Rethinking FIB-4: The hidden zonal bias in alpha-1 antitrypsin deficiency
Abdulrasak, Mohammed LU
(2025)
In Hepatology communications
9(8).
- Abstract
- Noninvasive fibrosis scores, particularly Fibrosis-4 (FIB-4), are widely used in hepatology due to their accessibility and simplicity.1 The FIB-4 index combines age, AST, platelet count, and ALT into a formula validated primarily in hepatitis C and metabolic dysfunction–associated steatotic liver disease, which typically cause zone III (centrilobular) hepatocyte injury and transaminase elevation.1,2
In contrast, alpha-1 antitrypsin deficiency (AATD) represents a distinct pattern of injury, with fibrosis originating in zone I (periportal) hepatocytes due to intracellular retention of Z-type alpha-1 antitrypsin polymers.3 This pathogenesis is often not associated with overt hepatocyte necrosis, and consequently, serum ALT levels may... (More) - Noninvasive fibrosis scores, particularly Fibrosis-4 (FIB-4), are widely used in hepatology due to their accessibility and simplicity.1 The FIB-4 index combines age, AST, platelet count, and ALT into a formula validated primarily in hepatitis C and metabolic dysfunction–associated steatotic liver disease, which typically cause zone III (centrilobular) hepatocyte injury and transaminase elevation.1,2
In contrast, alpha-1 antitrypsin deficiency (AATD) represents a distinct pattern of injury, with fibrosis originating in zone I (periportal) hepatocytes due to intracellular retention of Z-type alpha-1 antitrypsin polymers.3 This pathogenesis is often not associated with overt hepatocyte necrosis, and consequently, serum ALT levels may remain within or near normal limits even in the presence of significant fibrosis. This short communication highlights a systematic underestimation of fibrosis in AATD when using FIB-4, due to a zonal mismatch between disease biology and biomarker dynamics. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/58412648-f3fa-4f18-891f-f204e422f372
- author
- Abdulrasak, Mohammed
LU
- organization
- publishing date
- 2025-08-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Hepatology communications
- volume
- 9
- issue
- 8
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:40658811
- scopus:105011139523
- ISSN
- 2471-254X
- DOI
- 10.1097/HC9.0000000000000775
- language
- English
- LU publication?
- yes
- id
- 58412648-f3fa-4f18-891f-f204e422f372
- date added to LUP
- 2025-07-15 21:32:09
- date last changed
- 2025-08-22 04:01:43
@article{58412648-f3fa-4f18-891f-f204e422f372,
abstract = {{Noninvasive fibrosis scores, particularly Fibrosis-4 (FIB-4), are widely used in hepatology due to their accessibility and simplicity.1 The FIB-4 index combines age, AST, platelet count, and ALT into a formula validated primarily in hepatitis C and metabolic dysfunction–associated steatotic liver disease, which typically cause zone III (centrilobular) hepatocyte injury and transaminase elevation.1,2<br/><br/>In contrast, alpha-1 antitrypsin deficiency (AATD) represents a distinct pattern of injury, with fibrosis originating in zone I (periportal) hepatocytes due to intracellular retention of Z-type alpha-1 antitrypsin polymers.3 This pathogenesis is often not associated with overt hepatocyte necrosis, and consequently, serum ALT levels may remain within or near normal limits even in the presence of significant fibrosis. This short communication highlights a systematic underestimation of fibrosis in AATD when using FIB-4, due to a zonal mismatch between disease biology and biomarker dynamics.}},
author = {{Abdulrasak, Mohammed}},
issn = {{2471-254X}},
language = {{eng}},
month = {{08}},
number = {{8}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Hepatology communications}},
title = {{Rethinking FIB-4: The hidden zonal bias in alpha-1 antitrypsin deficiency}},
url = {{http://dx.doi.org/10.1097/HC9.0000000000000775}},
doi = {{10.1097/HC9.0000000000000775}},
volume = {{9}},
year = {{2025}},
}