Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV

Leona Dold*, Mette J. Nielsen, Michael Praktiknjo, Carolynne Schwarze-Zander, Christoph Boesecke, Jan Christian Wasmuth, Jenny Bischoff, Jürgen Kurt Rockstroh, Morten A. Karsdal, Ulrich Spengler, Jonel Trebicka, Christian P. Strassburg, Diana J. Leeming, Bettina Langhans

*Corresponding author for this work

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Background and aims: Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. Methods: This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. Results: Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. Conclusion: Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.

Original languageEnglish
Article number52
JournalBMC Infectious Diseases
Number of pages9
Publication statusPublished - 24. Jan 2023


  • Endotrophin
  • Hepatic steatosis
  • HIV
  • Liver fibrosis
  • PC3X
  • PRO-C5
  • PRO-C6
  • Extracellular Matrix/metabolism
  • Humans
  • Procollagen/blood
  • Liver Cirrhosis/blood
  • Antiretroviral Therapy, Highly Active
  • Fatty Liver/blood
  • Collagen Type III/blood
  • HIV Infections/blood
  • Collagen Type VI/blood
  • Biomarkers/blood
  • Collagen Type V/blood
  • Retrospective Studies
  • Liver/diagnostic imaging


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