Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Hepatitis B virus exposure in human immunodeficiency virus seropositive Cuban patients

In order to estimate the prevalence of serological markers of exposure to Hepatitis B Virus (HBV), 295 subjects were selected at random from the National Registry of human immunodeficiency virus positive subjects. Evidence of exposure to HBV was defined as: testing Hepatitis B surface antigen (HBsAg) and anti-Hepatitis B core antigen (anti-HBc) positive or anti-HBc positive only. Overall, 133 (45.5%) were positive for anti-HBc and 15 (5.1%) resulted positive to HBsAg. Significant statistical association was found between male sex and exposure to HBV (p<0.01). Homosexual or bisexual behavior was found to be strongly associated to HBV exposure (p<0.001). In conclusion, the prevalence of HBV serological markers is higher in Cuban HIV positive subjects compared to the Cuban general population.

Prevalence of human immunodeficiency virus infection in alcoholics

To verify the prevalence of infection by human immunodeficiency virus (HIV) in alcoholics we studied 131 alcoholic patients (119 males and 12 females) with a mean age of 44.3 ± 10.8 years. Serum samples were collected from this group and analysed, by ELISA, for antibodies against HIV as well as for serological markers for hepatitis B virus (HBV) and hepatitis C virus (HCV). As we have previously described, we found a high prevalence of HBV (26.4%) and HCV (4.2%) markers as compared to the prevalence of these markers in samples of normal blood donors from Uberlândia's Hemocentro Regional, which are 4% and 0.4%, respectively. Of the 131 patients, four (3%) had antibodies against HIV, three (75%) of which were injecting drug users (IDU). In the HIV-negative group, only one patient was an IDU. The prevalence of HIV in our population, according to data from the city's Health Secretary, varies from 3.1% to 6.2%. We conclude that, at least for the moment, alcoholism per se, did not constitute an important risk factor for HIV infection. However, acquired immunodeficiency syndrome is a rather recent disease as compared to hepatitis B and C and, as the transmission routes are similar for HIV and hepatitis viruses, an increase in the incidence of HIV infection in alcoholics may be just a question of time.

Strategic Framework and Action Plan for the Prevention and Control of Hepatitis C in NI (PDF 182 KB)

2004 - 2007

High occurrence of hepatitis E virus in samples from wastewater treatment plants in Switzerland and comparison with other enteric viruses.

Hepatitis E virus (HEV) is responsible for many enterically transmitted viral hepatitides around the world. It is currently one of the waterborne diseases of global concern. In industrialized countries, HEV appears to be more common than previously thought, even if it is rarely virulent. In Switzerland, seroprevalence studies revealed that HEV is endemic, but no information was available on its environmental spread. The aim of this study was to investigate -using qPCR- the occurrence and concentration of HEV and three other viruses (norovirus genogroup II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31 wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV were detected in 40 out of 124 WWTP influent samples, showing that HEV is commonly present in this region. The frequency of HEV occurrence was higher in summer than in winter. No HEV was detected in WWTP effluent samples, which indicates a low risk of environmental contamination. HEV occurrence and concentrations were lower than those of norovirus and adenovirus. The autochthonous HEV genotype 3 was found in all positive samples, but a strain of the non-endemic and highly pathogenic HEV genotype I was isolated in one sample, highlighting the possibility of environmental circulation of this genotype. A porcine fecal marker (porcine adenovirus) was not detected in HEV positive samples, indicating that swine are not the direct source of HEV present in wastewater. Further investigations will be necessary to determine the reservoirs and the routes of dissemination of HEV.

Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

Viral Hepatitis Markers in Antepartum and Postpartum Women in Rio de Janeiro, Brazil

A seroprevalence study was carried out among a group of women in Rio de Janeiro to determine the prevalence of different markers for viral hepatitis given the limited data among healthy populations. Blood samples collected and tested from 874 women before or after delivery in a public county maternity hospital demonstrated age to be directly related to markers for hepatitis A virus and hepatitis B virus (HBV) infection. The prevalence of HBV and hepatitis C virus infection were lower than that observed in the blood donor population and might be explained by the younger age group and gender.

Seguimiento a 5 años de pacientes con hepatits crónica C y respuesta viral sostenida

L'objectiu va ser avaluar la persistència de resposta viral sostinguda als 5 anys de seguiment en pacients amb hepatitis crònica per virus C tractats amb interferó pegilat i ribavirina. Des d'agost de 2001 fins a maig de 2004, es van incloure tots els pacients del nostre centre tractats amb interferó pegilat i ribavirina que van assolir resposta viral sostinguda. Es van recollir dades demogràfiques, histològiques, bioquímics i virològiques durant el tractament i als 5 anys d'haver obtingut la resposta viral sostinguda. Només un dels pacients va presentar recurrència virològica (taxa de recurrència viral a llarg termini molt baixa).

Report of the Tribunal of Inquiry into the Infection with HIV and Hepatitis C of Persons with Haemophilia and Related Matters

Pursuant to a resolution of Dail Eireann passed on the 2nd day of June 1999 and a resolution of Seanad Eireann on the 2nd day of June 1999, the Minister for Health & Children, Brian Cowen, T.D., on the 8th of September 1999 made an Order appointing a Tribunal to which the Tribunals of Inquiry (Evidence) Act 1921 (as adapted and amended) applied, to inquire urgently into and report and make such findings and recommendations as it saw fit to the Clerk of Dail Eireann on the definite matters of urgent public importance set out in sub-paragraphs 1 to 14 of the resolutions passed by Dail Eireann and Seanad Eireann.   Download document here   &bull; Appendix 1-5 (4.03 MB)&bull; Appendix 6-10 (13.7 MB)&bull; Appendix 11-14 (1.06 MB)&bull; Appendix 15-19 (1.25 MB)&bull; Appendix 20-25 (2.75 MB)&bull; Appendix 26-30 (1.59 MB)&bull; Appendix 31-35 (2.12 MB)&bull; Appendix 36-40 (4.13 MB&bull; Appendix 41-45 (613 KB)&bull; Appendix 46-50 (884 KB)&bull; Appendix 51-54 (6.08 MB)

Seroprevalence of Hepatitis B virus infection among an afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.