Q J Med 1976; 45: 351-372
© 1976 Association of Physicians
research-article |
Alpha-l-antitrypsin Deficiency and Liver Disease in Adults
From the Departments of Medicine and Pathology, Southampton University Hospitals, and The Nuffield Department of Medicine, Radcliffe Infirmary Oxford
Received 18 August 1975 Thirteen adult patients (aged 16 to 73 years) from 12 families are described with liver disease and alpha-l-antitrypsin deficiency.
Long-term observation of several of these patients suggests that the liver disease may be only slowly progressive, but review of possible factors aggravating this has failed to reveal any obvious clues. Progression to death from hepatic failure was the commonest outcome, but one patient developed a malignant hepatoma and two others died because of intraperitoneal haemorrhage due to ruptured cirrhotic nodules—a complication not hitherto described in association with this condition.
Diagnosis of alpha-l-antitrypsin deficiency was based on serological, histological, immunopathological and genetic studies. The most useful screening test in liver disease was found to be the demonstration of PAS positive globules in liver biopsy material which is diagnostic when shown to be antigenically identical with alpha-l-antitrypsin by immunofluorescence or immunoperoxidase, the latter being a superior technique. Serum estimation of alpha-l-antitrypsin deficiency was performed by immunoelectrophoretic and immunodiffusion techniques, the former being preferred because it gave more consistent results. Both methods, however, were of limited value since wide variations in the serum values are commonly found in normal and abnormal states. Genotyping was carried out using starch gel electrophoresis and although of value in family studies, its value as a diagnostic aid is limited because of technical difficulties and also because alpha-l-antitrypsin accumulation in the liver may be found in both homozygous and heterozygous states.
It is suggested that adult liver disease associated with abnormalities in alpha-l-antitrypsin may be more common than has hitherto been reported. This condition should be systematically sought in all cases of liver disease of uncertain aetiology.