Faculty Bibliography

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)

AIM: To assess variables associated with failure to complete treatment and failure to achieve SVR at 12 weeks post therapy (SVR12). METHODS: Data were collected from providers and specialty pharmacies through Trio Health's disease management program. Analyses included 7831 patients who initiated DAAs from Oct 2015 to Dec 2016 excluding lost to follow up or expired patients. Variables associated with treatment discontinuation or virologic failure through chi-square or T-tests (p=0.1) were subsequently assessed via stepwise logistic regression. Multicollinearity between variables was addressed by exclusion of the variable with smaller effect on model prediction. RESULTS: 3% (261) patients discontinued the intended therapy and did not achieve SVR. Of the 97% (7570) that completed, 79% (5996/7570) had SVR results available. 3% (186/5996) of those assessed for SVR had detectable virus and 97% (5810/5996) achieved SVR12. Variables identified as significantly associated with discontinuation and/or virologic failure across all genotypes are indicated in the TABLE. Factors found not to be significantly associated include baseline viral load, hemoglobin, GT1 subtype, GT2, GT4-6, HIV, hypertension, diabetes, anxiety, depression, certain regimens, prior transplant, and practice type. Additional assessments restricted by genotype result in shifts in significant variables relative to the overall results (data not shown). SUMMARY: Univariate analyses suggest that less complex therapy and shorter treatment duration may reduce discontinuations. Multivariate analyses are consistent with this premise, but highlight specific regimen choices and cirrhosis in addition to younger age. For patients that complete therapy, older age, male gender and more severe disease (cirrhosis, prior treatment) are associated with failure to achieve SVR12 (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.

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.

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).

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.