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Purpose: To examine nativity differences of co-occurring liver disease (LD) and heart failure (HF) on 13-year mortality among Mexican American older adults., Methods: Prospective cohort study of 1601 Mexican Americans aged ≥ 75 years from the Hispanic Established Population for the Epidemiologic Study of the Elderly (2004/05-2016). Participants were grouped into four groups: no LD and no HF (n = 1138), LD only (n = 53), HF only (n = 382), and both LD and HF (n = 28). We used Cox proportional hazards regression model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of death over time., Results: The HR of death, as a function of HF only, was 1.32 (95% CI=1.07-1.62) among US-born and 1.36 (95% CI=1.04-1.78) among foreign-born participants, vs. those with no LD and no HF. Among foreign-born participants, the HR of death as a function of LD and HF was 3.39 (95% CI=1.65-6.93) vs. those without either. LD alone was not associated with mortality in either group. Among US-born, co-occurring LD and HF was not associated with mortality., Conclusions: Foreign-born participants with both LD and HF were at higher risk of mortality over 13 years of follow up., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Fontan operation is the current standard of care for single-ventricle congenital heart disease. Individuals with a Fontan circulation (FC) exhibit central venous hypertension and face life-threatening complications of hepatic fibrosis, known as Fontan-associated liver disease (FALD). The fundamental biology and mechanisms of FALD are little understood. Here, we generated a transcriptomic and epigenomic atlas of human FALD at single-cell resolution using multiomic snRNA-ATAC-seq. We found profound cell type-specific transcriptomic and epigenomic changes in FC livers. Central hepatocytes (cHep) exhibited the most substantial changes, featuring profound metabolic reprogramming. These cHep changes preceded substantial activation of hepatic stellate cells and liver fibrosis, suggesting cHep as a potential first "responder" in the pathogenesis of FALD. We also identified a network of ligand-receptor pairs that transmit signals from cHep to hepatic stellate cells, which may promote their activation and liver fibrosis. We further experimentally demonstrated that activins A and B promote fibrotic activation in vitro and identified mechanisms of activin A's transcriptional activation in FALD. Together, our single-cell transcriptomic and epigenomic atlas revealed mechanistic insights into the pathogenesis of FALD and may aid identification of potential therapeutic targets.

Studies that examine racial disparities in health outcomes often include analyses that account or adjust for baseline differences in co-morbid conditions. Often, these conditions are defined as dichotomous (Yes/No) variables, and few analyses include clinical and/or laboratory data that could allow for more nuanced estimates of disease severity. However, disease severity - not just prevalence - can differ substantially by race and is an underappreciated mechanism for health disparities. Thus, relying on dichotomous disease indicators may not fully describe health disparities. This study explores the effect of substituting continuous clinical and/or laboratory data for dichotomous disease indicators on racial disparities, using data from the Queen's Medical Center's (QMC) cardiac surgery database (a subset of the national Society of Thoracic Surgeon's cardiothoracic surgery database) as an example case. Two logistic regression models predicting in-hospital mortality were constructed: (I) a baseline model including race and dichotomous (Yes/No) indicators of disease (diabetes, heart failure, liver disease, kidney disease), and (II) a more detailed model with continuous laboratory values in place of the dichotomous indicators (eg, including Hemoglobin A1c level rather than just diabetes yes/no). When only dichotomous disease indicators were used in the model, Native Hawaiian and other Pacific Islander (NHPI) race was significantly associated with in-hospital mortality (OR: 1.57[1.29,2.47], P=.04). Yet when the more specific laboratory values were included, NHPI race was no longer associated with in-hospital mortality (OR: 1.67[0.92,2.28], P=.28). Thus, researchers should be thoughtful in their choice of independent variables and understand the potential impact of how clinical measures are operationalized in their research., Competing Interests: None of the authors identify a conflict of interest., (©Copyright 2023 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root causes that drive these inequities. Understanding the role that social determinants of health play in the disparate health outcomes that are currently observed is critically important. We must forge and/or strengthen collaborations between patients, community members, other key stakeholders, health care providers, health care institutions, professional societies, and legislative bodies. Herein, we provide a high-level review of current disparities in chronic liver disease and describe actionable strategies that have potential to bridge gaps, improve quality, and promote equity in liver care., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic and social justice movement have highlighted the impact of social determinants of health (SDOH) and structural racism in the United States on both access to care and patient outcomes. With the evaluation for liver transplantation being a highly subjective process, there are multiple ways for SDOH to place vulnerable patients at a disadvantage. This policy corner focuses on three different methods to reverse the deleterious effects of SDOH-identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach., (© 2021 by the American Association for the Study of Liver Diseases.)

Introduction and Objectives: After the implementation of "Share 35", several concerns arose such as the potential to increase travel distance, costs, and decreased liver availability. These elements could have a negative impact on waitlist outcomes among ethnic minorities. We aimed to determine waitlist survival after the implementation of the Share 35 policy in non-Hispanic white and Hispanic patients., Materials and Methods: We identified non-Hispanic whites and Hispanics who were listed for liver transplantation from June 18th, 2013 to June 18, 2018. We excluded pediatric patients, patients with acute hepatic necrosis, re-transplants, multiorgan transplant, living donor, and exception cases. The primary outcome was death or removal from the waitlist due to clinical deterioration. We used competing risk analysis to compare waitlist survival between the two groups., Results: There were 23,340 non-Hispanic whites and 4938 Hispanics listed for transplant. On competing risk analysis, Hispanic patients had a higher risk of being removed from the waitlist for death or clinical deterioration compared to their counterpart (SHR 1.23, 95% CI 1.13-1.34; P < 0.001)., Conclusion: After the implementation of Share 35, disparities are still present and continue to negatively impact outcomes in minority populations especially Hispanic patients., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear., Methods: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy., Results: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease., Conclusion: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Several studies have explored the associations between interleukin-6 (IL-6) gene polymorphisms and the susceptibility to liver diseases, however, results remain ambiguous. The goal of this study was to conduct a meta-analysis to provide more credible evidence., Methods: Studies identified in the PubMed, Cochrane Library, and EMBASE databases were used to perform a meta-analysis via the STATA software. Pooled odds ratios (OR) were calculated under fixed- and random-effects models to estimate the potential genetic associations., Results: Twenty-five case-control studies involving 5813 cases and 5298 controls were included in this meta-analysis. Overall, the pooled results suggested that rs1800795 polymorphism was significantly associated with the risk of liver diseases in heterozygote (GC vs CC; OR = 1.57) and dominant (GG+GC vs CC: OR = 1.47) models; rs1800796 polymorphism was significantly associated with the susceptibility to liver diseases in heterozygote (GG vs GC; OR = 0.58) and recessive (GG vs GC+CC: OR = 0.68) models; rs1800797 polymorphism was significantly associated with genetic predisposition to liver diseases in homozygote (GG vs AA: OR = 1.63), heterozygote (GA vs AA; OR = 1.53) and dominant (GG + GA vs AA: OR = 1.61) models. A similar conclusion was found in the HBV, HCV, HCC, NASH and alcoholic liver disease of all ethnic populations for rs1800795; HBV and Asian subgroups for rs1800796; HCV and non-Asian subgroups for rs1800797. However, IL-6 rs2069837 and rs2066992 polymorphisms did not exhibit significant associations with the risk of liver diseases under any genetic models., Conclusion: This meta-analysis suggests that patients carrying G (rs1800795), C (rs1800796) or G (rs1800797) allele or genotypes of IL-6 may be more likely to suffer from liver diseases, which was ethnic-dependent.

Background & Aims: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States., Methods: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases., Results: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed., Conclusions: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database., Methods: The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy., Results: Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS)., Conclusions: This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.

Aim: To compare the prevalence of chronic liver disease (CLD) risk factors in a representative sample of Mexican-Americans born in the United States (US) or Mexico, to a sample of adults in Mexico., Methods: Data for Mexican-Americans in the US were obtained from the 1999-2014 National Health and Nutrition Examination Survey (NHANES), which includes persons of Mexican origin living in the US ( n = 4274). The NHANES sample was restricted to Mexican-American participants who were 20 years and older, born in the US or Mexico, not pregnant or breastfeeding, and with medical insurance. The data in Mexico were obtained from the 2004-2013 Health Worker Cohort Study in Cuernavaca, Mexico ( n = 9485). The following known risk factors for liver disease/cancer were evaluated: elevated aminotransferase levels (elevated alanine aminotransferase was defined as > 40 IU/L for males and females; elevated aspartate aminotransferase was defined as > 40 IU/L for males and females), infection with hepatitis B or hepatitis C, metabolic syndrome, high total cholesterol, diabetes, obesity, abdominal obesity, and heavy alcohol use. The main independent variables for this study classified individuals by country of residence ( i.e ., Mexico vs the US) and place of birth ( i.e ., US-born vs Mexico-born). Regression analyses were used to investigate CLD risk factors., Results: After adjusting for socio-demographic characteristics, Mexican-American males were more likely to be obese, diabetic, heavy/binge drinkers or have abdominal obesity than males in Mexico. The adjusted multivariate results for females also indicate that Mexican-American females were significantly more likely to be obese, diabetic, be heavy/binge drinkers or have abdominal obesity than Mexican females. The prevalence ratios and prevalence differences mirror the multivariate analysis findings for the aforementioned risk factors, showing a greater risk among US-born as compared to Mexico-born Mexican-Americans., Conclusion: In this study, Mexican-Americans in the US had more risk factors for CLD than their counterparts in Mexico. These findings can be used to design and implement more effective health promotion policies and programs to address the specific factors that put Mexicans at higher risk of developing CLD in both countries., Competing Interests: Conflict-of-interest statement: All authors declare no potential conflicts of interest relevant to this article.

Objective: Current chronic liver disease (CLD) mortality surveillance methods may not adequately capture data on all causes of CLD mortality. The objective of this study was to calculate and compare CLD death rates in New Mexico and the United States by using both an expanded definition of CLD and estimates of the fractional impact of alcohol on CLD deaths., Methods: We defined CLD mortality as deaths due to alcoholic liver disease, cirrhosis, viral hepatitis, and other liver conditions. We estimated alcohol-attributable CLD deaths by using national and state alcohol-attributable fractions from the Centers for Disease Control and Prevention's Alcohol-Related Disease Impact application. We classified causes of CLD death as being alcohol-attributable, non-alcohol-attributable, or hepatitis C. We calculated average annual age-adjusted CLD death rates during five 3-year periods from 1999 through 2013, and we stratified those rates by sex, age, and race/ethnicity., Results: By cause of death, CLD death rates were highest for alcohol-attributable CLD. By sex and race/ethnicity, CLD death rates per 100 000 population increased from 1999-2001 to 2011-2013 among American Indian men in New Mexico (67.4-90.6) and the United States (38.9-49.4), American Indian women in New Mexico (48.4-63.0) and the United States (27.5-39.5), Hispanic men in New Mexico (48.6-52.0), Hispanic women in New Mexico (16.9-24.0) and the United States (12.8-13.1), non-Hispanic white men in New Mexico (17.4-21.3) and the United States (15.9-18.4), and non-Hispanic white women in New Mexico (9.7-11.6) and the United States (7.6-9.7). CLD death rates decreased among Hispanic men in the United States (30.5-27.4)., Conclusions: An expanded CLD definition and alcohol-attributable fractions can be used to create comprehensive data on CLD mortality. When stratified by CLD cause and demographic characteristics, these data may help states and jurisdictions improve CLD prevention programs.

To assess the potential of individual bile acids (IBA) and their profiles as mechanistic biomarkers of liver injury for humans in real world situations, we interrogated samples collected under minimum controlled conditions (ie subjects were not fasted). Total bile acids (TBA) have been considered to be biomarkers of liver injury for decades, and more recently, monitoring of IBA has been proposed for differentiation of variety of etiologies of liver injury. We established a LC-MS/MS methodology to analyze nine IBA, generated reference ranges, and examined effects of age, gender, and ethnicity for each IBA. Furthermore, we evaluated the ability of IBA and their profiles to detect hepatic injury in subjects with a broad range of liver impairments. To date, our study utilized the largest total cohort of samples (N = 645) that were divided into 2 groups, healthy or liver impaired, to evaluate IBA as biomarkers. The TBA serum levels in the Asian ethnic group trended higher when compared to other ethnic groups, and the serum concentrations of IBA, such as glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), chenodeoxycholic acid (CDCA), and taurochenoxycholic acid (TCDCA) were significantly increased. To our knowledge, this report is the first to describe ethnic differences in serum concentrations of IBAs. In patients with hepatic impairments, with the exception of deoxycholic acid (DCA), the concentrations of IBAs were significantly elevated when compared with healthy subjects. The conjugated bile acids displayed greater differences between healthy subjects and subjects with hepatic impairments than non-conjugated bile acids. Furthermore, the subjects with hepatic impairments exhibited distinct profiles (signatures) of IBAs that clustered subjects according the nature of their liver impairments. Although additional studies are needed, our data suggested that the analysis of IBA has the potential to become useful for differentiation of various forms of liver injury.

Purpose: Chronic hepatitis B virus (HBV) affects specific subpopulations in the United States, including individuals born in HBV-endemic countries and persons engaging in high-risk behaviors., Methods: The 2003-2013 HBV registry data and surveillance investigations for Philadelphia, PA were matched to death certificate data to examine demographic, risk factor, and cause of death characteristics among HBV-infected populations. Bivariate analysis compared investigated foreign-born (FB) and US-born chronic HBV individuals. Multivariable logistic regression assessed associations between HBV-status, birth origin, demographic information, and liver-related death., Results: Of 773 investigated HBV-infected individuals, 159 were US-born and 614 were FB and of primarily non-Hispanic Asian descent. Behavioral risk factors were more often reported by US-born individuals. HBV-infected FB decedents were twice as likely as US-born decedents to have a liver-related cause of death, whereas HIV/AIDS and drug overdose were more likely causes of death among those born in the United States., Conclusions: There are two HBV-infected populations in Philadelphia: 1) FB individuals most likely infected at birth or during early childhood and 2) US-born individuals with behaviors suggestive of risk-related HBV acquisition. These findings illustrate the need for both FB and US-born individuals with ongoing risk behaviors to receive routine HBV screening, vaccination if indicated, and medical care for outcomes of chronic HBV infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate trends in premature death rates by cause of death, age, race, and urbanization level in the United States., Methods: We calculated cause-specific death rates using the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years in 2 time periods: 1999 to 2001 and 2013 to 2015. We defined 48 subpopulations by 10-year age groups, race/ethnicity, and county urbanization level (large urban, suburban, small or medium metropolitan, and rural)., Results: The age-adjusted premature death rates for all adults declined by 8% between 1999 to 2001 and 2013 to 2015, with decreases in 39 of the 48 subpopulations. Most decreases in death rates were attributable to HIV, cardiovascular disease, and cancer. All 9 subpopulations with increased death rates were non-Hispanic Whites, largely outside large urban areas. Most increases in death rates were attributable to suicide, poisoning, and liver disease., Conclusions: The unfavorable recent trends in premature death rate among non-Hispanic Whites outside large urban areas were primarily caused by self-destructive health behaviors likely related to underlying social and economic factors in these communities.

Background: Patients with chronic liver disease are at high risk for developing liver cancer. Factors associated with screening awareness and doctor-patient communication regarding liver cancer were examined., Study: Four hundred sixty-seven patients with chronic liver disease at a tertiary-care clinic participated in a phone survey regarding awareness of cancer screening, doctor-patient communication, and health behaviors. Medical records were retrospectively reviewed for data on liver disease etiology and dates of liver imaging tests., Results: Seventy-nine percent of patients reported awareness of liver cancer screening, and 50% reported talking to their doctor about liver cancer. Patients with higher education, abstinence from alcohol, and liver cirrhosis were more likely to be aware of liver cancer screening (P=0.06, 0.005, <0.0001). Whites, patients with higher education, and those with cirrhosis were more likely to talk to their doctor about liver cancer (P=0.006; P=0.09, <0.0001). Awareness of liver cancer screening (79%) was similar to that of colorectal cancer screening (85%), lower than breast cancer screening (91%), and higher than prostate cancer screening (66%). Patients who were aware of liver cancer screening and reported talking to their doctor about liver cancer were significantly more likely to receive consistent liver surveillance (odds ratio, 4.81; 95% confidence interval, 2.62-8.84 and odds ratio, 1.97; 95% confidence interval, 1.19-3.28, respectively)., Conclusions: Our study demonstrates the importance of effective physician communication with chronic liver disease patients on the risks of developing liver cancer and the importance of regular screening, especially among nonwhites and patients with lower education.

Background: Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis., Methods: Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis., Results: 19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis., Conclusions: The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients.

Background: South Asians have a low body mass index and high prevalence of cardiovascular disease (CVD) relative to other racial/ethnic groups. Radiographically detected ectopic fat distribution is better associated with CVD than body mass index. We assessed whether differences in ectopic fat depots explained differences in the prevalence/severity of coronary artery calcium (CAC), a predictor of incident CVD events, among South Asians compared with other racial/ethnic groups., Methods and Results: We examined the associations of radiographically detected visceral, intermuscular, intrahepatic, and pericardial fat with CAC among adults without baseline CVD. We compared 803 South Asians in the Mediators of Atherosclerosis in South Asians Living in America to 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis: 2622 whites, 1893 blacks, 1496 Latinos, and 803 Chinese Americans. We adjusted for body mass index and known CVD risk factors. South Asians had the highest intrahepatic fat and lowest pericardial fat volume (PFV). There was a positive graded association between ectopic fat and higher CAC scores in all the groups with the strongest associations observed with PFV. PFV was independently associated with CAC severity in South Asians (P=0.01) and blacks (P=0.05) and borderline in whites (P=0.06). PFV partially explained the higher CAC burden in South Asians compared with blacks, but not the other racial/ethnic groups., Conclusions: Differences in PFV explain a small fraction of the higher CAC burden in South Asians. Our findings suggest that ectopic fat depots may not explain the elevated CAC risk in South Asians., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Preventing alcohol-related harms, including those causing liver disease, is a public health priority in the UK, especially in Scotland, but the effects of ethnicity are not known. We assessed liver- and alcohol-related events (hospitalisations and deaths) in Scotland using self-reported measures of ethnicity., Methods: Linking Scottish NHS hospital admissions and mortality to the Scottish Census 2001, we explored ethnic differences in hospitalisations and mortality (2001-2010) of all liver diseases, alcoholic liver disease (ALD) and specific alcohol-related diseases (ARD). Risk ratios (RR) were calculated using Poisson regression with robust variance, by sex, adjusted for age, country of birth and the Scottish Index of Multiple Deprivation (SIMD) presented below. The White Scottish population was the standard reference population with 95% confidence intervals (CI) calculated to enable comparison (multiplied by 100 for results)., Results: For all liver diseases, Chinese had around 50% higher risks for men (RR 162; 95% CI 127-207) and women (141; 109-184), as did Other South Asian men (144; 104-201) and Pakistani women (140; 116-168). Lower risks for all liver diseases occurred in African origin men (42; 24-74), other White British men (72; 63-82) and women (80; 70-90) and other White women (80; 67-94). For ALD, White Irish had a 75% higher risk for men (175; 107-287). Other White British men had about a third lower risk of ALD (63; 50-78), as did Pakistani men (65; 42-99). For ARD, almost 2-fold higher risks existed for White Irish men (182; 161-206) and Any Mixed Background women (199; 152-261). Lower risks of ARD existed in Pakistani men (67; 55-80) and women (48; 33-70), and Chinese men (55; 41-73) and women (54; 32-90)., Conclusions: Substantial variations by ethnicity exist for both alcohol-related and liver disease hospitalisations and deaths in Scotland: these exist in subgroups of both White and non-White populations and practical actions are required to ameliorate these differences., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Introduction: Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US-Mexico border in South Texas and elucidate indications of chronic disease in young men., Methods: We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population-based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups., Results: Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%-23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5-50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men., Conclusions: We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study.

Objective: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC)., Method: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005)., Conclusions: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

Background: Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are major causes of morbidity and mortality among Hispanics. Disparities in the incidence of HCC and in CLD deaths by nativity in Hispanics have been reported. Whether individual-level risk factors could explain these disparities was assessed in a prospective study of 36,864 Hispanics (18,485 US-born and 18,379 foreign-born) in the Multiethnic Cohort., Methods: Risk factors were assessed with a baseline questionnaire and Medicare claim files. During a 19.6-year follow-up, 189 incident cases of HCC and 298 CLD deaths were identified., Results: The HCC incidence rate was almost twice as high for US-born Hispanic men versus foreign-born Hispanic men (44.7 vs 23.1), but the rates were comparable for women (14.5 vs 13.4). The CLD mortality rate was about twice as high for US-born Hispanics versus foreign-born Hispanics (66.3 vs 35.1 for men and 42.2 vs 19.7 for women). Heavy alcohol consumption was associated with HCC and CLD in foreign-born individuals, whereas the current smoking status, hepatitis B/C viral infection, and diabetes were associated with both HCC and CLD. After adjustments for these risk factors, the hazard rate ratios for HCC and CLD death were 1.58 (95% confidence interval, 1.00-2.51) and 1.85 (95% confidence interval, 1.25-2.73), respectively, for US-born Hispanics versus foreign-born Hispanics., Conclusions: US-born Hispanics, particularly males, are at greater risk for HCC and death from CLD than foreign-born Hispanics. Overall known differences in risk factors do not account for these disparities. Future studies are warranted to identify factors that contribute to the elevated risk of HCC development and CLD death in US-born Hispanics. Cancer 2016;122:1444-1452. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Aim: The present study was designed to explore mutations of NPHP2 and NPHP3 and clinical features in 18 Chinese infantile nephronophthisis (NPHP) patients., Methods: Patients were subjected to screen for mutations in both NPHP2 and NPHP3, and clinical data were collected., Results: Eighteen patients from 17 families were included in this study. Eight of 17 (47.1%) patients detected were identified to have mutations in NPHP3, but none had a mutation in NPHP2. Of the patients with NPHP3 mutations, four had compound heterozygous mutations, and the other four harboured single heterozygous mutations. Ten of the NPHP3 mutations were novel. Low molecular weight proteinuria was observed in all 16 detected patients. Renal histology were available in seven children, five patients showed infantile type NPHP features, and the other two patients from the same family showed juvenile type NPHP features. Liver involvement was observed in all patients with NPHP3 mutations and congenital heart disease in two patients harbouring NPHP3 mutation of c.2369 T > C (p.L790P)., Conclusions: In this group of infantile NPHP patients, mutations of NPHP3 were prevalent, whereas mutation of NPHP2 was absent. Genotype to phenotype correlations were observed in patients with NPHP3 mutations and all patients with NPHP3 mutations showed renal-hepatic phenotype., (© 2015 Asian Pacific Society of Nephrology.)

Background: The influence of ethnicity on pain complicating ultrasound-guided percutaneous liver biopsy (US-guided PLB) and its clinical impact has not been reported to date., Methods: Consecutive adults from a multiethnic background, undergoing an US-guided PLB, were independently assessed for pain up to 6 h after the procedure. Clinical and demographic parameters were analysed to determine independent predictors of significant pain after PLB. Willingness to undergo a repeat procedure was assessed 1 week after PLB., Results: Data from 203 patients (median age 50 years; 43.9% female; ethnicity: Malay 41.5%, Chinese 40%, Indian 18%; median BMI 27.7 kg/m; median waist circumference 92.0 cm) were analysed. Pain after US-guided PLB was experienced in 133 (61.1%) patients, with severity grades as follows: none, n=81 (39.9%); mild, n=56 (27.6%); moderate, n=51 (25.1%); and severe, n=15 (7.4%). Analgesia requirements correlated well with severity of pain. Independent predictors of significant pain after PLB (moderate and severe categories) in patients included age less than 50 years [odds ratio (OR) 3.0], female sex (OR 3.7), Indian ethnicity (OR 2.9) and Malay ethnicity (OR 2.7), but not number of needle passes, BMI and educational levels. Patients who experienced moderate/severe pain were less willing to undergo a repeat PLB compared with those who experienced mild/no pain (60.9 vs. 82.8%, P=0.001)., Conclusion: Ethnicity has an important role in the development of pain after US-guided PLB. This has a significant impact on willingness to repeat the procedure.

Background: There are no reliable epidemiological data on sarcoidosis in the French West Indies, although this disease is known to be more frequent and more severe in Black African-Americans and West Indians., Objectives: This retrospective study aimed to assess the incidence and prevalence of sarcoidosis in Guadeloupe over a 7-year period and to determine its epidemiological, clinical, and evolutionary characteristics., Methods: Patients were identified through the computerized databases of the three pathology laboratories and two hospitals on the islands of Guadeloupe. Histologically proven cases of sarcoidosis were selected. All patients were recalled at a single study time-point., Results: A total of 75 patients were identified. These included 44 women and 31 men (sex ratio: 1.4), with a mean ± standard deviation (SD) age of 47 ± 14 years and Fitzpatrick skin types IV-VI. The average incidence was 2.28 per 100,000 inhabitants per year (95% confidence interval [CI] 1.69-3.02). The prevalence of sarcoidosis in 2009 was 21.09 per 100,000 inhabitants (95% CI 16.00-26.18). Most patients (61/71, 85.9%) exhibited multiple organ involvement; the mean ± SD number of organs involved was 2.6 ± 1.1. The initiation of systemic therapy was required in 75.7% of cases. Several lines of treatment were necessary in 41.5% of affected patients. At the study time-point, seven patients were found to have died. Four of these deaths were directly attributable to sarcoidosis (mortality rate: 5.3%)., Conclusions: This epidemiological study on sarcoidosis in Guadeloupe reveals a low incidence of the disease and a high degree of severity as evidenced by the average number of affected organs, the high frequency of extrathoracic organ involvement, the frequent use of corticosteroids, and a mortality rate of 5.3%., (© 2014 The International Society of Dermatology.)

Background: Primary iron overload in African Americans has been reported predominantly from autopsy studies., Methods: We characterized hepatic iron phenotypes in 83 African Americans who underwent liver biopsy during the interval 1990 to 1995. We tabulated pathology report form data, iron grades in hepatocytes (0-4) and Kupffer cells (0-3) and abnormal liver histology. Increased iron was defined as hepatocyte or Kupffer iron grades ≥ 2, respectively. Heavy iron was defined as hepatocyte iron grade 3 or 4. Primary iron overload was defined as the presence of grade 3 or 4 hepatocellular iron in the absence of evidence of chronic alcohol effect, viral hepatitis, steatosis, unexplained inflammation, chronic erythrocyte transfusion or chronic ingestion of iron supplements., Results: There were 37 men and 46 women (mean age: 53 ± 15 [SD] years). We observed heavy ethanol consumption, 12.0%; viral hepatitis, 26.5%; steatosis without heavy ethanol consumption, 43.4%; inflammation, 45.6%; fibrosis, 26.2% and bridging fibrosis/cirrhosis, 29.4%. Logistic regression on bridging fibrosis/cirrhosis revealed positive associations with heavy ethanol consumption (P = 0.0410) and viral hepatitis (P = 0.0044). The 22 patients (26.5%) with increased iron had greater mean age, proportion of men and heavy ethanol consumption. Five patients had heavy iron staining, among whom were 3 women (mean age: 54 years) with primary iron overload. Two of the 3 women had cirrhosis and diabetes mellitus., Conclusions: Among 83 adult African Americans who underwent liver biopsy, 3.6% had hepatic iron phenotypes consistent with primary iron overload.

Background & Aims: Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC) and chronic liver disease (CLD), but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee intake with HCC and CLD in 162,022 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the US Multiethnic Cohort (MEC)., Methods: We collected data from the MEC, a population-based prospective cohort study of >215,000 men and women from Hawaii and California, assembled in 1993-1996. Participants reported coffee consumption and other dietary and lifestyle factors when they joined the study. During an 18-year follow-up period, there were 451 incident cases of HCC and 654 deaths from CLD. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression, adjusting for known HCC risk factors., Results: High levels of coffee consumption were associated with reduced risk of incident HCC and CLD mortality (Ptrend ≤ .0002). Compared with non-coffee drinkers, those who drank 2-3 cups per day had a 38% reduction in risk for HCC (RR = 0.62; 95% CI: 0.46-0.84); those who drank ≥4 cups per day had a 41% reduction in HCC risk (RR = 0.59; 95% CI: 0.35-0.99). Compared with non-coffee drinkers, participants who consumed 2-3 cups coffee per day had a 46% reduction in risk of death from CLD (RR = 0.54; 95% CI: 0.42-0.69) and those who drank ≥4 cups per day had a 71% reduction (RR = 0.29; 95% CI: 0.17-0.50). The inverse associations were similar regardless of the participants' ethnicity, sex, body mass index, smoking status, alcohol intake, or diabetes status., Conclusions: Increased coffee consumption reduces the risk of HCC and CLD in multiethnic US populations., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Liver disease is a major cause of morbidity and mortality worldwide. Large numbers of liver function tests (LFTs) are performed in primary care, with abnormal liver biochemistry a common finding. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Metabolic syndrome, common in people from South Asia, is an important risk factor for NAFLD., Aim: It is hypothesised that a large gap exists between numbers of patients with abnormal LFTs and those with recorded liver diagnoses, and that NAFLD is more common among adults of South Asian ethnic groups., Design and Setting: A cross-sectional study of 690,683 adults in coterminous general practices in a region with high ethnic diversity., Method: Data were extracted on LFTs, liver disease, and process of care measures from computerised primary care medical records., Results: LFTs were performed on 218,032 patients, of whom 31 627 had elevated serum transaminases. The prevalence of abnormal LFTs was highest among individuals of Bangladeshi ethnicity. Of the patients with abnormal LFTs, 88.4% did not have a coded liver diagnosis. NAFLD was the most frequently recorded liver disease and was most common among Bangladeshi patients. In a multivariate analysis, independent risk factors for NAFLD included Bangladeshi ethnicity, diabetes, raised BMI, hypertension, and hypercholesterolaemia., Conclusion: Abnormal LFTs are common in the population, but are underinvestigated and often remain undiagnosed. Bangladeshi ethnicity is an important independent risk factor for NAFLD., (© British Journal of General Practice 2014.)

Objectives: The aim of the present article was to determine the prevalence of liver involvement in Hispanic patients with cystic fibrosis (CF) and identify associations with age and severity of liver involvement., Methods: We used 1994-2005 Epidemiologic Study of CF data to compare abnormal liver findings between Hispanic and non-Hispanic white patients with CF., Results: Of 30,727 patients with CF, 5015 had liver involvement. Of 1957 Hispanic patients, 20.8% had liver involvement compared with 16.0% of 28,770 non-Hispanic white patients (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.23-1.54). This higher prevalence of liver involvement persisted after adjusting for demographics and meconium ileus and was especially high in the first year of life (adjusted OR 3.14, 95% CI 2.27-4.35). Ten percent of infants with only elevated liver enzymes progressed to more severe liver disease., Conclusions: The Hispanic population with CF has more liver involvement (both elevated liver enzymes and clinical liver disease) than the non-Hispanic white population with CF, especially during the first year of life.

Objectives: We compared chronic liver disease (CLD) mortality from 1999 to 2009 between American Indians and Alaska Natives (AI/ANs) and Whites in the United States after improving CLD case ascertainment and AI/AN race classification., Methods: We defined CLD deaths and causes by comprehensive death certificate-based diagnostic codes. To improve race classification, we linked US mortality data to Indian Health Service enrollment records, and we restricted analyses to Contract Health Service Delivery Areas and to non-Hispanic populations. We calculated CLD death rates (per 100,000) in 6 geographic regions. We then described trends using linear modeling., Results: CLD mortality increased from 1999 to 2009 in AI/AN persons and Whites. Overall, the CLD death rate ratio (RR) of AI/AN individuals to Whites was 3.7 and varied by region. The RR was higher in women (4.7), those aged 25 to 44 years (7.4), persons residing in the Northern Plains (6.4), and persons dying of cirrhosis (4.0) versus hepatocellular carcinoma (2.5), particularly those aged 25 to 44 years (7.7)., Conclusions: AI/AN persons had greater CLD mortality, particularly from premature cirrhosis, than Whites, with variable mortality by region. Comprehensive prevention and care strategies are urgently needed to stem the CLD epidemic among AI/AN individuals.

Unlabelled: This study is to explore the effect of ALAD polymorphism on hematopoietic, hepatic and renal toxicity from lead in occupational exposure workers., Methods: We conducted a cross-sectional study on 156 workers with occupational exposure to lead between 2002 and 2007. The results of laboratory examinations were analyzed., Results: The authors found that workers with the ALAD 1-1 genotype were associated with higher blood lead level than those with the ALADl-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The urine ALA and blood ZPP levels in workers with the ALAD 1-1 genotype were higher than those with the ALADl-2 genotype. The serum Cr level in workers with the ALADl-1 genotype was much higher than those with the ALADl-2 genotype especially in higher lead exposure level., Conclusions: The ALAD-2 protein might modify the kinetics of lead in blood at a relatively higher blood lead level and protect against hematopoietic, hepatic and renal toxicity from lead. Urine ALA, blood ZPP and serum Cr levels might be considered as effective biological monitoring partners of lead induced hematopoietic and renal toxicology.

Aims: To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of eltrombopag in chronic liver disease (CLD)., Methods: The PK/PD model was developed using data from 79 CLD patients using nonlinear mixed-effects modelling., Results: The PK of eltrombopag were described by a two-compartment model with dual sequential first-order absorption. Gender, race and severity of CLD were predictors of the apparent clearance of eltrombopag. The PD of eltrombopag in CLD were adequately described by a four-compartment lifespan model, in which eltrombopag stimulated platelet precursor production rate. East Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag. Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak platelet counts was longer for the CLD population compared with patients who had immune thrombocytopenic purpura, but was comparable to patients with hepatitis C. Likewise, it took a longer time for platelet counts to rebound back to baseline once eltrombopag treatment was discontinued., Conclusions: The time course of the platelet response in CLD was different from that in immune thrombocytopenic purpura but comparable to that in hepatitis C., (© 2013 The British Pharmacological Society.)

Background: Controlled attenuation parameter (CAP) is a non-invasive method of measuring hepatic steatosis using a process based on transient elastography. We investigated the diagnostic accuracy of CAP in detecting hepatic steatosis in patients with chronic liver disease (CLD)., Methods: A total of 135 patients with CLD who underwent liver biopsy and CAP were consecutively enrolled in this prospective study. The performance of CAP for detection of hepatic steatosis compared with liver biopsy was calculated using area under receiver operating characteristics curves (AUROC). Steatosis was categorized into S0 (<5%), S1 (5-33%), S2 (34-66%) and S3 (>66% of hepatocytes)., Results: Male gender predominated (n = 87, 64%) and the median age was 51 years. The aetiologies of CLD included non-alcoholic fatty liver disease (n = 56, 41.5%) and chronic viral hepatitis because of hepatitis B (n = 47, 34.8%) and C (n = 12, 8.9%). Steatosis repartition was: S0 31.1% (n = 42), S1 43.7% (n = 59), S2 18.5% (n = 25) and S3 6.7% (n = 9) respectively. In the multivariate analysis, steatosis grade and body mass index were independently associated with CAP (all P < 0.001), whereas fibrosis stage and activity grade were not. The AUROCs of CAP were 0.885 for ≥S1 (sensitivity 73.1%, specificity 95.2%), 0.894 for ≥S2 (sensitivity 82.4%, specificity 86.1%) and 0.800 for S3 (sensitivity 77.8%, specificity 84.1%). The optimal cut-off CAP values that maximized the Youden index were 250 dB/m (≥S1), 299 dB/m (≥S2), and 327 dB/m (=S3) respectively., Conclusions: Our data showed that CAP had high diagnostic accuracy for detecting hepatic steatosis in patients with CLD and suggested that CAP is also applicable for Asian patients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Interleukin-4 (IL-4) is a pleiotropic cytokine that plays an important role in the immune system. Emerging evidences have shown that the common polymorphism (-590C/T; rs2243250 C>T) in the IL-4 gene may play an important role in the development of various liver diseases, but individually published studies revealed inconclusive results. This meta-analysis aims to derive a more precise estimation of the association between the IL-4 -590C/T polymorphism and susceptibility to liver disease. A literature search of PubMed, Embase, Web of Science and China BioMedicine databases was conducted on articles published before January 1st, 2013. Crude odds ratio with 95% confidence intervals were calculated to assess the strength of this association. Ten case-control studies were assessed with a total 1,140 patients and 1,649 healthy controls. The meta-analysis results indicated that the IL-4 -590T polymorphism might increase the risks of hepatitis B (HBV) and hepatitis C (HCV) infections. Further subgroup analyses showed significant associations between the IL-4 -590T polymorphism and increased risks of liver diseases among Caucasian populations, but similar associations were not found among Asian populations. Univariate and multivariate meta-regression analyses showed that differences in ethnicity and clinical subtype are the major sources of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that the IL-4 -590T polymorphism may play an important role in increasing HBV and HCV infection risks, especially among Caucasian populations.

Purpose: The aim of this study was to validate the Chronic Liver Disease Questionnaire (CLDQ) for use in Brazilian population., Method: A total of 200 patients with chronic liver disease and varying disease severity answered a socio-demographic questionnaire, t CLDQ, and the Medical Outcome Study Short Form 36 (SF-36). Patients returned in 1-15 days to answer CLDQ again. The Cronbach's alpha of the total CLDQ score was 0.95 and fluctuated between 0.69 and 0.83 in its six domains., Results: The intra-class correlation between total CLDQ scores in two evaluations was 0.97 and in all domains was >0.93. CLDQ was moderately correlated with the SF-36, 0.63 (total CLDQ vs. vitality, SF-36), 0.62 (CLDQ and mental health, SF-36), 0.62 (preoccupation, CLDQ, vs. General Health, SF-36), 0.59 (fatigue, CLDQ, vs. vitality, SF-36), 0.59 (activity, CLDQ, vs. vitality, SF-36), and 0.59 (fatigue, CLDQ, vs. mental health, SF-36). The highest scores were found in non-cirrhotic group. Child A patients had higher average scores than Child B and C groups in all domains, while patients with MELD <15 scored higher than patients with MELD ≥15., Conclusion: CLDQ-BR was validated in Brazilian population and was appropriate for use in patients with liver disease of different etiologies and degrees of severity.

Unlabelled: Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8)., Conclusions: African-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Recurrent pyogenic cholangitis (RPC), or oriental cholangiohepatitis, is characterized by intrabiliary pigment stone formation, whose main manifestation consists of recurrent episodes of cholangitis, although other biliopancreatic complications can also occur. RPC develops mainly in Asian patients, in whom this entity is one of the main causes of acute abdominal pain. The differential diagnosis should be established with all other entities associated with intrahepatic stone formation, which is more common in Asian countries compared with the predominance of gallstone formation in the West. The diagnostic and therapeutic approach requires collaboration among gastroenterologists, radiologists and gastrointestinal surgeons. We review the most important clinical, diagnostic and therapeutic features of this entity, which, although clearly predominant in Asia, is increasingly diagnosed in our setting., (Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.)

Background/aims: Serum alanine aminotransferase (ALT) is an easily available, low-cost screening tool for detecting silent chronic liver disease. Recent studies have suggested that the currently accepted healthy ALT thresholds be lowered., Methods: In this retrospective cross-sectional study, we determined upper thresholds for ALT values in a nationally representative healthy cohort (n = 3337) from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV). Sensitivity and specificity of the currently used ALT threshold (40 IU/L, regardless of gender) was compared against study-derived, gender-specific ALT thresholds for detecting individuals at risk for chronic liver disease in 27 913 health check-up participants., Results: The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free KNHANES participants were 34 IU/L for men and 25 IU/L for women. The prevalence of ALT elevation among health check-up participants was 11.0% in currently used thresholds, and increased to 22.6% with study-derived, gender-specific thresholds. Of the population who were additionally defined to have elevated ALT levels under new ALT threshold, 65.7% were at risk for chronic liver disease. Sensitivity for detecting individuals at risk for chronic liver disease improved from 18 to 33% with new thresholds whereas a trade-off in specificity (from 96 to 88%) was observed., Conclusions: It is recommendable to lower the current ALT thresholds to better identify individuals at risk for chronic liver disease., (© 2012 John Wiley & Sons A/S.)

Introduction: Identifying liver fibrosis is important to evaluate the severity of liver damage and to establish a prognosis. Utility of non-invasive markers of liver fibrosis has been proved in adults but there are few reports in children. The aim of this study was to evaluate Fibrotest® score and APRI suitability to identify children with liver fibrosis., Material and Methods: 68 children with chronic liver disease requiring liver biopsy were prospectively included from three 3rd-level pediatric hospitals. The same pathologist evaluated all liver biopsies; fibrosis degree was determined by METAVIR score. Serum samples were obtained to determine Fibrotest® and APRI. AUROC were used to determine cut-off and differentiate between advanced fibrosis (METAVIR F3, F4) and no fibrosis (F0)., Results: 68 biopsies were evaluated; METAVIR > F3 was identified in 26 (38%). Non invasive liver fibrosis markers to differentiate between advanced and no fibrosis were: Fibrotest® AUROC = 0.90 (95% CI 0.77-1.00) (cut-off value 0.35) sensitivity 88.00% (95% CI 68-96) and specificity 80% (95% CI 29-98); and for APRI AUROC = 0.97 (95% CI 0.92-1.00) (cut-off value 0.82), sensitivity 88% (95% CI 68-96) and specificity = 100% (95% CI 46-100)., Conclusion: These results suggest the utility of Fibrotest® and APRI to identify advanced fibrosis; they can be recommended to select patients for liver biopsy and during patient follow-up.

Latinos in the US are disproportionately affected by chronic liver disease, which is the sixth most common cause of death among this group. In Mexico, cirrhosis and other liver diseases are the fourth leading cause of general mortality. The objective of this study was to contrast the liver disease risk factors, knowledge, and prevention practices reported among separate samples of Mexicans living in Los Angeles, CA and in Cuernavaca, Mexico. We assessed the prevalence of specific risk factors (body mass index, waist circumference, and alcohol consumption), the level of knowledge about liver disease in general, hepatitis B (HBV), and hepatitis C (HCV), as well as prevention activities such as screening and vaccination. Data were collected from in-person interviews and anthropometric measures obtained from Mexican adults aged 18-70 years. Chi-square and t tests were used to compare the results between groups. Numerous similarities were observed in the bi-national samples, including high prevalence of obesity, abdominal obesity, and high levels of alcohol consumption. Most participants in both countries recognized that excessive alcohol consumption is a risk factor for liver disease, but only 60% correctly identified hepatitis C, being overweight or obese, or having diabetes as risk factors. Few participants reported having been screened for HBV or HCV, vaccinated for HBV, or having the intention of getting screened for HBV or HCV. US participants reported significantly higher levels of prevention activities and screening intentions than those in Mexico. Identifying the specific risk factors, levels of knowledge and prevention activities that affect specific racial/ethnic populations is important in order to effectively target efforts to prevent liver disease.

Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Introduction: Access to orthotopic liver transplantation (OLT) varies among different ethnic groups. The aim of this study was to determine if distance from transplantation center (DT) impedes referral pattern and accessibility to OLT among ethnic groups., Method: This is a retrospective cohort study of all patients evaluated for OLT at our center (2002-2007). The ZipCode Basic software was used to compute distance between the candidate's residence and transplantation center., Results: Five hundred one patients were evaluated during the study period and there were 439 (87.6%) whites 43 (8.6%) African Americans (AA), and others (3.8%). The median DT was 36.8 miles (range, 0.5-231), and there was no significant correlation with the Model for End-Stage Liver Disease (MELD) at presentation (P=.87). Although AA had a higher likelihood of residing closer to a transplantation center they were more likely to have a higher MELD at presentation (20 vs 15.4; P<.001) and less likely to be referred early to initiate OLT evaluation (11.6% vs 26.4%; P=.04). Additionally, type of insurance correlated with higher MELD at presentation., Conclusion: DT was not a contributory factor to the observed access disparity in our patient population, rather the insurance type and disease severity as determined using MELD differed significantly among ethnic groups., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Liver cirrhosis is within the top 10 causes of death in Latin-American countries and recent evidence suggests that Hispanics in the USA have a more aggressive course of many types of liver disease and show lower response to treatment of hepatitis C compared with other ethnic groups. Although environmental factors are very important, they do not appear to fully account for the observed ethnic differences in the incidence of cirrhosis and progression rates. Genome-wide association studies have been a powerful tool to identify genetic variants that directly confer susceptibility to liver disease. Here, we review the current knowledge on genetic variants associated with the most common types of liver disease that may contribute to ancestry-related differences in disease progression and mortality.

Introduction: Liver disease is a major health issue in Mexico. Although several studies have been performed to analyze the impact of liver diseases on the Mexican population, none has compared the prevalence and impact of liver disease between states within Mexico., Aim: To analyze trends in mortality associated with liver diseases from 2000 to 2007 at the national and state levels., Methods: Data was obtained from the Ministry of Health (number of deaths) and the National Population Council (CONAPO) (population at risk) and mortality rates were analyzed using statistical software., Results: Mortality due to viral hepatitis, liver tumors, and cirrhosis increased over the study period. Alcohol-related mortality decreased but was still the main cause of liver-related deaths. Viral hepatitis infection occurred predominantly in the northern states and liver tumors occurred predominantly in the central region. Alcohol-related deaths were elevated along the Pacific shoreline and deaths associated with cirrhosis occurred mainly in the central and southern states., Conclusion: Incidence of liver-related mortality has increased and will continue to do so in the future.