Alpha1-Antitrypsin Deficiency and Autophagy

The Z deficiency allele (PI*Z) of SERPINA1, which encodes the serine protease inhibitor (PI) alpha1-antitrypsin, results in the formation of intrahepatic inclusions that cause cirrhosis. The only curative therapy for patients with severe liver disease is transplantation. Hidvegi and colleagues recently described a new approach to clear the pathologic inclusions in cell and animal models of liver disease consequent to the Z mutation. The authors used the antiepileptic drug carbamazepine to stimulate “self-eating,” or autophagy.1 The questions now are whether this approach will be useful for treating the liver disease associated with alpha1-antitrypsin . . .