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

Objectives We 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. Methods People living with...

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Published in:	Liver international Vol. 44; no. 2; pp. 603 - 613
Main Authors:	D'Anna, Stefano, Carrara, Stefania, Mazzotta, Valentina, Antinori, Andrea, Antinori, A., Antinori, S., Di Perri, G., Quiros‐Roldan, E., Sarmati, L., Suligoi, B., von Schloesser, F., d’Arminio Monforte, A., Castagna, A., Ceccherini‐Silberstein, F., Lo Caputo, S., Maggiolo, F., Perno, C. F., Bandera, A., Cingolani, A., Cozzi‐Lepri, A., Giacomelli, A., Gori, A., Guaraldi, G., Lichtner, M., Madeddu, G., Malagnino, V., Mussini, C., Pinnetti, C., Santoro, M. M., Fanti, I., Tavelli, A., Cernuschi, M., Cosmaro, L., Calvino, V., Carrara, S., Prota, G., Truffa, S., Vincenti, D., D’Errico, Y., Rovito, R., Saracino, A., Santoro, C., Comi, L., Viale, P., Cretella, S., Erne, E. M., Pieri, A., Menzaghi, B., Celesia, B., Falasca, K., Segala, D., Ferrara, S., Blanchi, S., Molteni, C., Nunnari, G., Pellicanò, G., Rizzardini, G., Puoti, M., Bono, V., Lolatto, R., Moioli, M. C., Diotallevi, S., Tincati, C., Sangiovanni, V., Gentile, I., Fusco, F. M., Rizzo, V., Cattelan, A. M., Leoni, D., Cascio, A., Francisci, D., Sozio, F., Blanc, P., Bonelli, S. I., Lazzaretti, C., Mastroianni, C., Latini, A., Mazzotta, V., Lamonica, S., Capozzi, M., Stingone, C., Plazzi, M. M., Coledan, I, De Vito, A., Montagnani, F, Di Giuli, C., Calleri, G., Tascini, C, Manfrin, V., Farinacci, D.
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-02-2024
Subjects:	Antiviral agents CD4 antigen Cirrhosis death Delta infection Genotypes HBV infection HCV infection Hepatitis B surface antigen Hepatitis C Hepatitis delta virus HIV HIV infection Human immunodeficiency virus immunodepression Immunosuppressive agents Liver Liver diseases Liver transplantation Regression analysis Regression models Ribonucleic acid Risk RNA severe liver disease severe liver disease death HCV infection HBV infection HIV infection Delta infection immunodepression
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Summary:	Objectives We 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. Methods People 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. Results A 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). Conclusions One‐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.
Bibliography:	Antonella d'Arminio Monforte and Alessandro Tavelli contributed equally to the manuscript. The Icona Foundation Study Group Members are listed in the acknowledgments section. Handling Editor Dr. Alessio Aghemo ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1478-3223 1478-3231
DOI:	10.1111/liv.15804