Abstract

Background: Patients with Alpha-1-antitrypsin Pi*ZZ homozygotes are at risk for developing liver cirrhosis and hepatocellular carcinoma. However, there is a high degree of variability in the clinical manifestations of patients with A1AT Pi*ZZ suggesting that genetic and environmental disease modifiers play an important role in the disease process. The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising worldwide. We aimed to determine the impact of NAFLD in the development of hepatic events in patients with A1AT Pi*ZZ homozygotes.

Methods: All patients with A1AT Pi*ZZ homozygous state seen at a large tertiary care academic institution were identified using the data pooling technique by the information and technology department at University of Iowa Hospitals and Clinics. Patients with NAFLD were identified using ICD codes. Clinical and demographic data as well as hepatic events (ascites, hepatic encephalopathy, esophageal varices, or hepatocellular carcinoma), if any, were also extracted. Logistic regression analysis was performed to determine the impact of NAFLD in the development of hepatic events in patients with A1AT ZZ. Odds ratio (OR) with 95% confidence intervals were calculated.

Results: We identified 53 patients with A1AT ZZ phenotype, 29 (55%) were males. Twenty (38%) of the 53 A1AT ZZ patients had a diagnosis of NAFLD. Of the 53 patients, 14 (26%) developed hepatic events. Eleven (55%) of the 20 patients with A1ATD and NAFLD developed hepatic events, while only 3 (9%) of the 33 patients with A1ATD and without NAFLD developed hepatic events (p<0.001). On logistic regression analysis, NAFLD was significantly associated with the development of hepatic events in patients with A1AT Pi*ZZ, unadjusted OR 12.2 (CI: 2.78-53.6), p<0.001). When adjusted for age, sex, and BMI, NAFLD remained a significant risk factor for the development of hepatic events in patients with Pi*ZZ with an adjusted OR 15.2, (CI: 2.5-94.4), p=0.003.

Conclusion: A1AT ZZ homozygous individuals who also develop NAFLD have a higher risk for the development of hepatic events as compared to those who do not have NAFLD. A1AT ZZ patients should thus be screened for the presence of fatty liver disease and aggressive control of metabolic risk factors should be initiated. A1AT ZZ patients should be strongly advised to avoid weight gain and follow a healthy lifestyle as early in life as possible. Larger studies are needed to confirm our findings.