between the ages of 10 and 20 and 45 and 70 years and has To determine the clinical, biochemical, and histologia relatively benign course at least in adults, 3 whereas LKMcal features, and outcome of childhood autoimmune 1 positive patients have a more severe disease with progreshepatitis (AIH), we reviewed the medical records of 52 sion to cirrhosis despite immunosuppressive treatment. gest that ANA/SMA positive AIH has two peaks of incidence median age: 10.5, range 2.3-14.9 years). At presentation, four children were positive for ANA alone (titer range: 1:80-1:320), 10 for SMA alone (titer range: 1:40-1:2560) and 14 for both ANA (titer range: 1:20-1:5120) and SMA (titer range: 1:40-1:1280). In two paAbbreviations: AIH, autoimmune hepatitis; ANA/SMA, nuclear and/or smooth muscle

Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.

SUMMARY 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)' fragment of an anti-human IgG reduced non-T lymphocyte cytotoxicity. T-cell cytotoxicity was restricted to HBeAg-positive

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ABSTRACT— Hepatocytes isolated from patients with chronic liver disease are often covered by immunoglobulin. The aim of the present study was to establish whether this surface immunoglobulin (SIg) mediates liver cell damage. Freshly isolated hepatocytes from percutaneous liver biopsy of 16 patients with chronic active hepatitis (CAH) (6 HBsAg positive), 3 with HBsAg‐positive chronic lobular hepatitis (CLH), 5 with HBsAg‐positive chronic persistent hepatitis (CPH) and 12 with minor histological abnormalities (MHA) (5 HBsAg positive) were divided into two aliquots. One was studied for the presence of membrane‐bound immunoglobulin and the third component of complement by direct immunofluorescence and the other was incubated, in an allogeneic cytotoxic assay, with peripheral blood mononuclear cells prepared from healthy volunteers as a source of effectors for antibody‐dependent cell‐mediated cytotoxicity (ADCC). Liver biopsies were scored for portal and parenchymal inflammatory activity. The percentage of SIg positive hepatocytes was significantly higher in patients with CAH (median 52.5%) than in patients with CLH/CPH (20.5%) or in patients with MHA (1%). Percentages of SIg‐positive liver cells were significantly correlated with total liver biopsy scores and with both portal or parenchymal scores considered independently. SIg were found to belong to the IgG class in all groups of patients. When hepatocytes were cultured with normal human lymphocytes, allogeneic cytotoxicity values were significantly higher in patients with CAH (median 34%) than in patients with CLH and CPH (18%) or in those with MHA (12%). Percentage cytotoxicity was positively correlated with total biopsy scores and with portal activity but not with parenchymal activity, suggesting that ADCC might play a damaging role mainly in the portal areas. Our results show that in HBsAg‐positive and in HBsAg‐negative chronic liver disease IgG on the liver cell membrane is associated with increased susceptibility to in vitro cytotoxicity by killer cells and with increased severity of histological liver damage, suggesting a direct role for these antibodies in the generation of the liver injury.