Baseline HCV‐RNA levels in genotype 1 chronic hepatitis C patients: The role of different cut‐off points
Authors: Maria Buti, Juan J. Sánchez‐Ruano, Rosa M. Morillas, Rafael Esteban
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Buti is on the speakers' bureau for Gilead, Janssen, MSD, and Bristol‐Myers Squibb. Dr. Sanchez‐Ruano advises, is on the speakers' bureau of, and received grants from Gilead. He is on the speakers bureau for Janssen. Dr. Morillas consults, advises, and is on the speakers' bureau for Bristol‐Myers Squibb and AbbVie. She advises and is on the speakers' bureau for Gilead. She is on the speakers' bureau for Janssen and MSD. Dr. Esteban consults and is on the speakers' bureau for Gilead, Janssen, MSD, and Bristol‐Myers Squibb. TO THE EDITOR: We would like to congratulate Kwo et al.1 on their recent clinical trial with simeprevir plus sofosbuvir. Their important article has demonstrated high sustained virological response (SVR) rates among hepatitis C virus (HCV) genotype 1 (GT1) patients without cirrhosis who received simeprevir plus sofosbuvir in the OPTIMIST‐1 trial. This study was a multicenter, randomized, open‐label study assessing the efficacy and safety of 12‐ and 8‐week treatments with simeprevir plus sofosbuvir in 310 treatment‐naïve and treatment‐experienced patients without cirrhosis. SVR12 with simeprevir plus sofosbuvir for 12 weeks without ribavirin was 97% (150 of 155) and the global SVR 12 weeks posttreatment (SVR12) with simeprevir plus sofosbuvir for 8 weeks without ribavirin 83% (128 of 155).1 The global SVR12 rate achieved with 8 weeks of simeprevir plus sofosbuvir was lower than that observed after 8 weeks of treatment with sofosbuvir plus ledipasvir in HCV GT1‐infected patients without cirrhosis.2 However, this was not a head‐to‐head comparison, and the patient populations were different, because OPTIMIST‐1 included treatment‐experienced patients. Nonetheless, in the 8‐week arm, a similar relationship between baseline HCV RNA and achieving SVR12 was observed with both treatment approaches. After exploring a range of cut‐off points of baseline HCV RNA, a viral load of 4,000,000 IU/mL was identified as the optimal cut‐off point, predicting a response in patients treated with simeprevir in combination with sofosbuvir without ribavirin for 8 weeks. Using this cut‐off point, patients with baseline HCV RNA ≤4,000,000 UI/mL achieve a similar SVR 12, 96% (54 of 56) for 12 weeks as the 96% (46 of 48) for 8 weeks. Considering the data gathered from the OPTIMIST‐1 trial, we have analyzed the prevalence of low‐baseline HCV RNA (<4,000,000 or <6,000,000 IU/mL) in a large cohort of chronic hepatitis C GT1 patients in Spain.3 This has been a cross‐sectional study of HCV GT1 pretreatment serum samples from 48 Spanish hospitals from 14 regions. HCV‐RNA levels from 680 HCV GT1 patients before starting treatment were collected. HCV RNA was classified according to three cut‐off levels (<4,000,000, <6,000,000, and <10,000,000 IU/mL). Data on baseline treatment status and liver stiffness was also recorded. The majority of patients evidenced a low HCV RNA (78.2%; <4,000,000 IU/mL), and no relationship was found between HCV‐RNA concentrations and baseline liver fibrosis or previous treatment status (Tables 1 and 2). This post‐hoc analysis of an extensive representative sample of different areas of Spain clearly evidences that pretreatment HCV RNA in HCV GT1 patients is generally low (below 4,000,000 UI/mL) with independence of fibrosis degree. The implications of these findings for treatment duration probably deserves further evaluation. Table 1 - Pretreatment HCV RNA in HCV GT1 Patients According to Three Different Cut‐off Points HCV RNA, UI/mL N % <4,000,000 532 78.2 4,000,000‐6,000,000 64 9.4 >6,000,000 84 12.4 Table 2 - Pretreatment HCV RNA in HCV GT1 Patients Relating Cut‐off Points and Fibrosis Degree Fibrosis Degree HCV RNA, UI/mL F0‐F2 F3 F4 Total <4,000,000 N (%) 236 (79.2) 62 (68.1) 125 (82.2) 423 (78.2) 4,000,000‐6,000,000 N (%) 29 (9.7) 10 (11.0) 13 (8.6) 52 (9.6) >6,000,000 N (%) 33 (11.1) 19 (20.9) 14 (9.2) 66 (12.2)