The venerable drug colchicine has garnered significant recent attention due to its endorsement by the United States Food and Drug Administration as an anti-inflammatory medication for cardiovascular diseases. However, the administration of this drug at its minimal available dose of 0.5 mg has been associated with certain adverse reactions.Once colchicine is administered, the drug disappears from blood in a short time and distributes in the leukocytes for a certain period of time that elicits anti-inflammatory effect.Consequently, an in-depth comprehension of the pharmacokinetics of lower dosages within leukocytes assumes important for its broader application in routine clinical contexts. In this study, we present a comprehensive analysis of the pharmacological disposition of colchicine in the plasma, polymorphonuclear leukocytes, and mononuclear leukocytes among healthy Japanese male subjects, following both single and multiple oral administrations of 0.5 mg and 0.25 mg doses of colchicine. Our investigation reveals that colchicine persists within leukocyte populations even when administered at reduced dosages. The findings herein hold promise for mitigating the adverse effects associated with its use in the treatment of inflammatory cardiovascular disorders.

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.