Intravenous 2-hydroxypropyl-ß-cyclodextrin (Trappsol® Cyclo™) demonstrates biological activity and impacts cholesterol metabolism in the central nervous system and peripheral tissues in adult subjects with Niemann-Pick Disease Type C1: Results of a phase 1 trial.

BACKGROUND: Niemann-Pick Disease Type C1 (NPC1) is a disorder of intracellular cholesterol and lipid trafficking that leads to the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment, resulting in systemic manifestations (including hepatosplenomegaly and lung infiltration) and neurodegeneration. Preclinical studies have demonstrated that systemically administered 2-hydroxypropyl-ß-cyclodextrin (HPßCD; Trappsol® Cyclo™) restores cholesterol metabolism and homeostasis in peripheral organs and tissues and in the central nervous system (CNS). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of HPßCD in peripheral tissues and the CNS in adult subjects with NPC1. METHODS: A Phase 1, randomized, double-blind, parallel group study enrolled 13 subjects with NPC1 who received either 1500 mg/kg or 2500 mg/kg HPßCD intravenously every 2 weeks for a total of 7 doses (14 weeks). Subjects were 18 years or older, with a confirmed diagnosis of NPC1 and evidence of systemic involvement on clinical assessment. Pharmacokinetic evaluations in plasma and cerebrospinal fluid (CSF) were performed at the first and seventh infusions. Pharmacodynamic assessments included biomarkers of systemic cholesterol synthesis (serum lathosterol) and degradation (serum 4ß-hydroxycholesterol), secondary sphingomyelin storage (plasma lysosphingomyelin-509, now more accurately referred to as N-palmitoyl-O-phosphocholineserine [PPCS]), and CNS-specific biomarkers of neurodegeneration (CSF total Tau) and cholesterol metabolism (serum 24(S)-hydroxycholesterol [24(S)-HC]). Safety monitoring included assessments of liver and kidney function, infusion related adverse events, and hearing evaluations. RESULTS: Ten subjects completed the study, with 6 at the 1500 mg/kg dose and 4 at the 2500 mg/kg dose. One subject withdrew following the first infusion after experiencing hypersensitivity pneumonitis, and 2 subjects withdrew after meeting a stopping rule related to hearing loss. Overall, HPßCD had an acceptable safety profile. The observed pharmacokinetic profile of HPßCD was similar following the first and seventh infusions, with a plasma half-life of 2 h, a maximum concentration reached at 6 to 8 h, and no evidence of accumulation. Serum biomarkers of cholesterol metabolism showed reduced synthesis and increased degradation. Compared to Baseline, filipin staining of liver tissue showed significant reductions of trapped unesterified cholesterol at both dose levels at Week 14. Plasma PPCS levels were also reduced. HPßCD was detected at low concentrations in the CSF (maximum, 33 µM) at both dose levels and persisted longer in CSF than in plasma. Total Tau levels in CSF decreased in most subjects. Serum levels of 24(S)-HC, a cholesterol metabolite from the CNS that is exported across the blood-brain barrier and into the circulation, decreased after both the first and seventh doses. Hence, pharmacodynamic assessments in both peripheral and CNS-related tissue show target engagement. While not the aim of the study, subjects reported favorable impacts on their quality of life. CONCLUSIONS: The plasma pharmacokinetics and pharmacodynamics of HPßCD administered at two intravenous dose levels to subjects with NPC1 were comparable to those observed in preclinical models. HPßCD cleared cholesterol from the liver and improved peripheral biomarkers of cholesterol homeostasis. At low CSF concentrations, HPßCD appeared to be pharmacologically active in the CNS based on the increased efflux of 24(S)-HC and reduction in CSF total Tau, a biomarker of CNS neurodegeneration. These data support the initiation of longer-term clinical trials to evaluate the safety and efficacy of intravenous HPßCD in subjects with NPC1. (ClinicalTrials.gov numbers: present trial, NCT02939547; open-label extension of the present trial, NCT03893071; global pivotal trial, NCT04860960).

Race/Ethnicity-specific Disparities in In-Hospital Mortality and Hospital Charges Among Inflammatory Bowel Disease-related Hospitalizations in the United States.

GOAL: The goal of this study was to evaluate disparities in hospital outcomes among inflammatory bowel disease (IBD) related hospitalizations in the United States with a focus on ethnicity-specific disparities. BACKGROUND: IBD-related hospitalizations contribute to significant morbidity and health care economic burden. METHODS: IBD-related hospitalizations (identified with ICD-9) among US adults were evaluated using 2007 to 2013 Nationwide Inpatient Sample. In-hospital mortality between groups was evaluated using χ and multivariate logistic regression models, stratified by Crohn's disease (CD) and ulcerative colitis (UC). Inflation-adjusted total hospitalization charges were evaluated using Student t test and multivariate linear regression. RESULTS: Among 224,500 IBD-related hospitalizations (77.8% CD, 22.2% UC), overall in-hospital mortality was low (0.99% CD, 0.78% UC). Although Hispanic UC patients had a trend towards higher odds of in-hospital mortality compared with non-Hispanic whites (OR, 1.54; 95% CI, 0.95-2.51; P=0.08), no ethnicity-specific disparities were observed in CD. From 2007 to 2013, mean inflation-adjusted hospitalization charges increased from $29,632 to $41,484, P<0.01 in CD and from $31,449 to $43,128 in UC, P<0.01. On multivariate regression, hospitalization charges in Hispanic CD patients were $9302 higher (95% CI, 7910-10,694; P<0.01) and in Asian CD patients were $7665 higher (95% CI, 4859-10,451; P<0.001) than non-Hispanic whites. Compared with non-Hispanic white UC patients, Hispanics had $6910 (95% CI, $4623-$9197) higher charges and African Americans had $3551 lower charges (95% CI, -$5002 to -$2101). CONCLUSIONS: Although most IBD hospitalizations in the United States were among non-Hispanic whites, Hispanic patients with IBD had a trend towards higher in-hospital mortality and contributed to significantly higher hospitalization charges.

A Comprehensive Analysis of Liver Transplantation Outcomes Among Ethnic Minorities in the United States.

GOALS: The aim of this study was to perform a comprehensive assessment of liver transplant (LT) outcomes among US adults with a specific focus on understanding race/ethnicity-specific disparities. BACKGROUND: Despite improvements in the liver allocation and LT-related care, disparities in LT outcomes persist. STUDY: Using data from the 2005 to 2016 United Networks for Organ Sharing LT registry, we evaluated waitlist survival, probability of receiving LT, and post-LT survival among US adults stratified by race/ethnicity and liver disease etiology. Kaplan-Meier methods evaluated unadjusted waitlist and post-LT outcomes, and multivariate regression models evaluated adjusted waitlist and post-LT outcomes. RESULTS: Among 88,542 listed for LT patients (41.3% hepatitis C virus, 25.3% alcoholic liver disease, 22.3% nonalcoholic steatohepatitis, 11.1% hepatitis C virus/alcoholic liver disease), significant race/ethnicity-specific disparities were observed. Compared with non-Hispanic whites, Hispanics had a significantly lower risk of waitlist death [hazard ratio (HR)=0.84, 95% confidence interval (CI): 0.79-0.90, P<0.001]. Compared with non-Hispanic whites, significantly lower likelihood of receiving LT was observed in African Americans (HR=0.94, 95% CI: 0.91-0.98, P<0.001), Hispanics (HR=0.70, 95% CI: 0.68-0.73, P<0.001) and Asians (HR=0.74, 95% CI: 0.69-0.80, P<0.001). Compared with non-Hispanic whites, African Americans had a significantly higher risk of 5-year post-LT death (HR=1.31, 95% CI: 1.23-1.39, P<0.001). CONCLUSION: Among US adults awaiting LT, significant race/ethnicity-specific disparities in LT outcomes were observed. Despite evaluating an era after implementation of the Model for End-Stage Liver Disease, ethnic minorities continue to demonstrate a lower probability of receiving LT, and significantly higher risk of death post-LT in African Americans.

Updated Assessment of Colorectal Cancer Incidence in the U.S. by Age, Sex, and Race/Ethnicity.

BACKGROUND: Whether recent updates to colon cancer screening guidelines benefit men and women or all race/ethnic groups equally is not clear. AIMS: The aim of this study is to evaluate age-, sex-, and race/ethnicity-specific trends in CRC incidence and disease burden among adults. METHODS: Using 2000-2014 surveillance, epidemiology, and end results database, annual CRC incidence (per 100,000 persons/year) among U.S. adults was categorized by age (using 10-year age intervals) and stratified by sex and race/ethnicity. Comparison of incidence between groups utilized the z-statistic with p < 0.05 indicating statistical significance. RESULTS: Overall, CRC incidence was the highest among patients aged ≥ 80 years (330.8 per 100,000 persons/year), which was significantly higher in men versus women (377.2 vs. 304.3 per 100,000 persons/year, p < 0.001). CRC incidence in younger individuals was 22.8 per 100,000 persons/year (age 40-49) and 6.8 per 100,000 persons/year (age 30-39). CRC incidence was significantly higher in African Americans compared to non-Hispanic whites. From 2000 to 2014, CRC incidence declined in all age groups over age 60, remained stable in age 50-59, and demonstrated proportional increases in among age 20-49 years. While CRC incidence in all race/ethnic groups aged ≥ 60 years declined, Hispanics aged 50-59 increased 21.9%, but remained stable in other race/ethnic groups. Race/ethnicity-specific disparities in CRC incidence in patients aged 20-49 were also observed. CONCLUSIONS: While CRC incidence has declined among U.S. adults aged ≥ 60, increasing incidence among patients aged < 50 is concerning. Identifying risk factors among "average-risk" patients is needed to better implement targeted screening of individuals not currently meeting CRC screening criteria.

Low Rates of Linkage and Retention Into Care Among Patients With Chronic HBV Infection.

Successful linkage and retention of newly diagnosed hepatitis B virus (HBV) patients is critical for disease monitoring. Existing studies have demonstrated significant gaps in the HBV care continuum among U.S. veterans1 and have mostly focused on adherence to laboratory testing or initial linkage. However, retention is especially important, given that decisions to start antiviral therapies are often not made until subsequent evaluation, and studies report high rates of becoming treatment-eligible among patients who were not eligible at initial evaluation.2 Given the existing system and socioeconomic barriers in access to care, understanding contributors to gaps and delays in HBV linkage and retention among safety-net populations is critical. We aim to evaluate prevalence and predictors of linkage and retention among HBV patients at an urban safety-net hospital.

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct-acting antiviral therapies in the United States.

Direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection achieve high cure rates, reducing HCV-related disease progression to cirrhosis and hepatocellular carcinoma. We aim to evaluate the impact of DAAs on US liver transplant (LT) waitlist outcomes. We retrospectively evaluated US adults (age ≥18) with and without chronic HCV listed for LT before and after the widespread use of sofosbuvir, allowing a 6-month period after approval (Era 1: 1/1/2002-5/31/2014 vs Era 2: 6/1/2014-12/31/2016) using the United Network for Organ Sharing registry. Overall, LT waitlist survival and likelihood of receiving LT were evaluated with multivariate Cox regression models. From 2002 to 2016, 158 045 patients were listed for LT. While the number of patients listed for HCV has been decreasing since 2012, the proportion of HCV patients with concurrent HCC is increasing by 3.33% per year (R2 : 0.99, P < 0.001 by simple linear regression). While there was no difference in likelihood of LT between HCV and non-HCV patients, those listed in Era 2 had lower likelihood of LT (HR: 0.91, P < 0.001), more pronounced in the HCV cohort (HR: 0.83, P < 0.001) compared to the non-HCV cohort (HR: 0.93, P < 0.001). Compared to non-HCV patients, higher waitlist mortality was seen in HCV patients in Era 1 (HR: 1.08, P < 0.001) but not in Era 2 (HR: 1.02, P = 0.75). Since the introduction of DAAs for HCV treatment, number of patients with HCV listed for LT has declined. In the post-DAA era, HCV patients on the LT waitlist had improved waitlist mortality.

Assessing the safety of beta-blocker therapy in cirrhosis patients with ascites: A meta-analysis.

BACKGROUND & AIMS: Beta-blocker therapy is effective at reducing risks of variceal bleeding. However, beta-blockers may detrimentally exacerbate the underlying haemodynamic changes in cirrhosis. A systematic review and meta-analysis was performed to evaluate impact of beta-blockers on all-cause mortality among cirrhosis patients with ascites. METHODS: A literature search identified studies that evaluated beta-blocker vs no beta-blocker therapy in cirrhosis patients with ascites. The primary outcome was all-cause mortality with subcohort analysis of patients with refractory or severe ascites. Quality of observational studies was assessed with Newcastle-Ottawa Scale and overall certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Eight observational studies, representing 3627 cirrhosis patients with ascites (1630 treated with beta-blockers and 1997 not treated), were included. Pooled all-cause mortality was 38.6% in beta-blocker group vs 42.2% in no beta-blocker group (RR 0.93, 95% CI 0.77-1.13, χ2  = 54.03, I2  = 87%). Subcohort analysis of cirrhosis patients with refractory or severe ascites demonstrated 33.3% mortality in beta-blocker group vs 32.1% in no beta-blocker group (RR 0.99, 95% CI 0.70-1.40, χ2  = 32.99, and I2  = 82%). Three studies were good quality and five studies were fair quality. GRADE rating was 'very low' certainty of evidence, given concern for bias and inconsistency stemming from significant heterogeneity. CONCLUSION: No significant increase in all-cause mortality was observed in cirrhosis patients with ascites treated with beta-blockers. However, given the low certainty of the evidence, high quality prospective studies are needed.

Low Rates of Retention Into Hepatocellular Carcinoma (HCC) Surveillance Program After Initial HCC Screening.

GOALS: To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients. BACKGROUND: Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening. METHODS: We retrospectively evaluated all consecutive adults with cirrhosis from 2014 to 2017 at a single underserved safety net hospital system to determine rates of HCC surveillance at 6 months and at 1 year beyond initial screening. Rates of HCC surveillance was stratified by sex, race/ethnicity, and etiology of liver disease. Multivariate Cox proportional hazards models evaluated predictors of retention into HCC surveillance. RESULTS: Among 235 cirrhosis patients [hepatitis C virus: 35.7%, hepatitis B virus (HBV): 15.7%, alcoholic cirrhosis: 36.2%, nonalcoholic steatohepatitis (NASH): 8.1%], mean age of cirrhosis diagnosis was 54.2±8.9 years. Overall, 74.8% received initial screening within 1 year of cirrhosis diagnosis. Among those who completed initial screening, 47.6% [95% confidence interval (CI), 41.4-54.2) received second surveillance within 1 year. On multivariate analyses, patients with NASH and HBV were significantly more likely to receive second HCC surveillance compared with hepatitis C virus, HBV (hazard ratio, 2.32; 95% CI, 1.18-4.56; P=0.014) and NASH (hazard ratio, 2.49; 95% CI, 1.22-5.11; P=0.012). No sex or race-specific/ethnicity-specific differences in HCC surveillance retention were observed. CONCLUSIONS: Although overall rates of initial HCC screening among cirrhosis patients is nearly 75%, retention into continued HCC surveillance is poor, with less than half of patients undergoing subsequent HCC surveillance. Cirrhosis patients with HBV and NASH were more likely to be retained into HCC surveillance.

Medicaid and Uninsured Hepatocellular Carcinoma Patients Have More Advanced Tumor Stage and Are Less Likely to Receive Treatment.

GOALS: To evaluate the impact of insurance status on tumor stage at diagnosis, treatment received, and overall survival among adults with hepatocellular carcinoma (HCC). BACKGROUND: Insurance status affects access to care, which impacts timely access to cancer screening for early detection and treatment. STUDY: Using the 2007 to 2012 Surveillance, Epidemiology, and End Results (SEER) database, we retrospectively evaluated US adults with HCC. Insurance status included Medicare/commercial insurance (MC), Medicaid (MA), and no insurance (NI). HCC tumor stage was evaluated using SEER staging system and Milan criteria. HCC treatment and survival were evaluated using multivariate logistic regression and Cox proportional hazards models. RESULTS: Among 32,388 HCC patients (71.2% MC, 23.9% MA, and 4.9% NI), patients with MA or NI were significantly less likely to have localized tumor stage at time of diagnosis compared with MC [NI vs. MC; odds ratio, 0.41; 95% confidence interval (CI), 0.78-0.92; P<0.001]. MA and NI patients were less likely to receive treatment, and specifically less likely to receive surgical resection or liver transplantation compared with MC patients, even after correcting for tumor stage at diagnosis (odds of surgical resection or liver transplant in NI vs. MC: odds ratio, 0.26; 95% CI, 0.21-0.33; P<0.001). NI patients (hazard ratio, 1.39; 95% CI, 1.29-1.50; P<0.001) had significantly lower survival compared with MC patients. CONCLUSIONS: Among US adults with HCC, MA, or NI patients had more advanced tumor stage at diagnosis, lower rates treatment, and significantly lower overall survival. Ensuring equal insurance coverage may improve access to care and mitigate some disparities in HCC outcomes.

A Pilot Program Integrating Hepatitis B Virus (HBV) Screening into an Outpatient Endoscopy Unit Improves HBV Screening Among an Ethnically Diverse Safety-Net Hospital.

BACKGROUND: Safety-net hospitals are enriched in ethnic minorities and provide opportunities for high-impact hepatitis B virus (HBV) screening. AIM: We aim to evaluate the impact of a pilot program integrating HBV screening into outpatient endoscopy among urban safety-net populations. METHODS: From July 2015 to May 2017, consecutive adults undergoing outpatient endoscopy were prospectively assessed for HBV screening eligibility using US Preventative Services Task Force guidelines. Rates of prior HBV screening were assessed, and those eligible but not screened were offered HBV testing. Multivariate logistic regression models evaluated predictors of test acceptance among eligible patients. RESULTS: Among 1557 patients (47.1% male, 69.4% foreign born), 65.1% were eligible for HBV screening, among which 24.5% received prior screening. In our pilot screening program in the endoscopy unit, 91.4% (n = 855) of eligible patients accepted HBV testing. However, only 55.3% (n = 415) of those that accepted actually completed HBV testing. While there was a trend toward higher rates of test acceptance among African-Americans compared to non-Hispanic whites (OR 3.31, 95% CI 0.96-11.38, p = 0.06), no other sex-specific or race/ethnicity-specific disparities in HBV test acceptance were observed. Among those who completed HBV testing, we identified 10 new patients with chronic HBV (2.4% prevalence). Only 24.5% of eligible patients received prior HBV screening among our cohort. CONCLUSIONS: Our pilot program integrating HBV screening into outpatient endoscopy successfully tested an additional 415 patients, improving overall HBV screening from 24.5 to 75.6%. Integrating HBV testing into non-traditional settings has potential to bridge the gap in HBV screening among safety-net systems.

Sub-optimal Testing and Awareness of HCV and HBV Among High Risk Individuals at an Underserved Safety-Net Hospital.

Sub-optimal screening for chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV) among high risk groups delays diagnosis and treatment. We aimed to evaluate overall rates of HCV and HBV screening and patient knowledge of their testing result. Adults age ≥18 years undergoing elective outpatient endoscopy at a large, urban safety-net hospital from July 2015 to July 2016 were prospectively evaluated to determine rates of HCV and HBV testing, the results of those completed tests, and patient knowledge of test results among high risk individuals (as determined by U.S. Preventative Services Task Force). Among 1125 patients (52.3% male, 70.4% foreign-born), 66.5% were high risk for chronic HCV; only 30.9% received prior testing. 14.7% had positive chronic HCV infection. Patients born in the 1945-1965 cohort were more likely to have received prior HCV testing compared to those born outside of this cohort (32.7 vs. 16.9%, p = 0.01). Among patients who received HCV screening, 29.3% were aware of test results. Overall, 61.6% were high risk for chronic HBV; only 25.1% received prior testing. 4.1% were positive for chronic HBV. Compared to Caucasians, Asians (19.0 vs. 44.4%, p < 0.001) and Hispanics (20.0 vs. 44.4%, p < 0.001) were less likely to have previous HBV testing. Among patients who received prior HBV screening, 18.4% were aware of test results. Less than one-third of high risk patients received HCV and HBV screening among an ethnically diverse safety-net population. Equally low rates of patient knowledge of testing results were observed.

Improvements in hepatitis B virus screening before rituximab therapy: A community-based, safety-net hospital experience.

BACKGROUND: Individuals with chronic hepatitis B virus infection (HBV) or previously resolved HBV are at increased risk of HBV exacerbation or reactivation when they receive treatment with anti-CD20 monoclonal antibodies (against B-lymphocyte antigen cluster of differentiation 20 [CD20], an activated-glycosylated phosphoprotein) like rituximab (RTX). The objective of the current study was to evaluate the rates of appropriate HBV screening before patients started receiving RTX, at the initiation of HBV treatment, and during HBV flares among an underserved safety-net population. METHODS: In total, 244 consecutive adults who received treatment with RTX from 2006 to 2015 at an urban safety-net hospital were evaluated to determine appropriate HBV screening (HBV surface antigen [HBsAg] and HBV total core antibody [HBcAb]) before starting RTX. The initiation of prophylactic antiviral therapy and the development of HBV flares after starting RTX were evaluated. Predictors of appropriate HBV screening were evaluated using multivariate logistic regression models. RESULTS: Most patients were women (52.7%; n = 128) and of Hispanic ethnicity (30.7%; n = 74). Before starting RTX, 60.5% (n = 147) of patients received appropriate HBV screening. The HBV screening rates before RTX improved from 14.7% (2006-2009) to 74.7% (2010-2012), and to 87.1% (2013-2015; P < .01. Two of 7 (28.6%) HBsAg-positive patients who did not receive antiviral therapy experienced HBV flares and 1 died, and 2 of 27 patients (7.4%) HBcAb-positive/HBsAg-negative patients who did not receive antiviral therapy experienced HBV reactivation. No patient-specific or disease-specific predictors of receiving HBV screening before RTX therapy were identified. CONCLUSIONS: Among adults receiving RTX therapy in a single community-based hospital system, HBV screening rates were suboptimal, and 28.6% of HBsAg-positive patients and 7.4% of HBsAg-negative/HBcAb-positive patients who did not receive antiviral treatment experienced HBV reactivation or flare. Cancer 2017;123:650-656. © 2016 American Cancer Society.

Older Patients With Hepatocellular Carcinoma Have More Advanced Disease, Lower Rates of Treatment, and Lower Survival.

GOALS: To evaluate age-specific disparities in cancer stage at diagnosis, receipt of treatment, and survival among adults with hepatocellular carcinoma (HCC). BACKGROUND: HCC has become the fastest rising cause of cancer-related deaths in the United States. The aging population coupled with the rising incidence of HCC will result in an emerging cohort of older patients with HCC placing significant burden health care systems. STUDY: Using 2003 to 2011 Surveillance, Epidemiology, and End Results data, a US population-based cancer registry, we retrospectively evaluated age-specific disparities in cancer stage at diagnosis, receipt of treatment, and survival among adults with HCC. Multivariate logistic regression models evaluated HCC stage at diagnosis and HCC treatment received. Multivariate Cox proportional hazard models evaluated long-term survival. RESULTS: Compared with HCC patients below 50 years old, patients aged 70 years or older were less likely to have HCC within Milan criteria [odds ratio, 0.58; confidence interval (CI), 0.54-0.63; P<0.001]. Older age was also associated with significantly lower rates of receiving HCC treatment. Even after adjusting for stage of disease, patients aged 70 years or older had the lowest odds of receiving any HCC treatment compared with patients below 50 years old (odds ratio, 0.52; CI, 0.46-0.60; P<0.001). On multivariate Cox regression, HCC patients aged 70 years or older had significantly lower survival compared with patients below 50 years old (hazards ratio, 1.22; CI, 1.15-1.30; P<0.001). CONCLUSIONS: Among US adults with HCC, patients aged 70 years or older were less likely to have HCC within Milan criteria at diagnosis, less likely to receive any HCC treatment, and had significantly lower long-term survival.

Race/Ethnicity-Specific Disparities in the Severity of Disease at Presentation in Adults with Ulcerative Colitis: A Cross-Sectional Study.

BACKGROUND: While ulcerative colitis (UC) is well studied in Caucasian populations, less data are available on UC patients of racial/ethnic minorities, including variations in disease severity at presentation. AIM: To evaluate race/ethnicity-specific disparities in UC disease presentation among an ethnically diverse underserved population. METHODS: We performed a cross-sectional study of all consecutive UC adults among a large ethnically diverse safety-net hospital from July 2014 to May 2016 to compare race/ethnicity-specific disparities in severity of disease at presentation. Severity was evaluated using the clinician-based simple clinical colitis activity index (SCCAI) and the Mayo score at time of presentation. Multivariate ordered logistic regression models were used to evaluate associations with SCCAI and Mayo scores. RESULTS: Among 98 UC patients (56.1% male, mean age 40.1 (SD 14.2), 32.0% were African-American, 26.7% Hispanic, 16.0% Asian, and 20.0% Caucasian. Mean Mayo score was 6.6 and mean SCCAI score was 6.5. When stratified by race/ethnicity, SCCAI scores were significantly higher in non-Caucasians compared to Caucasians (7.0 vs 4.6, p = 0.03) and in Asians compared to Caucasians (8.0 vs 4.6, p = 0.02). There was a trend toward higher mean SCCAI in Hispanics compared to Caucasians (6.9 vs 4.6, p = 0.07). Mayo scores at presentation demonstrated similar trends. On multivariate logistic regression, Asians (OR 5.26, 95% CI 1.24-22.42) and Hispanics (OR 3.74; 95% CI 1.02-13.66) had more severe disease at presentation than Caucasians based on SCCAI. CONCLUSIONS: Among a diverse underserved cohort of UC patients, racial/ethnic minority patients with UC, specifically Asians and Hispanics, had more severe disease at presentation compared to Caucasians. The differences may reflect disparities in timely access to specialty care and treatment and deserves greater attention and research.

Race/Ethnicity-Specific Outcomes Among Chronic Hepatitis C Virus Patients Listed for Liver Transplantation.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC) and need for liver transplantation (LT). It is unclear if HCV-related LT outcomes vary by race/ethnicity. AIMS: We aim to evaluate ethnic disparities specifically among patients with chronic HCV in the USA. METHODS: Using data from the United Network for Organ Sharing 2003-2013 LT registry, we evaluated race/ethnicity-specific disparities in LT waitlist survival and probability of receiving LT among chronic HCV patients listed for LT. RESULTS: Among 43,478 HCV patients listed for LT (70.0% non-Hispanic white, 10.8% black, 16.3% Hispanic, 2.9% Asian), HCV-related LT waitlist registrations increased by 21.5% from 2003 to 2013. During this period, the proportion of HCV patients with HCC increased by 237%, and in 2013, HCV patients with HCC accounted for 33.0% of HCV-related waitlist registrations. When stratified by race/ethnicity, Hispanics with HCV had significantly lower waitlist mortality (OR 0.83; 95% CI 0.74-0.94; p < 0.01) compared to non-Hispanic whites, but no significant differences were seen among blacks and Asians. Furthermore, compared to non-Hispanic whites, Hispanics were significantly less likely to receive LT (OR 0.58; 95% CI 0.53-0.62; p < 0.001), but no differences were seen among blacks or Asians. CONCLUSION: Among patients with chronic HCV in the USA, the MELD score has reduced race/ethnicity-specific disparities in waitlist mortality. However, Hispanic HCV patients had significantly better waitlist survival and lower probability of receiving LT, possibly reflecting slower disease progression compared to non-Hispanic whites with chronic HCV.

Cirrhosis Patients with Nonalcoholic Steatohepatitis Are Significantly Less Likely to Receive Surveillance for Hepatocellular Carcinoma.

BACKGROUND: Disparities in receipt of hepatocellular carcinoma (HCC) surveillance contribute to disparities in overall survival outcomes. AIM: We aim to evaluate disparities in receipt of routine HCC surveillance among patients with cirrhosis in a large urban safety-net hospital. METHODS: Consecutive adults (age ≥ 18) with cirrhosis from July 1, 2014, to December 31, 2015, were retrospectively evaluated to determine rates of receiving appropriate HCC surveillance within 6 months and 1 year after diagnosis of cirrhosis. Rates of HCC surveillance were stratified by sex, race/ethnicity, and liver disease etiology. Multivariate Cox proportional hazards models were utilized to evaluate for predictors of receiving appropriate HCC surveillance. RESULTS: Among 157 cirrhosis patients enrolled [hepatitis C virus (HCV): 29.9%, hepatitis B virus: 13.4%, alcoholic cirrhosis: 44.6%, nonalcoholic steatohepatitis (NASH): 8.9%], mean age of cirrhosis diagnosis was 53.8 ± 9.0 years. Among these patients, 49% received (n = 77) HCC surveillance within 6 months and 78% (n = 123) were surveyed within 1 year of cirrhosis diagnosis. On multivariate analyses, patients with NASH cirrhosis were significantly less likely to receive HCC surveillance compared with chronic HCV cirrhosis patients (HR 0.44, 95% CI 0.19-0.99, p < 0.05). No significant sex-specific or race/ethnicity-specific disparities in receipt of HCC surveillance were observed. CONCLUSION: Among a diverse safety-net hospital population, sub-optimal HCC surveillance rates were observed: Only 49% of cirrhosis patients received HCC surveillance within 6 months, and 78% of cirrhosis patients received HCC surveillance within 1 year. Differences in rates of HCC screening by liver disease etiology were observed.

The Need for an Integrated Patient Navigation Pathway to Improve Access to Colonoscopy After Positive Fecal Immunochemical Testing: A Safety-Net Hospital Experience.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. Delays in access to colonoscopy following positive fecal immunochemical test (FIT) contribute to increased CRC incidence and mortality. To evaluate intervals from positive FIT result to receipt of colonoscopy among underserved safety-net populations. We retrospectively evaluated all average CRC risk adults who had positive FIT results from 2012 to 2015 at an ethnically diverse safety-net hospital system. Interval from positive FIT to receipt of colonoscopy was evaluated with Kaplan Meier methods and multivariate Cox proportional hazards models. Among 467 patients with positive FIT (48.4 % men, 39.5 % black, 22.5 % white, 17.4 % Asian, 9.7 % Hispanic, mean age 59.5 ± 9.8 years), mean time from positive FIT to receipt of colonoscopy was 220.5 days (SD 158.5). Compared to men, there was a trend towards longer time from FIT positive to colonoscopy among women (237.1 vs. 198.7 days, p = 0.07). No race/ethnicity-specific disparities in time to colonoscopy were observed. Compared to 2012-2013, there was a 27.2 % reduction in time from FIT positive to colonoscopy in 2014-2015 (173.9 vs. 238.8 days, p < 0.01). Among patients undergoing colonoscopy, 46.3 % had adenomatous polyps, 27.4 % had high risk adenomatous polyps, and 5.6 % had CRC. Among an ethnically diverse safety-net hospital system, improvements in access to colonoscopy after positive FIT were observed. However, patients still waited nearly 6 months from time of positive FIT to undergoing colonoscopy. Delays in receipt of colonoscopy are complex and reflect system-level and individual patient-level barriers.

Black Patients with Colorectal Cancer Have More Advanced Cancer Stage at Time of Diagnosis: A Community-Based Safety-Net Hospital Experience.

Colorectal cancer (CRC) remains a leading cause of morbidity and mortality in the U.S. Disparities in access to care contribute to advanced CRC stage at diagnosis, and these disparities are most pronounced among underserved populations and ethnic minorities. We aim to evaluate race/ethnicity-specific disparities in CRC stage at diagnosis among an ethnically diverse, urban safety-net hospital. We retrospectively evaluated all adult CRC patients diagnosed from January 1, 2009 to October 1, 2015. CRC cases were confirmed by histopathology specimens from biopsies and/or surgical resection. CRC staging utilized American Joint Committee on Cancer (AJCC) staging systems and were stratified by race/ethnicity. Multivariate logistic regression models were utilized to evaluate disparities in AJCC stage at presentation (stage 3-4 vs. stage 0-2). Among 311 patients with CRC [51.5% male, 25.3% black, 18.7% Hispanic, 32.0% Asian, and mean age at diagnosis 58.1 years (SD 10.3)] 61.4% had advanced ACC stage 3-4 CRC at diagnosis. Among black patients with CRC, 73.3% had AJCC stage 3-4 cancer at time of diagnosis. On multivariate regression, blacks were nearly four times more likely to have advanced AJCC stage 3-4 CRC at diagnosis compared to whites (OR 3.70; 95% CI 0.97-14.11; p = 0.055). Among a diverse underserved population, over 60% of CRC were AJCC stage 3-4 at diagnosis, and nearly 75% of blacks with CRC had AJCC stage 3-4 at diagnosis. Advanced stage CRC at diagnosis limits options for potentially curative therapies, and increases the risk for cancer recurrence and mortality.

Race/ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest rising causes of cancer-related deaths in the United States, with disparities observed in cancer incidence and survival between ethnic groups. This report provides updated analyses on race-specific disparities in US HCC trends. METHODS: This large, population-based cohort study was conducted using Surveillance, Epidemiology, and End Results cancer registry data from 2003 to 2011 to investigate race-specific disparities in HCC incidence and survival. Survival was analyzed using Kaplan-Meier methods and multivariate Cox proportional-hazards models. RESULTS: From 2003 to 2011, Asians had the highest HCC incidence, followed by blacks, Hispanics, and non-Hispanic whites. During the same period, Hispanics had the greatest increase in HCC incidence (+35.8%), whereas Asians experienced a 5.5% decrease. Although patients aged ≥65 years had the highest HCC incidence among all racial/ethnic groups, the higher HCC incidence in Asians was observed only for patients ages <50 and ≥65 years, whereas HCC incidence among patients ages 50 to 64 years was similar among Asians, blacks, and Hispanics. The overall 5-year HCC survival rate was highest among Asians (26.1%; 95% confidence interval [CI], 24.5%-27.6%) and lowest among blacks (21.3%; 95% CI, 19.5%-23.1%). On multivariate regression, Asians (hazard ratio, 0.83; 95% CI, 0.79-0.87; P < .001) and blacks (hazard ratio, 0.94; 95% CI, 0.89-0.99; P = .01) had significantly higher survival compared with non-Hispanic whites. CONCLUSIONS: Asians were the only group to demonstrate a declining HCC incidence in the form of a shift from advanced HCC to more localized HCC. These findings most likely reflect improved screening and surveillance efforts for this group. Cancer 2016;122:2512-23. © 2016 American Cancer Society.

Birth cohort-specific disparities in hepatocellular carcinoma stage at diagnosis, treatment, and long-term survival.

BACKGROUND & AIMS: Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim to evaluate birth cohort-specific disparities in HCC stage at diagnosis, treatment rates, and overall survival with a focus on the 1945-1965 birth cohort. METHODS: A population-based retrospective cohort study of adult patients with HCC identified in the Surveillance, Epidemiology, and End Results 2003-2011 registry evaluated birth cohort-specific disparities in the prevalence and outcomes of HCC, including multivariate logistic regression models to evaluate disparities in HCC stage at diagnosis and HCC treatment received. Birth cohort-specific survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazard models. RESULTS: The proportion of HCC represented by the 1945-1965 cohort increased by 64% from 2003-2011, and accounted for 57.4% of all HCC in 2011. Compared to patients born after 1965, the 1945-1965 cohort were more likely to have HCC within Milan criteria (OR, 3.66; 95% CI, 3.13-4.28; p<0.001). However, among patients with HCC within Milan criteria, the 1945-1965 cohort had no difference in receipt of surgical treatment, but had higher overall long-term survival (HR, 0.82; 95% CI, 0.69-0.97; p<0.03). CONCLUSIONS: The 1945-1965 birth cohort accounts for the majority of HCC in the United States. Despite earlier HCC stage at diagnosis, no difference in receipt of surgical treatment was observed, but higher overall survival was achieved.