Showing papers on "Hepatitis published in 1975"

Transfusion-associated hepatitis not due to viral hepatitis type A or B.

Abstract: Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.

Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites

Abstract: Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Eximination of isoniazid metabolites revealed that rapid acetylators hydrolze much more isoniazid to isonic otinic hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazed is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.

On the Role of Sexual Behavior in the Spread of Hepatitis B Infection

Abstract: There is a significant excess of serologic evidence of hepatitis type B infection in two high-promiscuity populations: patients with venereal diseases and their unrelated sexual contacts (...

Serial studies of hepatitis-associated antigen and antibody in patients receiving antitumor chemotherapy for myeloproHferative and lymphoproliferative disorders.

Abstract: The effects of antitumor chemotherapeutic agents on hepatitis B antigen (HBAg) and antibody (HBAb) were studied serially in 25 patients with myeloproliferative and in 60 patients with lymphoproliferative disorders. HBAg was detected at some time in 17 patients, and HBAb in 40 patients. Seventeen patients who had HBAb detected immediately pretreatment had a decrease in HBAb titer which paralleled the fall in white blood cell count. In 5 of these patients, HBAg appeared when HBAb titers fell. In 3 of the 5 patients, a reappearance of HBAb was observed with disappearance of HBAg from the serum, and in the 2 other patients HBAg persisted once it appeared. In all 3 patients who had HBAg at the time of initiation of chemotherapy, bone marrow suppression was associated with a marked increase in HBAg titer. The increase in HBAg titer was associated with hepatocellular damage, as manifested by an elevation in serum transaminase enzymes. These observations suggest that antitumor chemotherapeutic agents reduce HBAb titers. In some patients, HBAg appears after a decrease in HBAb titers. In patients with preexisting HBAg, such therapy leads to large increases in HBAg titer. Whether this appearance or increase of HBAg is related to an inhibition of antibody formation, allowing expression of preexisting antigen, or to an inhibition of cellular immunity, allowing viral proliferation, is uncertain.

Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil.

Abstract: We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.

The relation of infection with the hepatitis B agent to primary hepatic carcinoma.

Abstract: In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets.

Abstract: This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.

The pathogenesis of arthritis associated with acute hepatitis-B surface antigen-positive hepatitis. Complement activation and characterization of circulating immune complexes.

Abstract: Circulating immune complexes were identified in cryoproteins isolated from serial samples of serum from six patients with acute viral hepatitis with and without arthritic symptoms. Cryoprecipitates were analyzed for the presence of hepatitis-B surface antigen (HBsAg) and hepatitis-B surface antibody (anti-HBs) by hemagglutination inhibition and hemagglutination. Complement components were detected by counter electrophoresis, and immunoglobulins were detected by gel diffusion. HBsAg, IgG, and IgM were identified in cryoprecipitates from all hepatitis patients, but were higher in concentration in patients with arthritis. Only cryoprecipitates from hepatitis patients with arthritis contained IgA and complement components C3, C4, and C5 as well as IgG and IgM, which disappear with resolution of the arthritis. The subtypes of IgG in these cryoprecipitates were predominantly the complement-fixing IgG1 and IgG3, HBsAg and anti-HBs were concentrated several-fold in the cryoprecipitates when compared to the serum concentration. Sequential studies in two patients demonstrated that the initial appearance of anti-HBs in the cryoprotein complex was associated with the detection in the complex of IgM suggesting a primary immune response to HBsAg. The C3 activator fragment (C3A) of the properdin complex was found in fresh serum obtained from three hepatitis patients with arthritis and not in uncomplicated hepatitis. The cryoprecipitable immune complexes from patients with arthritis converted C3PA in fresh normal sera to C3A in vitro whereas cryoprotein isolated from patients with uncomplicated hepatitis had no such effect. Thus, the transient appearance of circulating complement-fixing immune complexes in patients with the arthritis of acute hepatitis is associated with activation of both classical and alternate complement pathways and suggests that they play an important role in the pathogenesis of these serum sickness-like extrahepatic symptoms.

Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations.

Abstract: A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.

A New Antigen-Antibody System: Clinical Significance in Long-Term Carriers of Hepatitis B Surface Antigen

Abstract: A new antigen-antibody system was recently described in hepatitis B surface antigen (HBsAg)-positive sera. Despite indications of heterogeneity in specificity, the designations "eantigen" and "eantibodies" are used for the system as such in this article. Eight of 17 long-term carriers of HBsAg with a histological picture of chronic persistent hepatitis or chronic aggressive hepatitis carried theeantigen, while none had demonstrableeantibodies in serum. Ten of 12 healthy carriers with e antibodies were blood donors who had donated 95 units of blood; none of these carriers was associated with a reported case of posttransfusion hepatitis. In five individuals in the incubation stage of hepatitis B,eantigen appeared simultaneously with HBsAg but before the rise in transaminase levels. This finding further linkseantigen to hepatitis B. (JAMA231:356-359, 1975)

Dane particles, DNA polymerase, and e-antigen in two different categories of hepatitis B antigen carriers.

Abstract: Two different categories of hepatitis B antigen carriers have been investigated. One comprises patients treated with dialysis and known to be highly infectious. The other consists of blood donors foun

Experimental infection of chimpanzees with hepatitis A virus.

Abstract: The susceptibility of chimpanzees to viral hepatitis type A was examined with immine electron microscopy. Of four seronegative infant chimpanzees, two were inoculated with a hepatitis A acute-phase stool filtrate rich in 27 nm virus-like hepatitis A antigen (HA Ag) particles, and two were inoculated with an HA Ag-negative preinfection stool filtrate. One of each pair of chimpanzees was inoculated intravenously, the other orally. One month later both chimpanzees that had received the HA Ag-positive filtrate developed biochemical, histologic, and clinical evidence of acute viral hepatitis. HA Ag particle (27 nm) were detected in their stools by immune electron microscopy; particle shedding followed a pattern similar to that in human volunteers. Immune electron microscopy also showed that antibody HA Ag had developed in the convalescent-phase sera of the infected chimpanzees. Control animals remained free of illness at this time but did develop hepatitis three to five weeks after exposure to the two infected chimpanzee-. The infectious inoculum was titrated in two additional seronegative chimpanzees. It was concluded that hepatitis a can be successfully transmitted to seronegative chimpanzees. Moreover, these studies provide further evidence that the 27-nm virus-like HA Ag particle is the etiologic agent of viral hepatitis type A.

Hepatitis B Virus Infection in Dentists

Abstract: To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strains of that agent in the general population for severa...

Hepatitis B Immune Globulin as a Prophylactic Measure for Spouses Exposed to Acute Type B Hepatitis

Abstract: Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one — identified as HBIG — that had a high concentration (442 μg per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk. (N Engl J Med 293:1055–1059, 1975)

Hepatitis B Virus Infection in Chimpanzees: Titration of Subtypes

Abstract: Thirty-four chimpanzees were inoculated with sera containing the adw, ayw, adr, or ayr subtype of hepatitis B surface antigen (HBs Ag). Twenty-nine of the animals became infected with hepatitis B virus, and in every instance the subtype of HBs Ag in the infected animal was the same as the subtype in the inoculum. Infectivity titers were established for the adw and ayw inocula. The patterns of serologic events varied in the infected animals but included most of the typical patterns of serologic change seen in human cases of type B hepatitis. Mild disease, manifested by elevated concentrations of serum enzymes and changes detected by liver biopsy, occurred in 23 of the 29 infected animals.

Epidemiology of hepatitis B in hospital personnel.

Abstract: To identify occupational categories and work areas of possible risk for acquisition of nosocomial hepatitis B by hospital personnel, serologic sampling for hepatitis B surface antigen (HBSAg) and antibody (anti-HBS) by radioimmunoassay was carried out in 513 employees of a large metropolitan hospital serving predominantly indigent patients. HBSAg was detected in 0.7%, HBSAg and anti-HBS in 0.4%, and anti-HBS in 13.3% of the study population. No significant difference in seropositivity was noted between sexes. Furthermore, neither exposure to patients with hapatitis nor previous blood transfusion correlated with serologic evidence of hepatitis B infection. However, frequency and intensity of exposure to blood products was associated with serologic evidence of infection: 18.9% of those with frequent blood contact were positive for HBSAg or anti-HBS, compared with 11.4% of those without blood product exposure (p less than .05). Direct patient contact, apart from blood exposure, did not appear operative as a major factor in hepatitis B transmission in this population. Accordingly, occupational categories and work areas with highest risk for acquisition of nosocomial hepatitis B were those with greatest blood exposure.

Hepatitis in dental professionals.

Abstract: To characterize some epidemiologic characteristics of viral hepatitis among dentists, information was obtained with a mailed questionnaire from 434 dentists and 787 attorneys in Dade County, Florida. Dentists had a significantly higher incidence of hepatitis than did lawyers, 6.7% vs 2.4%, with the highest rate among oral surgeons (21%). The incidence of hepatitis B antigenemia among asymptomatic dentists was not significantly higher than that of volunteer blood donors. Twenty-two percent of dentists with hepatitis reported treating more than ten drug addicts per year, as compared with 10% of those dentists without hepatitis. No differences were noted between dentists with and without hepatitis in methods of sterilization, the wearing of gloves during procedures, or the use of disposable needles. The increased risk of hepatitis among dentists, however, may be related to the omission of adequate prophylactic measures, particularly when treating high-risk patients such as drug abusers. (JAMA232:1228-1230, 1975)

Physical, chemical, and morphologic dimensions of human hepatitis. A virus strain CR326

Abstract: CR326 human hepatitis A virus purified by isopycnic banding from infected marmoset sera was shown to consist of 27 nm spherical particles on electron microscopic examination. The particles were identified as hepatitis A virus by tests for infectivity and by specific neutralization of infectivity with convalescent human hepatitis A serum. Also, indentical 27 nm viruses in liver extracts gave specific reactions with hepatitis A antisera when tested by immune electron microscopy. The bouyant density of the virus in CsCl was 1.34 and it was heat (60 degrees), ether and acid stable but was destroyed by heat (100 degrees), formalin (1:4000) and ultraviolet irradiation. Electron microscopic studies of sections of infected marmoset liver showed intracytoplasmic virus particles, usually in vesicles. Presumptive findings for RNA, together with the intracytoplasmic location of the virus, indicated the virus to be of RNA-type. The attributes of the virus indicate it is closely related to the enterovirus family and not to hepatitis B virus.

Recent advances in the study of the epidemiology of hepatitis B.

Abstract: Recent advances in the study of hepatitis B shed much light on the basic epidemiologic patterns of this unique infection. The spectrum of host responses following exposure is unusually wide. Hepatitis B appears to be one of the most widespread infections; the total number of chronic carriers of the hepatitis B antigen has been estimated as at least 120 million. The following factors have been found to be closely associated with the risk of hepatitis B; geography, sex, age at testing, age at primary infection, socioeconomic status, ethnicity, occupation, sharing a household with a carrier, sexual promiscuity, and immunologic responsiveness. Data concerning the infectivity of an asymptomatic carrier are ambiguous; whether a carrier can transmit the virus by sexual intercourse also remains unknown. Available evidence seems to suggest that genetic factors may be of importance in the aggregation and segregation of hepatitis B.