Liver transplantation is an effective treatment for various end-stage liver diseases, and the shortage of donor livers is one of the main obstacles affecting the development of liver transplantation. Xenotransplantation holds promise as a potential solution to the organ shortage. By using gene-editing technology to modify animal genes, their physiological compatibility with humans can be improved. Combining this with new immunosuppressive drugs can reduce the occurrence of rejection, thereby increasing the survival time of the graft. Due to the more complex structure and physiological functions of the liver, inter-species incompatibility is more pronounced in liver xenotransplantation compared to heart or kidney. The molecular mechanisms related to xenograft rejection and coagulation disorders post-operation require further research. This article reviews the latest research progress domestically and internationally, the historical development of liver xenotransplantation, the main current challenges, and clinical applications, aiming to enhance clinicians' understanding of liver xenotransplantation.
Intrahepatic cholangiocarcinoma (iCCA) occurs within the liver, between the bile duct and the secondary bile duct. It is the second most common primary liver cancer after hepatocellular carcinoma, and its incidence rate is increasing worldwide. The mortality rate is alarming because of its clinical asymptomatic features (often leading to delayed diagnosis), high invasiveness, and treatment resistance. Early diagnosis, molecular pathological biology, accurate staging, and personalized multidisciplinary treatment are current challenges for researchers and physicians. Furthermore, iCCA is difficult to treat due to its high heterogeneity at the clinical, genomic, epigenetic, and molecular levels. However, recent advances in molecular, surgical, and targeted therapies, along with the recognition that the etiology, risk factors, pathophysiology, molecular biology, and clinical management of iCCA differ completely from those of hilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA), have prompted the International Liver Cancer Association and the European Association for the Study of the Liver to commission international specialized experts to draft evidence-based guidelines for physicians involved in the diagnosis, treatment, and prognosis. Herein, the key points of the guidelines are excerpted.
Objective: To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice. Methods: Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance. Results: The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group (P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention (P<0.05). Conclusion: Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.
Primary Sclerosing Cholangitis(PSC) is a rare, chronic liver disease characterized by bile duct inflammation and concentric fibrogenesis. To date, there has been no evidence that any drug therapy can alter the natural course of this disease. PSC is often concomitant with inflammatory bowel disease(IBD), but the pathogenesis remains unclear. Oral antibiotics have been shown to improve PSC and concomitant IBD, and vancomycin is the most widely used. Therefore, this paper reviews literatures on the application of vancomycin in PSC, aiming to explore therapeutic approaches for PSC that target other pathophysiological pathways.
Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC (n=84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.
Objective: To investigate the influence of ascites grading and non-selective β- blockers (NSBBs) on the 1-year prognosis of patients with acute-on-chronic liver failure (ACLF). Methods: A total of 1 386 patients with ACLF were graded for ascites and followed up for one year. Kaplan-Meier Log-rank test and Cox regression were used for multivariate regression to analyze the effects of ascites grading and NSBBs on the 1-year prognosis of ACLF. Results: The incidence of ascites in 1 836 patients with ACLF was 77.56% on admission. Ascites grade was related to the 1-year prognosis of ACLF [log rank (Mantel-Cox) χ2=21.384, p=0.000]. Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin time activity(PTA), urea, MELD-Na score, and application of NSBBs were closely related to the 1-year prognosis of ACLF. The result of Kaplan-Meier Log-rank test for patients treated with NSBBs in the grade 2/3 ascites group suggest that NSBBs can improve the 1-year survival rate of ACLF patients with grade 2 and grade 3 ascites ( log rank (Mantel-Cox) χ2=6.113, p=0.013). Conclusions: Ascites grading and application of NSBBs can affect the 1-year prognosis of ACLF. NSBBs may be beneficial to the long-term prognosis of ACLF. Patients treated with NSBBs before the onset of ACLF should continue NSBBs treatment.
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