IgG4-related Sclerosing Cholangitis Research Articles

Relapse of IgG4-related sclerosing cholangitis after steroid therapy: image findings and risk factors

To compare imaging data from IgG4-related sclerosing cholangitis (IgG4-SC) obtained at initial attack and at relapse, and to determine risk factors predicting relapse of IgG4-SC after steroid therapy. Twenty-three patients with relapsed IgG4-SC and 36 non-relapsed patients were included. Computed tomography, magnetic resonance cholangiography, and endoscopic retrograde cholangiography were used to determine biliary and extrabiliary involvement. Images taken at the time of the initial attack were compared with those taken at relapse. Risk factors were determined by comparing clinical and imaging factors in the relapse and non-relapse groups. In comparison to the initial attack, relapsed IgG4-SC was characterised by more frequent extrapancreatic and multiple bile duct strictures, increased bile duct segment involvement, thicker bile duct walls, and a less frequent association with autoimmune pancreatitis (AIP) (P ≤ 0.016). Compared with non-relapse, relapse was significantly associated with less frequent use of maintenance steroid therapy, more frequent extrapancreatic and multiple bile duct strictures, increased bile duct segment involvement, and thicker bile duct walls during the initial attack (P ≤ 0.021). Relapsed IgG4-SC presented with a more aggressive appearance on imaging than the initial attack. The degree of bile duct involvement and use of maintenance steroid therapy were associated with relapse of IgG4-SC.

Inflammatory bowel disease of primary sclerosing cholangitis: A distinct entity?

This is a review of the characteristic findings of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) and their usefulness in the diagnosis of sclerosing cholangitis. PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD. IBD-associated with PSC (PSC-IBD) shows an increased incidence of pancolitis, mild symptoms, and colorectal malignancy. Although an increased incidence of pancolitis is a characteristic finding, some cases are endoscopically diagnosed as right-sided ulcerative colitis. Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon. The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition. The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are similar to those of PSC. The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.

Cholangiocarcinoma with respect to IgG4 Reaction.

IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.

Cholangiocarcinoma with respect to IgG4 reaction

IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.

Nationwide survey for primary sclerosing cholangitis and IgG4‐related sclerosing cholangitis in Japan

We previously conducted nationwide surveys for primary sclerosing cholangitis (PSC) in Japan, and demonstrated several characteristic features of Japanese PSC patients, yet patients with IgG4-related sclerosing cholangitis (IgG4-SC) might be misdiagnosed as PSC. Since the clinical diagnostic criteria of IgG4-SC were established in 2012, we again conducted a nationwide survey to investigate the characteristics of PSC and IgG4-SC lacking pancreatic involvement. The design was a questionnaire-based, multi-center retrospective study. The enrolled subjects were patients with PSC and IgG4-SC without pancreatic involvement diagnosed after 2005. We enrolled 197 PSC and 43 IgG4-SC patients without pancreatic lesions. The male dominance was significantly evident in IgG4-SC (P = 0.006). In patients with PSC, two peaks in age distribution were clearly observed. IgG4-SC was not detected in any patient younger than 45 years of age. At presentation, serum albumin and IgM were significantly higher in PSC, while serum IgG and IgG4 were significantly elevated in IgG4-SC. Inflammatory bowel disease (IBD) was detected in only 68/197 PSC patients (34%). The prognosis of IgG4-SC was considerably better than that of PSC. We confirmed several interesting clinical details of PSC in Japanese patients: two peaks in the age distribution and lower prevalence of IBD.

Establishment of a serum IgG4 cut‐off value for the differential diagnosis of IgG4‐related sclerosing cholangitis: A Japanese cohort

IgG4-related sclerosing cholangitis (IgG4-SC) must be precisely distinguished from primary sclerosing cholangitis and cholangiocarcinoma (CC) because the treatments are completely different. However, the pathological diagnosis of IgG4-SC is difficult. Therefore, highly specific non-invasive criteria such as serum IgG4 should be established. This study established a cut-off for serum IgG4 to differentiate IgG4-SC from respective controls using serum IgG4 levels measured in Japanese centers. A total of 344 IgG4-SC patients were enrolled in this study. As controls, 245, 110, and 149 patients with pancreatic cancer, primary sclerosing cholangitis, and CC, respectively, were enrolled. IgG4-SC patients were classified into three groups: type 1 (stenosis only in the lower part of the common bile duct), type 2 (stenosis diffusely distributed throughout the intrahepatic and extrahepatic bile ducts), and types 3 and 4 (stenosis in the hilar hepatic region) with 246, 56, and 42 patients, respectively. Serum IgG4 levels were compared, and the cut-offs were established. The cut-off obtained from receiver operator characteristic curves showed similar sensitivity and specificity to that of 135 mg/dL when all IgG4-SC and controls were compared. However, a new cut-off value was established when subgroups of IgG4-SC and controls were compared. A cut-off of 182 mg/dL can increase the specificity to 96.6% (4.7% increase) for distinguishing types 3 and 4 IgG4-SC from CC. A cut-off of 207 mg/dL might be useful for completely distinguishing types 3 and 4 IgG4-SC from all CC. Serum IgG4 is useful for the differential diagnosis of IgG4-SC and controls.

Differentiating Immunoglobulin G4-Related Sclerosing Cholangitis from Hilar Cholangiocarcinoma

Background/AimsFew studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC.MethodsWe retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC.ResultsIn patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01).ConclusionsAn integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.

Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune pancreatitis. However, the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC responds well to steroid therapy, whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention. Since IgG4-SC was first described, it has become a third distinct clinical entity of sclerosing cholangitis. The aim of this review was to introduce the diagnostic methods for IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical, serological, morphological, and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis. When intrapancreatic stenosis is detected, pancreatic cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident, PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC should be discriminated by ultrasonography, intraductal ultrasonography, bile duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL.

IgG4-related intrahepatic sclerosing cholangitis resulting in sepsis caused by secondary suppurative inflammation: report of a case

We report a case of pre-disseminated intravascular coagulation caused by secondary suppurative inflammation in a patient with immunoglobulin (Ig) G4-related sclerosing cholangitis. The patient was a 78-year-old man in whom a localized stenosis of the intrahepatic bile duct was found without any other bile duct stricture or symptoms. He underwent surgical resection 6months later for acute severe cholangitis and sepsis caused by bile duct obstruction. The resected specimen contained an abscess and nodulary mass in the liver. Immunohistochemical analysis revealed IgG4-positive plasma cell infiltration, whereby we diagnosed IgG4-related sclerosing cholangitis. As IgG4-related sclerosing cholangitis limited to within the intrahepatic portion is extremely rare, we present this case with a review of the literature.

IgG4-Related Sclerosing Cholangitis Mimicking Cholangiocarcinoma

IgG4-related disease has gained increased attention worldwide. While the initial focus was on autoimmune pancreatitis which was first described in Asian populations and turned out to be of relevance in Western populations too, the scope has recently broadened towards a notion of a multi-systemic disease with very diverse manifestations such as autoimmune pancreatitis, IgG4-related sclerosing cholangitis (IgG4-SC), retroperitoneal fibrosis and tubulointerstitial nephritis. IgG4-SC (also known as IgG4-associated cholangitis, IAC) represents a rare but clinically challenging differential diagnosis in patients with obstructive jaundice and proximal extra- or intrahepatic biliary strictures which can be mistaken for cholangiocarcinoma (CC). We present the case of a 79-year-old male patient who presented with obstructive jaundice and biliary strictures at the hepatic duct bifurcation without any evidence for autoimmune pancreatitis and without elevation of serum IgG4-concentrations who underwent hemihepatectomy for suspected CC. However, on histological examination of the resection specimen CC could not be confirmed. It was only after several episodes of obstructive jaundice had reoccurred that the diagnosis of IgG4-SC could be established by reexamination of the surgical specimen which showed extensive infiltration with IgG4-positive plasma cells. Appropriate medical treatment with steroids and azathioprine led to complete remission of the disease. Early recognition of IgG4-SC can save patients from potential harmful and unnecessary surgical interventions. Here we describe the clinical features of this rare case of IgG4-SC with extensive liver tissue infiltration with IgG4-positive cells but without elevated serum IgG4 concentration or evidence of autoimmune pancreatitis. We describe diagnostic criteria for IgG4-SC and review recent insights in pathophysiology and treatment options.

The role of peroral video cholangioscopy in patients with IgG4-related sclerosing cholangitis

The cholangioscopic features of IgG4-related sclerosing cholangitis (IgG4-SC) remain undefined. The aim of this study was to clarify these endoscopic features using peroral video cholangioscopy (PVCS) in IgG4-SC patients. PVCS was performed in 33 patients: IgG4-SC (n=13); primary sclerosing cholangitis (PSC; n=5); and cholangiocarcinoma (n=15), which included hilar cholangiocarcinoma (HCCA; n=5) and distal cholangiocarcinoma (DCCA; n=10). The most frequent findings on PVCS in the IgG4-SC patients were dilated (62%) and tortuous (69%) vessels, and absence of partially enlarged vessels. The incidence of dilated and tortuous vessels was significantly higher in IgG4-SC patients than in PSC patients (p=0.015). Scarring and pseudodiverticula were found significantly more often in PSC patients than in IgG4-SC patients (p=0.001 and p=0.0007, respectively). The incidence of partially enlarged vessels was significantly higher in DCCA patients than in IgG4-SC patients (p=0.004). In contrast, the incidence of dilated vessels was significantly higher in IgG4-SC patients than in HCCA patients (p=0.015). PVCS performed after corticosteroid therapy showed resolution of bile duct stenosis and dilated, tortuous, or partially enlarged vessels, as well as resolution of friability in all patients with IgG4-SC. Cholangioscopy was useful in differentiating IgG4-SC from PSC. In addition, monitoring the patterns of proliferative vessels on PVCS may be useful to differentiate IgG4-SC from cholangiocarcinoma.

IgG4‐related sclerosing cholangitis with autoimmune pancreatitis and periaortitis: Case report and review of the literature

Immunoglobulin G4 (IgG4)-related systematic disease (IgG4-RSD) is a systemic fibroinflammatory condition characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs including pancreas, bile duct, gallbladder, salivary glands, kidney, lung, prostate, retroperitoneum and even the thyroid gland. It may affect one or two and sometimes more than three organs. Early diagnosis and treatment could not prevent sclerosis and permanent damage of the affected organ but also avoid other organ involvement. Here we present a rare case of IgG4-RSD affecting pancreas, biliary duct system and abdominal aorta. A review of the literature was also made mainly concerning IgG4-related sclerosing cholangitis (IgG4-SC) and periaortitis.

A Case of IgG4-related Sclerosing Cholangitis Overlapped with Primary Biliary Cirrhosis

IgG4-related sclerosing cholangitis (IgG4-SC) and primary biliary cirrhosis (PBC) can both cause liver dysfunction. While IgG4-SC is associated with IgG4-related diseases such as autoimmune pancreatitis, PBC is associated with various autoimmune diseases. However, there is only one case report of an association between IgG4-SC and PBC, and this association has not been elucidated further. The treatments for these two diseases are different, i.e., corticosteroid treatment is performed for IgG4-SC and ursodeoxycholic acid is given for PBC. We report a case of IgG4-SC overlapping with PBC in a 45-year-old man who was successfully treated by combination therapy with prednisolone and ursodeoxycholic acid.

IgG4-related sclerosing cholangitis mimicking cholangiocellular carcinoma in a patient with obstructive jaundice

IgG4-related disease has gained increased attention worldwide. While the initial focus was on autoimmune pancreatitis which was first described in Asian populations and turned out to be of relevance in Western populations too, the scope has recently broadened towards a notion of a multi-systemic disease with very diverse manifestations such as autoimmune pancreatitis, IgG4-related sclerosing cholangitis (IgG4-SC), retroperitoneal fibrosis and tubulointerstitial nephritis. IgG4-SC (also known as IgG4-associated cholangitis, IAC) represents a rare but clinically challenging differential diagnosis in patients with obstructive jaundice and proximal extra- or intrahepatic biliary strictures which can be mistaken for cholangiocellular carcinoma (CCC). We present a very rare case of a 79-year-old male patient with a normal serum IgG4-level and without any evidence for autoimmune pancreatitis who presented with obstructive jaundice and biliary strictures at the hepatic duct bifurcation and who underwent hemihepatectomy for suspected CCC. However, on histological examination of the resection specimen CCC could not be confirmed. It was only after several episodes of obstructive jaundice reoccurred that the diagnosis of IgG4-SC could be established by reexamination of the surgical specimen, which showed a dense IgG4-positive lymphoplasmocytic infiltrate. Appropriate medical treatment with steroids and azathioprine led to complete remission of the disease. IgG4-SC represents a rare but important differential diagnosis in patients with obstructive jaundice since it usually responds well to steroids and early recognition can save patients from unnecessary surgery.

A Case of IgG4-related Sclerosing Cholangitis with a Normal Serum IgG4 Level: Report of a Case

Although hilar cholangioma is the most common cause of stricture of the hilar bile duct, several diseases can contribute to stenosis. Here, we report on a patient with immunoglobulin (Ig) G4-related sclerosing cholangitis (IgG4-SC) of the hilar bile duct arising from obstructive jaundice. The patient had undergone laparoscopic cholecystectomy for the removal of gallstones. The differential diagnosis for icterus included hilar cholangiocarcinoma, primary sclerosing cholangitis, IgG4 sclerosing cholangitis, ischemic bile duct stenosis, a complication of cholecystitis, amputation neuroma, and iatrogenic stenosis. Numerous examinations were performed, but a definite diagnosis remained elusive. Because cholangiocarcinoma could not be ruled out, we proposed surgical resection. The patient subsequently underwent extended right liver lobectomy and intrahepatic cholangiojejunostomy. Pathological examination revealed numerous inflammatory cell infiltrates resembling IgG4-positive antibody plasma cells in the stromal layer of the stenotic bile duct walls. Hypertrophy of the nerve fiber fascicles was not observed. The serum IgG4 level of the patient was within the normal range. Few reports of IgG4-SC with a normal serum IgG4 level have been published. When this condition presents as it did in the present case, establishing a definite diagnosis can be difficult.

Diagnostic criteria for IgG4-related sclerosing cholangitis based on cholangiographic classification

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria for IgG4-SC based on cholangiographic classification by comparison with several diagnostic modalities. We classified 62 IgG4-SC patients into three groups on the basis of cholangiographic findings to allow differentiation from PCa, PSC, and CC: Group A IgG4-SC showed features similar to PCa (Type 1, n=32), Group B showed similarity to PSC (Type 2, n=15), and Group C showed similarity to CC (Type 3, 4, n=15). Thirty-five patients with PCa, 40 with PSC, and 32 CC were enrolled as controls. We retrospectively compared the clinical, imaging, serological, and histopathological features and involvement of other organs between Group A and PCa, Group B and PSC, and Group C and CC. Association with autoimmune pancreatitis (AIP) (P<0.001) and involvements with other organs (specificity 100%) were common useful diagnostic parameters in all three IgG4-SC groups. A high serum IgG4 level was a useful parameter in Groups A and B (P<0.001). Discriminant analysis of cholangiograms (P<0.001), liver biopsy (specificity 100%), and exclusion of inflammatory bowel disease (specificity 100%) were useful parameters in Group B. Intraductal ultrasonography findings (P<0.001) and exclusion of malignancy by bile duct biopsy (specificity 100%) were useful parameters in Group C. We established diagnostic criteria for IgG4-SC (sensitivity 100%, specificity 96.3%) by incorporating parameters that showed P<0.001 or 100% specificity. Diagnostic criteria for IgG4-SC based on cholangiographic classification are useful for distinguishing it from PCa, PSC, and CC.

Autoimmune pancreatitis and biliary intraepithelial neoplasia of the common bile duct: A case with diagnostically challenging but pathogenetically significant association

Autoimmune pancreatitis (AIP) (also called IgG4-related sclerosing pancreatitis (IgG4-SP)) and IgG4-related sclerosing cholangitis (IgG4-SC) are frequently associated with each other. It is generally believed that association of these diseases with pancreatobiliary malignancy is, however, rare. Here, we report on the case of a patient with AIP whose biliary cytology revealed severely atypical cells. Surgically resected specimens from this patient showed typical AIP with IgG4-SC, as well as a mildly elevated lesion in the common bile duct with varying degrees of cellular atypia. In addition, the atypical cells tested positive for the mucin-core protein, MUC5AC and p53 overexpression. These findings led us to diagnose the common bile duct lesion as biliary intraepithelial neoplasia (BilIN, mainly BilIN-1/2). Recently, associations between K-ras mutations and pancreatobiliary carcinoma have been reported in patients with AIP. This case, therefore, provides important new insight into the potential association of AIP and/or IgG4-SC with malignancy (or precursor lesions) of the pancreatobiliary system.

Immunoglobulin G4‐positive plasma cell infiltration in explanted livers for primary sclerosing cholangitis

To explore whether immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) contributes to end-stage primary sclerosing cholangitis (PSC) in the United Kingdom. This study consisted of 41 patients who underwent liver transplantation for advanced PSC. Explanted livers were examined histologically with an emphasis on IgG4-positive plasma cell infiltration. Thirty-nine cases (95%) had minimal or mild infiltration of IgG4-positive plasma cells (≤ 30 cells/high-power field). In contrast, two cases (5%) showed plasma cell IgG4-positivity in more than 100 cells/high-power field. IgG4-positive plasma cells were accumulated preferentially in a (xantho)granulomatous tissue within large bile ducts. Except for the presence of IgG4-positive plasma cells, there was no significant histological difference between IgG4-positive and negative cases. Both showed sclerosing cholangitis with bile duct erosion and xanthogranulomatous reaction more in keeping with PSC than typical IgG4-SC. Clinically, the two patients differed from typical IgG4-related disease, in that both had associated ulcerative colitis, and one of them was younger than expected for IgG4-SC (28 years old). No classical IgG4-SC could be identified in patients explanted for PSC. The two cases identified with numerous IgG4-positive plasma cells suggest a superimposed immune mechanism of uncertain nature. A prospective study is needed to assess whether such cases will be steroid-sensitive.

IgG4-related sclerosing cholangitis: liver biopsy findings

IgG4-related autoimmune disease is a recently recognized clinical entity associated with autoimmune pancreatitis, various systemic extrapancreatic lesions and an elevated serum IgG4 level.1 IgG4-related sclerosing cholangitis (IgG4-SC) is one of the extrapancreatic manifestations of this entity, which needs to be differentiated from primary sclerosing cholangitis (PSC) as these two diseases appear similar at presentation, but follow different clinical courses. In this issue, we will discuss the histopathologic findings of IgG4-SC based on a liver biopsy case of a 65-year-old patient with autoimmune pancreatitis.

Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy and cholangiography correlation

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from primary sclerosing cholangitis (PSC). In this study, we performed a retrospective study to reveal cases in which liver needle biopsy was useful for differential diagnosis. Nineteen patients with IgG4-SC and 22 patients with PSC were studied. All patients underwent endoscopic retrograde cholangiography and liver needle biopsy. We defined small bile duct involvement of IgG4-SC histologically as damage to the small bile duct associated with infiltration of ≥10 IgG4+ plasma cells per high power field (HPF). Clinicopathological characteristics were compared between IgG4-SC patients with and without small bile duct involvement. Small bile duct involvement was observed in 5 (26%) of the patients with IgG4-SC. Patients with small bile duct involvement showed a higher incidence of intrahepatic biliary strictures on cholangiography (80 vs. 21%, p = 0.038). Conversely, 4 of 7 (57%) patients with intrahepatic biliary strictures on cholangiography had histologically evident small duct involvement. The number of IgG4+ plasma cells was significantly correlated with the site of the most proximal stricture on cholangiograms (p = 0.021). The number of IgG4+ plasma cells per HPF was significantly higher in IgG4-SC patients with intrahepatic biliary strictures than in those with PSC (13.4 vs. 0.4 cells/HPF, p < 0.001). Involvement of small bile ducts is more frequent in patients with intrahepatic biliary strictures on cholangiography, and liver needle biopsy is especially useful for these patients.