ABSTRACT
Objective@#Screening of patients with familial primary biliary cholangitis by using whole-exome sequence to find common low-frequency mutations and to explore its pathogenesis. @*Methods@#The confirmed data of PBC patients diagnosed in Xijing hospital from 2005 to 2016 were collected, and their first-degree relatives' autoantibodies were screened for diagnosis. DNA extraction from PBC patients and normal controls in two high-incidence families was performed for whole-exome sequencing, and the low-frequency mutations in the family were screened. @*Results@#A total of 435 PBC patients and 946 first-degree relatives were screened, and 18 (1.90%) first-degree relatives were also diagnosed with PBC, which was distributed in 16 families (3.68%). The whole-exome sequencing results showed that the common low-frequency mutations of 7 patients in 2 families consisted of 16 single nucleotide polymorphisms and 2 InDel markers, of which ANO2(rs17788563) may be correlated to the pathogenesis of PBC. @*Conclusion@#There is high-incidence of PBC in the family members of PBC patients with low-frequency mutation sites and their sites may be involved in the pathogenesis of PBC.
ABSTRACT
Primary sclerosing cholangitis (PSC)is a chronic cholestatic liver disease characterized by inflammation, fibrosis,and stricture of the intra- and/ or extrahepatic bile ducts. PSC is frequently insidious onset,but may aggravate progressively and ultimately leading to biliary cirrhosis and eventually hepatic failure. Most of the PSC patients are associated with inflammatory bowel disease,and the risk of hepatobiliary malignancy especially cholangiocarcinoma increases significantly. So far,the mechanism of PSC is not clearly known and lacking effective medical therapy. This article provides a comprehensive review on advances in diagnosis and treatment of PSC,including the consensus on imaging diagnosis,prognostic stratification and new drugs in ongoing trials.
ABSTRACT
Inflammatory response and immune dysfunction play important roles in the progression of acute-on-chronic liver failure (ACLF) and may lead to systemic inflammatory response syndrome.Excessive inflammatory and immune response may result in increased susceptibility to infection and finally lead to multiple organ dysfunction syndrome (MODS).Elimination of liver injury and correction of immune dysfunction can prevent sepsis and/or MODS and improve patients' survival.Up to now,immunotherapy for ACLF has not been recommended in related guidelines.However,as an important pathophysiological change of ACLF and a key event closely associated with incidence rate and mortality rate,persistent activation of hepatic and systemic inflammatory response and immune cel1 dysfunction urges us to consider immunoregulatory treatment,in order to block and reverse disease progression.This article introduces potential immunoregulatory drugs for the treatment of ACLF,including albumin,glucocorticoids,granulocyte colony-stimulating factor,artificial liver support system,and mesenchymal stem cell transplantation,and discusses some promising targets for immunotherapy.
ABSTRACT
Inflammatory response and immune dysfunction play important roles in the progression of acute-on-chronic liver failure (ACLF) and may lead to systemic inflammatory response syndrome.Excessive inflammatory and immune response may result in increased susceptibility to infection and finally lead to multiple organ dysfunction syndrome (MODS).Elimination of liver injury and correction of immune dysfunction can prevent sepsis and/or MODS and improve patients' survival.Up to now,immunotherapy for ACLF has not been recommended in related guidelines.However,as an important pathophysiological change of ACLF and a key event closely associated with incidence rate and mortality rate,persistent activation of hepatic and systemic inflammatory response and immune cel1 dysfunction urges us to consider immunoregulatory treatment,in order to block and reverse disease progression.This article introduces potential immunoregulatory drugs for the treatment of ACLF,including albumin,glucocorticoids,granulocyte colony-stimulating factor,artificial liver support system,and mesenchymal stem cell transplantation,and discusses some promising targets for immunotherapy.