Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy

Table 1 Studies evaluating the relationship between muscle alterations and minimal hepatic encephalopathy in cirrhosis

First author (year)	Number of patients	Methods to identify sarcopenia and/or myosteatosis	Tests to detect minimal hepatic encephalopathy	Results
Merli et al[23], (2013)	300 hospitalized cirrhotics	Anthropometric measurements (MAMC) and hand grip strenghth	PHES battery (NCT-A, NCT-B, LT, SDT, LTT): 5 paper pencil tests	MHE prevalence was higher in pts with malnutrition compared to those without (49% vs 30%, P < 0.001). At multivariate analysis, only protein malnutrition (OR 2.15, 95%CI: 1.1-4.1, P = 00.02) and hyponatremia (OR 4.6, 95%CI: 1.9-9, P = 00.01) were independent predictors of MHE. Venous blood ammonia levels resulted significantly higher in patients with vs those without muscle depletion (85 ± 64 vs 61 ± 46 µg/dL, P = 0.025) and in patients with vs those without a decreased muscle strength (81 ± 62 µg/dL vs 63 ± 45 µg/dL, P = 0.047)
Hanai et al[56], (2017)	120 cirrhotic patients	Bioelectrical impedance analysis and hand grip strenght	NCT-A, NCT-B, DST, BDT	The prevalence of MHE was higher in patients with sarcopenia than in those without sarcopenia (P = 0.01). In the multivariate analysis, serum BCAA levels (OR = 2.98, 95%CI: 1.08-8.34, P = 0.03) and sarcopenia (OR 3.31, 95%CI: 1.19-9.42, P = 0.02) were found to be associated with MHE. Ammonia levels were similar in sarcopenic and non-sarcopenic patients
Kalaitzakis et al[57], (2007)	128 cirrhotic patients	BMI, weight loss, MAMC and triceps skinfold	NCT-A, NCT-B	Multivariate analysis showed that the time needed to perform number connection test was independently associated to age, the Child–Pugh score, diabetes and malnutrition (P < 0.05). Plasma ammonium ion was also related to BMI (r = 0.26, P = 0.006) and to muscle mass expressed as mid-arm muscle circumference (r = 0.28, P = 0.003) but not to fat mass expressed as triceps skin-fold thickness (r = 0.02, NS)
Nardelli et al[22], (2019)	89 cirrhotic patients	CT scan to evaluate sarcopenia and myosteatosis	PHES battery (NCT-A, NCT-B, LT, SDT, LTT): 5 paper pencil tests	Both myosteatosis (62.5% vs 12.5%, P < 0.001) and sarcopenia (84% vs 31%, P < 0.001) were more frequent in patients with MHE. At multivariate analysis, the variables independently associated to the presence of MHE were: sarcopenia, previous overt HE and myosteatosis. Venous ammonia was significantly higher in patients with sarcopenia (62.6 ± 17.7 μg/dL vs 41.4 ± 16.1 μg/dL, P < 0.001) and in patients with myosteatosis (65.2 ± 19.2 μg/dL vs 46.7 ± 17.1 μg/dL, P < 0.001) and inversely correlated to both parameters
Gioia et al[25], (2019)	27 cirrhotic patients submitted to TIPS	CT scan to evaluate sarcopenia and myosteatosis before and after TIPS	PHES battery (NCT-A, NCT-B, LT, SDT, LTT): 5 paper pencil tests	PHES and ammonia significantly improved in the patients with amelioration in Skeletal Muscle Index (SMI) > 10% (n = 16) and not in those without (n = 11) (PHES: -1.6 ± 2 vs -4.8 ± 2.1, P = 0.0005; ammonia: 48.5 ± 28.7 μg/dL vs 96 ± 31.5 μg/dL, P = 0.0004). Moreover, the prevalence of minimal HE (12.5% vs 73%, P = 0.001) was significantly reduced in patients with muscle improvement
Tapper et al[58], (2019)	106 cirrhotic patients	Anthropometric measurements (MAMA), hand grip strenght and CT scan to evaluate muscle assesment	ICT	Hand grip correlated strongly with skeletal muscle area (correlation coefficient 0.64, P < 0.001) and mildly with ICT performance (0.34, P = 0.002)

MHE: Minimal hepatic encephalopathy; HE: Hepatic encephalopathy; NCT-A: Number connection test part A; NCT-B: Number connection test part B; LTT: Line tracing test; SDT: Symbol digit test; ICT: Inhibitory control test; TIPS: Transjugular intrahepatic portosystemic shunt; PHES: Phychometric Hepatic Encephalopathy Score; CT: Computed tomography; NS: Not significant; BMI: Body mass index.