Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy

PLoS One. 2015 Sep 29;10(9):e0138838. doi: 10.1371/journal.pone.0138838. eCollection 2015.

Abstract

Objectives: To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients.

Methods: Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals.

Results: Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years.

Conclusion: TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Biomarkers / blood
  • Biopsy / methods*
  • Cohort Studies
  • Coinfection / virology
  • Disease Progression
  • Elasticity Imaging Techniques*
  • Female
  • HIV Infections / complications
  • HIV Infections / diagnosis*
  • HIV Infections / virology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / diagnosis*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver / pathology
  • Liver / surgery
  • Liver / virology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / virology
  • Male
  • Prospective Studies
  • ROC Curve
  • Severity of Illness Index

Substances

  • Anti-Retroviral Agents
  • Biomarkers

Grant support

This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #148522), by SHCS project #474 and by the SHCS research foundation. The data are gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers). The study was supported by an unrestricted grant from Schering-Plough. Biopredictive offered a 50% discount for Fibrotest calculations. ELF-test was financed by Siemens. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.