Association of hepatic steatosis and liver fibrosis with chronic obstructive pulmonary disease among adults.

With high prevalence and substantial mortality, metabolic dysfunction-associated steatotic liver disease and chronic obstructive pulmonary disease (COPD) are significant public health concerns. Utilizing a large, population-based dataset from the National Health and Nutrition Examination Survey, our study probes the relationship between COPD prevalence and hepatic steatosis and fibrosis, as measured by Vibration-Controlled Transient Elastography. We analyzed data from 693 individuals with COPD and 7229 without. Through weighted multivariate logistic regression analysis, a restricted cubic spline curve, and threshold effect analysis, we investigated the correlation between the severity of hepatic steatosis and fibrosis and the presence of COPD. Our findings revealed a positive correlation between the controlled attenuation parameter (CAP) and COPD prevalence [OR = 1.03 (95% CI 1.01, 1.05)], even after multivariate adjustment. Furthermore, we observed a U-shaped association between CAP and COPD, where the inflection point, CAP value of 264.85 dB/m, corresponded to the lowest COPD prevalence. Our study emphasizes a substantial and complex link between hepatic steatosis and COPD. These findings urge healthcare professionals to factor liver health into COPD management and prompt further exploration into the underlying mechanisms. This could pave the way for the development of improved prevention and treatment strategies.

Metabolic dysfunction-associated fatty liver disease increases the risk of complications after radical resection in patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in hepatocellular carcinoma (HCC) patients is increasing, yet its association with postoperative complications of HCC remains unclear. The aim of this study was to investigate the impact of MAFLD on complications after radical resection in HCC patients. METHODS: Patients with HCC who underwent radical resection were included. Patients were stratified into MAFLD group and non-MAFLD group. Clinical features and post-hepatectomy complications were compared between the two groups, and logistic regression analysis was used to determine independent risk factors associated with post-hepatectomy complications. RESULTS: Among the 936 eligible patients with HCC who underwent radical resection, concurrent MAFLD was diagnosed in 201 (21.5%) patients. Compared to the non-MAFLD group, the MAFLD group exhibited a higher incidence of complications, including infectious and major complications after radical resection in HCC patients. The logistic regression analysis found that MAFLD was an independent risk factor for complications, including infectious and major complications in HCC patients following radical resection (OR 1.565, 95%CI 1.109-2.343, P = 0.012; OR 2.092, 95%CI 1.386-3.156, P < 0.001; OR 1.859, 95% CI 1.106-3.124, P = 0.019; respectively). Subgroup analysis of HBV-related HCC patients yielded similar findings, and MAFLD patients with type 2 diabetes mellitus (T2DM) exhibited a higher incidence of postoperative complications compared to those without T2DM (all P < 0.05). CONCLUSIONS: Concurrent MAFLD was associated with an increased incidence of complications after radical resection in patients with HCC, especially MAFLD with T2DM.

Obesity Is Associated with Fatty Liver and Fat Changes in the Kidneys in Humans as Assessed by MRI.

BACKGROUND: Obesity is associated with metabolic syndrome and fat accumulation in various organs such as the liver and the kidneys. Our goal was to assess, using magnetic resonance imaging (MRI) Dual-Echo phase sequencing, the association between liver and kidney fat deposition and their relation to obesity. METHODS: We analyzed MRI scans of individuals who were referred to the Chaim Sheba Medical Center between December 2017 and May 2020 to perform a study for any indication. For each individual, we retrieved from the computerized charts data on sex, and age, weight, height, body mass index (BMI), systolic and diastolic blood pressure (BP), and comorbidities (diabetes mellitus, hypertension, dyslipidemia). RESULTS: We screened MRI studies of 399 subjects with a median age of 51 years, 52.4% of whom were women, and a median BMI 24.6 kg/m2. We diagnosed 18% of the participants with fatty liver and 18.6% with fat accumulation in the kidneys (fatty kidneys). Out of the 67 patients with fatty livers, 23 (34.3%) also had fatty kidneys, whereas among the 315 patients without fatty livers, only 48 patients (15.2%) had fatty kidneys (p < 0.01). In comparison to the patients who did not have a fatty liver or fatty kidneys (n = 267), those who had both (n = 23) were more obese, had higher systolic BP, and were more likely to have diabetes mellitus. In comparison to the patients without a fatty liver, those with fatty livers had an adjusted odds ratio of 2.91 (97.5% CI; 1.61-5.25) to have fatty kidneys. In total, 19.6% of the individuals were obese (BMI ≥ 30), and 26.1% had overweight (25 < BMI < 30). The obese and overweight individuals were older and more likely to have diabetes mellitus and hypertension and had higher rates of fatty livers and fatty kidneys. Fat deposition in both the liver and the kidneys was observed in 15.9% of the obese patients, in 8.3% of the overweight patients, and in none of those with normal weight. Obesity was the only risk factor for fatty kidneys and fatty livers, with an adjusted OR of 6.3 (97.5% CI 2.1-18.6). CONCLUSIONS: Obesity is a major risk factor for developing a fatty liver and fatty kidneys. Individuals with a fatty liver are more likely to have fatty kidneys. MRI is an accurate modality for diagnosing fatty kidneys. Reviewing MRI scans of any indication should include assessment of fat fractions in the kidneys in addition to that of the liver.

Association between serum cotinine and hepatic steatosis and liver fibrosis in adolescent: a population-based study in the United States.

Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12-19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [ß = 0.41 (0.07, 0.76), p = 0.018] and 0.05-2.99 ng/ml [ß = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

Extent to which weight loss contributes to improving metabolic dysfunction-associated and metabolic and alcohol related/associated steatotic liver disease: a study on Japanese participants undergoing health checkups.

Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups. Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves. Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction. Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population.

Associations between serum ferritin baselines and trajectories and the incidence of metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

BACKGROUND AND AIMS: Evidence from prospective cohort studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and longitudinal changes in serum ferritin (SF) still limited. This study aimed to investigate the associations of SF baselines and trajectories with new-onset MASLD and to present a MASLD discriminant model. METHODS: A total of 1895 participants who attended health examinations at least three times in a hospital in Dalian City between 2015 and 2022 were included. The main outcome was the incidence of MASLD. The associations between SF baselines and trajectories with the risk of MASLD were analyzed by Cox proportional hazards regression, restricted cubic spline (RCS) analysis and time-dependent receiver operating characteristic (ROC) curve analysis. In addition, a MASLD discrimination model was established using logistic regression analyses. RESULTS: Among the 1895 participants, 492 developed MASLD during follow-up. Kaplan-Meier analysis indicated that participants in the low-stable trajectory group had a longer MASLD-free time compared with participants in other groups. Compared with those in the low-stable trajectory group, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of new-onset MASLD in the medium-high, high-stable and high-high trajectory groups were 1.54(1.18-2.00), 1.77(1.35-2.32) and 1.55(1.07-2.26), respectively (Ptrend < 0.001). The results were robust in subgroup and sensitivity analyses. Multivariate Cox proportional regression showed that SF was an independent risk factor of MASLD (HR = 1.002, 95%CI: 1.000-1.003, P = 0.003). The restricted cubic spline demonstrated a nonlinear relationship between SF and the risk of MASLD. The 8-variable model had high discriminative performance, good accuracy and clinical effectiveness. The ROC curve results showed that AUC was greater than that of the FLI, HSI and ZJU models (all P < 0.01). CONCLUSIONS: Not only a higher baseline SF but also SF changing trajectory are significantly associated with risk of new-onset MASLD. SF could be a predictor of the occurrence of MASLD.

Liver and cardiovascular disease outcomes in metabolic syndrome and diabetic populations: Bi-directional opportunities to multiply preventive strategies.

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

A prospective study on the prevalence of at-risk MASH in patients with type 2 diabetes mellitus in the United States.

BACKGROUND: There are limited data on the prevalence and treatment of at-risk metabolic dysfunction-associated steatohepatitis (MASH) among patients with type 2 diabetes (T2DM) in the United States. AIM: To estimate the prevalence of at-risk MASH in a prospectively recruited cohort of adults with T2DM using new nomenclature endorsed by multiple societies. METHODS: This prospective study enrolled adults aged ≥50 with T2DM from primary care and endocrinology clinics in southern California from 2016 to 2023. Metabolic dysfunction-associated steatotic liver disease (MASLD) was defined by an magnetic resonance imaging proton density fat fraction ≥5% and at least one metabolic risk factor without any other chronic liver disease or secondary cause for hepatic steatosis. RESULTS: We included 530 adult patients with T2DM. The mean (±SD) age and body mass index (BMI) were 64.4 (±8.1) years and 31.5 (±6.1) kg/m2, respectively. Among patients with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis was 69.6%, 13.6% and 6.8%, respectively. Among patients with co-existing T2DM and obesity, the prevalence of MASLD, at-risk MASH and cirrhosis was 77.8%, 15.9% and 9.0%, respectively, and was higher than in participants without obesity (p < 0.0001, 0.0543 and 0.0128, respectively). CONCLUSION: Among adults aged ≥50 years with T2DM, the prevalence of MASLD, at-risk MASH and cirrhosis is high, posing a significant risk for liver-related morbidity and mortality. Approximately 14% of patients with T2DM may be candidates for pharmacologic therapies specific to MASH-related fibrosis.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

AIMS/HYPOTHESIS: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity. METHODS: A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis. RESULTS: The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03. CONCLUSION: Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma.

OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Overall and Sex-Specific Associations of Serum Lipid-Soluble Micronutrients with Metabolic Dysfunction-Associated Steatotic Liver Disease among Adults in the United States.

This study examined overall and sex-specific associations of serum lipid-soluble micronutrients including α- and γ-tocopherols, 25-hydroxy-vitamin D (25(OH)D), retinol, and six major carotenoids with metabolic dysfunction-associated steatotic lever disease (MASLD) using the 2017-2018 National Health and Nutrition Examination Survey. This analysis included 3956 adults (1991 men, 1965 women) aged ≥ 20 years. Steatotic liver disease was determined through transient elastography examination. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for MASLD associated with micronutrients were estimated using logistic regressions. Higher serum α-tocopherol (highest vs. lowest quartile: OR = 1.53, 95% CI = 1.05-2.22, p = 0.03) and γ-tocopherol (highest vs. lowest quartile: OR = 4.15, 95% CI = 3.00-5.74, p < 0.0001) levels were associated with increased odds of MASLD. Higher serum 25(OH)D levels were associated with reduced odds of MASLD (highest vs. lowest quartile: OR = 0.41, 95% CI = 0.27-0.61, p = 0.0001). Inverse associations with the condition were also observed for carotenoids (α-carotene, ß-carotene, α-cryptoxanthin, ß-cryptoxanthin, combined lutein and zeaxanthin, and lycopene) in the serum (Ps < 0.05). The results were comparable between men and women, except for those on α-tocopherol, for which a positive association was only observed for men (p = 0.01). Our results suggest potential protective associations of serum 25(OH)D and carotenoids with MASLD. The positive associations between tocopherols and MASLD may reflect pathophysiological conditions associated with the condition.

Esteatosis hepática metabólica y nefropatía diabética: una llamada a la acción / Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action

La incidencia y la prevalencia de hígado graso no alcohólico o enfermedad hepática metabólica (EHmet) está en aumento y es mayor en pacientes con diabetes mellitus tipo 2 (DM2). El riesgo cardiovascular y renal está claramente incrementado en estos pacientes, especialmente cuando se desarrolla nefropatía diabética. El eje cardio-reno-hepato-metabólico, conformado por la enfermedad cardiovascular (ECV), la enfermedad renal crónica (ERC), la EHmet y la DM2, tiene una base fisiopatogénica común. La relación clínica entre todos los componentes es inevitable y multidireccional, pudiendo la EHmet preceder al desarrollo de complicaciones cardiovasculares y renales, y también empeorar el pronóstico de las mismas una vez desarrolladas. En esta revisión enfatizamos la importancia de buscar y tratar la EHmet en pacientes con ERC y DM2 con el objetivo de identificar pacientes de mayor riesgo y de mejorar su pronóstico.(AU)

Non-alcoholic fatty liver disease or metabolic-associated fatty liver disease (MAFLD) is a common condition with increasing prevalence and incidence, specially in patients with type 2 diabetes mellitus (DM2). Both cardiovascular and renal disease are clearly increased in these patients, particularly in those with diabetic nephropathy. In the liver–heart–kidney–metabolic axis, the common pathophysiological basis of MAFLD, cardiovascular disease (CVD), chronic kidney disease (CKD), and DM2 is the same. The clinical relationship between all of them is clear and is multidirectional: MAFLD may precede the development of cardiovascular and renal disease, and may also worsen the prognosis of these complications once developed. In this review we emphasize the importance of targeting MAFLD in diabetic kidney disease, with the goal of detecting high-risk patients in order to improve their prognosis.(AU)

Acute cholecystitis, obesity, and steatohepatitis constitute the lethal triad for bile duct injury (BDI) during laparoscopic cholecystectomy.

OBJECTIVE: The most feared complication during laparoscopic cholecystectomy remains a bile duct injury (BDI). Accurately risk-stratifying patients for a BDI remains difficult and imprecise. This study evaluated if the lethal triad of acute cholecystitis, obesity, and steatohepatitis is a prognostic measure for BDI. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry was performed. All laparoscopic cholecystectomy cases within the main NSQIP database for 2012-2019 were queried. Two study cohorts were constructed. One with the lethal triad of acute cholecystitis, BMI ≥ 30, and steatohepatitis. The other cohort did not have the full triad present. Multivariate analysis was performed via logistic regression modeling with calculation of odds ratios (OR) to identify independent factors for BDI. An uncontrolled and controlled propensity score match analysis was performed. RESULTS: A total of 387,501 cases were analyzed. 36,887 cases contained the lethal triad, the remaining 350,614 cases did not have the full triad. 860 BDIs were identified resulting in an overall incidence rate 0.22%. There were 541 BDIs within the lethal triad group with 319 BDIs in the other cohort and an incidence rate of 1.49% vs 0.09% (P < 0.001). Multivariate analysis identified the lethal triad as an independent risk factor for a BDI by over 15-fold (OR 16.35, 95%CI 14.28-18.78, P < 0.0001) on the uncontrolled analysis. For the controlled propensity score match there were 29,803 equivalent pairs identified between the cohorts. The BDI incidence rate remained significantly higher with lethal triad cases at 1.65% vs 0.04% (P < 0.001). The lethal triad was an even more significant independent risk factor for BDI on the controlled analysis (OR 40.13, 95%CI 7.05-356.59, P < 0.0001). CONCLUSIONS: The lethal triad of acute cholecystitis, obesity, and steatohepatitis significantly increases the risk of a BDI. This prognostic measure can help better counsel patients and potentially alter management.

Impact of Longitudinal Alcohol Use Patterns on Long-Term Risk of Cirrhosis Among US Veterans With Steatotic Liver Disease.

BACKGROUND & AIMS: Conflicting data exist on the impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aimed to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among veterans with steatotic liver disease. METHODS: US veterans with steatotic liver disease were identified from January 2010 through December 2022. Alcohol use was assessed using documented Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1-2 for women and 1-3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow-up. RESULTS: There were 1,156,189 veterans with steatotic liver disease identified (54.2% no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have a 43% higher incidence of cirrhosis compared with patients reporting no alcohol use. Compared with patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow-up experienced a 39% reduction in long-term risk of cirrhosis (hazard ratio, 0.61; 95% CI, 0.45-0.83; P < .01). CONCLUSIONS: One in 9 veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared with no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease.

Prevalence and risk factors of metabolic dysfunction-associated steatotic liver disease in south Central Uganda: A cross-sectional survey.

BACKGROUND: Despite numerous risk factors and serious consequences, little is known about metabolic dysfunction-associated steatotic liver disease (MASLD) at population level in Africa. AIM: The aim of the study was to estimate the prevalence and risk factors of MASLD in people living with and without HIV in Uganda. METHODS: We collected data from 37 communities in South Central Uganda between May 2016 and May 2018. We estimated MASLD prevalence using the fatty liver index and advanced liver fibrosis using the dynamic aspartate-to-alanine aminotransferase ratio. We collected additional data on sociodemographics, HIV and cardiovascular disease (CVD) risk factors. We used multivariable logistic regression to determine the association between HIV, CVD risk factors and MASLD. RESULTS: We included 759 people with HIV and 704 HIV-negative participants aged 35-49. MASLD prevalence was 14% in women and 8% in men; advanced liver fibrosis prevalence was estimated to be <1%. MASLD prevalence was more common in women (15% vs. 13%) and men (9% vs. 6%) with HIV. Being female (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.4-3.3) was associated with a higher odds of MASLD after adjustment for confounders; HIV infection was borderline associated with MASLD (OR = 1.4; 95% CI: 1.0-2.0). CONCLUSIONS: In a relatively young cohort in Uganda, 14% of women and 8% of men had MASLD. There was an indication of an association between HIV and MASLD in multivariable analysis. These data are the first to describe the population-level burden of MASLD in sub-Saharan Africa using data from a population-based cohort.

Prevalence of at-risk MASH, MetALD and alcohol-associated steatotic liver disease in the general population.

BACKGROUND: The prevalence of at-risk metabolic dysfunction-associated steatohepatitis (at-risk MASH) has not been systematically assessed. AIM: To delineate the prevalence of at-risk MASH in a large population-based cohort. METHODS: We conducted a cross-sectional analysis of 40,189 patients in the UK Biobank who underwent liver MRI. Hepatic steatosis was determined by proton density fat fraction (PDFF) ≥5%. Based on AASLD criteria, participants were classified as alcohol-associated steatotic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), combined metabolic alcoholic liver disease (MetALD) and at-risk MASH. RESULTS: Among 40,189 patients, 10,886 (27.0%) had a PDFF ≥5%, indicating SLD. Among patients with SLD, 1% had ALD, 89.0% had MASLD, 7.9% had MetALD and 2.2% had at-risk MASH. The at-risk MASH group, which included 0.6% of the general population, had the highest mean liver fat on MRI and the highest BMI. Serum biomarkers highlighted increased inflammation and metabolic changes in at-risk MASH. The prevalence of MASLD was significantly higher among men with a BMI ≥30 kg/m2. Non-obese women showed only a 12% risk of MASLD. Conversely, MetALD had similar prevalence in obese men and women and was absent in non-obese women. CONCLUSIONS: MASLD is prevalent among patients with elevated PDFF on MRI. There are different sex- and BMI-specific prevalence of different steatotic liver disorders. At-risk MASH demonstrates the most severe metabolic and inflammatory profiles. This study provides novel estimates for the at-risk MASH population that will be eligible for treatment with pharmacologic therapy when approved by regulatory authorities.

A natural language processing algorithm accurately classifies steatotic liver disease pathology to estimate the risk of cirrhosis.

BACKGROUND: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction-associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by the free-text nature of pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score MASLD histology features. METHODS: From the Mass General Brigham health care system electronic medical record, we identified all patients (1987-2021) with steatosis on index liver biopsy after excluding excess alcohol use and other etiologies of liver disease. An NLP algorithm was constructed in Python to detect steatosis, lobular inflammation, ballooning, and fibrosis stage from pathology free-text and manually validated in >1200 pathology reports. Patients were followed from the index biopsy to incident decompensated liver disease accounting for covariates. RESULTS: The NLP algorithm demonstrated positive and negative predictive values from 93.5% to 100% for all histologic concepts. Among 3134 patients with biopsy-confirmed MASLD followed for 20,604 person-years, rates of the composite endpoint increased monotonically with worsening index fibrosis stage (p for linear trend <0.005). Compared to simple steatosis (incidence rate, 15.06/1000 person-years), the multivariable-adjusted HRs for cirrhosis were 1.04 (0.72-1.5) for metabolic dysfunction-associated steatohepatitis (MASH)/F0, 1.19 (0.92-1.54) for MASH/F1, 1.89 (1.41-2.52) for MASH/F2, and 4.21 (3.26-5.43) for MASH/F3. CONCLUSIONS: The NLP algorithm accurately scores histological features of MASLD from pathology free-text. This algorithm enabled the construction of a large and high-quality MASLD cohort across a multihospital health care system and disclosed an accelerating risk for cirrhosis based on the index MASLD fibrosis stage.

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

AIMS: Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. METHODS: 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). RESULTS: At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. CONCLUSION: This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

Surveillance of the liver in type 2 diabetes: important but unfeasible?

Fatty liver plays a pivotal role in the pathogenesis of the metabolic syndrome and type 2 diabetes. According to an updated classification, any individual with liver steatosis and one or more features of the metabolic syndrome, without excess alcohol consumption or other known causes of steatosis, has metabolic dysfunction-associated steatotic liver disease (MASLD). Up to 60-70% of all individuals with type 2 diabetes have MASLD. However, the prevalence of advanced liver fibrosis in type 2 diabetes remains uncertain, with reported estimates of 10-20% relying on imaging tests and likely overestimating the true prevalence. All stages of MASLD impact prognosis but fibrosis is the best predictor of all-cause and liver-related mortality risk. People with type 2 diabetes face a two- to threefold increase in the risk of liver-related death and hepatocellular carcinoma, with 1.3% progressing to severe liver disease over 7.7 years. Because reliable methods for detecting steatosis are lacking, MASLD mostly remains an incidental finding on imaging. Regardless, several medical societies advocate for universal screening of individuals with type 2 diabetes for advanced fibrosis. Proposed screening pathways involve annual calculation of the Fibrosis-4 (FIB-4) index, followed by a secondary test such as transient elastography (TE) for intermediate-to-high-risk individuals. However, owing to unsatisfactory biomarker specificity, these pathways are expected to channel approximately 40% of all individuals with type 2 diabetes to TE and 20% to tertiary care, with a false discovery rate of up to 80%, raising concerns about feasibility. There is thus an urgent need to develop more effective strategies for surveying the liver in type 2 diabetes. Nonetheless, weight loss through lifestyle changes, pharmacotherapy or bariatric surgery remains the cornerstone of management, proving highly effective not only for metabolic comorbidities but also for MASLD. Emerging evidence suggests that fibrosis biomarkers may serve as tools for risk-based targeting of weight-loss interventions and potentially for monitoring response to therapy.