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Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcoholic fatty liver disease: a retrospective cohort
  1. Kuo-Tung Tang1,2,3,
  2. Jean-François Dufour4,5,
  3. Po-Hung Chen6,
  4. Ruben Hernaez7,8,
  5. Susan Hutfless6
  1. 1Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan
  2. 2Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
  3. 3School of Medicine, National Yang-Ming University, Taipei, Taiwan
  4. 4Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, Bern, Switzerland
  5. 5Department of Biomedical Research, University of Bern, Bern, Switzerland
  6. 6Division of Gastroenterology & Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  7. 7Section of Gastroenterology, Michael E DeBakey VA Medical Center, Houston, Texas, USA
  8. 8Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA
  1. Correspondence to Dr Susan Hutfless; shutfle1{at}


Objective Elevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD.

Design This retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure.

Results This study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25–1.90).

Conclusion In the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.

  • IBD
  • TNF-alpha
  • liver cirrhosis
  • nonalcoholic steatohepatitis

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  • Contributors K-TT and SH designed and conceived the study, conducted data analysis, and drafted and revised the manuscript. J-FD, P-HC and RH revised the manuscript. All authors discussed the results and contributed to the final manuscript.

  • Funding K-TT received financial support from Taichung Veterans General Hospital and Veterans Affairs Council, R.O.C. P-HC is supported by National Center for Advancing Translational Sciences KL2TR001077. P-HC and SH are investigators at the Hopkins Digestive Diseases Basic & Translational Research Core Center P30DK089502 and received support from the Helmsley Charitable Trust. RH is an investigator at the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, Texas, USA.

  • Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was conducted in compliance with the Declaration of Helsinki and has been approved by the Institutional Review Board at Johns Hopkins University (IRB No. 00054790).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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