Risk Of Chronic Hepatitis Research Articles

486 INDUSTRIAL, BUT NOT FRUIT FRUCTOSE INTAKE IS INDEPENDENTLY ASSOCIATED WITH SEVERE LIVER FIBROSIS IN GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS

Background and Aims: Many foreign-born persons in the U.S. are at high risk of chronic hepatitis B (HBV) and C (HCV) infections, yet are not aware of their infection, and lack healthcare coverage or linkage to care. Methods: A unique partnership, the Hepatitis Outreach Network, combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene, and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. Comprehensive HBV and HCV screening identifies infected patients, who then receive further evaluation from either local or Mount Sinai physicians, combined with patient-navigators who organize follow-up visits. Results: Of 1603 persons screened, 76 had HBV and 75 had HCV. Importantly, screening for HCV based on traditional risk factors would have missed 67% of those who tested positive. Of the 76 persons with HCV infection, 49 (64%) received a medical evaluation (26 with local providers and 23 at Mount Sinai). Of the 49 HCVinfected persons evaluated, treatment was recommended in 11 and begun in 8 (73%). Of the 76 persons with HBV infection, 43 (57%) received a medical evaluation (31 with local providers and 12 at Mount Sinai). Of the 43 HBV-infected persons evaluated, treatment was recommended and begun in 5 (100%). Conclusion: Hepatitis Outreach Network has successfully established novel proof of concept for identifying HBV and HCV infections in foreign-born persons through use of several unique elements that effectively link them to care.

Immune Responses to Hepatitis C Virus (HCV) Infection and the Prospects for an Effective HCV Vaccine or Immunotherapies

Infection with hepatitis C virus (HCV) typically leads to persistent infection, with >170 million people estimated to be affected worldwide, putting them at risk for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Importantly, 20%-30% of individuals are able to control the virus spontaneously, usually within 6 months of exposure. This suggests that HCV vaccines and immunotherapies are a distinct possibility. We discuss here the role of T cells in controlling HCV, the gaps in our understanding of protective HCV immunity, and the recent introduction of a HCV T-cell vaccine into clinical trials.

Hepatitis B in the United States: A major health disparity affecting many foreign-born populations

In this issue of Hepatology, Kowdley et al. estimate 3.45% or 1.23-1.42 million of all foreignborn persons in the United States, are living with hepatitis B, a rate more than 10-fold higher than the prevalence of the general US population (0.27%) (1). High rates of chronic hepatitis B among the U.S. foreign born reflect the large global burden of hepatitis B, 370 million persons around the world, and the migration to the United States from countries where prevalence of HBV is highest. More than 60% of new immigrants to the United States come from countries of increased hepatitis B endemicity (HBsAg prevalence of >2%). Most HBV-infected persons from these countries become infected at birth or during early childhood, when the risk for chronic HBV infection is greatest; 25% of persons with chronic HBV remain at risk of premature death from hepatitis B-related liver disease (e.g., hepatocellular carcinoma [HCC]) (2). In the United States, estimates of HBV prevalence are derived from the National Health and Nutrition Examination Survey (NHANES). However, this survey underrepresents some populations with high hepatitis B virus (HBV) prevalence. For example, NHANES data do not identify respondents born in most Asian or any African countries or report racial/ethnic categories that indicate origins in these countries (3,4). These limitations in data collection mask Page 1 of 8 Hepatology

The different epidemic and evolution of HCV genotypes

Hepatitis C virus (HCV) is a prevalent and globally distributed human pathogen that currently infects an estimated 170 million people. Chronic HCV infection significantly increases the risk of chronic hepatitis. The virus exhibits a very high degree of genetic diversity that is classified six genotypes and sub-classified more than 80 subtypes by phylogenetic analysis. The various genotypes and subtypes of HCV have been associated with different epidemiological and geographical spread patterns. Genotypes 1 and 2 are globally distributed; genotype 3 is predominant in Asia, North America and parts of Europe; similar regional patterns of endemic diversity have been found for genotype 4 in Europe, Middle East and Central Africa, for genotype 5 in parts of Africa and Europe, and for genotype 6 in Southeast Asia and North America. Up to date, four HCV genotypes, including genotype 1, 2, 3 and 6, were identified in China. Genotypes 1b and 2a were mainly found in Northern China. The fast spreading of genotypes 3 and 6 in Southern and South-Western China was reported by recent studies. It's deduced that Yunnan may become an important source of HCV epidemic and spread, which will cause great changes in the distribution of HCV genotypes and subtypes, and a variety of transmission. With the development of evolution theory and related analysis methods, such as coalescent theory and evolutionary molecular, it is possible to understand the characters of virus evolution and migration. For HCV, the further understanding on the prevalence and evolution characters of various genotypes is very important for the deep investigation of HCV epidemic and the development of prevention strategy.

A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region

We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia's Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P= 6.53 × 10(-22); odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.35-1.74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P= 2.91 × 10(-12); OR = 0.72, 95% CI = 0.63-0.81); and a gene rich HLA Class III interval (rs9267665; P = 1.24 × 10(-17); OR = 2.05, CI = 1.64-2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.

Oncologists and Hepatitis B: A Survey to Determine Current Level of Awareness and Practice of Antiviral Prophylaxis to Prevent Reactivation

Background/Aims: The risk of chronic hepatitis B virus reactivation under the influence of chemotherapy or immunosuppression is being increasingly recognized. However, many oncologists either have not observed this complication or are not aware of current recommendations for hepatitis B prophylaxis. Our aims were to determine the awareness of the reactivation risk and to understand the screening and prevention practices among oncologists. Methods: A questionnaire survey was administered to oncologists in the Washington, D.C., area. Results: Responses from 131 practitioners to the 10 questions were received. Nearly 80% of respondents were aware of reactivation, but only 30% had seen a case and only 56% were aware of prophylactic therapy. Fourteen percent of oncologists screened all patients, whereas 86% screened selectively based on risk factors. Most (76%) would use prophylaxis in a patient with active hepatitis B virus, but only about half would treat chronic carriers or those with resolved infection. Regarding choice of prophylaxis, nearly half (48%) were unsure of which agent to use. Conclusions: Improving awareness of hepatitis B virus reactivation and antiviral prophylaxis in the oncology community seems warranted.

The epidemiology of transfusion‐associated hepatitis C in a children's hospital

Children transfused with blood and blood products before 1992 are at risk for chronic hepatitis C virus (HCV) infection. To determine the prevalence of HCV infection and risks associated with acquisition of HCV, a single-institution lookback study was performed. A total of 5473 infants and children who received transfusions between 1982 and 1992 were identified. A control population of 600 age-, sex-, race- and zip code-matched children who did not receive transfusions with the same exclusions provided background seroprevalence data. Patients were tested for antibodies to HCV, confirmed with second generation recombinant immunoblot assay (RIBA) and when appropriate quantitative and qualitative HCV RNA by reverse transcription polymerase chain reaction (PCR). Viral persistence was assessed by serial PCR determinations for HCV RNA. Of the 5473 eligible patients, 4726 were locatable and 2758 were tested. Forty-three children (1.6%) were persistently anti-HCV enzyme immunoassay (EIA)-positive, confirmed by RIBA; 39 were positive for the presence of HCV RNA. Four cleared their virus as assessed by two negative HCV PCRs 6 months apart. There was a borderline higher number of children with HCV who received fresh whole blood than those who tested HCV-negative. Because HCV infection is generally asymptomatic, children are not identified unless they are specifically tested. We identified, enrolled, tested, and confirmed a new diagnosis of HCV infection in 43 patients. As HCV treatments become increasingly effective, it is important to identify silently infected individuals, particularly when the infection was iatrogenically induced.

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (chi (2) = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3'-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.

The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St Jude Children's Research Hospital hepatitis C seropositive cohort

AbstractChildhood cancer survivors transfused before 1992 are at risk for chronic hepatitis C (HCV) infection. In 1995, St Jude Children's Research Hospital initiated an epidemiologic study of childhood cancer survivors with transfusion-acquired HCV. Of the 148 survivors with HCV confirmed by second-generation enzyme immunoassay, 122 consented to participate in the study. Their current median age is 29 years (range, 9 to 47 years). At enrollment, polymerase chain reaction (PCR) testing indicated chronic infection in 81.1%; genotype 1 was the most common viral genotype. Liver biopsy in 60 patients at a median of 12.4 years from the diagnosis of malignancy showed mild (28.8%) or moderate (35.6%) fibrosis; 13.6% had cirrhosis. Elevated body mass index was associated with histologic findings of increased steatosis (P= .008). Antimetabolite chemotherapy exposure was associated with early progression of fibrosis. Significant quality-of-life deficits were observed in noncirrhotic adult survivors. Antiviral therapy resulted in clearance of infection in 17 (44%) of 38 patients to date. Six patients have died; 1 patient with decompensated cirrhosis died of variceal bleeding. Despite a young age at HCV infection, the progression of liver disease in childhood cancer survivors is comparable to that seen in adults.

Methadone therapy is associated with a reduced risk of chronic hepatitis C virus (HCV) infection in patients who are positive for HCV antibody

Methadone therapy is associated with a reduced risk of chronic hepatitis C virus (HCV) infection in patients who are positive for HCV antibody

The importance of preventing hepatitis C virus infection among injection drug users in the United States.

Injection drug use is the single most important risk factor for acquiring hepatitis C virus (HCV) infection. Injection drug users acquire this infection rapidly after initiating injection practices, and up to 90% of them are chronically infected with HCV. HCV infection is a major cause of chronic liver disease, and persons infected with HCV are at risk for chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they risk transmitting HCV infection to others. Preventive measures for HCV infection are limited. The heterogeneous nature of HCV and its ability to undergo rapid mutation appear to prevent the development of an effective neutralizing immune response, obstructing development of a vaccine. Prevention of HCV infection must rely on educational and programmatic efforts aimed at preventing drug use, providing substance abuse treatment for persons who inject illicit drugs, and encouraging safer injection practices. These efforts should include messages about the risk and prevention of all blood-borne pathogens, including HCV, hepatitis B virus, and human immunodeficiency virus.

Mortality of chromium plating workers in Japan--a 16-year follow-up study

Health hazards due to exposure to chromium in the chromium plating industry has been documented in only a few epidemiological studies. A prospective cohort study was conducted to examine the health hazards of chromium plating with a follow-up period of over sixteen years. Subjects were 1193 male metal platers in the small-scale chromium plating plants in Tokyo. They were divided into a chromium plater subgroup (n = 623) and non-chromium plater subgroup (n = 567) and were followed up from October 1976 through December 1992. The 95% confidence interval (95%CI) of the standardized mortality ratio (SMR) was used to evaluate statistical significance. In the chromium plating subgroup, the risk of chronic hepatitis or liver cirrhosis was significantly elevated (SMR 2.34; 95%CI 1.17-4.19) and a trend toward statistical significance was seen for the risk of lung cancer (SMR 1.18; 95%CI 0.99-3.04). No significantly elevated risk was seen in the non-chromium plating subgroup. We concluded that, as the number of disease-specific deaths was small, further follow-up is necessary.

HEPATITIS C VIRUS INFECTION AND ALLOGENEIC BONE MARROW TRANSPLANTATION

Serum antibodies to hepatitis C virus (HCV) were tested for inpatients undergoing allogeneic BMT to determine the risk of acquiring HCV infection and the role of HCV in posttransplant liver complications. The HCV seroconversion rate was evaluated according to the date of BMT and blood donor screening at the time. Anti-HCV antibodies (anti-HCV) were detected with a second-generation ELISA and confirmed with a second-generation radioimmunoblot assay. All patients received leukocyte-depleted blood products and most received apheresis platelet concentrates. One hundred twenty of 181 consecutive patients transplanted from January 1987 to December 1991 were anti-HCV-negative before BMT, had at least 6 months of follow-up, and were thus evaluated for the seroconversion rate. Before screening for non-A, non-B hepatitis, 14% of the patients seroconverted to HCV (0.44% per unit transfused). After introduction of screening for alanine aminotransferase and antibodies to hepatitis B core antigen the risk of seroconversion was 4% per patient (0.26% per unit). When, in addition, blood was screened for anti-HCV the risk fell to 1.6% (0.03% per unit). Positive anti-HCV status before and after BMT was not predictive of veno-occlusive disease, liver graft-versus-host disease (GVHD), or death due to liver dysfunction. In contrast, the risk of chronic hepatitis was significantly increased.

Non-A, non-B hepatitis; factors involved in progression to chronicity.

A cross-sectional, longitudinal study was undertaken on a group of acute non-A, non-B hepatitis patients, as well as on a control group of hepatitis B patients, in order to assess both the prevalence of the most important factors favoring infection, and the relevance of these factors in promoting evolution towards chronic liver disease. Exposures to unknown risk factors were present in 47.4% of acute non-A, non-B infections, followed by blood transfusions (17.9%), sporadic exposures (17.9%) and drug addiction (16.6%). Unknown as well as sporadic exposures showed a greater prevalence in control population if compared to non-A, non-B cases, while drug addiction was equally represented in the two groups, and blood transfusion nearly absent from control group. The risk of evolution to chronic liver disease was about 13 times greater in non-A, non-B group than in controls, with the greatest risk for drug addicts and the lowest for patients with unknown exposures. Among patients with known exposures, the lowest risk of chronic hepatitis was observed in post-transfusion and in sporadic cases, while the greatest was observed in drug addicts.