ABSTRACT
BACKGROUND: Cirrhosis is responsible for substantial health and economic burden in the USA. Reducing this burden requires better understanding of how rates of cirrhosis mortality vary by race and ethnicity and by geographical location. This study describes rates and trends in cirrhosis mortality for five racial and ethnic populations in 3110 US counties from 2000 to 2019. METHODS: We estimated cirrhosis mortality rates by county, race and ethnicity, and year (2000-19) using previously validated small-area estimation methods, death registration data from the US National Vital Statistics System, and population data from the US National Center for Health Statistics. Five racial and ethnic populations were considered: American Indian or Alaska Native (AIAN), Asian or Pacific Islander (Asian), Black, Latino or Hispanic (Latino), and White. Cirrhosis mortality rate estimates were age-standardised using the age distribution from the 2010 US census as the standard. For each racial and ethnic population, estimates are presented for all counties with a mean annual population greater than 1000. FINDINGS: From 2000 to 2019, national-level age-standardised cirrhosis mortality rates decreased in the Asian (23·8% [95% uncertainty interval 19·6-27·8], from 9·4 deaths per 100 000 population [8·9-9·9] to 7·1 per 100 000 [6·8-7·5]), Black (22·8% [20·6-24·8], from 19·8 per 100 000 [19·4-20·3] to 15·3 per 100 000 [15·0-15·6]), and Latino (15·3% [13·3-17·3], from 26·3 per 100 000 [25·6-27·0] to 22·3 per 100 000 [21·8-22·8]) populations and increased in the AIAN (39·3% [32·3-46·4], from 45·6 per 100 000 [40·6-50·6] to 63·5 per 100 000 [57·2-70·2] in 2000 and 2019, respectively) and White (25·8% [24·2-27·3], from 14·7 deaths per 100 000 [14·6-14·9] to 18·5 per 100 000 [18·4-18·7]) populations. In all years, cirrhosis mortality rates were lowest among the Asian population, highest among the AIAN population, and higher in males than females for each racial and ethnic population. The degree of heterogeneity in county-level cirrhosis mortality rates varied by racial and ethnic population, with the narrowest IQR in the Asian population (median 8·0 deaths per 100 000, IQR 6·4-10·4) and the widest in the AIAN population (55·1, 30·3-78·8). Cirrhosis mortality increased over the study period in almost all counties for the White (2957 [96·9%] of 3051 counties) and AIAN (421 [88·8%] of 474) populations, but in a smaller proportion of counties for the Asian, Black, and Latino populations. For all racial and ethnic populations, cirrhosis mortality rates increased in more counties between 2000 and 2015 than between 2015 and 2019. INTERPRETATION: Cirrhosis mortality increased nationally and in many counties from 2000 to 2019. Although the magnitude of racial and ethnic disparities decreased in some places, disparities nonetheless persisted, and mortality remained high in many locations and communities. Our findings underscore the need to implement targeted and locally tailored programmes and policies to reduce the burden of cirrhosis at both the national and local level. FUNDING: US National Institutes of Health (Intramural Research Program, National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; Intramural Research Program, National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research).
Subject(s)
Ethnicity , Health Status Disparities , Liver Cirrhosis , Humans , United States/epidemiology , Liver Cirrhosis/mortality , Liver Cirrhosis/ethnology , Ethnicity/statistics & numerical data , Male , Female , Middle Aged , Racial Groups/statistics & numerical data , Aged , AdultABSTRACT
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. MATERIALS AND METHODS: We cross-sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. RESULTS: Adjusting for age, sex, body mass index, and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21-8.76, p = 0.019), an effect comparable to that of possessing the major PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13-1.16, p = 0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91-33.86, p = 0.005). DISCUSSION: Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors-rather than genes or ethnicity-may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease.
Subject(s)
Lipase , Membrane Proteins , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/ethnology , Non-alcoholic Fatty Liver Disease/epidemiology , Male , Female , Middle Aged , Lipase/genetics , Adult , Membrane Proteins/genetics , Cross-Sectional Studies , Hispanic or Latino/genetics , Hispanic or Latino/statistics & numerical data , Socioeconomic Factors , 17-Hydroxysteroid Dehydrogenases/genetics , Disease Progression , Aged , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Liver Cirrhosis/ethnology , Liver Cirrhosis/epidemiology , Acyltransferases , Phospholipases A2, Calcium-IndependentABSTRACT
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and 10%-20% occurs in lean individuals. There is little data in the literature regarding outcomes in an ethnically-diverse patient populations with MASLD. Thus, we aim to investigate the natural history and ethnic disparities of MASLD patients in a diverse population, and stratified by body mass index categories. METHODS: We conducted a retrospective multicenter study on patients with MASLD at the Banner Health System from 2012 to 2022. Main outcomes included mortality and incidence of cirrhosis, cardiovascular disease, diabetes mellitus (DM), liver-related events (LREs), and cancer. We used competing risk and Cox proportional hazard regression analysis for outcome modelling. RESULTS: A total of 51 452 (cross-sectional cohort) and 37 027 (longitudinal cohort) patients were identified with 9.6% lean. The cohort was 63.33% European ancestry, 27.96% Hispanic ancestry, 3.45% African ancestry, and 2.31% Native American/Alaskan ancestry. Median follow-up was 45.8 months. After adjusting for confounders, compared to European individuals, Hispanic and Native American/Alaskan patients had higher prevalence of cirrhosis and DM, and individuals of Hispanic, African, and Native American/Alaskan ancestry had higher mortality and incidence of LREs and DM. Lean patients had higher mortality and incidence of LREs compared with non-lean patients. CONCLUSION: Native American/Alaskan, Hispanic, and African patients had higher mortality and incidence of LREs and DM compared with European patients. Further studies to explore the underlying disparities and intervention to prevent LREs in lean patients, particularly several ethnic groups, may improve clinical outcomes.
Subject(s)
Health Status Disparities , Humans , Male , Female , Retrospective Studies , Middle Aged , Aged , Cross-Sectional Studies , Adult , Body Mass Index , Liver Cirrhosis/mortality , Liver Cirrhosis/ethnology , Incidence , Ethnicity/statistics & numerical data , Diabetes Mellitus/ethnology , Diabetes Mellitus/mortality , Cardiovascular Diseases/mortality , Cardiovascular Diseases/ethnology , Proportional Hazards Models , United States/epidemiology , Longitudinal StudiesABSTRACT
BACKGROUND: Among patients with cirrhosis, it remains unclear whether there are racial/ethnic differences in cirrhosis complications and mortality. We examined the associations between race/ethnicity and risk for hepatocellular carcinoma (HCC), cirrhosis decompensation, and all-cause mortality overall and by cirrhosis etiology. METHODS: US Veterans diagnosed with cirrhosis from 2001 to 2014 (n = 120,992), due to hepatitis C virus (HCV; n = 55,814), alcohol-associated liver disease (ALD; n = 36,323), hepatitis B virus (HBV; n = 1,972), nonalcoholic fatty liver disease (NAFLD; n = 17,789), or other (n = 9,094), were followed through 2020 for incident HCC (n = 10,242), cirrhosis decompensation (n = 27,887), and mortality (n = 81,441). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with non-Hispanic White patients, Hispanic patients had higher risk for HCC overall (aHR, 1.32; 95% CI, 1.24-1.41) and by cirrhosis etiology, particularly for ALD- (aHR, 1.63; 95% CI, 1.42-1.87) and NAFLD-cirrhosis (aHR, 1.76; 95% CI, 1.41-2.20), whereas non-Hispanic Black patients had lower HCC risk in ALD- (aHR, 0.79; 95% CI, 0.63-0.98) and NAFLD-cirrhosis (aHR, 0.54; 95% CI, 0.33-0.89). Asian patients had higher HCC risk (aHR, 1.70; 95% CI, 1.29-2.23), driven by HCV- and HBV-cirrhosis. Non-Hispanic Black patients had lower risk for cirrhosis decompensation overall (aHR, 0.71; 95% CI, 0.68-0.74) and by cirrhosis etiology. There was lower risk for mortality among all other racial/ethnic groups compared with non-Hispanic White patients. CONCLUSIONS: Race/ethnicity is an important predictor for risk of developing HCC, decompensation, and mortality. IMPACT: Future research should examine factors underlying these racial/ethnic differences to inform prevention, screening, and treatment for patients with cirrhosis.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis C , Liver Cirrhosis , Veterans , Humans , Carcinoma, Hepatocellular/ethnology , Carcinoma, Hepatocellular/mortality , Ethnicity , Hepacivirus , Hepatitis C/complications , Hepatitis C/ethnology , Liver Cirrhosis/complications , Liver Cirrhosis/ethnology , Liver Neoplasms/ethnology , Liver Neoplasms/mortality , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , Male , Female , Adult , Middle Aged , AgedABSTRACT
Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population.
Subject(s)
Fatty Acids , Non-alcoholic Fatty Liver Disease , Obesity , Overweight , Adult , Humans , Diabetes Mellitus, Type 2/complications , Fatty Acids/administration & dosage , Hispanic or Latino , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/ethnology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/ethnology , Obesity/complications , Obesity/ethnology , Overweight/complications , Overweight/ethnology , United States , DietABSTRACT
BACKGROUND: Liver diseases are important contributors to the mortality gap between Indigenous and non-Indigenous Australians. AIMS: This cohort study examined factors associated with hospital admissions and healthcare outcomes among Indigenous Australians with cirrhosis. METHODS: Patient-reported outcomes were obtained by face-to-face interview (Chronic Liver Disease Questionnaire and Short Form 36 (SF-36)). Clinical data were extracted from medical records and through data linkage for 534 patients (25 indigenous). Cumulative overall survival (Kaplan-Meier), rates of hospital admissions and emergency presentations, and costs were assessed by indigenous status. Incidence rate ratios (IRR; Poisson regression) were reported. RESULTS: Indigenous Australians admitted to hospital with cirrhosis had lower educational status compared with non-indigenous patients (79.2% vs 43.4%; P < 0.001). The two groups had, in general, similar clinical characteristics including disease severity (P = 0.78), presence of cirrhosis complications (P = 0.67), comorbidities (P = 0.62), rates of cirrhosis-related admissions (P = 0.86) and 5-year survival (P = 0.30). However, indigenous patients had a lower score in the SF-36 domain related to bodily pain (P = 0.037), more cirrhosis admissions via the emergency department (IRR = 1.42, 95% confidence interval (CI) 1.10-1.83) and fewer planned cirrhosis admissions (IRR = 0.32, 95% CI 0.14-0.72). The total cost for cirrhosis-related hospital admissions for 534 patients over 6 years (July 2012 to June 2018) was A$13.7 million. The cost of cirrhosis-related hospital admissions was double for indigenous patients (cost ratio = 2.04, 95% CI 2.04-2.05). CONCLUSIONS: Our data highlight the disparities in health service use and patient-reported outcomes, despite having similar clinical profiles. Integration between primary care, Aboriginal Community Controlled Health Organisations and liver specialists is critical for appropriate health service delivery and effective use of resources. Chronic liver disease costs the community dearly.
Subject(s)
Australian Aboriginal and Torres Strait Islander Peoples , Hospitalization , Liver Cirrhosis , Humans , Australia/epidemiology , Cohort Studies , Hospitalization/economics , Hospitalization/statistics & numerical data , Hospitals , Liver Cirrhosis/economics , Liver Cirrhosis/epidemiology , Liver Cirrhosis/ethnology , Liver Cirrhosis/therapy , Australian Aboriginal and Torres Strait Islander Peoples/statistics & numerical dataABSTRACT
Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/pathology , Cell-Free Nucleic Acids/genetics , Hispanic or Latino/genetics , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Mutation , Aged , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/ethnology , Carcinoma, Hepatocellular/genetics , Cell-Free Nucleic Acids/blood , Female , High-Throughput Nucleotide Sequencing , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/ethnology , Liver Cirrhosis/genetics , Liver Neoplasms/blood , Liver Neoplasms/ethnology , Liver Neoplasms/genetics , MaleABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease is inconsistently associated with ischemic stroke, with one study suggesting an association in women and not men. The relative importance of liver fibrosis, as opposed to fatty liver, for cardiovascular risk is increasingly appreciated. We hypothesized that advanced liver fibrosis is associated with incident ischemic stroke risk, and especially in women. METHODS: We performed a case-cohort study in the REasons for Geographic and Racial Differences in Stroke cohort. Black and white individuals aged 45 and older were recruited between 2003 and 2007 and followed for ischemic stroke. The Fibrosis-4 (FIB-4) score and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated using baseline data for stroke cases and a cohort random sample; advanced liver fibrosis was classified using validated cutoffs. Cox proportional hazards models were used to estimate hazard ratios (HR) of stroke after adjusting for potential confounders. Sex differences were assessed. RESULTS: There were 572 incident ischemic strokes (285 in women) over 5.4 (SD, 2.2) years. Advanced liver fibrosis was not significantly associated with ischemic stroke overall using the FIB-4 (HR 1.44; 95% CI 0.49-4.28) or NFS (HR 1.76; 95% CI 0.67-4.61). However, liver fibrosis was associated with stroke in women (HR 3.51; 95% CI 1.00-12.34) but not men (HR 0.70, 95% CI 0.16-3.16) (P = 0.098 for interaction) when using FIB-4. A similar but non-significant sex difference was seen for NFS. CONCLUSION: Advanced liver fibrosis may be associated with a higher risk of ischemic stroke in women but not men.
Subject(s)
Ischemic Stroke/ethnology , Liver Cirrhosis/ethnology , Non-alcoholic Fatty Liver Disease/ethnology , Aged , Aged, 80 and over , Black People , Female , Humans , Incidence , Ischemic Stroke/diagnosis , Liver Cirrhosis/diagnosis , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Prospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , White PeopleABSTRACT
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.
Subject(s)
Alcohol Drinking , Diabetes Mellitus, Type 2/complications , Liver Diseases/etiology , Alcohol Drinking/adverse effects , Asian People/ethnology , Cross-Sectional Studies , Elasticity Imaging Techniques , Fatty Liver/diagnostic imaging , Fatty Liver/epidemiology , Fatty Liver/ethnology , Fatty Liver/etiology , Female , Humans , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Liver Cirrhosis/ethnology , Liver Cirrhosis/etiology , Liver Diseases/diagnostic imaging , Liver Diseases/epidemiology , Liver Diseases/ethnology , Male , Negative Results , Prevalence , Severity of Illness IndexABSTRACT
BACKGROUND & AIMS: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection. METHODS: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up. RESULTS: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p <0.001). HDV viral load at baseline was significantly lower in responders than in non-responders. CONCLUSION: Place of birth, HDV genotype and persistent viremia constitute the main determinants of liver involvement and response to treatment in chronic HDV-infected patients. LAY SUMMARY: Chronic liver infection by hepatitis delta virus (HDV) is the most severe form of chronic viral hepatitis. Despite the fact that at least 15-20 million people are chronically infected by HDV worldwide, factors determining the severity of liver involvement are largely unknown. By investigating a large cohort of 1,112 HDV-infected patients followed-up in France, but coming from different areas of the world, we were able to determine that HDV genotype, place of birth (reflecting both viral and host-related factors) and persistent viremia constitute the main determinants of liver involvement and response to treatment.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis D, Chronic , Hepatitis Delta Virus , Liver Cirrhosis , Liver Neoplasms , Viremia , Adult , Carcinoma, Hepatocellular/ethnology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Female , France/epidemiology , Hepatitis D, Chronic/complications , Hepatitis D, Chronic/diagnosis , Hepatitis D, Chronic/epidemiology , Hepatitis D, Chronic/therapy , Hepatitis Delta Virus/genetics , Hepatitis Delta Virus/isolation & purification , Hepatitis Delta Virus/pathogenicity , Humans , Interferons/therapeutic use , Liver Cirrhosis/diagnosis , Liver Cirrhosis/ethnology , Liver Cirrhosis/etiology , Liver Neoplasms/ethnology , Liver Neoplasms/pathology , Liver Neoplasms/virology , Male , Residence Characteristics/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Viral Load/methods , Viral Load/statistics & numerical data , Viremia/diagnosis , Viremia/ethnologyABSTRACT
BACKGROUND AND AIMS: Epidemiological data on dietary risk factors for nonalcoholic fatty liver disease (NAFLD) from population-based studies, particularly in an ethnically diverse population, are scarce. We examined dietary factors in relation to NAFLD risk in African Americans, Japanese Americans, Latinos, native Hawaiians, and whites in the Multiethnic Cohort (MEC). APPROACH AND RESULTS: A nested case-control analysis was conducted within the MEC, a large prospective study with >215,000 older adult participants in Hawaii and California. NAFLD was identified using Medicare claims data, and controls were selected among participants without liver disease and individually matched to cases by birth year, sex, ethnicity, and length of Medicare enrollment. Diet was assessed at baseline through a validated quantitative food frequency questionnaire. Diet-NAFLD associations were quantified by odds ratios and 95% confidence intervals using multivariable conditional logistic regression. The study consisted of 2,974 NAFLD cases (518 with cirrhosis, 2,456 without cirrhosis) and 29,474 matched controls. Red meat (P trend = 0.010), processed red meat (P trend = 0.004), poultry (P trend = 0.005), and cholesterol (P trend = 0.005) intakes were positively associated with NAFLD, while dietary fiber intake (P trend = 0.003) was inversely associated with risk. Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis (P heterogeneity ≤0.014). CONCLUSIONS: Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population. Decreasing the consumption of cholesterol, red and processed meat, and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease.
Subject(s)
Diet , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , Risk Assessment , Cholesterol, Dietary , Cohort Studies , Correlation of Data , Diet/ethnology , Diet/statistics & numerical data , Dietary Fiber , Ethnicity , Female , Food Preferences/ethnology , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/ethnology , Liver Cirrhosis/etiology , Male , Medicare/statistics & numerical data , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/ethnology , Non-alcoholic Fatty Liver Disease/physiopathology , Red Meat , Risk Assessment/ethnology , Risk Assessment/statistics & numerical data , Risk Factors , United States/epidemiologyABSTRACT
BACKGROUND: Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW). METHODS: We used multivariable Cox regression to assess whether this "Hispanic paradox" applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database. RESULTS: Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease. CONCLUSIONS: Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.
Subject(s)
Hispanic or Latino/statistics & numerical data , Liver Cirrhosis/ethnology , Population Surveillance , Registries , Risk Assessment/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Socioeconomic Factors , Survival Rate/trends , United States/epidemiologyABSTRACT
Sonazoid is a commonly used contrast agent for characterizing liver tumors in ultrasonography (US). We performed flash imaging in the post-vascular phase of contrast-enhanced US (CEUS) to investigate associations between collapse of Sonazoid microbubbles (MB) and progression of liver disease. This study enrolled 409 patients (205 men, 204 women) with hepatitis C virus-related liver disease (CLD) between 2007 and 2017 (mean age 60 ± 14 y; range 20-90 y). In the post-vascular phase, 10 min after administering Sonazoid, flash imaging was performed to burst MB in the liver parenchyma; the range of bubble destruction was measured from the surface of the liver. The range of bubble destruction, stage of fibrosis, shear wave velocity (Vs), serologic markers and fibrosis-4 (FIB4) index were analyzed in 259 patients who underwent liver biopsy. Fibrosis stage was F0-1 in 108 patients, F2 in 73, F3 in 38 and F4 in 40. In 150 patients with cirrhosis, diagnosis was made based on imaging findings. The range of bubble destruction was 42.0 ± 10.4 mm in F0-1 patients, 42.9 ± 13.2 mm in F2, 51.5 ± 15.9 mm in F3 and 55.4 ± 17.3 mm in F4 and was significantly increased according to progression of fibrosis staging. The range of bubble destruction was positively correlated with Vs (râ¯=â¯0.34; p < 0.01), total bilirubin (râ¯=â¯0.25; p < 0.01) and FIB4 index (râ¯=â¯0.38; p < 0.01). In contrast, the range of bubble destruction was negatively correlated with serum levels of albumin (râ¯=â¯-0.34; p < 0.01), platelet count (râ¯=â¯-0.35; p < 0.01) and prothrombin time (râ¯=â¯-0.36; p < 0.01). The results indicated that flash imaging in the post-vascular phase of CEUS was a non-invasive assessment and could predict disease progression in patients with CLD.
Subject(s)
Contrast Media , Disease Progression , Hepatitis C, Chronic/complications , Image Enhancement/methods , Liver Cirrhosis/diagnostic imaging , Ultrasonography/methods , Adult , Aged , Aged, 80 and over , Female , Ferric Compounds , Humans , Iron , Liver/diagnostic imaging , Liver Cirrhosis/ethnology , Male , Microbubbles , Middle Aged , Oxides , ROC Curve , Severity of Illness Index , Young AdultABSTRACT
BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample. METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease. The presence and absence of advanced fibrosis in NAFLD was determined by the NAFLD fibrosis score, FIB-4 score, and aspartate aminotransferase-to-platelet ratio index. RESULTS: The prevalence of NAFLD-related advanced fibrosis increased from 2.6% [95% confidence interval (CI) 2.1-3.1] in 2005-2008 and 4.4% (95% CI 3.7-5.1) in 2009-2012, to 5.0% (95% CI 4.2-5.9) in 2013-2016 using HSI as the NAFLD prediction model; and from 3.3% (95% CI 2.5-4.5) in 2005-2008 and 6.4% (95% CI 3.7-5.1) in 2009-2012, to 6.8% (95% 5.3-8.7) in 2013-2016 using USFLI (p < 0.01). A similar trend was observed in entire NHANES cohort regardless of NAFLD status. While the prevalence of advanced fibrosis increased steadily in non-Hispanic whites through the duration of the study, it leveled off during 2013-2016 in non-Hispanic blacks. CONCLUSIONS: Prevalence of advanced fibrosis associated with NAFLD increased steadily from 2005 to 2016. More importantly, race/ethnicity-based temporal differences were noted in the prevalence of NAFLD-related advanced fibrosis during the study.
Subject(s)
Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Liver Cirrhosis/ethnology , Non-alcoholic Fatty Liver Disease/ethnology , White People/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Liver Cirrhosis/etiology , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Nutrition Surveys , Prevalence , Time Factors , United States/epidemiologyABSTRACT
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. METHODS: We utilized NHANES data for 2011-2016. We defined NAFLD using recently derived US-FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non-Hispanic whites. RESULTS: NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non-Hispanic whites. Asian Americans with NAFLD had lower BMI and waist circumference than non-Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR = 2.70, 95% CI: 1.00-7.27). CONCLUSIONS: Asian Americans have lower prevalence of NAFLD than non-Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non-Hispanic Whites.
Subject(s)
Asian/statistics & numerical data , Cardiovascular Diseases/ethnology , Liver Cirrhosis/ethnology , Non-alcoholic Fatty Liver Disease/ethnology , White People/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Diabetes Mellitus, Type 2/ethnology , Female , Humans , Liver Cirrhosis/etiology , Logistic Models , Male , Middle Aged , Nutrition Surveys , Obesity/ethnology , Prevalence , Risk Factors , Smoking/ethnology , United States/epidemiology , Young AdultABSTRACT
OBJECTIVE: Congenital hepatic fibrosis (CHF) is a developmental disorder of the portobiliary system characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. The aim of our study was to identify the disease-causing gene of a Chinese family with CHF. PATIENTS AND METHODS: Whole-exome sequencing was performed in the family with CHF and variants were confirmed by Sanger sequencing. Online bioinformatics tools were used to evaluate the pathogenicity of the missense variants. Liver specimens were reviewed to confirm the histopathological diagnosis. RESULTS: The compound heterozygous variants c.7994T>C, p.(Leu2665Pro) and c.8518C>T, p.(Arg2840Cys) in PKHD1 were identified in a Chinese family with CHF by whole-exome sequencing. Liver histomorphology was reviewed to confirm the diagnosis of CHF. CONCLUSION: We have identified variations in PKHD1 in a Chinese family with CHF. Our study extends the mutation spectrum of CHF and provides information for genetic counseling of patients' family members.
Subject(s)
Genetic Diseases, Inborn/genetics , Liver Cirrhosis/genetics , Mutation, Missense , Receptors, Cell Surface/genetics , Asian People/genetics , Biopsy , Child , China/epidemiology , Computational Biology , DNA Mutational Analysis , Female , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/ethnology , Genetic Diseases, Inborn/therapy , Genetic Predisposition to Disease , Heredity , Heterozygote , Humans , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/ethnology , Liver Cirrhosis/therapy , Male , Pedigree , Phenotype , Tomography, X-Ray Computed , Exome Sequencing , Young AdultABSTRACT
BACKGROUND & AIMS: Advanced liver disease, which includes fibrosis and cirrhosis, has been reported to be more prevalent in Hispanics patients at the time of diagnosis of chronic hepatitis C virus (HCV) infection than non-Hispanic black or non-Hispanic white patients. We performed a propensity score-matched analysis to determine whether metabolic risk factors contribute to this disparity. METHODS: We collected data from persons with 748 HCV infection (22% Hispanic, 53% non-Hispanic black, and 26% non-Hispanic white; 23% with advanced liver disease), born from 1945 through 1965, diagnosed at 6 health care systems in Texas. Advanced liver disease was defined as a FIB-4 index score above 3.25. We examined the association between advanced liver disease and race or ethnicity, metabolic risk (based on diabetes mellitus and body mass index [BMI]) and heavy alcohol use in propensity score-matched analyses. RESULTS: In propensity-score matched models, among those who were obese (BMI ≥30) with a diagnosis of diabetes, the adjusted odds ratio of advanced liver disease for Hispanics vs non-Hispanic black was 7.89 (95% CI, 3.66-17.01) and adjusted odds ratio = 12.49 (95% CI, 3.24-48.18) for Hispanic vs non-Hispanic white patients (both P < .001). CONCLUSIONS: HCV-infected Hispanics with obesity and diabetes have a far higher risk for advanced liver disease than other racial or ethnic groups. These findings highlight the need for HCV treatment and management of probable concurrent fatty liver disease. Even after we accounted for metabolic risk factors, Hispanics were still at higher risk for advanced liver disease, indicating the potential involvement of other factors such as genetic variants.
Subject(s)
Hepatitis C, Chronic/diagnosis , Hispanic or Latino , Liver Cirrhosis/ethnology , Liver Function Tests/methods , Obesity/complications , Risk Assessment/methods , Body Mass Index , Female , Follow-Up Studies , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/ethnology , Humans , Incidence , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Male , Middle Aged , Obesity/ethnology , Prevalence , Retrospective Studies , United States/epidemiologyABSTRACT
Worldwide, â¼184 million people have chronic hepatitis C virus (HCV) infection.1 Persistent racial disparities in outcomes are observed among HCV-infected patients. Hispanic patients with chronic HCV are more likely than non-Hispanic white (NHW) patients to develop advanced hepatic fibrosis and inflammation.2,3 Conversely, black patients with HCV infection are at lowest risk. The factors that contribute to this racial disparity are multifactorial, including lifestyle, genetics, and medical care. Limited data in other diseases suggest that genetic ancestry determined using ancestry-informative markers (AIMs) may help explain racial and ethnic differences in disease risk or severity.4 AIMs are sets of single-nucleotide polymorphisms (SNPs) that determine a person's ancestral continent of origin and the genetic ancestry proportions assigned to each individual serves as a proxy for his or her genetic ancestral background. We examined the risk of hepatic fibrosis and inflammation in HCV-infected patients according to both genetic ancestry and self-reported race/ethnicity.
Subject(s)
Black People/genetics , Hepatitis C, Chronic/complications , Inflammation/genetics , Liver Cirrhosis/genetics , Mexican Americans/genetics , White People/genetics , Adult , Black or African American/genetics , Aged , Female , Hispanic or Latino/genetics , Hospitals, Veterans , Humans , Inflammation/ethnology , Inflammation/etiology , Liver Cirrhosis/ethnology , Liver Cirrhosis/etiology , Male , Middle Aged , Polymorphism, Single Nucleotide , Principal Component Analysis , Self Report , Severity of Illness Index , VeteransABSTRACT
Objective: To evaluate the incidence, and the characteristics of organ failure in relationship to prognosis in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) patients using chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score for judgments of clinical treatment and prognosis. Methods: Clinical data of 316 patients who were diagnosed as HBV-ACLF during hospitalization from February 2015 to February 2016 were retrospectively analyzed. Intrahepatic and extrahepatic organ failures were assessed according to CLIF-SOFA score, and the relationship between clinical characteristics and prognosis was analyzed. Continuity variables were analyzed by analysis of variance, or Kruskal-Wallis H test. Comparison of the categorical data were done using χ (2) or Fisher's exact test, and the predictive efficacy of various prognostic scores was compared using the area under the receiver operating characteristic curve (AUROC) and Z-test. Results: Of 316 cases (87.3% men) of HBV-ACLF, the mean age was (45 ± 11) years old. 78.8% of patients with underlying liver disease had hepatitis B virus induced cirrhosis. Mortality rates in patients without liver transplantation at 28 days, 90 days and 180 days were 20.5% (63/307), 36.7% (110/300) and 39.2% (116/296), respectively. According to the CLIF-SOFA score, 89.9% (284 patients) had organ failure at baseline, of which 97.5% had liver failure (Total bilirubin ≥ 12 mg/dl) and only 2.5% had coagulation, kidney, circulation or respiratory failure without liver failure. Besides liver failure, the incidence of extrahepatic organ failure was coagulation (23.1%), kidney (5.7%), brain (3.8%), circulation (1.3%) and respiratory failure (0.3%). With increasing number of organ failure, the mortality rate of two and three or more organ failures were 69.6% and 69.2%, respectively, which was significantly higher than that of single organ failure and non-organ failure patients (27% and 6.9%, respectively; P < 0.001). Liver failure with coagulation failure (International normalized ratio≥2.5 or platelet count≤20×10(9)/L) had worst prognosis with a mortality rate of up to 75% at 90 days. Conclusion: According to the CLIF-SOFA score, the main organ failure in patients with HBV-ACLF in China is liver failure. The mortality rate in patients with two or more organ failures is as high as 70% within 3 months. Therefore, timely manner liver transplantation should be considered.
Subject(s)
Acute-On-Chronic Liver Failure/diagnosis , Hepatitis B virus , Hepatitis B/diagnosis , Liver Cirrhosis/diagnosis , Acute-On-Chronic Liver Failure/complications , Acute-On-Chronic Liver Failure/ethnology , Acute-On-Chronic Liver Failure/mortality , Adult , Asian People , China/epidemiology , Female , Hepatitis B/complications , Hepatitis B/ethnology , Hepatitis B/mortality , Humans , Incidence , Liver Cirrhosis/complications , Liver Cirrhosis/ethnology , Liver Cirrhosis/mortality , Male , Middle Aged , Organ Dysfunction Scores , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.