Determinants of worse liver‐related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort

Author:

d’Arminio Monforte Antonella1,Tavelli Alessandro1,Salpini Romina2,Piermatteo Lorenzo3,D'Anna Stefano2,Carrara Stefania4,Malagnino Vincenzo5ORCID,Mazzotta Valentina6,Brancaccio Giuseppina7,Marchetti Giulia Carla8,Rosselli Del Turco Elena9,Rossotti Roberto10ORCID,Mussini Cristina11,Antinori Andrea6,Lo Caputo Sergio12,Ceccherini Silberstein Francesca3ORCID,Gaeta Giovanni Battista13,Svicher Valentina3,Puoti Massimo10,

Affiliation:

1. ICONA Foundation Milan Italy

2. Department of Biology University of Rome Tor Vergata Rome Italy

3. Department of Experimental Medicine University of Rome Tor Vergata Rome Italy

4. Unity of Microbiology and Biobank INMI Rome Italy

5. Department of Medicine of Systems University of Rome Tor Vergata Rome Italy

6. Clinical and Research Infectious Diseases Department INMI Rome Italy

7. Infectious Diseases, Department of Molecular Medicine University of Padua Padua Italy

8. Department of Health Sciences ASST Santi Paolo e Carlo, Clinic of Infectious Diseases, University of Milan Milan Italy

9. Department of Medical and Surgical Sciences Alma Mater Studiorum Bologna University Bologna Italy

10. Infectious Diseases Unit ASST Grande Ospedale Metropolitano Niguarda, Niguarda Ca’ Granda Hospital Milan Italy

11. Clinic of Infectious Diseases University Hospital of Modena, University of Modena and Reggio Emilia Modena Italy

12. Clinic of Infectious Diseases University of Foggia Foggia Italy

13. University L. Vanvitelli Infectious Diseases Unit Naples Italy

Abstract

AbstractObjectivesWe aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver‐related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV‐RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated.MethodsPeople living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV‐RNA and HDV genotypes were tested. Primary end‐point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine‐grey regression models were used to evaluate the association of HDV Ab, HDV‐RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end‐points: time to SLRE or death; HDV Ab and HDV‐RNA prevalence.ResultsA total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV‐RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB‐4 > 3.25 were independent factors of HDV Ab positivity. In a median follow‐up of 5 years, 37 PLWH (4.1% at 5‐year) developed SLRE and 97 (12.0%) reached the SLRE or death end‐point. HDV‐RNA positive (independently from HDV‐RNA copy level) PLWH had a 4.6‐fold (95%CI 2.0–10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6–30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0–14.5).ConclusionsOne‐fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

Funder

Gilead Sciences

Publisher

Wiley

Subject

Hepatology

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