Simeprevir and Sofosbuvir (SMV–SOF) for 12 Weeks for the Treatment of Chronic Hepatitis C Genotype 1 Infection

A Real World (Transplant) Hepatology Practice Experience

Anjana A. Pillai, MD; Joel Wedd MD, MPH; J.P. Norvell, MD; Samir Parekh, MD; Nicole Cheng, P.A.-C.; MMSc, MHS; Nikita Young, BSN, RN; James R. Spivey, MD; Ryan Ford, MD


Am J Gastroenterol. 2016;111(2):250-260. 

In This Article

Abstract and Introduction


Objectives: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF.

Methods: This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol.

Results: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African-American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort.

Conclusions: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease.


There are at least 3.2 million people in the United States today with chronic hepatitis C virus (HCV) infection, a disease more prevalent than HIV.[1,2] Accounting for nearly 75% of cases, genotype 1 is the most common type of HCV encountered in the United States.[3] Over half of the patients with chronic HCV have F2 METAVIR fibrosis score or higher, and the peak incidence of cirrhosis, hepatocellular carcinoma (HCC), and death related to HCV is yet to be realized in the absence of a cure.[4]

HCV-related liver disease is the most common indication for liver transplantation (LT) in the United States today, and recurrent HCV infection in the liver allograft is universal in the absence of effective antiviral therapy.[5–7] Recurrent HCV after LT is associated with reduced graft and patient survival and historically has been the most common cause of graft and patient loss.[5,6] Interferon-based antiviral regimens have poor efficacy and are difficult to tolerate, especially for patients with advanced liver fibrosis and those who are post-liver transplant.[8–10] The recent development of direct acting antiviral (DAAs) agents has allowed the option to treat HCV genotype 1-infected patients with an all-oral regimen for shorter duration and with a favorable side-effect profile.

Simeprevir (SMV) is a once-daily second generation HCV NS3/4A protease inhibitor, and sofosbuvir (SOF) is a once daily first in class HCV nucleotide analogue NS5B polymerase inhibitor. Both of these drugs were initially FDA approved to be used in combination with pegylated interferon (pegIFN) and ribavirin (RBV) to treat patients with HCV genotype 1 infection.[11–16]

Although new DAAs have proven to be expensive, a 12-week course of SMV and SOF is more cost effective for patients with genotype 1 HCV than 24 weeks of SOF and RBV among IFN ineligible/intolerant individuals.[17] Also, if curing HCV can prevent the development of decompensated cirrhosis or HCC, the cost and life-years saved by avoiding LT, hospitalizations, and death should outweigh the cost of HCV therapy.[17] In patients with advanced liver fibrosis, curing HCV has been shown to improve all-cause mortality.[18] Although prior advances in treatment of HCV appeared promising in clinical trials such as the initial controlled studies of protease inhibitors, initial experience with "real world" treatment proved to be problematic with high incidence of serious adverse events and poor patient tolerability.[19]

In this study, we report retrospective data from the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without RBV for a fixed 12-week duration irrespective of prior interferon therapy, transplant status, or fibrosis stage (the study was conducted prior to FDA approval of SMV–SOF and thus prior to the current recommendation for 24 weeks of treatment for patients with cirrhosis). This paper analyzes the largest number of patients to date from a single center treated outside of a clinical trial for genotype 1 HCV using the SMV–SOF combination. The goal was to define sustained virologic response (SVR) rates in a "real world" analysis and to explore predictors of treatment response.