High prevalence of hepatitis C infection among Brazilian hemodialysis patients in Rio de Janeiro: a one-year follow-up study

Nearly 400 hemodialysis patients treated at 5 different hemodialysis units in Rio de Janeiro were tested for one year for the presence of hepatitis C and B markers. During the same period, samples were also obtained from 35 continuous ambulatory peritoneal dialysis (CAPD) patients and from 242 health care workers. Depending on the hemodialysis unit studied, anti-HCV prevalence rates ranging from 47% to 82% (mean 65%) were detected. CAPD patients showed a lower prevalence of 17%. The prevalence of antibodies against hepatitis C virus (anti-HCV) among health care workers was 2.9%. We observed a hepatitis C attack rate of 11.5% per year in the anti-HCV-negative hemodialysis patient population. An average of 9.4% of the hemodialysis patients were chronic carriers of hepatitis B virus (HBV) (range 1.8% - 20.4%), while 48.9% showed markers of previous HBV infection. The HBV attack rate was 4.5% per year (range 0% - 6%). These results indicate an alarming high prevalence of anti-HCV among hemodialysis patients of this studied region.

GB virus C/Hepatitis G virus and other putative hepatitis non A-E viruses

The identification of the major agents causing human hepatitis (Hepatitis A, B, C, D and E Viruses) was achieved during the last 30 years. These viruses are responsible for the vast majority of human viral hepatitis cases, but there are still some cases epidemiologically related to infectious agents without any evidence of infection with known virus, designated as hepatitis non A - E. Those cases are considered to be associated with at least three different viruses: 1 - Hepatitis B Virus mutants expressing its surface antigen (HBsAg) with altered epitopes or in low quantities; 2 - Another virus probably associated with enteral transmitted non A-E hepatitis, called Hepatitis F Virus. Still more studies are necessary to better characterize this agent; 3 - Hepatitis G Virus or GB virus C, recently identified throughout the world (including Brazil) as a Flavivirus responsible for about 10% of parenteral transmitted hepatitis non A-E. Probably still other unknown viruses are responsible for human hepatitis cases without evidence of infection by any of these viruses, that could be called as non A-G hepatitis.

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

The influence of the human genome on chronic viral hepatitis outcome

The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a) the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b) protective alleles influencing hepatitis B virus (HBV) and hepatitis C virus (HCV) evolution; c) prejudicial alleles influencing HBV and HCV; d) candidate genes associated with HBV and HCV evolution; d) other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others). Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.

Infecção pelo Vírus da Hepatite B em Doentes Sujeitos a Terapêutica Imunossupressora ou Quimioterapia Citotóxica. A Propósito de um Caso Clínico

A reactivação do vírus da hepatite B em doentes com neoplasias hematológicas é uma complicação frequente da quimioterapia ou da terapêutica imunomoduladora. Os autores descrevem o caso dum doente com linfoma não-Hodgkin e história de infecção passada pelo VHB que desenvolveu hepatite fulminante após quimioterapia. Os mecanismos de reactivação do VHB são discutidos e as recomendações sobre profilaxia são apresentadas.

Immunization status of residents in pediatrics at the Federal University of São Paulo, Brazil

Vaccination of health care workers is an efficient way to reduce the risk of occupational infection and to prevent nosocomial transmission to vulnerable patients. Despite this, achieving high immunization rates among those professionals is a challenge. We assessed the immunization status of Residents in Pediatrics at the Federal University of São Paulo from June to December 2008. Their immunization records were checked and evaluated according to the Brazilian Immunization Schedule for health care workers. Considering all required vaccines, only 3.1% of the 64 Residents were up-to-date with their immunizations. Influenza was the vaccine with the lowest uptake (3.1%) and measles and rubella were diseases with the highest evidence of immunity (62.5% each). Only 37.5% of Residents had received three hepatitis B vaccine doses with a subsequent serology confirming seroconversion. Moreover, the vast majority of Residents in Pediatrics who were not up-to-date were unaware of the fact. Both medical schools and Pediatric Residence programs should not only offer information but also check vaccination records in an effort to keep their healthcare workers´ vaccinations up-to-date.

Evaluation of a new vaccine based on pDNA and recombinant protein against Helicobacter pylori

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

LIVER BIOPSY: IMPORTANCE OF SPECIMEN SIZE IN THE DIAGNOSIS AND STAGING OF CHRONIC VIRAL HEPATITIS

Liver biopsy is the gold standard method for the grading and staging of chronic viral hepatitis, but optimal biopsy specimen size remains controversial. The aim of this study was to evaluate the quality of liver specimen (number of portal tracts) and to evaluate the impact of the number of portal tracts in the staging of chronic hepatitis. Material and Methods: 468 liver biopsies from consecutive patients with hepatitis C virus and hepatitis B virus infection from 2009 to 2010 were evaluated. Results: The length of fragment was less than 10 mm in 43 cases (9.3%), between 10 and 14 mm in 114 (24.3%), and ≥ 15 mm in 311 (64.4%); of these, in 39 (8.3%) cases were ≥ 20 mm. The mean representation of portal tracts was 17.6 ± 2.1 (5-40); in specimens ≥ 15 mm the mean portal tract was 13.5 ± 4.7 and in cases ≤ 15 mm was 11.4 ± 5.0 (p = 0.002). Cases with less than 11 portal tracts were associated with F3, and cases with 11 or more portal tracts with F2 (p = 0.001). Conclusion: this study demonstrated the good quality of liver biopsy and a relationship between the macroscopic size of the fragment and the number of portal tracts.

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Hepatitis D virus infection in the Western Brazilian Amazon - far from a vanishing disease

INTRODUCTION: A decline in hepatitis D virus (HDV) occurrence was described in Europe and Asia. We estimated HDV prevalence in the Brazilian Amazon following hepatitis B vaccination. METHODS: This is a cross-sectional survey of HDV measured by total antibodies to HDV (anti-HD T). RESULTS: HDV prevalence was 41.9% whiting HBsAg carries and was associated with age (PR = 1.96; 95% CI 1.12-3.42; p = 0.01), hepatitis B virus (HBV) infection (PR = 4.38; 95% CI 3.12-6.13; p < 0.001), and clinical hepatitis (PR =1.44; 95% CI 1.03-2.00; p = 0.03). Risk factors were related to HDV biology, clinical or demographic aspects such as underlying HBV infection, clinical hepatitis and age. CONCLUSIONS: Our study demonstrated that HDV infection continues to be an important health issue in the Brazilian Amazon and that the implementation of the HBV vaccination in rural Lábrea had little or no impact on the spread of HDV. This shows that HDV has not yet disappeared from HBV hyperendemic areas and reminding that it is far from being a vanishing disease in the Amazon basin.

Positive serology for viral hepatitis and donor self-exclusion in Southern Brazil

Introduction Despite the great advances in serological testing for transfusion-transmitted infections, the selection of blood donors by blood bank operators remains the only way to avoid transmission within the testing window period. Part of this selection is the self-exclusion form, on which the donors can exclude their blood from donation without any explanation. This study assessed the clinical and epidemiological characteristics related to positivity for viral hepatitis and to the use of the confidential self-exclusion (CSE) form. Methods This transversal study analyzed the data collected from blood donors' files in a hospital in Southern Brazil. Univariate and multivariate analyses identified the clinical and epidemiological variables related to positive serologies of viral hepatitis and to whether the donor was self-excluded. Results Of the 3,180 donors included in this study, 0.1% tested positive for HBsAg, 2.1% for anti-HBc, and 0.9% for anti-HCV. When the 93 donors with positive serologies for viral hepatitis were compared with those who were negative, a greater proportion of the positive serology group was found to have had a history of blood transfusions (OR=4.908; 95%CI=1.628 - 14.799; p<0.01), had repeatedly donated (OR=2.147; 95%CI=1.236 - 3.729; p<0.01), and used the CSE form for self-exclusion (OR=7.139; 95%CI=2.045 - 24.923; p<0.01). No variables were independently associated with self-exclusion. Conclusions A history of blood transfusion, repeated donations, and self-exclusion are factors that should be considered during viral hepatitis screenings in blood banks.

Hepatitis virus and hepatocellular carcinoma in Brazil: a report from the State of Espírito Santo

IntroductionFew studies have examined hepatocellular carcinoma (HCC) in Brazil, and the incidence and risk factors for this type of malignancy vary greatly geographically. In this paper, we report several risk factors associated with HCC diagnosed at the University Hospital in Vitória, ES, Brazil.MethodsWe reviewed 274 cases of HCC (January 1993 to December 2011) in which hepatitis B (HBV) and C (HCV) virus infection and chronic alcoholism were investigated. A diagnosis of hepatocellular carcinoma was confirmed by histology or by the presence of a characteristic pattern on imaging.ResultsHCC with associated liver cirrhosis was noted in 85.4% of cases. The mean ages of men and women were 56.6 years and 57.5 years, respectively. The male-to-female ratio was 5.8:1. Associated risk factors included the following: HBV, 37.6% (alone, 23.4%; associated with chronic alcoholism, 14.2%); HCV, 22.6% (alone, 13.5%; associated with chronic alcoholism, 9.1%), chronic alcoholism, 17.1%, non-alcoholic steatohepatitis, 2.6% and cryptogenic, 19.3%. The male-to-female ratio was higher in cases associated with HBV or chronic alcoholism compared with HCV-associated or cryptogenic cases. In 40 cases without associated cirrhosis, the male-to-female ratio and mean age were lower than those in cirrhosis-associated cases.ConclusionsThese results demonstrate that the main risk factor associated with HCC in the State of Espírito Santo is HBV. Chronic alcoholism is an important etiological factor, alone or in association with HBV or HCV infection.

Occult HBV infection status among chronic hepatitis C and hemodialysis patients in Northeastern Egypt: regional and national overview

INTRODUCTION: Occult hepatitis B infection (OBI) is considered to be one of the major risks for patients suffering from end-stage renal disease (ESRD) on regular hemodialysis (HD) and patients with chronic hepatitis C virus (HCV) infection. This study compared the prevalence of OBI among these two high-risk groups in the Suez Canal region, Northeastern Egypt, to obtain a better national overview of the magnitude of OBI in this region. METHODS: Serum samples were collected from 165 HD patients and 210 chronic HCV-infected patients. Anti-HCV antibody, hepatitis B surface antigen (HBsAg), total hepatitis B core (anti-HBc) antibody, and hepatitis B surface antibody (anti-HBs) were detected by enzyme-linked immunosorbent assay (ELISA). HCV RNA was detected using a quantitative real-time RT-PCR assay, and HBV was detected using a nested PCR. RESULTS: All patients were negative for HBsAg. A total of 49.1% and 25.2% of the patients in the HD and HCV groups, respectively, were anti-HBc-positive. In addition, more anti-HBs-positive patients were detected in the HD group compared to the HCV group (52.1% and 11.4%, respectively). Three cases were positive for HBV DNA in the HD group, while eighteen positive cases were detected in the HCV group. Both study groups showed significant differences in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level as well as anti-HBc, anti-HBs and HBV-DNA positivity. CONCLUSIONS: OBI was more prevalent among chronic HCV patients than HD patients in the Suez Canal region, Egypt, with rates of 8.5% and 1.8%, respectively. However, more precise assessment of this infection requires regular patient follow-up using HBV DNA detection methods.

Determinants of hepatitis A vaccine immunity in a cohort of human immunodeficiency virus-infected children living in Switzerland.

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4(+) T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4(+) T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed.

Prevalence of antibodies to Hepatitis C virus in populations at low and high risk for sexually transmited diseases in Rio de Janeiro

In order to investigate the sexual transmission of the Hepatitis C Virus (HCV), the prevalence of specific antibodies in populations at high and low risk for sexually transmitted diseases (STDs) was evaluated. The population at low risk for STDs was composed of persons who voluntarity donated blood at the Hospital Universitário Clementino Fraga Filho (HUCFF) between July and November, 1990 (n = 2494). The population at high risk for STDs was drawn from an ongoing study on the natural history of Human Immunodeficiency Virus (HIV) infection (n = 210, 187 with sexual risk factors for HIV infection). All samples were screened using a first generation ELISA. Repeat reactive samples were then tested in a second generation RIBA. For all ELISA positive samples, two sex and age-matched ELISA negative controls were selected. Data pertaining to the presence of antibodies to the Hepatitis B core antigen (anti-HBC antibodies) and to Treponema pallidum were abstracted from the medical records. The prevalence of RIBA 2 confirmed HCV infection among the blood donors was 2.08%, which is well above the reported prevalence in similar populations from developed western countries. Among the HIV infected homosexuals, the encountered prevalence was 7.96% (p < 0.0005). For the whole group with sexually acquired HIV infection, the prevalence was 8.02% (p < 0.000005). Anti-HBc antibodies were more frequently present in anti-HCV RIBA-2 confirmed positive blood donors than in controls (p < 0.001). 33.3% of the HCV-positive blood donors and 11.04% controls were found to be anti-HBc positive (p < 0.0005). As for the FTA-ABs, 17.6% HCV-positive donors and 4,9% controls were positive (p < 0.01). 5.9% samples from blood donors were both anti-HBc and FTA-ABS positive, whereas none of the controls reacted in both tests (p < 0.05). The association between HCV, Hepatitis B infection and syphilis in individuals at low risk for parenterally transmitted diseases suggests that sexual transmission contributes to the maintenance of the endemicity of HCV in the local population.