Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies.

BACKGROUND: Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST. METHODS: Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible. RESULTS: Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%). CONCLUSION: Sofosbuvir-based therapies are effective and safe in patients receiving OST.

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

Association of chronic liver disease with depression: a population-based study.

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.

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

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. METHODS: Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. RESULTS: A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11-1.76), OR = 1.39 (0.98-1.97), and OR = 2.17 (1.19-3.95); respectively)]. CONCLUSIONS: This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD.

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

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 χ 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.

Monoclonal and polyclonal antibodies against the HCV envelope proteins.

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.