Liver Injury Due to Hormonal Contraceptives in the Modern Era.
4 affiliations
- 1Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, USA.
- 2UNC Health, Chapel Hill, USA.
- 3NIH/NIDDK, Bethesda, USA.
- 4Duke Clinical Research Institute, Durham, USA.
Abstract
Background and aims
Hormonal agents and their association with liver injury remain a concern in clinical practice. This study aimed to characterise the biochemical and clinical features of hormonal agent-associated liver injury and compare them with a control group of age- and gender-matched cases of liver injury caused by non-hormonal drugs.Methods
Of 2123 adjudicated drug-induced liver injury cases enrolled in the Drug-Induced Liver Injury Network (2004-2024), 20 high-confidence cases (1.3%) were attributed to hormonal agents. These cases were compared with age- and sex-matched non-hormonal drug-induced liver injury (DILI) controls, and analyses assessed clinical features, biochemical patterns, outcomes, HLA alleles and candidate genetic variants associated with cholestatic liver disease.Results
The median age of women was 22 years. Most presented within 2-12 weeks with jaundice and pruritus, predominantly with cholestatic or mixed patterns of liver enzyme elevations, but a hepatocellular pattern was not uncommon at 28%. The route of administration did not appear to influence DILI risk. Half underwent a liver biopsy, and half required hospitalization, but none died or required liver transplantation. Compared with other DILI cases, hormonal agent-associated liver injury was more often cholestatic, with jaundice and pruritus, and less frequently associated with fever or rash. No HLA association was identified, although the intronic MROH2A variant rs6722064 ranked as the top potential candidate for increased risk [OR (95% CI) = 3.58 (1.67, 7.65), p = 0.001].Conclusions
Hormonal agent-associated liver injury presents with a distinctive mixed or cholestatic pattern and often lacks the inflammatory features seen in other DILI cases. These findings underscore the need for greater clinical awareness to improve patient outcomes.
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BibTeX
@article{vuppalanchi2026liver,
title = {{Liver Injury Due to Hormonal Contraceptives in the Modern Era.}},
author = {Raj Vuppalanchi and A Sidney Barritt and Anjali Rai and Huiman Barnhardt and Sherry Gu and Yi-Ju Li and Naga Chalasani and Drug‐Induced Liver Injury Network},
journal = {Liver international : official journal of the International Association for the Study of the Liver},
year = {2026},
month = nov,
doi = {10.1111/liv.70945},
url = {https://europepmc.org/article/MED/42969678},
note = {CC BY},
}
RIS
TY - JOUR
TI - Liver Injury Due to Hormonal Contraceptives in the Modern Era.
AU - Raj Vuppalanchi
AU - A Sidney Barritt
AU - Anjali Rai
AU - Huiman Barnhardt
AU - Sherry Gu
AU - Yi-Ju Li
AU - Naga Chalasani
AU - Drug‐Induced Liver Injury Network
PY - 2026
DA - 2026/11/02
JO - Liver international : official journal of the International Association for the Study of the Liver
DO - 10.1111/liv.70945
UR - https://europepmc.org/article/MED/42969678
AB - Background and aims Hormonal agents and their association with liver injury remain a concern in clinical practice. This study aimed to characterise the biochemical and clinical features of hormonal agent-associated liver injury and compare them with a control group of age- and gender-matched cases of liver injury caused by non-hormonal drugs.Methods Of 2123 adjudicated drug-induced liver injury cases enrolled in the Drug-Induced Liver Injury Network (2004-2024), 20 high-confidence cases (1.3%) were attributed to hormonal agents. These cases were compared with age- and sex-matched non-hormonal drug-induced liver injury (DILI) controls, and analyses assessed clinical features, biochemical patterns, outcomes, HLA alleles and candidate genetic variants associated with cholestatic liver disease.Results The median age of women was 22 years. Most presented within 2-12 weeks with jaundice and pruritus, predominantly with cholestatic or mixed patterns of liver enzyme elevations, but a hepatocellular pattern was not uncommon at 28%. The route of administration did not appear to influence DILI risk. Half underwent a liver biopsy, and half required hospitalization, but none died or required liver transplantation. Compared with other DILI cases, hormonal agent-associated liver injury was more often cholestatic, with jaundice and pruritus, and less frequently associated with fever or rash. No HLA association was identified, although the intronic MROH2A variant rs6722064 ranked as the top potential candidate for increased risk [OR (95% CI) = 3.58 (1.67, 7.65), p = 0.001].Conclusions Hormonal agent-associated liver injury presents with a distinctive mixed or cholestatic pattern and often lacks the inflammatory features seen in other DILI cases. These findings underscore the need for greater clinical awareness to improve patient outcomes.
SN - 1478-3223
SN - 1478-3231
ER -