Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis.

Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.

Screening of familial primary biliary cholangitis and research on low-frequency mutations by whole-exome sequencing / 中华肝脏病杂志

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.

Advances in Diagnosis and Treatment of Primary Sclerosing Cholangitis / 胃肠病学

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.

Immunotherapy for acute-on-chronic liver failure / 临床肝胆病杂志

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.

Immunotherapy for acute-on-chronic liver failure / 临床肝胆病杂志

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.