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Selected Publication:
Leitner, M.
Alpha1-Antitrypsin deficiency and liver injury at the Medical University of Graz
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2021. pp. 44
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- Authors Med Uni Graz:
- Advisor:
- Jahnel Jörg
- Wagner Martin
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- Abstract:
- Background: A1AT deficiency is an inherited disease, which primarily leads to lung and liver diseases. Due to the low penetrance of liver disease in genetically affected individuals, the variable natural course and limited specific treatment, many patients with A1AT related liver disease remain undiagnosed. The aim of this study is to determine the number of patients with A1AT deficiency and related liver diseases at the Medical University of Graz and to summarize the natural course of liver disease of these patients. Methods: In this retrospective study we collected data of patients with A1AT deficiency, who visited the Medical University of Graz over the last 16 years. We assessed the time point of diagnosis, severity and complications of liver diseases (i.e. elevated LFTs, steatosis, fibrosis, cirrhosis, HCC, liver transplantation (LTx) or neonatal liver diseases) as well as the natural course and related our findings to the molecular phenotype (i.e. ZZ or MZ phenotype). In addition, we also investigated A1AT deficiency in children and reported the results separately. Results: In total, 148 patients with A1AT deficiency and known phenotype were identified. 93 (62.8%) showed the MZ phenotype, 40 (27%) showed the ZZ phenotype, 8 (5.4%) showed the SZ phenotype, 5 (3.4%) showed the MS phenotype and 2 (1.4%) showed the MMalton phenotype. 62.5% of the ZZ phenotypes and 63.4% of the MZ phenotypes showed signs of liver disease. In ZZ phenotypes with liver disease, 52% showed only biochemical signs of liver disease, 28% developed fibrosis or cirrhosis, with 4% developing HCC and 20% requiring LTx. 28% of the ZZ phenotypes presented with neonatal liver diseases in infancy. In MZ phenotypes with liver disease, 88.1% showed only biochemical signs of liver disease, 10.2% developed fibrosis or cirrhosis, with 1.7% developing HCC and 5.1% requiring LTx. Only 1.7% of MZ phenotypes presented with neonatal liver diseases in infancy. There was no significant change in mean AST or ALT values over an observation period of at least 10 years in both ZZ and MZ phenotypes. Interestingly, ZZ phenotypes showed significantly lower rates of liver steatosis than MZ phenotypes (8% vs. 27.1%, p=0.026). Conclusions: Our study population showed a higher percentage of advanced liver diseases than usually reported in population studies. From this observation we conclude that referral to our tertiary hospital center is more likely taking place only at late disease stages. In contrast to the patients with advanced liver diseases, those adult patients with only mild elevations of LFTs did not progress over an observation period of at least 10 years. Therefore we conclude, that patients with A1AT deficiency, especially pediatric patients, need to be consequently followed up to detect any deterioration in their liver status early. An interesting and unexpected finding of our study was that patients with ZZ phenotype might potentially be protected from liver steatosis. This, however, needs to be determined in larger setting.