Intravenous immunoglobulin and hepatitis C virus: the Boston episode.
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Adolescent↗
Biomedical subjects
M J Alter
Publications and source records attributed to M J Alter.
Effect of immune globulin on the prevention of experimental hepatitis C virus infection.
The efficacy of postexposure prophylaxis for the prevention of hepatitis C virus (HCV) infection was studied in experimentally infected chimpanzees. Three chimpanzees were inoculated with HCV: Two were treated 1 h later with anti-HCV--negative intravenous immune globulin (IGIV) or hepatitis C immune globulin (HCIG), and a third animal was not treated. HCV infection was detected in all 3 animals within a few days of inoculation. Once passively transferred anti-HCV declined in the HCIG-treated animal, there was an increase of HCV antigen (Ag)--positive hepatocytes followed by reappearance of anti-HCV; HCV Ag disappeared concordant with the development of acute hepatitis. Acute hepatitis C developed in both the IGIV-treated and untreated chimpanzees, with peak liver enzyme activity on day 59, but was delayed in the HCIG-treated animal until day 146. Postexposure HCIG treatment markedly prolonged the incubation period of acute hepatitis C but did not prevent or delay HCV infection. IGIV had no effect on the course of HCV infection.
Animals↗
Epidemiology of hepatitis C.
Hepatitis C occurs worldwide and in all age and racial/ethnic groups studied. The most efficient transmission is through percutaneous exposure to infectious blood, but may also occur as a result of inapparent parenteral and mucosal exposure. Although hepatitis C virus may be inefficiently transmitted in some settings, the high rate of persistent infection with this virus creates a large reservoir of persons who are infectious to others, resulting in multiple opportunities for transmission to occur.
Adult↗
Will hepatitis A become a vaccine-preventable disease?
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Adult↗
Epidemiology of hepatitis C in the West.
Most hepatitis C occurs among young adults with high-risk behaviors or lifestyles. Although the most efficient transmission of HCV is through large or repeated percutaneous exposures to infectious blood, transmission also seems to occur through occupational exposure, sexual activity, household contact, and perinatal exposure. The risk of transmission in these settings is most likely dependent on the titer of virus as well as the type and size of the inoculum and the route of transmission. The apparent inconsistency of results between studies is probably a result of the small sample sizes, in that insufficient numbers of infectious persons are included, as well as the variations in methodology and serologic testing. Although HCV may be inefficiently transmitted by inapparent parenteral or mucosal exposures, the high rate of persistent infection with HCV creates a large reservoir of persons who are infectious to others. Current preventive measures, such as donor screening, prevent only a small proportion of the disease. Epidemiologic studies to define the risk of, and the factors facilitating transmission of HCV in other settings, still need to be conducted to develop measures to prevent most disease acquisition.
Chronic Disease↗
Occupational risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections among funeral service practitioners in Maryland.
OBJECTIVE: To estimate the risk of exposure and infection with bloodborne pathogens, a seroepidemiologic survey was conducted among funeral service practitioners (FSPs) in Maryland. METHOD: Of 262 members of the Maryland State Funeral Directors Association, 130 (49%) volunteered to participate in the study. In addition to a brief questionnaire, designed to assess both occupational and non-occupational risk factors for bloodborne pathogen infection, participants were screened for markers of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and past hepatitis B virus (HBV). Titers for antibodies to hepatitis B surface antigen (anti-HBs) also were examined and compared with history of hepatitis B vaccination. RESULTS: Seroprevalence for HIV, HBV, and HCV infection was 0.8%, 4.6%, and 0%, respectively. Nearly 19% of participants reported at least one bloodborne exposure in the past 6 months. The one HIV infection and all but two of the HBV infections were correlated with well-established non-occupational risk behaviors. Disposable gloves were worn by 96%, and eating, drinking, or smoking during embalming were infrequent. Sixty-one percent of FSPs reported having received one or more doses of hepatitis B vaccine at some time in the past. Of those who reported having received all three doses of vaccine, 67% had adequate titers to hepatitis B surface antibody, the marker of protection related to vaccination. CONCLUSION: Compared with prior studies of FSPs, this study found a low rate of occupational exposures and a high rate of hepatitis B vaccination, suggesting improved compliance with recommendations for preventing transmission of bloodborne pathogens in the workplace.
Funeral Rites↗
Liver histology in anti-HCV-positive persons with normal or minimally elevated aminotransferases.
The significance of a positive hepatitis C virus (HCV) screening test in asymptomatic blood donors with normal or near normal aminotransferases was studied along with the usefulness of HCV RNA polymerase chain reaction (PCR) testing for predicting chronic hepatitis in these individuals. One hundred and thirty-nine volunteer blood donors who were found positive by second generation ELISA for antibodies to HCV agreed to participate in the study. Thirty-one of them were supplemental test positive, had ALT values less than twice normal, and were followed over a minimum of 12 months. Thirteen consented to percutaneous liver biopsy and also had HCV RNA determination by PCR. Ten of the 13 subjects were positive for HCV RNA by PCR. Of the nine who were positive for HCV RNA and had adequate tissue for evaluation, seven had evidence of chronic hepatitis, three with limiting plate necrosis. Lobular inflammation was similar in severity to that found in the portal region. In addition, two had periportal fibrosis, and one had bridging fibrosis. Of the three subjects who were negative for HCV RNA, only one had portal inflammation which was limited to the portal region. None of these three had lobular changes, or periportal or bridging fibrosis. Of the three normal biopsies, two were from subjects who were negative for HCV RNA. The sensitivity and specificity of HCV RNA testing for chronic hepatitis was 87.5% and 50%, respectively, yielding an overall accuracy of 75%. We conclude that asymptomatic blood donors with antibodies to HCV, normal or mildly elevated liver tests, and HCV RNA may have abnormal liver histology indicating the potential for progressive liver disease. HCV RNA testing by PCR may be clinically useful as a noninvasive means to discriminate between those with and without chronic liver disease.
Biopsy↗
Reduced risk of hepatitis B and hepatitis C among injection drug users in the Tacoma syringe exchange program.
OBJECTIVES: This case-control study examined the association between syringe exchange use and hepatitis B and C in injection drug users. METHODS: Case patients included 28 injection drug users with acute hepatitis B and 20 with acute hepatitis C reported to the health department in a sentinel hepatitis surveillance county; control subjects were injection drug users with no markers of exposure to hepatitis B or C (n = 38 and 26, respectively) attending health department services during the same period. Data were abstracted from clinic records. RESULTS: Seventy-five percent of case patients with hepatitis B and 26% of control subjects had never used the exchange; similar proportions were found for the hepatitis C case and control groups. After adjustment for demographic characteristics and duration of injecting drugs, nonuse of the exchange was associated with a sixfold greater risk of hepatitis B (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 1.5, 20.4) and a sevenfold greater risk of hepatitis C (OR = 7.3; 95% CI = 1.6, 32.8). CONCLUSIONS: The results suggest that use of the exchange led to a significant reduction in hepatitis B and hepatitis C in the county and may have also prevented a substantial proportion of human immunodeficiency virus infections in injection drug users.
Acute Disease↗
Hepatitis B virus infection in high-risk inner-city neighborhoods in San Francisco.
To examine the extent of hepatitis B virus infection (HBV) in an inner-city community, we determined the prevalence, incidence, and correlates of HBV seroreactivity in a representative sample of unmarried whites, African-Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. Unmarried men and women aged 20 to 44 years were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Hepatitis B infection was determined by testing specimens for antibody to hepatitis B core antigen (anti-HBc). Of blood samples available from 1,108 participants from the initial survey, 159 (14%) were anti-HBc positive. There was a strong positive association between anti-HBc positivity and positive serological tests for human immunodeficiency virus, herpes virus type 2, and syphilis. In women and heterosexual men, after controlling for other variables, anti-HBc positivity was significantly associated with older age (P < .001), nonwhite ethnicity (P < .01), less education (P < .05), injection drug use (P < .001), being paid for sex (P < .05), and lifetime number of sexual partners (P < .05). Among homosexually active men, after controlling for other variables, anti-HBc positivity was significantly associated with nonwhite ethnicity (P < .001), injection drug use in a sexual partner (P < .05), and number of lifetime sexual partners (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Transmission of hepatitis C virus--route, dose, and titer.
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Female↗
Enzyme immunoassay for the detection of antibody to hepatitis E virus based on synthetic peptides.
Five synthetic peptides were prepared based on the nucleotide sequence of open reading frames 2 and 3 encoded in the hepatitis E virus (HEV) genome and were used to develop an enzyme immunoassay (EIA) for the detection of anti-HEV activity in sera. Three different approaches were employed to ascertain the optimal preparation of these peptides as an immunodiagnostic reagent, including (1) a mixture of unconjugated peptides, (2) conjugating individual peptides to bovine serum albumin (BSA) followed by mixing each conjugate at various concentrations, and (3) mixing the peptides before conjugation with BSA to create an artificial antigen complex. The third method was superior in discriminating anti-HEV activity in sera previously tested by Western blot (WB). A frequency distribution of optical density values demonstrated that the peptide-based EIA was able to readily discriminate anti-HEV positive sera from sera devoid of anti-HEV activity. To confirm anti-HEV activity a neutralization test was developed using a mixture of 5 unconjugated peptides. With the exception of sera containing high levels of anti-HEV activity, all sera were neutralized greater than 50%. Strong sera required a higher dilution before a 50% neutralization was achieved. The sensitivity of the WB compared to EIA was 89.5% with and overall concordance of 94.8%. The peptide-EIA was used to determine anti-HEV activity in sera collected from various populations worldwide. In six outbreaks of ET-NANB hepatitis in various geographic regions, anti-HEV activity was demonstrated in 78-100% of cases. The peptide-EIA also detected anti-HEV activity in 14 out of 14 follow-up sera obtained 4-6 months after onset of disease and in 2 of 2 of these patients 5 yr after the acute episode. Anti-HEV activity was found in 8.5% of sera obtain from a healthy population residing in an HEV endemic region and 0.5% in two non-endemic regions (P < 0.001). These data demonstrate that a synthetic peptide-based EIA is sensitive for detecting anti-HEV activity in the sera of patients with acute hepatitis E, convalescents, and among healthy individuals.
Acute Disease↗
Hepatitis C virus infection in sexually active homosexual men.
While hepatitis C virus (HCV) is known to be transmitted parenterally, the role of sexual transmission remains unclear. In order to examine the association of sexual risk factors with HCV seroprevalence at a time when unprotected sexual practices were still quite common, 435 homosexual men recruited from a municipal sexually transmitted disease clinic with behavioural data and serologic specimens from 1983-1984 were evaluated. Overall, 25% of men reporting injecting drug use (IDU) and 5% of men with no IDU were anti-HCV positive; the rate in the non-IDU was significantly higher than age-matched rates in blood donors (summary odds ratio 3.5, 95% confidence interval 2.8-4.2). In addition to IDU, amphetamine and phencyclidine use were also associated with anti-HCV positivity on univariate analysis. Sexual risk factors for anti-HCV positivity included anal receptive intercourse, 'fisting', having an IDU sexual partner, a self-reported history of genital herpes and HIV seropositivity. On multivariate analysis, only IDU was significantly associated with anti-HCV positivity. Thus, sexual practices appear to play a minor role in transmission of HCV.
Cohort Studies↗
Multiple unconfirmed-reactive screening tests for viral antibodies among blood donors.
BACKGROUND: In December 1991, the United States Food and Drug Administration received reports of blood donations with unconfirmed reactivity on screening tests for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus (HCV). Of 91 donors with these test results, 57 (63%) reported a recent influenza vaccination. STUDY DESIGN AND METHODS: To determine the extent of unconfirmed reactivity, the time at which it began, and its association or nonassociation with specific manufacturers' tests, a nationwide survey of blood centers was conducted. A case-donation was defined as a blood donation that was repeatedly reactive, but not confirmed positive, on at least two of the three tests from May 1990 through December 1991. RESULTS: Among 14 million donations screened by 110 centers, 582 case-donations were identified. An increase in case-donations was evident in the fall of 1990 (2.8/100,000 donations). In 1991, rates increased from 0.9 per 100,000 donations in the first quarter to 1.3, 3.2, and 19.7 in subsequent quarters. A significantly higher rate of case-donations was observed among donations tested with one of the two available anti-HCV screening tests (8.0 vs. 1.2/100,000 donations; risk ratio = 6.8; 95% CI = 5.4-8.5). CONCLUSION: Although unconfirmed reactivity on multiple screening tests appeared to be seasonal, its documentation prior to the availability of influenza vaccine in 1991 and higher rates among donations tested with one manufacturer's anti-HCV test indicated that test-specific factors were also involved.
Antibodies, Viral↗
Occupational exposure to hepatitis C virus: a dilemma.
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Chronic Disease↗
Hepatitis C, hepatitis B, and human immunodeficiency virus infections among non-intravenous drug-using patients attending clinics for sexually transmitted diseases.
The seroprevalences of and risk factors for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis were determined among 1257 consecutive non-intravenous drug-using patients attending Baltimore sexually transmitted diseases clinics: 122 (9.7%) had antibodies to HCV (anti-HCV), 192 (15.3%) had antibodies to HBV (anti-HBc), 44 (3.5%) had antibodies to HIV (anti-HIV), and 60 (4.8%) were seropositive for syphilis. For males, independent predictors of anti-HCV were age > 29 years and lack of condom use in the month before their visit. Males with any one serologic marker (anti-HCV, anti-HBc, anti-HIV, or syphilis) were more likely to have each of the other markers. For females, anti-HCV was independently associated with age > 29 years and > 1 male sex partner in the prior month. Females with anti-HIV or anti-HBc were more likely to have anti-HCV. These observations among non-intravenous drug-using patients suggest that sexual transmission of HCV may occur.
Adolescent↗
Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation.
Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.
Adolescent↗
Review of serologic testing for hepatitis C virus infection and risk of posttransfusion hepatitis C.
Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis and cirrhosis worldwide. Screening volunteer donors for antibody to HCV (anti-HCV) has reduced the risk of posttransfusion hepatitis C to less than 1.0% per recipient. Virtually all persons with acute HCV infection seem to become chronically infected, and an average of 67% acquire chronic liver disease with persistently elevated liver enzyme values. Among anti-HCV-positive blood donors, 70% to 90% are HCV RNA positive, but less than half have biochemical evidence of liver disease. The extraordinarily high rate of persistent infection observed in humans and the lack of protection against rechallenge with homologous HCV strains demonstrated in experimental studies in chimpanzees suggest that HCV fails to induce an effective neutralizing antibody response. This raises major concerns for the development of effective passive or active immunoprophylaxis against hepatitis C.
Blood Donors↗
The epidemiology of viral hepatitis in the United States.
Hepatitis types A, B, and C are the most important forms of viral hepatitis in the Unites States. High-risk sexual and drug use behavior have been associated with epidemics of hepatitis A and endemic transmission of both hepatitis B and hepatitis C. Immune globulin preparations and vaccines have been developed that effectively prevent hepatitis A and hepatitis B. In the absence of such preventive measures, the prevention of hepatitis C will depend on a better understanding of the host and environmental factors that facilitate transmission of this disease.
Hepatitis A↗