Hepatitis C virus (HCV) is the main cause of chronic hepatitis worldwide. Chronic hepatitis ultimately results in the development of hepatocellular carcinoma (HCC). However, the mechanism of hepatocarcinogenesis in chronic HCV infection is still unclear. The ability of the core protein of HCV to modulate gene transcription, cell proliferation and cell death may be involved in the pathogenesis of HCC. Here, we report the development of HCC in two independent lines of mice transgenic for the HCV core gene, which develop hepatic steatosis early in life as a histological feature characteristic of chronic hepatitis C. After the age of 16 months, mice of both lines developed hepatic tumors that first appeared as adenomas containing fat droplets in the cytoplasm. Then HCC, a more poorly-differentiated neoplasia, developed from within the adenomas, presenting in a 'nodule-in-nodule' manner without cytoplasmic fat droplets; this closely resembled the histopathological characteristics of the early stage of HCC in patients with chronic hepatitis C. These results indicate that the HCV core protein has a chief role in the development of HCC, and that these transgenic mice provide good animal models for determining the molecular events in hepatocarcinogenesis with HCV infection.

Sarcopenia is defined by muscle loss and muscle dysfunction. Sarcopenia is classified into primary and secondary types, based on the cause. Primary sarcopenia is mainly aging-related sarcopenia, whereas secondary sarcopenia is the reduced muscle mass and strength that accompanies an underlying disease. Given the essential role of the liver in metabolism, secondary sarcopenia due to nutritional disorders or other factors can frequently occur in liver disease. In 2015, the Japan Society of Hepatology (JSH) decided to establish its own assessment criteria for sarcopenia in liver disease because the number of liver disease patients with sarcopenia is expected to increase and there is cumulative evidence to indicate sarcopenic patients have poor clinical outcomes. A working group to create assessment criteria for sarcopenia has thus been established by the JSH. In this article, we summarize the current knowledge with regard to sarcopenia and present the assessment criteria for sarcopenia in liver disease proposed by the JSH (1st edition). To the best of our knowledge, this is globally the first proposed assessment criteria for sarcopenia specializing in liver disease.

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Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, which finally leads to development of hepatocellular carcinoma. Chronic hepatitis C is characterized by several histological features in the liver which discriminate it from other forms of hepatitis : bile duct damage, lymphoid follicles and steatosis (fatty change). Little is known, however, about the role of HCV or its viral proteins in the pathogenesis of hepatitis. Recently, the core protein of HCV has been suggested to have a transcriptional regulatory function, and thereby to

Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation [1][2][3] . The gut microbiota is considered to be a critical determinant of human health and longevity [4][5][6][7][8] . Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian's faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5a-reductase (5AR) and 3bhydroxysteroid dehydrogenase (3bHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium.These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity. MainThe microbiome has long been recognized as a key player in determining the health status of ageing individuals through its role in controlling digestive functions, bone density, neuronal activity, immunity, and resistance to pathogen infection [9][10][11][12][13] . Microbial consortia in elderly individuals often show increased interindividual variability and reduced diversity, and are thus being linked to immunosenescence, chronic systemic inflammation, and frailty 6,14 . An integrated understanding of the dynamic balance and functions of microbial members with respect to ageing is essential for establishing a strategy toward rational manipulation of the microbiota for restoring and/or maintaining tissue homeostasis and overall health.Centenarians (aged 100 years and older) are known to be less susceptible to age-related diseases including hypertension, diabetes, obesity, and cancer 3,15 . Moreover, centenarians have likely survived periods of hunger and several bouts with infectious diseases such as influenza, tuberculosis, shigellosis, and salmonellosis 16 . It has been postulated that there are centenarian-specific members of the gut microbiota which, rather than representing a mere consequence of ageing, might actively contribute to maintaining homeostasis, resilience, and healthful ageing [4][5][6]8 . In this study, we aimed