Pathology and pathogenesis of liver disease in alpha-1-antitrypsin deficient individuals.

SINCE the report of Laurell and Eriksson in 1963, in which they showed an increased frequency of emphysema in individuals with alpha-1-antitrypsin deficiency, this combination has been described by numerous authors. Eriksson (1965) mentioned that some of the emphysematic patients had cirrhosis of the liver. This was also found by others (Thuesen Pedersen, Weeke and Georg, 1969), but was initially assumed to be an unrelated coincidence. The report of Sharp et al. (1969) was the first to draw a definite relationship between liver disease and alpha-l-antitrypsin deficiency. Sharp (1971) has continued his studies on liver disease in alpha-1-antitrypsin deficient children and several other reports have also confirmed the frequent finding of cholestasis and cirrhosis in these children (Johnson and Alper, 1970; Glasgow et al., 1971; Porter et al., 1972; Aagenaes et al., 1972; Talamo and Feingold, 1973). The clinical picture in infancy is mainly one of cholestasis with jaundice, light stools and dark urine. Of our six patients in Oslo, three have been admitted with suspected biliary atresia and two have been admitted with umbilical bleeding. Laboratory findings are those of intrahepatic cholestasis, with increased transaminase, alkaline phosphatase, some increase in serum lipids, some steatorrhoea and an increase in serum bilirubin and bile acids. Table 1 shows that in our last three patients where radioactive Rose Bengal tests have been performed, this test conformed well with an intrahepatic cholestasis, with a Rose Bengal excretion during the first 2 days between 10 and 20% of the injected amount. The duration of the cholestasis is most often a few months, and pruritis does not seem to be very