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A hybrid training system (HTS) combining antagonist muscle electrical stimulation and voluntary muscle contraction has been developed using eccentric antagonist muscle contractions with electrical stimulation as resistance to voluntary muscle contractions. We devised an exercise method using HTS combined with a cycle ergometer (HCE). The purpose of this study was to compare the muscle strength, muscle volume, aerobic functions and lactate metabolism of HCE and a volitional cycle ergometer (VCE). A total of 14 male participants performed exercise on a bicycle ergometer for 30 min per session, 3 times per week for 6 weeks. We divided 14 participants into an HCE group (7 participants) and a VCE group (7 participants). The workload was set at 40% of each participant's peak oxygen uptake ( V. O2peak). Electrodes were placed over each motor point on the quadriceps and hamstrings. The V. O2peak and anaerobic threshold significantly increased before and after training when using HCE rather than VCE. The HCE group had significantly increased extension and flexion muscle strength at 180 degrees/s in post-training measurements over pre-training measurements. Knee flexion muscle strength at 180 degrees/s tended to increase in the HCE group compared to the VCE group. The quadricep muscle cross-sectional area was significantly increased in the HCE group compared to the VCE group. Additionally, the HCE group had significantly decreased maximal lactate, measured every 5 min during exercise at the end of study, between pre and post-training. Thus, HCE may be a more effective training method for muscle strength, muscle mass and aerobic functions at 40% of each participant's V. O2peak than conventional cycling exercise. HCE could be applied not only as aerobic exercise but also as resistance training. [ABSTRACT FROM AUTHOR]

Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk. [ABSTRACT FROM AUTHOR]

Reduction in activity links to the development and progression of non-alcoholic fatty liver disease (NAFLD). Brain-derived neurotrophic factor (BDNF) is known to regulate an activity. We aimed to investigate the association between reduction in activity and BDNF in patients with NAFLD using data-mining analysis. We enrolled 48 NAFLD patients. Patients were classified into reduced (n = 21) or normal activity groups (n = 27) based on the activity score of the Chronic Liver Disease Questionnaire-NAFLD/non-alcoholic steatohepatitis. Circulating BDNF levels were measured using an enzyme-linked immunoassay. Factors associated with reduced activity were analyzed using decision-tree and random forest analyses. A reduction in activity was seen in 43.8% of patients. Hemoglobin A1c and BDNF were identified as negative independent factors for reduced activity (hemoglobin A1c, OR 0.012, p = 0.012; BDNF, OR 0.041, p = 0.039). Decision-tree analysis showed that "BDNF levels ≥ 19.1 ng/mL" was the most important classifier for reduced activity. In random forest analysis, serum BDNF level was the highest-ranked variable for distinguishing between the reduced and normal activity groups (158 valuable importance). Reduced activity was commonly seen in patients with NAFLD. Data-mining analyses revealed that BNDF was the most important independent factor corresponding with the reduction in activity. BDNF may be an important target for the prevention and treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20–40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240–4.570, p = 0.0091) as an independent factor for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. We demonstrated that in-hospital exercise improved frailty in patients with HCC, which was confirmed by propensity score matching analysis. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC. Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20–40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI −0.17 vs. −0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240–4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062–4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC. [ABSTRACT FROM AUTHOR]

The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC. [ABSTRACT FROM AUTHOR]