Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders:from molecular mechanisms to clinical implications

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality.Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders,which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries.Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases.In this review,we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations,epidemiology,and aberrant cellular composition involving the biliary ductules,cholangiocytes,immune system,fibroblasts,and the microbiome.We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies.This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.

Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future

Hepatocellular carcinoma(HCC)is a common cancer,and the body’s immune responses greatly affect its progression and the prognosis of patients.Immunological suppression and the maintenance of self-tolerance in the tumor microenvironment are essential responses,and these form part of the theoretical foundations of immunotherapy.In this review,we first discuss the tumor microenvironment of HCC,describe immunosuppression in HCC,and review the major biomarkers used to track HCC progression and response to treatment.We then examine antibody-based therapies,with a focus on immune checkpoint inhibitors(ICIs),monoclonal antibodies that target key proteins in the immune response(programmed cell death protein 1,anti-cytotoxic T-lymphocyte associated protein 4,and programmed deathligand 1)which have transformed the treatment of HCC and other cancers.ICIs may be used alone or in conjunction with various targeted therapies for patients with advanced HCC who are receiving first-line treatments or subsequent treatments.We also discuss the use of different cellular immunotherapies,including T cell receptor(TCR)T cell therapy and chimeric antigen receptor(CAR)T cell therapy.We then review the use of HCC vaccines,adjuvant immunotherapy,and oncolytic virotherapy,and describe the goals of future research in the development of treatments for HCC.