Hepatitis C Virus Infection In Individuals Research Articles

Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems

Background and objectivesAccurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems (“cobas HCV”) by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. MethodsThe limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test version 2.0 (“CAP/CTM HCV v2”) were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, “SVR12”). ResultsThe cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2–8.0 log10 IU/mL) for GT 1–6, with high accuracy (≤0.16 log10 difference) and precision (standard deviation 0.04–0.14 log10) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R2 = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log10 with a 95% CI: 0.03–0.06 log10). For the diagnosis of chronic HCV, positive and negative percent agreement between cobas HCV and the comparator NAAT were 98.8–100% on the cobas 6800 and 8800 systems. Clinical specificity of cobas HCV using samples from HCV antibody negative subjects with non-HCV related liver diseases was 99.6% and 100% on cobas 6800 and 8800 systems. In therapeutic monitoring and SVR12 prediction during experimental treatment for chronic HCV GT 1 infections, undetectable HCV RNA by cobas HCV at different on-treatment weeks had a PPV 76.8%–79.4%, NPV 29.9%–100%, and OR 1.64–47.52. During therapy of HCV GT 2 and GT 3, treatment week 4 and 12 results were: PPV, 84.7% and 75.3%; NPV, 47.8% and 50.0%; OR, 5.09 and 3.05. ConclusionsThe cobas HCV test is highly sensitive, specific, and accurate HCV RNA test for GT 1–6. It demonstrates excellent correlation with the FDA-approved CAP/CTM HCV v2 test. It is useful clinically for detection of active HCV infection in individuals that have had a positive anti-HCV antibody test result and in monitoring treatment response.

Hepatitis C virus infection in vulnerable populations: a seroprevalence study of homeless, people who inject drugs and prisoners in London, UK

BackgroundInjecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in homeless people and prisoners. Capturing accurate data on disease prevalence within these groups is challenging, and this problem hinders efforts to develop targeted strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these vulnerable populations. MethodsWe conducted a cross-sectional study between May 1, 2011, and June 30, 2013, in London, UK. Using the National Health Service Find and Treat service, we recruited participants from 39 hostels for the homeless, 20 drug treatment services, and a prison. Inclusion criteria were age over 18 years, capacity to consent, and being identified as homeless (living in a homeless hotel), having a history of drug use (using services at drug treatment centres), or being a prisoner at the time of the study. A questionnaire was administered and blood samples were collected to be tested for HCV. FindingsWe recruited 1207 individuals, of whom 491 were homeless (40·7%), 205 were drug users (17·0%), and 511 were prisoners (42·3%). 98 (8·1%) of the 1207 participants had active HCV infection and 38 (3·1%) had a previous HCV infection. Among HCV-positive individuals, 77 (56·6%) had a history all three risk factors (homelessness, imprisonment, and drug use), 37 (27·3%) had two risk factors, and 22 (15·4%) had one risk factor. Multivariate logistic regression identified three factors associated with increased risk of HCV infection: duration of injecting (odds ratio for <1 year 12·62, 95% CI 6·22–25·57; 2–9 years 50·04, 24·80–100·95; and ≥10 years 67·34, 32·29–140·46), age more than 30 years (3·00, 1·33–6·76), and UK-born non-white (0·38, 0·15–0·99). Separate multivariate analysis showed that alcohol problems (2·92, 1·24–6·89), age 30–49 years (8·29, 1·06–64·73), and age more than 50 (13·85, 1·67–114·85) increased the risk of HCV infection in individuals who were not injecting drugs. InterpretationHomeless services, drug treatment services, and prisons provide good opportunities for identifying HCV-positive individuals. More than half of HCV-infected individuals had the three intersecting risk factors, highlighting the vulnerability of these patients. Reducing the burden of HCV among these vulnerable groups is fundamental to lessen HCV transmission. FundingNational Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (reference number RP-PG-0407-10340). RWA is funded by a Wellcome Trust research training fellowship (097980/Z/11/Z). DNA is funded by an Indonesia Presidential Scholarship.

Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically HIV-infected individuals.

Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1. We selected individuals that had the last negative and first positive HCV RNA test less than 1 year apart. Bivariate linear mixed-effects regression was used to model trends in HIV RNA level and CD4 cell count from 2 years before the last negative HCV RNA test until the first of the following dates: start of anti-HCV medication, change in combination antiretroviral therapy (cART) status, and end of follow-up. At the estimated time of HCV co-infection, of 89 individuals, 63 (71%) were cART-treated and 26 (29%) were not on cART. In persons on cART, median CD4 cell count declined from 587 to 508 cells per cubic millimeter (P < 0.0001) during the first 5 months after HCV infection and returned to 587 cells per cubic millimeter after 2.2 years. Also, the probability of an HIV RNA >50 copies per milliliter peaked to 18.6% at HCV co-infection, with lower probabilities 6 months before (3.5%, P = 0.006 compared with peak probability) and after (2.9%, P = 0.009). In persons not on cART, no significant impact of HCV co-infection on trends in the HIV RNA level or CD4 cell count was observed. Acute HCV infection in cART-treated, chronically HIV-infected patients was associated with a temporary decrease in CD4 cell counts and increased risk of HIV viremia >50 copies per milliliter. This may increase the risk of further HIV transmission.

Association of cytotoxic T-lymphocyte antigen 4 genetic polymorphism, hepatitis C viral infection and B-cell non-Hodgkin lymphoma: an Egyptian study

Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36–2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and − 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24–6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01–15.98 for − 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and − 318 C/T promoter polymorphisms with HCV infection.

Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies

It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection.

Induction Versus Noninduction Antiviral Therapy for Chronic Hepatitis C Virus in Patients with Congenital Coagulation Disorders: A Canadian Multicentre Trial

Patients with congenital coagulation disorders and chronic hepatitis C virus (HCV) infection have multiple risk factors (ie, infection predominantly with genotype-1 HCV, long duration of the disease, HIV coinfection and male sex) for poor response to antiviral therapy. The present study compared induction therapy with interferon-alpha (IFN-alpha)-2b with standard IFN-alpha2b therapy. Pegylated IFN was not available at the time that the study was initiated. A randomized study was performed comparing the efficacy of traditional IFN-alpha2b therapy (group A -- three million units, three times weekly for 24 to 48 weeks) and daily ribavirin (1.0 g to 1.2 g according to weight for 24 to 48 weeks), with induction IFN-alpha2b therapy (group B -- three million units, daily for eight weeks followed by the same dose administered three times a week for a further 16 to 40 weeks) and daily ribavirin (same dose as above) in IFN-naive patients with congenital coagulation disorders and chronic HCV infection. Between 2000 and 2003, 54 HIV-negative patients were recruited and randomly assigned to group A or B (n=27 each). Both groups were comparable in terms of age, sex, ethnicity, body mass index, baseline HCV RNA titre, viral genotype, liver fibrosis stage and type of coagulation disorder. Induction therapy did not significantly alter sustained virological response rates (group A 50%, group B 50%; P=1.0). Multiple logistic regression analysis indicated that induction therapy did not benefit individuals with difficult-to-treat infection (ie, those infected with genotypes 1 and 4, or those with high baseline viral loads). There was no benefit with induction antiviral therapy for HCV infection in individuals with congenital coagulation disorders.

Utility of hepatitis C virus RNA determinations in hepatic tissue as an end point for interferon treatment of chronic hepatitis C

A total of 41 patients with chronic hepatitis C virus (HCV) defined as abnormal liver injury test results for 6 months or more and HCV RNA positivity in plasma were studied to determine if the liver might not be the only focus of HCV infection in individuals treated with interferon alfa (IFN-α). All patients were examined for the presence of confounding liver disease and tested negatively for such findings. All tested positively for HCV RNA and had an abnormal hepatic histology. All were treated with IFN for 6 months at a dosage of 5 million units daily. After 6 months of therapy, 29 (71%) had normal alanine transaminase (ALT) values, and 25 (61%) tested negatively for HCV RNA. After 6 months of follow-up, without IFN therapy, 17 (41%) still had normal ALT values, and 16 (39%) still tested negatively for HCV RNA in serum. Patients who continued to test negatively for HCV RNA in serum after 6 months of follow-up also tested negatively for HCV RNA in the liver at the end of IFN therapy. Only 2 subjects who tested negatively for HCV RNA in the liver at the end of treatment relapsed after discontinuing IFN therapy. In contrast, patients who tested positively for HCV RNA in the liver after 6 months of therapy relapsed and tested positively for HCV RNA in serum during the 6 months of follow-up. These results suggest that (1) a nonhepatic site of HCV infection may exist; (2) this putative extrahepatic site appears to be less responsive to IFN therapy than in the liver and (3) this unknown extrahepatic site of infection may be the source of HCV reactivation in cases that relapse during IFN follow-up periods.

Utility of hepatitis C virus RNA determinations in hepatic tissue as an end point for interferon treatment of chronic hepatitis C

A total of 41 patients with chronic hepatitis C virus (HCV) defined as abnormal liver injury test results for 6 months or more and HCV RNA positivity in plasma were studied to determine if the liver might not be the only focus of HCV infection in individuals treated with interferon alfa (IFN-α). All patients were examined for the presence of confounding liver disease and tested negatively for such findings. All tested positively for HCV RNA and had an abnormal hepatic histology. All were treated with IFN for 6 months at a dosage of 5 million units daily. After 6 months of therapy, 29 (71%) had normal alanine transaminase (ALT) values, and 25 (61%) tested negatively for HCV RNA. After 6 months of follow-up, without IFN therapy, 17 (41%) still had normal ALT values, and 16 (39%) still tested negatively for HCV RNA in serum. Patients who continued to test negatively for HCV RNA in serum after 6 months of follow-up also tested negatively for HCV RNA in the liver at the end of IFN therapy. Only 2 subjects who tested negatively for HCV RNA in the liver at the end of treatment relapsed after discontinuing IFN therapy. In contrast, patients who tested positively for HCV RNA in the liver after 6 months of therapy relapsed and tested positively for HCV RNA in serum during the 6 months of follow-up. These results suggest that (1) a nonhepatic site of HCV infection may exist; (2) this putative extrahepatic site appears to be less responsive to IFN therapy than in the liver; and (3) this unknown extrahepatic site of infection may be the source of HCV reactivation in cases that relapse during IFN follow-up periods. (HEPATOLOGY 1995; 22:1109–1112.).