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Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH‐mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH‐related liver cirrhosis and HCC. In the present study, a steatohepatitis‐related HCC model, hepatocyte‐specific phosphatase and tensin homolog (Pten)‐deficient (Pten Δhep) mice were fed a high‐fat (HF) diet with/without ezetimibe. In the standard‐diet group, ezetimibe did not reduce the development of liver tumors in Pten Δhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF‐positive cells and vascular endothelial cells in the tumors of Pten Δhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in Pten Δhep mice on the HF diet. Tumor cells were highly proliferative with HF‐diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in Pten Δhep mice with hypercholesterolemia.

Aim The major transmission mode of hepatitis A virus (HAV) in Japan is the fecal–oral route by contaminated foods. In contrast, HAV infection is well documented as a sexually transmitted disease in Europe and North America. The present study was undertaken to determine the full‐genome sequence of HAV and trace the transmission route of HAV in Japanese men who have sex with men (MSM). Methods In 2018, we encountered three Japanese MSM with acute hepatitis A co‐infected with HIV for 4–12 years. Serum samples obtained from these patients were used for HAV full‐genome analyses. Results Isolated HAV strains were segregated into subgenotype IA. The three HAV strains shared 100% identity within the 481‐nucleotide partial sequence. The entire nucleotide sequence showed that the three strains were 99.97% similar to each other with only two nucleotide substitutions. At the amino acid level, the three strains differed from each other by only one or two amino acids. All three strains obtained in the present study were >99.6% identical to the 66 reported strains isolated from Taiwan and European countries during 2015–2017. In addition, these 66 strains include the RIVM‐HAV16‐090 (EuroPride) strain, which has been involved in HAV outbreaks among MSM worldwide. Conclusions We determined for the first time the full‐genome sequence of HAV isolated from Japanese MSM with acute hepatitis A and found that the strains were identical to those from MSM worldwide. Thus, these HAV strains were imported to Japan from foreign countries through MSM.

Background: Magnifying narrow band imaging system is useful for the diagnosis of early gastric cancer. However, it is difficult for the operator of the scope to maintain the correct distance between the tip of the endoscope and the gastric mucosa for appropriate visualization. The newly developed optimal band imaging system can reconstruct good spectral images derived from ordinary endoscopic images and enhance the mucosal surface without magnification as well as with low magnification. This imaging technique is based on narrowing the bandwidth of the conventional image arithmetically, using spectral estimation technology. Methods: We evaluated endoscopic features of 30 lesions with elevated-type, 32 lesions with depressed-type and two lesions with flat-type early gastric cancer using this new system. Results: We found the best images in all cases of early gastric cancers by using a specific combination of the following three wavelengths available in this system: 470 nm for blue, 500 nm for green and 550 nm for red.The optimal band images showed the depressed-type early gastric cancer as reddish lesions distinct from the surrounding yellowish non-cancerous area, leading to a clear demarcation line between the cancerous and non-cancerous mucosa without magnification. Moreover, 30-40-fold magnified optimal band images showed a clearly irregular microvascular pattern or a microstructure pattern of the mucosal surface in all types of gastric cancers. Conclusion: This new system can provide useful information for diagnosing various types of early gastric cancers without and with low magnification.