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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.

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 cell 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.