Severe Viral Hepatitis Research Articles

Controlled trial of corticosteroid therapy in severe acute viral hepatitis

Controlled trial of corticosteroid therapy in severe acute viral hepatitis

Bile duct and liver pathology in biliary atresia.

AbstractProgression to cirrhosis despite restoration of bile flow by successful portoenterostomy suggests that factors other than obstruction alone are operative in biliary atresia. This paper describes pathologic changes at all levels of the hepatobiliary secretory apparatus from hepatocyte to common duct, exhibited in liver biopsies, resected portions of liver adjacent to the porta hepatis, and extrahepatic duct remnants from 17 patients operated upon for relief of biliary atresia. In both intra‐ and extrahepatic bile ducts, there were epithelial changes interpreted as occurring in a sequence of vacuolar degeneration, necrosis, inflammatory infiltration, and proliferative epithelial repair that precede obliterative fibrosis. From their distribution, it is inferred that these cytopathologic changes may not be simply due to distal obstruction. These ductal epithelial changes are similar to those that occur in livers of some patients with severe viral hepatitis. The association of these changes with giant cell transformation in all cases suggests that they reflect a common etiology for ductal and hepatocellular damage in the neonatal hepatitis‐biliary atresia spectrum. The persistence of these changes in liver biopsies following portoenterostomy suggests that they may be of pathogenetic significance in the progressive liver disease seen in most patients with biliary atresia.

Differentiation of T Cells in Nude Mice

Cells bearing the T-cell differentiation alloantigens TL and Thy-1 were enumerated in preparations of spleen and lymph node cells of nu/nu mice. Healthy nu/nu mice had few or no demonstrable TL+ or Thy-1+ cells whereas mice with viral hepatitis, including some born of nu/nu X nu/nu matings, had many. Healthy nu/nu mice were treated daily with the thymic hormone thymopoietin or with ubiquitin, polypeptides that induce the differentiation of TL+Thy-1" cells from TL-Thy-1- precursors in vitro. After 14 days, 20 to 40 percent of their spleen cells were of the TL+Thy-1+ phenotype typical of thymocytes and 10 to 25 percent of their lymph node cells were TL-Thy-1+, typical of later T-cell differentiation. Similar frequencies of such cells were found in untreated nu/nu mice suffering from severe viral hepatitis. These data conform to the current view that prothymocytes are preprogrammed cells whose maturation to thymocytes, normally induced in the thymus by thymopoietin, can be triggered by other agents under abnormal circumstances. Tests of T-cell function were not included in this study.

Long Term Follow-Up Studies of Patients Surviving Fulminant Viral Hepatitis

Long term follow-up studies (3 to 46 months) were conducted in 22 patients who had survived severe acute viral hepatitis with coma. Complete clinical and biochemical resolution of the hepatitis was observed in all patients within 45 to 75 days after the onset of the acute hepatitis. The only identifiable sequela of the fulminant episode was the persistence of hepatitis B antigen in 1 of 16 initially hepatitis B antigen-positive patients. Three patients suffered a second attack of acute viral hepatitis 4 to 10 months after recovery from the fulminant episode. Mild unresolved hepatitis followed the second episode in 1 patient. Follow-up liver biopsy made in 13 patients (2 to 37 months after the fulminant episode) showed no liver disease related to the fulminant hepatitis except for mild unresolved hepatitis in the hepatitis B antigen carrier. It appears that patients surviving fulminant viral hepatitis rarely, if ever, develop chronic liver disease, in spite of the extreme degrees of hepatic necrosis occurring during the acute illness.

A clinical study of the effect of arginine on blood ammonia

1. 1. The ability of intravenously administered L-arginine hydrochloride to decrease the blood ammonia was investigated in fifteen patients with elevation in blood ammonia and varying degrees of encephalopathy associated with several disease entities. 2. 2. In every case there was a reduction in the ammonia levels of the blood following arginine therapy. Improvement in the mental status of the patient accompanied the fall in blood ammonia. Two of three patients with severe viral hepatitis who were given arginine while in deep coma responded in twenty-four to thirty-six hours with marked clinical and biochemical improvement and eventual recovery. 3. 3. The decrease in the level of ammonia in the blood that occurred after administration of arginine was always accompanied by a significant rise in the blood urea nitrogen, suggesting that the effect of arginine on the blood ammonia may be mediated through its role in the urea cycle. 4. 4. Further clinical experiences with substances such as arginine which can effectively lower the blood ammonia should serve to delineate more clearly the pathologic importance of ammonia intoxication in clinical desease.

Adrenal hormone therapy in viral hepatitis: IV. The effect of gamma globulin and oral cortisone in the acute disease

Summary<ul><li>1.Twenty-two patients with acute viral hepatitis were given oral cortisone in conjunction with the administration of large amounts of gamma globulin intramuscularly at the beginning and end of hormonal therapy.</li><li>2.Gamma globulin failed to prevent relapses: four occurred, an incidence similar to that in ACTH- or cortisone-treated subjects without conjunct gamma globulin therapy.</li><li>3.Oral cortisone produced a rapid initial drop in bilirubinemia but failed to influence significantly the total duration of illness except in two patients receiving therapy over a three-week period.</li><li>4.Even under ideal circumstances cortisone does not shorten the duration of disease sufficiently, in our opinion, to run the increased risk of relapse, and thus is not recommended for the routine treatment of viral hepatitis. It may have a place in the treatment of severe and progressive viral hepatitis and certainly deserves further trial in fulminant hepatitis with coma.</li></ul>