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Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The growing trend towards an aging population, along with an alarming rise in obesity and diabetes, may have significant implications for the burden of NAFLD. Aim: To assess the impact of NAFLD on the elderly. Methods: We utilised data from the Global Burden of Disease study between 2010 and 2019 to conduct a comprehensive analysis of the prevalence, mortality, and disability‐adjusted life years (DALYs) associated with NAFLD in the elderly (65–89 years), stratified by region, nation, sociodemographic Index and sex. Results: Globally, there were an estimated 228 million cases, 87,230 deaths and 1.46 million DALYs attributed to NAFLD in the elderly. Geographically, the Western Pacific region had the highest burden of NAFLD in the elderly. From 2010 to 2019, there was an increasing prevalence rate in all areas, with the most pronounced change observed in the Western Pacific region (annual percentage change (APC) +0.95%, p < 0.001). Over the study period, there was a more rapid increase in NAFLD prevalence in men (APC +0.74%, p < 0.001) than in women (APC +0.63%, p < 0.001). In most regions, death and DALYs rates have declined, with the exception of the Americas, where there was a slight increase (APC +0.25%, p = 0.002 and 0.38%, p < 0.001, respectively). Conclusion: Over the past decade, the burden of NAFLD in the elderly has been increasing, necessitating immediate and inclusive measures to tackle the rising burden. [ABSTRACT FROM AUTHOR]

Summary: Background/Aims: Metabolic syndrome (MetS) affects over one third of the US adult population. Despite its close association with non‐alcoholic fatty liver disease (NAFLD), the traditional definition of MetS does not account for the presence of NAFLD. The present study thus aims to evaluate the inclusion of NAFLD in the diagnostic criteria of metabolic syndrome on its accuracy of capturing individuals with metabolic dysregulation and its prediction of adverse events. Methods: Data collected from NHANES between 1999 and 2018 was analysed. Clinical characteristics and outcomes between individuals with metabolic syndrome from both the American Heart Association/National Heart, Lung, and Blood Institute (MetS) and the study's proposed diagnostic criteria (MetS2) were evaluated. Outcomes in both groups were evaluated with multivariate analyses, and further subgroup analysis on individuals matched with Coarsened Exact Matching was performed. Results: Of 46,184 individuals included, 32.54% and 40.54% fulfilled MetS and MetS2 criteria respectively. Considering NAFLD in the definition of metabolic syndrome, a further 8.00% (n = 3694) were included. MetS was significantly associated with all‐cause (HR: 1.184, 95% CI: 1.110–1.263, p < 0.001) and cardiovascular disease (CVD) mortality (SHR: 1.288, 95% CI: 1.233–1.347, p < 0.001), and major adverse cardiovascular events (MACE). MetS2 was similarly associated with all‐cause (HR: 1.175, 95% CI: 1.088–1.269, p < 0.001), CVD mortality (SHR: 1.283, 95% CI: 1.245–1.323, p < 0.001) and MACE. Conclusion: Inclusion of NAFLD allows for identification a greater proportion of the population with metabolic risk. This allows for early intervention and potential to lift some burden off the global healthcare system. [ABSTRACT FROM AUTHOR]

Summary: Background: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta‐analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks. Aim: To examine by an updated meta‐analysis the association between these medications and HCC risk. Methods: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable‐adjusted hazard ratios (HRs) for HCC were pooled using a random effects model. Results: Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37–0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non‐alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27–0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31–1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow‐up <60 months for aspirin (I2 = 0%). Conclusion: Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design. [ABSTRACT FROM AUTHOR]

As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population. This study analyses the 2017–2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications. 2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 − 0.58) in non-drinkers and 33% (CI: 0.26 − 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 − 3.22, p<.01) after adjustment for confounders. There were no significant differences in the odds of significant fibrosis, advance fibrosis, cirrhosis, cardiovascular disease and stroke between non-drinkers and modest drinkers. The odds of malignancy in non-drinkers were almost significantly less than modest drinkers (OR: 0.28, CI:0.08 − 1.02, p=.053). Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management. [ABSTRACT FROM AUTHOR]

Objectives & background: Anonymous live organ donors or unspecified donors are individuals willing to be organ donors for any transplant recipient with whom they have no biological or antecedent emotional relationship. Despite excellent recipient outcomes and the potential to help address organ scarcity, controversy surrounds the unconditional act of gifting one's organs to an unrelated recipient. This qualitative systematic review provides insights into the first-hand experiences, motivations, and challenges that unspecified donors face. Methods: A systematic search was conducted on Medline, Embase, CINAHL, PsycINFO, and Web of Science database for qualitative literature regarding unspecified living donors' motivations and experiences in liver and kidney transplantation. An inductive thematic analysis was conducted to generate themes and supportive subthemes. Results: 12 studies were included. The four major themes were (i) motivations, (ii) perception of risks, (iii) donor support, and (iv) benefits of donation. Unspecified donors demonstrated a deep sense of social responsibility but tended to underestimate health risks in favour of benefits for recipients. Despite the lack of emotional support from family and friends, the decision to donate was a resolute personal decision for donors. Majority benefitted emotionally and did not express regret. Conclusion: This qualitative review bridges the gap in literature on unspecified living donor psychology and provides a comprehensive understanding of the decision-making matrix and experiences of donors. [ABSTRACT FROM AUTHOR]

Background: Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes. Methods and findings: Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, p<0.001), followed by cognitive behavioural therapy (CBT) (SMD: -0.75, 95% CI: -0.99 to -0.52, p<0.001), antidepressants (SMD: -0.73, 95% CI: -1.14 to -0.31, p<0.001), and lastly, combination therapy (SMD: -0.15, 95% CI: -0.28 to -0.03, p = 0.016). No treatment modalities was found to be more effective in reducing depression scores when compared to one another. Additional analysis showed that these treatment modalities did not have significant impact on the overall mortality, cardiac mortality and recurrent myocardial infarction. Conclusion: This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD is associated with dyslipidemia, and cardiovascular mortality remains the leading cause of death. While statins are the first-line therapy in hyperlipidemia, their utilization has been suboptimal. Hence, we examined the use of statins in NAFLD and mortality. Analysis was performed with the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. Longitudinal outcomes were assessed with survival analysis. Of 12,538 NAFLD patients, 6,452 were indicated for hyperlipidemia treatment. Statin usage was highest among high-risk individuals (44.28%) and lowest among low-risk individuals (8.48%). The risk of overall (HR: 0.87, CI: 0.76 to 0.99, p = 0.04) and cancer-related (SHR: 0.73, CI: 0.54 to 0.99, p = 0.04) mortality was significantly lower in NAFLD patients with statins. There was no significant decrease in cardiovascular-related mortality. Over concerns of hepatotoxicity and lack of evidence in reducing mortality events, statins remain underutilized in NAFLD. However, statin use was associated with a significant reduction in overall and cancer-related mortality. The lack of reduction in cardiovascular disease mortality is likely a selection bias of patients, where individuals with higher risk are more likely to receive treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: Non‐alcoholic fatty liver disease (NAFLD) affects one‐fourth of the global population. Yet, the care of these patients is limited and awareness of NAFLD remains low in the general public. Investigations into the lives of these patients are often forgotten and traditional quantitative studies only paint part of the picture. Aim: To assess the first‐hand accounts of these individuals and their perspective on living with NAFLD. Methods: A systematic search was conducted on Medline, Embase, CINAHL, PsycINFO and Web of Science database for qualitative literature regarding patients' perspectives on NAFLD. An inductive thematic analysis was conducted to generate themes and supportive subthemes. Results: We incuded eight articles in the review. There were three major themes including the impact on the quality of life, knowledge and information, and attitudes and perceptions on care. The impact of the quality of life details the emotional and physical distress of NAFLD. Knowledge and information include the lack of sufficient communication between healthcare providers and patients with a distinct knowledge gap. Attitudes and perceptions on care extrapolate the current active participation of patients and needs of the patients and the future care that they desire. Conclusion: This review synthesises first‐hand accounts of individuals with NAFLD. With the growing burden of NAFLD, future public interventions must consider individual views for success to be found. The identified themes serve as a forefront for consideration for public policies. Ultimately, NAFLD is a multisystem disease, which must be managed by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Non‐alcoholic steatohepatitis (NASH) is the most common cause of liver disease. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta‐analysis evaluating drug classes through comparing histological outcomes and targets of drugs. Approach and Results: Medline, EMBASE and CENTRAL were searched for randomised controlled trials evaluating NASH drugs in biopsy‐proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, at least 2‐point reduction in Non‐alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and at least 1‐point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. Among 49 included trials, treatments modulating energy (Risk ratio (RR): 1.92, Credible intervals (Crl): 1.59‐2.34) were most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.66, Crl: 0.65‐4.50), bile acids (RR: 1.37, Crl: 0.99‐1.92) and inflammation (RR: 1.00, Crl: 0.75‐1.33). Energy and bile acids modulation were effective in at least 2‐point NAS reduction without worsening of fibrosis (RR: 1.52, Crl 1.30‐1.77; RR: 1.69, Crl 1.41‐2.03) and at least 1‐point reduction in fibrosis (RR: 1.26, Crl:1.05‐1.49; RR: 1.54, Crl: 1.20‐1.97). Conclusions: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies. [ABSTRACT FROM AUTHOR]

Objective: Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile. Methods: Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters. Results: Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: − 0.693; 95% CI: − 1.112 to − 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices. Conclusions: NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function. [ABSTRACT FROM AUTHOR]

Objective: As there has been so far no consensus on the best endoscopic resection technique, a meta‐analysis was conducted to compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for treating rectal carcinoid tumors. Methods: MEDLINE and EMBASE databases were searched for articles on the treatment of rectal carcinoid tumors using ESD vs EMR published up to October 2020 for outcomes including en bloc and complete resection, margin involvement, procedure time, requirement for additional surgery, bleeding, perforation and recurrence. Risk ratio and weighted mean differences were used for a DerSimonian and Laird random effects pairwise meta‐analysis. Single‐arm meta‐analyses of proportions and random effects meta‐regression analysis were also conducted. Results: Twenty‐two studies involving 1360 rectal carcinoid tumors were included, in which 655 and 705 rectal carcinoid tumors were resected with ESD and EMR, respectively. The resection efficacy of ESD was comparable to that of EMR for tumors <10 mm. However, there were a significantly higher complete resection rate, and lower rates of vertical margin involvement and requirement for additional surgery using ESD than using EMR for tumors ≤20 mm. ESD had a longer procedure time and an increased likelihood of bleeding than EMR. Conclusions: ESD is more effective in providing a curative treatment for rectal carcinoid tumors ≤20 mm in size as ESD can achieve a higher complete resection rate with lower vertical margin involvement than EMR. While they are suitable for treating rectal carcinoid tumors <10 mm as both techniques provide similar efficacy. [ABSTRACT FROM AUTHOR]

Summary: To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post‐orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post‐OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta‐analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single‐arm meta‐analysis. Post‐OLT fracture incidence was reported in nine studies (n = 591). Total fracture incidence was 6.6% (CI: 3.4–12.4%) in bisphosphonate group and 19.1% (CI: 14.3–25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18–0.77; P = 0.008). Overall fractures were significantly lower in the oral group (n = 263; OR = 0.26; CI: 0.08–0.85; P = 0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16–1.26; P = 0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post‐OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post‐OLT. [ABSTRACT FROM AUTHOR]