AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study.

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Glycemic status, insulin resistance, and mortality from lung cancer among individuals with and without diabetes.

BACKGROUND: The effects of glycemic status and insulin resistance on lung cancer remain unclear. We investigated the associations between both glycemic status and insulin resistance, and lung cancer mortality, in a young and middle-aged population with and without diabetes. METHODS: This cohort study involved individuals who participated in routine health examinations. Lung cancer mortality was identified using national death records. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% CIs for lung cancer mortality risk. RESULTS: Among 666,888 individuals (mean age 39.9 ± 10.9 years) followed for 8.3 years (interquartile range, 4.6-12.7), 602 lung cancer deaths occurred. Among individuals without diabetes, the multivariable-adjusted HRs (95% CI) for lung cancer mortality comparing hemoglobin A1c categories (5.7-5.9, 6.0-6.4, and ≥ 6.5% or 39-41, 42-46, and ≥ 48 mmol/mol, respectively) with the reference (< 5.7% or < 39 mmol/mol) were 1.39 (1.13-1.71), 1.72 (1.33-2.20), and 2.22 (1.56-3.17), respectively. Lung cancer mortality was associated with fasting blood glucose categories in a dose-response manner (P for trend = 0.001) and with previously diagnosed diabetes. Insulin resistance (HOMA-IR ≥ 2.5) in individuals without diabetes was also associated with lung cancer mortality (multivariable-adjusted HR, 1.41; 95% CI, 1.13-1.75). These associations remained after adjusting for changing status in glucose, hemoglobin A1c, insulin resistance, smoking status, and other confounders during follow-up as time-varying covariates. CONCLUSIONS: Glycemic status within both diabetes and prediabetes ranges and insulin resistance were independently associated with an increased risk of lung cancer mortality.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Recompensation in MASLD-related cirrhosis via metabolic bariatric surgery.

The prognosis of patients with decompensated cirrhosis is poor, with significantly increased liver-related mortality rates. With the rising tide of decompensated cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD), the role of metabolic bariatric surgery (MBS) in achieving hepatic recompensation is garnering increasing attention. However, the complexity of preoperative assessment, the risk of postoperative disease recurrence, and the potential for patients to experience surgical complications of the MBS present challenges. In this opinion article we analyze the potential of MBS to induce recompensation in MASLD-related cirrhosis, discuss the mechanisms by which MBS may affect recompensation, and compare the characteristics of different MBS procedures; we highlight the therapeutic potential of MBS in MASLD-related cirrhosis recompensation and advocate for research in this complex area.

Liver Fibrosis Assessed Via Noninvasive Tests is Associated With Incident Heart Failure in a General Population Cohort.

BACKGROUND & AIMS: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. RESULTS: A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure. CONCLUSION: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis.

OBJECTIVE: Epidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between primary hypothyroidism and the risk of MASLD. DESIGN: We systematically searched PubMed, Scopus and Web of Science from database inception to 31 January 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging or International Classification of Diseases codes. A meta-analysis was performed using random-effects modelling. RESULTS: We identified 24 cross-sectional and 4 longitudinal studies with aggregate data on ~76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement treatment, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects OR 1.43, 95% CI 1.23 to 1.66; I2=89%). Hypothyroidism was also associated with a substantially higher risk of metabolic dysfunction-associated steatohepatitis or advanced fibrosis (n=5 studies; random-effects OR 2.84, 95% CI 2.07 to 3.90; I2=0%). Meta-analysis of data from four longitudinal studies showed that there was a marginally non-significant association between hypothyroidism and risk of developing MASLD over a median 4.5-year follow-up (random-effects HR 1.39, 95% CI 0.98 to 1.97; I2=85%). Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. CONCLUSION: This large and updated meta-analysis provides evidence that primary hypothyroidism is significantly associated with both an increased presence of and histological severity of MASLD.

MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Relationship between Helicobacter pylori infection and risk of metabolic dysfunction-associated steatotic liver disease: An updated meta-analysis.

BACKGROUND: Recent observational studies examining the association between Helicobacter pylori infection and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) have reported conflicting results. We performed a meta-analysis to quantify the magnitude of the association between H. pylori infection and the risk of MASLD. METHODS: We systematically searched three large electronic databases to identify eligible observational studies (published up to 30 November 2023) in which liver biopsy, imaging methods or blood-based biomarkers/scores were used for diagnosing MASLD. Data from selected studies were extracted, and meta-analysis was performed using common and random-effects modelling. Statistical heterogeneity among published studies, subgroup analyses, meta-regression analyses and publication bias were assessed. RESULTS: A total of 28 observational studies (24 cross-sectional and 4 longitudinal studies) were identified, including 231 291 middle-aged individuals of predominantly Asian ethnicity (~95%). Meta-analysis of cross-sectional studies showed that H. pylori infection was significantly associated with a small increase in the risk of prevalent MASLD (n = 24 studies; random-effects odds ratio 1.11, 95% CI 1.05-1.18; I2 = 63%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was significantly associated with an increased risk of developing incident MASLD over a mean 5-year follow-up (n = 4 studies; random-effects odds ratio 1.20, 95%CI 1.08-1.33; I2 = 44%). Sensitivity analyses did not modify these results. The funnel plot did not reveal any significant publication bias. CONCLUSIONS: H. pylori infection is associated with a mildly increased risk of prevalent and incident MASLD. Further well-designed prospective and mechanistic studies are required to better decipher the complex link between H. pylori infection and the risk of MASLD.

Current status and future trends of the global burden of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

The future of International Classification of Diseases coding in steatotic liver disease: An expert panel Delphi consensus statement.

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

AIMS: To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. MATERIALS AND METHODS: A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. RESULTS: During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. CONCLUSIONS: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

Body composition and metabolism in adults with molecularly-confirmed Silver-Russell syndrome.

CONTEXT: Low birth weight, as seen in Silver-Russell syndrome (SRS), is associated with later cardiometabolic disease. Data on long term outcomes and adult body composition in SRS are limited. OBJECTIVE: To evaluate body composition and metabolic health in adults with SRS. DESIGN: This was an observational study. Body composition and metabolic health were assessed at a single appointment. Individuals with SRS were compared with unaffected men and women (from the Southampton Women's Survey (SWS)). SETTING: Clinical research facilities across the UK. PARTICIPANTS: 25 individuals with molecularly-confirmed SRS aged ≥18 years. MAIN OUTCOME MEASURES: Fat mass, lean mass, bone mineral density (BMD), blood pressure, lipids, and blood glucose were measured. RESULTS: 25 adults with SRS were included (52% female). The median age was 32.9 years (range 22.0-69.7). Fat percentage was greater in the SRS group than the SWS cohort (44.1% vs 30.3%, p<0.001). Fat mass index was similar (9.6 vs 7.8, p=0.3). Lean mass percentage (51.8% vs 66.2%, p<0.001) and lean mass index (13.5 kg/m2 vs 17.3 kg/m2, p<0.001) were lower in the SRS group than the SWS cohort. BMD was lower in the SRS group than the SWS cohort (1.08 vs 1.24, p<0.001) (all median values). Total cholesterol was ≥5mmol/L in 52.0%. Triglyceride levels were ≥1.7mmol/L in 20.8%. Fasting blood glucose levels were ≥6.1mmol/L in 25.0%. Hypertension was present in 33.3%. CONCLUSIONS: Adults with SRS have an unfavourable body composition and predisposition to cardiometabolic disease. These results support the need for a health surveillance strategy to mitigate adverse outcomes.

High-Sensitivity C-Reactive Protein Is Associated With Heart Failure Hospitalization in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease and Normal Left Ventricular Ejection Fraction Undergoing Coronary Angiography.

BACKGROUND: Systemic chronic inflammation plays a role in the pathophysiology of both heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated fatty liver disease. This study aimed to investigate whether serum hs-CRP (high-sensitivity C-reactive protein) levels were associated with the future risk of heart failure (HF) hospitalization in patients with metabolic dysfunction-associated fatty liver disease and a normal left ventricular ejection fraction. METHODS AND RESULTS: The study enrolled consecutive individuals with metabolic dysfunction-associated fatty liver disease and normal left ventricular ejection fraction who underwent coronary angiography for suspected coronary heart disease. The study population was subdivided into non-HF, pre-HFpEF, and HFpEF groups at baseline. The study outcome was time to the first hospitalization for HF. In 10 019 middle-aged individuals (mean age, 63.3±10.6 years; 38.5% women), the prevalence rates of HFpEF and pre-HFpEF were 34.2% and 34.5%, with a median serum hs-CRP level of 4.5 mg/L (interquartile range, 1.9-10 mg/L) and 5.0 mg/L (interquartile range, 2.1-10.1 mg/L), respectively. Serum hs-CRP levels were significantly higher in the pre-HFpEF and HFpEF groups than in the non-HF group. HF hospitalizations occurred in 1942 (19.4%) patients over a median of 3.2 years, with rates of 3.7% in non-HF, 20.8% in pre-HFpEF, and 32.1% in HFpEF, respectively. Cox regression analyses showed that patients in the highest hs-CRP quartile had a ≈4.5-fold increased risk of being hospitalized for HF compared with those in the lowest hs-CRP quartile (adjusted-hazard ratio, 4.42 [95% CI, 3.72-5.25]). CONCLUSIONS: There was a high prevalence of baseline pre-HFpEF and HFpEF in patients with metabolic dysfunction-associated fatty liver disease and suspected coronary heart disease. There was an increased risk of HF hospitalization in those with elevated hs-CRP levels.

MASLD: a systemic metabolic disorder with cardiovascular and malignant complications.

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common chronic liver disease globally and is currently estimated to affect up to 38% of the global adult population. NAFLD is a multisystem disease where systemic insulin resistance and related metabolic dysfunction play a pathogenic role in the development of NAFLD and its most relevant liver-related morbidities (cirrhosis, liver failure and hepatocellular carcinoma) and extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain types of extrahepatic cancers. In 2023, three large multinational liver associations proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) should replace the term NAFLD; the name chosen to replace non-alcoholic steatohepatitis was metabolic dysfunction-associated steatohepatitis (MASH). Emerging epidemiological evidence suggests an excellent concordance rate between NAFLD and MASLD definitions-that is, ~99% of individuals with NAFLD meet MASLD criteria. In this narrative review, we provide an overview of the literature on (a) the recent epidemiological data on MASLD and the risk of developing CVD and malignant complications, (b) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of these extrahepatic complications and (c) the diagnosis and assessment of CVD risk and potential treatments to reduce CVD risk in people with MASLD or MASH.