R. Jardi

Community-Based Seroepidemiological Survey of Hepatitis E Virus Infection in Catalonia, Spain

ABSTRACT The objective of the study was to investigate the prevalence of immunoglobulin G (IgG) antibodies to hepatitis E virus (HEV) infection in a population sample from Catalonia and to analyze the demographic and clinical variables associated with the presence of these antibodies. A total of 1,280 subjects between 15 and 74 years of age were selected randomly from urban and rural areas. Data for sociodemographic and clinical variables were collected by using a questionnaire. IgG antibodies to HEV were determined by an immunoenzymatic method. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for studied variables. Multiple logistic regression analysis was used to determine which variables were independently associated with the prevalence of HEV infection. Anti-HEV antibodies were detected in 96 (7.3%) of the 1,280 samples analyzed. The prevalence of antibodies was greater among males (7.8%) than among women (7%) and increased with age for both sexes, from 3% among subjects 15 to 24 years of age to 12% among subjects ≥65 years of age. Bivariate analysis of the sociodemographic and clinical variables showed an association between the prevalence of hepatitis E virus infection and minor surgery (OR, 1.96; 95% CI, 1.24 to 3.11), abdominal surgery (OR, 1.74; 95% CI, 1.12 to 2.73), and, for women, being uniparous or multiparous (OR, 2.84; 95% CI, 1.19 to 6.79). The multivariate analysis showed an association with minor surgery only (OR, 1.68; 95% CI, 1.03 to 2.70). In conclusion, anti-HEV antibodies were detected in 7.3% of the Catalan population. The seroprevalence of anti-HEV antibodies increased with age and was associated with previous minor surgery.

Prevalence of Hepatitis E Virus Infection in Children in the Northeast of Spain

ABSTRACT The prevalence of immunoglobulin G (IgG) anti-hepatitis E virus (anti-HEV) antibodies was studied with a representative sample of 1,249 healthy children aged between 6 and 15 years. IgG anti-HEV antibodies were detected in 57 (4.6%) of the 1,249 samples analyzed, suggesting that some children are exposed to HEV in early childhood.

Anti-HD IgM as a marker of chronic delta infection.

The value of anti-HD IgM as a marker of chronic delta infection was evaluated by correlating its presence in serum with that of HD-Ag in liver cells and with the degree of inflammatory activity. Thirty-six patients with HBsAg-positive chronic hepatitis and anti-HD at high titers were studied. Overall, the liver cells of 26 patients contained HD-Ag and 27 were positive for IgM anti-HD. The correlation between both markers was excellent: 25 cases were positive for both serum anti-HD IgM and intrahepatic HD-Ag and 8 were negative for both markers. There was only 1 HD-Ag-positive patient, who was anti-HD IgM-negative. Two patients were anti-HD IgM-positive and HD-Ag-negative. Histological damage was more severe in anti-HD IgM-positive cases than in those negative for this marker (Knodells index 13.5 vs 11.9, P less than 0.01). We conclude that anti-HD IgM is a good marker of chronic active delta infection.

Clinical and serological outcome of acute delta infection

To assess the clinical and serological outcome of hepatitis delta virus (HDV) infection, 59 patients with acute delta hepatitis were followed for 6-28 months. Forty-two patients had simultaneous HDV and HBV coinfection (anti-HBc IgM-positive, group I) and 17 were HBsAg carriers with HDV superinfection (anti-HBc IgM-negative, group II). Overall, serum HD-Ag and anti-HD IgM were the most sensitive markers for diagnosis of delta infection during the first 2 weeks after onset of symptoms. The clinical presentation was similar in both groups; 4 patients (1 in group I and 3 in group II) (7%) developed fulminant hepatitis, but none of them died. The majority of patients with HBV-HDV coinfection (group I) eventually recovered, whereas all HBsAg carriers with HDV superinfection (group II) developed chronic liver disease. Liver histology in these patients showed chronic active hepatitis and/or cirrhosis in 90%. The hepatic lesion was probably due to persistent HDV infection, as indicated by the presence of intrahepatic HD-Ag and/or persistence of serum anti-HD IgM in 90% of the patients.

Infrequent detection of hepatitis E virus RNA in pregnant women with hepatitis E virus antibodies in Spain

Targeted therapy for HCC has been the focus of study in recent years. To this end, targeted therapy for HCC has focused on EGFR and vascular endothelial growth factor receptors (1, 2). In a phase II trial, it was found that patients with advanced HCC treated with combined bevacizumab and erlotinib had a median progress-free survival of 39 weeks (95% CI, 26–45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48–78 weeks; 15.65 months). This study highlighted the potential beneficial effect of bevacizumab and erlotinib for treating HCC. Gefitinib is another EGFR–tyrosine kinase inhibitor with the same mechanism of action as erlotinib. Previous studies concerning gefitinib as a targeted therapy for HCC were performed using animal or in vitro models (3–8). Findings from these studies suggested that gefitinib may inhibit HCC growth by blocking several pathways, including the PTEN/Akt signalling pathway (8), and inhibit HCC metastasis by blocking the fibronectininduced activation of ERK, p38, Akt, cell proliferation and invasion (7). We have described the case of a patient with advanced HCC and lung metastasis who received gefitinib treatment. The clinical response to this treatment was positive, as indicated by a prolonged duration of survival and shrunken tumour.

Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long-term treatment

Aliment Pharmacol Ther 2010; 32: 97–104

Changes in different regions of hepatitis B virus gene in hepatitis B 'e' antigen-negative patients with chronic hepatitis B: the effect of long-term lamivudine therapy.

Background : Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence.

Estudio de la replicación del virus de la hepatitis B e infección por otros virus hepatotropos en pacientes con infección crónica por el virus B

AIM: To study hepatitis B virus (HBV) replication in a series of patients with HBV infection and to analyze the frequency of associated hepatitis C virus (HCV) and hepatitis D (HDV) infection. PATIENTS AND METHOD: Serological markers of HBV, HCV and HDV, transaminase values and HBV DNA were studied in serum samples from 463 patients with chronic HBV infection. RESULTS: Three hundred ninety-six (85.5%) were classified as hepatitis B, 33 (7.1%) as hepatitis B and C, 17 (3.6%) as hepatitis B and D and 17 (3.6%) as hepatitis B, C and D. Sixty-seven percent of patients with hepatitis B and 33% of those with chronic hepatitis B were asymptomatic HBsAg carriers. HVB DNA was identified in 27.7% of patients with hepatitis B, in 24% of those with hepatitis B and C, in 11.7% of those with hepatitis B and D and in 29.4% of those with hepatitis B, C and D. HBV DNA and elevated transaminase levels were found in 63% of HBeAg-positive patients and in only 16% of those who were anti-HBe-positive. These latter were considered candidates for antiviral treatment. CONCLUSIONS: In our environment, most patients with HBV infection are asymptomatic HBsAg carriers. Viral replication and elevated alanine aminotransferase levels were found in 22% of the patients. Consequently, these patients are candidates for antiviral treatment. Between 3.6% and 7.1% of patients with hepatitis B presented coinfection with HCV or HDV, or both. No significant differences were found in HBV replication among the different groups.

Detection of hepatitis delta virus RNA in human liver tissue by non-radioactive in situ hybridization

Several studies have demonstrated the presence of serum HDV-RNA by molecular hybridization in patients with chronic D infection, but there is scarce information about the presence of HDV-RNA in hepatic tissue. The presence of HDV-RNA by in situ hybridization (ISH) with a non-radioactive probe in paraffin-embedded hepatic tissue was studied in 29 patients with chronic delta hepatitis (20 with and 9 without intrahepatic delta antigen) and correlate their presence with the expression of hepatic delta antigen and serum HDV-RNA by dot-blot hybridization. HDV-RNA was detected by in situ hybridization in 18 cases: 16 of the 20 (80%) biopsies with intrahepatic delta antigen and 2 of the 9 (22%) without. HDV-RNA was not detected in any of the control cases. Serum HDV-RNA was found in 19 cases: 18 (90%) of 20 chronic delta hepatitis cases with tissular delta antigen and one of the 9 without intrahepatic delta antigen. All patients except one, who was positive for intrahepatic HDV-RNA, showed serum HDV-RNA. However, in two cases ISH detected hepatic HDV-RNA without tissular HDAg; one of these also had serum HDV-RNA and in the other positivity for hepatic HDV-RNA by ISH was the only marker of viral delta replication. In conclusion, detection of HDV-RNA in hepatic tissue by in situ hybridization with a digoxygenin-labelled probe is a rapid and sensitive method that could be a useful tool for diagnosis of HDV infection in clinical laboratories.

1108 ULTRA-DEEP-PYROSEQUENCING OF PRECORE REGION OF HEPATITIS B VIRUS

1107 PRIME/BOOST IMMUNIZATION WITH DNA AND ADENOVIRAL VECTORS PROTECTS WOODCHUCKS FROM HEPATITIS D VIRUS INFECTION M. Fiedler, A. Schumann, A. Kosinska, M. Lu, L. Johrden, O. Wildner, M. Roggendorf. Institut fur Virologie, Abt. fur Klinische Chemie, Universitatsklinikum Essen, Essen, Institut fur Virologie, Universitat Bochum, Bochum, Paul-Ehrlich-Institut, Langen, Germany E-mail: melanie.fiedler@uni-due.de