Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2017; 23(26): 4759-4766
Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4759
Eight-week ledipasvir/sofosbuvir in non-cirrhotic, treatment-naïve hepatitis C genotype-1 patients with hepatitis C virus-RNA < 6 million: Single center, real world effectiveness and safety
Nyan L Latt, Beshoy T Yanny, Derenik Gharibian, Rita Gevorkyan, Amandeep K Sahota
Nyan L Latt, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL 32224, United States
Beshoy T Yanny, Amandeep K Sahota, Division of Gastroenterology and Hepatology, Kaiser Permanente, Los Angeles Medical Center, Los Angeles, CA 90027, United States
Derenik Gharibian, Pharmacy Operations Office, Kaiser Permanente, Los Angeles Medical Center, Los Angeles, CA 90027, United States
Rita Gevorkyan, Department of Clinical Operations, Kaiser Permanente Southern California, CA 91107, United States
Author contributions: Latt NL and Sahota AK designed the research; Latt NL and Yanny BT performed the data abstraction, contributed to the analysis; Latt NL wrote the paper; Gharibian D and Sahota AK provided clinical advice and supervised the report; Gevorkyan R helped with the data abstraction and provided clinical advice.
Institutional review board statement: This study was reviewed and approved by Kaiser Permanente Southern California Institutional Review Board.
Informed consent statement: Patients were not required to give informed consent to the study. The study was qualified for an ‘exempt status’ by the Institutional Review Board due to its retrospective nature. We collected only the existing data from electronic medical records, the date were stored without any patient identifiers.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nyan L Latt, MD, Transplant Hepatology Fellow, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, United States. latt.nyan@mayo.edu
Telephone: +1-904-9563256 Fax: +1-904-9563359
Received: January 16, 2017
Peer-review started: January 18, 2017
First decision: February 9, 2017
Revised: March 8, 2017
Accepted: June 9, 2017
Article in press: June 12, 2017
Published online: July 14, 2017
Processing time: 176 Days and 6.9 Hours
Abstract
AIM

To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA < 6 million IU/mL.

METHODS

We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/mL. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment.

RESULTS

Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment (imaging, AST, platelet count) and 47% had documented liver fibrosis testing (biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734 (P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/mL was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/mL was associated with significantly higher SVR 98% with OR = 0.22 (95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/mL. No death or morbidities were reported.

CONCLUSION

Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/mL.

Keywords: Hepatitis C; Sustained viral response; Ledipasvir; Cirrhosis; Sofosbuvir

Core tip: We highlight that sustained viral response (SVR) outcomes in patients with their non-cirrhotic status determined by clinical judgment using simple, cheap, non-invasive tests such as platelet count, sonographic finding of spleen size and hepatic morphology, are comparable with those who had specialized tests such as liver biopsy, vibration-controlled transient elastography or specialized serum biomarker test. We also validate the fact that hepatitis C virus (HCV) RNA plays a role in predicting SVR (AUROC = 0.743, 95%CI: 0.66-0.82) with a cutoff value of 2.2 million IU/mL. Significantly higher 98% SVR was observed among HCV RNA < 2.2 million IU/mL, compared to 92% SVR with HCV RNA ≥ 2.2 million IU/mL.