A review of hepatitis E virus.

SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.

Host Immune Status and Response to Hepatitis E Virus Infection

The hepatitis E virus (HEV) has a global distribution and is known to have caused large waterborne epidemics of icteric hepatitis. Transmission is generally via the fecal-oral route. Some reports have suggested parenteral transmission of HEV. Anti-HEV prevalence data among chronic hemodialysis (HD) patients are few and give conflicting results. This cross-sectional study was conducted in August of 2004. We tested 324 chronic HD patients attending three different units in the city of Tabriz, northwestern part of Iran, for anti-HEV antibody. A specific solid- phase enzyme-linked immunoassay (Diapro, Italy) was used. The overall seroprevalence of hepatitis E was 7.4 %(95% CI: 4.6%–10.6%). The prevalence rate of HBV and HCV infection were 4.6% (95% CI: 2.3%–6.9%) and 20.4% (95% CI: 16%–24.8%), respectively. No significant association was found between anti-HEV positivity and age, sex, duration of hemodialysis, positivity for hepatitis B or C virus infection markers and history of transfusion. We observed high anti-HEV antibody prevalence; there was no association between HEV and blood borne infections (HBV, HCV, and HIV) in our HD patients. This is the first report concerning seroepidemiology of HEV infection in a large group of chronic HD individuals in Iran.

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Hepatitis E virus infection in hemodialysis patients: A seroepidemiological survey in Iran

Hepatitis E virus (HEV) is the causative agent for enteric non-A, non-B hepatitis. Transmission is mainly via the fecal-oral route but the possibility of an additional parenteric transmission has been raised. Patients undergoing chronic hemodialysis (HD) have an increased risk of exposure to blood transmitted agents. Previous studies concerning prevalence of antibodies to HEV (anti-HEV) among HD patients gave conflicting results. The aim of the study presented here was to determine the prevalence of anti-HEV among HD patients of a well-defined semi-rural region in central Greece (Thessalia region). All patients (n=351, 234 males, mean age 60 ′ 14 years) who were being treated in the HD units of central Greece (n=5) during 2001 were tested for anti-HEV antibody. Two commercially available specific solid-phase enzyme-linked immunoassays were applied for anti-HEV detection. Hepatitis B virus markers, antibodies to HCV, HIV and HTLV were also screened in all patients by commercially available assays. Serum aminotransferase (AST, ALT) levels were measured by spectrophotometry. 17 anti-HEV-positive patients were found and prevalence was 4.8%, varying from 1.8 - 9.8% in the various HD units. Prevalence of HBsAg and anti-HCV was 5.7% (2.9 - 15%) and 23.6% (11.5 - 36.2%) respectively. The anti-HEV prevalence was increased compared to healthy blood donors in Greece (0.26%, p < 0.01). The highest prevalence of anti-HEV was seen at the HD unit of the General Hospital of Karditsa (9.8%). Risk factors for anti-HEV antibody were not identified: no association was found between anti-HEV positivity and age or sex, duration of HD, hepatitis B or C virus infection markers, previously elevated aminotransferase levels or history of transfusion. Our investigation of HEV infection in the cohort of HD patients in central Greece showed that the prevalence of anti-HEV was greater than in healthy blood donors. There was no association to blood borne infections (HBV, HCV). The high prevalence of anti-HEV we found in one HD unit was probably related to a local infection in the past. However, long-term prospective studies are needed in an attempt to identify whether intra-unit factors are also responsible for the increased prevalence of serologic markers of HEV infection among HD patients.

Hepatitis E virus antibodies in hemodialysis patients: an epidemiological survey in central Greece.

AIM: To assess the hepatitis B virus (HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure (ESRF) patients from Central Greece. METHODS: Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DNA by real-time polymerase chain reaction. Only serum samples with repeatedly detectable HBV-DNA were considered positive. IgG antibodies to hepatitis C virus (anti-HCV) were tested by a third generation enzyme linked immunosorbent assay (ELISA), while IgG antibodies to hepatitis E virus (anti-HEV) were tested by two commercially available ELISAs. RESULTS: HBV-DNA was detected in 15/366 patients (4.1%) and HBsAg in 20/366 (5.5%). The prevalence of occult HBV infection was 0.9% (3/346 HBsAgnegative patients). Occult HBV was not associated with a specific marker of HBV infection or anti-HCV or anti-HEV reactivity. There was no significant difference in HBV-DNA titres, demographic and biochemical features, between patients with occult HBV infection and those with HBsAg-positive chronic HBV infection. CONCLUSION: In central Greece, 4% of ESRF patients had detectable HBV-DNA, though in this setting, the prevalence of occult HBV seems to be very low (0.9%).

Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece

Background. The aim of this study was to determine the prevalence of hepatitis E virus (HEV) infection among patients undergoing haemodialysis (HD) and to evaluate whether chronic haemodialysis is associated with an increased risk of HEV infection. Methods. Serum samples from 420 HD patients and 316 healthy volunteers were tested for IgG and IgM antibodies to HEV (anti-HEV). Anti-HEV testing was done by an enzyme immunoassay (EIA) based on recombinant proteins of HEV (Abbott Labs). All anti-HEV IgG positive sera were confirmed using synthetic peptides. Results. Anti-HEV IgG was confirmed in 27/420 (6.4%) of the HD patients and in 7/316 (2.2%) of the reference group (P=0.007). However, multiple logistic regression analysis showed that the prevalence of anti-HEV IgG was not significantly higher in HD patients compared with the reference group, after controlling for age and sex. No patient was found positive for anti-HEV IgM. The presence of anti-HEV was associated with sex in HD patients (P=0.04). No significant association was found between anti-HEV and underlying renal disease, anti-HCV, anti-HBc, blood transfusions, history of elevated transaminases, history of clinical hepatitis and renal transplantation. A marginal association, which was observed with the duration of haemodialysis in univariate analysis (P=0.07), was not confirmed in multivariate analysis. Conclusions. Chronic haemodialysis is not associated with an increased risk of exposure to HEV, and the high prevalence of anti-HEV IgG in HD patients reported in uncontrolled studies is possibly due to the confounding effect of age and sex.

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Hepatitis E virus (HEV) infection in haemodialysis patients

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Hepatitis E virus (HEV) infection in haemodialysis patients