Acquired PiZZ alpha-1 antitrypsin deficiency in a liver transplant recipient.

Abstract

Most people with a severe alpha-1 antitrypsin (AAT) deficiency have a PiZZ genotype. The estimated frequency of PiZZ is 1 in 2000–7000 (1). Liver disease in AAT deficiency is a storage hepatopathy with periodic acid-Schiff-positive diastase resistant (PAS-D) globules of AAT within the cytoplasm of periportal hepatocytes (2), but few patients present clinical evidence of liver disease (3). A 45-year-old male with end stage alcoholic liver cirrhosis received a cadaveric liver transplant in 1996. The donor was a 43-year-old male with normal liver function tests and without known history of liver or pulmonary disease, who died from a severe head injury following a car accident. He received immunosuppressive therapy with prednisone, azathioprine and cyclosporine. The postoperative course was uneventful and without episodes of rejection. He was discharged to home 24 days posttransplant. Seventeen months posttransplant, he remained asymptomatic but a routine check-up showed: bilirubin, 0.7 mg/dl; AST, 83 U/L (5–40); ALT, 135 U/L (5–40); GGT, 136 U/L (5–45); alkaline phosphatase, 470 U/L (91–258). Relapse in alcohol abuse and other possible causes of late posttransplant liver dysfunction were ruled out; a liver biopsy showed a mild lymphocytic portal hepatitis and globules of AAT within periportal hepatocytes. The serum AAT was then studied and found to be repeatedly low, between 29.5 and 35.1 mg/dl. Prior to transplantation, AAT serum was normal at 205 mg/dl. The phenotype was now PiZZ; a retrospective study of the pretransplant liver tissues showed a PiMM genotype in the recipient and PiZZ in the donor. Postreperfusion liver biopsy was restudied and showed few large AAT deposits without liver disease (Fig 1). The patient was treated with ursodeoxycholic acid and remained asymptomatic over the next 6 years with uneven, slightly elevated cholestatic enzymes: bilirubin, 0.7–1.5 mg/dl; AST, 35–60 U/L; ALT; 35–67 U/L; GGT, 250–531 U/L, alkaline phosphatase, 320–415 U/L. A repeated biopsy at 6 years posttransplant showed numerous PAS-D globules and a mild chronic portal hepatitis with portal fibrosis (Fig 1).Figure 1. (A, B) Postreperfusion liver biopsy from the donor liver showing a few large PAS positive diastase resistant intracytoplasmic globules in periductal hepatocytes (A,: arrows ) and anti α-1 antitrypsin antibodies (B, arrows ) with positive immunofluorescent stain. The biopsy taken six years later shows diffuse, numerous, small PAS positive globules in many hepatocytes (C) with positive immunofluorescent stain with specific antiserum (D). Moderate portal fibrosis is better seen with Mason’s trichrome (E) and silver reticulin stain (F).This case represents a liver transplant from a healthy donor with an acquired PiZZ phenotype and an unknown PiZZ AAT deficiency. The recipient developed a late rise of cholestatic enzymes with mild, asymptomatic portal hepatitis and fibrosis associated with AAT deposits. A rapid course of recurrent hepatitis C has been described in association with AAT deficiency transmitted from the donor (4). Living donors are regularly checked for AAT deficiency (5); any AAT deficient livers, as well as those from cadaveric donors, can probably be used anyway, provided that the donor liver presents no liver disease and the recipient’s hepatopathy is not likely to recur.