Reversing malnutrition and low muscle strength with targeted enteral feeding in patients awaiting liver transplant: A randomized controlled trial.

BACKGROUND AND AIMS: Most patients with decompensated cirrhosis fail to meet their nutrition targets. The impact of nasogastric feeding (NGF) on malnutrition in cirrhosis remains unknown. This study aims to assess the impact of pretransplant NGF on pre-liver transplant and post-liver transplant outcomes. APPROACH AND RESULTS: This single-center, prospective randomized controlled trial of 55 patients with severe malnutrition and low handgrip strength (HGS) compared a standard high-energy high-protein diet to diet plus supplemental nocturnal NGF while awaiting transplant. The primary outcome was a change in HGS. The median age was 58.5 years (IQR: 51.1-64), median MELD was 24 (20-28.5), and 32 (58%) patients were male. The median duration of NGF was 63.0 days (34.5-127), following which time the median between-group difference in HGS was 3.6 kg (95% CI: 1.7-5.2, p <0.001), an increase of 20% from baseline. Mid-upper-arm circumference, triceps skinfold, and immune function all increased significantly with NGF. Muscle and nutritional parameters continued to improve with increasing duration of feeding. NGF significantly increased daily energy intake between groups by 1285 kcal (95% CI: 860-1677) and protein intake by 51 g (95% CI: 32-71) (both p <0.001). All NGF patients met >100% of their measured nutritional requirements. Posttransplant clinical outcomes were similar between groups. CONCLUSIONS: Targeted enteral feeding before liver transplant improves HGS, anthropometry, and immune function in severely malnourished patients with cirrhosis. These findings provide a strong rationale for early consideration of NGF to reverse malnutrition and improve muscle strength. Appropriately powered studies should explore whether NGF can also impact clinically relevant outcomes including pretransplant and posttransplant mortality.

Continuous home terlipressin infusion increases handgrip strength and reduces ascites-A prospective randomized crossover study.

BACKGROUND AND AIMS: Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. APPROACH AND RESULTS: This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. CONCLUSIONS: This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.

Benefits of phone consultation for endoscopy-related clinics in the COVID-19 pandemic.

BACKGROUND AND AIM: During COVID-19 outbreak, restrictions to in-person consultations were introduced with a rise in telehealth. An indirect benefit of telehealth could be better attendance. This study aimed to assess "failure-to-attend" (FTA) rate and satisfaction for two endoscopy-related compulsory telehealth clinics during the COVID-19 outbreak. METHODS: Consecutive patients booked for endoscopy-related telehealth clinics at a tertiary hospital were prospectively assessed. In-person clinic control data were assessed retrospectively. Sample size was calculated to detect an anticipated increase in attendance of 8%. Secondary outcomes included FTA differences between clinics and evaluation of patients and doctors satisfaction. Satisfaction was assessed based on six Likert scale questions used in previous telehealth research and asked to both patients and doctors (6Q_score). This study was exempt from IRB review after institutional IRB review. RESULTS: There were 691 patients booked for appointments in our endoscopy clinics during the study periods (373 in 2020). FTA rates were lowered by half during the compulsory telehealth clinics (12.6% to 6.4%, P < 0.01). The patient 6Q_score was higher for the advanced endoscopy clinic (84.6% vs 73.8%, P < 0.01), while the doctor 6Q_score was similar between both advanced clinics and post endoscopy clinics (91.1% vs 92.5% respectively, P = 0.80). An in-person follow-up consultation was suggested for 3.5% of the appointments, while the necessity of physical examination was flagged in 5.1%. CONCLUSIONS: The use of phone consultations in endoscopy-related clinics during the COVID-19 outbreak has improved FTA rates while demonstrating high satisfaction rates. The need for in-person follow-up consultations and physical examination were low.

Risk stratification in acute upper GI bleeding: comparison of the AIMS65 score with the Glasgow-Blatchford and Rockall scoring systems.

BACKGROUND AND AIMS: The American College of Gastroenterology recommends early risk stratification in patients presenting with upper GI bleeding (UGIB). The AIMS65 score is a risk stratification score previously validated to predict inpatient mortality. The aim of this study was to validate the AIMS65 score as a predictor of inpatient mortality in patients with acute UGIB and to compare it with established pre- and postendoscopy risk scores. METHODS: ICD-10 (International Classification of Diseases, Tenth Revision) codes identified patients presenting with UGIB requiring endoscopy. All patients were risk stratified by using the AIMS65, Glasgow-Blatchford score (GBS), pre-endoscopy Rockall, and full Rockall scores. The primary outcome was inpatient mortality. Secondary outcomes were a composite endpoint of inpatient mortality, rebleeding, and endoscopic, radiologic, or surgical intervention; blood transfusion requirement; intensive care unit (ICU) admission; rebleeding; and hospital length of stay. The area under the receiver-operating characteristic curve (AUROC) was calculated for each score. RESULTS: Of the 424 study patients, 18 (4.2%) died and 69 (16%) achieved the composite endpoint. The AIMS65 score was superior to both the GBS (AUROC, 0.80 vs 0.76, P < .027) and the pre-endoscopy Rockall score (0.74, P = .001) and equivalent to the full Rockall score (0.78, P = .18) in predicting inpatient mortality. The AIMS65 score was superior to all other scores in predicting the need for ICU admission and length of hospital stay. AIMS65, GBS, and full Rockall scores were equivalent (AUROCs, 0.63 vs 0.62 vs 0.63, respectively) and superior to pre-endoscopy Rockall (AUROC, 0.55) in predicting the composite endpoint. GBS was superior to all other scores for predicting blood transfusion. CONCLUSION: The AIMS65 score is a simple risk stratification score for UGIB with accuracy superior to that of GBS and pre-endoscopy Rockall scores in predicting in-hospital mortality and the need for ICU admission.

Portal Hypertension in Malnutrition and Sarcopenia in Decompensated Cirrhosis-Pathogenesis, Implications and Therapeutic Opportunities.

Malnutrition and sarcopenia are highly prevalent in patients with decompensated cirrhosis and are associated with poorer clinical outcomes. Their pathophysiology is complex and multifactorial, with protein-calorie malnutrition, systemic inflammation, reduced glycogen stores and hormonal imbalances all well reported. The direct contribution of portal hypertension to these driving factors is however not widely documented in the literature. This review details the specific mechanisms by which portal hypertension directly contributes to the development of malnutrition and sarcopenia in cirrhosis. We summarise the existing literature describing treatment strategies that specifically aim to reduce portal pressures and their impact on nutritional and muscle outcomes, which is particularly relevant to those with end-stage disease awaiting liver transplantation.

Transjugular intrahepatic portosystemic shunt insertion improves muscle mass but not muscle function or frailty measures.

INTRODUCTION: Sarcopenia in cirrhosis is associated with poor outcomes. While transjugular intrahepatic portosystemic shunt (TIPS) insertion improves radiological measures of muscle mass, its impact on muscle function, performance and frailty has not been evaluated. METHODS: Patients with cirrhosis referred for TIPS were prospectively recruited and followed for 6 months. L3 CT scans were used to calculate skeletal muscle and adipose tissue parameters. Handgrip strength, Liver Frailty Index and short physical performance battery were serially monitored. Dietary intake, insulin resistance, insulin-like growth factor (IGF)-1, and immune function using QuantiFERON Monitor (QFM) were measured. RESULTS: Twelve patients completed the study with a mean age of 58 ±â€…9 years and model for end-stage liver disease score of 16 ±â€…5. At 6 months post-TIPS, skeletal muscle area increased from 139.33 cm 2  ±â€…22.72 to 154.64 ±â€…27.42 ( P  = 0.012). Significant increases were observed in the subcutaneous fat area ( P  = 0.0076) and intermuscular adipose tissue ( P  = 0.041), but not muscle attenuation or visceral fat. Despite marked changes in muscle mass, no improvements were observed in handgrip strength, frailty, or physical performance. At 6 months post-TIPS, IGF-1 ( P  = 0.0076) and QFM ( P  = 0.006) increased compared to baseline. Nutritional intake, hepatic encephalopathy measures, insulin resistance and liver biochemistry were not significantly impacted. CONCLUSION: Muscle mass increased following TIPS insertion as did IGF-1, a known driver of muscle anabolism. The lack of improvement in muscle function was unexpected and may relate to impairment in muscle quality and the effects of hyperammonaemia on muscle contractile function. Improvements in QFM, a marker of immune function, may suggest a reduction in infection susceptibility in this at-risk population and requires further evaluation.

Outcomes of patients with hepatorenal syndrome undergoing liver transplantation in the era of terlipressin.

BACKGROUND: The efficacy of terlipressin in improving pre-liver transplant renal function in hepatorenal syndrome (HRS) has been well documented, however, its impact on post-transplant renal function remains poorly described. This study aims to describe the impact of HRS and terlipressin on post-liver transplant renal function and survival. METHODS: A single-centre, retrospective, observational study was conducted to identify post-transplant outcomes of patients diagnosed with HRS undergoing liver transplant (HRS cohort) and those undergoing transplant for non-HRS, non-hepatocellular carcinoma cirrhotic indications (comparator cohort) between January 1997 and March 2020. The primary outcome was serum creatinine at 180 days post-liver transplant. Other renal outcomes and overall survival were secondary outcomes. RESULTS: 109 patients with HRS and 502 comparator patients underwent liver transplant. The comparator cohort was younger than the HRS cohort (53 vs. 57 years, P < 0.001). The median creatinine at day 180 post-transplant was higher in the HRS transplant group (119 µmol/L vs. 103 µmol/L, P < 0.001), however, this association lost significance following multivariate analysis. Seven patients (7%) in the HRS cohort received a combined liver-kidney transplant. There was no significant difference in the 12-month post-transplant survival between the two groups (94% vs. 94%, P = 0.5). CONCLUSION: Patients with HRS treated with terlipressin who subsequently undergo liver transplantation have post-transplant renal and survival outcomes comparable to patients transplanted for cirrhosis without HRS. This study supports the practice of liver-only transplant in this cohort and the reservation of renal allografts for those who have primary renal disease.

Safety and efficacy of outpatient continuous terlipressin infusion for the treatment of portal hypertensive complications in cirrhosis.

BACKGROUND/AIM: Therapeutic options are limited for patients with hepatorenal syndrome (HRS), diuretic refractory ascites and hepatic hydrothorax who are awaiting liver transplant. We assessed the safety and efficacy of continuous terlipressin infusion (CTI) for treating these conditions in an outpatient setting. METHOD: All patients treated with CTI from May 2013 through March 2018 at our institution were initiated in-hospital on bolus dose terlipressin therapy for 24-72 h prior to commencing CTI for home therapy. Daily home visits for clinical assessment and medication administration were provided. Adverse events, effects of treatment on renal function, model for end-stage liver disease (MELD) score, and paracentesis/thoracentesis requirements were assessed. RESULTS: Twenty-three patients were included (HRS = 17; refractory ascites = 4; refractory hepatic hydrothorax = 2). Median (range) duration of outpatient CTI was 50 (1-437) days with a total of 2482 patient days of treatment. Fourteen patients (60.9%) received a liver transplant; of whom 13 (92.9%) were alive at the end of the study period. There were no cardiac or ischemic complications and no serious adverse events reported. In patients with HRS, median serum creatinine significantly decreased from 202.0 µmol/L at baseline to 125.5 µmol/L at day 14 of CTI (P = 0.0003) and remained stable thereafter. Median MELD score decreased from 22.5 to 19.0 at end of CTI (P = 0.008). Median frequency of paracentesis/thoracentesis was 4 per month prior to CTI versus 1.52 during treatment. CONCLUSION: Transplant-eligible and otherwise stable patients can be managed with CTI at home for an extended duration under supervision without adverse consequences.

Video consultations during the coronavirus disease 2019 pandemic are associated with high satisfaction for both doctors and patients.

BACKGROUND AND AIM: Telehealth has become the standard of care during the COVID-19 outbreak. This study aimed to assess doctor and patient satisfaction of endoscopy-related telehealth clinics with video consultations. METHODS: A prospective observational study of patients consecutively booked to attend two endoscopy-related telehealth clinics at an ambulatory tertiary care setting was conducted from July to October 2020. Data collected from our previously published study using phone consultations (data collected in April-May 2020) were used as a control arm. The primary outcome (satisfaction) was assessed through the six-question score (6Q_score) as per previous research. Secondary outcomes included failure-to-attend (FTA) rate and perceived necessity of physical examination/in-person follow-up appointment. RESULTS: There were 962 endoscopy clinic appointments between July and October, of which 157 were conducted through video. Data on 127 doctor questionnaires and 94 patient questionnaires were analyzed. The median age (years) of patients reviewed via video [57, interquartile range (IQR) 48-66] was lower than those reviewed via phone (65, IQR 55-74, P < 0.01). Patient average 6Q_score was higher with video compared to phone (85.1% vs 78.4%, P = 0.01), as was doctors' 6Q_score (97.5% vs 91.9%, P = 0.02). FTA rates remained similar between the two assessments (6.4% in April/May and 4.4% between July/October, P = 0.12). The requirement for in-person follow-up/physical examination was identified in two video consultations (1.6%). CONCLUSION: Video consultations during the COVID-19 outbreak demonstrated higher patient and doctor satisfaction compared to phone consultations. There was no significant difference in FTA rates and need for in-person follow-up consultations/physical examination between the telehealth two modalities.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

Continuous terlipressin infusion is associated with improved diet intake and muscle strength in patients awaiting liver transplant.

BACKGROUND & AIMS: Portal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters. METHODS: Nutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date). RESULTS: Nineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001). CONCLUSION: Continuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characteristics usually demonstrate progressive decline. This validates both the aetiological role of portal hypertension in malnutrition and represents a promising new anabolic therapy. LAY SUMMARY: Malnutrition and poor muscle strength are common in liver disease and often get worse while patients await liver transplant. Terlipressin is a medication used to treat portal hypertension in patients with hepatorenal syndrome. It is usually given for a few days or weeks in patients confined to hospital. Our centre provides outpatient terlipressin for weeks to months as a bridge to liver transplant. In patients treated with terlipressin at our hospital, we observed a substantial increase in their dietary intake and muscle strength, which may improve their quality of life and outcomes after liver transplant.