Computed tomography (CT) is often used in the diagnosis of sarcopenia. In this study, we validated the assessment of sarcopenia by the psoas muscle volume using versatile software. The study involved a retrospective analysis of data from 190 patients with liver disease who underwent grip-strength testing and abdominal pelvic computed tomography. To assess sarcopenia, SYNAPSE 3D was used to obtain the skeletal muscle index, the psoas muscle index (PMI), and the simple method. We also used the recently proposed PMI cutoff values, for which the usefulness has been evaluated (O-PMI). The cutoff value of the psoas muscle volume index (PMVI) was determined using one of the diagnostic methods as the gold standard. All diagnostic methods showed that patients with sarcopenia had shorter survival, with O-PMI having the highest hazard ratio (HR) (HR, 6.12; 95% confidence interval [CI], 2.6–14.41; p < 0.001). Even when sarcopenia could not be diagnosed by O-PMI, low PMVI was associated with shorter survival (HR, 3.53; 95% CI, 1.34–9.32; p = 0.01). PMVI may be useful in the evaluation of sarcopenia, including the identification of poor overall survival in cases that cannot be diagnosed by O-PMI, which is considered more useful than PMI.

Although there have been advances in the prevention and diagnosis of hepatocellular carcinoma (HCC) in recent years, many HCC patients are still diagnosed with advanced stage. Systemic therapy is indicated for unresectable HCC (uHCC) with major vascular invasion and/or extrahepatic metastases, and the atezolizumab plus bevacizumab (atezo/bev) combination is currently recommended as first-line treatment for uHCC. Recently, sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reportedly associated with prognosis in uHCC patients treated with sorafenib or lenvatinib. There are few reports on muscle strength assessments, including grip strength (GS), despite their importance in accurate sarcopenia diagnosis, and furthermore, there is no evidence regarding atezo/bev therapy. In this study, we investigated whether sarcopenia affects the clinical outcome of atezo/bev therapy. This study included 64 uHCC patients on atezo/bev therapy and assessed their GS and SMI, and SMI was measured using bioelectrical impedance analysis (BIA). We diagnosed sarcopenia based on GS and BIA-SMI and compared the clinical outcomes in the sarcopenia and non-sarcopenia groups. Of these patients, 28 had sarcopenia, and 36 had non-sarcopenia. Adverse events (AEs) frequently occurred, and the albumin-bilirubin score significantly decreased after atezo/bev therapy in the sarcopenia group than in the non-sarcopenia group. The median progression-free survival was 4.7 (0.4–26.4) and 10.6 (1.1–24.5) months in the sarcopenia and non-sarcopenia groups, respectively. The median overall survival (OS) was 12.6 (1.4–27.7) months in the sarcopenia group and was not reached in the non-sarcopenia group, indicating a significant difference in the Kaplan-Meier survival curves for both groups (p < 0.01). In multivariate analysis, sarcopenia was significantly associated with OS. In conclusion, sarcopenia was significantly associated with poor clinical outcomes based on the occurrence of AEs and decreased liver function in uHCC patients on atezo/bev therapy. GS and SMI are important parameters for accurately diagnosing sarcopenia.

Galectins are widely distributed throughout the animal kingdom, from marine sponges to mammals. Galectins are a family of soluble lectins that specifically recognize β-galactoside-containing glycans and are categorized into three subgroups based on the number and function of their carbohydrate recognition domains (CRDs). The interaction of galectins with specific ligands mediates a wide range of biological activities, depending on the cell type, tissue context, expression levels of individual galectin, and receptor involvement. Galectins affect various immune cell processes through both intracellular and extracellular mechanisms and play roles in processes, such as apoptosis, angiogenesis, and fibrosis. Their importance has increased in recent years because they are recognized as biomarkers, therapeutic agents, and drug targets, with many other applications in conditions such as cardiovascular diseases and cancer. However, little is known about the involvement of galectins in liver diseases. Here, we review the functions of various galectins and evaluate their roles in liver diseases.

Sarcopenia-related factors, including the skeletal muscle index (SMI), are reportedly associated with prognosis in patients with hepatocellular carcinoma (HCC) receiving various treatments. However, there is no evidence relating to hepatic arterial infusion chemotherapy (HAIC). In this study, we investigated whether a low SMI was associated with worse clinical outcomes of HAIC. Seventy patients with advanced HCC were included. Clinical outcomes were compared between the decreased SMI (n = 27) and non-decreased SMI (n = 43) groups, which were classified according to changes in the SMI after 3 weeks of treatment. In the prognostic analysis, patients in the decreased SMI group had significantly shorter progression-free and overall survival (OS) than those in the non-decreased SMI group. In addition, poor nutritional status and liver function were associated with an immediate decrease in the SMI after HAIC. The therapeutic effect was worse in the decreased SMI group than in the non-decreased SMI group, although the incidence of adverse events did not significantly differ. In multivariate analysis, a decreased SMI at 3 weeks after HAIC was identified as a significant independent factor associated with OS. A decreased SMI in patients with advanced HCC undergoing HAIC was associated with poor prognosis. It is effective to monitor the SMI to evaluate general conditions and predict clinical outcomes.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is one of the leading causes of cancer-related deaths worldwide. Regorafenib, a multi-kinase inhibitor, is used as a second-line treatment for advanced HCC. Here, we aimed to investigate the mechanism of the antitumor effect of regorafenib on HCC and evaluate altered microRNA (miRNA) expression. Cell proliferation was examined in six HCC cell lines (HuH-7, HepG2, HLF, PLC/PRF/5, Hep3B, and Li-7) using the Cell Counting Kit-8 assay. Xenografted mouse models were used to assess the effects of regorafenib in vivo. Cell cycle analysis, western blotting analysis, and miRNA expression analysis were performed to identify the antitumor inhibitory potential of regorafenib on HCC cells. Regorafenib suppressed proliferation in HuH-7 cell and induced G0/G1 cell cycle arrest and cyclin D1 downregulation in regorafenib-sensitive cells. During miRNA analysis, miRNA molecules associated with the antitumor effect of regorafenib were found. Regorafenib suppresses cell proliferation and tumor growth in HCC by decreasing cyclin D1 via alterations in intracellular and exosomal miRNAs in HCC.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.