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.

Exercise physiology in cirrhosis and the potential benefits of exercise interventions: A review.

Reduction in muscle mass is a highly prevalent phenomenon in cirrhosis and is now well-documented to be associated with significant morbidity and mortality. Research into muscle loss in cirrhosis remains limited by an ongoing poor understanding of its relationship with muscle function, physical activity, and aerobic capacity. Alterations in exercise physiology have been documented in studies of individuals with cirrhosis that provide important information on physical function that is not captured by simple quantification of muscle mass. Despite expert consensus recommending regular exercise in end-stage liver disease to maintain muscle mass and function, there is little evidence guiding clinicians as to which form of exercise or delivery mechanism is most effective. It also remains unproven whether any specific intervention can alter clinically relevant outcomes. This review article summarizes the available literature regarding the changes in exercise physiology observed in cirrhosis, the associated impact on physical capacity, and the results of existing trials that examine the potential benefits of exercise delivery in patients with cirrhosis, particularly pertaining to their impact on exercise physiology.

Hearts above water: Palliative care during a pandemic.

Social workers and nurses, as members of interprofessional palliative medicine teams, faced unfamiliar challenges and opportunities as they endeavored to provide humanistic care to patients and families during the coronavirus (COVID-19) pandemic. Typical methods for engaging patients and families in medical decision-making became thwarted by visitation restrictions and patients' dramatic health declines. This paper presents an innovative social work and nursing intervention aimed at enhancing humanistic patient/family care and advanced directive dialogs. Through incorporating a narrative synthesis of the teams' reflective journals from COVID-19, the paper chronicles the intervention implementation, patient/family responses, and team members' personal and professional meaning-making processes.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Handgrip Strength Adds More Prognostic Value to the Model for End-Stage Liver Disease Score Than Imaging-Based Measures of Muscle Mass in Men With Cirrhosis.

Sarcopenia is associated with mortality in cirrhosis, but there is no gold standard for its diagnosis. The comparative utility of different diagnostic methods is unknown. This single-center observational cohort study followed 145 men referred for liver transplant evaluation between 2005 and 2012. Muscle mass was estimated by handgrip strength, dual energy X-ray absorptiometry (DEXA) lean mass, and single-slice computed tomography (CT) scan at the fourth lumbar vertebra. Recorded outcomes included time to death or liver transplantation. The median (interquartile range [IQR]) age was 54 years (47-59 years), and Model for End-Stage Liver Disease (MELD) score was 17 (14-23). Of 145 men, 56 died with a median (IQR) time to death of 7.44 months (3.48-14.16 months). In total, 79 men underwent transplantation with median (IQR) time to transplant of 7.20 months (3.96-12.84 months). The prevalence of sarcopenia differed between diagnostic modalities with 70.3% using CT muscle mass, 45.9% using handgrip strength, and 38.7% using DEXA. Muscle mass was inversely associated with wait-list mortality for measured CT muscle mass (hazard ratio [HR], 0.94; 95% confidence interval (CI), 0.90-0.98; P = 0.002), DEXA muscle mass (HR, 0.99; 95% CI, 0.99-0.99; P = 0.003), and handgrip strength (HR, 0.94; 95% CI, 0.91-0.98; P = 0.002). These results retained significance independent of the MELD score. In predicting mortality, the MELD-handgrip strength bivariate Cox model was superior to a MELD-CT muscle Cox model (P < 0.001). In conclusion, handgrip strength combined with MELD score was the superior predictive model in this novel study examining 3 commonly employed techniques to diagnose sarcopenia in cirrhosis. Handgrip strength has additional potential clinical benefits because it can be performed serially without the radiation dose, cost, and access issues attributable to CT and DEXA.

Use of Dual X-ray Absorptiometry in men with advanced cirrhosis to predict sarcopenia-associated mortality risk.

INTRODUCTION: Reduced muscle area on CT scan is an independent predictor of mortality in cirrhosis. We examine for the first time the relationship between dual energy x-ray absorptiometry (DEXA) lean mass parameters on outcomes in cirrhotic men awaiting liver transplantation. MATERIALS AND METHODS: We retrospectively reviewed DEXA scans performed during transplant assessment between 2001 and 2016. Baseline data including the presence of ascites and MELD score were recorded. DEXA lean mass measures were adjusted for height. The primary outcome was 12-month wait-list mortality. RESULTS: Four hundred twenty men with median age 55.4 years [interquartile range 49.2; 59.4] and MELD 16 [12; 20] were studied. Median follow-up was 58.5 [28.8; 109] months. 12-month wait-list mortality was 12.4%. Appendicular lean mass was inversely associated with mortality (HR 0.78 [0.62; 0.98], P = 0.03). Lean mass of arms (HR 0.37 [0.16; 0.83], P  = 0.02) rather than legs (HR 0.77 [0.58; 1.03], P  = 0.08) was responsible for this association. Upper limb lean mass showed a significant interaction with MELD score in predicting wait-list mortality, particularly within 4 months. Total lean mass was not associated with mortality but increased in conjunction with increasing ascites (OR for ascites 1.20 [1.15; 1.25], P < 0.001 for each unit increase in MELD). CONCLUSION: Upper limb lean mass by DEXA is strongly associated with mortality in men awaiting liver transplantation. The superiority of upper limb lean mass probably relates to confounding of lower limb measures by fluid retention. This DEXA parameter represents a novel and reproducible measure of sarcopenia in cirrhosis.

Branched-chain amino acid supplementation does not improve measures of sarcopenia in cirrhosis: results of a randomised controlled trial.

BACKGROUND: Sarcopenia is associated with adverse outcomes in cirrhosis. Branched-chain amino acids (BCAA) target several pathways that lead to muscle loss in this population. AIMS: We aimed to evaluate the impact of BCAA supplementation on sarcopenia measures in patients with cirrhosis. METHODS: We conducted a 12-month double-blinded, randomised, controlled trial of BCAA supplementation (30 g daily) compared to an equicaloric, equi-nitrogenous whey protein in volunteers with cirrhosis and reduced muscle strength. The primary endpoint was an increase in grip strength and upper limb lean mass measured on DEXA. Mean-adjusted differences (MAD, 95% CI) between groups at 6 and 12 months are reported as treatment effect using a linear mixed model for repeated measures. RESULTS: A total of 150 volunteers entered the trial (74 BCAA, 76 control), with a median age of 58 years [IQR 48; 63] and MELD of 14 [12; 17]. At 12 months, 57% in the BCAA arm and 61% in the control arm met the primary endpoint (p = 0.80). No significant between-group difference was found in grip strength (MAD -0.15 kg [-0.37; 0.06], p = 0.29) or upper limb lean mass (1.7 kg [-0.2; 3.6], p = 0.22) at 12 months. No significant differences in other body composition parameters, physical performance, frailty, rates of hospitalisation or mortality were found between the BCAA and the control group. Fatigue improved across the entire cohort, without significant between-group differences. 15% of volunteers reported side effects, with distaste higher in the BCAA arm (p = 0.045). CONCLUSION: BCAA supplementation did not improve measures of muscle strength, mass or performance or physical frailty compared to a whey protein supplement in a randomised controlled setting. ACTRN12618000802202.

Novel Use of the Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition for the Treatment of Crohn's Disease During Pregnancy.

The Crohn's Disease Exclusion Diet (CDED) with partial enteral nutrition (PEN) is an emerging treatment option for Crohn's disease (CD). A 35-year-old pregnant woman presented with newly diagnosed ileal CD. At 14/40 gestation, CDED + PEN was prescribed without drug therapy. Outcomes included Harvey-Bradshaw Index, weight, and bowel wall thickness/Limberg score measured on intestinal ultrasound (IUS). In this patient, CDED + PEN achieved clinical and biochemical remission, improvements on IUS, gestational weight gain, and healthy birth weight without drug therapy. Sustained remission was achieved postpartum. Our case highlights the potential effectiveness of CDED + PEN to induce remission for active CD during pregnancy.

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.

Redefining Nutritional Requirements in End-Stage Liver Disease: Towards a Personalized Approach.

Malnutrition is ubiquitous in cirrhotic patients presenting for liver transplant (LT). Providing an appropriate energy prescription is fundamental to effective nutrition therapy. We aimed to compare measured energy expenditure (mEE) with predicted energy expenditure (pEE) in patients awaiting LT and determine clinical factors associated with mEE. In this prospective observational study, energy expenditure was measured by indirect calorimetry in 110 adult patients referred for LT and predicted by commonly utilized equations (Harris-Benedict, Schofield, and EASL guidelines). Nutritional status, anthropometry, muscle function, biochemical and clinical data were also collected. The median model for end-stage liver disease (MELD) was 19 (IQR 13, 25), and the majority were Child-Pugh B (51%) or C (37%). Malnutrition was evident in 85%. Median mEE by calorimetry was 1756 (1531, 2104) kcal/d and significantly higher than pEE as per Harris-Benedict 1480 (1322, 1722) kcal/d and Schofield 1474 (1349, 1723) kcal/d (both p < 0.001), but lower than EASL guidelines (35 kcal/kg) when an activity factor was applied to mEE; 2283 (1990, 2735) kcal/d versus 2590 (2178, 3010) kcal/d (p < 0.001). Hypermetabolism (mEE:pEE > 1.2) was evident in 48% of the cohort. Multivariate analysis found MELD, Child-Pugh class, diuretic use, and severe malnutrition to be independent predictors of hypermetabolism. A new liver-specific predictive model has been developed, showing superior agreement with mEE than common predictive equations. In conclusion, there is a poor correlation between mEE and pEE in patients awaiting LTs, and hypermetabolism is common. Relying on historical predictive equations in this patient population may result in significant under or over-feeding. A tailored energy prescription based on indirect calorimetry or a liver-specific predictive model is recommended for LT candidates.

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

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.

Malnutrition and low muscle strength are independent predictors of clinical outcomes and healthcare costs after liver transplant.

BACKGROUND & AIMS: Malnutrition and sarcopenia are associated with increased morbidity and mortality in cirrhosis but conflicting data are reported after liver transplantation (LT), with little known about the economic burden of malnutrition at LT. This study aims to investigate the impact of pre-transplant malnutrition and muscle strength on post-transplant clinical outcomes and healthcare costs. METHODS: Pre-transplant nutritional status (via subjective global assessment, SGA) and handgrip strength (HGS) were assessed in patients transplanted from 2009-2017. Descriptive statistics and regression analysis were used to analyse the association between nutrition and muscle function with post-LT clinical outcomes and hospital costs. RESULTS: 373 patients (70% male, median age 55 [IQR: 47, 60]) were transplanted, with 79% malnourished and mean HGS 31.4 ± 9.35 kg for males and 17.6 ± 5.78 kg for females. Malnutrition and reduced HGS independently predicted adverse post-transplant outcomes. ICU length of stay (LOS) was associated with severe malnutrition (HR (time to discharge (TTD)) 0.706, p = 0.014) and low HGS (HR (TTD) 0.692, p = 0.003); hospital LOS with severe malnutrition (HR (TTD) 0.759, p = 0.049) and low HGS (HR (TTD) 0.730, p = 0.011), and post-transplant infection with severe malnutrition (OR 1.76, p = 0.042) and low HGS (OR 1.83, p = 0.015). Accordingly, hospital costs were 30% higher in severely malnourished compared to well-nourished recipients (p = 0.012). Neither malnutrition or impaired HGS were associated with post-transplant mortality. CONCLUSIONS: This large cohort study demonstrates malnutrition and muscle weakness are independently associated with early post-transplant morbidity, namely infection and ICU and hospital LOS; with significantly increased hospital costs. Strategies to combat malnutrition and deconditioning pre-transplant may improve patient and health system outcomes after LT.

Nutraceuticals for the treatment of sarcopenia in chronic liver disease.

BACKGROUND AND AIMS: Sarcopenia, defined as loss of muscle mass, strength and function, is associated with adverse clinical outcomes in patients with cirrhosis. Despite improved understanding of the multifaceted pathogenesis, there are few established therapies to treat or prevent muscle loss in this population. This narrative review examines the available literature investigating the role of nutraceuticals for the prevention or treatment of muscle wasting in chronic liver disease. METHODS: A comprehensive search or Medline and PubMED databases was conducted. Reference lists were screened to identify additional articles. RESULTS: A number of nutritional supplements and vitamins target the specific metabolic derangements that contribute to sarcopenia in cirrhosis including altered amino acid metabolism, hyperammonaemia and inflammation. Branched chain amino acid (BCAA) supplementation has proposed anabolic effects through dual pathways of enhanced ammonia clearance and stimulation of muscle protein synthesis. l-carnitine also has multimodal effects on muscle and shows promise as a therapy for muscle loss through anti-inflammatory, antioxidant and ammonia lowering properties. Other nutraceuticals including l-ornithine l-aspartate, omega-3 polyunsaturated fatty acids and zinc and vitamin D supplementation, may similarly have positive effects on muscle homeostasis, however further evidence to support their use in cirrhotic populations is required. CONCLUSION: Nutraceuticals offer a promising and likely safe adjunct to standard care for sarcopenia in cirrhosis. While there is most evidence to support the use of BCAA and l-carnitine supplementation, further well-designed clinical trials are needed to elucidate their efficacy as a therapy for muscle loss in this population.

Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey.

BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1-2, 2-3 and >3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.

Malnutrition in cirrhosis: More food for thought.

Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications. The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated. Anorexia and liver decompensation symptoms lead to poor dietary intake; metabolic changes characterised by elevated energy expenditure, reduced glycogen storage, an accelerated starvation response and protein catabolism result in muscle and fat wasting; and, malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed. Malnutrition is therefore a considerable challenge to manage effectively, particularly as liver disease progresses. A high energy, high protein diet is recognised as standard of care, yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation. In this review, we seek to detail the factors which contribute to poor nutritional status in liver disease, and highlight complexities far greater than "poor appetite" or "reduced oral intake" leading to malnutrition. We also discuss management strategies to optimise nutritional status in this patient group, which target the inter-related mechanisms unique to advanced liver disease. Finally, future research requirements are suggested, to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.

Home parenteral nutrition provision modalities for chronic intestinal failure in adult patients: An international survey.

BACKGROUND & AIMS: The safety and effectiveness of a home parenteral nutrition (HPN) program depends both on the expertise and the management approach of the HPN center. We aimed to evaluate both the approaches of different international HPN-centers in their provision of HPN and the types of intravenous supplementation (IVS)-admixtures prescribed to patients with chronic intestinal failure (CIF). METHODS: In March 2015, 65 centers from 22 countries enrolled 3239 patients (benign disease 90.1%, malignant disease 9.9%), recording the patient, CIF and HPN characteristics in a structured database. The HPN-provider was categorized as health care system local pharmacy (LP) or independent home care company (HCC). The IVS-admixture was categorized as fluids and electrolytes alone (FE) or parenteral nutrition, either commercially premixed (PA) or customized to the individual patient (CA), alone or plus extra FE (PAFE or CAFE). Doctors of HPN centers were responsible for the IVS prescriptions. RESULTS: HCC (66%) was the most common HPN provider, with no difference noted between benign-CIF and malignant-CIF. LP was the main modality in 11 countries; HCC prevailed in 4 European countries: Israel, USA, South America and Oceania (p < 0.001). IVS-admixture comprised: FE 10%, PA 17%, PAFE 17%, CA 38%, CAFE 18%. PA and PAFE prevailed in malignant-CIF while CA and CAFE use was greater in benign-CIF (p < 0.001). PA + PAFE prevailed in those countries where LP was the main HPN-provider and CA + CAFE prevailed where the main HPN-provider was HCC (p < 0.001). CONCLUSIONS: This is the first study to demonstrate that HPN provision and the IVS-admixture differ greatly among countries, among HPN centers and between benign-CIF and cancer-CIF. As both HPN provider and IVS-admixture types may play a role in the safety and effectiveness of HPN therapy, criteria to homogenize HPN programs are needed so that patients can have equal access to optimal CIF care.

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.