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ORIGINAL PAPER

100% Sustained Virological Response and Fibrosis Improvement in Real-Life Use of Direct Acting Antivirals in Genotype-1b Recurrent Hepatitis C following Liver Transplantation

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Speranta Iacob1,2, Razvan Cerban1,2, Corina Pietrareanu¹, Carmen Ester1,2, Razvan Iacob1,2, Cristian Gheorghe1,2, Irinel Popescu³, Liana Gheorghe1,2

1) Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute;
2) Carol Davila University of Medicine and Pharmacy;
3) Dan Setlacec Centre of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.272.100

ABSTRACT
Background: Nowadays, interferon-free therapy using new direct-acting antivirals (DAA) has dramatically increased the cure rate across different HCV-infected patient populations, including groups traditionally viewed as difficult-to-treat (patients with co-infections, cirrhosis and liver transplant – LT recipients) with marked improvement in safety and tolerability.
Aim: To present our experience with DAA therapy in LT recipients, as well as to compare pre- and posttreatment liver stiffness (LS) and noninvasive fibrosis scores.
Methods: Our cohort consisted of 89 patients with genotype 1 (GT1) recurrent hepatitis C after LT.
Seventy six patients received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and 13 sofosbuvir/ ledipasvir±ribavirin. Fibroscan®, FIB4 and APRI scores were performed in all patients before and 12 weeks after DAA therapy.
Results: We analyzed 45 (50.5%) males and 44 (49.5%) females with a mean age of 55±7.7 years. Median time since LT was 20.9 months. At baseline, 53 (59.6%) of patients had severe necroinflammation at Fibromax®; advanced fibrosis (F3, F4) was encountered in 35 (39.4%) and grade 3 steatosis in 33 (37.1%) of LT recipients.
End of therapy (EOT) virological response (VR) was 100%. Sustained virological response 12 weeks after therapy (SVR12) was 97.7% in the intention-to-treat analysis and 100% in per protocol analysis. There was a significant improvement in LS between antiviral therapy initiation and SVR12: 11.9±1.05kPa vs 8.8±0.6kPa (p<0.0001), as well as in APRI (2.7±0.3 vs 0.4±0.05, p<0.0001) and FIB4 (4.6±0.5 vs 2.5±0.2, p<0.0001) scores.
Conclusion: In HCV positive recipients, DAA regimens are highly effective and safe. A significant decrease of LS by transient elastography and fibrosis non-invasive scores can be observed after successful therapy.
Key words: hepatitis C – liver transplantation – antiviral therapy.
Abbreviations: AE: adverse events; AFP: alpha fetoprotein; ALP: alkaline phosphatase; ALT: alanine aminotransferases; AST: aspartate aminotransferases; DAA: direct-acting antivirals; GGT: gamma glutamyl transpeptidase; GT1: genotype 1; HC: Hepatitis C; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HIV: human immunodeficiency virus; INR: international normalized ratio; ITT: intention to treat; LDV/SOF: ledipasvir/sofosbuvir; LLD: lower limits of detection; LLQ: lower limits of quantification; LS: liver stiffness; LSM: liver stiffness measurement; LT: liver transplant; NHIA: National Health Insurance Agency; OBV/ PTV/r +DSV: Ombitasvir/Paritaprevir/ritonavir plus dasabuvir (3D); RBV: ribavirin; SAE: serious adverse events; SOF+DAC±RBV: sofosbuvir+daclatasvir+ribavirin; SVR: sustained virological response; TE: transient elastography; VR: virological response