The Acute Hepatic Failure Study Group (AHFSG) has conducted a double-blinded, randomized evaluation of hydrocortisone in patients with acute hepatic failure. From July 1975 through August 1978, a 38-month period, 18 medical centers in the United States and one in Canada participated in this trial. A total of 64 patients were accessed and found eligible to participate in the study; two of them were subsequently eliminated from our analysis. Eighteen patients received placebo; 23 received 400 mg hydrocortisone per day, and 21 patients were administered 800 mg hydrocortisone per day. We did not observe any therapeutic effect of hydrocortisone, and the survival rates for placebo versus 400 mg and versus 800 mg hydrocortisone per day were 22%, 9%, and 24%, respectively. Fulminant hepatitis associated with drug hepatotoxicity or non-A, non-B hepatitis seemed to have a worse prognosis than fulminant B, although these differences were not significant. Serum α-fetoprotein had a modest prognostic value of survival and seemed to be limited to fulminant B. The AHFSG recommends, therefore, that corticosteroid use in acute hepatic failure with hepatic encephalopathy be discontinued.

We examined beta 2-microglobulin (B2MG) excretion, an index of tubular function, in patients with hepatorenal syndrome, in whom tubular function is generally regarded as normal. Urine B2MG was significantly higher in these patients than in control patients with normal serum creatinine concentration. Patients with high urine B2MG concentration had markedly higher serum bilirubin than did patients with normal values (31 +/- 3 vs. 10 +/- 8 mg%, p less than 0.001), whereas prothrombin activity, serum albumin and serum B2MG concentration were similar. A "threshold" serum bilirubin concentration of about 23 mg% differentiated patients with normal and high urine B2MG values. Renal morphology at autopsy was unremarkable in both groups. Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice. This measurement cannot, therefore, be used to make a diagnosis of acute tubular injury, as due to aminoglycosides, in such patients.

We have studied the effect of short-term high-dose prednisone therapy on aminotransferase levels and hepatitis B virus markers in 6 patients with chronic type B hepatitis. All showed a decrease in amino transferase levels during treatment. This was followed by a transient increase in aminotransferase levels after prednisone was discontinued. In 5 patients, there was a decrease in hepatitis B virus deoxyribonucleic acid polymerase activity at the time of postprednisone peak of aminotransferase levels. Three of them became transiently deoxyribonucleic acid polymerase negative. All the patients have remained hepatitis B e antigen-positive throughout the period of observation. We have also found transient deoxyribonucleic acid polymerase negativity unrelated to prednisone therapy in 2 patients with chronic type B hepatitis: in one during a superimposed episode of acute type A hepatitis, and in the other during a period of pronounced alanine aminotransferase elevation. We postulate that these periods of deoxyribonucleic acid polymerase negativity are due to a decreased number of hepatitis B virus-infected cells in the liver as a consequence of hepatic necrosis.

The occurrence of hepatitis A virus (HAV) infection in a small boarding school for mildly to moderately mentally retarded children in Umka, Yugoslavia, in the spring of 1979, six years after the last recognized occurrence, provided an opportunity to study the spread of the agent among 79 classroom and dormitory contacts. Only 51% of those who had entered subsequent to the prior outbreak had detectable antibody (anti-HAV) with immunoglobulin G predominance, and the proportion within the first six years of training did not vary. Both findings suggest a lack of endemicity during the interval. The outbreak ended spontaneously just before the summer vacation with an anti-HAV prevalence of 90%. The ratio of silent to overt cases was approximately 2:1. HAV was found in fecal samples from susceptible residents with inapparent infection as well as those with hepatitis. Among those with prior experience, there were no significant anti-HAV increases to suggest HAV reinfection in this group. Overall, 32% were seropositive for markers of past or chronic hepatitis B virus (HBV) infection, but this status did not correlate with sex, year of training, or HAV experience. Only one instance of HBV transmission was observed in the same interval as the 26 HAV infections.

Eighty-three women with acute icteric hepatitis during pregnancy were followed for evidence of viral transmission to their infants. Six women had acute hepatitis A as diagnosed by appearance of anti-HAV during convalescence. Except for passively acquired antibodies which were present at birth, anti-HAV did not appear in these infants, and there was no clinical or biochemical evidence for hepatitis during follow-up. Sixty-five pregnant women had acute hepatitis B during pregnancy or in the immediate postpartum period. Transmission to infants often occurred when both maternal HBsAg and HBeAg were positive at delivery of postpartum. A majority of these infants never developed jaundice, have remained persistently HBsAg-positive, and have had periodic serum ALT elevations during follow-up. Twelve women had acute non-A, non-B hepatitis during pregnancy. Infants born to 6 of these women near term had transient elevations of serum ALT values at 4-8 wk of age, suggesting maternal transmissibility of the non-A, non-B viral agent.

We have analyzed the frequency of chronicity and its distribution according to epidemiologic background following acute non-A, non-B hepatitis. Eighteen of 45 cases (40%) developed chronic liver disease. The incidence of chronicity was significantly higher following transfusion and among drug addicts (54% and 58%) than among patients without obvious source of infection (20%). Chronic active hepatitis developed in 4 of 13 patients (31%) with posttransfusion hepatitis. This lesion was not observed among the addicts or the patients without obvious source for the acute hepatitis.

Previous investigations have emphasized the high mortality of bleeding esophageal varices in hospitalized patients with cirrhosis.However,

We looked for hepatitis A virus (HAV) infection as an etiological agent among patients with fulminant hepatitis and chronic active hepatitis. Among 42 patients with hepatitis B surface antigen (HBsAg)-negative fulminant disease, we detected seroconversion by immune adherence hemagglutination for antibody to HAV (anti-HAV) in 3 of 10 survivors, as well as an increasing anti-HAV score by immune electron microscopy. In the 32 HBsAg-negative nonsurvivors, we found 3 patients with anti-HAV detectable by immune electron microscopy and radioimmunoassay, but not by immune adherence hemagglutination. We classified the latter cases as presumptively attributable to HAV. In 10 survivors among 30 HBsAg-positive patients with fulminant disease, we did not detect any instances of anti-HAV seroconversion. In the 20 HBsAg-positive nonsurvivors, 1 case had anti-HAV detectable by immune electron microscopy and radioimmunoassay but not by immune adherence hemagglutination. This case was also considered to be presumptively caused by HAV. In addition, we studied anti-HAV in patients with chronic active hepatitis. The incidence of anti-HAV in 13 HBsAg-positive cases was 31%, which did not differ from the 32% found in 22 HBsAg-negative cases. There was one seroconversion for anti-HAV in 1 patient with HBsAg-negative chronic active hepatitis, but this appeared to be an epiphenomenon. We looked for fecal shedding of HAV in 14 patients with HBsAg-negative chronic active hepatitis without success.

To define more completely the period of fecal excretion of virus during hepatitis A virus infection, we studied 24 fecal samples from six children with clinical illness during an epidemic of type A hepatitis. As determined by immune electron microscopy, the six patients had detectable viral excretion before or by the time of the first abnormality in serum glutamic-pyruvic transaminase (alanine aminotransferase). Viral excretion reached a peak early and declined to undetectable levels before levels of serum enzyme reached a peak. These data accord with epidemiologic evidence that the person who already has symptoms and signs of type A hepatitis is unlikely to transmit the infection to others. Immune electron microscopy, therefore, may be a better index to the period of communicability than studies of experimental infection in human subjects. This conclusion would imply that precautions against fecal contamination are not usually necessary for patients hospitalized with type A hepatitis.

Antibody to hepatitis A virus demonstrable by immune electron microscopy appeared early but remained at low levels for several weeks. Antibody detectable by immune adherence hemagglutination was delayed.

In outbreaks of type A hepatitis in Los Angeles, USA, and Rosario, Argentina, virus particles were isolated from faeces. The geographically diverse strains were identical in appearance and serological reactivity. They differed only in buoyant density, but other workers have also obtained inconsistent results in estimating this. We conclude that the virus strains in the two epidemics were identical.