Long term clinical outcomes of home parenteral nutrition in Singapore.

BACKGROUND AND OBJECTIVES: Home parenteral nutrition (HPN) is a life sustaining therapy for patients with chronic intestinal failure. Reported outcomes for Asian HPN patients are scarce. We aim to review the clinical outcomes of adult and paediatric HPN patients in our cohort which caters for 95% of Singaporean HPN patients. METHODS AND STUDY DESIGN: This is a retrospective review of HPN patients from an adult (2002-2017) and paediatric cohort (2011-2017) from the largest tertiary PN centres in Singapore. Patient demographics and clinical outcomes were reviewed. RESULTS: There were 41 adult and 8 paediatric HPN patients. Mean age was 53.0(±15.1) (adults) and 8(±1.8) years-old (paediatrics). Mean duration of HPN was 2.6(±3.5) and 3.5(±2.5) years. Leading indications for adult HPN were short bowel syndrome (SBS) (n=19,46.3%), mechanical obstruction (n=9,22.0%), and gastrointestinal dysmotility disorders (GID) (n=5,12.2%). Thirteen adult (31.7%) patients had underlying malignancy, with seven (17.3%) receiving palliative HPN. Indications for HPN amongst paediatric patients was GID (n=5,62.5%) and SBS (n=3,37.5%). Central line-associated bloodstream infection (CLABSI)/1000catheter-days was 1.0(±2.1) and 1.8(±1.3). Catheter associated venous thrombosis (CAVT)/1000catheter-days was 0.1(±0.4) and 0.7(±0.8). Biochemical Intestinal Failure Associated Liver Disease (IFALD) was found in 21.9% and 87.5%. For adults, median overall survival was 90-months (4.3,175.7,95%CI), with actuarial survival of 70.7%(1-year) and 39.0%(5-years). Median survival for adult patients with malignancy was 6-months (4.2,7.7,95%CI), actuarial survival of 85.7%(3-months) and 30.7%(1-year). One adult patient died from PN related complications. No paediatric deaths were noted. CONCLUSIONS: Whilst patient numbers were modest, we report comparable complication and survival rates to other international centres in both our adult and paediatric cohorts.

Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

BACKGROUND & AIMS: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH. METHODS: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture. RESULTS: Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated ß -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH. CONCLUSIONS: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH. LAY SUMMARY: The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis.

Validation of the Expanded Baveno-VI Criteria for Screening Gastroscopy in Asian Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND: The expanded Baveno-VI criteria may further reduce the need for screening gastroscopy compared to Baveno-VI criteria. AIM: We sought to validate the performance of these criteria in a cohort of compensated advanced chronic liver disease (cACLD) patients with predominantly hepatitis B infection. METHODS: Consecutive cACLD patients from 2006 to 2012 with paired liver stiffness measurements and screening gastroscopy within 1 year were included. The expanded Baveno-VI criteria were applied to evaluate the sensitivity (SS), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the presence of high-risk varices (HRV). RESULTS: Among 165 cACLD patients included, 17 (10.3%) had HRV. The commonest etiology of cACLD was chronic hepatitis B (36.4%) followed by NAFLD (20.0%). Application of expanded Baveno-VI criteria avoided more screening gastroscopy (43.6%) as compared to the original Baveno-VI criteria (18.8%) without missing more HRV (1 with both criteria). The overall SS, SP, PPV and NPV of the expanded Baveno-VI criteria in predicting HRV were 94.1%, 48.0%, 17.2% and 98.6%, respectively. CONCLUSION: Application of the expanded Baveno-VI criteria can safely avoid screening gastroscopy in 43.6% of cACLD patients with an excellent ability to exclude HRV.

Approximately 50% of acute intestinal failure (AIF) patients on short-term parenteral nutrition (PN) have intestinal failure-associated liver disease (IFALD) without effect on hospital length of stay and mortality.

INTRODUCTION: Patients with intestinal failure (IF) are often dependent on PN for provision of calories and nutrients for survival. Similar to chronic intestinal failure (CIF) patients, those who have AIF are also at risk of IFALD, which is a poorly understood but potentially fatal condition. The local incidence of IFALD amongst AIF patients is not known. OBJECTIVES: The primary objective of this study was to determine the incidence of IFALD in AIF patients on short-term PN. Secondary objectives were to analyse patient and PN risk factors of IFALD, and clinical outcomes of length of stay (LOS) and inpatient mortality. DESIGN: This was a retrospective cross-sectional cohort study of hospitalised adult patients with AIF prescribed with short-term PN. All adult patients aged 21 years and above who received PN for at least 5 consecutive days and had normal liver function tests (LFTs) at the time of PN initiation were included in this study. RESULTS: A total of 171 patients were enrolled in this study, with 77 (45%) having deranged LFTs at the end of PN therapy and categorised under the IFLAD group. The patient cohort was predominantly male (92 [54%]) and had a median age of 68 years (IQR 59-76). Patients with IFALD at the end of PN therapy had higher diabetes prevalence (36% vs 26%, p = 0.2) and were on PN for a longer duration (median [IQR]: 12 [8-17] vs 8 [6-15] days, p = 0.003) than those without IFALD. There were no significant differences in patient and PN characteristics between the IFLAD and non-IFALD group. The multivariable models showed that the IFALD cohort had longer hospital stays (HR 0.90, 95% CI 0.65-1.23) and lower odds of inpatient death (OR 0.75, 95% CI 0.12-4.60), though both findings are not statistically significant (p = 0.5, 0.7). CONCLUSION: In this study, IFALD is a common phenomenon in AIF and the incidence was found to be an estimated 50% amongst patients on short-term PN with similar clinical outcomes between the two groups.

Approach to Abnormal Liver Biochemistries in the Primary Care Setting.

Liver biochemistries are commonly ordered in the primary care setting, and they may return abnormal even in an asymptomatic patient. Primary care physicians need to have a systematic way of interpreting any derangement in these tests so that further investigations, referrals, and management can be arranged appropriately. This review dwells into patterns of liver biochemistry derangement, common aetiologies to consider, history and examinations that are required, initial investigations to order, and when to refer urgently to the emergency department.