TY - JOUR
T1 - Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after orthotopic liver transplantation
AU - Beinhardt, Sandra
AU - Al-Zoairy, Ramona
AU - Kozbial, Karin
AU - Stättermayer, Albert F
AU - Maieron, Andreas
AU - Stauber, Rudolf
AU - Strasser, Michael
AU - Zoller, Heinz
AU - Graziadei, Ivo
AU - Rasoul-Rockenschaub, Susanne
AU - Trauner, Michael
AU - Ferenci, Peter
AU - Hofer, Harald
N1 - Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2018/7
Y1 - 2018/7
N2 - BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT.PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%.RESULTS: Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1).CONCLUSION: RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.
AB - BACKGROUND & AIMS: Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT.PATIENTS & METHODS: A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%.RESULTS: Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1).CONCLUSION: RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.
KW - Aged
KW - Antiviral Agents/therapeutic use
KW - Austria
KW - Benzimidazoles/therapeutic use
KW - Carbamates
KW - Carcinoma, Hepatocellular/epidemiology
KW - Drug Therapy, Combination
KW - Female
KW - Fluorenes/therapeutic use
KW - Follow-Up Studies
KW - Hepacivirus/genetics
KW - Hepatitis C, Chronic/complications
KW - Humans
KW - Imidazoles/therapeutic use
KW - Liver Neoplasms/epidemiology
KW - Liver Transplantation
KW - Male
KW - Middle Aged
KW - Pyrrolidines
KW - Recurrence
KW - Ribavirin
KW - Simeprevir/therapeutic use
KW - Sofosbuvir/therapeutic use
KW - Sustained Virologic Response
KW - Valine/analogs & derivatives
UR - http://www.scopus.com/inward/record.url?scp=85041226214&partnerID=8YFLogxK
U2 - 10.1111/liv.13652
DO - 10.1111/liv.13652
M3 - Journal article
C2 - 29197145
SN - 1478-3223
VL - 38
SP - 1188
EP - 1197
JO - Liver International
JF - Liver International
IS - 7
ER -