The emerging clinical significance of hepatitis C.
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Genome, Viral↗
Biomedical subjects
R D Aach
Publications and source records attributed to R D Aach.
Alcohol and other substance abuse and impairment among physicians in residency training.
Substance abuse and impairment are serious societal problems. Physicians have historically had high rates of substance abuse, which has been viewed as an occupational hazard. Most authorities agree that the rate of alcoholism among practicing physicians is similar to that among control populations and that the rates of other substance abuse are greater, although some studies have shown no difference. Data about substance abuse among residents in training are limited but suggest that the use of benzodiazopines is greater than that among age-matched peers, whereas the use of alcohol is similar between the two groups. Medical institutions, including those with teaching programs, have legal and ethical responsibilities concerning substance abuse among current and future physicians. Many training programs, however, do not provide educational programs on this subject, do not have faculty trained in substance abuse medicine, and do not have a formal system to address the problem of residents who are suspected or known to be substance abusers. This position paper examines the extent of substance abuse, including alcohol abuse, among physicians in residency training. It outlines approaches to the problem and delineates responsibilities of institutions and residency program directors. Recommendations are made to establish an informational program and a clearly defined, organized process to address the problems of substance abuse among residents. Careful and humane approaches can be used to identify and treat residents with substance abuse problems and thus allowing them to complete their training as competent and drug-free professionals.
Alcoholism↗
Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays.
BACKGROUND: The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. METHODS: We used two first-generation enzyme-linked immunoassays (EIAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. RESULTS: Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatitis developed in these 111 patients, the first-generation EIAs detected anti-HCV in 51 (46 percent), and the second-generation assay detected anti-HCV in an additional 16 (14 percent), for a total of 60 percent. Of 40 controls, 37 were anti-HCV-negative initially, and none seroconverted after hepatitis developed. If the 3 percent rate of non-A, non-B, non-C hepatitis among the controls (37 of 1235) was applied to the 1247 transfusion recipients, only 74 of the 111 cases of hepatitis were attributable to the transfusion. Thus, 91 percent (67 of 74) of the cases of post-transfusion hepatitis were caused by HCV. Of the 99 donors, 60 were HCV-positive (9 on second-generation tests only) and 39 were not. CONCLUSIONS: Nearly all cases of non-A, non-B post-transfusion hepatitis are caused by HCV. Screening with a second-generation assay improves the rate of detection of HCV infection in patients with post-transfusion hepatitis and in blood donors. The use of this test showed a 3.6 percent risk of non-A, non-B, non-C hepatitis, which was not significantly different from the rate in the controls (3.0 percent).
Blood Donors↗
Non-A, non-B hepatitis and antibody to hepatitis C virus.
Stored serum samples from the Transfusion-transmitted Viruses Study in the 1970s were tested for the presence of antibody to hepatitis C virus (anti-HCV). Single specimens from five control subjects who did not receive transfusions tested negative for anti-HCV. Of four control subjects who did not receive transfusions and who developed non-A, non-B (NANB) hepatitis after hospitalization, three remained anti-HCV negative; the fourth person with postoperative NANB hepatitis tested anti-HCV positive before the operation. Five transfusion recipients with posttransfusion hepatitis B virus infection remained seronegative; a sixth with NANB hepatitis as well as hepatitis B virus infection had seroconversion for anti-HCV. Five of nine transfusion recipients with NANB hepatitis had anti-HCV seroconversion. These results show that present anti-HCV testing demonstrates an etiologic basis for approximately half of the cases of transfusion-associated NANB hepatitis, particularly those that develop chronicity. Although cases of NANB hepatitis without seroconversion may be explained otherwise, they may be caused by another, presently unidentified, virus.
Blood Transfusion↗
The treatment of chronic type B viral hepatitis.
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Carrier State↗
Hepatitis B virus antibody in blood donors and the occurrence of non-A, non-B hepatitis in transfusion recipients. An analysis of the Transfusion-Transmitted Viruses Study.
Patients who received transfusions and nontransfused control patients were followed to assess the incidence and cause of post-transfusion hepatitis and to identify donor factors that might relate to risk of hepatitis. We evaluated as risk factors in donors the presence of antibody to hepatitis B virus compared with elevated alanine aminotransferase (ALT) level. Units of blood that were positive for antibody to hepatitis B core antigen (anti-HBc) were associated with a twofold to threefold greater risk of non-A, non-B hepatitis in the recipients than were units without anti-HBc. In the absence of specific serologic tests for non-A, non-B agents, screening of donors for anti-HBc might be considered. Our data suggest that the incidence of non-A, non-B hepatitis might have been reduced by about one third by such screening. However, elevated ALT levels in donors had a similar association with non-A, non-B hepatitis in recipients but would have resulted in fewer units of blood being discarded than would screening for anti-HBc.
Alanine Transaminase↗
Use of conventional and IgM-specific radioimmunoassays for anti-hepatitis A antibody in an outbreak of hepatitis A.
During a common source outbreak of hepatitis A, we studied the characteristics and utility of commercially available radioimmunoassays for total and IgM-specific antibody to hepatitis A virus. IgM hepatitis A antibody was detectable in all serum specimens obtained up to 119 days following onset from the seven persons with hepatitis A, and as long as 347 days in one person. Acute infection could also be documented by a four-fold or greater increase in titers of hepatitis A antibody, although as long as nine weeks was required between the times acute and convalescent specimens were obtained. The radioimmunoassay for IgM-specific hepatitis A antibody had greater specificity (99 percent versus 84 percent) and a higher positive prediction value (88 percent versus 23 percent) for the diagnosis of acute hepatitis A than did the radioimmunoassy for hepatitis A antibody. Uses of the radioimmunoassay for IgM-specific hepatitis A antibody include rapid diagnosis of acute hepatitis A, differentiation between recent and past hepatitis A infection, and screening for recent hepatitis A infection in epidemiologic investigation.
Adult↗
The distribution of serum alanine aminotransferase levels in a blood donor population.
The authors studied the distribution of alanine aminotransferase (ALT) levels in 10,034 volunteer blood donors. The mean +/- SD ALT value was 21.4 +/- 19.3 IU/liter; 549 (5.5%) of the donors had a ALT value greater that 45 IU; 2.5 per cent had ALT values greater than 60 IU. In general, ALT levels were higher in males than in females, and were age related; peak values occurred in the third decade of life for males and between 50-60 years of age in females. ALT values greater than 45 IU were found significantly more often in males, in donors of both sexes 30-40 years of age, in married donors, in non-Caucasians, and in those whose education level was no higher than high school. Follow-up samples in donors with an initial ALT greater than 45 IU, revealed that 67% continued to have ALT values above 45 IU 2-8 weeks following initial sampling, and 40% had an ALT greater than 45 IU when tested again six months after entry into the study. ALT values greater than 60 IU were associated with a significantly increased prevalence of antibody of hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) occurring together. No statistically significant association was found between transaminase activity and the prevalence of anti-HBs or anti-HBc alone, or with hepatitis A antibody. These findings demonstrate that there are defined sociodemographic and serologic features of donors with elevated ALT values.
Age Factors↗
What a difference an antigen makes.
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Carcinoma, Hepatocellular↗
Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study.
To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.
Adolescent↗
The clinical course and chronic sequelae of hepatitis B virus infection.
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Acute Disease↗
Transfusion-transmitted viruses study: experimental evidence for two non-A, non-B, hepatitis agents.
Plasma, serum, and a concentrate of factor VIII, implicated in human cases of non-A, non-B (NANB) hepatitis, were inoculated into four chimpanzees. All four animals demonstrated significant elevations of alanine aminotransferase levels within five weeks. After recovery from these NANB hepatitis episodes, the chimpanzees were cross-challenged with different inocula. A second episode of NANB hepatitis occurred after challenge in three animals. Reproducibility of the results was established by reversing the sequence of inoculation in two of the animals. A known infectious concentrate of factor VIII failed to induce hepatitis in a previously infected chimpanzee although the animal remained susceptible to a third inoculum, an event suggesting that the first inoculum might contain the same NANB hepatitis agent as the concentrate of factor VIII, which was supported by results of a subsequent cross-challenge experiment. Reinfection did not occur in two chimpanzees injected with their initial challenge strain of NANB hepatitis virus, providing evidence that strain-specific immunity had been established. Thus, experimental evidence is provided for the presence of two NANB hepatitis agents, supporting clinical and epidemiologic studies that favor the existence of more than one etiologic agent.
Alanine Transaminase↗
Post-transfusion hepatitis: current perspectives.
Viral hepatitis is still the most serious post-transfusion complication. Despite the routine screening of donor blood for the hepatitis type B surface antigen in the United States, post-transfusion hepatitis develops in approximately 7% of blood recipients. Type B hepatitis accounts for only 10% to 15% of cases; non-A, non-B hepatitis constitutes the remainder. Non-A, non-B hepatitis is usually asymptomatic and anicteric but often runs a prolonged course manifested by persistent or intermittent elevations of alanine aminotransferase levels. The risk of developing non-A, non-B hepatitis is increased considerably when blood from paid rather than volunteer donors is transfused. Although there are currently no definitive preventive measures that can be used to reduce the attack rate, the possibility of developing a serologic test fot the non-A, non-B agent is under active investigation.
Blood Donors↗
A partial characterization of hepatitis B e antigen.
Partially purified hepatitis B e antigen (HBeAG) was prepared by ultracentrifugation, ammonium sulfate precipitation, and molecular sieve chromatography of sera obtained from asymptomatic carriers of hepatitis B surface antigen. The antigenic specificity of the HBeAG preparations was investigated further with affinity chromatography. The results indicated that HBeAG is distinct and separable from DNA polymerase activity. Columns coupled with either goat IgG prepared from antiserum to human IgG or antibody to HBeAg bound all detectable HBeAg and bound 31% and 100% of the IgG, respectively, from a partially purified HBeAg preparation. Rate zonal sucrose sedimentation and molecular sieve and ion-exchange chromatography indicated a variability in molecular weight and charge; this finding suggested a heterogenous population of immunoreactivities containing HBeAg. Our preliminary results suggest the existence of an HBeAg-IgG complex.
Carrier State↗
Hepatitis B e antigen, DNA polymerase activity, and infection of household contacts with hepatitis B virus.
To determine if the presence of hepatitis B e antigen (HBeAg) and elevated DNA polymerase activity in the serum of chronic HBeAg carriers indicate increased contagiousness in a household setting, the household contacts of 74 carriers were prospectively evaluated for serologic evidence of hepatitis B infection. Thirty of the HBsAg carriers had HBeAg and 44 had anti-HBe. Twenty-eight HBeAg-positive carriers regularly demonstrated elevated DNA polymerase when serially drawn serum samples were analyzed. None of the anti-HBE-positive carriers demonstrated elevation of DNA polymerase activity. Both household contacts of HBeAg-positive and anti-HBe-positive carriers demonstrated serologic evidence of hepatitis B infection (HBsAg, anti-HBs, and anti-HBc). However, infection was significantly more frequent among spouses and sexual partners of carriers who had either HBeAg (P less than 0.001) or elevated DNA polymerase activity (P less than 0.001). Thus, the data indicate that a particular subpopulation of spouses and sexual partners of hepatitis B carriers are at significantly greater risk for acquiring infection.
Adult↗
Filtration and immunoprecipitation in the elimination of DNA polymerase activity associated with bacterial contamination of sera positive for hepatitis B e antigen and its corresponding antibody.
Samples of serum inoculated with Escherichia coli and serum that became contaminated with bacteria after exposure to a laboratory atmosphere demonstrated elevated DNA polymerase activity. The levels of activity were well within the range of values found in hepatitis B e antigen (HBeAg)-positive samples. The bacterial polymerase activity was markedly reduced by a single passage of serum samples through a 0.22-micron Millipore filter prior to analysis. Repeated filtration did not result in a substantial further decrease in polymerase activity. In sera that were heavily contamined with E. coli, however, filtration was not successful in reducing bacteria-associated polymerase activity to a base-line uncontaminated level. In such instances double antibody immunoprecipitation proved effective in elimination of bacterial activity. When bacterial contamination of serum samples is a possibility, specimens should be subjected to either Millipore filtration or immunoprecipitation prior to analysis, particularly when correlation of DNA polymerase activity with HBeAg and its corresponding antibody is attempted.
Antibodies, Viral↗