PaulV. Holland

Transmissible agent in non-A, non-B hepatitis.

Plasma or serum from 4 patients with acute or chronic non-A, non-B post-transfusion hepatitis (P.T.H.) and from a blood-donor implicated in two cases of P.T.H. was inoculated into 5 chimpanzees. Biochemical and histological evidence of hepatitis developed in these 5 chimpanzees but not in a control animal. The mean incubation period in the chimpanzees was 13.4 weeks, compared with 7.7 weeks in the 4 patients with P.T.H. The peak alanine aminotransferase (A.L.T.) levels in the 5 chimpanzees were 265, 212, 219, 70, and 62 I.U./l. Histological changes ranged from mild to conspicuous hepatitis and generally correlated with the degree of A.L.T. elevation. There was no evidence of clinical disease and all animals went on to biochemical and histological recovery. There was no serological evidence of type A or type B hepatitis. Hepatitis was transmitted by serum derived from patients with chronic as well as acute hepatitis, strongly suggesting a chronic carrier state for the agent responsible for non-A, non-B hepatitis. Non-A, non-B hepatitis thus seems to be due to a transmissible agent which can persist and remain infectious for long periods.

Failure of Australia antibody to prevent post-transfusion hepatitis.

Abstract In a prospective study of 64 patients who received multiple transfusions at the time of open-heart surgery, the presence in the serum of Australia antibody was studied in relation to the development of post-transfusion hepatitis. Australia antibody developed in 2 of 32 patients with hepatitis and in 4 or 32 patients without hepatitis. Australia antigen was found in 4 of the patients with hepatitis but was not detected in those without hepatitis. The coexistence of both Australia antigen and Australia antibody was not demonstrated in any patient. In 2 patients Australia antibody, which was shown to be present before the onset of post-transfusion hepatitis, did not prevent the disease. The occurrence of hepatitis in patients with antibody to the Australia antigen suggests that such antibody does not completely protect against hepatitis, or, alternatively, that the hepatitis was caused by an agent serologically distinct from Australia antigen.

PATHOGENESIS OF THE ACUTE RENAL FAILURE ASSOCIATED WITH INCOMPATIBLE TRANSFUSION

Abstract Erythrocyte stroma which is free of haemoglobin and is of a compatible bloodgroup is innocuous when given intravenously, but in 2 patients acute renal damage followed the infusion of incompatible stroma. Neither intravascular haemolysis nor haemoglobinuria are necessary for the production of the renal complications seen after incompatible transfusion. The complex of the antibody with the bloodgroup antigen on the erythrocyte membrane can, by itself, induce renal failure.

RELATION OF HEPATITIS-B-ANTIGEN SUBTYPES IN SYMPTOM-FREE CARRIERS TO GEOGRAPHICAL ORIGIN AND LIVER ABNORMALITIES

Abstract Hepatitis-B-antigen (HBAg) subtypes and possible liver abnormalities were investigated in 63 symptom-free HBAg-positive blood-donors in Toronto. 38 (60%) had the determinant d, while 25 (40%) had y. Most donors who were subtype adw were born in Canada, China, Germany, and the West Indies, whereas most donors who were ayw originated from Mediterranean countries. All 8 donors who were adr were from China. Thus the subtype of chronic HBAg carriers appeared to be related to their country of origin rather than their country of residence. Evidence of liver dysfunction, mainly raised serum-glutamic-pyruvictransaminase and liver-biopsy abnormalities were almost equally common in the adw, adr, and the ayw groups (30%, 25%, and 26%, respectively). 14 HBAg-positive, first-degree relatives of 9 blood-donors were also subtyped; all had the same subtype as the index case to whom they were related.

RISK OF TRANSFUSING BLOOD CONTAINING ANTIBODY TO HEPATITIS-B SURFACE ANTIGEN

Abstract 362 blood-transfusion recipients, whose sera were initially negative for hepatitis-B antigen (HB s Ag), were prospectively followed for clinical and serological evidence of exposure to hepatitis-B virus (H.B.V.) and for the development of hepatitis unrelated to H.B.V. None of the donor units received by these patients contained detectable HB s Ag. Of the 362 transfusion recipients, 23 (6%) developed 25 episodes of hepatitis; only 4 of these 25 episodes were serologically related to H.B.V. Based on the absence of antibody to HB s Ag anti-HB s ) prior to transfusion, 278 of the patients were considered susceptible to H.B.V. infection. Of these susceptible patients, 133 received at least one unit of blood containing anti-HB s ; when compared with the 145 who did not receive anti-HB s , there was no significant difference in biochemical or overt hepatitis B (3/133 vs. 1/145), in serological response to H.B.V. 5/133 vs. 5/145), or in hepatitis unrelated to H.B.V. 11/133 vs. 6/145). It is concluded that blood containing detectable anti-HB s carries no increased risk of transmitting hepatitis B compared with blood which lacks this antibody.

GAMMA-GLOBULIN FOR HEPATITIS-VIRUS B PREVENTION OR EXTENSION ?

Abstract Inferential evidence is presented that attenuation of hepatitis-B-antigen (H.B. Ag)-positive hepatitis may favour the progression of acute to chronic liver disease and the development of a persistent H.B. Ag carrier state. These considerations may be relevant to the use of antibody to the hepatitisB antigen (anti-H.B. Ag) in the prophylaxis of hepatitis B. Based on preliminary encouraging results, controlled trials to test the efficacy of anti-H.B. Ag are being planned or are in progress. It is urged that these trials go beyond questions relevant to acute, overt hepatitis and specifically examine the possible induction of chronic liver disease and a persistent viral carrier state.