Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD and non-MAFLD HCC. RESULTS: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% CI; 34.5% - 63.0%) and 12.4% (95% CI; 8.3% - 17.3%), respectively. In HCC due to chronic hepatitis B, C and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI; 30.2% - 50.3%), 54.1% (95% CI; 40.4% - 67.6%) and 64.3% (95% CI; 52.7% - 75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. CONCLUSION: MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

Parenteral nutrition-related complications in older patients with acute intestinal failure: A descriptive cohort study.

INTRODUCTION: Reported outcomes for parenteral nutrition (PN)-related complications in older adult patients with acute intestinal failure who are receiving PN in the acute hospital setting are limited. Our study aims to compare PN-related complications between older and younger adult patients. METHODS: A retrospective descriptive study of inpatients who were administered PN from January 1, 2019, to December 31, 2019, was performed. Patients were categorized into older (≥65 years old) and younger (<65 years old) adult groups. RESULTS: Two hundred thirty-five patients were included. There were 103 patients in the older adult group (mean age: 73.9 [SD: 6.9] years) and 132 patients in the younger adult group (mean age: 52.4 [SD: 12.5] years). There was a significantly higher Charlson Comorbidity Index score and lower Karnofsky score in the older adult group. The older adult group received significantly lower total energy (20.8 [SD: 7.8] vs 22.8 [SD: 6.3] kcal/kg/day), dextrose (3.1 [SD: 1.4] vs 3.6 [SD: 1.4] g/kg/day), and protein (1.1 [SD: 0.4] vs 1.2 [SD: 0.3] g/kg/day) than the younger group received. The mean length of stay was significantly shorter in the older adult group (35.9 [SD: 21.3] vs 59.8 [SD: 55.3]; P < 0.05). There was no significant difference in PN-related complications and clinical outcomes (catheter-related bloodstream infections, hypoglycemia or hyperglycemia, fluid overload, or inpatient mortality) between the two groups. CONCLUSION: Despite more comorbidities in the older adult, the usage of PN in older adult patients with acute intestinal failure was associated with neither an increased rate of PN-related complications nor worse clinical outcomes when compared with that of younger patients.

Approximately 1 in 10 ambulatory inflammatory bowel disease patients are at risk of malnutrition: A prospective Singapore cohort.

OBJECTIVES: Prevalence of malnutrition among ambulatory inflammatory bowel disease (IBD) patients in Singapore is unknown. We aimed to evaluate the prevalence of ambulatory IBD patients at risk of malnutrition (ARMN) using Malnutrition Universal Screening Tool (MUST) and its clinical outcomes. METHODS: IBD patients were recruited from March to June 2018 and followed up for 6 months. ARMN patients were defined as having a MUST score of 2 or more compared with those not at risk (non-ARMN). RESULTS: Altogether 217 patients were recruited, including 128 (59.0%) with ulcerative colitis (UC) and 89 (41.0%) with Crohn's disease (CD). The mean body mass index (BMI) was 23.5 ± 4.5 kg/m2 ; 35 (16.1%) patients were on biologics, and 52 (24.0%) were on steroids. Among them 25 (11.5%) patients were ARMN, with a predominance of UC (n = 15, 60.0%). The majority of ARMN patients were underweight (n = 23, 92.0%) while 114 (59.4%) non-ARMN patients were overweight. ARMN patients had a significantly lower albumin (38.3 g/L vs 41.9 g/L) and a significantly increased proportion of patients with C-reactive protein ≥5 mg/L (36.0% vs 19.3%). There was a trend towards longer hospital stay among ARMN patients, although this was not statistically significant. Use of biologics or immunomodulators and albumin levels were associated with being ARMN. CONCLUSION: Using MUST, 11.5% of our ambulatory IBD patients in Singapore were identified to be ARMN. Among ARMN patients, a trend was demonstrated towards a longer hospital stays for admitted patients. This underscores the need to actively screen ambulatory IBD patients for malnutrition.

Virtual monitoring for stable chronic hepatitis B patients does not reduce adherence to medications: A randomised controlled study.

INTRODUCTION: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB. METHODS: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1-10. RESULTS: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients - 76 (80.9%) in VMC group and 74 (75.5%) in control group - had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group (p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively (p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm. DISCUSSION: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients.

The use of standardized commercially available parenteral nutrition as a bridge to customized compounded bag in the acute hospital setting is safe and feasible.

BACKGROUND & AIMS: The use of standardized commercially available parenteral nutrition (SCAPN) as a starter bag to bridge to customized compounded PN offers the advantage of starting PN on the same day of consult, avoiding delays in nutrition delivery. We aim to evaluate the safety and feasibility of using SCAPN as a bridge to compounded PN in the acute hospital setting. METHODS: Retrospective review of patients on PN from Aug 2018 to Sep 2019 was performed. SMOFKABIVEN® Peripheral 800 kcal in 1206 ml was used. Electrolyte replacements on the day and the day after PN commencement were compared between SCAPN and compounded PN. Results were reported as means (95% confidence intervals). P value < 0.05 was considered statistically significant. RESULTS: 135 (78.5%) patients received SCAPN while 37 (21.5%) received compounded PN on the first day of PN. Baseline characteristics of both groups were almost similar with higher BMI in the SCAPN. Baseline serum potassium 4.0 (3.9, 4.1) vs 4.0 (3.8, 4.1), p = 0.46; phosphate 1.1 (1.0, 1.1) vs 1.1 (1.0, 1.3), p = 0.40 and magnesium 0.8 (0.8, 0.9) vs 0.9 (0.9, 1.0), p < 0.05 for SCAPN and compounded PN respectively. Follow-up serum potassium was 3.9 (3.8, 3.9) vs 3.9 (3.8, 4.1), p = 0.36; phosphate 0.9 (0.9, 0.9) vs 1.1 (1.0, 1.2), p < 0.05 and magnesium 0.9 (0.9, 0.9) vs 0.9 (0.9, 1.0), p = 0.18. Baseline calories and protein were lower in SCAPN group. Electrolyte replacements were similar in both groups at baseline and follow up. CONCLUSION: Using our in-house protocol, the use of a SCAPN as a bridge to customized compounded PN is safe and feasible.

Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome: A prospective multi-centre cohort study.

BACKGROUND: Autoimmune markers including plasma cells (PC), anti-smooth-muscle antibody (ASMA), anti-nuclear antibody (ANA), and raised immunoglobulin G (IgG) are commonly observed in non-alcoholic steatohepatitis (NASH), however their clinical significance is unknown. AIM: To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes. METHODS: Consecutive patients with biopsy proven NASH from Christchurch Hospital, New Zealand and Singapore General Hospital (SGH) were included between 2005 to 2016 in a prospective multi-centre cohort study. Patients with other causes of chronic liver disease were excluded. IgG > 14 g/L or globulin fraction > 50%, ANA ≥ 1:40, SMA ≥ 1:40 were considered positive. Multivariate analysis was performed to assess which markers were independently associated with mortality and hepatic decompensation. RESULTS: Total 261 patients were included of which 201 were from SGH. The median age was 53 and 51.9% were male. Advanced fibrosis was present in 31.4% at diagnosis. PC, ASMA, ANA and raised IgG were observed in 13.1%, 4.9%, 27.8% and 30.1% of patients respectively. After multivariate analysis, elevated IgG [Hazard Ratio (HR) 6.79, 95%CI: 2.93-17.15] and fibrosis stage (HR 1.37, 95%CI: 1.03-1.87) were found to be independently associated with increased risk of liver decompensation. Age (HR 1.06, 95%CI: 1.02-1.10) and elevated IgG (HR 3.79, 95%CI: 1.90-7.68) were independent factors associated with higher mortality risk. CONCLUSION: Elevated IgG, rather than ANA, ASMA or plasma cells, is independently associated with increased risk of hepatic decompensation and mortality in NASH. It could hence be important for prognostication.

Association between non-alcoholic fatty liver disease and subclinical atherosclerosis in Western and Asian cohorts: an updated meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences. METHODS: This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted. RESULTS: 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as 'high quality', with the remaining 25 of 'moderate quality'. CONCLUSIONS: There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.

Modified minimal-contact COVID-19 workflow allows for safe, remote parenteral nutrition prescribing in non-critically ill patients.

BACKGROUND: In line with recent guidance from the American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) to minimize healthcare team exposure by clustering care and relying on other providers or telehealth to collect relevant nutrition assessments, our nutrition support team has adopted a modified workflow using information technology to provide parenteral nutrition (PN) remotely in a safe and timely manner. We aim to compare our prescribing adequacy and PN-related complications before and during the coronavirus disease 2019 (COVID-19) outbreak using the modified workflow in non-critically ill patients. METHODS: This study reviewed a prospectively recruited cohort of adults receiving PN in the general wards or high-dependency units from December 5, 2019, to April 15, 2020. Demographic data, nutrition assessment, PN prescriptions, blood results, electronic notes, capillary blood glucose monitoring, and catheter-related bloodstream infection rates were reviewed for patients who received PN. RESULTS: We found that patients who started PN during COVID-19 were more malnourished with lower body mass index and higher proportion of Subjective Global Assessment B/C scores (52 [92.9%] vs 36 [73.5%], P < .005). The proportion of patients who achieved target energy amounts within 5 days was similar in both groups. Protein prescription was >1 g/kg/day in both groups, though there was a trend of higher protein prescription during COVID-19. Complications were similar in both groups. CONCLUSION: Our study demonstrates that minimal contact with effective multidisciplinary communication using the modified workflow can allow for safe and timely PN administration.

Clinical profile of non-alcoholic fatty liver disease in nonobese patients.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome. Worryingly, it has been increasingly reported among nonobese patients. This study aims to analyse patient characteristics of biopsy-proven NAFLD in an Asian cohort and explore differences stratified by body mass index (BMI). METHODS: Clinical, laboratory, and histological data were collected from 263 adults with biopsy-proven NAFLD. Patients with and without obesity (BMI cut-off 25) were compared. The ability to predict advanced liver fibrosis with three non-invasive scores, the NAFLD Fibrosis score (NFS), Fibrosis-4 (FIB4), and the aspartate aminotransferase to platelet ratio index (APRI), was compared. RESULTS: Obese subjects had a lower mean age (49.5 ± 12.5 vs 54.0 ± 12.9 years, P = 0.017), a higher prevalence of diabetes (52.4% vs 36.8%, P = 0.037), and a higher waist circumference (113.9 ± 16.0 cm vs 87.0 ± 18.4 cm, P = 0.022). The prevalence of dyslipidaemia (68.0% vs 61.4%, P = 0.353) and hypertension (61.7% vs 49.1%, P = 0.190) was comparable between the two groups. The distribution of non-alcoholic steatohepatitis (NASH) (63.1% versus 61.4%, P = 0.710) and advanced fibrosis (31.6% versus 26.3%, P = 0.447) were also similar in both groups. All three non-invasive scores (NFS, FIB4, and APRI) performed poorly in predicting advanced fibrosis in nonobese patients with NAFLD. The FIB4 was the most accurate non-invasive score in predicting advanced fibrosis in the obese group. CONCLUSIONS: Obese and nonobese patients are equally at risk of NASH and advanced fibrosis. While the FIB4 is the most accurate non-invasive score in predicting advanced fibrosis among obese individuals, further research is warranted to develop a nonobese specific score to correctly identify nonobese NAFLD patients with advanced fibrosis.

Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern. In the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH), the presence of significant fibrosis at index assessment is associated with poor prognosis and increased mortality. Hence, there is a growing need to accurately assess and stage fibrosis. Liver biopsy, the current gold standard, has limitations with sampling error and is invasive, with associated inherent risk. This has led to a host of non-invasive means of assessing fibrosis, which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over time. This review discusses, comprehensively, the various tools available to the clinician for the assessment of fibrosis, including the various scoring systems used in liver biopsy, the non-invasive means of serum biomarkers, such as the highly-validated NAFLD fibrosis score, and the imaging-based modalities, such as transient elastography and magnetic resonance elastography.