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.

Rising global burden of cancer attributable to high BMI from 2010 to 2019.

BACKGROUND: High body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear. METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study. RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI. CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the latest term for steatotic liver disease associated with metabolic syndrome. MASLD is the most common cause of chronic liver disease and is the leading cause of liver-related morbidity and mortality. It is important that all stakeholders be involved in tackling the public health threat of obesity and obesity-related diseases, including MASLD. A simple and clear assessment and referral pathway using non-invasive tests is essential to ensure that patients with severe MASLD are identified and referred to specialist care, while patients with less severe disease remain in primary care, where they are best managed. While lifestyle intervention is the cornerstone of the management of patients with MASLD, cardiovascular disease risk must be properly assessed and managed because cardiovascular disease is the leading cause of mortality. No pharmacological agent has been approved for the treatment of MASLD, but novel anti-hyperglycemic drugs appear to have benefit. Medications used for the treatment of diabetes and other metabolic conditions may need to be adjusted as liver disease progresses to cirrhosis, especially decompensated cirrhosis. Based on non-invasive tests, the concepts of compensated advanced chronic liver disease and clinically significant portal hypertension provide a practical approach to stratifying patients according to the risk of liver-related complications and can help manage such patients. Finally, prevention and management of sarcopenia should be considered in the management of patients with MASLD.

Frequency of significant steatosis and compensated advanced chronic liver disease among adults with chronic liver disease.

BACKGROUND: With changes in the epidemiology and treatment of chronic liver disease (CLD), the impact of various etiologies of liver disease on steatosis and advanced fibrosis are uncertain. METHODS: A retrospective study was conducted among liver disease patients of various etiologies undergoing transient elastography (TE) over a 9-year duration. RESULTS: Data for 2886 patients were analyzed and had the following demographics: The median age was 60 (IQR: 45-69) years, 51% were males, and ethnicity was predominantly Chinese (52.5%), followed by Malays (34%) and Indians (12.3%). The median CAP score was 272 (IQR: 219-319) dB/m and the median liver stiffness measurement (LSM) score was 6.5 (IQR: 4.9-9.7) kPa. Hepatic steatosis occurred across the spectrum of etiologies of CLD. Among patients with steatosis, the most common etiologies were nonalcoholic fatty liver disease (NAFLD) at 62% and chronic hepatitis B (CHB) at 26.3%. TE findings suggestive of cACLD (10.1-15 kPa) and highly suggestive of cACLD (>15 kPa) were observed in 11.3% and 12.4% of patients, respectively. NAFLD was found to be the most common etiology for cases with suggestive of cACLD (47.2%) and highly suggestive of cACLD (41.5%). CONCLUSION: Hepatic steatosis is common in CLD, regardless of etiology. Compared with other etiologies, NAFLD is now the leading cause of cACLD.

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis.

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression. INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. FUNDING: Innovative Medicines Initiative 2.

Development and validation of the Adult cirrhosiS Knowledge Questionnaire.

BACKGROUND: Assessing a patient's knowledge regarding liver cirrhosis is important to improve patient outcomes. This study aimed to develop and validate the Adult cirrhosiS Knowledge Questionnaire (ASK-Q) to assess patients' knowledge regarding liver cirrhosis from multiple aspects. METHODS: A 24-item ASK-Q with four domains: self-understanding (5 items), aetiology (5 items), complications (5 items) and management (9 items) of liver cirrhosis was developed based on literature review and expert panel input. It was then piloted in five English-speaking patients with liver cirrhosis. These patients commented that the font size was too small. Hence, the font was enlarged and the final version of the ASK-Q was administered to English-speaking patients with liver cirrhosis, aged ≥18 years, with or without decompensation, at a tertiary hospital, from September 2020 to November 2021, at baseline and fortnight later. Patients with encephalopathy were excluded. RESULTS: 120/135 patients agreed to participate (response rate = 88.9%). The overall median score was 59.1 (45.6-68.2). A total of 7/22 (31.8%) items were "easy", 14/22 (63.6%) items were "moderately easy" and 1/22 (4.5%) items were "difficult". Exploratory factor analysis extracted nine factors, and two items were omitted. The ASK-Q was able to discriminate the knowledge level of patients with and without tertiary education [59.1 (50.0-72.7) vs. 54.5 (36.4-63.6); P < 0.05]. The overall Kuder-Richardson coefficient was 0.760, indicating adequate internal consistency. At retest, 77/120 patients participated (response rate = 64.2%) and 15/22 items were not statistically significant, indicating adequate reliability. CONCLUSIONS: The ASK-Q was found to be a valid and reliable questionnaire for evaluating the knowledge of liver cirrhosis among English-speaking adult patients.

Epidemiological trends of gastrointestinal and liver diseases in Malaysia: A single-center observational study.

BACKGROUND AND AIM: The spectrum of gastrointestinal (GI) and liver diseases is recognized to have a geographical variation, which may be due to environmental or genetic differences. We aimed to explore this further in a specialist clinic serving a multi-ethnic Asian urban population. METHODS: A retrospective analysis of outpatient data from this institution's electronic medical records was conducted between January and June 2019. Clinical diagnoses of GI and liver diseases and associated demographic information were collected. RESULTS: Data from 3676 adult patients (median age 62 years, female 51.1%) were available for analysis. The frequency of luminal GI, liver and pancreato-biliary diseases were 34.2%, 63.2%, and 2.6%, respectively. Among luminal GI diseases, 38.6% were functional gastrointestinal disorders and 61.4% had an organic cause. A higher proportion of patients of Indian ethnicity were diagnosed with IBD compared with other ethnic groups (India 21.9%, Malay 16.5%, Chinese 12.2%, P = 0.001). Among liver diseases, the most common etiologies were HBV (44.4%) and NAFLD (39.3%). Cirrhosis and/or hepatocellular carcinoma were present in 18% of liver diseases, with NAFLD as the most frequent etiology. Among patients with NAFLD, a higher proportion of ethnic Malays and Indians were evident (Malay 53.8% vs Chinese 28.7% vs Indian 61.1%, P < 0.001). In contrast, a greater proportion of ethnic Chinese were diagnosed with HBV compared with other ethnic groups (Malay 30.9% vs Chinese 57.5% vs Indian 8.4%, P < 0.001). CONCLUSION: The spectrum of GI and liver diseases has a peculiar epidemiology, particularly with reference to the ethnic predilection of certain diseases.

Non-alcoholic fatty liver disease and obesity among adult donors are major challenges to living-donor liver transplantation: A single-center experience.

OBJECTIVES: Obesity and non-alcoholic fatty liver disease (NAFLD) are rampant in South East Asia. There is paucity of data exploring its' impact on donor suitability for living donor liver transplantation (LDLT). We aimed to describe and examine the factors related to non-utilization of potential donors in our LDLT programme. METHODS: This is an analysis of prospectively collected data on potential donors for an adult LDLT programme, between January 2017 and December 2019. RESULTS: Fifty-five donors for 33 potential recipients were evaluated. The mean age was 31.6 ± 8.5 years, 52.7% were female and the ethnic divisions were: Chinese (50.9%), Indian (25.5%) and Malay (23.6%). The mean body mass index (BMI) among potential donors was 25.1 ± 4.0 kg/m2; 25.5% of donors had normal BMI, 23.6% were overweight and 50.9% were obese. Using the CAP modality of Fibroscan®, we identified the following grades of hepatic steatosis: 36.6% S0, 19.5% S1, 2.4% S2 and 41.5% S3. The non-utilization rate of our donors was 74.5% (41/55) and the main reasons were significant hepatic steatosis and/or obesity. Compared to suitable donors, unsuitable donors had significantly greater mean BMI, mean CAP scores, higher rates of dyslipidaemia and NAFLD. CONCLUSION: NAFLD and obesity represent major challenges to an emerging LDLT programme in Malaysia.

Common musculoskeletal disorders in chronic liver disease patients.

Chronic liver disease (CLD) is the commonest ailment affecting the hepatobiliary system. Six significant pathologies related to CLD include hepatic osteodystrophy (HO), increased infection susceptibility, sarcopenia, osteonecrosis of the femoral head (OFH), increased risk of periprosthetic complications and fracture. Hepatic osteodystrophy, which comprises osteopenia, osteoporosis, and osteomalacia, refers to alterations in bone mineral metabolism found in patients with CLD. The HO prevalence ranges from 13 to 95%. Low complement levels, poor opsonization capacity, portosystemic shunting, decreased albumin levels, and impaired reticuloendothelial system make the cirrhotic patients more susceptible to developing infectious diseases. Septic arthritis, osteomyelitis, prosthetic joint infection, and cellulitis were common types of CLD-associated infectious conditions. The incidence of septic arthritis is 1.5 to 2-fold higher in patients with cirrhosis. Sarcopenia, also known as muscle wasting, is one of the frequently overlooked manifestations of CLD. Sarcopenia has been shown to be independent predictor of longer mechanical ventilation, hospital stay, and 12-month mortality of post-transplantation. Alcohol and steroid abuse commonly associated with CLD are the two most important contributory factors for non-traumatic osteonecrosis. However, many studies have identified cirrhosis alone to be an independent cause of atraumatic osteonecrosis. The risk of developing OFH in cirrhosis patients increases by 2.4 folds and the need for total hip arthroplasty increases by 10 folds. Liver disease has been associated with worse outcomes and higher costs after arthroplasty. Cirrhosis is a risk factor for arthroplasty complications and is associated with a prolonged hospital stay, higher costs, readmission rates, and increased mortality after arthroplasty. Greater physician awareness of risk factors associated with musculoskeletal complications of CLD patients would yield earlier interventions, lower healthcare costs, and better overall clinical outcomes for this group of patients.

Hydroxyurea associated ileocecal valve ulcer: evidence for causality.

Hydroxyurea is an antimetabolite drug that is commonly used in many hematological disorders. Ulcer formation in the gastrointestinal tract is a rare phenomenon associated with this drug. We report a case of a 73-year-old woman who was found to have an isolated ileocecal valve ulcer while on hydroxyurea 1 g daily for essential thrombocythemia. A comprehensive evaluation ruled out all other causes. The cytoreductive therapy was switched to anagrelide and the endoscopic evaluation 6 months later showed complete healing of the ulcer. However, the hydroxyurea was resumed due to increasing platelet counts and intolerance to dose increments of the anagrelide. Subsequently, the patient was found to have a recurrence of the ulcer. Apart from oral ulcers, there have also been reports of ulcers involving the small bowel and the colon associated with the use of hydroxyurea. The pathophysiology of the non-oral gastrointestinal ulceration in relation to this drug is unclear. Withdrawal of the drug typically leads to complete resolution. Increasing awareness of the rare association between the use of hydroxyurea and nonoral gastrointestinal ulcers is essential for early detection to prevent related complications.

Mesenchymal stem cell therapy for advanced liver cirrhosis: A case report.

Mesenchymal stem cell (MSC) transplant may offer an alternative to liver transplantation in patients with end-stage liver disease. However, its efficacy remains uncertain. MSC was performed on a 50-year-old male with decompensated (Child-Turcotte-Pugh grade C) alcoholic liver cirrhosis due to an absence of donors for adult-deceased and living-related liver transplantation. Autologous bone marrow-derived MSCs were harvested from the patient and cultured using standard protocols. The MSCs were subsequently re-administrated into the liver via hepatic intra-arterial infusion on two separate occasions. After infusion, there was an improvement in biochemical parameters (serum total bilirubin, serum albumin), and a reduction of diuretic use for ascites for up to 8 weeks. However, all biochemical and clinical parameters deteriorated on long-term follow-up without any further infusions. The patient eventually succumbed to his disease. MSC transplantation may have a clinical benefit on adult patients with end-stage liver cirrhosis, but this appears to be transitory.