Liver Transplantation in Alpha-1 Antitrypsin Deficiency: A Retrospective Case-Control Study in a Brazilian Center

Objectives:  Alpha-1 antitrypsin deficiency (AATD) is a rare genetic metabolic disease curable with liver transplantation (LT). The aim of this study was to comparatively evaluate patients with LT due to AATD and other causes.

Methods:  Observational, retrospective, analytical, case-control study evaluating 2,511 LT patients, 19 (0.75%) with AATD, from May 2002 to December 2024. Data were obtained by reviewing the medical records and stored in the REDCap program.

Results:  The median age of AATD and non-AATD (NAATD) patients was similar (56.3 [Δ7-71] and 52.4 [Δ6-78]; p = 0.92, respectively). Males predominated in both groups. The pre-LT Model for End-Stage Liver Disease (MELD)-Na scores for AATD and NAATD patients were 20 (Δ8-24) and 18 (Δ6-72), respectively. Two patients with AATD had positive serologies compatible with previous hepatitis B infection. Three patients also had a clinical epidemiological diagnosis of concomitant nonalcoholic fatty liver disease. The diagnosis of AATD was made only through explant in nine patients (n = 47.4%). The mean pre-transplant alpha-1 antitrypsin dosage was 33.42 mg/dL (Δ19-59.5). All patients who underwent immunophenotyping had the PiZZ phenotype. The indication for LT was decompensated cirrhosis (DC); three patients (16.4%) had concomitant hepatocellular carcinoma (HCC), one diagnosed only in the explant. The incidence of HCC was 15.9% (AATD) and 31.3% (NAATD) (p = 0.34). None of the patients with AATD had severe lung disease. The survival of patients with AATD submitted to LT at 30 days, 1, and 5 years was 94.7, 88.2, and 64.7%, respectively, similar to the other causes (91.4, 80.1, and 68.1%; p = 0.47).

Conclusion:  AATD was a rare cause of LT due to DC and HCC, predominantly in adults with piZZ phenotype without relevant pulmonary involvement, and whose diagnosis is frequently made after LT. The epidemiology, indication, prevalence of HCC, and survival were similar to those of other causes of LT.

Descriptors
Alpha-1 Antitrypsin Deficiency; Liver Transplantation; Cirrhosis; Hepatocellular Carcinoma; Retrospective Study