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: R Vukotic, F Conti, S Fagiuoli, M C Morelli, L Pasulo, M Colpani, F G Foschi, S Berardi, P Pianta, M Mangano, M F Donato, F Malinverno, S Monico, M Tamè, G Mazzella, L S Belli, R Viganò, P Carrai, P Burra, F P Russo, I Lenci, P Toniutto, M Merli, L Loiacono, R Iemmolo, A M Degli Antoni, A Romano, A Picciotto, M Rendina, P Andreone, AISF-SOFOLT Study group
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 24 Issue 10 Pg. 858-864 (10 2017) ISSN: 1365-2893 [Electronic] England
• PMID: 28370880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• RNA, Viral

Topics

• Aged
• Antiviral Agents (therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis (diagnosis, etiology)
• Hepatitis C (diagnosis, drug therapy, etiology, virology)
• Humans
• Kaplan-Meier Estimate
• Liver Cirrhosis (diagnosis, etiology)
• Liver Function Tests
• Liver Transplantation (adverse effects)
• Male
• Middle Aged
• RNA, Viral
• Recurrence
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Viral Load