Reversal of Hepatic Alpha-1-Antitrypsin Deposition After Portacaval Shunt

Abstract

End-to-side portacaval shunts were carried out in three children with the liver disease of alpha-1-antitrypsin deficiency and complications of portal hypertension. Their clinical courses have been stable for 3 1/2 to almost 7 years. Postoperative liver biopsy material from two of the patients showed the typical histopathological changes caused by portal diversion, as well as an apparent reduction in the quantity of alpha-1-antitrypsin particles in the hepatocytes. The metabolic changes caused by portal diversion have apparently created a more favourable equilibrium between the synthesis and excretion of the abnormal alpha-1-antitrypsin.

The ECK fistula in animals and humans

“…However, the most objective evidence that the natural history of the disease was favorably altered by portacaval shunt came from the histopathologic studies of biopsy specimens obtained operatively and postoperatively in patients 2 and 3. 182 In patient 2, a biopsy specimen obtained 9 months after the portal diversion showed a reduced number of hepatocytes containing α 1 -antitrypsin globules-28.5%, compared to 38.2% at the time the portacaval shunt was constructed. The hepatocytes were 22% smaller, and the amount of RER in their cytoplasm was greatly reduced.…”

“…182 Standard liver function tests have not changed greatly since the portacaval shunt, although the plasma ammonia levels have been elevated in both patients in whom measurement was systematically made. None of the three patients have had symptoms of encephalopathy, although patient 2 had mental slowness for the first 2 years after operation.…”

“…182 The first two patients had major hemorrhages from esophageal varices. The third had ascites, but the principal reason for operation was the hope of influencing the metabolism of the α 1 -antitrypsin.…”

“…172,182 With a better equilibrium between the production and transport of the α-globulin, it is possible that its intracellular accumulation has been slowed or probably even reversed.…”

The mother lode of liver transplantation, with particular reference to our new journal

“…23,24 Their use was now extended to the palliation of three congenital inborn errors of metabolism: glycogen-storage disease, 30,31 familial hypercholesterolemia, 26,32 and ␣ 1 -antitrypsin deficiency. 33,34 Because each of these errors can be corrected far more effectively by liver transplantation, [35][36][37][38][39] their treatment with portacaval shunting has been abandoned. Between 1965 and 1980, however, shunt surgery was the safest therapy available.…”