Sclerosing cholangitis (SC) represents a spectrum of chronic progressive cholestatic diseases of the intrahepatic and/or extrahepatic biliary system characterized by patchy inflammation, fibrosis, and stricturing. Primary and secondary SC must be distinguished given the different treatment modalities, risks of malignancy, and progression to portal hypertension, cirrhosis, and hepatic failure. This review focuses on secondary SC and the pathogenic mechanisms, risk factors, clinical presentation, and novel imaging modalities that help to distinguish between these conditions. We explore the detailed use of cholangiography and ultrasound imaging techniques.

IgG4-related disease is an immune-mediated chronic, systemic, and autoinflammatory disease that can affect various organs throughout the body. The most commonly affected areas are the pancreas and biliary system. Due to the diverse clinical manifestations of the disease, it affects widely distributed organs. Thus, it is often easy to misdiagnose or miss. The digestive tract is a rarely affected system, and most IgG4-related gastric diseases manifest as tumors detected by endoscopy. This article reports two special cases with IgG4-related disease involving atrophic gastritis and intestinal polyps to provide a more empirical and theoretical basis for clinical diagnosis and treatment.

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease. Sub-types of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype, disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed PubMed, MEDLINE and Embase with the search terms \"primary sclerosing cholangitis\", \"IgG4\", and \"IgG4-related sclerosing cholangitis (IgG4-SC)\". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSC-normal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features, organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes (B*07, DRB1*15), T-helper2 and T-regulatory cytokines (IL4, IL10, IL13) and chemokines (CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC, although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.

Autoimmune liver diseases (AILDs) are potentially life-threatening chronic liver diseases which include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and recently characterized IgG4-related sclerosing cholangitis. They are caused by immune attack on hepatocytes or bile ducts, with different mechanisms and clinical manifestations. The etiologies of AILDs include a susceptible genetic background, environment insults, infections, and changes of commensal microbiota, but remain complicated. Understanding of the underlying mechanisms of AILDs is mandatory for early diagnosis and intervention, which is of great importance for better prognosis. Thus, animal models are developed to mimic the pathogenesis, find biomarkers for early diagnosis, and for therapeutic attempts of AILDs. However, no animal models can fully recapitulate features of certain AILD, especially the late stages of diseases. Certain limitations include different living condition, cell composition, and time frame of disease development and resolution. Moreover, there is no IgG4 in rodents which exists in human. Nevertheless, the understanding and therapy of AILDs have been greatly advanced by the development and mechanistic investigation of animal models. This review will provide a comprehensive overview of traditional and new animal models that recapitulate different features and etiologies of distinct AILDs.

OBJECTIVE. The purpose of this article is to present the pathologic and clinical features of IgG4-related sclerosing cholangitis (ISC), illustrate the associated imaging findings, and discuss treatment of the disorder. CONCLUSION. ISC is an inflammatory disorder involving the biliary system and resulting in strictures. Although often associated with autoimmune pancreatitis, it may be an isolated disease. Differentiation of ISC from other forms of cholangitis and cholangiocarcinoma is difficult but necessary for management. Imaging is important in diagnosing and assessing the extent of disease and planning a management strategy.

The management of autoimmune hepatobiliary disorders remains a challenging and emerging area of investigation. An awareness of cholestatic liver diseases is critical to appropriate recognition and management of these challenging diseases, because patients often present asymptomatically, and diagnosis is limited by the lack of disease-specific markers and diagnostic studies. Furthermore, there is a paucity of treatment options because the pathophysiology underlying autoimmune biliary diseases remains largely unknown. This article discusses the natural history, clinical presentation, diagnosis, and medical and surgical management strategies for three dominant autoimmune biliary diseases: primary biliary cirrhosis, primary sclerosing cholangitis, and immunoglobulin G4-related hepatobiliary disease.