ABSTRACT
Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.
Subject(s)
Clonal Hematopoiesis , Disease Susceptibility , Hepatitis , Liver Cirrhosis , Animals , Mice , Clonal Hematopoiesis/genetics , Hepatitis/genetics , Inflammation/genetics , Liver Cirrhosis/genetics , Non-alcoholic Fatty Liver Disease/genetics , Odds Ratio , Disease ProgressionABSTRACT
BACKGROUND: Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community. METHODS: Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression. RESULTS: In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated ß per SD, 0.05 [95% CI, 0.01-0.09]; P=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (ß=0.11 [95% CI, 0.07-0.15]; P<0.001), forward pressure wave amplitude (ß=0.05 [95% CI, 0.01-0.09]; P=0.01), and central pulse pressure (ß=0.05 [95% CI, 0.01-0.09]; P=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P<0.001). CONCLUSIONS: Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.
Subject(s)
Aortic Diseases , Arterial Pressure , Fatty Liver , Liver Cirrhosis , Vascular Stiffness , Humans , Male , Female , Middle Aged , Aged , Fatty Liver/complications , Liver Cirrhosis/complications , Longitudinal Studies , Aortic Diseases/complications , Cross-Sectional StudiesABSTRACT
Recent updates in nomenclature and diagnostic criteria encompass the diverse phenotypes associated with steatotic liver disease (SLD).1 These updates aim to reflect the current understanding of SLD, promote disease awareness and research, and reduce stigma. Notably, the term metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as hepatic steatosis with at least 1 of 5 cardiometabolic criteria without any other cause of steatosis. A new category, MetALD, includes those with MASLD and high alcohol intake.1 We aimed to characterize SLD using this nomenclature in the Framingham Heart Study (FHS) and to quantify its association with cardiometabolic risk factors.
ABSTRACT
BACKGROUND AND AIMS: NAFLD strongly associates with cardiovascular disease (CVD) risk factors; however, the association between NAFLD and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality is unclear. APPROACH AND RESULTS: We included 10,040 participants from the Framingham Heart Study, the Coronary Artery Risk Development in Young Adults Study, and the Multi-ethnic Study of Atherosclerosis to assess the longitudinal association between liver fat (defined on CT) and incident CVD, CVD-related mortality, incident cancer, and all-cause mortality. We performed multivariable-adjusted Cox regression models including age, sex, diabetes, systolic blood pressure, alcohol use, smoking, HDL, triglycerides, and body mass index at baseline or time-varying covariates. The average age was 51.3±3.3 years and 50.6% were women. Hepatic steatosis was associated with all-cause mortality after 12.7 years of mean follow-up when adjusting for baseline CVD risk factors, including body mass index (HR: 1.21, 1.04-1.40); however, the results were attenuated when utilizing time-varying covariates. The association between hepatic steatosis and incident CVD was not statistically significant after we accounted for body mass index in models considering baseline covariates or time-varying covariates. We observed no association between hepatic steatosis and CVD-related mortality or incident cancer. CONCLUSIONS: In this large, multicohort study of participants with CT-defined hepatic steatosis, accounting for change in CVD risk factors over time attenuated associations between liver fat and overall mortality or incident CVD. Our work highlights the need to consider concurrent cardiometabolic disease when determining associations between NAFLD and CVD and mortality outcomes.
Subject(s)
Cardiovascular Diseases , Neoplasms , Non-alcoholic Fatty Liver Disease , Young Adult , Humans , Female , Middle Aged , Male , Non-alcoholic Fatty Liver Disease/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Risk Factors , Longitudinal Studies , Neoplasms/epidemiology , IncidenceABSTRACT
OBJECTIVE: Clinical guidelines have expanded the indications for nonalcoholic fatty liver disease (NAFLD) screening to type 2 diabetes mellitus and obesity, which are conditions common in populations who receive care in urban safety-net settings. This study aimed to evaluate safety-net primary care and endocrinology clinicians' knowledge of NAFLD, determine barriers and facilitators to screening, and examine perspectives on the use of electronic health record tools for risk assessment. METHODS: Sequential explanatory mixed methods using survey and qualitative interviews with primary care, primary care subspecialty, and endocrinology clinicians in an urban safety-net health care system. RESULTS: A total of 109 participants completed the survey (36.5% response rate), and 13 participated in interviews. Most respondents underestimated or did not know the prevalence of NAFLD (68%), did not use the recommended noninvasive tests for risk stratification (65%), and few were comfortable with screening for (27%) or managing (17%) NAFLD. Endocrinologists had greater knowledge of risk factors but lower rates of comfort and more often felt that screening was not their responsibility. The qualitative themes included the following: (1) lack of knowledge about screening, (2) concern for underdiagnosing NAFLD, (3) perception of severity impacts beliefs about screening, (4) screening should occur in primary care but is not normative practice, (5) concerns exist about benefit, (6) competing demands with a complex population hinder screening, and (7) a need for easier ways to integrate screening into practice. CONCLUSION: Knowledge gaps may hamper uptake of new guidelines for NAFLD screening in primary care and endocrinology clinics in an urban safety-net health care system. Implementation strategies focused on training and educating clinicians and informed by behavioral economics may increase screening.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Risk Factors , Obesity/epidemiology , Primary Health Care/methodsABSTRACT
DESCRIPTION: Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals. METHODS: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Lean NAFLD should be diagnosed in individuals with NAFLD and body mass index <25 kg/m2 (non-Asian race) or body mass index <23 kg/m2 (Asian race). BEST PRACTICE ADVICE 2: Lean individuals with NAFLD should be evaluated routinely for comorbid conditions, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. BEST PRACTICE ADVICE 3: Lean individuals with NAFLD should be risk stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis. BEST PRACTICE ADVICE 4: Lean individuals in the general population should not undergo routine screening for NAFLD; however, screening should be considered for individuals older than 40 years with type 2 diabetes mellitus. BEST PRACTICE ADVICE 5: NAFLD should be considered in lean individuals with metabolic diseases (such as type 2 diabetes mellitus, dyslipidemia, and hypertension), elevated liver biochemical tests, or incidentally noted hepatic steatosis. BEST PRACTICE ADVICE 6: Clinicians should query patients routinely regarding alcohol consumption patterns in all patients with lean NAFLD. BEST PRACTICE ADVICE 7: In patients with lean NAFLD, other causes of liver disease should be ruled out, including other causes of fatty liver, such as HIV, lipodystrophy, lysosomal acid lipase deficiency, familial hypobetalipoproteinemia, and medication-induced hepatic steatosis (methotrexate, amiodarone, tamoxifen, and steroids). BEST PRACTICE ADVICE 8: Current evidence is inadequate to support routine testing for genetic variants in patients with lean NAFLD. BEST PRACTICE ADVICE 9: Liver biopsy, as the reference standard, should be considered if there is uncertainty regarding contributing causes of liver injury and/or the stage of liver fibrosis. BEST PRACTICE ADVICE 10: Serum indices (NAFLD fibrosis score and Fibrosis-4 score) and imaging techniques (transient elastography and magnetic resonance elastography) may be used as alternatives to liver biopsy for fibrosis staging and patient follow-up. These tests can be performed at the time of diagnosis and repeated at intervals of 6 months to 2 years, depending on fibrosis stage and the patient's response to intervention. BEST PRACTICE ADVICE 11: If noninvasive tests (eg, Fibrosis-4 and NAFLD fibrosis score) are indeterminate, a second noninvasive test (eg, transient elastography or magnetic resonance elastography) should be performed to confirm the stage and prognosis of NAFLD. BEST PRACTICE ADVICE 12: In lean patients with NAFLD, lifestyle intervention, including exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to target a modest weight loss of 3%-5% is suggested. BEST PRACTICE ADVICE 13: Administration of vitamin E may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis, but without type 2 diabetes mellitus or cirrhosis. Oral pioglitazone 30 mg daily may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis. BEST PRACTICE ADVICE 14: The therapeutic role of glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors in the management of lean NAFLD is not fully defined and requires further investigation. BEST PRACTICE ADVICE 15: Hepatocellular carcinoma surveillance with abdominal ultrasound with or without serum α-fetoprotein twice per year is suggested in patients with lean NAFLD and clinical markers compatible with liver cirrhosis.
Subject(s)
Non-alcoholic Fatty Liver Disease , Thinness , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/therapy , Thinness/epidemiologyABSTRACT
BACKGROUND AND AIMS: While heavy alcohol use consistently associates with liver disease, the effects of nonheavy alcohol consumption are less understood. We aimed to investigate the relationship between nonheavy alcohol use and chronic liver disease. METHODS: This cross-sectional study included 2629 current drinkers in the Framingham Heart Study who completed alcohol use questionnaires and transient elastography. We defined fibrosis as liver stiffness measurement (LSM) ≥8.2 kPa. We defined at-risk nonalcoholic steatohepatitis (NASH) as FibroScan-aspartate aminotransferase (FAST) score >0.35 (90% sensitivity) or ≥0.67 (90% specificity). We performed logistic regression to investigate associations of alcohol use measures with fibrosis and NASH, adjusting for sociodemographic and metabolic factors. Subgroup analysis excluded heavy drinkers (>14 drinks per week for women or >21 for men). RESULTS: In this sample (mean age 54.4 ± 8.9 years, 53.3% women), mean LSM was 5.6 ± 3.4 kPa, 8.2% had fibrosis, 1.9% had NASH by FAST ≥0.67, and 12.4% had NASH by FAST >0.35. Participants drank 6.2 ± 7.4 drinks per week. Total drinks per week and frequency of drinking associated with increased odds of fibrosis (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.04-1.33; and aOR, 1.08; 95% CI, 1.01-1.16, respectively). Risky weekly drinking, present in 17.4%, also associated with fibrosis (aOR, 1.49; 95% CI, 1.03-2.14). After excluding 158 heavy drinkers, total drinks per week remained associated with fibrosis (aOR, 1.16; 95% CI, 1.001-1.35). Multiple alcohol use measures positively associated with FAST >0.35. CONCLUSIONS: In this community cohort, we demonstrate that nonheavy alcohol use associates with fibrosis and NASH, after adjustment for metabolic factors. Longitudinal studies are needed to determine the benefits of moderating alcohol use to reduce liver-related morbidity and mortality.
Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Humans , Female , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Cross-Sectional Studies , Liver Cirrhosis/etiology , Liver Cirrhosis/complications , Longitudinal Studies , Liver/diagnostic imaging , Liver/pathology , Alcohol Drinking/adverse effects , FibrosisABSTRACT
BACKGROUND: Higher diet quality is associated with a lower risk of NAFLD. OBJECTIVES: We examined the relationship between diet quality and hepatic fibrosis. METHODS: We analyzed cross-sectional associations between 3 a priori diet quality scores-the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and a modified Mediterranean-style Diet Score (MDS)-and hepatic fat [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)] measured by vibration-controlled transient elastography (VCTE) in 2532 Framingham Heart Study (FHS) participants and 3295 participants of the National Health and Nutrition Examination Survey (NHANES). RESULTS: Higher diet quality scores were associated with lower LSM in both FHS and NHANES after adjustment for demographic and lifestyle factors. Additional adjustment for CAP or BMI attenuated the observed associations. Association strength was similar across all 3 diet quality scores. Fixed-effect meta-analysis demonstrated that, under CAP-adjusted models, the LSM decreases associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2% (95% CI: 0.7%, 3.3%; P = 0.002), 2% (95% CI: 0.7%, 3.3%; P = 0.003), and 1.7% (95% CI: 0.7%, 2.6%; P = 0.001), respectively, whereas in the meta-analysis of BMI-adjusted models, LSM reductions associated with 1-SD increase of the DASH, AHEI, and MDS scores were 2.2% (95% CI: -0.1%, 2.2%; P = 0.07), 1.5% (95% CI: 0.3%, 2.7%; P = 0.02), and 0.9 (95% CI: -0.1%, 1.9%; P = 0.07), respectively. CONCLUSIONS: We demonstrated associations of higher diet quality with favorable hepatic fat and fibrosis measures. Our data suggest that a healthy diet may reduce the likelihood of obesity and hepatic steatosis as well as the progression of steatosis to fibrosis.
Subject(s)
Diet, Mediterranean , Non-alcoholic Fatty Liver Disease , Humans , Diet, Healthy , Nutrition Surveys , Cross-Sectional Studies , Liver Cirrhosis/prevention & control , Liver Cirrhosis/complications , Liver/pathology , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/prevention & controlABSTRACT
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with sugar-sweetened beverage (SSB) consumption in cross-sectional studies. In a prospective cohort, we examined the association of beverage consumption (SSB and diet soda) with incident NAFLD and changes in hepatic fat in the Framingham Heart Study (FHS). METHODS: We conducted a prospective observational study of participants from the FHS Third Generation and Offspring cohorts who participated in computed tomography sub-studies. Participants were classified according to their average SSB or diet soda consumption, which was derived from baseline and follow-up food frequency questionnaires: non-consumers (0-<1/month), occasional consumers (1/month-<1/week), and frequent consumers (≥1/week-≥1/day). Hepatic fat was quantified by the liver fat attenuation measurements on computed tomography scan. The primary dependent variable was incident NAFLD; secondarily, we investigated change in liver fat. RESULTS: The cohorts included 691 Offspring (mean age, 62.8 ± 8.2 years; 57.7% women) and 945 Third Generation participants (mean age, 48.4 ± 6.3 years; 46.6% women). In the Offspring cohort, there was a dose-response relationship with SSB consumption and incident NAFLD. Frequent SSB consumers had 2.53 times increased odds of incident NAFLD compared with non-consumers (95% confidence interval, 1.36-4.7) after multivariable analysis. For Offspring cohort participants, occasional and frequent consumers of SSB had a more adverse increase in liver fat compared with non-consumers. CONCLUSIONS: Higher average SSB intake is associated with increase in liver fat over 6 years of follow-up and increased odds of incident NAFLD especially among the older cohort, whereas no consistent association was observed for the younger Third Generation cohort.
Subject(s)
Non-alcoholic Fatty Liver Disease , Sugar-Sweetened Beverages , Female , Humans , Middle Aged , Aged , Adult , Male , Sugar-Sweetened Beverages/adverse effects , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Prospective Studies , Cross-Sectional Studies , Longitudinal Studies , Diet/adverse effectsABSTRACT
BACKGROUND AND AIMS: NAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration-controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver-related and all-cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear. APPROACH AND RESULTS: We performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3 ± 9.1 years) presenting for a routine study visit. We performed multivariable-adjusted logistic regression models to determine the association between LSM and obesity-related, vascular-related, glucose-related, and cholesterol-related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP ≥ 290 dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM ≥ 8.2 kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35-2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10-2.01), diabetes (OR, 2.67; 95% CI, 1.21-3.75), hypertension (OR, 1.52; 95% CI, 1.15-1.99), and low high-density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09-1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP. CONCLUSIONS: In our community-based cohort, VCTE-defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high-density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events.
Subject(s)
Cardiometabolic Risk Factors , Cardiovascular Diseases/epidemiology , Liver Cirrhosis/epidemiology , Metabolic Syndrome/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology , Cardiovascular Diseases/etiology , Elasticity Imaging Techniques , Female , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Longitudinal Studies , Male , Metabolic Syndrome/etiology , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , PrevalenceABSTRACT
BACKGROUND AND AIMS: Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. APPROACH AND RESULTS: Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. CONCLUSIONS: This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.
Subject(s)
Biomedical Research/standards , Clinical Coding/standards , Consensus , Electronic Health Records/standards , Non-alcoholic Fatty Liver Disease/diagnosis , Humans , Non-alcoholic Fatty Liver Disease/therapy , Reference StandardsABSTRACT
OBJECTIVES: To provide a standard for total abdominal muscle mass (TAM) quantification on computed tomography (CT) and investigate its association with cardiovascular risk in a primary prevention setting. METHODS: We included 3016 Framingham Heart Study participants free of cardiovascular disease (CVD) who underwent abdominal CT between 2002 and 2005. On a single CT slice at the level of L3/L4, we segmented (1) TAM-Area, (2) TAM-Index (= TAM-Area/height) and, (3) TAM-Fraction (= TAM-Area/total cross-sectional CT-area). We tested the association of these muscle mass measures with prevalent and incident cardiometabolic risk factors and incident CVD events during a follow-up of 11.0 ± 2.7 years. RESULTS: In this community-based sample (49% women, mean age: 50.0 ± 10.0 years), all muscle quantity measures were significantly associated with prevalent and incident cardiometabolic risk factors and CVD events. However, only TAM-Fraction remained significantly associated with key outcomes (e.g., adj. OR 0.68 [0.55, 0.84] and HR 0.73 [0.57, 0.92] for incident hypertension and CVD events, respectively) after adjustment for age, sex, body mass index, and waist circumference. Moreover, only higher TAM-Fraction was associated with a lower risk (e.g., adj. OR: 0.56 [0.36-0.89] for incident diabetes versus TAM-Area: adj. OR 1.26 [0.79-2.01] and TAM-Index: 1.09 [0.75-1.58]). CONCLUSION: TAM-Fraction on a single CT slice at L3/L4 is a novel body composition marker of cardiometabolic risk in a primary prevention setting that has the potential to improve risk stratification beyond traditional measures of obesity. KEY POINTS: ⢠In this analysis of the Framingham Heart Study (n = 3016), TAM-F on a single slice CT was more closely associated with prevalent and incident cardiometabolic risk factors as compared to TAM alone or TAM indexed to body surface area. ⢠TAM-F on a single abdominal CT slice at the level of L3/L4 could serve as a standard measure of muscle mass and improve risk prediction.
Subject(s)
Cardiovascular Diseases , Tomography, X-Ray Computed , Abdominal Muscles , Adult , Body Mass Index , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Risk FactorsABSTRACT
INTRODUCTION: The proportion of women editorial board members and authors of editorials in major gastroenterology journals is not known. METHODS: We determined the sex of editorial board members (n = 2,282) and authors of editorials (n = 1,705) across 6 journals from 1985 to 2020 at 5-year intervals. RESULTS: The proportion of women editorial board members increased from 2.9% in 1985 to 19.8% in 2020 (P < 0.0001) and women authors of editorials increased from 0% in 1985 to 22.2% in 2020 (P < 0.0001). DISCUSSION: The proportion of women represented over time has improved, but opportunities likely exist to improve further.
Subject(s)
Authorship , Gastroenterology , Periodicals as Topic , Bibliometrics , Female , Humans , WomenABSTRACT
BACKGROUND AND AIMS: Portal pressure can be used to identify patients with chronic liver disease who have progressed to cirrhosis. Portal pressure can also provide accurate prognostication for patients with cirrhosis. However, there are no practical means for assessment of portal pressure. Although it is well established that the gastric mucosal blood supply increases in patients with cirrhosis, this has been difficult to quantify reproducibly. Our group has developed a novel spectroscopic technology called spatially resolved subdiffuse reflectance spectroscopy (SRSRS), which enables quantification of mucosal microcirculation. We aim to ascertain if quantification of the gastric mucosal microcirculation with SRSRS correlates with clinical evidence of portal hypertension. METHODS: Patients undergoing EGD for clinical indications had 10 measurements taken in the endoscopically normal gastric fundus via SRSRS probe to assess the microcirculation. Cases were defined as patients with cirrhosis (n = 18), and controls were those without evidence of liver disease (n = 18); this was corroborated with transient elastography. RESULTS: The blood volume fraction (P = .06) and subdiffuse reflectance (P = .02) from a shallow depth in the gastric fundus were higher in patients with cirrhosis than those without. These markers were combined to yield an overall optical marker that can differentiate patients with cirrhosis from controls with a sensitivity of 72% and specificity of 94% (area under receiver operating curve, 0.82). CONCLUSIONS: Spectroscopic quantification of gastric fundal mucosal microcirculation is a promising surrogate of clinical correlates of portal hypertension. This approach may represent a less-intrusive surrogate biomarker for liver disease prognostication and potentially response to therapy.
Subject(s)
Hypertension, Portal , Biomarkers , Gastric Mucosa , Humans , Hypertension, Portal/diagnostic imaging , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Microcirculation , Spectrum AnalysisABSTRACT
BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. RESULTS: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. CONCLUSION: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals.
Subject(s)
Communicable Diseases/epidemiology , End Stage Liver Disease/epidemiology , Length of Stay/trends , Liver Cirrhosis/epidemiology , Safety-net Providers/trends , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Communicable Diseases/diagnosis , Communicable Diseases/drug therapy , Cross Infection/diagnosis , Cross Infection/drug therapy , Cross Infection/epidemiology , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/physiology , End Stage Liver Disease/diagnosis , End Stage Liver Disease/drug therapy , Female , Hospital Mortality/trends , Hospitals, Urban/trends , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Many individuals presumed to have nonalcoholic fatty liver disease (NAFLD) consume moderate amounts of alcohol. Little is known about patterns of alcohol use in patients with NAFLD or how drinking behaviors affect liver fat. METHODS: We conducted a cross-sectional study of 2475 participants of the Framingham Heart Study with hepatic steatosis, as determined by computed tomography. We performed multivariable-adjusted logistic regression models to evaluate the association between alcohol drinking patterns and hepatic steatosis. Models were adjusted for sociodemographic factors, diet, and the components of the metabolic syndrome. We excluded heavy alcohol users, defined as women who consume more than 14 alcohol drinks per week and men who consume more than 21 alcohol drinks per week. RESULTS: In our sample (mean age, 49.8 ± 10.2 y; 50.3% women), the prevalence of hepatic steatosis was 17.5%. The total number of alcohol drinks per week and the maximum drinks consumed per drinking day each were associated with hepatic steatosis (adjusted odds ratio [aOR], 1.15; 95% CI, 1.02-1.29 and aOR 1.15; 95% CI, 1.02-1.30). Binge drinking occurred in 25.4% of individuals with presumed NAFLD and was associated with an increased odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98) among alcohol users. In a beverage-specific analysis, alcohol use patterns were associated with hepatic steatosis among beer drinkers, but not among wine drinkers. CONCLUSIONS: In a cross-sectional study of participants of the Framingham Heart Study with hepatic steatosis, we observed an association between alcohol use and liver fat, even after excluding heavy alcohol users from our analysis. Alcohol use therefore appears to be a risk factor for NAFLD. Prospective studies are needed to validate these findings and determine if alcohol use should be a focus for research, prevention, and treatment of presumed NAFLD.
Subject(s)
Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Risk FactorsABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is associated with increased liver- and cardiovascular disease (CVD)-related morbidity and mortality. In cross-sectional analyses, NAFLD clusters with several cardiometabolic traits including obesity,1,2 hypertension,3 diabetes,1 and dyslipidemia.3 However, liver fat is dynamic and changes over time. Aside from limited prior studies evaluating diet or exercise interventions, little is known about the association between changes in liver fat and the incidence of CVD risk factors. Additionally, previous studies often have limited follow-up; evaluate only select populations, such as individuals with obesity4,5 or diabetes6-8; and may not account for changes in weight or body mass index (BMI). The aim of the present study was to examine, in a longitudinal cohort, the natural history of liver fat change and the association with the incidence of multiple CVD risk factors.
Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Heart Disease Risk Factors , Humans , Liver , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Risk FactorsABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease is associated with cardiovascular risk factors in cross-sectional analyses. However, less is known about how changes in liver fat associate with the progression of cardiovascular risk factors. METHODS: A substudy (n = 808) drawn from the Framingham Heart Study underwent serial computed tomography scans 6 years apart. We performed multivariable-adjusted regression to determine the association between changes in liver fat and progression of cardiovascular risk factors. RESULTS: Each standard deviation increase in liver fat was associated with adverse progression of systolic blood pressure, diastolic blood pressure, fasting glucose, high-density lipoprotein and log triglycerides. After adjusting for baseline cardiovascular risk, baseline body mass index (BMI), and change in BMI, increasing liver fat was significantly associated with adverse changes in fasting glucose and triglycerides. CONCLUSIONS: In a longitudinal cohort, increasing liver fat over 6 years was associated with progression of cardiovascular risk factors, even after accounting for BMI changes.
Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Blood Glucose , Blood Pressure , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Heart Disease Risk Factors , Humans , Liver/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Risk FactorsABSTRACT
BACKGROUND & AIMS: Non-alcoholic fatty liver disease confers increased risk for cardiovascular disease, including heart failure (HF), for reasons that remain unclear. Possible pathways could involve an association of liver fat with cardiac structural or functional abnormalities even after accounting for body size. METHODS: We analysed N = 2356 Framingham Heart Study participants (age 52 ± 12 years, 52% women) who underwent echocardiography and standardized computed tomography measures of liver fat. RESULTS: In cross-sectional multivariable regression models adjusted for age, gender, cohort and cardiovascular risk factors, liver fat was positively associated with left ventricular (LV) mass (ß = 1.45; 95% confidence interval (CI): 0.01, 2.88), LV wall thickness (ß = 0.01; 95% CI: 0.00, 0.02), mass volume ratio (ß = 0.02; 95% CI 0.01, 0.03), mitral peak velocity (E) (ß = 0.83; 95% CI 0.31, 1.36) and LV filling pressure (E/e' ratio) (ß = 0.16; 95% CI 0.09, 0.23); and inversely associated with global systolic longitudinal strain (ß = 0.20, 95% CI 0.07, 0.33), diastolic annular velocity (e') (ß = -0.12; 95% CI - 0.22, -0.03), and E/A ratio (ß = -0.01; 95% CI - 0.02, -0.00). After additional adjustment for body mass index (BMI), statistical significance was attenuated for all associations except for that of greater liver fat with increased LV filling pressure, a possible precursor to HF (ß = 0.11; 95% CI 0.03, 0.18). CONCLUSION: Increased liver fat was associated with multiple subclinical cardiac dysfunction measures, with most of associations mediated by obesity. Interestingly, the association of liver fat and LV filling pressure was only partially mediated by BMI, suggesting a possible direct effect of liver fat on LV filling pressure. Further confirmatory studies are needed.