Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3

Authors

  • Mattias Mandorfer,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Berit A. Payer,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Philipp Schwabl,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Sebastian Steiner,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Arnulf Ferlitsch,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Maximilian C. Aichelburg,

    1. Vienna HIV & Liver Study Group, Vienna, Austria
    2. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
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  • Albert F. Stättermayer,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • Peter Ferenci,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • Barbara Obermayer-Pietsch,

    1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria
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  • Katharina Grabmeier-Pfistershammer,

    1. Vienna HIV & Liver Study Group, Vienna, Austria
    2. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
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  • Michael Trauner,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Markus Peck-Radosavljevic,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
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  • Thomas Reiberger

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
    2. Vienna HIV & Liver Study Group, Vienna, Austria
    • Correspondence

      Thomas Reiberger, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria

      Tel: +43 140400 4744

      Fax: +43 140400 4735

      e-mail: thomas.reiberger@meduniwien.ac.at

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Abstract

Background & Aims

To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients.

Patients & Methods

25(OH)D deficiency (25(OH)DDEF), IR and low CD4+ T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml−1, HOMA-IR >2 and CD4nadir <200 cells × μl−1 respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group.

Results

Among 86 HIV/HCV, the median FPR was 0.167 units × years−1. While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05–8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05–15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4+ nadir and 25(OH)D levels.

Conclusions

Two potentially modifiable factors, CD4+ nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.

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