Nonalcoholic fatty liver disease: A potential consequence of tumor necrosis factor-inhibitor therapy

Linda A. Feagins, Avegail Flores, Cristina Arriens, Christina Park, Terri Crook, Andreas Reimold, Geri Brown

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Introduction Although tumor necrosis factor inhibitors (TNFi) might be expected to protect against nonalcoholic fatty liver disease (NAFLD), we have seen patients who appeared to develop NAFLD during TNFi treatment. We aimed to explore risk factors for this TNFi complication in a case-control study. Methods We reviewed clinic records at our VA hospital to identify patients with inflammatory diseases who developed aminotransferase elevations during TNFi therapy and who had liver biopsies showing NAFLD. These patients were matched with patients in each of three control groups: (i) inflammatory disease controls: patients on TNFi treatment with normal aminotransferase levels, (ii) nonalcoholic steatohepatitis (NASH) controls: patients with biopsy-proven NASH with no other inflammatory disease, and (iii) healthy controls. Genotyping was performed for PNPLA3, a gene predisposing to NASH. Results We identified eight cases (five steatohepatitis, three steatosis); elevated aminotransferase levels were first observed 1-63 months into TNFi therapy (average 12 months). TNFi therapy was stopped in five patients, whose aminotransferase levels then normalized within 2-8 months. There were no significant differences between cases and inflammatory disease controls in the frequency of features of metabolic syndrome. Cases had more methotrexate exposure than inflammatory controls (50 vs. 12.5%, P=0.28). PNPLA3 genotyping revealed mutations in 75% of cases, 38% of inflammatory controls, 88% of NASH controls, and 63% of healthy controls (P=NS). Conclusion Our findings suggest that NAFLD can be a side effect of TNFi therapy, and that methotrexate exposure and PNPLA3 gene mutations might be risk factors. Further studies are needed to determine how TNFi causes NAFLD and to confirm these risk factors.

Original languageEnglish (US)
Pages (from-to)1154-1160
Number of pages7
JournalEuropean Journal of Gastroenterology and Hepatology
Issue number10
StatePublished - Sep 18 2015


  • PNPLA3
  • inflammatory diseases
  • nonalcoholic steatohepatitis
  • tumor necrosis factor inhibitor

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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