PMID- 37144533
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20230512
IS  - 1531-7056 (Electronic)
IS  - 0267-1379 (Linking)
VI  - 39
IP  - 3
DP  - 2023 May 1
TI  - Cleaning up alpha-1 antitrypsin deficiency related liver disease.
PG  - 163-168
LID - 10.1097/MOG.0000000000000919 [doi]
AB  - PURPOSE OF REVIEW: Alpha-1 antitrypsin deficiency (AATD) is one of the most 
      common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) 
      gene affecting primarily the lung and the liver. This review summarizes the 
      pathophysiology and clinical manifestation of different AATD genotypes and 
      discusses the recent therapeutic developments. The focus is on the severe, rare 
      homozygous Pi *ZZ and the common heterozygous Pi *MZ genotype. RECENT FINDINGS: 
      Pi *ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and 
      cirrhosis than noncarriers and liver transplantation is currently the only 
      available therapeutic option. AATD constitutes a proteotoxic disorder arising 
      from hepatic AAT accumulation and the currently most promising data come from a 
      phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi *MZ 
      subjects display an increased risk of advanced liver disease and at the latter 
      stage, a faster deterioration than individuals without AAT mutation. SUMMARY: 
      Although the fazirsiran data offer a glimpse of hope to AATD patients, a 
      consensus on appropriate study endpoint, a careful patient selection as well as 
      monitoring of long-term safety will be essential for an approval.
CI  - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Rademacher, Laura
AU  - Rademacher L
AD  - Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, 
      University Hospital RWTH Aachen, Healthcare Provider of the European Reference 
      Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
FAU - Fromme, Malin
AU  - Fromme M
FAU - Strnad, Pavel
AU  - Strnad P
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230301
PL  - United States
TA  - Curr Opin Gastroenterol
JT  - Current opinion in gastroenterology
JID - 8506887
SB  - IM
MH  - Humans
MH  - *alpha 1-Antitrypsin Deficiency/complications/genetics
MH  - Liver Cirrhosis/etiology/therapy
MH  - Genotype
MH  - *Liver Transplantation/adverse effects
EDAT- 2023/05/05 06:42
MHDA- 2023/05/08 06:42
CRDT- 2023/05/05 05:45
PHST- 2023/05/08 06:42 [medline]
PHST- 2023/05/05 06:42 [pubmed]
PHST- 2023/05/05 05:45 [entrez]
AID - 00001574-202305000-00008 [pii]
AID - 10.1097/MOG.0000000000000919 [doi]
PST - ppublish
SO  - Curr Opin Gastroenterol. 2023 May 1;39(3):163-168. doi: 
      10.1097/MOG.0000000000000919. Epub 2023 Mar 1.