Background characteristics of patients are shown in Table 1. Of the 99 patients, median age was 70.0 years old and 61 patients (61.6%) were men. Etiology was hepatitis B virus (HBV) in 18 patients, hepatitis C virus (HCV) in 52 patients, and neither HBV nor HCV in 29 patients. Thirty HCV-infected patients achieved SVR among 52 patients. Among all patients, 29 (29.3%) did not have HCC, while 58 (58.6%) showed complications of gastroesophageal varices. Sixty patients were classified as Child-Pugh class A. For all patients, median grip strength was 24.6 kg and median SMI was 47.9 cm2/m2.
Difference between presence or absence of MHE
Table 2 shows a comparison of patient background characteristics between patients with and without MHE. Forty-eight patients were judged as positive for MHE. Body weight was lower in patients with MHE than in those without MHE. Concentrations of ammonia were similar between groups. In amino acid analysis (concentration of branched-chain amino acids (BCAA), that of Tyrosine and molar ratio of BCAA to tyrosine (BTR)), no differences were evident between groups. On the other hand, grip strength, body height, body weight, body mass index (BMI), skeletal muscle area at the L3 level, SMI, psoas muscle area and PMI differed significantly between groups. Median SMI in patients with and without MHE were 46.4 cm2/m2 and 51.2 cm2/m2, respectively.
Sarcopenia and muscle mass loss
In this cohort, 6 patients (6.7%) were diagnosed with sarcopenia. Figure 2 shows the incidence of MHE stratified by the presence of sarcopenia. Incidence of MHE in patients with and without sarcopenia was 50.0% and 48.4%, respectively (Fig. 2a). No significant difference in the incidence of MHE was evident regardless of muscle strength loss or muscle mass loss (Fig. 2b). However, we found that presence of either muscle mass loss or strength loss was significantly associated with higher incidence of MHE, whereas absence of either was not (Fig. 2c).
Predictive factors for incidence of MHE
Next, we performed univariate analysis to elucidate factors associated with MHE using all variables in table 2. Cut-off values of SMI and PMI defined by ROC curve were 50 cm2/m2 and 4.3 cm2/m2, respectively. Table 3 showed only the variables with statistically significant differences except for those that were not significantly different by univariate analysis. Body weight, BMI, concentration of BCAA, skeletal muscle area, SMI, psoas muscle area and PMI were significantly correlated with the presence of MHE (Table 3), whereas sarcopenia was not significantly associated with MHE. Since BMI and SMI include body weight and skeletal muscle area, respectively, we focused on BMI, concentration of BCAA and SMI, and performed multivariate analysis using these. As a result, SMI was detected as the only significant factor (≥ 50 cm2/m2, odds ratio (OR) 0.300, P = 0.006). Similarly, when using PMI instead of SMI, PMI was detected as the only significant factor (≥ 4.3 cm2/m2, odds ratio (OR) 0.192, P = 0.001) (Table 3). The incidence rate of MHE was 59.6% in patients with SMI < 50 cm2/m2, and 33.3% in patients with SMI ≥ 50 cm2/m2 and that was 71.4% in patients with PMI < 4.3 cm2/m2, and 35.9% in patients with PMI ≥ 4.3 cm2/m2, respectively (Fig. 3). In addition, the all six patients with sarcopenia belonged to the low BMI group, which was less than 24 kg/m2.
Incidence of MHE classified by sex and age
Since SMI varies among sex, we examined SMI and the incidence of MHE by sex. Median SMI was 51.0 cm2/m2 in males and 45.1 cm2/m2 in females (Table 4). The incidence of MHE was higher in the group with SMI below the cut-off level than in the group with SMI above the cut-off in both males and females (Fig. 4a). Regarding the frequency of MHE, there was a similar tendency in PMI (Fig. 4b). Next, patients with high age showed the possibility of declines in higher brain functions such as recognition and decision making. We also examined the incidence of MHE by age. Table 4 shows median SMI classified by the age threshold of 80 years old. While grip strength differed between subjects under or over 80 years old, SMI and PMI were similar between groups. The incidence of MHE differed significantly between groups classified using the SMI or PMI level below and above the cut-off level in patients <80 years old (Fig. 4c, d).