Can Immunoglobulin G4-related disease (IgG4-RD) cause isolated intrahepatic stricture without involvement of the common hepatic duct or common bile duct (CBD)?

From the Guidelines

Yes, IgG4-related disease (IgG4-RD) can cause isolated intrahepatic bile duct strictures without involvement of the common hepatic duct or common bile duct (CBD). IgG4-RD is a systemic fibroinflammatory condition that can affect multiple organs, including the biliary system. When it affects the biliary tract, it's sometimes referred to as IgG4-related sclerosing cholangitis. The disease can present with a variety of biliary involvement patterns, including isolated intrahepatic strictures, extrahepatic strictures, or a combination of both, as described in the British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis 1.

Key Characteristics of IgG4-SC

• The pathophysiology involves infiltration of IgG4-positive plasma cells and lymphocytes into the bile duct walls, leading to fibrosis, wall thickening, and stricture formation.
• Four characteristic patterns of biliary involvement have been defined: type 1, stenosis in the lower common bile duct; type 2a, intrahepatic stenosis with prestenotic dilatation; type 2b, intrahepatic stenosis and peripheral bile duct pruning; type 3, hilar and lower common bile duct stenosis; type 4, hilar stenosis only, as outlined in the guidelines 1.
• Diagnosis typically requires a combination of elevated serum IgG4 levels, characteristic imaging findings, histopathological confirmation when possible, and response to steroid therapy.

Treatment Approach

• Initial treatment usually involves prednisolone at 0.6-1 mg/kg/day (typically 30-40 mg daily) for 2-4 weeks, followed by a gradual taper over 3-6 months, as recommended in the guidelines for the treatment of IgG4-SC 1.
• Rituximab (1000 mg IV given twice, two weeks apart) may be used in steroid-resistant cases, with emerging evidence suggesting its efficacy in patients with IgG4-SC 1.
• Regular monitoring of liver function tests and imaging is essential to assess treatment response and detect disease recurrence.
• Consideration for continued immunosuppressive therapy is recommended for all patients with IgG4-SC, including those with multiorgan involvement in IgG4-RD, as stated in the guidelines 1.

From the Research

IgG4-Related Disease (IgG4-RD) and Intrahepatic Stricture

• IgG4-RD can cause intrahepatic stricture, as well as strictures in other parts of the biliary system 2, 3, 4, 5.
• The disease is characterized by chronic elevation of cholestatic enzyme levels, significant elevation of serum IgG4 levels, and diffuse or segmental narrowing of intra and/or extra hepatic bile ducts with thickening of the bile duct wall in imaging studies 4.
• IgG4-RD can present with isolated biliary involvement, including intrahepatic stricture, in approximately 10% of patients, while about 90% of patients have concomitant autoimmune pancreatitis 3.

Involvement of Common Hepatic or CBD

• IgG4-RD can involve the common hepatic duct or common bile duct (CBD), as well as other parts of the biliary system 2, 3, 4, 5.
• However, it is possible for IgG4-RD to cause isolated intrahepatic stricture without involvement of the common hepatic duct or CBD, although this may be less common 3, 4.
• The diagnosis of IgG4-RD is based on a combination of clinical, laboratory, and imaging findings, and it is essential to distinguish it from other forms of cholangitis and cholangiocarcinoma 2, 3, 6, 4, 5.

Diagnosis and Treatment

• The diagnosis of IgG4-RD is based on a combination of clinical, laboratory, and imaging findings, including serum IgG4 levels, noninvasive imaging, endoscopic ultrasound, and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography 3, 6, 4.
• Treatment with high-dose corticosteroids typically leads to the rapid and consistent induction of disease remission, although disease relapse is relatively common 3, 5.