV RNA at baseline. HCV titers for patients in lopinavir-ritonavir and nelfinavir groups, respectively, were as follows: baseline, 6.07 and 6.22 log IU/mL; week 24 of treatment, 6.68 and 6.48 log IU/mL; and week 48 of treatment, 6.32 and 6.44 log IU/mL. Of patients with a CD4+ cell count of <100 cells/mm3 at baseline, 5 of 11 in the nelfinavir group and 0 of 10 in the lopinavir-ritonavir group had an increase in the HCV load of >0.5 log IU/mL from baseline to week 48. The mean ALT level increased by 45 U/L at 24 weeks and 18 U/L at 48 weeks in the nelfinavir group but decreased by 18 U/L at 24 weeks and 7 U/L at 48 weeks in the lopinavir-ritonavir group. Eight patients in the nelfinavir group and 2 patients in the lopinavir-ritonavir group had grade 3 or 4 flares in the ALT level. CONCLUSIONS: HAART initiation is associated with increased HCV loads and ALT levels. A low baseline CD4+ cell count is associated with persistent increases in the HCV RNA load in nelfinavir-treated patients. These results warrant careful interpretation of abnormalities in the ALT load after HAART initiation in HCV-HIV-coinfected patients to prevent premature discontinuation of treatment.

Adult↗

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.

Adult↗

Increased transmission of vertical hepatitis C virus (HCV) infection to human immunodeficiency virus (HIV)-infected infants of HIV- and HCV-coinfected women.

The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers.

Causality↗

Long-term follow-up study of serum IgM antibody to hepatitis C virus (HCV), HCV replication, and liver disease outcome in chronic hepatitis C.

IgM anti-hepatitis C virus (HCV) and HCV RNA were longitudinally tested for 4.0-8.7 years in 40 patients with chronic HCV infection. Patients in disease remission usually lost IgM anti-HCV and HCV RNA, but most patients experiencing disease reactivation had increased levels of the IgM antibody or it reappeared before the biochemical relapse, even when HCV RNA was undetectable. IgM anti-HCV was detectable in most patients with ongoing viral replication and persistent liver disease. Despite long-term disease remission, IgM anti-HCV may persist and be detectable with or without evidence of serum HCV RNA; this indicates a possible disease reactivation, which could occur after several years of sustained transaminase normalization. Detection of IgM anti-HCV in chronic hepatitis C indicates an active immune response to persistent viral infection and should, therefore, be considered as a sensitive marker of active HCV replication and HCV-associated liver disease.

Adult↗