Duggal S, Kattamuri L, Sairam S. Three-year outcomes of tumor necrosis factor alpha inhibitor therapy in rheumatoid arthritis patients with elevated liver enzymes. World J Hepatol 2025; 17(7): 108051 [DOI: 10.4254/wjh.v17.i7.108051]
Corresponding Author of This Article
Shivangini Duggal, MD, Department of Internal Medicine, Texas Tech University Health Sciences Center, 4801 Alberta Ave, El Paso, TX 79905, United States. sduggal@ttuhsc.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Shivangini Duggal, Lakshmi Kattamuri, Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, United States
Shrilekha Sairam, Division of Rheumatology, Department of Internal Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, United States
Author contributions: Duggal S and Kattamuri L were responsible for the investigation and review of relevant data and articles; Sairam S was responsible for review and editing; Duggal S, Kattamuri L, and Sairam S were responsible for this paper, data analysis, and the original draft; all authors discussed the findings described in the case and approved the final manuscript.
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Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shivangini Duggal, MD, Department of Internal Medicine, Texas Tech University Health Sciences Center, 4801 Alberta Ave, El Paso, TX 79905, United States. sduggal@ttuhsc.edu
Received: April 8, 2025 Revised: April 29, 2025 Accepted: June 13, 2025 Published online: July 27, 2025 Processing time: 113 Days and 1.3 Hours
Abstract
BACKGROUND
Elevated liver enzymes in rheumatoid arthritis (RA) are often attributed to multiple factors including disease activity and treatment-related adverse effects. Tumor necrosis factor inhibitors (TNFi) have shown mixed effects on liver function, with varying safety profiles among agents.
AIM
To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes.
METHODS
A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1, 2019, and September 30, 2024. Out of the patients screened, 9 met the inclusion criteria. Trends in liver enzymes, fibrosis-4 (FIB-4) score, and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods.
RESULTS
Among 9 patients (4 on adalimumab, 5 on etanercept), the median age was 56 years [interquartile range (IQR): 49.5–64.5 years], 77.8% were female, and the median body mass index was 36.99 kg/m² (IQR: 30.95–43.43 kg/m²). Median baseline FIB-4 was 1.25 (IQR: 1.02–1.65), with no cirrhosis observed at baseline. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels declined consistently, with significant reductions from baseline to 3 years (P = 0.003). FIB-4 scores also significantly decreased (P = 0.003), while albumin, bilirubin, and Child-Pugh class remained stable at the 3-year follow-up. At 3 years, 66.7% achieved RA remission (P = 0.03).
CONCLUSION
TNFi therapy (adalimumab or etanercept) was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation, supporting its safety in our cohort of RA patients with liver involvement. Larger prospective studies are warranted to further validate these findings.
Core Tip: Rheumatoid arthritis (RA) patients often present with elevated liver enzymes, complicating the safe administration of immunosuppressive therapies. This retrospective study evaluated the hepatic safety of tumor necrosis factor inhibitors (TNFi)—etanercept and adalimumab—in RA patients with persistently elevated liver enzymes. Over a 3-year follow-up, TNFi therapy led to statistically significant improvements in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and fibrosis-4 scores, without hepatic decompensation or changes in Child-Pugh class. These findings suggest that TNFi therapy may be hepatologically safe and potentially beneficial in liver enzyme normalization among this high-risk population.
