Researchers studying the relationship between liver disease progression and liver disease-related clinical events in patients with the alpha-1 antitrypsin deficiency (AATD)-associated liver disease protease inhibitor ZZ (AATD-LD-PiZZ) genotype found that those without lung disease were more likely to require a liver transplant than those with lung disease.

“Among pts with [fibrosis stage 3] at baseline, those with [liver disease] alone progressed more than twice as fast to [fibrosis stage 3 with compensated cirrhosis] ≤ 5 y than pts with both [liver disease] and lung disease,” the authors wrote. The study will be presented at this year’s The Liver Meeting in November.

Data for the study were collected from the electronic health record at the Mayo Clinic Healthcare System from January 2004 to September 2021. Patients were placed into 2 groups (with and without lung disease) according to their status at baseline. Fibrosis was also assessed at baseline and during follow-up. Descriptive statistics and Kaplan-Meier analysis for time-to-event were used to analyze data.

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Five hundred-one patients had the AATD-PiZZ genotype; 316 qualified for the study. In the 2 study groups, with and without lung disease, the mean age of the participants was 52 vs 49 years, 59% vs 58% were male, respectively, and they were distributed by varying stages of fibrosis.

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At follow-up, 23% of patients without lung disease had a liver transplant vs 8% of patients with lung disease. In addition, liver disease occurred in 88 of 132 (67%) vs 24 of 65 (37%) patients, respectively, with 98% vs 100% among those with fibrosis stage 3 with compensated cirrhosis at baseline. 

“Patients with AATD-LD-PiZZ without concurrent lung disease were almost three times more likely to undergo liver transplant,” the authors said. Patients with only liver disease progressed more quickly to fibrosis stage 3 with compensated cirrhosis in less than 5 years than those who had both liver and lung disease. The authors suggested that more research is needed to elucidate the impact of lung disease on the progression of liver disease in AATD-LD-PiZZ.


Wu T, Hagiwara M, Gnass E, et al. Characterizing liver disease (LD) progression in alpha-1 antitrypsin deficiency (AATD) with versus (vs) without lung disease. Hepatology. 2022;76(S1):S137. doi:10.1002/hep.32697