543: Effects of Pregabalin and Gabapentin on Liver Enzymes in Patients with Chronic Neuropathic Pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Pharmacological treatments, Treatment/management

Background and Aims: Pregabalin and gabapentin are widely used in Malaysia for neuropathic pain, fibromyalgia, and partial epilepsy, and are generally considered to have favorable safety profiles. Although manufacturer data report low incidences of liver enzyme elevation, anecdotal reports and real-world clinical observations suggest variable findings, with limited comparative evidence on their long-term hepatic effects. This study aims to evaluate and compare the impact of pregabalin and gabapentin on liver function, focusing on changes in AST and ALT levels to assess potential hepatotoxicity in routine clinical practice.

Methods: This retrospective observational study included 365 patients with chronic neuropathic pain treated at the Pain Clinic, Hospital Kuala Lumpur, in 2024. Baseline liver function tests were reviewed, and changes in aspartate transaminase (AST) and alanine transaminase (ALT) levels during treatment were analyzed to assess potential hepatotoxicity. Eligible participants were aged ≥13 years, newly initiated on pregabalin or gabapentin and on a stable dose for at least four weeks, with documented normal baseline liver function. Patients with pre-existing liver disease, abnormal baseline enzymes, significant comorbidities, severe psychiatric disorders, or pregnancy/breastfeeding were excluded.

Results: Thirty-eight patients developed deranged liver function tests (LFT), with abnormal AST in 24 (63.2%) and abnormal ALT in 25 (65.8%), demonstrating overlapping enzyme abnormalities. In the gabapentin group (n=18), 55.6% had abnormal AST and 66.7% abnormal ALT. In the pregabalin group (n=20), 70.0% had abnormal AST and 65.0% abnormal ALT, showing comparable proportions between groups. Linear regression revealed no clinically meaningful association between cumulative dose and liver enzyme elevation (R² < 0.03). Although statistical significance was observed in selected gabapentin models (p < 0.05), effect sizes were negligible. These findings do not support dose-dependent hepatotoxicity of gabapentinoids.

Conclusions: In this retrospective observational study, liver function test derangement was relatively uncommon and occurred at comparable rates among patients treated with pregabalin and gabapentin. Although transaminase elevations were identified in a subset of patients, no statistically significant differences were observed between treatment groups, and regression analyses demonstrated minimal explanatory power, indicating no clinically meaningful dose–response relationship. Collectively, these findings suggest that gabapentinoids are associated with a low risk of hepatotoxicity in patients with chronic neuropathic pain.

References: 1) Malaysian Association Study of Pain. Management of Neuropathic Pain. 2nd edition 2012. Available at https://www.masp.org.my/index.cfm?menuid=21. Assessed 20 March 2025.
2) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Gabapentin.Available from: https://www.ncbi.nlm.nih.gov/books/NBK548252/. Assessed 20 March 2055.
3) Raouf M, Atkinson TJ, Crumb MW, Fudin J. Rational dosing of gabapentin and pregabalin in chronic kidney disease. J Pain Res. 2017 Jan 27;10:275-278.
4) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Pregabalin. [Updated 2020 Jul 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548053/. Assessed 20 March 2025.
5) Jackson CD, Clanahan MJ, Joglekar K, Decha-Umphai ST. Hold the Gaba: A Case of Gabapentin-induced Hepatotoxicity. Cureus. 2018 Mar 4;10(3):e2269.
6) Ali Jabbar Abdulhussein, Mahmood Kahtan, Ammar A. Fadhil. The Effect of Gabapentin on Liver Tissues and Enzymes in Rats. Journal of Pharmaceutical Negative Results. Volume 13. 2022.
7) Jose J. Statins and its hepatic effects: Newer data, implications, and changing recommendations. J Pharm Bioallied Sci. 2016 Jan-Mar;8(1):23-8.
8) Averbukh LD, Turshudzhyan A, Wu DC, Wu GY. Statin-induced Liver Injury Patterns: A Clinical Review. J Clin Transl Hepatol. 2022 Jun 28;10(3):543-552.

Presenting Author: MAK KIT MUN
Submitting Author: KIT MUN MAK

Senior Author: TAN HUNG LING

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• ALVIS LEE TIAN YEE: MD - HOSPITAL KUALA LUMPUR
• HUZAIFAH BIN ABDUL WAHAB: MBBS - HOSPITAL KUALA LUMPUR