Liver transplant and autoimmune liver diseases: An up-to-date review

Abstract

Autoimmune liver diseases, encompassing autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are chronic immune-mediated disorders that are uncommon but clinically significant due to their progressive nature, diagnostic complexity, and limited treatment options. These conditions may evolve into advanced fibrosis, cirrhosis, or liver failure, and liver transplantation, while life-saving, does not eliminate the underlying immune dysregulation and introduces risks of disease recurrence and complications from chronic immunosuppressive therapy, such as osteoporosis, infections, and metabolic disorders. Autoimmune hepatitis is characterized by hepatocellular inflammation and fibrosis associated with autoantibodies, including antinuclear antibodies, smooth muscle antibodies, anti–liver kidney microsomal type 1 antibodies, and anti–soluble liver antigen/liver pancreas antibodies, as well as aberrant B and T lymphocyte activity. Standard therapy relies on corticosteroids combined with azathioprine, but novel approaches are under investigation, including rituximab, zetomipzomib, and toll-like receptor 4 antagonists. Primary biliary cholangitis is marked by autoimmune-mediated destruction of small bile ducts, commonly associated with antimitochondrial antibodies, gp210, and sp100 antibodies. Ursodeoxycholic acid (UDCA) is the cornerstone of therapy, although up to 40% of patients show incomplete response, prompting interest in obeticholic acid, bezafibrate, peroxisome proliferator-activated receptor agonists, and setanaxib. Primary sclerosing cholangitis involves progressive intra- and extrahepatic duct fibrosis, associated with IgG4, perinuclear anti-neutrophil cytoplasmic antibodies, and an increased cancer risk, with emerging therapies such as norUDCA, farnesoid X receptor agonists, anti-tumor necrosis factor, anti-integrin agents, and autologous stem cell transplantation.

Keywords: Autoimmune liver diseases; Autoimmune hepatitis; Primary biliary cholangitis; Primary sclerosing cholangitis; Liver transplantation

Core Tip: Autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are chronic immune-mediated disorders that may progress to cirrhosis, liver failure and death. Although liver transplantation mostly ensures favorable survival rates, recurrence and complications remain significant challenges. Therefore, the understanding of immune mechanisms, the gut-liver axis, and novel targeted therapies offer new perspectives to improve long-term outcomes and optimize patient management.