Diagnostic utility of hepatitis E virus antigen-specific ELISA versus PCR testing in a cohort of post liver transplant patients in a large university hospital.

BACKGROUND: Hepatitis E virus (HEV) is an important infectious agent causing acute and chronic disease. Chronic hepatitis E affects immunocompromised people and serological testing is neither reliable nor sufficient to infer whether a patient has infection; therefore HEV RNA testing is the only reliable diagnostic test presently available. An HEV antigen-specific ELISA test is commercially available but is not yet in clinical use. OBJECTIVES: 1) determine the prevalence of HEV infection in the Royal Free Hospital (RFH) liver transplant cohort; 2) compare the diagnostic utility of HEV antigen-detection against the current gold standard; 3) consider screening strategies for HEV infection in immunocompromised groups. STUDY DESIGN: The serum samples of 490 post liver transplant patients visiting the outpatient clinic at the RFH over an eight-month period were tested for HEV with both an HEV antigen-specific ELISA and HEV RNA test. RESULTS: The prevalence of HEV infection was 0.20% (95% CI 0.0%-1.1%). The specificity of the ELISA was 98.2% with a positive predictive value of 10.0%. There was one true positive HEV case, which was picked up correctly by the antigen-specific ELISA. These results were improved by incorporating a neutralisation step into further ELISA tests. CONCLUSIONS: The antigen-specific ELISA test gave no false negative results, supporting its utility as a screening tool. There was one true antigen positive result. Further investigation including cost analysis is indicated to determine the efficacy of HEV antigen-specific ELISA testing in a screening context and in the clinical investigation of HEV infection in immunocompromised patients.

Confirmation of specificity of reactivity in a solid phase ELISA for the detection of hepatitis E viral antigen improves utility of the assay.

Genotype 3 hepatitis E virus (HEV) can lead to persistent infections in immunocompromised hosts. A recently available commercial assay for the detection of HEV antigen (HEV-Ag ELISA, Wantai diagnostics) may enable the study of HEV-Ag dynamics in such persistent infections, however currently there is no confirmatory test available. We generated a putative neutralising reagent from a pool of four convalescent blood donor samples and explored neutralising activity against HEV antigens from clinical samples, HEV tissue-culture and virus-like particles. Using this neutralisation method we were able to differentiate true reactivity from non-specific reactivity in plasma, stool and urine samples. This could also facilitate the introduction of HEV-Ag detection as a screening assay or the study of HEV-Ag in different body fluids.

Hepatitis E: the current state of play.

The hepatitis E virus (HEV) is a major cause of acute hepatitis globally. Genotypes 1 and 2 (G1 and G2) are obligate human pathogens transmitted faeco-orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 (G3 and G4) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food-borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self-limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion-transmitted HEV, which has been reported from countries classically considered HEV-endemic but also non-endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.

Outcomes of starting first-line antiretroviral therapy in hepatitis B virus/HIV-coinfected patients in Ghana.

OBJECTIVES: HIV/hepatitis B virus (HBV) coinfection is common in Ghana, where first-line antiretroviral therapy (ART) comprises lamivudine with zidovudine or stavudine and nevirapine or efavirenz. Little is known about ART outcomes in the context of coinfection. This study evaluated outcomes of ART among HIV/HBV-coinfected Ghanaians, focusing on locally available parameters. PATIENTS AND METHODS: An observational study comparing clinical and virological outcomes in HIV-infected individuals who were either hepatitis B surface antigen (HBsAg) positive or HBsAg negative was conducted over 36 months. Clinical events, hepatic transaminases, CD4 count and body mass index (BMI) were evaluated among 143 HBsAg-positive and 228 HBsAg-negative patients. In a random subset of HBsAg-positive patients, HBV-DNA levels and polymerase sequences were analysed. RESULTS: Comparing HBsAg-positive and HBsAg-negative patients, 44/143 (30.8%) and 83/228 (36.4%) defaulted follow-up, 15/143 (10.5%) and 30/228 (13.2%) experienced a new clinical event, and 8/143 (5.6%) and 11/228 (4.8%) discontinued their initial regimen, respectively. Transaminase levels were higher in HBsAg-positive patients, although elevations were low grade. HBV coinfection was associated with an adjusted 2.04 (95% CI 0.59-3.49) cells/mm(3)/month smaller CD4 cell increase; there was no significant effect on BMI changes. After a median of 9 months of ART, 64/66 (97.0%) patients showed detectable HBV-DNA (median 3.3 log(10) IU/mL; IQR 2.6-6.2); 12/53 (22.6%) of these showed lamivudine-associated resistance mutations. CONCLUSIONS: HIV/HBV-coinfected Ghanaians tolerated first-line ART well, but experienced blunted CD4 cell responses. There was evidence of ongoing HBV replication, mild but persistent transaminase elevations and emerging lamivudine resistance in a proportion of treated patients, indicating the potential for progressive liver damage.