Z Gastroenterol 2014; 52 - P47
DOI: 10.1055/s-0034-1376031

Revisiting Liver Disease Progression in HIV/HCV-coinfected Patients: The Influence of Vitamin D, Insulin resistance, Immune status, IL28B and PNPLA3

M Mandorfer 1, 2, BA Payer 1, 2, P Schwabl 1, 2, S Steiner 1, 2, A Ferlitsch 1, 2, MC Aichelburg 2, 3, AF Stättermayer 1, P Ferenci 1, B Obermayer-Pietsch 4, K Grabmeier-Pfistershammer 3, M Trauner 1, 2, M Peck-Radosavljevic 1, 2, T Reiberger 1, 2
  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  • 2Vienna HIV & Liver Study Group, Vienna, Austria
  • 3Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
  • 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University Graz, Graz, Austria

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 levels (25(OH)D), 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.

Methods: 25(OH)D deficiency (25(OH)DDEF), IR and low CD4 T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D< 20ngxmL-1, HOMA-IR> 2 and CD4nadir< 200cellsxµL-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 0.1667unitsxyears-1. While the prevalence of prior alcohol abuse (highFPR: 46% vs. lowFPR: 25%; P= 0.037), lowCD4NAD (highFPR: 43% vs. lowFPR: 22%; P= 0.039) and 25(OH)DDEF (highFPR: 78% vs. lowFPR: 41%; P< 0.001) was higher among highFPR patients, the prevalence of IR (highFPR: 55% vs. lowFPR: 49%; P= 0.553) was comparable. The association between 25(OH)DDEF and FPR (highFPR: 90% vs. lowFPR: 31%; P< 0.001) was confirmed in a subgroup of patients with METAVIR F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C (highFPR: 38% vs. lowFPR: 31%; P= 0.483) and PNPLA3 non-C/C (highFPR: 46% vs. lowFPR: 43%; P= 0.775) was similar, while PNPLA3 G/G (highFPR: 11% vs. lowFPR: 0%; P= 0.031) was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.947; 95% CI: 1.05 – 8.24; P = 0.034) 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 (ρ= 0.447; P< 0.001), HCV-genotype 3 (ρ= 0.252; P= 0.034), CD4+ nadir (ρ=-0.288; P= 0.015), lowCD4NAD (ρ= 0.286; P= 0.016) and 25(OH)D (ρ=-0.246; P= 0.038).

Conclusions: Two potentially modifiable factors, CD4+ nadir and 25(OH)D, 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. The findings of our study suggest, that early initiation of combined antiretroviral therapy, as well as vitamin D supplementation and vitamin D receptor ligands could be of therapeutic value for the reduction liver fibrosis progression in HIV/HCV-coinfected patients.