Faculty Bibliography

BACKGROUND:Social determinants of health (SDOH), i.e., social, behavioral and environmental factors, are increasingly recognized for their important influence on health outcomes. Data are limited on the influence of SDOH, substance use characteristics, and their interactions on pursuit of hepatitis C virus (HCV) care among individuals with opioid use disorder (OUD). Linkage to HCV care remains low in this population despite high HCV prevalence and incidence. AIMS/OBJECTIVE:To investigate the influence of SDOH, substance use factors, and their interactions on HCV treatment uptake among OUD patients in a methadone treatment program. METHODS:Information on patient demographics, SDOH, substance use characteristics, and co-morbid medical conditions were obtained from the paper and electronic medical records of OUD patients on methadone. We applied multiple correspondence analysis, k-means algorithm, and logistic regression with least absolute shrinkage and selection operator penalty to identify variables and clusters associated with pursuit of HCV care. RESULTS:Data from 161 patients (57% male, 60% Caucasian, mean age 45 years) were evaluated. Being employed, the absence of support systems, and a history of foster care were the strongest positive predictors of treatment pursuit. The use of crack/cocaine as the initial illicit substance, criminal activity without incarceration, and the absence of a family history of chemical dependency were the strongest negative predictors. We identified clusters among persons with OUD based upon their likelihood to pursue HCV management. CONCLUSION/CONCLUSIONS:Utilizing data from the medical record, we were able to identify factors positively and negatively associated with linkage-to-care for HCV. We were also able to divide patients into clusters of factors associated with linkage-to-care for HCV. These results could be used to identify individuals with OUD based upon their readiness for HCV care.

AIM/OBJECTIVE:To understand the role of knowledge as a promoter of hepatitis C virus (HCV) screening among primary care physicians (PCP). METHODS:., birth between 1945 and 1965) screening. Response stratification and weighting were used to account for nonresponse and to permit extension of responses to the entire survey population. Associations between various predictors including demographic characteristics, level of training, and HCV treatment experience and HCV knowledge were assessed. RESULTS:-value = 0.03). CONCLUSION/CONCLUSIONS:Comprehensive knowledge of HCV is critical to motivate HCV screening. PCP-targeted educational interventions are required to expand the HCV workforce and linkage-to-care opportunities as we seek global HCV eradication.

Background/UNASSIGNED:It is unknown whether ribavirin (RBV) coadministration modifies the early rate of decline of hepatitis C virus (HCV) RNA in the liver versus plasma compartments, specifically. Methods/UNASSIGNED:This partially randomized, open-label, phase 2 study enrolled treatment-naive, noncirrhotic patients with HCV genotype 1a. Patients were randomized 1:1 into Arms A and B, and then enrolled in Arm C. Patients received ombitasvir/paritaprevir/ritonavir plus dasabuvir for 12 weeks with either: no RBV for the first 2 weeks followed by weight-based dosing thereafter (Arm A), weight-based RBV for all 12 weeks (Arm B), or low-dose RBV (600 mg) once daily for all 12 weeks. Fine needle aspiration (FNA) was used to determine HCV RNA decline within liver. Results/UNASSIGNED:Baseline HCV RNA was higher and declined more rapidly in plasma than liver; however, RBV dosing did not impact either median plasma or liver HCV RNA decline during the first 2 weeks of treatment. Liver-to-plasma drug concentrations were variable over time. The most common adverse event was pain associated with FNA. Conclusions/UNASSIGNED:Coadministration of RBV had minimal visible impact on the plasma or liver kinetics of HCV RNA decline during the first 2 weeks of treatment, regardless of RBV dosing.

BACKGROUND:The hepatitis C virus (HCV) core antigen (HCVcAg) may be an alternative diagnostic method to HCV RNA especially in populations such as substance users, the homeless or in resource-limited settings. AIMS:To evaluate performance of HCVcAg test in patients with opioid use disorder (OUD) on methadone in order to document its performance characteristics in the target population and to ensure that its specificity remains consistent across different populations. METHODS:HCVcAg levels from 109 methadone-maintained patients were compared to HCV RNA levels. RESULTS:Mean age was 53.8±7.8years, 59.6% were male, 68.8% African American, and 44% HCV-infected. HCVcAg was detectable in 47 of 48 HCV-infected, and undetectable in all HCV RNA negative patients. The HCVcAg assay had sensitivity of 97.9% and specificity of 100%. Correlation with HCV RNA levels was excellent (r=0.88, 95% CI 0.76; 0.95, p<0.01). CONCLUSION:HCVcAg has excellent performance for the diagnosis of HCV infection in patients with OUD on methadone.

Direct-acting antivirals for hepatitis C virus infection may revolutionize treatment among persons with substance use disorders. Despite persons with substance use disorders having the highest hepatitis C virus prevalence and incidence, the vast majority have not engaged into care for the infection. Previously, interferon-based treatments, with substantial side effects and the propensity to exacerbate mental health conditions, were major disincentives to pursuit of care for the infection. Direct-acting antivirals with viral eradication rates of >90%, significantly improved side effect profiles, and shorter treatment duration are dramatic improvements over prior treatment regimens that should promote widespread hepatitis C virus care among persons with substance use disorders. The major unmet need is strategies to promote persons with substance use disorders engagement into care for hepatitis C virus. Although physical integration of treatment for substance use and co-occurring conditions has been widely advocated, it has been difficult to achieve. Telemedicine offers an opportunity for virtual integration of behavioral and medical treatments that could be supplemented by conventional interventions such as hepatitis C virus education, case management, and peer navigation. Furthermore, harm reduction and strategies to reduce viral transmission are important to cease reinfection among persons with substance use disorders. Widespread prescription of therapy for hepatitis C virus infection to substance users will be required to achieve the ultimate goal of global virus elimination. Combinations of medical and behavioral interventions should be used to promote persons with substance use disorders engagement into and adherence with direct-acting antiviral-based treatment approaches. Ultimately, either physical or virtual colocation of hepatitis C virus and substance use treatment has the potential to improve adherence and consequently treatment efficacy.

An ultra-performance liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of direct acting antiviral drug concentrations in human liver fine needle aspirates. Liver fine needle aspirate (FNA) biopsy samples were homogenized in acetonitrile to stabilize the analytes and precipitate protein. The acetonitrile supernatants were diluted with internal standards and mobile phase. Separation was achieved with a Waters Acquity BEH C18 column (50×2.1mm, 1.7um) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 4.25min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 12.5 to 5000ng/mL for dasabuvir and the m1 metabolite of dasabuvir, 1.25 to 2500ng/mL for ombitasvir and ritonavir, and 5.00 to 5000ng/mL for paritaprevir. The intra- and inter-day accuracy and precision were less than 13.7% in low, medium, and high quality control samples. The validated method was applied to the analysis of a liver fine needle aspirate of a patient undergoing direct acting antiviral therapy for hepatitis C virus.

The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA₁, FNA₃, and FNA₅); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C_max] and area under the concentration-time curve from 0 to 24 h [AUC_0-24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA₃ and FNA₅, with 18% bias, and FNA₁ and FNA₃, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

PURPOSE:), and other quantitative pharmacokinetic (PK) parameters, for hepatic fibrosis stage; to compare this accuracy with a previously published semiquantitative metric, contrast enhancement index (CEI); and to assess variability of these parameters between liver regions. MATERIALS AND METHODS:This was a case-control study design. Dynamic Gd-EOB-DTPA-enhanced 1.5T magnetic resonance imaging (MRI) was performed prospectively in 22 subjects with varying known stages of hepatic fibrosis. PK parameters and CEI were derived from the whole livers and from three fixed regions of interest (ROIs) in all subjects. Spearman rank correlation coefficients were computed to assess the relationship between fibrosis stages and each parameter. Receiver operating characteristic (ROC) curves were constructed to discriminate severe fibrosis (stages 3-4) from nonsevere fibrosis (stages 0-2). The coefficient of variation (CV) was calculated to assess variability in parameters between ROIs. RESULTS:) (R = -0.48, 95% CI [-0.75,-0.05], P = 0.03). CONCLUSION:, derived from dynamic contrast-enhanced MRI, correlates with fibrosis stage and may contribute to a noninvasive biomarker of hepatic fibrosis. LEVEL OF EVIDENCE:2 J. Magn. Reson. Imaging 2017;45:1177-1185.