Oketsu is a characteristic pathophysiology in Kampo and traditional East Asian medicine that includes mul­tiple aspects of hemodynamic disorder. Anti­-oketsu drugs or the Kampo formulation used for oketsu show sig­nificant clinical effects on various disorders; however, their underlying mechanisms still remain unclear. We aimed to clarify the characteristics of the pharmacological effects of anti-­oketsu drugs on the microcirculation using a microscopic live imaging technique. Three Kampo formulations, namely tokakujokito, keishibukuryo­gan, and tokishakuyakusan were orally administrated to C57BL/6 mice at a dose of 300 mg/kg diluted in dis­tilled water. Live imaging was performed on the subcutaneous vessels of the mice, including the arteries (di­ameter > 50 μm), arterioles (diameter 10-50 μm) and capillaries (diameter < 10 μm). Tokakujokito widely increased erythrocyte flow velocity and blood flow volume from arteries to capillaries within 60 min of ad­ministration. The effects of keishibukuryogan on the vasodilation of the arterioles were remarkable, and con­tinued up to 120 min after administration. The pharmacological target of tokishakuyakusan was the capillaries, increasing their erythrocyte velocity and blood flow volume;its effect was more slowly expressed than those of the other formulations. Our results clearly demonstrate the sequential and special effects of anti-­oketsu drugs on hemodynamics. These differences may provide pharmacological information on the clinical usage of traditional Kampo formulations.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. Methods: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. Results: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). Conclusions Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.