Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

BACKGROUND AND AIMS: Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. METHODS: 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. RESULTS: We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. CONCLUSIONS: In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Effect of faecal microbial transplant via colonoscopy in patients with severe obesity and insulin resistance: A randomized double-blind, placebo-controlled Phase 2 trial.

AIM: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy. MATERIAL AND METHODS: In a double-blind, randomized controlled trial, subjects with a body mass index ≥ 35 kg/m2 and insulin resistance were randomized, in a 1:1 ratio in blocks of four, to either allogenic (from healthy lean donor; n = 15) or autologous FMT (their own stool; n = 13) delivered in the caecum and were followed for 3 months. The main outcome was homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes were glycated haemoglobin levels, lipid profile, weight, gut hormones, endotoxin, appetite measures, intestinal microbiome (IM), metagenome, serum/faecal metabolites, quality of life, anxiety and depression scores. RESULTS: In the allogenic versus autologous groups, HOMA-IR and clinical variables did not change significantly, but IM and metabolites changed favourably (P < 0.05): at 1 month, Coprococcus, Bifidobacterium, Bacteroides and Roseburia increased, and Streptococcus decreased; at 3 months, Bacteroides and Blautia increased. Several species also changed significantly. For metabolites, at 1 month, serum kynurenine decreased and faecal indole acetic acid and butenylcarnitine increased, while at 3 months, serum isoleucine, leucine, decenoylcarnitine and faecal phenylacetic acid decreased. Metagenomic pathway representations and network analyses assessing relationships with clinical variables, metabolites and IM were significantly enhanced in the allogenic versus autologous groups. LDL and appetite measures improved in the allogenic (P < 0.05) but not in the autologous group. CONCLUSIONS: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favourable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change. LDL and appetite variables may also benefit.

Case Studies of Intradialytic Total Parenteral Nutrition in Nocturnal Home Hemodialysis.

The standard use of intradialytic parenteral nutrition has yielded heterogeneous clinical results. Confounders include patient selection, limited dialysis sessional duration, and frequency. Nocturnal home hemodialysis provides an intensive form of kidney replacement therapy (5 sessions per week and 8 hours per treatment). We present a series of 4 nocturnal home hemodialysis patients who required intradialytic total parenteral nutrition (IDTPN) as their primary source of caloric intake. We describe the context, effectiveness, and complications of IDTPN in these patients. Our patients received a range of 1200 to 1590 kCal (including 60 to 70 g of amino acids) with each IDTPN session for up to 27 months. As the availability of home hemodialysis continues to grow, the role of supplemental or primary IDTPN will require further research for this vulnerable patient population.

Manipulation of intestinal microbiome as potential treatment for insulin resistance and type 2 diabetes.

PURPOSE: Increasing evidence suggests that the intestinal microbiome (IM) and bacterial metabolites may influence glucose homeostasis, energy expenditure and the intestinal barrier integrity and lead to the presence of systemic low-grade inflammation, all of which can contribute to insulin resistance (IR) and type 2 diabetes (T2D). The purpose of this review is to explore the role of the IM and bacterial metabolites in the pathogenesis and treatment of these conditions. RESULTS: This review summarizes research focused on how to modulate the IM through diet, prebiotics, probiotics, synbiotics and fecal microbiota transplant in order to treat IR and T2D. CONCLUSION: There is an abundance of evidence suggesting a role for IM in the pathogenesis of IR and T2D based on reviewed studies using various methods to modulate IM and metabolites. However, the results are inconsistent. Future research should further assess this relationship.

Phenotypic and genetic analysis of an adult cohort with extreme obesity.

CONTEXT: Adult extreme obesity (EO) is a growing health concern. The prevalence of known obesity associated co-morbidities namely cardio-metabolic and neuro-psychiatric disease in EO is not fully established. The contribution of pathogenic genetic variants, previously implicated in early childhood onset obesity, to adult EO is also not established. OBJECTIVE: We undertook phenotypic and genetic analysis of adult patients with extreme obesity (EO, BMI > 50). Specifically, we assessed the prevalence of eating disorders, cardio-metabolic, and neuro-psychiatric disease and the presence of pathogenic variants in known monogenic obesity genes. DESIGN: A total of 55 patients with EO from a single site bariatric surgery referral program were assessed for the presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease. The 54 obese (O) patients with a BMI < 50 from the same program were identified for phenotypic comparison. The 45 EO patients underwent whole exome sequencing to identify deleterious variants in known monogenic obesity genes. OUTCOMES: (1) Presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease in EO compared to O. (2) Onset of obesity in the EO group. (3) Presence of deleterious variants in genes previously implicated in monogenic obesity in the EO group. RESULTS: The EO group had higher prevalence of lifetime neuro-psychiatric disease (67.3% vs. 37%, p = 0.001) and sleep apnea (74.6% vs. 51.9%, p = 0.01) but lower prevalence of type 2 diabetes (30.1% vs. 50%, p = 0.045) compared to O. There were no significant differences in binge eating, dyslipidemia, hypertension, and cardiac disease. In the EO group, we found previously unreported singleton variants in NTRK2 (pS667W, bio-informatically predicted to be deleterious) and BDNF (pE23K). No previously confirmed loss of function variants in monogenic obesity genes were found. CONCLUSIONS: Adults with EO have significantly increased prevalence of neuro-psychiatric disease and a possibly lower burden of type 2 diabetes compared to less obese patients. Known monogenic causes of obesity were not highly prevalent in this cohort. Further studies are warranted to confirm these preliminary findings.

Non-alcoholic fatty liver disease and obesity: the role of the gut bacteria.

Non-alcoholic fatty-liver disease (NAFLD) is now considered one of the leading causes of liver disease worldwide and is associated with metabolic syndrome and obesity. There are several factors contributing to the disease state. Recent research suggests that the intestinal microbiota (IM) and bacterial products may play a role through several mechanisms which include increased energy uptake, intestinal permeability and chronic inflammation. In addition to diet and exercise, treatment options targeting the IM are being investigated and include the use of pre-, pro- and synbiotics as well as the possibility of fecal microbial transfers. This literature review explores the relationship between NAFLD and the IM as well as highlight new IM treatment options that may become available in the near future.

Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids.

UNLABELLED: In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross-sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty-two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long-chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH). CONCLUSION: Well-defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS.

Effect of a Sodium-Restricted Diet on Intake of Other Nutrients in Heart Failure: Implications for Research and Clinical Practice.

BACKGROUND: Sodium restriction is the primary dietary therapy for heart failure (HF) patients. Currently, it is unknown if changing diets to reduce dietary sodium in HF causes secondary changes to the intake of other nutrients in this patient population already at nutritional risk. METHODS AND RESULTS: HF patients (n = 16; 52 ± 12 years old; 78% male) followed a sodium-restricted diet for 1 week. Nutritional changes were documented at baseline and after a <2,000 mg/d sodium-restricted diet, as measured by food records before baseline and each day during the study. After a 49% reduction in dietary sodium (3,626 ± 956 to 1,785 ± 696 mg/d), we observed a significant reduction in calorie (2,467 ± 748 to 1,931 ± 388 kcal/d; P < .016), carbohydrate (293 ± 108 to 232 ± 56 g/d; P = .013), calcium (995 ± 496 to 609 ± 208 mg/d; P < .004), thiamine (2.0 ± 0.8 to 1.5 ± 0.8 mg/d; P = .020), and folate (412 ± 192 to 331 ± 172 µg/d; P = .019) intakes. There was a decrease in saturated fat (32 ± 18 to 21 ± 6 g/d; P = .032) and a trend to lower total fat (89 ± 34 to 68 ± 19 g/d; P = .066) and higher potassium (1,262 ± 328 to 1,405 ± 268 mg/1,000 kcal; P = .055) intakes. CONCLUSIONS: We found multiple unintentional nutritional consequences with dietary sodium reduction in HF patients. These findings highlight the need to consider the whole diet when counseling HF patients to lower sodium intake.

Factors associated with nutritional decline in hospitalised medical and surgical patients admitted for 7 d or more: a prospective cohort study.

This prospective cohort study was conducted in eighteen Canadian hospitals with the aim of examining factors associated with nutritional decline in medical and surgical patients. Nutritional decline was defined based on subjective global assessment (SGA) performed at admission and discharge. Data were collected on demographics, medical information, food intake and patients' satisfaction with nutrition care and meals during hospitalisation; 424 long-stay (≥7 d) patients were included; 38% of them had surgery; 51% were malnourished at admission (SGA B or C); 37% had in-hospital changes in SGA; 19·6% deteriorated (14·6% from SGA A to B/C and 5% from SGA B to C); 17·4% improved (10·6% from SGA B to A, 6·8% from SGA C to B/A); and 63·0 % patients were stable (34·4% were SGA A, 21·3% SGA B, 7·3% SGA C). One SGA C patient had weight loss ≥5%, likely due to fluid loss and was designated as stable. A subset of 364 patients with admission SGA A and B was included in the multiple logistic regression models to determine factors associated with nutritional decline. After controlling for SGA at admission and the presence of a surgical procedure, lower admission BMI, cancer, two or more diagnostic categories, new in-hospital infection, reduced food intake, dissatisfaction with food quality and illness affecting food intake were factors significantly associated with nutritional decline in medical patients. For surgical patients, only male sex was associated with nutritional decline. Factors associated with nutritional decline are different in medical and surgical patients. Identifying these factors may assist nutritional care.

Intestinal microbiota in patients with nonalcoholic fatty liver disease.

UNLABELLED: Despite evidence that the intestinal microbiota (IM) is involved in the pathogenesis of obesity, the IM composition of patients with nonalcoholic fatty liver disease (NAFLD) has not been well characterized. This prospective, cross-sectional study was aimed at identifying differences in IM between adults with biopsy-proven NAFLD (simple steatosis [SS] or nonalcoholic steatohepatitis [NASH]) and living liver donors as healthy controls (HC). Fifty subjects were included: 11 SS, 22 NASH, and 17 HC. One stool sample was collected from each participant. Quantitative real-time polymerase chain reaction was used to measure total bacterial counts, Bacteroides/Prevotella (herein referred to as Bacteroidetes), Clostridium leptum, C. coccoides, bifidobacteria, Escherichia coli and Archaea in stool. Clinical and laboratory data, food records, and activity logs were collected. Patients with NASH had a lower percentage of Bacteroidetes (Bacteroidetes to total bacteria counts) compared to both SS and HC (P = 0.006) and higher fecal C. coccoides compared to those with SS (P = 0.04). There were no differences in the remaining microorganisms. As body mass index (BMI) and dietary fat intake differed between the groups (P < 0.05), we performed linear regression adjusting for these variables. The difference in C. coccoides was no longer significant after adjusting for BMI and fat intake. However, there continued to be a significant association between the presence of NASH and lower percentage Bacteroidetes even after adjusting for these variables (P = 0.002; 95% confidence interval = -0.06 to -0.02). CONCLUSION: There is an inverse and diet-/BMI-independent association between the presence of NASH and percentage Bacteroidetes in the stool, suggesting that the IM may play a role in the development of NAFLD.

Impact of a formal mentoring program on academic promotion of Department of Medicine faculty: a comparative study.

PURPOSE: To evaluate the impact of a formal mentoring program on time to academic promotion and differences in gender-based outcomes. METHODS: Comparisons of time to promotion (i) before and after implementation of a formal mentoring program and (ii) between mentored and non-mentored faculty matched for covariates. Using paired-samples t-testing and mixed repeated measures ANCOVA, we explored the effect of mentor assignment and influence of gender on time to promotion. RESULTS: Promotional data from 1988 to 2010 for 382 faculty members appointed before 2003 were compared with 229 faculty members appointed in 2003 or later. Faculty appointed in 2003 or later were promoted 1.2 years (mean) sooner versus those appointed before 2003 (3.7 [SD = 1.7] vs. 2.5 [SD = 2], p < 0.0001). Regardless of year of appointment, mentor assignment appears to be significantly associated with a reduction in time to promotion versus non-mentored (3.4 [SD = 2.4] vs. 4.4 [SD = 2.6], p = 0.011). Gender effects were statistically insignificant. Post hoc analyses of time to promotion suggested that observed differences are not attributable to temporal effects, but rather assignment to a mentor. CONCLUSIONS: Mentoring was a powerful predictor of promotion, regardless of the year of appointment and likely benefited both genders equally. University resource allocation in support of mentoring appears to accelerate faculty advancement.

The effect of malnutrition on adult Covid-19 patient's ICU admission and mortality in Covid-19 isolation and treatment centers in Ethiopia: A prospective cohort study.

BACKGROUND: A new coronavirus was first identified in Wuhan, China in December 2019. Since the times of the 1918 influenza pandemic, malnutrition has been known as a risk factor for severity and mortality from viral pneumonia. Similarly, the recently identified SARS-Cov2 infection (COVID-19) and related pneumonia may be closely linked to malnutrition. Therefore, this study will contribute to new knowledge and awareness of the recording and evaluation of each COVID-19 patient's nutritional status by assessing the effect of malnutrition on ICU admission and death of COVID-19 patients in developing countries. METHOD: We conducted a prospective cohort study in adult COVID-19 patients admitted to selected COVID-19 Isolation and Treatment Centers, Addis Ababa, Ethiopia. Baseline data of the patients were collected using interviewer-administered structured questionnaire and data on the adverse outcomes of follow up were extracted from follow up chart. The main clinical outcomes (ICU admission and death) were captured every week of follow up. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on ICU admission and death. RESULTS: A total of 581 COVID-19 patients were enrolled. From the total of recruited patients, 346 (59.6%) were males and 235 (40.4%) were females. The mean age of the respondents was 55 years (16.45) years. The Cox proportional hazard model controlled for sex, age group, number of co-morbidities, and number of medications found that malnutrition at admission was associated with ICU admission and death. When compared to well-nourished patients, the rate of ICU admission was significantly associated and found to be higher among underweight [(adjusted hazard ratio (AHR) = 10.02, 95% CI: (8.64-12.10)] and overweight [(AHR = 7.7, 95% CI: (6.41-9.62)] patients. The rate of survival probability was significantly associated and was found to be better among well-nourished patients (AHR = 0.06, 95% CI : (0.01-0.44) when compared with malnourished COVID-19 patients. CONCLUSION: Malnutrition at the time of admission was shown to increase the risk of ICU admission and mortality among COVID-19 patients. Therefore, it is vital to evaluate patients' nutritional condition early in their admission and provide timely intervention to minimize the effects on patients and the healthcare system.

Use of teduglutide in adults with short bowel syndrome-associated intestinal failure.

Short bowel syndrome (SBS) is a rare gastrointestinal disorder associated with intestinal failure (SBS-IF) and poor health-related outcomes. Patients with SBS-IF are unable to absorb sufficient nutrients or fluids to maintain significantly metabolic homeostasis via oral or enteral intake alone and require long-term intravenous supplementation (IVS), consisting of partial or total parenteral nutrition, fluids, electrolytes, or a combination of these. The goal of medical and surgical treatment for patients with SBS-IF is to maximize intestinal remnant absorptive capacity so that the need for IVS support may eventually be reduced or eliminated. Daily subcutaneous administration of the glucagon-like peptide 2 analog, teduglutide, has been shown to be clinically effective in reducing IVS dependence and potentially improving the health-related quality of life of patients with SBS-IF. The management of patients with SBS-IF is complex and requires close monitoring. This narrative review discusses the use of teduglutide for patients with SBS-IF in clinical practice. The screening of patient eligibility for teduglutide treatment, initiation, monitoring of efficacy and safety of treatment, adapting or weaning off IVS, and the healthcare setting needed for SBS-IF management are described, taking into consideration data from clinical trials, observational studies, and clinical experience.

Clinical Overview of Sarcopenia, Frailty, and Malnutrition in Patients With Liver Cirrhosis.

Sarcopenia, frailty, and malnutrition in patients with liver cirrhosis are commonly observed and are associated with higher long-term mortality. Therefore, recognizing patients with increased nutritional risk and providing recommended interventions are essential in the long- and short-term management of cirrhosis, especially as alcoholic and non-alcoholic fatty liver disease continues to rise. Various assessment tools are available to gauge frailty and malnutrition but are infrequently used. Given the global burden of liver cirrhosis, periodic screening for malnutrition, sarcopenia, and frailty is desperately needed as it improves liver transplantation outcomes. Necessary steps include addressing knowledge gaps in professional healthcare workers and patients and using standardized assessment tools to counteract physical deconditioning as early as possible. One potential method for assessing sarcopenia involves using computed tomography to evaluate the skeletal muscle index. Regarding frailty, useful tools for longitudinal assessment include the liver frailty index and the Karnofsky performance status. Addressing educational requirements related to malnutrition involves seeking guidance from dieticians, who can provide counseling on achieving sufficient calorie and protein intake to combat the progression of malnutrition.

Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure.

BACKGROUND & AIMS: Although home parenteral nutrition (PN) can save the lives of patients with massive bowel loss that results in short-bowel syndrome and intestinal failure, quality of life is impaired by PN and its complications. We examined the 12-month tolerability and efficacy of teduglutide to reduce PN dependency. METHODS: Patients who received teduglutide (0.05 or 0.10 mg/kg/d) for 24 weeks in a randomized controlled trial were eligible for a 28-week double-blind extension study; 52 patients were given 52 weeks of the same doses of teduglutide. We investigated the safety, tolerability, and clinical efficacy (defined as a clinically meaningful ≥20% reduction in weekly PN volume from baseline) at week 52. RESULTS: The most common adverse events reported included headache (35%), nausea (31%), and abdominal pain (25%); 7 patients withdrew because of adverse events (gastrointestinal disorders in 4). Both groups had progressive reduction in PN. At week 52, 68% of the 0.05-mg/kg/d and 52% of the 0.10-mg/kg/d dose group had a ≥20% reduction in PN, with a reduction of 1 or more days of PN dependency in 68% and 37%, respectively. Four patients achieved complete independence from PN. CONCLUSIONS: For patients with short-bowel syndrome intestinal failure, the efficacy of teduglutide was maintained over 52 weeks and the safety profile was sufficient for it to be considered for long-term use. Further studies are needed to determine whether these effects will translate into improved quality of life and reduced PN complications. ClinicalTrials.gov number, NCT00172185.

In critically ill adult patients with COVID-19, lower energy and higher protein intake are associated with fewer mechanical ventilation and antibiotic days but not with ICU length of stay.

BACKGROUND: Coronavirus disease 2019 (COVID-19) nutrition management guidelines recommend hypocaloric, high-protein feeding in the acute phase of critical illness. This study aimed to determine, among critically ill adults with COVID-19, whether nutrition support affects outcomes in nonobese patients when providing a mean energy intake of ≥20 kcal/kg/day vs <20 kcal/kg/day and protein intake of ≥1.2 g/kg/day vs <1.2 g/kg/day, using actual body weight, and in patients with obesity when providing ≥20 kcal/kg/day vs <20 kcal/kg/day and a protein intake of ≥2 g/kg/day vs <2 g/kg/day using ideal body weight. METHODS: This retrospective study included adults with COVID-19 on mechanical ventilation (MV) admitted to the intensive care unit (ICU) from 2020 to 2021. Clinical and nutrition parameters were recorded the first 14 days of ICU stay. RESULTS: One hundred four patients were included: 79 (75.96%) were male and had a median age of 51 years and body mass index of 29.65 kg/m2 . ICU length of stay (LOS) was not affected by nutrition intake, but patients receiving <20 kcal/kg/day had fewer MV days (P = 0.029). In a subgroup analysis, MV days were lower in the nonobese group receiving <20 kcal/kg/day (P = 0.012). In the obese group, those receiving higher protein intake had fewer antibiotic days (P = 0.013). CONCLUSION: In critically ill patients with COVID-19, lower energy and higher protein intake were respectively associated with fewer MV days and, in patients with obesity, fewer antibiotic days, but they had no effect on ICU LOS.

Relationship between dietary intake components and hepatic fibrosis in those with obesity before and 1 year after bariatric surgery.

OBJECTIVES: Non-alcoholic fatty liver disease is highly prevalent in the bariatric population but not all patients develop liver fibrosis. Considering that fibrosis may affect clinical outcomes, it is important to assess and treat contributing factors. In this population, it is not clear whether dietary intake is a contributor. The objective was to determine the relationship between dietary intake components and liver fibrosis before and 1 y after Roux-en-Y gastric bypass (RYGB). METHODS: This was a prospective cross-sectional (n = 133) study conducted between 2013 and 2022. In addition, a subgroup of 44 patients were followed for 1 y post-RYGB. Anthropometrics, biochemical measurements, and 3-d food records and liver biopsies were obtained presurgery and, in a subgroup of patients, as for the cohort, 1 y post-RYGB. RESULTS: In the cross-sectional study, 78.2% were female, with a median age of 48 y and body mass index of 46.8 kg/m2; 33.8% had type 2 diabetes mellitus and 57.1% had metabolic syndrome. In a multivariate analysis, age (odds ratio; 95% CI) (1.076; 1.014-1.141), alanine transaminase (1.068; 1.025-1.112), calorie intake (1.001; 1.000-1.002), and dietary copper (0.127; 0.022-0.752) were independently associated with fibrosis (<0.05). At 1 y post-RYGB, no independent risk factors were associated with persistent fibrosis. CONCLUSIONS: In bariatric patients before surgery, higher age, alanine transaminase, and total calorie and lower copper intakes were independent risk factors associated with liver fibrosis. These relationships were no longer observed after RYGB, likely due to the effect of surgery on weight and similar postsurgery diet among patients.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

PURPOSE: Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS: This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS: One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION: Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Adipose Tissue and Plasma Markers Associated with HbA1c Pre- and Post-bariatric Surgery: a Cross-sectional and Cohort Study.

PURPOSE: Obesity can be associated with chronic inflammation and dysregulated expression of inflammatory adipokines that contribute to insulin resistance and type 2 diabetes. This may also affect the clinical response to bariatric surgery. Our objective was whether baseline visceral adipose tissue features and plasma adipokine are associated with HbA1c ≥0.06 at the time of Roux-en-Y gastric bypass (RYGB) surgery and with persistently elevated HbA1c at 12 months post-RYGB. METHODS: During the surgery, adipose biopsies and plasma were collected for adipokine/cytokine profile. Clinical and biochemical measurements were also collected at the time of RYGB and, in those with baseline elevated HbA1c, at 12 months post-RYGB. RESULTS: In the cross-sectional study, 109 patients (82.6% female; age 49 years; BMI 46.98 kg/m2) participated. Of those with elevated HbA1c at baseline (n = 61), 47 patients had repeated measurements at 12 months post-RYGB (23% drop-out). Using a multivariate logistic regression model, older age (adjusted odds ratio (aOR), 1.14; 95% confidence interval (CI), 1.06-1.22) and higher plasma resistin (aOR, 5.30; 95% CI, 1.25-22.44) were associated with higher odds of HbA1c ≥ 0.06, whereas higher plasma adiponectin (aOR, 0.993; 95% CI, 0.99-0.996) was associated with lower odds of HbA1c ≥0.06. In addition, baseline higher average adipose cell area (aOR, 1.0017; 95% CI, 1.0002-1.0032) and plasma resistin (aOR, 1.0004; 95% CI, 1.0000-1.0009) were associated with higher odds of having persistently elevated HbA1c at 12 months post-RYGB. CONCLUSION: Our study suggests that baseline plasma adipokine dysregulation, specifically high resistin, and adipocyte hypertrophy may affect the clinical response to RYGB.

Comparing mixed oil to soybean oil lipid emulsion in patients on home parenteral nutrition: a pilot prospective double-blind, crossover, randomized trial.

BACKGROUND: Home parenteral nutrition (HPN) can be associated with increased liver enzymes, catheter-related bloodstream infections (CRBSI), and hospitalizations. Mixed oil (MO) versus soybean oil (SO) lipid emulsion reduces risks in hospitalized patients, but there are no randomized double-blinded controlled trials in HPN. Therefore, the primary objective was to test the study's feasibility such as recruitment and retention in the HPN population and the secondary objective was to assess changes in liver enzymes between MO and SO as well as other clinical and biochemical outcomes. METHODS: This 13-month prospective double-blind crossover randomized pilot trial took place in Toronto, Canada. Participants were HPN patients who were a part of the HPN program at Toronto General Hospital. We recruited patients from the HPN program. HPN patients receiving SO were randomized to either MO or SO, and the study duration was 6 months in each arm (MO or SO) with a 1-month washout period resuming SO. As this is a crossover trial design, the patient is his/her own control. The main outcome measures were descriptions of study feasibility, namely the study recruitment and retention. We also collected biochemical parameters, CRSBI, hospitalization rate, antibiotic use, and mortality. Demographic, nutritional, clinical, and laboratory data were collected at baseline, 3 and 6 months of each arm. The primary analysis population was defined as the per-protocol population who completed the trial including all lipid measurements. RESULTS: A total of 65 HPN patients were assessed, and 60 met the inclusion criteria for the study. Thirty-five percent (21/60) were randomized using a computer-generated random number sequence generator: 10 participants were randomized to receive SO first while 11 were randomized to receive MO first. At 13 months, 3/10 who received SO first completed the study, whereas 9/11 who received MO first completed the study. This did not meet our a priori criteria for success in recruitment and retention. Between types of lipid emulsions, there were no significant differences in changes in liver enzymes or biochemical and clinical outcomes, despite significant changes in plasma free fatty acid composition reflecting MO or SO. CONCLUSIONS: Overall, this pilot trial demonstrated that the use of a prospective double-blind, crossover, randomized trial design was not feasible to conduct in the HPN population because of difficulties in recruiting and retaining patients. In addition, there was no significant impact of MO versus SO lipid emulsion on liver enzymes or most parameters. The lack of significance may be attributed to low sample size from low recruitment and high drop-out rate, short study duration (6 months/arm), and complex care. In a future definitive trial, a multicenter study of longer duration and a larger sample size is recommended, and drop-outs may be reduced by using a parallel study design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02796833. Registered on 13 June 2016-retrospectively registered.