Hepatitis C virus infection in haemodialysis and kidney transplant patients

Chronic infection with hepatitis C virus (HCV) is an important global health problem. The prevalence of HCV is significantly higher in haemodialysis and kidney transplant patients, as compared to the general population. In spite of the relatively milder liver disease activity reported in HCV-infected haemodialysis patients, HCV infection adversely affects survival. Likewise, HCV has a detrimental effect on both patient and graft survival after kidney transplantation. However, patient survival is significantly better with kidney transplantation compared to remaining on dialysis; therefore, HCV infection alone should not be a contraindication to transplantation. Combination antiviral therapy with pegylated interferon-alpha and low-dose ribavirin is currently evolving in haemodialysis patients. Interferon-alpha (standard/pegylated) is relatively contraindicated after kidney transplantation because of an increased risk of allograft rejection. Therefore, antiviral treatment of transplant candidates while on dialysis remains the best option and may avoid the risk of HCV-associated liver and renal disease after transplantation. Large multi-centre clinical trials are required in HCV-infected haemodialysis and kidney transplant patients in order to define optimal therapeutic strategies before and after transplantation.     

Hepatitis C virus infection in French hemodialysis units: a multicenter study

The aims of the study were: (i) to evaluate the prevalence of hepatitis C virus (HCV) antibodies (third generation tests) and RNA (standardized ultrasensitive RT-PCR assay) in a large cohort of hemodialysis patients, and (ii) to correlate HCV markers with bioclinical features and alanine-aminotransferase (ALT) activity. Antibodies were assayed by two methods in 1,323 patients (60% men, median age 65 years, median hemodialysis duration 3 years) attending 25 French hemodialysis centers including 9 self-care units. RNA was assayed using the Cobas Amplicor 2.0 method in pooled samples from 10 anti-HCV(-/-) patients and on individual samples from the other patients. Of the 16.3% patients (range 0-44%) tested (+/+) for HCV antibodies (anti-HCV), 2.3% tested (+/-) and 81.4% tested (-/-). 70% of the anti-HCV(+/+) patients and 3% of the HCV(+/-) patients were RNA(+). Pooled analysis revealed that 5/1077 anti-HCV(-/-) patients (0.5%) were RNA(+); all 5 displayed subsequently an increase in ALT and became anti-HCV(+/+). Mean ALT was higher (multiple of normal) in anti-HCV(+/+) RNA(+) patients than in anti-HCV(+/+) RNA(-) patients (0.46 +/- 0.08 vs. 0.22 +/- 0.07, P < 0.0001) and similar in all the RNA(-) patients, whatever their HCV antibody status. Multivariate analysis demonstrated that HCV status was linked to hemodialysis duration, previous kidney transplantation and positive anti-HBc. To summarize, the determination of the RNA status of anti-HCV(+/-) patients may have clinical relevance if a policy of isolation is contemplated. Standardized ultrasensitive RT-PCR assay combined with a pooling strategy is a promising method for use in epidemiological studies.     

Immunoblot in the serological diagnosis of hepatitis C virus infection

The objective of the study was to assess three immunoblot assays, the Deciscan HCV Plus, the Riba and the Inno-Lia, on 44 discordant samples with three EIA kits. These immunoblots were considered as confirmation reagents. A result was considered as a false positive by anti-HCV antibody assay if the three immunoblots were negative or if two immunoblots were negative with the third being indeterminate and a negative virological genomic diagnosis observed on all the samples. The result was positive if at least two immunoblots out of three were positive. Thus, 34 samples were considered as false positive and ten samples were excluded because it was impossible to conclude between true or false positive result. The 44 discordant results were never confirmed as positive by the use immunoblot or PCR. The three immunoblots were negative for half of the samples and two immunoblots and one indeterminate were observed for 77% of the samples. The false positive results by the Monolisa assay were more often found indeterminate with the Deciscan assay than with the other immunoblots. That was also checked for Vitros/Riba pair. One of the explanations could be the use of common antigens for the reagents from the same manufacturer. The Inno-Lia test is the most specific immunoblot according to the results obtained in our study.     

Hepatitis B virus transmission in Brazilian hemodialysis units: serological and molecular follow-up

A serological and molecular study of hepatitis B virus (HBV) infection was carried out in dialysis units in Central Brazil. Between 1995 and 1999, serum samples from all HBsAg-positive hemodialysis patients (n = 43) were tested for HBeAg/anti-HBe and subtyping by monoclonal ELISA. HBV DNA was detected by PCR and positive samples were genotyped by restriction fragment polymorphism pattern (RFLP) methodology. TheHBsAg prevalence declined in this population during the survey period (12-5.8%). HBeAg and anti-HBe were detected in 23 (53.5%) and 18 (41.9%) sera, respectively. Thirty-six samples could be HBsAg subtyped: 21 were subtype ayw(3), 14 belonged to adw(2) and one was identified as adw(4). HBV DNA was present in 30 serum samples. Of these, 20 (66.7%) were genotype D, 9 (30%) genotype A, and 1 (3.3%) genotype F. In addition, the RFLP pattern could be determined in samples from 18/20 genotype D patients: D3 (10 strains), D7 (7 strains) and D4 (1 strain); from 8/9 genotype A patients: A1 (6 strains) and A3 (2 strains); and from the patient infected with genotype F: F1. Patterns D3 and D7 were associated closely with HBV infection in the two largest hemodialysis units studied. These findings confirm the value of the RFLP method as an effective molecular epidemiological tool for elucidating HBV transmission in hemodialysis units.     

Hepatitis C virus infection

Hepatitis C virus (HCV) infection is a major public health problem. Up to 3% of the world's population is infected with HCV, and at least 200 000 adults in the UK carry the virus. Of those exposed to HCV, 80% become chronically infected, and at least 30% of carriers develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. This review provides an overview of selected features of the molecular biology and pathogenesis of HCV infection, and thereafter discusses in detail the epidemiology of HCV, the hepatic and extra-hepatic diseases caused by the virus, and the current treatment options for both acute and chronic virus infection. The special cases of healthcare workers, prison inmates and individuals coinfected with human immunodeficiency virus and HCV are considered in detail.     

Molecular and serological diagnosis of Chikungunya virus infection

INTRODUCTION: In 2005-2006, during the Chikungunya virus outbreak in La Réunion (Indian Ocean), we urgently established the molecular and serological methods for the diagnosis of Chikungunya virus (CHIKV) from various types of samples. METHODS: CHIKV RNA was detected using a highly sensitive real-time RT PCR assay. A co-extracted and co-amplified internal control RNA was used to identify RT PCR inhibitors. Depending on their nature samples were pretreated before nucleic acid extraction. Viral loads were measured using a synthetic RNA calibrator. CHIKV immunoglobulin (Ig) G and M antibodies were detected by ELISA either from sera or from blood absorbed on filter paper. RESULTS: CHIKV RNA was found in various types of samples such as plasma, cerebrospinal fluid, and placenta, but was not found in some samples including maternal milk and synovial samples. Detection of IgG from filter paper absorbed blood is specific and sensitive. Routine data showed that maternally transferred IgG and naturally acquired IgM persist at least 12 and 18 months, respectively. DISCUSSION: The techniques enabled the diagnosis of chikungunya in known and newly described forms of the disease. They are used for routine diagnosis and large scale surveys.     

Hepatitis C virus infection in cameroon: A cohort-effect

A hepatitis C virus (HCV) serological study conducted in 2003 on 1,434 individuals in Yaounde and other HCV seroepidemiological studies on 2,066 sera sampled between 1993 and 1997 in four geographically distinct rural areas (Ntem, Mekas, Yokadouma, and Nditam) in Cameroon, are described. Two patterns of HCV seroprevalence were observed. The first pattern, represented by Nditam and Yokadouma populations, showed low HCV seroprevalence rates (2.9% and 3.3%, respectively) increasing moderately with age (9.0% and 16.7% after age 50). The second pattern showed high seroprevalence rates (6.9% for Yaounde, 14.4% and 16.7% for Ntem and Mekas, respectively). These rates increased dramatically with age (32.8%-49.5% after age 50). The age-specific anti-HCV prevalence curve of the 1993 Mekas survey paralleled those of the 1997 Ntem and 2003 Yaounde surveys. Using the year of birth as the x-axis, the three curves closely matched each other. This clearly indicates a cohort effect for which the seroprevalence trends are clearly related with the year of birth, rather than the age. The highest prevalence was observed among people born around 1940.     

Dobrava virus infection: serological diagnosis and cross-reactions to other hantaviruses

Recent data have shown that Dobrava (DOB) hantavirus is the cause of severe haemorrhagic fever with renal syndrome (HFRS) in central and eastern Europe. To determine whether serological assays need to be based on the homologous viral antigen rather than on closely related hantavirus antigens, acute and convalescent sera from patients with HFRS collected in former Yugoslavia were examined for IgM and IgG to three hantavirus antigens; DOB, Hantaan (HTN) and Puumala (PUU). Focus reduction neutralization test was included for comparison and confirmation of the enzyme-linked immunosorbent assay (ELISA) results. Although the results showed that the cross-reactivity was high between these three antigens during the acute phase of the disease, one of 155 patients serum samples reacted only in the DOB antigen-based IgM assay. The evaluation of IgG reactivities revealed that a DOB antigen-based IgG ELISA has to be used in sero-epidemiological studies; 7.1% (11/155) of the acute phase/early convalescent sera and 12.5% (2/16) of the late convalescent sera, respectively, reacted only with the homologous DOB antigen.     

Hepatitis C virus infection in HIV-infected patients

Because of shared routes of transmission, hepatitis C and HIV coinfection is common in the United States, affecting 15% to 30% of HIV-infected individuals. In the era of highly effective antiretroviral therapy, hepatitis C virus (HCV)-related liver disease has emerged as a significant cause of morbidity and mortality. Accordingly, the Infectious Diseases Society of America and the American Association for the Study of Liver Disease guidelines for the management of HCV recommend that patients with HIV/HCV undergo medical evaluation for HCV-related liver disease and consideration for HCV treatment and, if indicated, orthotopic liver transplantation. However, the treatment of patients with HIV/HCV is complicated by the relatively high prevalence of medical and psychiatric comorbidities and the challenges of anti-HCV therapy in the setting of HIV disease and antiretroviral therapy. Nonetheless, recently completed randomized controlled trials provide evidence of the safety, tolerability, and efficacy of HCV treatment with pegylated interferon-’a plus ribavirin in HIV-infected individuals. This review focuses on the epidemiology, natural history, and management of HCV in the HIV-infected patient.     

Hepatitis C virus infection in hemodialyzed patients

In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in noninfected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.     

Hepatitis C virus infection and assisted reproduction

BACKGROUND: In assisted reproduction, hepatitis C virus (HCV) transmission may pose a risk for the baby, technicians, and gametes or embryos from non-contaminated parents. This study aimed at determining the prevalence and risk factors for HCV infection in a group of infertile couples. METHODS: HCV infection was investigated in 409 patients attending the infertility clinic at Hospital de Clínicas de Porto Alegre, Brazil, between 1997 and 1998. Serum was screened for anti-HCV using ELISA and for hepatitis B surface antigen (HBsAg) using an enzyme-linked fluorescent assay (ELFA). HCV infection and semen viraemia was also investigated using HCV RNA detection. RESULTS: The overall prevalence of anti-HCV was 3.2% (8/248) among women and 3.7% (6/161) among men. All subjects were negative for hepatitis B virus (HBV) and human immunodeficiency virus (HIV). From the 14 HCV-positive patients, two were lost, and serum was collected from the remaining 12 patients for assessment of HCV RNA, resulting in five HCV-positive cases (one woman and four men). Only one of the HCV-positive men had viraemia levels >500 000 RNA copies/ml. There was a significant risk associated with being HCV-positive in women with HCV-positive male partners (P < 0.001). In male patients, the correlation between use of intravenous drugs and HCV-positivity was also significant (P < 0.001). CONCLUSIONS: Since the risk for vertical and laboratory HCV infection is not well determined, and HCV prevalence is not negligible in this group, we recommend that infertile patients be screened before assisted reproductive techniques.     

Hepatitis E virus infection in haemodialysis patients: a case-control study in Saudi Arabia.

To determine the prevalence of antibody to hepatitis E virus (IgM anti-HEV) among haemodialysis patients and evaluate whether there was an increased risk of infection and exposure to HEV in an area of endemic viral hepatitis, serum samples obtained from 83 Saudi patients on chronic haemodialysis (group 1), 400 sex- and age-matched healthy subjects (group 2) and hospital patients (group 3) were tested for the IgM anti-HEV and IgG anti-HEV. The prevalence of anti-HEV among the patients (group 1) and the healthy controls were 4.8% and 0.3%, respectively. The difference (4.5%) was statistically significant, with a calculated odds ratio (OR) of 20.2 (95% CI = 2.1-481.0; P = 0.0002). In contrast, there was no significant difference in the prevalence rates of IgG anti-HEV (7.2% vs 10.8%) in both groups. In nonhaemodialysis patients with various diseases, 1.6% (1 of 64) of outpatients (group 3) and none (0 of 113) of the ward patients (group 4) was positive for IgM anti-HEV. Thus, the prevalence (4 of 83) of IgM anti-HEV in the haemodialysis patients was significantly higher than the rate (1 of 177) in the combined groups of nonhaemodialysis hospital patients. The calculated OR was 8.9 (95% CI = 0.92, 212.8; P = 0.037). IgM antibody to hepatitis A virus (IgM anti-HAV) was not detected in any subjects, and the prevalence rates of IgG anti-HAV were similar in the patients and controls (72.3% and 74.3% in groups 1 and 2, respectively, and 75.7% combined groups 3 and 4). The study indicated a significantly higher risk of acute HEV infection among patients on chronic haemodialysis. It is possible that these were nosocomial infections acquired by person-to-person transmission in the haemodialysis unit. However, it is more probable that the infections were community acquired, a conclusion supported albeit indirectly by the lack of a significant difference between the prevalence in haemodialysis patients (4.8%) and outpatients (1.6%). In areas of endemic HEV, appropriate strategies should be adopted to prevent the risk of HEV among haemodialysis patients.     

Hepatitis C virus infection in intravenous drug users

Intravenous drug use (IVDU) remains a major means of hepatitis C virus (HCV) transmission. In this study, 101 drug users were studied prospectively after cessation of IVDU. Of these, 75.8% were anti-HCV positive, and 71.4% had elevated levels of alanine aminotransferase. These levels decreased significantly within 1 month of IVDU cessation (p 0.02). Liver biopsies showed minimal or mild fibrosis in 32 (71%) of 45 subjects, and severe fibrosis in two (4.4%) subjects. Anti-HCV-positive intravenous drug users in this study presented with mild liver disease and variable stages of disease progression. Biochemical disease activity might be affected by IVDU.     

Hepatitis C virus infection: when silence is deception

Hepatitis C virus (HCV) uses complex and unique mechanisms to prevent, evade or subvert innate and adaptive immune responses and to establish persistent infection and chronic hepatitis. Recently developed experimental systems have significantly facilitated the analysis of HCV replication, virus-host interaction and pathogenesis of chronic hepatitis and have provided new insights into the mechanisms of HCV clearance and persistence.