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Fifty four infants with hepatobiliary disease and conjugated hyperbilirubinaemia of more than two weeks' duration were identified in a defined area of south east England in a prospective study between January 1971 and December 1973. The overall incidence was one case per 2500 live births. The cases were regularly reviewed and all survivors except one were assessed at age 10 years. Nine of 11 with extrahepatic biliary atresia died from liver disease by 2 years of age, one died at 5 years, and the survivor has cirrhosis with portal hypertension. Four out of seven with alpha 1 antitrypsin deficiency died aged 1 to 3 years from liver disease and one of the survivors has cirrhosis. All three infants with intrauterine infection and one with chromosomal abnormality died in infancy. Three children with other associated factors, choledochal cyst, galactosaemia, and rhesus isoimmunisation, recovered completely with no persisting liver disease. Two of 29 with cryptogenic hepatitis died, but only a further two have signs of persisting liver disease. Perinatal complications were more common in this group. Four of the 27 children surviving to the age of 10 years are educationally subnormal. Prognosis for infants with intrahepatic liver disease in the absence of known associated factors is good and every effort should be made to minimise the short term effects of cholestasis. [ABSTRACT FROM AUTHOR]

Chronic hepatitis implies that clinical and biochemical features of hepatitis have been present for at least 6 months; but irreversible liver damage may occur with subclinical disease suggesting that pathological features should also define chronicity. We examined 28 children with hepatitis B negative chronic active hepatitis to determine whether the severity of abnormal biochemical tests of liver function, raised serum immunoglobulin concentrations, and positive serum autoantibodies, which are characteristic features in immunosuppressant responsive disease, varied with the duration of symptoms. The pattern of abnormality in these patients was similar whether the disease had been present for less than three months, from three to 6 months, or for more than 6 months, and apart from lack of hyperbilirubinaemia was similar in patients presenting with complications of cirrhosis without previous symptoms of liver disease. Two children died of liver disease. The remainder showed a clinical, biochemical, and immunological response to prednisolone or azathioprine, or both. These drugs have now been withdrawn in 8 patients without relapse, and disease activity is completely suppressed in 13. Unfortunately, 15 survivors have definite cirrhosis and a further five have possible cirrhosis. Eight of 10 survivors with symptoms of more than 6 months duration before treatment have cirrhosis compared with two of 12 with symptoms of less than 6 months. It is suggested that consideration of this diagnosis at onset of symptoms and immediate immunosuppressant treatment after appropriate confirmatory investigations may reduce the incidence of cirrhosis in hepatitis B negative chronic active hepatitis in children. [ABSTRACT FROM AUTHOR]

A prospective epidemiological study of the Neonatal Hepatitis Syndrome in S.E. England showed Alpha-1-Antitrypsin Deficiency (Pi ZZ) to be present in seven out of fifty-two patients. Data are considered from these seven patients, and from a further six cases from outside this area. The nature of acute illness, pathological changes on early liver biopsy, and short-term prognosis show considerable variability, but in general the hepatitis is more severe in patients with Alpha-1-A.T. deficiency than in those in whom no aetiological factor was found. [ABSTRACT FROM PUBLISHER]

Anti-lymphocytic antibodies (ALA) have been described in a variety of autoimmune disorders. We have investigated the presence of ALA in autoimmune chronic active hepatitis (aCAH) starting in childhood. Using a modified Terasaki technique ALA were found in 17 of 18 patients with aCAH but in only one of 15 patients with alpha-1-anti-trypsin deficiency or Wilson's disease and three of 27 aged-matched healthy controls (P < 0.0005 for both). Sera from 12 patients with uncontrolled aCAH had significantly higher cytotoxicity values than sera from six children with inactive disease (P < 0.01). ALA were directed to T but not B lymphocytes and were not reactive with specific HLA antigens. No preferential killing was observed against CD4 or CD8 positive T lymphocytes. Characterization of ALA revealed them to be cold-reactive IgM. The possible role of ALA in aCAH is discussed. [ABSTRACT FROM AUTHOR]

An indirect immunofluorescence technique was used to investigate the immunoglobulin class, IgG subclass, light chain type and complement fixing ability of anti-liver kidney microsomal antibody (anti-LKM) in the sera of six children and five adults with autoimmune chronic active hepatitis (aCAH), Anti-LKM titres ranged from 1/80 to 20,480. In the children, the antibody belonged to the IgG1 subclass alone (titre l/80-1/20,480) and was able to fix complement (titre 1/40 -1/5120). In the adult group, antibody belonged to the IgG1 subclass in three cases (titre 1 40-1 640 whilst two belonged to both IgG1 (titre 1/640) and lgG4 (titre 1/40, 1/640). Such subclass restriction is similar to that found in other autoimmune disorders and may be genetically determined. Investigation of' the light chain constituent of anti-LKM revealed that the kappa to lambda ratio was consistent with a polyclonal antibody response. To investigate the nature of the antigen to which anti-LKM is directed, the ability of these sera to bind to the surface membrane of isolated human hepatoma cells (Alexander cells) was investigated. Four of the eleven sera showed significant binding activity. Prior incubation of these four sera with Alexander cells abolished their membrane binding activity, but did not alter the anti-LKM titre. These results suggest that anti-LKM binds to cytoplasmic constituents alone and does not cross-react with surface antigens. [ABSTRACT FROM AUTHOR]

To investigate the function of activated T lymphocytes in autoimmune chronic active hepatitis, 7 of 15 T-cell clones from the peripheral blood of 8 patients were studied. These clones showed specificity for liver-membrane antigen with proliferation when stimulated by rabbit liver cell membranes. 6 of these clones reacted with liver-specific lipoprotein complex, and 1 clone (and 3 subclones) responded to the asialoglycoprotein receptor (ASGPR), both known targets of immune attack in autoimmune chronic active hepatitis. 2 of these clones stimulated autologous B lymphocytes to produce liver-membrane-specific autoantibodies and antibody to the ASGPR. These results suggest that liver-membrane-specific activated T lymphocytes in peripheral blood may be important in the autoimmune attack of chronic active hepatitis. [ABSTRACT FROM AUTHOR]