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Publications

Journal Article Ahead of print

PubMed: 42860594 DOI: 10.1111/hiv.70322

Chronic alanine aminotransferase elevation in people with HIV: Time trends over 22 years and genetic predisposition.

HIV Med

Authors: Noemi R Simon, Carlotta Mondoka, Christian W Thorball, Isabella C Schoepf, Lene Ryom, Irene Abela, Charles Béguelin, Urs Führer, Helen Kovari, Catia Marzolini, Annalisa Marinosci, Christian Kahlert, Luigia Elzi, David Haerry, Matthias Cavassini, Bruno Ledergerber, Jacques Fellay, Gilles Wandeler, Philip E Tarr

Affiliations

  • Infectious Diseases Service and University Center for Internal Medicine, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.
  • Division of Infectious Diseases, University Hospital Basel, Basel, Switzerland.
  • Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
  • Biomedical Data Science Center, Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Center of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Department of Infectious Diseases, Hvidovre University Hospital, Copenhagen, Denmark.
  • Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Biel Hospital, Biel, Switzerland.
  • Center for Infectious Diseases, Klinik im Park Hirslanden, Zurich, Switzerland.
  • Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, University Hospital Lausanne and University of Lausanne, Lausanne, Switzerland.
  • Division of Infectious Diseases, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland.
  • Centre for Experimental Therapeutics, University of Liverpool, Liverpool, UK.
  • Division of Infectious Disease, Geneva University Hospital, Geneva, Switzerland.
  • Division of Infectious Diseases, Kantonsspital St Gallen, St. Gallen, Switzerland.
  • Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Division of Infectious Diseases, Repubblica e Cantone Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • University of Southern Switzerland, Lugano, Switzerland.
  • Positivrat, Bern, Switzerland.
  • Infectious Diseases Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
  • Department of Clinical Research, University Hospital Basel, Basel, Switzerland.

Abstract

INTRODUCTION

Chronic elevation of alanine aminotransferase (cALT) is common in people with HIV. Published reports on cALT prevalence time trends have not been uniform. It is unknown whether genetic background is associated with cALT in people with HIV.

METHODS

cALT was defined as ALT levels (male, >50 U/L, female, >35 U/L) at ≥2 consecutive, 6-monthly per protocol Swiss HIV Cohort Study (SHCS) visits. We calculated cALT prevalence plus trends in time-updated clinical and HIV-related cALT risk factors per calendar year in SHCS participants without viral hepatitis co-infection. In cALT cases and matched controls, we obtained uni- and multivariable odds ratios (ORs) for cALT, adjusting additionally for a polygenic risk score (PGS) associated with transaminase levels in the general population.

RESULTS

Between 2002 and 2023, 8'909 SHCS participants contributed 203'832 ALT values obtained per protocol, and 8'414 cALT events occurred. The yearly cALT prevalence increased significantly (p < 0.001) from 7.5% (95% confidence interval, 6.3%-8.9%) in 2002 to the highest level of 10.1% (9.1%-11.1%) in 2005, followed by a significant (p < 0.001) decline to 5.3% (4.8%-5.9%) in 2018, with stable rates thereafter (p = 0.280). An increased multivariable cALT-OR was noted for obesity (OR = 2.84; 1.99-4.07), for 6-12-month exposure to non-nucleoside reverse transcriptase inhibitors (OR = 2.09; 1.09-4.03) and tenofovir disoproxil fumarate (OR = 1.99; 1.15-3.46). Participants with unfavourable genetic background (top vs. bottom quintile of PGS) had a multivariable-adjusted cALT-OR of 4.44 (3.09-6.39).

CONCLUSION

cALT prevalence has decreased by almost half in people with HIV in Switzerland since 2005. Unfavourable genetic background is a strong independent risk factor for cALT.

MeSH

Alanine Transaminase, Tenofovir, Alanine, Genetic Predisposition To Disease, Transaminases, Prevalence, Risk Factors, Genetic Background, Genetic Risk Score