Risk factors and seroprevalence of hepatitis E evaluated in frozen-serum samples (2002-2003) of pregnant women compared with female blood donors in a Southern region of Brazil.

Hepatitis E has always been related to morbidity in pregnant women. Its epidemiology is not well understood in Brazil. Therefore, we tested sera from 209 pregnant women and 199 female blood donors, collected at a single center in Curitiba, Brazil. The Wantai assay was used for testing the anti-hepatitis E virus (anti-HEV), immunoglobulin G (IgG), and an in-house polymerase chain reaction process for testing HEV RNA. Anti-HEV was detected in 22.5% of the total group, 19% in the pregnant women group, and 26% in the blood donor group (P = 0.11), a much higher prevalence when compared with other studies in Brazil. Demographical analysis showed that 92.4% were born in the South Region of Brazil, 4.9% in the Southeast, and 2.7% were distributed over other regions of the country. With respect to their origin, 99% were from the South, 0.7% from the Southeast, and 0.2% from the Central-West regions. Income, education, race, number of pregnancies, and abortion did differ significantly when comparing both the groups (P < 0.001). Age >30 (P = 0.012) and the number (>3) of pregnancies (P = 0.008) were related to anti-HEV positivity. All anti-HEV IgG-positive females were HEV RNA negative. In conclusion, HEV positivity was found in one out of five young women, which showed an urgent need for further epidemiological studies in Brazil.

Viral dominance patterns in chronic hepatitis delta determine early response to interferon alpha therapy.

Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients' characteristics and inflammatory features; 109 HDV-infected patients treated with PEG-IFNa-2α within the international multicentre, prospective HIDIT-2 trial were studied. Patients were classified as D- or B-dominant if the viral load of one virus exceeded that of the other virus by more than 1log10 . Otherwise, no viral dominance (ND) was described. We used Luminex-based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA-positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B-dominance, 17% showed nondominance. D-dominance was associated with downregulation of 4 interleukins (IL-2ra, IL-13, IL-16 and IL-18) and 5 chemokines/cytokines (CTACK (CCL27), MCP-1 (CCL2), M-CSF, TRAIL and ICAM-1) while no analyte was increased. In addition, D-dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B-dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D-dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG-IFNa-2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D-dominant patients.

[From the national competence network for viral hepatitis (HepNet) emerged the German Liver Foundation (Deutsche Leberstiftung)]. / Vom Kompetenznetz Hepatitis (HepNet) zur Deutschen Leberstiftung.

The competence network for viral hepatitis (HepNet) was founded in 2002 with funding from the German government and has influenced the research on viral hepatitis in Germany. HepNet collaborator sites have been involved in numerous national and international investigator-initiated, as well as industry-sponsored, phase 1-3 studies. Within the HepNet Study-House, many groundbreaking investor-initiated trials have been completed and are still ongoing. For example, the acute hepatitis C trials and trials on chronic hepatitis D (delta), which led to therapy optimization. Continuation of the competence network on viral hepatitis has been achieved by the foundation of the German Liver Foundation, which has been an external cooperation partner of the German Center for Infection Research (DZIF) for two years. The well-established HepNet Study-House acts here as the clinical trial platform for all DZIF hepatitis trials.

Course and treatment of chronic hepatitis E virus infection in lung transplant recipients.

OBJECTIVE: Persistent hepatitis E virus (HEV) infections have been described in various transplant cohorts. However, the frequency and the course of HEV infection in lung transplant recipients (Lu-Tr) are not well defined. METHODS: We retrospectively analyzed serum from 95 Lu-Tr for HEV RNA and anti-HEV immunoglobulin-G (IgG) (with the MP assay). Anti-HEV seroprevalence was compared to that of 537 healthy individuals. Prospective HEV screening was subsequently initiated in Lu-Tr. RESULTS: Elevated liver enzymes were observed in 44/95 (46.3%) patients. Anti-HEV IgG was present in 5/95 patients (5.3%), revealing a slightly higher prevalence compared to controls (2%, 11/537; P = 0.07). Chronic HEV infection with detectable viral replication was confirmed by polymerase chain reaction in 3 (3.2%) patients, all of whom demonstrated clinical and biochemical features of active liver disease (maximum alanine aminotransferase [ALTmax ] 89, 215, and 270 IU/L, respectively). One patient had died from multi-organ failure in combination with liver cirrhosis before HEV diagnosis. Two additional patients with chronic hepatitis E were identified during prospective screening (ALTmax 359 and 318 IU/L). All patients still alive commenced ribavirin therapy for 5 months, with dose adjustment (400-600 mg/day) according to renal function and hemoglobin level. Sustained resolution of HEV infection occurred in 2 patients. One patient is still under treatment, and the fourth died from graft failure considered unrelated to ribavirin therapy. CONCLUSION: Chronic hepatitis E should be considered in the differential diagnosis of elevated liver enzymes, which are commonly seen in Lu-Tr. We observed 1 case of end-stage liver cirrhosis and death in an HEV-infected subject, who was not treated with ribavirin. Given this potentially devastating consequence, ribavirin therapy of persistent HEV infection appears to be acceptably safe and effective in Lu-Tr. However, larger prospective studies are warranted.