Search

BACKGROUND: Direct-acting antivirals (DAAs) are expected to improve outcomes for patients with hepatitis C virus (HCV) infection after liver transplantation (LT). We aim to evaluate trends in post-LT outcomes with availability of DAAs. METHODS: We retrospectively evaluated US adults transplanted from January 1, 2002, to March 31, 2018, using the United Network for Organ Sharing Registry, stratified by pre-DAA (January 1, 2002– to December 31, 2013) vs. post-DAA (January 1, 2014–, to March 31, 2018) eras. Adjusted multivariate Cox regression analyses and competing risk models evaluated likelihood of graft failure, death, and retransplantation (re-LT). RESULTS: Among 97,147 patients, 30.2% had HCV infection and 19.4% had hepatocellular carcinoma (HCC). Of all patients, 31.9% experienced graft failure, 27.1% died after LT, and 4.7% underwent re-LT. The post-DAA era experienced lower likelihood of graft failure (hazard ratio [HR] = 0.69, p

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

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) outcomes among Asians may differ by the Asian ethnic subgroup. We aim to evaluate the impact of the Asian ethnic subgroup on HCC tumor stage, treatment received, and overall survival among US adults. METHODS: Using the 2004–2012 Surveillance, Epidemiology, and End Results U.S. cancer registry, we retrospectively evaluated disparities in HCC tumor stage at diagnosis, HCC treatment received, and overall survival among Asian adults, stratified by Asian ethnic subgroups. Multivariate regression models evaluated the independent impact of Asian ethnic subgroups on the HCC tumor stage at diagnosis, treatment received, and overall long-term survival. RESULTS: Among 8160 Asians with HCC, Southeast Asian (SEA) patients accounted for 26% of all HCC, followed by Chinese (CH) (22%), and Filipinos (FP) (14.0%) patients. Japanese (JP) patients were significantly older than those of the other subgroups (mean 71.1, SD 10.8, P < 0.01). When evaluating HCC stage, FP patients were less likely to have localized HCC and less likely to have HCC within the Milan criteria than CH HCC patients. When evaluating HCC treatment, pacific islanders (PI), FP and SEA patients were significantly less likely to any receive HCC treatment than CH patients. Overall five-year HCC survival was highest among CH HCC patients (33.1%) and lowest among FP (19.9%) and JP patients (22.0%). CONCLUSION: Among Asians with HCC in the US, significant disparities among Asian ethnic subgroups exist. More advanced disease was seen among FP patients, less HCC treatment was seen among FP and SEA patients, and significantly higher mortality was seen among FP, SEA, and JP patients with HCC.

To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients.Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening.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.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.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.

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.

BACKGROUND AND AIMS: Delays in diagnosis of chronic hepatitis B virus infection (HBV) may be more common among underserved safety-net populations, contributing to more advanced disease at presentation. We aim to evaluate rates of and predictors of cirrhosis and cirrhosis-related complications among adults with chronic HBV. METHODS: We retrospectively evaluated consecutive chronic HBV adults from gastroenterology clinics from July 2014 to May 2016 at a community-based safety-net hospital. Prevalence of cirrhosis or cirrhosis-related complications (ascites, variceal bleeding, hepatic encephalopathy (HE), hepatocellular carcinoma (HCC)) at initial presentation was stratified by sex and race/ethnicity. Predictors of cirrhosis or cirrhosis-related complications at presentation were evaluated with multivariate logistic regression. RESULTS: Among 329 chronic HBV patients (mean age 49.1 years, 55.3% male, 66.5% Asian, 18.6% HBeAg positive) 27.7% had cirrhosis at presentation, 4.3% ascites, 3.7% variceal bleeding, 4.9% HE, and 4.0% HCC. Compared to women, men were more likely to have cirrhosis (34.6% vs. 19.1%, P

Individuals from the 1945-1965 birth cohort account for the majority of hepatocellular carcinoma (HCC) cases in the United States. Understanding trends in HCC among this birth cohort is vital given the increasing burden of chronic liver disease among this group. We retrospectively evaluated trends and disparities in HCC tumor stage at the time of diagnosis among the 1945-1965 birth cohort in the United States using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Tumor stage at the time of HCC diagnosis was assessed using Milan criteria and SEER HCC staging systems. Among 38,045 patients with HCC within the 1945-1965 birth cohort (81.6% male, 50.1% non-Hispanic white, 16.2% African American, 12.6% Asian, 19.8% Hispanic), 66.2% had Medicare or commercial insurance, 27.2% had Medicaid, and 6.6% were uninsured. During the period 2004-2006 to 2013-2014, the number of patients with HCC from the 1945-1965 birth cohort increased by 58.7% (5.9% increase per year). While the proportion of patients with HCC within the Milan criteria increased with time (36.4% in 2003-2006 to 46.3% in 2013-2014; P

Aims Better understanding risk factors for metabolic syndrome (MetS) will allow early targeted intervention to mitigate long term risk. We aim to determine the disparate impact of each individual MetS component on overall risk of developing MetS, stratified by sex, race/ethnicity, and age. Methods Using data from the 2003–2014 National Health and Nutrition Examination Survey (NHANES), MetS prevalence among adults (age ≥18) was stratified by sex, race/ethnicity, age, and by individual MetS components (e.g. hypertension (HTN), diabetes mellitus (DM), waist circumference, serum high density lipoprotein (HDL), serum triglycerides (TG). Mutlivariate logistic regression models were used to evaluate the disparate impact of each risk factor on MetS risk. Results Overall MetS prevalence was 33.3%, with the highest prevalence among older individuals, among women, and among Hispanics. When stratified by each individual component of MetS, low serum HDL was the strongest predictor of MetS risk overall and among both men and women, among all race/ethnic groups, and among all age groups (overall: OR 20.1, 95% CI 18.6–21.7). While presence of DM also increased an individual’s risk of MetS, DM was the weakest predictor of MetS. Conclusions Among U.S. adults, low serum HDL carries the strongest risk in predicting development of MetS. This effect was seen among men and women, among all race/ethnic groups, and among all age groups, highlighting the importance of low serum HDL as a marker of MetS risk.

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.

Esophageal variceal hemorrhage is a complication of cirrhosis that carries high mortality, and can be reduced with timely endoscopic variceal screening and treatment. We aim to evaluate overall rates of and disparities in receipt of endoscopic variceal screening among an ethnically diverse urban safety-net hospital. All consecutive adults with cirrhosis (7/1/2014 to 12/31/2015) were retrospectively evaluated to determine the rates of receiving esophageal variceal screening within 6 months and within 1 year after cirrhosis diagnosis. Race-/ethnicity-specific differences in rates of variceal screening were compared using chi-square testing and multivariate regression methods. Among 157 patients (65% male, 33.8% Hispanic, 22.3% African-American, 44.6% alcoholic liver disease, 29.9% chronic HCV), 56.8% received variceal screening within 6 months and 65.8% received screening within 1 year. Compared to non-Hispanic whites with cirrhosis, African-Americans (52.2 vs. 76.2%, p

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. To evaluate race/ethnicity-specific disparities in UC disease presentation among an ethnically diverse underserved population. 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. 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. 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.

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

With effective antiviral therapies, rates of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation (LT) are expected to decrease. We aim to evaluate overall trends in LT waitlist registrations, waitlist survival and likelihood of receiving LT among chronic HBV patients in the United States. Using the United Network for Organ Sharing database, we retrospectively evaluated adults (age≥18) with chronic HBV (with and without HCC) listed for LT from 1992 to 1996 (Era 1) vs 1997 to 2004 (Era 2) vs 2005-2015 (Era 3). Multivariate Cox-regression models evaluated probability of waitlist survival and receiving LT. Overall, 6797 chronic HBV adults were listed for LT. While the total number of HBV patients listed for LT remained stable, the proportion of HBV patients with HCC increased from 5.4% in Era 1 to 39.0% in Era 3. Compared to Era 1, waitlist mortality was higher in Era 2 (HR: 4.55, P

Disparities in receipt of hepatocellular carcinoma (HCC) surveillance contribute to disparities in overall survival outcomes. We aim to evaluate disparities in receipt of routine HCC surveillance among patients with cirrhosis in a large urban safety-net hospital. 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. 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

To evaluate age-specific disparities in cancer stage at diagnosis, receipt of treatment, and survival among adults with hepatocellular carcinoma (HCC).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.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.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; P0.001]. 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; P0.001). 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; P0.001).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.

Background Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009. Results Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer. Conclusions These expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.

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

Whether recent updates to colon cancer screening guidelines benefit men and women or all race/ethnic groups equally is not clear. The aim of this study is to evaluate age-, sex-, and race/ethnicity-specific trends in CRC incidence and disease burden among adults. 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

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.

BACKGROUND & AIMS The rising prevalence of obesity and diabetes mellitus (DM) among hepatitis C virus (HCV) patients contributes to concurrent nonalcoholic fatty liver disease (NAFLD). We aim to evaluate the impact of concurrent obesity or DM on waitlist survival and probability of liver transplantation (LT) among adults with chronic HCV awaiting LT. METHODS Using 2003-2013 United Network for Organ Sharing data, we evaluated the impact of obesity and DM among adults with chronic HCV awaiting LT: non-obese, non-DM vs. obese, non-DM (obese) vs. non-obese, DM (DM) vs. obese and DM. Overall, LT waitlist survival and probability of receiving LT were evaluated using Kaplan-Meier and multivariate logistic regression models. RESULTS From 2003-2013, there were 43 478 new LT waitlist registrants with chronic HCV (21.0% with HCC, 79% without HCC). Obesity was associated with lower probability of receiving LT (OR, 0.91; 95% CI, 0.85-0.97; P < 0.01), and lower probability of waitlist mortality (OR, 0.80; 95% CI, 0.72-0.89; P < 0.001) when compared to non-obese patients. DM among HCV patients did not impact probability of waitlist survival or receiving LT. When evaluating post-LT survival, compared to non-obese, non-DM patients, obese HCV patients had significantly lower post-LT mortality (HR 0.86; 95%CI, 0.81-0.92; P < 0.001); whereas, HCV patients with DM had significantly higher post-LT mortality (HR, 1.22; 95% CI, 1.12-1.33; P < 0.001). CONCLUSION Among adults with chronic HCV awaiting LT in the US, obesity is associated with lower probability of receiving LT, but did not impact waitlist survival. DM among chronic HCV patients did not impact waitlist survival or probability of LT.

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.

OBJECTIVE Inflammatory bowel disease (IBD) patients with Clostridium difficile co-infection (CDCI) have an increased risk of morbidity and mortality. We aim to evaluate the impact of CDCI on in-hospital outcomes among adults with IBD hospitalized in the USA. PATIENTS AND METHODS Using the 2007-2013 Nationwide Inpatient Sample, hospitalizations among US adults with Crohn's disease (CD), ulcerative colitis (UC) and CDCI were identified using ICD-9 coding. Hospital charges, hospital length of stay (LOS), and in-hospital mortality was stratified by CD and UC and compared using χ-testing and Student's t-test. Predictors of hospital charges, LOS, and in-hospital mortality were evaluated with multivariate regression models and were adjusted for age, sex, race/ethnicity, year, insurance status, hospital characteristics, and CDCI. RESULTS Among 224 500 IBD hospitalizations (174 629 CD and 49 871 UC), overall prevalence of CDCI was 1.22% in CD and 3.41% in UC. On multivariate linear regression, CDCI was associated with longer LOS among CD [coefficient: 5.30, 95% confidence interval (CI): 4.61-5.99, P

AIM To evaluate trends and disparities in hepatocellular carcinoma (HCC) outcomes among Hispanic patients in the United States with a focus on tumor stage at diagnosis. METHODS We retrospectively evaluated all Hispanic adults (age > 20) with HCC diagnosed from 2004 to 2014 using United States Surveillance, Epidemiology, and End Results (SEER) cancer registry data. Tumor stage was assessed by SEER-specific staging systems and whether HCC was within Milan criteria at diagnosis. Multivariate logistic regression models evaluated for predictors of HCC within Milan criteria at diagnosis. RESULTS Overall, Hispanics accounted for 19.8% of all HCC (73.3% men, 60.9% had Medicare or commercial insurance, 33.5% Medicaid, and 5.6% uninsured). Thirty-eight percent of Hispanic HCC patients were within Milan criteria at diagnosis. With latter time periods, significantly more patients were diagnosed with HCC within Milan criteria, and in 2013-2014, 42.6% had HCC within Milan criteria. On multivariate regression, Hispanic males (OR vs females: 0.76, 95%CI: 0.68-0.83, P < 0.001), Hispanics > 65 years (OR vs age < 50: 0.67, 95%CI: 0.58-0.79, P < 0.001), and uninsured patients (OR vs Medicare/commercial: 0.49, 95%CI: 0.40-0.59, P < 0.001) were significantly less likely to have HCC within Milan criteria at diagnosis. CONCLUSION While one in five HCC patients in the United States are of Hispanic ethnicity, only 38% were within Milan criteria at time of diagnosis, and thus over 60% were ineligible for liver transplantation, one of the primary curative options for HCC patients. Improved efforts at HCC screening and surveillance are needed among this group to improve early detection.

Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease (NAFLD) among chronic hepatitis C (HCV) patients may contribute to higher hepatocellular carcinoma (HCC) risk. To perform a systematic review evaluating the impact of DM, body mass index (BMI), or steatosis on HCC risk among chronic HCV patients. A structured keyword search of PubMed from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of DM, BMI, or steatosis with HCC among adults with chronic HCV. Studies involving HCV patients co-infected with human immunodeficiency virus, hepatitis B virus, or other chronic liver diseases with the exception of NAFLD were excluded. Quality assessment utilized the Newcastle–Ottawa scale. Nine studies (seven cohorts, two case–controls) met inclusion criteria for the final analysis. Five of seven studies analyzing DM demonstrated significantly increased HCC risk associated with concurrent DM with effect sizes ranging from HR 1.73 (95 % CI 1.30–2.30) to RR 3.52 (95 % CI 1.29–9.24). One of three studies analyzing BMI demonstrated a significant association with HCC risk (BMI ≥ 30.0 vs. BMI

Safety-net hospitals are enriched in ethnic minorities and provide opportunities for high-impact hepatitis B virus (HBV) screening. We aim to evaluate the impact of a pilot program integrating HBV screening into outpatient endoscopy among urban safety-net populations. 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. 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. 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.

Cholesteryl ester storage disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ∼3%-5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to ∼1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% confidence interval [CI]: 51%-69%) of reported mutations among multiethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is ∼0.8 per 100,000 (∼1 in 130,000; 95% CI: ∼1 in 90,000 to 1 in 170,000). Conclusion: These data indicate that CESD may be underdiagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies, since c.894G>A is not common in these racial groups. (HEPATOLOGY 2013;53:958–965)

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. We aim to evaluate ethnic disparities specifically among patients with chronic HCV in the USA. 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. 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

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

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

The increasing prevalence of metabolic syndrome (MetS) and MetS related complications in the U.S. poses a serious public health burden. We aim to identify high risk groups at greatest risk of developing MetS in the U.S.Using data from the 2001-2012 National Health and Nutrition Examination Survey (NHANES), MetS prevalence among adults (age≥18) was stratified by sex, race/ethnicity and age to identify groups at greatest risk of MetS. Mutlivariate logistic regression models evaluated for predictors of MetS.Overall, the prevalence of MetS in the U.S. was 78 million during the study period. There was a greater prevalence of MetS in females compared to males (34.4% vs. 29.6%, p0.001). Females had a 25% higher risk of MetS compared to males (OR, 1.25; 95% CI, 1.18-1.32, p0.001). Hispanics had a higher risk of MetS when compared to non-Hispanic whites (OR, 1.13; 95% CI, 1.04-1.23, p0.01). The prevalence of MetS increased with increasing age (age40: 17.5% vs. age 40-49: 29.7% vs. age 50-59: 37.5% vs. age 60-69: 44.4% vs. age ≥70: 47.0%, p0.001), and individuals age 70 and over were more than 5 times more likely to have MetS than those less than age 40 (OR, 5.12, 4.71-5.57, p0.001) CONCLUSIONS: The high prevalence of MetS in the U.S. affects females, Hispanics, and older individuals the greatest. The aging population and increasing Hispanic population further highlight the huge burden of disease MetS will place on the healthcare system in the U.S.

An injection of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to mice lacking Niemann Pick type C (NPC) protein results in delayed neurodegeneration, decreased inflammation, and prolonged lifespan. Changes in sterol balance observed in Npc1(-/-) mice 24 h after HP-β-CD administration suggest that HP-β-CD facilitates the release of accumulated lysosomal cholesterol, the molecular hallmark of this genetic disorder. Current studies were performed to evaluate the time course of HP-β-CD effects. Within 3 h after HP-β-CD injection, decreases in cholesterol synthesis rates and increases in cholesteryl ester levels were detected in tissues of Npc1(-/-) mice. The levels of RNAs for target genes of sterol-sensing transcription factors were altered by 6 h in liver, spleen, and ileum. Despite the cholesterol-binding capacity of HP-β-CD, there was no evidence of increased cholesterol in plasma or urine of treated Npc1(-/-) mice, suggesting that HP-β-CD does not carry sterol from the lysosome into the bloodstream for ultimate urinary excretion. Similar changes in sterol balance were observed in cultured cells from Npc1(-/-) mice using HP-β-CD and sulfobutylether-β-CD, a variant that can interact with sterol but not facilitate its solubilization. Taken together, our results demonstrate that HP-β-CD works in cells of Npc1(-/-) mice by rapidly liberating lysosomal cholesterol for normal sterol processing within the cytosolic compartment.

While unesterified cholesterol (C) is essential for remodeling neuronal plasma membranes, its role in certain neurodegenerative disorders remains poorly defined. Uptake of sterol from pericellular fluid requires processing that involves two lysosomal proteins, lysosomal acid lipase, which hydrolyzes C esters, and NPC1 (Niemann-Pick type C1). In systemic tissues, inactivation of either protein led to sterol accumulation and cell death, but in the brain, inactivation of only NPC1 caused C sequestration and neurodegeneration. When injected into the CNS of the npc1 −/− mouse, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a compound known to prevent this C accumulation, diffused throughout the brain and was excreted with a t ½ of 6.5 h. This agent caused suppression of C synthesis, elevation of C esters, suppression of sterol regulatory-binding protein 2 (SREBP2) target genes, and activation of liver X receptor-controlled genes. These findings indicated that HP-β-CD promoted movement of the sequestered C from lysosomes to the metabolically active pool of C in the cytosolic compartment of cells in the CNS. The ED 50 for this agent in the brain was ∼0.5 mg/kg, and the therapeutic effect lasted >7 d. Continuous infusion of HP-β-CD into the ventricular system of npc1 −/− animals between 3 and 7 weeks of age normalized the biochemical abnormalities and completely prevented the expected neurodegeneration. These studies support the concept that neurons continuously acquire C from interstitial fluid to permit plasma membrane turnover and remodeling. Inactivation of NPC1 leads to lysosomal C sequestration and neurodegeneration, but this is prevented by the continuous, direct administration of HP-β-CD into the CNS.