Reply to "Comments on the Editor Re: The Relationship of Obesity, Nutritional Status and Muscle Wasting in Patients Assessed for Liver Transplantation, Nutrients 2019, 11, 2097."

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The Relationship of Obesity, Nutritional Status and Muscle Wasting in Patients Assessed for Liver Transplantation.

INTRODUCTION: Obesity co-exists with malnutrition and muscle atrophy in patients with cirrhosis. Muscle wasting is a feature of sarcopenia, a known determinant of patient outcomes. This is the first description of a relationship between obesity, subjective global assessment (SGA) of nutritional status and muscle wasting in patients with cirrhosis. METHODS: The relationship between body mass index (BMI with obesity defined as ≥ 30 kg/m2), nutritional status (assessed by liver-specific subjective global assessment-SGA) and muscle wasting (assessed by corrected total cross-sectional psoas muscle area-cTPA) was analysed in patients with cirrhosis considered for liver transplantation between 1 January 2012 and 31 December 2014. RESULTS: There were 205 patients, of whom 70% were males. The mean age was 52 ± 0.7 years and the Model for End-Stage Liver Disease (MELD) score was 16.8 ± 0.5. Overall, 31% of patients were obese and 56% of well-nourished (SGA A) individuals were obese. Muscle wasting was identified in 86% of all patients, irrespective of their nutritional status (A, B, C). All obese males classified as well-nourished (SGA A) were sarcopenic and 62% of obese females classified as SGA A were sarcopenic. Muscle wasting was worse in obese individuals (cTPA 230.9 mm2/m2 ± 12.9, p < 0.0001) and more likely to be associated with hepatic encephalopathy (p = 0.03). Univariate and multivariate analysis demonstrated testosterone deficiency was significantly associated with muscle wasting (p = 0.007) but not obesity (p = 0.8). CONCLUSION: Obesity combined with muscle wasting is common in patients with cirrhosis. Muscle wasting is common in well-nourished (SGA A) obese patients. Consequently, all patients assessed for liver transplantation should undergo additional screening for malnutrition and muscle wasting irrespective of BMI.

Supplementation with Synbiotics and/or Branched Chain Amino Acids in Hepatic Encephalopathy: A Pilot Randomised Placebo-Controlled Clinical Study.

INTRODUCTION: Hepatic encephalopathy (HE) is common in patients with cirrhosis and is characterised by reduced hepatic ammonia clearance. This is accompanied by alterations in gut bacteria that may be ameliorated with synbiotics (pro- and prebiotics). Branched chain amino acids (BCAAs) are thought to have a role in the detoxification of ammonia. We investigated the effects of the administration of synbiotics and/or BCAAs in treating HE. METHODS: Participants with overt HE were randomised in a blinded placebo-controlled study to receive synbiotics, BCAAs, or a combination of BCAAs and Synbiotics. Relevant biochemical and nutritional data and depression and anxiety scores (DASS-21) were collected at entry, 4 weeks, and on completion, at 8 weeks. The Trail Making Test (TMT) and Inhibitory Control Test (ICT) were used to assess cognitive function in patients withHE. Results were analysed using linear mixed effects regression analyses. RESULTS: Sixty-one participants were enrolled and 49 who returned for at least 1 follow-up review were included in the intention to treat analysis. The mean age was 55.8 ± 6.1 years and 86% were males. Despite evidence of a placebo effect, there was significant improvement in TMT B and ICT weighted lures in participants who received combined synbiotics/BCAAs treatment compared to placebo at study completion (p ≤ 0.05). Cognitive improvement occurred without a significant change in ammonia levels. CONCLUSION: To our knowledge, this is the first study reporting that combined synbiotics and BCAAs improve HE, and that may be beneficial in the management of HE. A larger study is needed to confirm these results.