Faculty Bibliography

BACKGROUND: At baseline, the presence of virus with NS5A RASs has been shown to impact the efficacy of NS5A containing regimens in patients with G1a chronic HCV infection. Therefore, the purpose of the current analysis was to describe the utilization and effectiveness of EBR/GZR in G1a chronic HCV patients with or without NS5A RASs in the United States. METHODS: A subgroup analysis of an EBR/GZR treated cohort previously derived using data collected from US providers and specialty pharmacies through Trio Health's disease management platform was used. The cohort was restricted to TN chronic HCV G1a patients who initiated EBR/GZR therapy between Jan 28, 2016 (FDA approval) and Dec 31, 2016. The primary SVR analysis was a Per Protocol (PP) analysis defined as all patients that completed their intended therapy and who received an SVR testing at 12 weeks (SVR12) post therapy. RESULTS: 234 patients met the inclusion criteria for the subgroup analysis and NS5A RASs testing was conducted in 58% (135/234) of the cohort. Approximately 9% (12/135) of those tested had an NS5A RAS present. 50% (6/12) of these patients were treated for 16 weeks with ribavirin (RBV), 8% (1/12) for 12 weeks with RBV, 25% (3/12) were treated for 12 weeks without RBV, 17% (2/12) for 16 weeks without RBV. Of patients that did not have an NS5A RAS present, 95% (111/117) were treated for 12 weeks without RBV. At present, only 126 patients of the overall G1a cohort have completed therapy with an SVR12 of 98% (124/126) (TABLE). Of those with an NS5A RAS present, the SVR12 was 100% (2/2) in those treated for 16 weeks with RBV, 100% (1/1) in those treated for 12 weeks and 100% (1/1) in those treated for 16 weeks. The SVR12 was 98% (60/61) in those patients who did not have an NS5A RAS present. CONCLUSIONS: Based on preliminary data, EBR/GZR appears to be highly effective in treating G1a patients regardless of the presence of NS5A RASs. Full SVR data will be presented at the meeting (Table presented)

Background: Lengthening EBR/GZR treatment to 16 weeks and/or adding RBV is recommended for select GT1 HCV subgroups. However, real-world utilization patterns previously reported (J Hepat 2017 66: S295) suggests utilization of this dosing recommendation is low. This study examines 12 and 16 week EBR/GZR +/-RBV in different patient subgroups. Methods: Data were collected from providers and specialty pharmacies through Trio Health's disease management program. Patients (n=442) with GT1 HCV who initiated EBR/GZR therapy between Jan 28, 2016 (FDA approval) to Dec 31, 2016 were included. Results: 401 (91%) received 12-week EBR/GZR, 12 (3%) 12-week EBR/GZR+RBV, 11 (2%) 16-week EBR/GZR, and 18 (4%) 16-week EBR/GZR+RBV. Possible baseline NS5A resistance was identified in 13/285 patients with GT1A HCV. In this subgroup, 3/13 (23%) received 12-week EBR/GZR, 1/13 (8%) received 12-week EBR/GZR+RBV, 2/13 (15%) received 16-week EBR/GZR, and 7/13 (54%) received 16-week EBR/GZR+RBV. For the complete GT1 population, the +RBV subgroup had a higher fraction of patients that were treatment experienced (TE, 43%, 13/30) compared to the-RBV group (17%, 69/412). For the complete GT1 population, the 16-week subgroup had a higher proportion of GT1A subtype (93%, 27/29) compared to the 12-week group (62% GT1A, 258/413). Other characteristics including gender, age, baseline viral load, and cirrhosis were similar between regimens or between groups defined by RBV addition or therapy duration. SVR12 results at time of abstract submission were available for 262/442 patients. Overall per protocol (PP) SVR12 was 97% (253/262). Across the GT1 subgroups (defined by subtype, prior treatment experience, and fibrosis) that received EBG/GZR for 12-week regimen without RBV, the PP was SVR12 <=94%. (TABLE) Summary: The majority of patients were treated for 12 weeks without RBV in real world practice and Zepatier was found to be highly effective. Full SVR12 data across sub populations will be presented at the conference (Table presented)

AIM: To examine changes in treatment preferences with approval of new therapies for HCV and assess outcomes with preferred treatments and in subgroups that historically have reduced cure rates. METHODS: Data were collected from providers and specialty pharmacies through Trio Health's disease management program. HCV-infected patients (n=7098) who initiated anti-HCV therapy from Jan to Dec 2016 were included. RESULTS: In 2016, 6 regimens accounted for 99% (7027/7098) of initiated treatment: 67% (4730) ledipasvir/sofosbuvir (LDV/SOF) +/-ribavirin (RBV), 12% (848) SOF/velpatasvir (SOF/VEL) +/-RBV, 7% (493) daclatasvir (DCV) + SOF +/-RBV, 6% (445) elbasvir/grazoprevir (EBR/GZR) +/-RBV, 5% (371) SOF + RBV, and 2% (140) ombitasvir-paritaprevir-ritonavir, and dasabuvir (PrOD) +/-RBV. Population characteristics and per protocol (PP) SVR12 rates by time period and genotype (GT) are provided in the TABLE. The regimen distribution by GT differed between Jan-Jun (1H) and Jul-Dec (2H) of 2016. By GT, PP SVR12 rates in 2H2016 increased or remained the same as 1H2016. PP SVR12 rates in subgroups with impaired kidney function, HIV coinfection, prior treatment experience, prior transplant, or cirrhosis were <=95%. SUMMARY: PP SVR12 rates increased slightly from 1H to 2H2016 for most patients. Subgroups stratified by characteristics historically associated with reduced SVR12 rates achieved per protocol SVR12 of 95% or higher (Table presented)

BACKGROUND: Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naive to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. AIM: To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. METHODS: We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naive genotype 1 HCV patients. RESULTS: A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. CONCLUSIONS: In treatment-naive HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.

Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilitate timely care and improve outcomes. With risks and misclassification associated with invasive tests, such as liver biopsy, noninvasive imaging modalities for liver fibrosis assessment have gained popularity. Therefore, the American Gastroenterological Association prioritized clinical guidelines on the role of elastography in CLDs, focusing on vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE). To inform these clinical guidelines, the current technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for diagnostic accuracy studies. This technical review addresses focused questions related to: (1) comparative diagnostic performance of VCTE and MRE relative to nonproprietary, serum-based fibrosis markers for detection of cirrhosis in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), NAFLD, and alcoholic liver diseases; (2) performance of specific VCTE-defined liver stiffness cutoffs as a test replacement strategy (to replace liver biopsy) in making key decisions in the management of patients with CLDs; and (3) performance of specific VCTE-defined liver stiffness cutoffs as a triage test to identify patients with low likelihood of harboring high-risk esophageal varices (EVs) or having clinically significant portal hypertension (for presurgical risk stratification). This technical review does not address performance of other noninvasive modalities for assessing fibrosis (eg, acoustic radiation force pulse imaging or shear wave elastography) or steatosis (controlled attenuation parameter or magnetic resonance imaging-estimated proton density fat fraction).

BACKGROUND & AIMS: All-oral regimens are associated with high cure rates in hepatitis C virus-genotype 1 (HCV-GT1) patients. Our aim was to assess the value of cure to the society for treating HCV infection. METHODS: Markov model for HCV-GT1 projected long-term health outcomes, life years, and quality-adjusted life years (QALYs) gained. The model compared second-generation triple (sofosbuvir+pegylated interferon+ribavirin [PR] and simeprevir+PR) and all-oral (ledipasvir/sofosbuvir and ombitasvir+paritaprevir/ritonavir+dasabuvir+/-ribavirin) therapies with no treatment. Sustained virological response rates were based on Phase III RCTs. We assumed that 80% and 95% of HCV-GT1 patients were eligible for second-generation triple and all-oral regimens. Transition probabilities, utility and mortality were based on literature review. The value of cure was calculated by the difference in the savings from the economic gains associated with additional QALYs. RESULTS: Model estimated 1.52 million treatment-naive HCV-GT1 patients in the US. Treating all eligible HCV-GT1 patients with second-generation triple and all-oral therapies resulted in 3.2 million and 4.8 million additional QALYs gained compared to no treatment respectively. Using $50,000 as value of QALY, these regimens lead to savings of $185 billion and $299 billion; costs of these regimens were $109 billion and $128 billion. The value of cure with second-generation triple and all-oral regimens was $55 billion and $111 billion, when we conservatively assumed only drug costs. Cost savings were greater for HCV-GT1 patient cured with cirrhosis compared to patients without cirrhosis. CONCLUSIONS: The recent evolution of regimens for HCV GT1 has increased efficacy and value of cure.

AIM/OBJECTIVE:To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed. METHODS:Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir). RESULTS:/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22). CONCLUSION/CONCLUSIONS:The SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.