Search

The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.To review the early developmental factors associated with NAFLD.Databases MEDLINEOf 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.

Background and aims The shift in the changing aetiology of cirrhosis requiring liver transplantation (LT) has resulted in an increasing prevalence of coronary artery disease (CAD) that can potentially impact post-liver transplant outcomes. This systematic review and meta-analysis aim to evaluate the prevalence of CAD, risk factors, and outcomes of patients diagnosed with CAD pre-liver transplant. Methods Medline and Embase were searched for articles describing CAD in pre-LT patients. Meta-analysis of proportions using the generalized linear mix model was conducted to analyse the pooled prevalence of CAD in pre-LT patients. Associated risk factors for CAD in pre-LT patients and outcomes were evaluated in conventional pairwise meta-analysis. Results A total of 39 studies were included. The pooled prevalence of patients diagnosed with CAD before LT was 15.9% (CI: 9.8%-24.7%). Age, male gender, diabetes, hypertension, hyperlipidemia, smoking, non-alcoholic steatohepatitis, hepatitis B and hepatocellular carcinoma were significantly associated with CAD. Patients from high-income countries especially North America, Europe, and South America, with the associated risk factors were at increased risk for CAD pre-LT. CAD pre-LT was associated with an increased odds of overall mortality (OR: 1.4; CI: 1.4 - 1.4; p = 0.01) and cardiac-related mortality (OR: 1.2; CI: 1.1 - 1.3; p = 0.03). A total of 48.7% of included articles considered presence of cardiovascular risk factors for screening of CAD. However, 10.3% of studies screened for CAD in pre-LT patients via invasive coronary angiography only, without stress testing or risk stratification. Conclusion This study demonstrates the high prevalence of CAD in pre-LT patients, associated risk factors and outcomes. There is heterogeneity among guidelines and practice in screening for pre-LT CAD, and more studies are needed to establish consensus.

Current guidelines have limited consensus on the approach to portal venous thrombosis (PVT) in cirrhotic patients. While there is rising interest in direct oral anticoagulants (DOACs) use for PVT, current evidence is limited by small sample size and lack of comparisons to traditional anticoagulants. Thus, a network meta-analysis was conducted to compare the use of DOACs with traditional anticoagulants. Medline and Embase were searched for articles about anticoagulation use in cirrhotic patients with nontumorous PVT for articles on DOACs, warfarin, low-molecular weight heparin (LMWH) or antithrombin III. A network analysis was conducted using risk ratios (RR) with surface under the cumulative ranking curve (SUCRA). A single-arm meta-analysis was used to summarize the outcomes of DOAC treatment. A total of 10 articles were included in the study. 79.5% (CI 38.8–95.9) of DOACs patients achieved complete or partial recanalization and 9.80% (CI 4.50–20.0) experienced a bleeding event. DOACs were superior to LMWH (RR 2.299, CI 1.037–5.093, p = 0.040), warfarin (RR 1.762, CI 1.017–3.053, p = 0.043) and no treatment (RR 3.489, CI 1.394–8.733, p = 0.008) in complete recanalization. For partial recanalization, while DOACs were not superior to any treatment, they had the highest probability in achieving partial recanalization in SUCRA analysis. Bleeding risk and mortality were similar compared to other treatments. The network analysis supports the use of DOACs in cirrhotic patients, with significant rates of complete recanalization compared to other treatments without increasing bleeding risk. DOACs can potentially be considered for nontumorous PVT in cirrhosis.

In light of a global organ shortage, living donor transplantation has become increasingly relevant as an alternative to deceased donor transplantation. While current research has revolved around the medical aspects of transplantation, there remains a paucity of literature regarding the quality of life (QOL) of living donors. Hence, this review aims to provide a comprehensive outline of the current landscape of living liver and kidney transplantation, with a focus on the mental health and wellbeing of donors. As highlighted in previous studies, organ donation has a significant impact on both physical and mental aspects of donor wellbeing, with marked deteriorations occurring in the short term. Furthermore, other qualitative aspects such as financial burden contribute greatly to donor distress, reflecting a need for improved donor care. To address these pertinent issues, recommendations for a successful transplant program are detailed in this review, which encompasses psychological and social aspects of donor care throughout the donation process. Further research can be done on the impact of recipient deaths on donor QOL and appropriate interventions. Overall, given the selfless sacrifices of living donors, the care of their mental wellbeing is essential. Therefore, greater emphasis should be placed on the provision of adequate psychosocial support for them.

Cardiovascular disease contributes to a high rate of morbidity and mortality after liver transplantation (LT). However, the progression of cardiac function and cardiac remodeling in LT recipients remains poorly understood. This study sought to evaluate the progression of cardiac function and structure in LT recipients and identify independent predictors of prognosis using echocardiography.From 2009 to 2019, 178 adult LT recipients at a tertiary academic transplant center were retrospectively studied. Transthoracic echocardiograms 1-year pre- and post-LT were assessed. Primary outcomes were progression of systolic and diastolic function. Secondary outcomes included left ventricular remodeling, all-cause mortality, and heart failure readmission post-LT. Subgroup analyzes were performed for etiology of native liver disease. A multivariable model was constructed to examine independent predictors of outcomes.Systolic function significantly worsened, with reduction in stroke volume (45-37 ml/mThis study showed reduced systolic and improved diastolic function in LT recipients and highlighted the utility of pre-LT echocardiogram in the prognostication and risk stratification of LT candidates.

Following liver transplant (LT), osteoporosis is a severe complication that causes morbidity. However, the incidence and risk factors of osteoporosis and fractures have not been well described. Single-arm meta-analysis of studies reporting osteopenia, osteoporosis, and fractures post-LT was performed with meta-regression for study period. Dichotomous variables, continuous variables and time-to-event variables were pooled in odds ratio, weighted mean difference and hazard ratio, respectively. For risk factors with limited data, a systematic review of literature was conducted. There was a significant increase in both osteoporosis and fractures compared to non-LT patients. Osteopenia, osteoporosis and incident fractures were newly diagnosed in 34.53% (CI: 0.17-0.56, n = 301), 11.68% (CI: 0.05-0.24, n = 1251) and 20.40% (CI: 0.13-0.30, n = 4322) of LT patients, respectively. Female gender (P = 0.017) increased risks of osteoporosis but not older age and BMI. Older age, lower pre-LT bone mineral density (BMD), presence of bone disease pre-LT were significant risk factors for fractures but not female gender, post-menopausal state, BMI, smoking and alcohol. There is a high incidence of skeletal complications post-LT. Older age, lower pre-LT BMD and presence of bone disease pre-LT are significant risk factors that are associated with incident fractures physicians should be cognisant of in liver transplant recipients.

BACKGROUND Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF. AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation. METHODS Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device. RESULTS Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01). CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

Chronic kidney disease (CKD) remains a relatively common complication after liver transplantation (LT), and significantly impacts overall survival. We sought to assess the cumulative incidence, risk factors and mortality associated with post-LT CKD. CKD was defined as eGFR

BACKGROUND AND AIMS Pre-liver transplant (LT) chronic kidney disease (CKD) has emerged as a leading cause of postoperative morbidity. We aimed to report the prevalence, associated risk factors and clinical outcomes in patients with pre-LT CKD. METHODS Meta-analysis and systematic review were conducted for included cohort and cross-sectional studies. Studies comparing healthy and CKD patients pre-LT were included. Outcomes were assessed with pooled hazard ratios. RESULTS 15 studies were included, consisting of 82,432 LT patients and 26,754 with pre-LT CKD. Pooled prevalence of pre-LT CKD was 22.35% (CI: 15.30% - 32.71%). Diabetes mellitus, hypertension, viral hepatitis and non-alcoholic fatty liver disease, and older age were associated with increased risk of pre-LT CKD: (OR 1.72 CI: 1.15- 2.56, p = 0.01), (OR 2.23 CI: 1.76 - 2.83, p

The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD.Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis.Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P.001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD.There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society. Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR). Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60-2.89). Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version MM acknowledges support by Singapore Ministry of Health’s National Medical Research Council, under its NRMC Research Training Fellowship MOH-000193.

Background Hepatitis B virus (HBV) vaccination is indicated for all unexposed transplant recipients on long-term immunosuppression. However, vaccine response is often poor and monitoring overlooked. We conducted a service improvement project over five months to identify liver transplant (LT) recipients with inadequate anti-HBs titre and started them on a vaccination programme. Non-responders were identified for future intervention. Methods A cross-sectional study of all eligible LT recipients from 2008 to 2020 in a leading transplant centre in Singapore was conducted to determine the vaccine response in HBV-naive subjects. A standardised workflow was devised to identify barriers in vaccination and response monitoring. Transplant coordinators and pharmacists assisted physicians to identify and prescribe CDC-recommended vaccinations using a template, which include Engerix 40mcg of three doses, followed by rechecking anti-HBs titre one month after. A second 3-dose Engerix regimen was given if anti-HBs remains Results Of the 279 LT recipients, we excluded patients not on follow-up and patients with anti-HBc positivity. 75 patients were included. Prior to vaccination implementation, 9/75 (12%) were not checked for anti-HBs. Of the 66 checked, 40 required vaccination. 29/40 (72.5%) were started on the first cycle, and 21/40 (52.5%) completed. 11/20 (55%) patients were initiated on the second cycle. Post workflow implementation, 40 needed vaccination. 34/40 (85%) were started on the first cycle and 24/40 (60%) completed. 18/23 (78.3%) were started on a second cycle. 3/4 (75%) were non-responders (IDDF2021-ABS-0190 Figure 1). Our implementation coincided with the COVID-19 pandemic where more teleconsultation was used. COVID-19 vaccination was also prioritised over HBV vaccination. We postulate that these results would be further improved once physical consultations resumed. Conclusions The development of a standardised workflow can lead to improvement in anti-HBs testing and compliance to vaccination post-LT. These findings may be useful for other patients who are on long-term immunosuppression. Continual efforts from the multidisciplinary team are required to ensure the sustainability of effect.

Background Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP. Methods A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals. Results 99 articles, comprising a total of 5,861,142 individuals with cirrhosis were included (IDDF2021-ABS-0019 Figure 1. Summary of Findings). Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63% - 21.30%), highest in Africa (68.20%; CI: 12.17% - 97.08%), and lowest in North America (10.81%; CI: 5.32% - 20.73%; IDDF2021-ABS-0019 Figure 2. Summary of SBP prevalence by region). The summary of the global prevalence is found in figure 1. Prevalence of community-acquired SBP was 6.05% (CI: 4.32% - 8.40%), and 11.11% (CI: 5.84% - 20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.51% (CI: 7.28% - 17.74%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83% – 9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32% - 11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41% - 8.46%). A subgroup analysis was conducted to compare the rate of resistant SBP based on continent and summarized in figure 2. Subgroup analysis comparing prevalence, antibiotic resistance and outcomes between income groups. Conclusions SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios.A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes.Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026).This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.

Atrial Fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia. It is associated with significant morbidity and mortality, as it is a major risk factor for cerebral vascular accidents (CVA). Our aim was to determine the prevalence of pre-existing and new-onset AF among patients undergoing liver transplantation (LT) and its impact on post-transplant outcomes.Medline and Embase were searched. Single-arm analysis was conducted using the generalized linear mixed model to determine the prevalence of pre-existing and new-onset AF. Logistic regression was performed to analyze risk factors. Comparative meta-analysis in odds ratio was conducted for binary outcomes.Twenty articles were included, with 17 studies on pre-existing AF, and 7 including data on new-onset AF post-LT. The prevalence of pre-existing AF was 3.3% (CI 2.3-4.7) (14 studies, 45,070 patients) in pooled analysis. Significantly higher prevalence of pre-existing AF patients from North America was noted when compared to Europe (4.5%, CI 3.4-5.8 vs 1.5%, CI 0.8-2.7; p = 0.001). Body mass index (BMI), history of hypertension, diabetes, coronary artery disease (CAD), and cerebrovascular accidents (CVA) were risk factors for pre-existing AF. Pre-existing AF was significantly associated with major adverse cardiac or cerebrovascular events (MACCE) postoperatively (OR 8.02, 95%CI 5.40-11.90, p 0.001). New-onset AF post-LT had an incidence of 6.8% (CI 4.9-9.3), and was associated with increased risk of mortality (OR 2.31, 95% CI 1.76-3.02, p 0.001) and graft failure (OR 2.98, CI 1.99-4.47, p 0.001).AF is relatively more common among patients undergoing LT compared to the general non-transplant population. Additionally, it is associated with adverse outcomes including MACCE, thus warranting clinical attention. Thorough cardiac assessment, and close surveillance of post-operative AF may be clinically prudent.

Cardiovascular disease remains the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Studies examining the association of coronary heart disease (CHD) and NAFLD are cofounded by various cardiometabolic factors, particularly diabetes and body mass index. Hence, we seek to explore such association by investigating the global prevalence, independent risk factors, and influence of steatosis grade on manifestation of CHD among patients with NAFLD.Two databases, Embase and Medline, were utilized to search for articles relating to NAFLD and CHD. Data including, but not limited to, continent, diagnostic methods, baseline characteristics, prevalence of CHD, CHD severity, NAFLD severity, and risk factors were extracted.Of the 38 articles included, 14 reported prevalence of clinical coronary artery disease (CAD) and 24 subclinical CAD. The pooled prevalence of CHD was 44.6% (95% confidence interval [CI], 36.0%-53.6%) among 67,070 patients with NAFLD with an odds ratio of 1.33 (95% CI, 1.21%-1.45%; Plt; .0001). The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%; 95% CI, 15.0%-67.2%) than those with mild steatosis (29.6%; 95% CI, 13.1%-54.0%). The pooled prevalence of subclinical and clinical CAD was 38.7% (95% CI, 29.8%-48.5%) and 55.4% (95% CI, 39.6%-70.1%), respectively.Steatosis was found to be related with CHD involvement, with moderate to severe steatosis related to clinical CAD. Early screening and prompt intervention for CHD in NAFLD are warranted for holistic care in NAFLD.

A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease.A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

Background: Liver transplantation (LT) activities during the COVID-19 pandemic have been curtailed in many countries. The impact of various policies restricting LT on outcomes of potential LT candidates is unclear. Methods: We studied all patients on the nationwide LT waitlists in Hong Kong and Singapore between January 2016 and May 2020. We used continuous time Markov chains to model the effects of different scenarios and varying durations of disruption on LT candidates. Findings: With complete cessation of LT, the projected 1-year overall survival (OS) decreased by 3•6%, 10•51% and 19•21% for a 1-, 3- and 6-month disruption respectively versus no limitation to LT, while 2-year OS decreased by 4•1%, 12•55%, and 23•43% respectively. When only urgent (acute-on-chronic liver failure [ACLF] or acute liver failure) LT was allowed, the projected 1-year OS decreased by a similar proportion: 3•1%, 8•41% and 15•20% respectively. When deceased donor LT (DDLT) and urgent living donor LT (LDLT) were allowed, 1-year projected OS decreased by 1•2%, 5•1% and 8•85% for a 1-, 3- and 6-month disruption respectively. OS was similar when only DDLT was allowed. Complete cessation of LT activities for 3-months resulted in an increased projected incidence of ACLF and hepatocellular carcinoma (HCC) dropout at 1-year by 49•1% and 107•96% respectively. When only urgent LT was allowed, HCC dropout and ACLF incidence were comparable to the rates seen in the scenario of complete LT cessation. Interpretation: A short and wide-ranging disruption to LT results in better outcomes compared with a longer duration of partial restrictions. Funding: None to disclose.