Non-contrast Abbreviated MRI for the Detection of Hepatocellular Carcinoma in Patients with LI-RADS LR-3 and LR-4 Observations in MRI.

BACKGROUND AND AIMS: With ultrasound sensitivity limited in hepatocellular carcinoma (HCC) surveillance and few prospective studies on non-contrast abbreviated MRI (NC-AMRI), this study aimed to assess its diagnostic performance in detecting HCC. METHODS: This prospective study involved cirrhotic patients with contrast-enhanced MRI (CE-MRI) Liver Imaging Reporting and Data System (LI-RADS) LR-3 and LR-4 observations detected during HCC surveillance. Patients underwent average three complete CE-MRI rounds at 3-6 months interval, with approximately 12-month follow-up. NC-AMRI included diffusion-weighted(DWI), T2-weighted imaging(T2WI), and T1-weighted imaging(T1WI). NC-AMRI protocol images were analyzed for diagnostic performance, with subgroup analyses. CE-MRI and NC-AMRI images were independently reviewed by two experienced radiologists, with inter-reader agreement assessed with Kappa coefficient. The reference standard was the AASLD-defined presence of arterial hypervascularity and washout during the portal-venous or delayed phases on CE-MRI. RESULTS: In 166 CE-MRI follow-ups of 63 patients (median age: 63 years; 60.3% male, 39.7% female), 12 patients developed HCC, with average size of 19.6 mm. The NC-AMRI (DWI+T2WI+T1WI) showed 91.7% sensitivity (95%CI : 61.5-99.8) and 91.6% specificity (95%CI : 86.0-95.4), area under receiver operating characteristic 0.92 (95%CI : 0.83-1.00). Across different Body Mass Index categories, lesion size, Child-Turcotte-Pugh classes, Albumin-Bilirubin (ALBI) grades, and Model for End-Stage Liver Disease classes, sensitivity remained consistent. However, specificity differed significantly between ALBI grade 1 and 2 (86.7% vs. 98.4%,p = 0.010), and between viral and non-viral cirrhosis (93.8% vs. 80.8%,p = 0.010). CONCLUSIONS: NC-AMRI proved clinically feasible, and exhibits high diagnostic performance in HCC detection. ADVANCES IN KNOWLEDGE: This study highlights efficacy of NC-AMRI in detecting HCC among cirrhotic patients with LR-3 and LR-4 observations, representing significant progress in HCC surveillance.

Global burden of metabolic diseases, 1990-2021.

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex. METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI). RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]). CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.

Resmetirom and Metabolic Dysfunction-Associated Steatohepatitis: Perspectives on Multidisciplinary Management from Global Healthcare Professionals.

PURPOSE OF REVIEW: The approval of resmetirom brings great hope to patients with metabolic dysfunction-associated steatohepatitis (MASH). The purpose of this review is to explore its impact on the global health environment. The implementation of multidisciplinary management MASH is proposed. RECENT FINDINGS: Resmetirom has benefits in the treatment of MASH, and its safety and effectiveness have been studied. The adverse events (AEs) need to be noticed. To improve patient outcomes, a multimodal approach with medication such as resmetirom, combined with metabolic and bariatric surgery (MBS) and lifestyle interventions can be conducted. MASH, a liver disease linked with obesity, is a challenging global healthcare burden compounded by the absence of any approved pharmacotherapy. The recent conditional approval by the Food and Drug Administration (FDA) in the United States of resmetirom, an oral, liver-directed, thyroid hormone receptor beta-selective agonist, marks a significant milestone, offering a treatment option for adults with non-cirrhotic MASH and who have moderate to advanced liver fibrosis. This narrative review discusses the efficacy and safety of resmetirom and its role in the therapeutic landscape of MASH treatment. Despite the promising hepatoprotective effect of resmetirom on histological liver endpoints, its use need further research, particularly regarding ethnic differences, effectiveness and cost-effectiveness, production scalability, social acceptance and accessibility. In addition, integrating resmetirom with other multidisciplinary therapeutic approaches, including lifestyle changes and MBS, might further improve clinical liver-related and cardiometabolic outcomes of individuals with MASH. This review highlights the importance of a comprehensive treatment strategy, supporting continued innovation and collaborative research to refine treatment guidelines and consensus for managing MASH, thereby improving clinical patient outcomes in the growing global epidemic of MASH. Studies done to date have been relatively short and ongoing, the course of the disease is highly variable, the conditions of various patients vary, and given this complex clinical phenotype, it may take many years of clinical trials to show long-term benefits.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

MRI for hepatocellular carcinoma and the role of abbreviated MRI for surveillance of hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) constitutes the majority of liver cancers and significantly impacts global cancer mortality. While ultrasound (US) with or without alpha-fetoprotein is the mainstay for HCC surveillance, its limitations highlight the necessity for more effective surveillance tools. Therefore, this review explores evolving imaging modalities and abbreviated magnetic resonance imaging (MRI) (AMRI) protocols as promising alternatives, addressing challenges in HCC surveillance. AREAS COVERED: This comprehensive review delves into the evaluation and challenges of HCC surveillance tools, focusing on non-contrast abbreviated MRI (NC-AMRI) and contrast-enhanced abbreviated MRI protocols. It covers the implementation of AMRI for HCC surveillance, patient preferences, adherence, and strategies for optimizing cost-effectiveness. Additionally, the article provides insights into prospects for HCC surveillance by summarizing meta-analyses, prospective studies, and ongoing clinical trials evaluating AMRI protocols. EXPERT OPINION: The opinions underscore the transformative impact of AMRI on HCC surveillance, especially in overcoming US limitations. Promising results from NC-AMRI protocols indicate its potential for high-risk patient surveillance, though prospective studies in true surveillance settings are essential for validation. Future research should prioritize risk-stratified AMRI protocols and address cost-effectiveness for broader clinical implementation, alongside comparative analyses with US for optimal surveillance strategies.

Sequential SAFE Score and Transient Elastography for Detecting Significant Fibrosis in Asian Patients with MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD),1 represents a global public health issue. Fibrosis stage is the most important risk for long-term undesirable outcomes.2,3 From recent meta-analyses, all-cause and liver-related mortalities significantly increased from fibrosis stage 2 (significant fibrosis; F≥2) onward.4,5 In primary care setting, those with F≥2 should be referred to hepatologists; therefore, noninvasive tests to stratify risk of patients with MASLD are crucial. Steatosis-associated fibrosis estimator (SAFE) was recently developed to predict F≥2.6 SAFE has been externally validated and outperformed fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS).7,8 Recently, international guidelines proposed sequential diagnostic steps, initially using FIB-4 and then transient elastography (TE) in non-low-risk patients.9,10 However, the guidelines focused on identifying advanced fibrosis (F≥3), which might be too late. This study aimed to compare the performance among SAFE, FIB-4, and NFS, and evaluate SAFE-TE sequential approach. We hypothesized that by initially using SAFE, the proportion of patients misclassified as low risk despite already having F≥2 could be diminished.

Development of a diagnostic support system for the fibrosis of nonalcoholic fatty liver disease using artificial intelligence and deep learning.

Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI-PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI-PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p-value <0.001), which subgroup analysis of significant fibrosis (Metavir score F2-F4) and nonsignificant fibrosis (Metavir score F0-F1) demonstrated substantial correlated results (agreement = 80%, kappa = 0.61, p-value <0.001), corresponding with the correlation of advanced fibrosis (Metavir score F3-F4) and nonadvanced fibrosis groups (Metavir score F0-F2), (agreement = 89%, kappa = 0.74, p-value <0.001). SMART AI-PATHO, the first pivotal artificially intelligent diagnostic tool for the color-based NAFLD hepatic tissue staging in Thailand, demonstrated satisfactory performance as a pathologist to provide liver fibrosis scoring and steatosis grading. In the future, developing AI algorithms and reliable testing on a larger scale may increase accuracy and contribute to telemedicine consultations for general pathologists in clinical practice.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

BACKGROUND AND AIMS: The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. APPROACH AND RESULTS: In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. CONCLUSIONS: Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.

Expert consensus on the diagnosis and treatment of end-stage liver disease complicated by infections.

End-stage liver disease (ESLD) is a life-threatening clinical syndrome and when complicated with infection the mortality is markedly increased. In patients with ESLD, bacterial or fungal infection can induce or aggravate the occurrence or progression of liver decompensation. Consequently, infections are among the most common complications of disease deterioration. There is an overwhelming need for standardized protocols for early diagnosis and appropriate management for patients with ESLD complicated by infections. Asia Pacific region has the largest number of ESLD patients, due to hepatitis B and the growing population of alcohol and NAFLD. Concomitant infections not only add to organ failure and high mortality but also to financial and healthcare burdens. This consensus document assembled up-to-date knowledge and experience from colleagues across the Asia-Pacific region, providing data on the principles as well as evidence-based current working protocols and practices for the diagnosis and treatment of patients with ESLD complicated by infections.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

INTRODUCTION: Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. METHODS: Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. RESULTS: Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. DISCUSSION: Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy.

Background and aims: Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. Methods: We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. Results: Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). Conclusions: In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.

Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Correlation between neck circumference and hepatic steatosis determined by controlled attenuation parameter.

Neck circumference is an attractive method for determining metabolic profiles and has many advantages over waist circumference. However, the correlation between neck circumference and hepatic fibrosis has not been evaluated. The aim of this study was to evaluate the correlation between neck circumference and hepatic fibrosis and define the optimal cut-off point for neck circumference to determine hepatic fibrosis. A cross-sectional study (n = 333) was conducted among Thai healthcare workers at Phramongkutklao Hospital who received an annual health maintenance program. Neck circumference was measured at the lower margin of the laryngeal prominence. Fibroscan® with a controlled attenuation parameter was used to measure the degree of hepatic fibrosis and steatosis by an experienced, well-trained operator. In the cross-sectional analysis, it was found that the large circumference of the neck was associated with hepatic fibrosis (r = 0.19, p = .001) and hepatic steatosis (r = 0.58, p < .001). Hepatic fibrosis (r = 0.15, p = .004) and steatosis (r = 0.53, p < .001) were also associated with waist circumference. The neck circumferences of 40 and 34 cm were the best cut-offs for male and female participants, respectively.Neck circumference is closely related to hepatic fibrosis and steatosis, which should be promoted and has a better advantage than waist circumference in the screening of hepatic steatosis.

Machine learning improves the prediction of significant fibrosis in Asian patients with metabolic dysfunction-associated steatotic liver disease - The Gut and Obesity in Asia (GO-ASIA) Study.

BACKGROUND: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD). AIMS: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients. METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria). RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set). CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.

Effect of Preoperative Very Low-Calorie Diets on Hepatic Steatosis, Fibrosis, and Perioperative Outcomes of Bariatric Surgery.

Introduction: Preoperative weight loss through a very low-calorie diet (VLCD) has been shown to reduce liver volume and technical difficulty in patients undergoing metabolic and bariatric surgery (MBS). However, the effect of preoperative VLCD on liver histology and other outcomes is not well demonstrated. Our study aimed to explore the effect of a 2-week preoperative VLCD, compared with no-dietary intervention, on hepatic steatosis, fibrosis, weight loss, and other postoperative outcomes of MBS. Materials and Methods: This retrospective study was conducted at the Chulalongkorn Bariatric and Metabolic Institute, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The medical records of patients with severe obesity (body mass index ≥50 kg/m2) attending the clinic from January 2005 to December 2020 were reviewed. Clinical data and laboratory investigations were collected at baseline and at each follow-up visit, up to 5 years postoperatively. Hepatic steatosis and fibrosis were assessed by liver biopsy intraoperatively. Results: A total of 181 patients were included in this study. Preoperative VLCD was prescribed in 65 patients (VLCD group) and 116 patients received their usual diet (control group). Mean preoperative weight loss was 9.1 ± 6.1 kg in the VLCD group versus 0.0 ± 0.0 kg in the control group (P = .000). The VLCD group had significantly less number of patients with moderate and severe liver steatosis from the liver biopsy specimens (16.2% versus 46.3%; P = .008). However, there was no significant difference in fibrosis grade between those with VLCD and control (≥F2-fibrosis; 2.7% versus 7.5%; P = .118). Moreover, preoperative VLCD could reduce operating time in patients who underwent both laparoscopic Roux-en-Y gastric bypass (LRYGB; VLCD 163.4 ± 38.2 minutes versus control 215.1 ± 67.4 minute, P = .000) and laparoscopic sleeve gastrectomy (LSG; VLCD 110.8 ± 20.0 minutes versus control 131.0 ± 38.1 minutes, P = .004). During the 5-year follow-up, there were a significant difference of HbA1C between the VLCD and the control group (coefficient: -0.24 with 95% confidence interval [CI]: -0.44 to -0.04, P = .019), particularly in patients who underwent LRYGB (Coefficient: -0.26 with 95% CI: -0.49 to -0.03, P = .028), but not LSG. However, long-term weight loss outcomes and other biochemical outcomes were not different between the VLCD and the control group. Conclusion: Preoperative VLCD was associated with reduced liver steatosis and operative time in patients who underwent LRYGB and LSG. Moreover, preoperative VLCD significantly decreased HbA1C during a 5-year follow-up period. Therefore, it should be considered in patients with severe obesity, who will undergo MBS.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis.

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy.

BACKGROUND: Modified albumin-bilirubin (mALBI) grade has been established as a survival determinant in hepatocellular carcinoma (HCC) patients who receive locoregional and targeted therapies. AIM: To investigate whether mALBI could predict survival in unresectable HCC (uHCC) patients who were treated with atezolizumab plus bevacizumab (AB). METHODS: A single-center, retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023. An association between mALBI and patient survival was determined using Cox proportional hazards analysis. RESULTS: Of the 83 patients, 67 patients (80.7%) were male with the mean age of 60.6 years. Among them, 22 patients (26.5%) were classified as Barcelona Clinic Liver Cancer B, and 61 patients (73.5%) were classified as Barcelona Clinic Liver Cancer C. Cirrhosis was present in 76 patients (91.6%), with 58 patients classified as Child-Turcotte-Pugh (CTP) A and 18 as CTP B. The median overall survival (OS) and progression-free survival were 13.0 mo [95% confidence interval (CI): 5.2-20.8] and 9.0 mo (95%CI: 5.0-13.0), respectively. The patients were divided into two groups based on mALBI grades: 42 patients (50.6%) in the mALBI 1 + 2a group; and 41 patients (49.4%) in the mALBI 2b + 3 group. During the median follow-up period of 7.0 mo, the mALBI 1 + 2a group exhibited significantly better survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 3.0 mo (95%CI: 0.1-6.0, P < 0.001). In a subgroup of patients with CTP A, the mALBI 1 + 2a group also showed significantly longer survival compared to the mALBI 2b + 3 group, with a median OS that was not reached vs 6.0 mo (95%CI: 3.4-8.6, P < 0.001). In the multivariate analysis, both CTP class and mALBI grade were independently associated with survival, with adjusted hazard ratios (95%CI) of 2.63 (1.19-5.78, P = 0.020) and 3.90 (1.71-8.90, P = 0.001), respectively. CONCLUSION: mALBI grades can determine survival of uHCC patients receiving AB treatment, particularly those who have mildly impaired liver function. This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis.

BACKGROUND: The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. AIM: To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. METHODS: One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. RESULTS: Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). CONCLUSION: The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.