Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
Prof. Dr. Jin Ye
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
Intestinal microbiota, dominated by bacteria, plays an important role in the occurrence and the development of alcohol-associated liver disease (ALD), which is one of the most common liver diseases around the world. With sufficient studies focusing on the gut bacterial community, chronic alcohol consumption is now known as a key factor that alters the composition of gut bacterial community, increases intestinal permeability, causes intestinal dysfunction, induces bacterial translocation, and exacerbates the process of ALD via gut-liver axis. However, gut non-bacterial communities including fungi, viruses, and archaea, which may also participate in the disease, has received little attention relative to the gut bacterial community. This paper will systematically collect the latest literatures reporting non-bacterial communities in mammalian health and disease, and review their mechanisms in promoting the development of ALD including CLEC7A pathway, Candidalysin (a peptide toxin secreted by Candida albicans), metabolites, and other chemical substances secreted or regulated by gut commensal mycobiome, virome, and archaeome, hoping to bring novel insights on our current knowledge of ALD. Graphical abstract
15 October 2022 in Oxidative Medicine and Cellular Longevity
Nonalcoholic steatohepatitis (NASH) is a chronic and progressive disease whose treatment strategies are limited. Although time‐restricted feeding (TRF) is beneficial for metabolic diseases without influencing caloric intake, the underlying mechanisms of TRF action in NASH and its efficacy have not yet been demonstrated. We herein showed that TRF effectively alleviated NASH, producing a reduction in liver enzymes and improvements in liver pathology. Regarding the mechanisms by which TRF mitigates NASH, we ascertained that TRF inhibited ferroptosis and the expression of the circadian gene Per2. By adopting a hepatocyte‐specific Per2‐knockout (Per2△hep) mice model, we clarified the critical role of Per2 in exacerbating NASH. According to the results of our RNA‐Seq analysis, the knockout of Per2 ameliorated NASH by inhibiting the onset of ferroptosis; this was manifested by diminished lipid peroxidation levels, decreased mRNA and protein levels for ferroptosis‐related genes, and alleviated morphologic changes in mitochondria. Furthermore, using a ferroptosis inhibitor, we showed that ferroptosis significantly aggravated NASH and noted that this was likely achieved by regulation of the expression of peroxisome proliferator activated receptor (PPAR)α. Finally, we discerned that TRF and hepatocyte‐specific knockout of Per2 promoted the expression of PPARα. Our results revealed a potential for TRF to effectively alleviate high‐fat and high‐fructose diet‐induced NASH via the inhibition of Per2 and depicted the participation of Per2 in the progression of NASH by promoting ferroptosis, which was ultimately related to the expression of PPARα.
15 June 2021 in Journal of Clinical and Translational Hepatology
With an increasing understanding of hepatitis B, the antiviral indications have been broadening gradually. To evaluate the effectiveness of tenofovir alafenamide (TAF) in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and detectable hepatitis B virus (HBV) DNA, those who are ineligible for broader antiviral criteria from the Chinese CHB prevention guide (2019).
This study aimed to analyze the diagnostic accuracy of liver stiffness for predicting esophageal variceal grading and the risk of esophageal variceal bleeding (EVB) in cases of cirrhosis. Hematological and biochemical parameters were measured and transient elastography was performed in 88 patients with hepatitis B–related cirrhosis undergoing endoscopy for esophageal varices. Esophageal varices grade was highly correlated with liver stiffness measurement (LSM) and the liver stiffness spleen diameter-to-platelet score in cirrhosis. Compared with those from endoscopy, the LSM and the liver stiffness spleen diameter-to-platelet score for the absence of esophageal varices were as follows: area under the receiver operating characteristic curve (AUROC), 0.894/0.926; sensitivity, 0.836/0.818; and specificity, 0.875/1.000, respectively. The AUROC and the sensitivity and specificity of LSM and the liver stiffness spleen diameter-to-platelet score for predicting grade III esophageal varices were 0.954 and 0.901, respectively. The AUROCs of LSM and the liver stiffness spleen diameter-to-platelet score for discriminating grades II and III from grade I or the absence of esophageal varices were 0.958 and 0.941, respectively. We also found that EVB was closely associated with LSM and spleen diameter. The AUROC, sensitivity, and specificity were 0.855/0.819, 0.857/0.875, and 0.747/0.780, respectively. Meanwhile, LSM and spleen diameter were 2 independent factors for predicting EVB. These data suggest that LSM and the liver stiffness spleen diameter-to-platelet score could accurately rule out cirrhosis without esophageal varices and differentiate high- and low-risk patients. Furthermore, LSM and spleen diameter had excellent abilities to predict EVB.
Objective: To assess the efficacy of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) in the diagnosis of patients with fever of unknown origin (FUO), who were finally diagnosed as lymphoma. Subjects and Methods: A retrospective study was performed in the First Affiliated Hospital, School of Medicine of Zhejiang University, China, from March 2009 to March 2012. The PET/CT images of consecutive patients with FUO were analyzed. Within 1 week of PET/CT scanning, additional histological tests were also performed if clinically needed. Results: A total of 73 consecutive patients were included. Of these, 34 (47%) had a PET/CT finding suggestive of the presence of lymphoma and 29 (85%) had a diagnosis of confirmed lymphoma; 39 (53%) had a PET/CT result revealing the absence of lymphoma and 4 (10%) were diagnosed by biopsy as having lymphoma, . The most frequent lymphoma diagnosis was peripheral T cell lymphoma (n = 16; 55%), followed by diffuse large B cell lymphoma (n = 9; 31%). The accuracy of PET/CT was 88%. Conclusion: In this study, PET/CT had high diagnostic accuracy in patients with FUO resulting from lymphoma, which indicated that PET/CT scanning was a valuable diagnostic tool for these groups of patients with FUO.
4 March 2021 in Journal of Clinical and Translational Hepatology
Although ursodeoxycholic acid (UDCA) treatment in primary biliary cholangitis is effective in many patients, there are still many people who respond poorly to it. Identifying and intervening these patients early is important. Therefore, exploring the risk factors and proposing a predictor index to predict the UDCA treatment nonresponse earlier among primary biliary cholangitis patients were the aims of this research.