Heshaam M. Mir

Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients

BACKGROUND & AIMS Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens. METHODS A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5 years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs). RESULTS Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of

Moderate, excessive or heavy alcohol consumption: each is significantly associated with increased mortality in patients with chronic hepatitis C.

15,709/QALY at baseline cost of oral therapy. The ICER remained below

Association of Chronic Liver Disease with Depression: A Population-Based Study

50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease. CONCLUSIONS Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.

Mortality associated with alcohol-related liver disease.

The impact of moderate alcohol consumption on long‐term outcomes of chronic hepatitis C (CH‐C) infected patients remains controversial.

African americans are less likely to have clearance of hepatitis C virus infection: the findings from recent U.S. population data.

OBJECTIVE Chronic liver diseases (CLD) have been associated with depression. Our aim was to assess the association of different types of CLD with depression in a population-based cohort. METHODS We examined data from National Health and Nutrition Examination Survey (NHANES 2005-2010). We included adult patients with chronic hepatitis C (CH-C), chronic hepatitis B (CH-B), alcohol-related liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Patient Health Questionnaire (PHQ-9) survey was used as a depression screener. Univariate and multivariate analyses were performed to determine independent variables associated with each type of CLD and depression. RESULTS The cohort included 10,231 NHANES participants. After multivariate analysis, CH-C was independently associated with age (OR = 1.05, 95% CI: 1.03-1.07), male gender (OR = 1.88, 95% CI: 1.19-2.97), African American race/ethnicity (OR = 2.50, 95% CI:1.50-4.18), smoking (OR = 6.20, 95% CI: 1.62-23.68), injection drug use (OR = 52.86, 95% CI:32.87-85.03), and depression (OR = 2.87, 95% CI: 1.78-4.62). CH-B was independently associated with being non-Caucasian (for African Americans OR = 5.09, 95% CI: 2.41-10.76, for other races OR = 4.74, 95% CI: 2.32-9.70). ALD was independently associated with younger age (OR = 0.98, 95% CI: 0.96-0.99), male gender (OR = 1.53, 95% CI: 1.19-1.95), Mexican American race/ethnicity (OR = 2.63, 95% CI: 1.87-3.69), and moderate to heavy smoking (OR = 2.08, 95% CI: 1.46-2.96). Finally, presence of insulin resistance [OR = 2.65 95% CI: 1.98-3.55], diabetes [OR = 1.54 95% CI: 1.11-2.13], and Mexican American race/ethnicity [OR = 2.03(1.35-3.06)], were predictive of NAFLD. CONCLUSIONS Although depression has been suspected to be associated with a number of CLD, this association remains strong only for CH-C.

Monoclonal and polyclonal antibodies against the HCV envelope proteins.

Excessive alcohol use has been reported to be responsible for 80 000 annual deaths in the United States. However, the exact cause of death related to the excessive use of alcohol has not been fully explored.

Sa1067 Interferon-Based and Interferon-Free Regimens for Patients With Chronic Hepatitis C, Genotype 1: Potential Cost-Effectiveness of Biopsy-Guided Treatment Versus Treat All Strategies

Background: Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. African Americans are known to have a higher prevalence of HCV and lower response to anti-HCV therapy. GOAL: The aim of this study is to assess the differences in the prevalence of chronic HCV infection in according to patients’ ethnic background. Study: We used the recent National Health and Nutrition Examination Survey with extensive clinical and laboratory data. Active HCV infection was defined as having HCV-positive antibody with detectable HCV RNA by polymerase chain reaction. HCV clearance was defined as HCV-positive antibody with negative HCV RNA. Clinico-demographic data were compared between anti-HCV positive individuals with or without HCV clearance. The stratum-specific &khgr;2 test for independence was used. Logistic regression was used to identify independent predictors of HCV clearance. P-values ⩽0.05 were considered statistically significant. All analyses were run using SAS 9.1 and SUDAAN 10.0. Results: The cohort included 14,750 adults (age 47.6±0.75 y, 64% white, 21% African American, 10% Hispanics, and 63% male). Of these, 1.32±0.11% were anti-HCV positive with 75.94±4.72% having active HCV viremia. The only parameter significantly different between those who did or did not clear HCV was the proportion of African Americans: 8.0±3.7% versus 24.9±5.0%, P=0.0163. Indeed, the rate of HCV clearance was lowest among African Americans (9.3±3.5%) as compared with both whites (27.2±6.5%) and Hispanics 31.2±9.1% (P<0.05). In multivariate analysis, the only independent predictor of active HCV infection was African American race: odds ratio (95% confidence interval)=3.80 (1.31-11.06), P=0.0151. Conclusions African Americans not only have lower response to anti-HCV therapy but also are less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV.

Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study

The potential for developing efficient and efficacious therapies for hepatitis C virus continues to improve. Insight into the molecular processes involved in attachment, entry, and fusion suggests that antibodies could potentially inhibit viral replication at any or all of these stages, and the attachment and entry stages present the best target for antibodies that can attack the virus. Monoclonal and polyclonal antibodies present an important therapeutic option in this area, and this article assesses current investigations of several antibodies.

16 THE CHANGING FACE OF CHRONIC LIVER DISEASE (CLD) IN THE UNITED STATES: THE RISING EPIDEMIC OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Background: Chronic hepatitis C is a common cause of chronic liver disease worldwide. Standard treatment for genotype 1 patients uses a triple combination of pegylated-interferon alpha (PEG-IFN), ribavirin (RBV) and a direct acting antiviral (DDA), and is associated with 75-80% sustained virologic response (SVR). Aim: Determine cost-effectiveness of biopsyguided versus treat all patients with interferon-based versus interferon-free regimens for CH-C genotype 1. Methods: A decision analytic Markov model that simulated patients until death was used to compare four strategies for treating CH-C genotype 1: Triple therapy (PEG-IFN, RBV, and DAA) with biopsy-guidance (TT) or treat all without biopsy (TTA); Oral IFN-free regimenwith biopsy-guidance (OT) or treat all without biopsy (OTA). Strategies with biopsy initiated treatment at fibrosis stages F2-F4, with biopsies repeated every 5 years until age 70. The reference case was a treatment-naive 50-year-old. Parameters were taken from the literature. Treatment outcomes for Oral IFN-Free regimen (90% SVR) were based on trial results presented at scientific meetings. Baseline cost and utility of oral therapy were calibrated to match triple therapy. Drug costs were based on cost of acquisition. Effectiveness was measured in quality-adjusted life years (QALYs). Results: (See Table) OTA was most the effective strategy and was associated with the lowest risk of developing advanced liver disease. Also, OTA was the most cost-effective strategy, with an ICER of

512 THE POTENTIAL IMPACT OF INTERFERON FREE ORAL REGIMENS ON CLINICAL AND COST OUTCOMES OF PATIENTS WITH CHRONIC HEPATITIS C, GENOTYPE 1: A DECISION ANALYTIC ASSESSMENT

16,289/QALY. The ICER remained below