title: Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.
abstract: Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Vukotic
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Conti
authors.affiliation: Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Fagiuoli
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Morelli
authors.affiliation: Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pasulo
authors.affiliation: Dipartimento di Medicina Specialistica e dei Trapianti, U.S.C. Gastroenterologia Epatologia e Trapiantologia, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colpani
authors.affiliation: AUSL della Romagna, Presidio Ospedaliero di Faenza, Faenza, Italy.
authors.forename: F G
authors.initials: FG
authors.lastname: Foschi
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Berardi
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pianta
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mangano
authors.affiliation: Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy.
authors.forename: M F
authors.initials: MF
authors.lastname: Donato
authors.affiliation: Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Malinverno
authors.affiliation: Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico ed Univerisità di Milano, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Monico
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tamè
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mazzella
authors.affiliation: Dipartimento di Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy.
authors.forename: L S
authors.initials: LS
authors.lastname: Belli
authors.affiliation: Dipartimento di Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Viganò
authors.affiliation: Chirurgia biliopancreatica e Trapianto di Fegato, Università di Pisa, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Carrai
authors.affiliation: Dipartimento di Chirurgia, Oncologia e Gastroenterologia, Unità di Trapianto Multiviscerale, Ospedale Universitario Padova, Padua, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Burra
authors.affiliation: Dipartimento di Chirurgia, Oncologia e Gastroenterologia, Unità di Trapianto Multiviscerale, Ospedale Universitario Padova, Padua, Italy.
authors.forename: F P
authors.initials: FP
authors.lastname: Russo
authors.affiliation: Unità di Epatologia, Università Tor Vergata, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Lenci
authors.affiliation: Medicina Interna Sezione di Trapianto di Fegato, Università di Udine, Udine, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Toniutto
authors.affiliation: Dipartimento di Medicina Clinica La Sapienza, Gastroenterologia, Università di Roma, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Merli
authors.affiliation: I.R.C.C.S. L. Spallanzani, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Loiacono
authors.affiliation: Chirurgia Oncologica Epato-bilio-pancreatica e Chirurgia dei Trapianti di fegato, AOU di Modena, Modena, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Iemmolo
authors.affiliation: Unità di Malattie Infettive ed Epatologia, AOU di Parma, Parma, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Degli Antoni
authors.affiliation: Dipartimento di Medicina, Unità delle Emergenze epatologiche e dei Trapianti di fegato, Università di Padova, Padua, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.affiliation: Dipartimento di Medicina Interna, Università degli Studi di Genova, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Picciotto
authors.affiliation: Unità Operativa Gastroenterologia ed Endoscopia Digestiva, Policlinico Universitario di Bari, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rendina
authors.affiliation: Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi di Bologna, Bologna, Italy.
authors.forename: P
authors.identifier: 0000-0002-4794-9809
authors.initials: P
authors.lastname: Andreone
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006505:Hepatitis / Q000175:diagnosis / Q000209:etiology*; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D012008:Recurrence; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral
keywords: antiviral therapy; fibrosing cholestatic hepatitis; liver transplant; long-term outcome; severe hepatitis C virus recurrence