Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma.
liver transplantation
outcome
survival
treatment
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
01 Mar 2024
01 Mar 2024
Historique:
revised:
20
12
2023
received:
06
12
2023
accepted:
07
01
2024
medline:
1
3
2024
pubmed:
1
3
2024
entrez:
1
3
2024
Statut:
aheadofprint
Résumé
Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection.
METHODS
METHODS
We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups.
RESULTS
RESULTS
Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106).
CONCLUSIONS
CONCLUSIONS
In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Maurizio Biselli
(M)
Lorenzo Lani
(L)
Benedetta Stefanini
(B)
Valentina Santi
(V)
Alessandro Granito
(A)
Fabio Piscaglia
(F)
Francesco Tovoli
(F)
Luca Muratori
(L)
Francesca Benevento
(F)
Fabio Farinati
(F)
Gloria Allegrini
(G)
Calogero Cammà
(C)
Ciro Celsa
(C)
Paolo Giuffrida
(P)
Carmelo Marco Giacchetto
(CM)
Gabriele Rancatore
(G)
Maria Vittoria Grassini
(MV)
Roberta Ciccia
(R)
Alessandro Grova
(A)
Mauro Salvato
(M)
Valentina Adotti
(V)
Stefano Gitto
(S)
Fabio Marra
(F)
Martina Rosi
(M)
Vittoria Bevilacqua
(V)
Alberto Borghi
(A)
Fabio Conti
(F)
Anna Chiara Dall'Aglio
(AC)
Giorgio Ercolani
(G)
Federica Mirici
(F)
Laura Schiadà
(L)
Chiara Scorzoni
(C)
Giulia Scandali
(G)
Francesca Romana Ponziani
(FR)
Gabriele Missale
(G)
Andrea Olivani
(A)
Mario Capasso
(M)
Valentina Cossiga
(V)
Filomena Morisco
(F)
Ester Marina Cela
(EM)
Antonio Facciorusso
(A)
Valentina Lauria
(V)
Giorgio Pelecca
(G)
Fabrizio Chegai
(F)
Fabio Coratella
(F)
Mariano Ortenzi
(M)
Serena Dell'Isola
(S)
Roberto Filomia
(R)
Concetta Pitrone
(C)
Giovanni Raimondo
(G)
Assunta Sauchella
(A)
Elton Dajti
(E)
Federico Ravaioli
(F)
Filippo Oliveri
(F)
Gabriele Ricco
(G)
Veronica Romagnoli
(V)
Alessandro Inno
(A)
Fabiana Marchetti
(F)
Pietro Coccoli
(P)
Antonio Malerba
(A)
Alberta Cappelli
(A)
Cristina Mosconi
(C)
Matteo Renzulli
(M)
Luca Marzi
(L)
Informations de copyright
© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.
Références
Asselah T, Rizzetto M. Hepatitis D virus infection. N Engl J Med. 2023;389:58-70.
Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011;378:73-85.
Stroffolini T, Morisco F, Ferrigno L, et al. Acute Delta hepatitis in Italy spanning three decades (1991-2019): evidence for the effectiveness of the hepatitis B vaccination campaign. J Viral Hepat. 2022;29:78-86.
Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73:523-532.
Vlachogiannakos J, Papatheodoridis GV. New epidemiology of hepatitis delta. Liver Int. 2020;40(Suppl 1):48-53.
Puigvehí M, Moctezuma-Velázquez C, Villanueva A, Llovet JM. The oncogenic role of hepatitis delta virus in hepatocellular carcinoma. JHEP Rep. 2019;1:120-130.
Papatheodoridi A, Papatheodoridis G. Hepatocellular carcinoma: the virus or the liver? Liver Int. 2023;43(Suppl 1):22-30.
Romeo R, Petruzziello A, Pecheur EI, et al. Hepatitis delta virus and hepatocellular carcinoma: an update. Epidemiol Infect. 2018;146:1612-1618.
Farci P, Niro GA, Zamboni F, Diaz G. Hepatitis D virus and hepatocellular carcinoma. Viruses. 2021;13:830.
Wedemeyer H, Aleman S, Brunetto MR, et al. A phase 3, randomized trial of bulevirtide in chronic hepatitis D. N Engl J Med. 2023;389:22-32.
Cabibbo G, Petta S, Barbara M, et al. Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma. J Hepatol. 2017;67:65-71.
European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis delta virus. European Association for the Study of the liver. J Hepatol. 2023;79:433-460.
Bucci L, Garuti F, Lenzi B, et al. The evolutionary scenario of hepatocellular carcinoma in Italy: an update. Liver Int. 2017;37:259-270.
Garuti F, Neri A, Avanzato F, et al. The changing scenario of hepatocellular carcinoma in Italy: an update. Liver Int. 2021;41:585-597.
Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307:832-842.
European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. European Association for the Study of the liver. J Hepatol. 2018;69:406-460.
Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646-649.
Giannini E, Botta F, Testa E, et al. The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis. Am J Gastroenterol. 2002;97:2855-2860.
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5:649-655.
Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology. 1996;111:1018-1022.
Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee; et al. Position paper of the Italian Association for the Study of the liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis. 2013;45:712-723.
European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. European Association for the Study of the liver. J Hepatol. 2018;69:182-236.
Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-699.
Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462-503.
Kang H. The prevention and handling of the missing data. Korean J Anesthesiol. 2013;64:402-406.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496-509.
Fattovich G, Giustina G, Christensen E, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut. 2000;46:420-426.
Romeo R, Del Ninno E, Rumi M, et al. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009;136:1629-1638.
Romeo R, Foglieni B, Casazza G, Spreafico M, Colombo M, Prati D. High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in patients with chronic hepatitis delta. PLoS One. 2014;9:e92062.
Ghany MG. A glimmer of Hope for an orphan disease. N Engl J Med. 2023;389:81-82.
Anolli MP, Degasperi E, Allweiss L, et al. A 3-year course of bulevirtide monotherapy may cure HDV infection in cirrhotics. J Hepatol. 2023. doi:10.1016/j.jhep.2022.12.023
Dietz-Fricke C, Tacke F, Zöllner C, et al. Treating hepatitis D with bulevirtide - real-world experience from 114 patients. JHEP Rep. 2023;5:100686.
Verme G, Brunetto MR, Oliveri F, et al. Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci. 1991;36:1134-1136.
Costante F, Stella L, Santopaolo F. Molecular and clinical features of hepatocellular carcinoma in patients with HBV-HDV infection. J Hepatocell Carcinoma. 2023;10:713-724.
Vitale A, Morales RR, Zanus G, et al. Barcelona clinic liver cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study. Lancet Oncol. 2011;12:654-662.
Vitale A, Burra P, Frigo AC, et al. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona clinic liver cancer stages: a multicentre study. J Hepatol. 2015;62:617-624.
Vitale A, Cabibbo G, Iavarone M, et al. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept. Lancet Oncol. 2023;24:e312-e322.
Caviglia GP, Martini S, Ciancio A, et al. The hepatitis D virus in Italy. A vanishing infection, not yet a vanished disease. J Adv Res. 2021;33:183-187.
Giannini EG, Risso D, Testa R, et al. Prevalence and prognostic significance of the presence of esophageal varices in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006;4:1378-1384.
Giannini EG, Trevisani F. Improving survival of cirrhosis patients with hepatocellular carcinoma through application of standard of care. Hepatology. 2014;60:1446-1447.
Reggidori N, Bucci L, Santi V, et al. Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs. JHEP Rep. 2023;5:100784.
Vieira Barbosa J, Sahli R, Aubert V, Chaouch A, Moradpour D, Fraga M. Demographics and outcomes of hepatitis B and D: a 10-year retrospective analysis in a Swiss tertiary referral center. PLoS One. 2021;16(4):e0250347.
Da BL, Rahman F, Lai WC, et al. Risk factors for Delta hepatitis in a north American cohort: who should be screened? Am J Gastroenterol. 2021;116:206-209.
Jang TY, Wei YJ, Liu TW, et al. Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues. Sci Rep. 2021;11:8184.