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Lymphocytes from 39 patients with HBsAg positive chronic liver disease were incubated with their own hepatocytes to investigate mechanisms of lymphocyte-mediated liver damage. Cytotoxicity was significantly increased in 46% overall, and in 73% of those with chronic active hepatitis. Unlike HBsAg negative chronic active hepatitis where only non-T cells were cytotoxic, HBsAg positive patients had both cytotoxic T and non-T cells. A purified liver membrane complex (LSP) and aggregated IgG both blocked non-T cytotoxicity without affecting T cell cytotoxicity; this suggests that the former is probably an antibody-dependent cell-mediated reaction against normal membrane components. This was confirmed in preliminary studies which demonstrated that preincubation of hepatocytes with the F(ab)2' fragment of an anti-human IgG reduced non-T lymphocyte cytotoxicity. T-cell cytotoxicity was restricted to HBeAg-positive patients, suggesting a relationship between T-cell cytotoxicity and viral replication. Purified HBsAg, however, blocked cytotoxicity in only three of 11 cases. Non-T lymphocytes reacting with normal membrane components may contribute to liver damage in both 'autoimmune' and virus-associated chronic liver disease, whereas cytotoxic T-cells, probably reacting with viral determinants, are exclusive to those with viral replication.

Cellular immunity to the hepatitis B surface antigen (HBsAg) and a liver-specific lipoprotein was studied, using the leucocyte migration test, in 38 asymptomatic blood donors found to have HBsAg in the serum. Sensitization to HBsAg was found in 26% and was related to the presence of liver damage, being detected in 47% of those with elevated serum aspartate aminotransferase but in only 13% with normal enzyme levels. The frequency of sensitization to this antigen in those with chronic persistent or chronic aggressive hepatitis on biopsy was also higher than in those with unrelated or minimal changes. The findings using the liver-specific lipoprotein as antigen were similar and there was a correlation between the results obtained with this and the hapatitis B surface antigen. This study supports the hypothesis that a T-lymphocyte response to hepatitis B virus antigen can initiate an autoimmune reaction to antigens such as liver-specific lipoprotein on the hepatocyte surface, and that this reaction may be of importance in the production of chronic liver damage. In the absence of the T-cell response, the autoimmune reaction cannot occur and the virus is able to establish a harmless symbiotic union with the host.

Summary. A coagulation screen has been performed on 12 patients with acute liver failure. Six died and six recovered. All six fatal cases developed a haemorrhagic state with haemostatic failure. An attempt has been made to delineate the various mechanisms for the production of the coagulation defect. The significance of the different haematological parameters in assessing prognosis has been assessed. The study emphasizes the importance of the synthetic ability of the liver in determining survival prospects. A good correlation between the factor-VII level, which is a guide to liver synthesis, and recovery has been shown. The value of a specific factor-VII assay in acute liver failure appears considerable. Where this assay cannot be performed the clot opacity fibrinogen technique provides a reasonable guide to the prognosis. The presence or absence of DIG was not a determinant factor in survival in this series.

The possible importance of humoral immunity in the pathogenesis of fulminant hepatitis was investigated by comparing 17 patients with fulminant hepatitis type B with 20 patients with severe but non-fulminant disease. Hepatitis B surface antigen (HBsAg) was cleared from the serum significantly faster (P less than 0-001) in those with fulminant hepatitis, and in 41% anti-HBsAg (HBsAb) was detectable by radioimmunoassay (RIA) at presentation. In all 11 sera from patients with fulminant hepatitis that were examined by electron microscopy aggregates of HBsAg and HBsAb were seen. In contrast, HBsAb was never detected by RIA in those with non-fulminant hepatitis, and in only one serum specimen (5%) were aggregates seen on electron microscopy. A significant sex difference between fulminant and non-fulminant hepatitis was observed, 65% of patients with fulminant hepatitis but only 15% of patients with non-fulminant hepatitis being women (P less than 0-01). An enhanced production of HBsAb in fulminant hepatitis, by leading to free HBsAb in portal blood, may cause an Arthus reaction in the sinusoids of the liver with ensuing ischaemic necrosis of hepatocytes.

Summary A 24-year-old male with recurrent iron deficiency anaemia was found to have a generalized reduction in his immunoglobulin levels, granulomatous gastritis and impaired vitamin B12 absorption corrected by Intrinsic Factor. There is discussion of the possibility that cell mediated mechanisms may have been involved in the cause of the vitamin B12 malabsorption.

Summary The rate of endoscopically confirmed gastric ulcer relapse was compared in two groups of patients with newly healed benign gastric ulcers, receiving either cimetidine 400 mg nocte or matching placebo, over a period of 1 year. Six of 24 (25%) patients on cimetidine and 16 of 27 (59%) patients on placebo had endoscopically confirmed relapse. These included two patients in each group with asymptomatic relapses. The difference in the rate of relapse between the two groups was statistically significant (P = 0.01).

Human serum albumin stored for more than 10 years was studied. The biologic lifetime of this outdated albumin is only slightly shorter than that of freshly prepared human albumin. No determinations were done to determine safety or therapeutic efficacy.

58 patients with acute hepatitis type B, including 13 with fulminant hepatitis, were tested on presentation for HBeAg. Positive results were obtained in 24%. The frequency was highest in those with fulminant hepatitis (46% positive), and this was probably related to the earlier presentation of patients with this condition. Patients with acute hepatitis who were HBeAg-positive had had a significantly shorter duration of symptoms than those who were HBeAg-negative at presentation. HBeAg was still detectable more than 3 weeks after the onset of symptoms in only 2 patients, both of whom progressed to chronic active hepatitis. The early detection of HBeAg in patients with acute hepatitis is of no prognostic significance, but its persistence may provide the earliest evidence of potential chronicity.

The clinical relevance of the e antigen-antibody system was investigated in 61 people persistently positive for hepatitis-B surface antigen, including 22 healthy carriers. The e antigen was not detectable in any of the healthy carriers, whereas it was found in 15 out of 28 patients with chronic aggressive hepatitis and two out of 11 with chronic persistent hepatitis. Its presence therefore indicates chronic liver disease but its absence does not exclude it. It may prove to be a particularly useful prognostic aid in chronic persistent hepatitis, since one of the two patients in whom it was found later developed aggressive hepatitis. In contrast, e antibody is of little diagnostic help, for, though it was found mostly in healthy carriers (18;82%), it was also detectable in 9 (23%) of the patients with chronic hepatitis. In 13 (76%) of the patients positive for e antigen Dane particles were seen on electron microscopy, but these were also present in 5 (19%) of the patients positive for e antibody. These findings are consistent with other evidence suggesting that e antigen is not a surface component of the Dane particle, but rather an independent soluble protein manufactured by the host in response to infection with the hepatitis-B virus.