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Biomedical subjects

M J Alter

Publications and source records attributed to M J Alter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Protective effect of hepatitis B vaccine in chronic hemodialysis patients.

Hepatitis B virus (HBV) infection is a well-recognized risk in chronic hemodialysis patients. Although the risk has declined dramatically since the 1970s, outbreaks of HBV infection among these patients continue to occur. The Centers for Disease Control and Prevention (CDC) has recommended hepatitis B vaccination of hemodialysis patients since 1982; however, by 1996, only 36% of the approximately 200,000 US chronic hemodialysis patients had received the vaccine, perhaps in part because of doubts among dialysis personnel of its efficacy. We performed a case-control study to determine whether receipt of hepatitis B vaccine was associated with a decreased risk of acquiring HBV infection. We determined the vaccination status of all chronic hemodialysis patients at 98 US hemodialysis centers that reported patients with acute HBV infection on a nationwide mailed survey in 1995. A total of 111 hepatitis B surface antigen (HBsAg) positive case patients were compared with 12,500 control patients. Case patients were significantly less likely than control patients to have received hepatitis B vaccine (10.8% v 23.6%; odds ratio, 0.39; 95% confidence interval, 0.22-0.72). After stratifying by dialysis center to control for differing community and dialysis center risks of HBV infection, we found that the risk for HBV infection was 70% lower in vaccinated patients (adjusted odds ratio, 0.30; 95% confidence interval, 0.18-0.50). These results suggest that hepatitis B vaccine has a significant protective effect against acquiring HBV infection in chronic hemodialysis patients, and efforts should be expanded to increase the use of hepatitis B vaccine in this patient population.

Adult↗
PubMed1999

An outbreak of hospital-acquired hepatitis B virus infection among patients receiving chronic hemodialysis.

OBJECTIVE: To investigate a cluster of hepatitis B virus (HBV) infections between December 1995 and May 1996 among chronic hemodialysis patients in one county. SETTING: Two dialysis centers (A and B) and a hospital (C) in one county. PATIENTS: Six case-patients who were dialyzed in one of two centers, A and B, and had all been hospitalized between January and February 1996 at hospital C. METHODS: Patient 1, usually dialyzed in center A, sero-converted to hepatitis B surface antigen (HBsAg) in December 1995 and could have been the source of infection for the others, who seroconverted between March and April 1996. Two cohort studies were conducted: one among patients dialyzed in center A, to determine where transmission had occurred, and one among patients dialyzed at hospital C at the time patient 1 was hospitalized, to identify factors associated with infection. RESULTS: Four (15%) of the 26 susceptible patients dialyzed at center A became infected with HBV. Hospitalization at hospital C when patient 1 was hospitalized was associated with infection (P = .002). A cohort study of the 10 susceptible patients dialyzed at hospital C during the time patient 1 was hospitalized did not identify specific risk factors for infection. However, supplies and multidose vials were shared routinely among patients, providing opportunities for transmission. CONCLUSION: When chronic hemodialysis patients require dialysis while hospitalized, their HBsAg status should be reviewed, and no instrument, supplies, or medications should be shared among them.

Cohort Studies↗
PubMed1999

Hepatocellular carcinoma not related to hepatitis B virus infection among Alaska natives.

Chronic infection with hepatitis B or C viruses is a common underlying condition in patients with hepatocellular carcinoma worldwide. We studied serum and liver tissue from a cohort of Alaska natives with hepatocellular carcinoma (HCC) for evidence of hepatitis B, C and G viral infection using conventional serological tests as well as the sensitive polymerase chain reaction. Evidence of HBV infection was found in 25 and possible HCV infection in two cases. Among the remaining 11 patients, four had a history of recent or remote alcoholism while seven had no recognizable risk factors for HCC. Only one was seropositive for HGV RNA and that was an individual with a history of alcoholism. Non-tumorous liver tissue was available for study in six of these seven cases. Histological features of chronic hepatitis were present in five. Thus, at least five of 38 (13%) Alaska natives with HCC appeared to have chronic hepatitis not related to HBV or HCV infection, suggesting the possibility of some form of previously unrecognized chronic liver disease predisposing to HCC.

Adolescent↗
PubMed1998

Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group.

Few data are available to evaluate the performance of existing assays for antibody to the hepatitis E virus (anti-HEV). A panel of 164 randomized and coded sera was tested for anti-HEV by 12 different assays. The panel included a dilution series of an early convalescent human serum, known-positive sera (undiluted human sera obtained 2 months to 13 years after acute hepatitis E, and postinoculation chimpanzee sera), known-negative sera (preinoculation chimpanzee sera; sera from chimpanzees with hepatitis A virus, hepatitis B virus, or hepatitis C virus infection; and normal human sera), and sera obtained from previously tested U.S. blood donors without a history of hepatitis. Six tests detected anti-HEV in > or =90% of undiluted known-positive sera. The sensitivity of all of the assays with known-positive sera ranged from 17% to 100%, and the limit of detection by endpoint dilution ranged from 1:5 to 1:160. Ten tests were nonreactive for all of the 22 known-negative sera, one test was reactive for one serum, and one test was reactive for 5 sera. In pairwise comparisons of different tests in blood donor sera, the overall concordance ranged from 49% to 94% (median, 69%) and the concordance among reactive sera ranged from 0% to 89% (median, 32%). Several of these tests performed well in detecting anti-HEV in known positive sera. However, highly discrepant results among U.S. blood donor sera indicate that anti-HEV seroprevalence data in non-HEV-endemic countries may be unreliable and should be interpreted with caution.

Animals↗
PubMed1998

Hepatitis A virus sequence detected in clotting factor concentrates associated with disease transmission.

Since the early 1990s hepatitis A virus (HAV) infections among recipients of solvent-detergent treated factor VIII concentrates have occurred in Europe, South Africa and the United States. A review of the epidemiological and laboratory-based investigations of the outbreaks in Germany and Ireland were consistent with transmission by factor concentrates but limited information about transmission based upon nucleic acid sequences was obtained, and no clear chain of transmission could be established. Within the United States, hepatitis A infections associated with solvent detergent concentrate occurred in a single patient in 1993, and a cluster of cases in 1995. Although the 1993 factor concentrate was positive for virus, samples from the patient were not available. The virus present in the cluster of 1995 factor VIII patients, the factor concentrate they received, and the original plasma pool was identical, while the virus identified in the factor IX patient differed by a single base.

Detergents↗
PubMed1998

Hepatitis B vaccination of adolescent and adult high-risk groups in the United States.

Substantial progress has been made in implementing routine infant hepatitis B vaccination in the United States. However, in 1996, an estimated 65,000 acute hepatitis B cases occurred, the majority of which were among young adults in high-risk groups. Recent surveys have found very low vaccination coverage among several high-risk groups, including men who have sex with men and patients with sexually transmitted diseases (STDs). Targeted vaccination of persons with risk factors for hepatitis B virus (HBV) infection can be provided in a variety of settings including family planning clinics, STD clinics, drug treatment centres, detention centres, jails and prisons. However, vaccination programmes have been infrequently implemented in these settings and the majority of persons with acute hepatitis B cases have had a missed opportunity for vaccination in the past. Thus, in order to accelerate elimination of HBV transmission in the United States, increased efforts are needed to implement effective hepatitis B vaccination programmes targeted to adolescents and adults in high-risk groups.

Adolescent↗
PubMed1998

Progress toward elimination of hepatitis B virus transmission in the United States.

The strategy to eliminate hepatitis B virus (HBV) transmission in the United States is comprised of the following components: (1) preventing perinatal transmission, (2) routine infant vaccination, (3) catch-up vaccination of children in high-risk groups at any age, (4) catch-up vaccination of all children at 11-12 years of age and (5) vaccination of adolescents and adults in high-risk groups. According to recent surveys, > 85% of pregnant women are screened for hepatitis B surface antigen (HBsAg). Of infants born to HBsAg-positive women identified in 1995, 93% received appropriate immunoprophylaxis at birth; however, only 69% were fully vaccinated by 6-8 months of age. From 1991 (when routine infant hepatitis B vaccination was first recommended) to 1996, the proportion of 19-35-month-old children who have received three doses of hepatitis B vaccine has increased from < 10 to 83%. During this time, rates of acute hepatitis B in children 7-10 years of age have declined by 27% and rates among children 3-6 years of age have declined by 62%. Implementation of programmes for catch-up vaccination of all adolescents at 11-12 years of age and for vaccination of adolescents and adults in high-risk groups have only recently begun and no data are available to assess the progress of these programmes. However, 26% (13/50) of states now have laws requiring adolescents to be vaccinated in order to enter school. Current data indicate that substantial progress has been made in implementing a strategy to eliminate HBV transmission in the United States. Future efforts need to be focused on improving complete immunoprophylaxis of infants of HBsAg-positive mothers, increasing vaccine coverage among 11-12 year old children and implementing programmes to vaccine adolescents and adults in high-risk groups.

Adolescent↗
PubMed1998

Hepatitis C.

Hepatitis C virus (HCV) has emerged as a major cause of chronic liver disease worldwide. The widespread endemicity of HCV infection is the result of a combination of factors, including those related to the genetic diversity of the virus and the host response and those related to the specific settings and behaviors that have facilitated transmission. Most people who contract HCV infection become persistently infected, and the mechanism by which persistent infection is established seems to be related to the lack of development of an effective neutralizing immune response. The magnitude of the spread of HCV infection primarily is related to specific risk factors for transmission. The most important human behavior related to the transmission of HCV has been injection drug use, which in many developed countries has been the leading source of HCV infection during the past 20 to 30 years. The recognition of the clinical importance of HCV infection has resulted in a substantial amount of attention and resources rapidly directed toward developing new and improved therapies. The perception, however, of the public health importance of HCV infection is still limited. Despite the knowledge that injection drug use is the major source of HCV infection in the United States, this message has not been included in prevention and treatment programs, and the resources needed to support strong public health programs have yet to be identified.

Antiviral Agents↗
PubMed1998

The diverse patterns of hepatitis A epidemiology in the United States-implications for vaccination strategies.

Hepatitis A is the most frequently reported vaccine-preventable disease in the United States. Hepatitis A incidence and risk factors during 1983-1995 were examined among cases reported to the study's Sentinel Counties: Denver County, Colorado; Pierce County, Washington; Jefferson County, Alabama; and Pinellas County, Florida. Of 4897 serologically confirmed cases, 611 patients (13%) were hospitalized and 9 (0.2%) died. The average incidence was 14.7/100, 000 (range, 0.6-100.7/100,000, depending on county and year). The frequency of reported sources of infection varied by county, but the largest single group overall (52%) did not report a source. During 3-year communitywide outbreaks in Denver (1991-1993) and Pierce (1987-1989) Counties, rates increased 4- and 13-fold, respectively, and increased in all age, racial/ethnic, and risk groups. During communitywide outbreaks, hepatitis A is not limited to specific risk groups; sustained nationwide reductions in incidence are more likely to result from routine childhood vaccination than from targeted vaccination of high-risk groups.

Adolescent↗
PubMed1998

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.

Centers for Disease Control and Prevention, U.S.↗
PubMed1997

Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection. Sentinel Counties Viral Hepatitis Study Team.

BACKGROUND: Little is known about the relation of the newly discovered hepatitis G virus (HGV) to the cause and clinical course of acute and chronic viral hepatitis. METHODS: We selected patients from a surveillance study of acute viral hepatitis in four U.S. counties who had acute disease during 1985 to 1986 or 1991 to 1995. Serum samples were tested for HGV RNA by the polymerase chain reaction. RESULTS: HGV RNA was detected in 4 of 45 patients with a diagnosis of non-A-E hepatitis (9 percent), 23 of 116 patients with hepatitis C (20 percent), 25 of 100 patients with hepatitis A (25 percent), and 32 of 100 patients with hepatitis B (32 percent) (P<0.05 for the comparison of hepatitis B with hepatitis non-A-E or C). The clinical characteristics of the acute illness were similar for patients with HGV alone and those with hepatitis A, B, or C with or without HGV infection. During a follow-up period of one to nine years, chronic hepatitis did not develop in any of the patients with HGV alone, but 75 percent were persistently positive for HGV RNA, as were 87 percent of those with both hepatitis C and HGV infection. The rates of chronic hepatitis were similar in patients with hepatitis C alone (60 percent) and those with both hepatitis C and HGV infection (61 percent). CONCLUSIONS: The evidence from this surveillance study does not implicate HGV as an etiologic agent of non-A-E hepatitis. Persistent infection with HGV was common, but it did not lead to chronic disease and did not affect the clinical course in patients with hepatitis A, B, or C.

Acute Disease↗
PubMed1997

Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA.

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities raise two theoretical questions. First, could HGV coinfection play any role in the response of HCV to antiviral therapy and second, would this coinfected population have changes in serum HGV-RNA induced by interferon. To address these questions, 98 patients with documented chronic HCV underwent interferon therapy (3 million units three times a week) for 6 months. Response to therapy was categorized using standard biochemical criteria. Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%) patients with HCV infection had detectable serum HGV-RNA. There was no difference between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT) values, HCV-RNA levels, HCV genotype, histological severity, or other demographic features were analyzed. Interferon response was similar in both groups and HGV was not associated with outcome following therapy. Antiviral therapy appeared to induce a reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In two patients, the fall in serum HGV-RNA correlated with biochemical response, independent of changes in HCV-RNA. These observations indicate that a larger study of an HGV population is required to more clearly define the relationship between HCV and HGV coinfection and their response to antiviral therapy.

Aged↗
PubMed1997

Epidemiology of hepatitis C.

In the United States, the annual number of newly acquired acute hepatitis C virus (HCV) infections has declined from an estimated 180,000 in the mid 1980s to an estimated 28,000 in 1995. Approximately 25% to 30% of these infections are clinically apparent cases that are sufficiently symptomatic to gain medical attention. Deaths from fulminant hepatitis C are rare. The prevalence of antibody to HCV (anti-HCV) in the general population of the United States is 1.8%, corresponding to an estimated 3.9 million Americans infected with HCV, and an estimated 8,000 to 10,000 deaths each year result from HCV-associated chronic liver disease. HCV infection affects persons of all ages, but most acute cases of hepatitis C and the highest prevalence of anti-HCV are found among young adults. The highest proportion both of incident cases and prevalent infections is among whites, but the highest incidence and prevalence rates are among non-white racial/ethnic groups. In the past, transfusion of blood and blood products was an important source of HCV transmission, but currently, high-risk drug and sexual exposures account for most HCV transmission. Although the incidence of acute hepatitis C has declined, there is a large reservoir of chronically infected Americans who can serve as a source of transmission to others and who are at risk of the severe consequences of chronic liver disease.

Hepatitis C↗
PubMed1997

The epidemiology of acute and chronic hepatitis C.

Although the incidence of newly acquired acute hepatitis C virus (HCV) infection has declined, an estimated 3.9 million Americans are chronically infected with HCV, most of whom are young adults who will be at risk of the severe consequences of their infection in the next 10 to 20 years. The relative importance of the two most common exposures associated with the transmission of HCV has changed over time. Blood transfusions, which account for a substantial proportion of HCV infections acquired more than 10 years ago, account for only a small portion of recently acquired infections. In contrast, injection drug use has accounted for a substantial portion of HCV infections during both the remote and recent past. Sexual exposures, which have been poorly ascertained particularly among patients with chronic hepatitis C, may account for 10% to 20% of HCV transmissions. Physicians and other health care professionals need to be educated not only about the appropriate medical management of HCV infected patients, but also about the known and potential risks for HCV infection, the need to ascertain complete risk behavior histories from their patients, the appropriate evaluation of high-risk patients for evidence of infections, and the recommendations for prevention.

Acute Disease↗
PubMed1997

Sequence variation within a nonstructural region of the hepatitis G virus genome.

Nine sets of nested PCR primers from a 2.6-kb region of the hepatitis G virus (HGV) genome at nucleotide positions 5829 to 8421 were designed and used to analyze serum specimens obtained from patients with community-acquired non-A, non-B hepatitis who were HGV RNA positive. One set of primers was found to be most efficient in detecting HGV and was subsequently used to test 162 HCV-positive and 11 HCV-negative plasma units obtained from individual paid donors. HGV RNA was detected in 30 (17.3%) plasma units, 2 of which were found among the 11 HCV-negative specimens. A complete set of nine PCR fragments was obtained from two patients with community-acquired acute non-A, non-B hepatitis and from four paid donors. All PCR fragments were sequenced and were shown to have a nucleotide similarity of 85.9 to 92.3% and a derived amino acid similarity of 96.0 to 99.0%. The majority of nucleotide changes occurred in the third position of codons. The HGV nucleotide and protein sequences obtained in this study were compared with HCV sequences. Based on this analysis the 2.6-kb fragment was predicted to encode the C-terminal part of the putative NS4b, the entire NS5a, and almost the complete NS5b proteins. Putative protease cleavage sites separating these proteins were also predicted. In serial specimens obtained from the two HGV-infected patients, no significant variations were found in the HGV nucleotide and derived amino acid sequences over time. The HGV sequences obtained from one patient showed no changes over 6 months, whereas more than 99.0% homology was observed for sequences from the second patient over 2.5 years. Heterogeneity analysis performed on 10 sequences obtained in this study and corresponding regions from 6 known full-size sequences of the HGV genomes demonstrated notable discrete heterogeneity consistent with the existence of HGV genetic groups or types.

Amino Acid Sequence↗
PubMed1996

Hepatitis C virus infection associated with administration of intravenous immune globulin. A cohort study.

OBJECTIVE: To determine the risk of and risk factors for hepatitis C virus (HCV) infection among persons with immune deficiencies who had received intravenous immune globulin (IGIV) between March 1993 and February 1994. DESIGN: Retrospective cohort study. SETTING: An immunology program in a tertiary care hospital. PATIENTS: Of 341 persons who had received IGIV between March 1, 1993, and February 22, 1994, 278 (82%) were enrolled. The mean age for the enrolled persons was 9 years, and 99% had primary immune deficiencies. MAIN OUTCOME MEASURES: Evidence of HCV infection by detection in sera of antibody to HCV and/or HCV RNA by reverse transcriptase polymerase chain reaction. RESULTS: Twenty-three (11%) of 210 persons who received the IGIV Gammagard (Baxter Healthcare Corporation, Deerfield, Ill) became infected compared with none of 52 persons who received exclusively other IGIV products (P=.01). In a multivariate analysis, HCV infection was associated only with Gammagard produced from plasma screened by second-generation (multiantigen) anti-HCV tests (P=.03). Hepatitis C virus RNA was detected in Gammagard, and the risk of transmission to recipients increased with increasing quantity of HCV RNA infused, from 0 for those who received no HCV RNA-positive lots to 29% for the quartile of patients receiving the greatest amount (P<.001). At least 9 different lots of Gammagard were required to account for all cases. CONCLUSION: Gammagard was the only IGIV product implicated in the transmission of HCV. Infection was associated with higher quantities of HCV RNA in Gammagard produced from second-generation anti-HCV-screened plasma. Further studies are needed to determine reasons for the infectivity of Gammagard, and viral inactivation and removal steps are needed to ensure the safety of IGIV products.

Alanine Transaminase↗