Secondary sclerosing cholangitis and IgG4-sclerosing cholangitis - A review of cholangiographic and ultrasound imaging

Abstract

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.

Keywords: Cholangiography; IgG4-related sclerosing cholangitis; secondary cholangitis-critically Ill patients; secondary sclerosing cholangitis; ultrasound.

Figure 1

Cholangiographic stage of SCC-CIP according to Leonhardt et al. 2015.[25] Stage I: Multiple ribbon-like filling defects in the bile ducts (biliary casts). Stage II: rapidly progressive intrahepatic bile duct destruction beyond the second bifurcation of the intrahepatic bile ducts. Stage III: progressive destruction of the intrahepatic bile ducts, picture of a “pruned tree”. SCC-CIP: Secondary sclerosing cholangitis in critically ill patients

Figure 2

Bilioma. SSC-CIP. A 56-year-old male, intubation and ventilation for several weeks due to legionella pneumonia. Liver enzymes and cholestatic parameters are slightly elevated. Ultrasound shows a small asymmetrically shaped, smooth bordered anechoic lesion in the right liver lobe (a). The ERCP image shows destroyed and rarefied bile ducts in the left lobe of the liver. The complete right-sided biliary tree is not shown via the unblocked balloon catheter, stage III according to the classification of Leonhardt (b). SSC-CIP: Secondary sclerosing cholangitis in critically ill patients; ERCP: Endoscopic retrograde cholangiopancreaticography

Figure 3

Wall thickening of the bile ducts due to SSC-CIP in a male patient after long-term intensive therapy and several weeks of intubation and ventilation. Ultrasound shows hypoechoic wall thickening and lumen narrowing of the right and left hepatic bile in the hepatic bifurcation (arrows) (a). In the left hepatic duct (b) and the right hepatic duct (c), longer segments of wall thickening are visible on ultrasound (arrows). SSC-CIP: Secondary sclerosing cholangitis in critically ill patients

Figure 4

Irregular bile duct wall thickening due to SSC-CIP in a 62-year-old male patient after intensive therapy with long-term intubation and long-term ventilation. Recurrent removal of casts during ERCP. Ultrasound shows irregular wall thickening and lumen narrowing in the proximal common bile duct (a). The ERCP image shows contrast cavities in the hepatic sinus duct and common bile duct corresponding to casts. The right-sided bile ducts are rarefied (b). In the course, further bile duct destruction with intrahepatic rarefication occurs with an “pruned tree” appearance, stage III according to the classification of Leonhardt (c). SSC-CIP: Secondary sclerosing cholangitis in critically ill patients; Image source of ERCP: Steffen Hornoff and Matthias Mende, Sana Hospital Berlin-Lichtenberg, Endoscopy

Figure 5

Cholangiographic classification of IgG4-SC Type 1-4 according to Nakazawa et al. 2006 and 2012[126,127] und intrahepatic IgG4-SC Type 5 according to Mo et al. 2018.[128] Type 1: stenosis only in the distal (intrapancreatic) part of the common bile duct. Type 2: stenosis in the intrahepatic and extrahepatic bile ducts; extended narrowing of intrahepatic bile ducts with pre-stenotic dilation in type 2a and extended narrowing of intrahepatic bile ducts without pre-stenotic dilation and the reduced number of bile duct branches in type 2b. Type 3: stenosis in both hilar hepatic lesions and the distal part of the common bile duct. Type 4: stenosis only in the hilar hepatic lesions without stenosis of distal common bile duct. Type 5: Strict intrahepatic bile duct stenoses proximal to the hepatic bifurcation. IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis

Figure 6

IgG4-SC and IgG4-positive autoimmune pancreatitis. A 70-year-old female, history of IgG4 positive sialadenitis. Current findings: jaundice, dilated intra-and extrahepatic bile ducts and pancreas head mass. Initially a pancreatic head cancer was suspected. Serum IgG4 was 2-fold elevated. Endosonography showed a hypoechoic lesion in the pancreatic head (a) with marked enhancement in contrast-enhanced harmonic EUS (b). A sandwich-like thickening of the wall of the adjacent distal common bile duct with a smooth border of the inner and outer contour was observed (5mm, between markers; c). The diagnosis was made in the overall context of clinical history, elevated serum IgG4 and hyperenhancement of the pancreatic mass lesion. EUS-guided fine needle biopsy demonstrated no malignancy. The patient showed a rapid response to prednisolone treatment. IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis

Figure 7

IgG4-SC type 3; A 46-year-old male. Initial multifocal autoimmune pancreatitis type I with distal bile duct stenosis. EUS initially showed a hypoechoic lesion at the head of the pancreas with multiple vessels in contrast-enhanced power Doppler before starting Prednisolone therapy (a). After reduction of prednisolone therapy, recurrence of cholestasis. Ultrasound shows a smooth, symmetrical thickening of the wall of the hepatic bifurcation (b). In CEUS this is hyperenhanced in the arterial phase (c) and slightly hypoenhanced in the portal venous (d) and late phase (e). The laboratory values improved under therapy with prednisolone and then azathioprine. Balloon dilatation of stenoses in ERCP was performed several times. Via the blocked balloon catheter, ERCP reveals a short stricture involving the bifurcation of the common hepatic duct (f). IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis; CEUS: Contrast-enhanced ultrasound; Image source of ERCP: Steffen Hornoff and Matthias Mende, Sana Hospital Berlin-Lichtenberg, Endoscopy

Figure 8

IgG4-SC with AIP I (type 1) and multiple other organ manifestations of IgG4-related disease. A 48-year-old male. Longitudinal wall thickening of the bile ducts. Ultrasound shows wall thickening in the proximal common bile duct. The inner and outer contours are smooth, the inner contour is hyperechoic (a). In the left lobe of the liver, there is also a long-stretched wall thickening of the left hepatic duct (b) and of the segmental bile duct branch in the 2^nd liver segment (c). The bile ducts are not dilated. ERC shows short band-like subhilar stricture (arrow) and a second in the right hepatic duct in conjunction with a small diverticular outpouching (arrow) after injection of contrast medium via the blocked balloon catheter. The left hepatic duct is prominent with no biliary strictures in the left part of the biliary tree. The intrahepatic bile ducts are rarefied (d). IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis; AIP: Autoimmune pancreatitis; ERC: Endoscopic retrograde cholangiography

Figure 9

A 55-year-old male patients presenting with mild right upper quadrant pain and elevated liver enzymes, no obstructive jaundice, history of ulcerative colitis. pANCA was positive, serum IgG4 was not elevated. Transabdominal ultrasound shows slight dilatation of the RHD, caused by hypoechoic wall thickening of the CHD and proximal RHD (arrow; a). On CEUS, in the late arterial phase, slight hypoenhancement of the thickened wall compared to liver parenchyma is observed (arrow; b). Radial EUS shows slight wall hypoechoic thickening of the extrahepatic bile duct with reduction (common bile duct, CBD) and loss of anechoic lumen and irregular outer contour (CHD, between markers; arrows are directed to the blurred outline). Compared to the IgG4-SC case in Figure 8, complete loss of layering is observed (c). ERC delineates a long stricture of the CHD extending to right and left hepatic ducts (arrows; d). Please note the difference to the short-band like strictures and diverticular out pouch in the ERC-image of the IgG4-SC case in Figure 8. Stepwise balloon dilatation is performed with initial dentation of the balloon in the area of the tightest part of the stricture (arrowhead; e). IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis; CEUS: Contrast-enhanced ultrasound; ERC: Endoscopic retrograde cholangiography; RHD: Right hepatic duct; CHD: Common hepatic duct; pANCA: Perinuclear anti-neutrophil cytoplasmic antibodies

Figure 10

Intrahepatic cholangiocarcinoma in the left liver lobe, histologically confirmed. A 77-year-old female. US was performed because of elevated liver values. This showed a segmental dilatation of the bile ducts in the left lobe of the liver. In B-mode ultrasound, the cause was a hyperechogenic thickening of the wall without definable stratification, which led to lumen stenosis (a). In CEUS, the wall-thickening, lumen-stenosing process is hyperenhanced in the arterial phase after 16 s (b). Already at the end of the arterial phase at 32 s (c), a slight washout begins. This continues in the portalvenous phase at 48 s (d) and is very clear in the late phase after more than 2 min (e). Histological confirmation was made by percutaneous US-guided biopsy and hemihepatectomy was performed. The cholangiocarcinoma presented as rather hyperechoic. CEUS showed non-specific hyperenhancement in the arterial phase with a subsequent washout, as in the IgG4-SC shown. CEUS: Contrast-enhanced ultrasound; IgG4-SC: Immunoglobulin G4-related sclerosing cholangitis; US: Ultrasound