Percutaneous transhepatic cholangiography can improve the detection rate of biliary lesion characteristics in IgG4-related sclerosing cholangitis and is a necessary method for early diagnosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Percutaneous transhepatic cholangiography can improve the detection rate of biliary lesion characteristics in IgG4-related sclerosing cholangitis and is a necessary method for early diagnosis Cheng Wang, Ziman Zhu, Yalin Kong, Lin Zhang, Chengli Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9095183/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Although IgG4-associated sclerosing cholangitis (IgG4-SC) has been widely recognized, distinguishing it from cholangiocarcinoma remains challenging when MRI demonstrates biliary obstruction or abrupt cutoff. Moreover, conventional CT and MRI often fail to fully delineate the intraluminal morphology of stenotic bile ducts. Aims : To evaluate the diagnostic value of percutaneous transhepatic cholangiography (PTC) versus CT and MRI in depicting intraluminal morphology and identifying features suggestive of benign, compliant strictures in patients with IgG4-SC. Methods : We conducted a retrospective review of 20 patients diagnosed with IgG4-SC from our medical center. PTC findings were compared with contemporaneous CT and MRI images. In addition, PTC features of IgG4-SC were contrasted with those of classic cholangiocarcinoma. The utility of PTC for initial diagnosis and serial assessment of steroid response was analyzed. Results : In cases where CT/MRI showed biliary obstruction or cutoff, PTC more frequently demonstrated the typical features of IgG4-SC, with a higher diagnostic yield. PTC clearly identified long-segment, smooth, symmetric, and compliant strictures, which were distinctly different from the abrupt, irregular, and rigid strictures characteristic of malignant biliary tumors. Furthermore, PTC allows repeatable cholangiographic evaluation, enabling serial and timely monitoring of stricture changes in response to steroid therapy. Conclusions : For patients with IgG4-SC, injecting a contrast agent through a biliary drainage tube can clearly show the internal morphological characteristics of the bile duct lumen by virtue of the physiological elasticity of the bile duct wall. PTC can identify IgG4-SC earlier in suspected cases and is a very valuable supplementary diagnostic method in the diagnosis of this disease. Health sciences/Diseases Health sciences/Gastroenterology IgG4-related sclerosing cholangitis (IgG4-SC) Percutaneous transhepatic cholangiography (PTC) Cholangiocarcinoma (CC) Bile duct wall elasticity Differential diagnosis Figures Figure 1 Figure 2 Figure 3 1 Introduction IgG4-associated sclerosing cholangitis (IgG4-SC), a subtype of IgG4-related disease (IgG4-RD), is a benign biliary stricture disorder that is not uncommon in the Chinese population. A study from Peking University People's Hospital enrolled 62 patients with obstructive jaundice caused by non-neoplastic diseases between August 2014 and August 2016, among whom 13 were diagnosed with IgG4-SC [ 1 ]. Clinical evidence has confirmed that the overall response rate of IgG4-SC to steroid therapy reaches 90% [ 2 , 3 ]. Patients with IgG4-SC typically present with obstructive jaundice, and computed tomography (CT) and magnetic resonance imaging (MRI) often reveal biliary ductal interruption—an imaging feature that renders differentiation from cholangiocarcinoma extremely challenging [ 4 – 7 ]. Based on the location of biliary stenosis, IgG4-SC is classified into four subtypes [ 8 ], with type 4 characterized by hilar biliary stenosis. The diagnosis of IgG4-SC is relatively straightforward when accompanied by multi-organ involvement of IgG4-RD [ 9 ], while differentiation from hilar cholangiocarcinoma becomes markedly difficult in the absence of extra-biliary manifestations [ 10 , 11 ]. Although serum IgG4 levels serve as an important auxiliary diagnostic marker for IgG4-SC, elevated serum IgG4 is not specific to this disease: it can be detected in 5% of healthy individuals and 10% of patients with pancreatic or gallbladder carcinoma [ 12 ], and thus cannot be regarded as a sufficient diagnostic criterion for IgG4-SC. The 2012 Japanese Diagnostic Criteria for IgG4-SC [ 13 ] emphasized that biliary imaging findings of diffuse biliary wall thickening carry greater diagnostic weight than elevated serum IgG4 levels. Timely acquisition of characteristic imaging features is therefore crucial for the early clinical diagnosis of IgG4-SC. In our clinical work, we have found that patients with suspected IgG4-SC who undergo percutaneous transhepatic cholangial drainage (PTC) in the early stage can often be diagnosed more quickly. The reason is that PTC can clearly show the typical signs in the stenotic bile ducts, which is different from the "bile duct interruption" shown by magnetic resonance cholangiopancreatography (MRCP), thus helping to distinguish it from cholangiocarcinoma. Therefore, for patients with IgG4-SC, when MRCP has a blind spot, PTC is a key means to solve clinical problems. Furthermore, the detection of imaging changes and confirmation of therapeutic efficacy following short-term corticosteroid therapy constitute strong evidence for a definitive diagnosis of IgG4-SC. PTC has greater advantages in this regard, with more convenient operation and more direct image evidence. Therefore, we hope that this study will enhance the awareness of clinicians and radiologists regarding the use of PTC in diagnosing IgG4-SC. 2 Materials and methods This study does not involve human experiments or the use of human tissue samples. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations. A statement to confirm that all experimental protocols have been approved by the Ethics Committee of the Air Force Medical Center with Special Features. Since the samples and information involved in the study are derived from medical records and imaging films during clinical diagnosis and treatment, the risk to the subjects does not exceed the minimum risk. Waiving informed consent will not have an adverse impact on the patients' rights or health, and the privacy and personal identity information of the subjects will be protected. The requirement for informed consent to participate in the study has been waived by the Ethics Committee of the Air Force Medical Center. 2.1 Study Population A total of 20 patients with a clinical diagnosis of IgG4-SC admitted to our institution from June 2012 to July 2025 were retrospectively enrolled. All patients presented with obstructive jaundice, and imaging examinations confirmed extrahepatic biliary stenosis with obstruction and proximal biliary dilatation. All subjects underwent percutaneous transhepatic cholangiography (PTC), received a clinical diagnosis of IgG4-SC, and achieved gradual clinical improvement following glucocorticoid therapy. For comparative analysis, 10 patients with cholangiocarcinoma who had undergone PTC at our institution during the same period were also included in the study. 2.2 Imaging Examination Protocol All patients initially underwent contrast-enhanced upper abdominal CT, contrast-enhanced upper abdominal MRI, and magnetic resonance cholangiopancreatography (MRCP) as the standard imaging workup. For patients with biliary dilatation and total bilirubin levels exceeding 102 µmol/L, who remained undiagnosed after completing the above imaging examinations and for whom cholangiocarcinoma could not be ruled out, PTC was performed via the gallbladder and/or intrahepatic bile ducts. 2.3 Contrast-Enhanced Upper Abdominal CT and MRI Protocols CT examination: Conventional unenhanced upper abdominal CT was first performed, followed by intravenous injection of iodinated contrast medium with sequential scanning at the arterial phase (20–25 s post-injection), portal venous phase (65–70 s post-injection), and delayed phase (4–5 min post-injection). MRI examination: All MRI scans were performed on a 1.5T MRI scanner (Siemens Avanto, Germany) with an eight-channel abdominal phased-array coil, including unenhanced upper abdominal imaging and three-phase contrast-enhanced scanning. Gadolinium glucarate was administered intravenously for enhanced scanning at a dose of 0.05 mmol per kilogram of body weight. 2.4 Cholangiography Protocol For PTC cholangiography, 20–40 mL of 20% iohexol (a non-ionic contrast medium) was slowly injected over 5 seconds through the external end of the biliary puncture and drainage tube; the total volume of contrast medium was adjusted according to the degree of intra- and extrahepatic biliary dilatation. 2.5 Outcome Measures Morphological features of the stenotic biliary segment, including the length of the stenosis, presence of eccentricity, luminal uniformity, and biliary wall thickness, were evaluated and recorded. The detection rates of typical biliary stricture features of IgG4-SC by PTC, MRI, and CT were calculated, and the inter-method differences were statistically compared. PTC imaging features of biliary stenosis were compared between patients with IgG4-SC and those with cholangiocarcinoma. 3 RESULTS 3.1 PTC Superiority in Detecting Typical IgG4-SC Biliary Stricture Features Compared with MRI and CT, PTC demonstrated a significantly higher ability to detect the characteristic long-segment, linear, and uniform biliary narrowing of IgG4-SC. The detection rate of PTC for typical biliary luminal features of IgG4-SC was markedly higher than that of other imaging modalities (P < 0.001), as shown in Table 1 . This characteristic uniform narrowing was not observed in the PTC images of cholangiocarcinoma patients. PTC imaging revealed significant differences in biliary luminal features between IgG4-SC and cholangiocarcinoma, as detailed in Table 2 . In Case 1 of IgG4-SC, PTC clearly depicted typical hilar biliary stenosis (Fig. 1 A(a)), whereas contemporaneous MRI failed to visualize this characteristic finding (Fig. 1 A(b)). Case 4 of IgG4-SC presented with a nearly identical imaging pattern (Fig. 3A(a, b)). Case 2 of IgG4-SC had stenosis of the pancreatic segment of the common bile duct; PTC identified a long-segment uniform narrowing in this segment (Fig. 1 B(a)), while concurrent contrast-enhanced CT could not visualize the pancreatic segment of the common bile duct (Fig. 1 B(b)). In contrast, PTC images of cholangiocarcinoma patients consistently lacked this typical long-segment uniform biliary narrowing: in Cholangiocarcinoma Case 1, PTC showed that the contrast medium could not pass through the stenotic segment (Fig. 1 C(a)); in Cholangiocarcinoma Case 2, even though the contrast medium traversed the stenotic segment, the filling was uneven and non-uniform (Fig. 1 C(b)). 3.2 PTC in Evaluating Biliary Wall Uniformity and Luminal Eccentricity During PTC puncture and contrast injection, the operator could directly assess the uniformity of the stenotic biliary wall—a key distinguishing feature from cholangiocarcinoma. In IgG4-SC Case 3, PTC revealed that the drainage catheter was positioned along the central axis of the bile duct, with the inner wall of the stenotic segment closely apposed to the catheter (Fig. 2 A). Contemporaneous MRI only depicted biliary ductal interruption (Fig. 2 B) and failed to identify the non-eccentric nature of the lumen and wall. In contrast, PTC imaging of Cholangiocarcinoma Case 3 showed that the guidewire and drainage catheter were deviated to one side of the common bile duct lumen by intraluminal tumor tissue, with an eccentric biliary space at the stenotic segment (Fig. 2 C). 3.3 PTC in Evaluating Short-Term Glucocorticoid Therapy Efficacy PTC exhibited a distinct advantage over MRI in assessing the therapeutic efficacy of short-term glucocorticoid therapy in IgG4-SC patients. IgG4-SC Cases 1 and 4 presented with typical uniform hilar biliary narrowing; follow-up PTC after short-term glucocorticoid therapy showed dilatation of the stenotic biliary lumen compared with the baseline images (Figs. 3A and 3B). In IgG4-SC Case 5, MRI performed 1 month after glucocorticoid therapy still failed to distinguish the pancreatic segment biliary stenosis and only showed a reduction in proximal biliary dilatation relative to the pre-treatment state. Figure 3A(a): Simultaneous PTC via gallbladder puncture and intrahepatic bile duct puncture in IgG4-SC case 4 revealing typical “Y shaped” hilar biliary stenosis, characterized by long segment, homogeneous, and symmetrical narrowing. Figure 3A(b): Follow up PTC obtained only 7 days after corticosteroid therapy in IgG4-SC case 4 showing obvious resolution of biliary stenosis, with relief of obstruction and dilatation of the proximal bile duct. Figure 3B(a): PTC image of IgG4-SC case 1 showing typical “Y shaped” homogeneous, symmetrical, long segment stenosis of the hilar bile duct. Figure 3B(b): Follow up PTC obtained after 18 days of glucocorticoid therapy in IgG4-SC case 1 showing significant resolution of the biliary stricture. Figure 3C(a, b): MR images obtained 1 month after glucocorticoid therapy in IgG4-SC case 5, showing only reduced dilatation of the proximal extrahepatic bile duct, but without clear visualization of the continuous intrapancreatic common bile duct lumen, thus limiting evaluation of luminal changes. Table 1 Detection rates of biliary luminal features of IgG4-SC: PTC versus other imaging modalities IgG4-SC Typical image P chi-square Number of positive cases Number of negative cases Inspection method PTC 19 1 0.00* 28.248* MRCP\CT\MRI 2 18 * Note: All IgG4-SC patients with biliary obstruction underwent at least two additional imaging examinations (MRCP/CT/MRI) besides PTC. Statistical analysis was performed using the paired chi-square test (McNemar’s test). Table 2 Comparison of PTC imaging features of biliary stenosis between IgG4-SC and cholangiocarcinoma patients IgG4-SC Narrow segment length Bile duct wall elasticity The narrow cavity is centered Whether the lumen narrowing is uniform Long exist Yes uniform CC Short not exist No Uneven 4 Discussion 4.1 PTC Outperforms MRI and CT in Detecting Characteristic IgG4-SC Biliary Strictures Proximal biliary dilatation in patients with suspected IgG4-SC indicates severe stenosis at the distal biliary segment and impaired biliary drainage. Previous studies have noted that the differential diagnosis between IgG4-SC and cholangiocarcinoma becomes more challenging when MRI reveals biliary ductal interruption in IgG4-SC patients [ 14 ]. Additionally, elevated serum bilirubin levels can compromise the image quality of liver-specific MRI enhancement [ 15 ], further limiting the diagnostic value of MRI in this patient population. In such scenarios, PTC can clearly visualize the stenotic biliary lumen and identify its typical morphological features. This diagnostic superiority is attributable to the pathological nature of IgG4-SC stenosis: as an inflammatory stricture, it differs fundamentally from malignant biliary lesions in that the inflammatory tissue retains a certain degree of elasticity. During PTC, pressurized injection of contrast medium can distend the biliary lumen, expand the imaging field of view, and clearly depict the luminal morphology. Imaging of IgG4-SC typically shows circumferential symmetric thickening of the biliary wall with a smooth intima [ 16 ], whereas cholangiocarcinoma-induced local strictures are characterized by a rigid, uneven biliary wall. Furthermore, previous research has demonstrated that the stenosis length in IgG4-SC patients is significantly longer than that in patients with malignant biliary stenosis (23 mm vs. 7 mm) [ 17 ]. Collectively, these factors render PTC more effective in visualizing the biliary lumen with a higher detection rate for typical IgG4-SC features than MRI and CT. PTC can also reflect the elastic characteristics of IgG4-SC-related biliary strictures, providing robust evidence for the clinical diagnosis of IgG4-SC. 4.2 PTC Facilitates the Assessment of Biliary Wall Uniformity and Luminal Eccentricity—Details Indistinct on MRI Histopathologically, IgG4-SC is characterized by long-segment biliary strictures secondary to extensive lymphocytic and plasmacytic infiltration and biliary wall fibrosis [ 18 ]. During PTC puncture and catheterization in patients with suspected IgG4-SC, the operator can directly evaluate critical morphological features: whether the stenotic biliary lumen is eccentric, whether the biliary tract has a straight course, and whether the guidewire and catheter can be placed along the central axis of the original lumen. In contrast, MRI and CT lack the spatial resolution to clearly visualize the biliary space at the stenotic segment and cannot distinguish IgG4-SC from cholangiocarcinoma based on the morphological features of biliary stenosis alone. Therefore, PTC offers a distinct advantage over MRI in the differential diagnosis of suspected IgG4-SC in patients with established intrahepatic biliary dilatation. 4.3 PTC Is Superior to MRI in Evaluating the Efficacy of Short-Term Glucocorticoid Therapy for IgG4-SC IgG4-SC patients exhibit a rapid clinical response to first-line glucocorticoid therapy [ 19 ], with early changes in biliary dilatation observable shortly after treatment initiation; disease recurrence is also common during steroid tapering [ 20 ]. For patients with highly suspected IgG4-SC and an inconclusive diagnosis, a diagnostic steroid trial is a recommended clinical strategy [ 21 ]. In patients with highly suspected IgG4-SC who undergo a diagnostic corticosteroid trial and have already undergone biliary puncture and catheterization, PTC cholangiography enables repeated short-term evaluations of therapeutic efficacy. This allows for the timely detection of dilatation in the stenotic biliary lumen, providing objective evidence to confirm the efficacy of glucocorticoid therapy. In this regard, PTC is far more clinically valuable than MRI, and it also offers the advantages of being cost-effective and technically feasible. For patients with a questionable diagnosis of IgG4-SC, the therapeutic response to glucocorticoids serves as an important diagnostic criterion. Notably, different subtypes of IgG4-SC exhibit varying responses to steroid therapy [ 22 ], making the sensitive detection of short-term therapeutic responses particularly critical—an area where PTC demonstrates a clear clinical advantage. Additionally, even a significant elevation in serum IgG4 levels cannot completely rule out cholangiocarcinoma, as IgG4-SC and cholangiocarcinoma can coexist in the same patient. In such cases, the identification of typical malignant biliary features on PTC cholangiography can effectively avoid missed diagnosis of cholangiocarcinoma [ 23 ]. A previous study collected bile samples from 25 cholangiocarcinoma patients and 5 IgG4-SC patients during cholangiography and found that bile IgG4 levels were significantly elevated in IgG4-SC patients [ 24 ]. This finding suggests that PTC not only yields characteristic imaging results but also enables additional differential diagnostic tests, such as bile IgG4 level detection and exfoliative cytopathology, to distinguish IgG4-SC from cholangiocarcinoma. Endoscopic imaging of the stenotic biliary segment in IgG4-SC has revealed biliary vasodilation, tortuosity, and mucosal thickening [ 25 ]—the histopathological basis for the elasticity of IgG4-SC-related strictures, which allows the stenotic channel to be visualized upon pressurized contrast medium injection. Notably, type 4 IgG4-SC with hilar biliary stenosis is often not associated with autoimmune pancreatitis [ 26 ], making its differentiation from cholangiocarcinoma even more difficult [ 27 ]; however, cholangiography can easily identify the characteristic biliary strictures of this subtype. As an invasive cholangiography examination, PTC carries risks of complications such as bleeding and bile leakage, and is far less safe than non-invasive enhanced CT, enhanced MRI, and MRCP. It can only display the morphological features inside the bile duct lumen and cannot assess bile duct wall thickening, enhancement characteristics, or the involvement of surrounding tissues. In terms of differentiating benign from malignant bile duct strictures, PTC has limited value. However, based on the preceding text, we believe that PTC remains a key auxiliary method in the early diagnosis of some patients with IgG4-SC. Conclusion For patients with suspected IgG4-SC who present with biliary ductal interruption on CT/MRI and elevated serum bilirubin levels, performance of cholangiography is clinically warranted. Pressurized injection of contrast medium during cholangiography can significantly enhance the imaging resolution of the biliary lumen, which is particularly valuable for distinguishing benign from malignant biliary strictures in patients with normal serum IgG4 levels. Cholangiography is also recommended for patients with highly suspected IgG4-SC, as its greatest clinical value lies in the dynamic observation of changes in biliary strictures following glucocorticoid therapy. Compared with MRCP, cholangiography provides clearer and more accurate imaging of the biliary lumen and is characterized by cost-effectiveness and low susceptibility to technical interference. Nevertheless, the clinical diagnosis of IgG4-SC in the absence of pathological confirmation remains a major challenge, and further optimization of imaging diagnostic modalities for this disease is still needed. Abbreviations IgG4-SC, IgG4-related sclerosing cholangitis; PTC, Percutaneous transhepatic cholangiography; CC, cholangiocarcinoma Declarations Funding: The authors declare that no funding was received for this study. Author Contribution Author StatementResearch funding: The authors declare that no funding was received for this study.Conflict of interest: The authors declare no potential conflicts of interest.Informed consent: Written informed consent was obtained from all individual participants included in this study.Ethical approval: Ethical approval was not applicable for this study.Author ContributionsConceptualization: Cheng Wang, Ziman Zhu, Lin Zhang, Chengli Liu.Data curation: Cheng Wang, Chengli Liu, Yalin Kong.Formal analysis: Cheng Wang, Ziman Zhu, Lin Zhang.Methodology: Cheng Wang, Lin Zhang, Chengli Liu.Supervision: Chengli Liu.Writing – original draft: Cheng Wang. Acknowledgement We thank Medjaden Inc. for their valuable suggestions on revision. Data Availability All data generated or analyzed during this study are included in this published article and its supplement. References Suxing, Y. Wang Yi. 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Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis. Dig. Endosc . 31 (4), 422–430 (2019). Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformationfiles.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9095183","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":634823192,"identity":"88ba79e4-335b-4604-a341-c42cfc4e3816","order_by":0,"name":"Cheng Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYLACxgYgIf/44IMEAxsefv4GYrUwpCUbPKhIk5GccYBoLTlqkg/OHLYxaEjAr9rg+NnDL37usMmTdzjDbJDYdp7HgOEA44ePOXi0nMlLs+w9k1ZseLD34IPEtts85swNzJIzt+HWYnYgx8yYse1w4sZmvmQDkBbLhgNszLz4tJx/A9LyP3FjG4+ZRGLbOR6DAwkEtNzIMX7M2HYgcT4PUEvCmQOEtdjfeGPG2NuWnLhBgi3ZIKEimUdyxsFmvH6R7M8x/vCzzS5x/gzmgw9/GNjZ8/M3H/zwEY8WIGCTAJEGB+ACkGjCB5g/gEh5gupGwSgYBaNgxAIAll1cIdc+M4QAAAAASUVORK5CYII=","orcid":"","institution":"Department of Hepatobiliary Surgery, Air Force Medical Center, Air Force Medical University","correspondingAuthor":true,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Wang","suffix":""},{"id":634823193,"identity":"e6202455-496b-444f-96e2-1426d56b3d7a","order_by":1,"name":"Ziman Zhu","email":"","orcid":"","institution":"Department of Hepatobillary Surgery, The Fourth Medical Center, Chinese PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ziman","middleName":"","lastName":"Zhu","suffix":""},{"id":634823194,"identity":"db176a0b-49d5-4dc7-8e44-1995428773cd","order_by":2,"name":"Yalin Kong","email":"","orcid":"","institution":"Department of Hepatobiliary Surgery, Air Force Medical Center, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yalin","middleName":"","lastName":"Kong","suffix":""},{"id":634823195,"identity":"6867004e-568d-4fb0-9a8b-bcccf292cc7f","order_by":3,"name":"Lin Zhang","email":"","orcid":"","institution":"Department of Hepatobiliary Intervention, Hepatopancreatobiliary Center, Beijing Tsinghua Chang Gung Hospital, Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Zhang","suffix":""},{"id":634823196,"identity":"c37b657a-e3a4-427d-9a3a-e20bacd147dd","order_by":4,"name":"Chengli Liu","email":"","orcid":"","institution":"Department of Hepatobiliary Surgery, Air Force Medical Center, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengli","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2026-03-11 13:41:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9095183/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9095183/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108947106,"identity":"576167ec-b4fa-4602-b814-fcad8ae36c9f","added_by":"auto","created_at":"2026-05-11 06:26:59","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":324283,"visible":true,"origin":"","legend":"\u003cp\u003eA(a): A case of IgG4-SC (case 1) demonstrating homogeneous, symmetrical, long segment stenosis of the hilar bile duct with a typical “Y shaped” appearance. Figure 1A(b): Corresponding MRCP image of IgG4-SC case 1, in which the above biliary stricture features were not clearly visualized. Figure 1 B(a): PTC via percutaneous intrahepatic bile duct puncture in IgG4-SC case 2 clearly showing homogeneous long segment narrowing of the intrapancreatic bile duct. Figure 1 B(b): Contrast enhanced CT image obtained at the same time in IgG4-SC case 2, showing poor visualization of the intrapancreatic bile duct, making it impossible to evaluate the uniformity of stenosis. Figure 1C(a): PTC image of cholangiocarcinoma (case 1) showing abrupt interruption of the bile duct, without typical homogeneous stenosis, and failure of contrast agent to pass through the stricture. Figure 1C(b): PTC image of cholangiocarcinoma (case 2) showing passage of contrast agent through the stricture, but with discontinuous and irregular lumen morphology.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9095183/v1/2c2a278d0e94149d207899e1.jpeg"},{"id":108947058,"identity":"798d8f22-e2a6-4dc7-8d43-cdebefd56776","added_by":"auto","created_at":"2026-05-11 06:26:49","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":161489,"visible":true,"origin":"","legend":"\u003cp\u003eA: In case 3 with IgG4‑SC, the stenotic segment of the bile duct lumen was located centrally. The inner wall of the stenotic segment was closely apposed to the PTC drainage catheter, without intraluminal nodules or masses, and exhibited highly homogeneous stenosis. These fine anatomical details were not discernible on the corresponding MRI examination (Figure 2B). Figure 2C: PTC image of cholangiocarcinoma (case 3) showing the guidewire and catheter deviated to one side of the bile duct wall rather than being centrally positioned.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9095183/v1/a48a1a7493132b189c08ec03.jpeg"},{"id":108947167,"identity":"9ba4ae63-0b1f-4135-92d1-1629bddc7ba2","added_by":"auto","created_at":"2026-05-11 06:27:07","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":265991,"visible":true,"origin":"","legend":"\u003cp\u003eA(a): Simultaneous PTC via gallbladder puncture and intrahepatic bile duct puncture in IgG4-SC case 4 revealing typical “Y shaped” hilar biliary stenosis, characterized by long segment, homogeneous, and symmetrical narrowing. Figure 3A(b): Follow up PTC obtained only 7 days after corticosteroid therapy in IgG4-SC case 4 showing obvious resolution of biliary stenosis, with relief of obstruction and dilatation of the proximal bile duct.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9095183/v1/3c311275b2df9ee9566f91f9.jpeg"},{"id":109242791,"identity":"61bcd20e-c76a-48de-94d1-6bfcb982d1fa","added_by":"auto","created_at":"2026-05-14 07:11:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":950810,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9095183/v1/f463a8ab-adbd-4269-a75a-2336917c2792.pdf"},{"id":108947170,"identity":"d4d24739-112c-47c3-9e9b-4e7fce95ad4e","added_by":"auto","created_at":"2026-05-11 06:27:08","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":135034,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformationfiles.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9095183/v1/47c6923680eff4e528ac750d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Percutaneous transhepatic cholangiography can improve the detection rate of biliary lesion characteristics in IgG4-related sclerosing cholangitis and is a necessary method for early diagnosis","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIgG4-associated sclerosing cholangitis (IgG4-SC), a subtype of IgG4-related disease (IgG4-RD), is a benign biliary stricture disorder that is not uncommon in the Chinese population. A study from Peking University People's Hospital enrolled 62 patients with obstructive jaundice caused by non-neoplastic diseases between August 2014 and August 2016, among whom 13 were diagnosed with IgG4-SC [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Clinical evidence has confirmed that the overall response rate of IgG4-SC to steroid therapy reaches 90% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients with IgG4-SC typically present with obstructive jaundice, and computed tomography (CT) and magnetic resonance imaging (MRI) often reveal biliary ductal interruption\u0026mdash;an imaging feature that renders differentiation from cholangiocarcinoma extremely challenging [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on the location of biliary stenosis, IgG4-SC is classified into four subtypes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], with type 4 characterized by hilar biliary stenosis. The diagnosis of IgG4-SC is relatively straightforward when accompanied by multi-organ involvement of IgG4-RD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], while differentiation from hilar cholangiocarcinoma becomes markedly difficult in the absence of extra-biliary manifestations [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough serum IgG4 levels serve as an important auxiliary diagnostic marker for IgG4-SC, elevated serum IgG4 is not specific to this disease: it can be detected in 5% of healthy individuals and 10% of patients with pancreatic or gallbladder carcinoma [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and thus cannot be regarded as a sufficient diagnostic criterion for IgG4-SC. The 2012 Japanese Diagnostic Criteria for IgG4-SC [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] emphasized that biliary imaging findings of diffuse biliary wall thickening carry greater diagnostic weight than elevated serum IgG4 levels. Timely acquisition of characteristic imaging features is therefore crucial for the early clinical diagnosis of IgG4-SC.\u003c/p\u003e \u003cp\u003eIn our clinical work, we have found that patients with suspected IgG4-SC who undergo percutaneous transhepatic cholangial drainage (PTC) in the early stage can often be diagnosed more quickly. The reason is that PTC can clearly show the typical signs in the stenotic bile ducts, which is different from the \"bile duct interruption\" shown by magnetic resonance cholangiopancreatography (MRCP), thus helping to distinguish it from cholangiocarcinoma. Therefore, for patients with IgG4-SC, when MRCP has a blind spot, PTC is a key means to solve clinical problems. Furthermore, the detection of imaging changes and confirmation of therapeutic efficacy following short-term corticosteroid therapy constitute strong evidence for a definitive diagnosis of IgG4-SC. PTC has greater advantages in this regard, with more convenient operation and more direct image evidence.\u003c/p\u003e \u003cp\u003eTherefore, we hope that this study will enhance the awareness of clinicians and radiologists regarding the use of PTC in diagnosing IgG4-SC.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cp\u003eThis study does not involve human experiments or the use of human tissue samples. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations. A statement to confirm that all experimental protocols have been approved by the Ethics Committee of the Air Force Medical Center with Special Features. Since the samples and information involved in the study are derived from medical records and imaging films during clinical diagnosis and treatment, the risk to the subjects does not exceed the minimum risk. Waiving informed consent will not have an adverse impact on the patients' rights or health, and the privacy and personal identity information of the subjects will be protected. The requirement for informed consent to participate in the study has been waived by the Ethics Committee of the Air Force Medical Center.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Population\u003c/h2\u003e \u003cp\u003eA total of 20 patients with a clinical diagnosis of IgG4-SC admitted to our institution from June 2012 to July 2025 were retrospectively enrolled. All patients presented with obstructive jaundice, and imaging examinations confirmed extrahepatic biliary stenosis with obstruction and proximal biliary dilatation. All subjects underwent percutaneous transhepatic cholangiography (PTC), received a clinical diagnosis of IgG4-SC, and achieved gradual clinical improvement following glucocorticoid therapy. For comparative analysis, 10 patients with cholangiocarcinoma who had undergone PTC at our institution during the same period were also included in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Imaging Examination Protocol\u003c/h2\u003e \u003cp\u003eAll patients initially underwent contrast-enhanced upper abdominal CT, contrast-enhanced upper abdominal MRI, and magnetic resonance cholangiopancreatography (MRCP) as the standard imaging workup. For patients with biliary dilatation and total bilirubin levels exceeding 102 \u0026micro;mol/L, who remained undiagnosed after completing the above imaging examinations and for whom cholangiocarcinoma could not be ruled out, PTC was performed via the gallbladder and/or intrahepatic bile ducts.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Contrast-Enhanced Upper Abdominal CT and MRI Protocols\u003c/h2\u003e \u003cp\u003eCT examination: Conventional unenhanced upper abdominal CT was first performed, followed by intravenous injection of iodinated contrast medium with sequential scanning at the arterial phase (20\u0026ndash;25 s post-injection), portal venous phase (65\u0026ndash;70 s post-injection), and delayed phase (4\u0026ndash;5 min post-injection).\u003c/p\u003e \u003cp\u003eMRI examination: All MRI scans were performed on a 1.5T MRI scanner (Siemens Avanto, Germany) with an eight-channel abdominal phased-array coil, including unenhanced upper abdominal imaging and three-phase contrast-enhanced scanning. Gadolinium glucarate was administered intravenously for enhanced scanning at a dose of 0.05 mmol per kilogram of body weight.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Cholangiography Protocol\u003c/h2\u003e \u003cp\u003eFor PTC cholangiography, 20\u0026ndash;40 mL of 20% iohexol (a non-ionic contrast medium) was slowly injected over 5 seconds through the external end of the biliary puncture and drainage tube; the total volume of contrast medium was adjusted according to the degree of intra- and extrahepatic biliary dilatation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Outcome Measures\u003c/h2\u003e \u003cp\u003eMorphological features of the stenotic biliary segment, including the length of the stenosis, presence of eccentricity, luminal uniformity, and biliary wall thickness, were evaluated and recorded.\u003c/p\u003e \u003cp\u003eThe detection rates of typical biliary stricture features of IgG4-SC by PTC, MRI, and CT were calculated, and the inter-method differences were statistically compared.\u003c/p\u003e \u003cp\u003ePTC imaging features of biliary stenosis were compared between patients with IgG4-SC and those with cholangiocarcinoma.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 PTC Superiority in Detecting Typical IgG4-SC Biliary Stricture Features\u003c/h2\u003e \u003cp\u003eCompared with MRI and CT, PTC demonstrated a significantly higher ability to detect the characteristic long-segment, linear, and uniform biliary narrowing of IgG4-SC. The detection rate of PTC for typical biliary luminal features of IgG4-SC was markedly higher than that of other imaging modalities (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This characteristic uniform narrowing was not observed in the PTC images of cholangiocarcinoma patients. PTC imaging revealed significant differences in biliary luminal features between IgG4-SC and cholangiocarcinoma, as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eIn Case 1 of IgG4-SC, PTC clearly depicted typical hilar biliary stenosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA(a)), whereas contemporaneous MRI failed to visualize this characteristic finding (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA(b)). Case 4 of IgG4-SC presented with a nearly identical imaging pattern (Fig.\u0026nbsp;3A(a, b)). Case 2 of IgG4-SC had stenosis of the pancreatic segment of the common bile duct; PTC identified a long-segment uniform narrowing in this segment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB(a)), while concurrent contrast-enhanced CT could not visualize the pancreatic segment of the common bile duct (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB(b)). In contrast, PTC images of cholangiocarcinoma patients consistently lacked this typical long-segment uniform biliary narrowing: in Cholangiocarcinoma Case 1, PTC showed that the contrast medium could not pass through the stenotic segment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC(a)); in Cholangiocarcinoma Case 2, even though the contrast medium traversed the stenotic segment, the filling was uneven and non-uniform (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC(b)).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 PTC in Evaluating Biliary Wall Uniformity and Luminal Eccentricity\u003c/h2\u003e \u003cp\u003eDuring PTC puncture and contrast injection, the operator could directly assess the uniformity of the stenotic biliary wall\u0026mdash;a key distinguishing feature from cholangiocarcinoma. In IgG4-SC Case 3, PTC revealed that the drainage catheter was positioned along the central axis of the bile duct, with the inner wall of the stenotic segment closely apposed to the catheter (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Contemporaneous MRI only depicted biliary ductal interruption (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) and failed to identify the non-eccentric nature of the lumen and wall. In contrast, PTC imaging of Cholangiocarcinoma Case 3 showed that the guidewire and drainage catheter were deviated to one side of the common bile duct lumen by intraluminal tumor tissue, with an eccentric biliary space at the stenotic segment (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 PTC in Evaluating Short-Term Glucocorticoid Therapy Efficacy\u003c/h2\u003e \u003cp\u003ePTC exhibited a distinct advantage over MRI in assessing the therapeutic efficacy of short-term glucocorticoid therapy in IgG4-SC patients. IgG4-SC Cases 1 and 4 presented with typical uniform hilar biliary narrowing; follow-up PTC after short-term glucocorticoid therapy showed dilatation of the stenotic biliary lumen compared with the baseline images (Figs.\u0026nbsp;3A and 3B). In IgG4-SC Case 5, MRI performed 1 month after glucocorticoid therapy still failed to distinguish the pancreatic segment biliary stenosis and only showed a reduction in proximal biliary dilatation relative to the pre-treatment state.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure 3A(a): Simultaneous PTC via gallbladder puncture and intrahepatic bile duct puncture in IgG4-SC case 4 revealing typical \u0026ldquo;Y shaped\u0026rdquo; hilar biliary stenosis, characterized by long segment, homogeneous, and symmetrical narrowing. Figure\u0026nbsp;3A(b): Follow up PTC obtained only 7 days after corticosteroid therapy in IgG4-SC case 4 showing obvious resolution of biliary stenosis, with relief of obstruction and dilatation of the proximal bile duct.\u003c/p\u003e \u003cp\u003eFigure 3B(a): PTC image of IgG4-SC case 1 showing typical \u0026ldquo;Y shaped\u0026rdquo; homogeneous, symmetrical, long segment stenosis of the hilar bile duct. Figure\u0026nbsp;3B(b): Follow up PTC obtained after 18 days of glucocorticoid therapy in IgG4-SC case 1 showing significant resolution of the biliary stricture.\u003c/p\u003e \u003cp\u003eFigure 3C(a, b): MR images obtained 1 month after glucocorticoid therapy in IgG4-SC case 5, showing only reduced dilatation of the proximal extrahepatic bile duct, but without clear visualization of the continuous intrapancreatic common bile duct lumen, thus limiting evaluation of luminal changes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetection rates of biliary luminal features of IgG4-SC: PTC versus other imaging modalities\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eIgG4-SC Typical image\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003echi-square\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of positive cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of negative cases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInspection\u003c/p\u003e \u003cp\u003emethod\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.00*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e28.248*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMRCP\\CT\\MRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e*\u003c/b\u003e Note: All IgG4-SC patients with biliary obstruction underwent at least two additional imaging examinations (MRCP/CT/MRI) besides PTC. Statistical analysis was performed using the paired chi-square test (McNemar\u0026rsquo;s test).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of PTC imaging features of biliary stenosis between IgG4-SC and cholangiocarcinoma patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eIgG4-SC\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNarrow segment length\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBile duct wall elasticity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThe narrow cavity is centered\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWhether the lumen narrowing is uniform\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLong\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eexist\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003euniform\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enot exist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUneven\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4.1 PTC Outperforms MRI and CT in Detecting Characteristic IgG4-SC Biliary Strictures\u003c/h2\u003e \u003cp\u003eProximal biliary dilatation in patients with suspected IgG4-SC indicates severe stenosis at the distal biliary segment and impaired biliary drainage. Previous studies have noted that the differential diagnosis between IgG4-SC and cholangiocarcinoma becomes more challenging when MRI reveals biliary ductal interruption in IgG4-SC patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Additionally, elevated serum bilirubin levels can compromise the image quality of liver-specific MRI enhancement [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], further limiting the diagnostic value of MRI in this patient population.\u003c/p\u003e \u003cp\u003eIn such scenarios, PTC can clearly visualize the stenotic biliary lumen and identify its typical morphological features. This diagnostic superiority is attributable to the pathological nature of IgG4-SC stenosis: as an inflammatory stricture, it differs fundamentally from malignant biliary lesions in that the inflammatory tissue retains a certain degree of elasticity. During PTC, pressurized injection of contrast medium can distend the biliary lumen, expand the imaging field of view, and clearly depict the luminal morphology. Imaging of IgG4-SC typically shows circumferential symmetric thickening of the biliary wall with a smooth intima [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], whereas cholangiocarcinoma-induced local strictures are characterized by a rigid, uneven biliary wall. Furthermore, previous research has demonstrated that the stenosis length in IgG4-SC patients is significantly longer than that in patients with malignant biliary stenosis (23 mm vs. 7 mm) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Collectively, these factors render PTC more effective in visualizing the biliary lumen with a higher detection rate for typical IgG4-SC features than MRI and CT. PTC can also reflect the elastic characteristics of IgG4-SC-related biliary strictures, providing robust evidence for the clinical diagnosis of IgG4-SC.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.2 PTC Facilitates the Assessment of Biliary Wall Uniformity and Luminal Eccentricity\u0026mdash;Details Indistinct on MRI\u003c/h2\u003e \u003cp\u003eHistopathologically, IgG4-SC is characterized by long-segment biliary strictures secondary to extensive lymphocytic and plasmacytic infiltration and biliary wall fibrosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. During PTC puncture and catheterization in patients with suspected IgG4-SC, the operator can directly evaluate critical morphological features: whether the stenotic biliary lumen is eccentric, whether the biliary tract has a straight course, and whether the guidewire and catheter can be placed along the central axis of the original lumen. In contrast, MRI and CT lack the spatial resolution to clearly visualize the biliary space at the stenotic segment and cannot distinguish IgG4-SC from cholangiocarcinoma based on the morphological features of biliary stenosis alone. Therefore, PTC offers a distinct advantage over MRI in the differential diagnosis of suspected IgG4-SC in patients with established intrahepatic biliary dilatation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.3 PTC Is Superior to MRI in Evaluating the Efficacy of Short-Term Glucocorticoid Therapy for IgG4-SC\u003c/h2\u003e \u003cp\u003eIgG4-SC patients exhibit a rapid clinical response to first-line glucocorticoid therapy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], with early changes in biliary dilatation observable shortly after treatment initiation; disease recurrence is also common during steroid tapering [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. For patients with highly suspected IgG4-SC and an inconclusive diagnosis, a diagnostic steroid trial is a recommended clinical strategy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn patients with highly suspected IgG4-SC who undergo a diagnostic corticosteroid trial and have already undergone biliary puncture and catheterization, PTC cholangiography enables repeated short-term evaluations of therapeutic efficacy. This allows for the timely detection of dilatation in the stenotic biliary lumen, providing objective evidence to confirm the efficacy of glucocorticoid therapy. In this regard, PTC is far more clinically valuable than MRI, and it also offers the advantages of being cost-effective and technically feasible. For patients with a questionable diagnosis of IgG4-SC, the therapeutic response to glucocorticoids serves as an important diagnostic criterion. Notably, different subtypes of IgG4-SC exhibit varying responses to steroid therapy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], making the sensitive detection of short-term therapeutic responses particularly critical\u0026mdash;an area where PTC demonstrates a clear clinical advantage.\u003c/p\u003e \u003cp\u003eAdditionally, even a significant elevation in serum IgG4 levels cannot completely rule out cholangiocarcinoma, as IgG4-SC and cholangiocarcinoma can coexist in the same patient. In such cases, the identification of typical malignant biliary features on PTC cholangiography can effectively avoid missed diagnosis of cholangiocarcinoma [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. A previous study collected bile samples from 25 cholangiocarcinoma patients and 5 IgG4-SC patients during cholangiography and found that bile IgG4 levels were significantly elevated in IgG4-SC patients [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This finding suggests that PTC not only yields characteristic imaging results but also enables additional differential diagnostic tests, such as bile IgG4 level detection and exfoliative cytopathology, to distinguish IgG4-SC from cholangiocarcinoma.\u003c/p\u003e \u003cp\u003eEndoscopic imaging of the stenotic biliary segment in IgG4-SC has revealed biliary vasodilation, tortuosity, and mucosal thickening [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u0026mdash;the histopathological basis for the elasticity of IgG4-SC-related strictures, which allows the stenotic channel to be visualized upon pressurized contrast medium injection. Notably, type 4 IgG4-SC with hilar biliary stenosis is often not associated with autoimmune pancreatitis [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], making its differentiation from cholangiocarcinoma even more difficult [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]; however, cholangiography can easily identify the characteristic biliary strictures of this subtype.\u003c/p\u003e \u003cp\u003eAs an invasive cholangiography examination, PTC carries risks of complications such as bleeding and bile leakage, and is far less safe than non-invasive enhanced CT, enhanced MRI, and MRCP. It can only display the morphological features inside the bile duct lumen and cannot assess bile duct wall thickening, enhancement characteristics, or the involvement of surrounding tissues. In terms of differentiating benign from malignant bile duct strictures, PTC has limited value. However, based on the preceding text, we believe that PTC remains a key auxiliary method in the early diagnosis of some patients with IgG4-SC.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFor patients with suspected IgG4-SC who present with biliary ductal interruption on CT/MRI and elevated serum bilirubin levels, performance of cholangiography is clinically warranted. Pressurized injection of contrast medium during cholangiography can significantly enhance the imaging resolution of the biliary lumen, which is particularly valuable for distinguishing benign from malignant biliary strictures in patients with normal serum IgG4 levels. Cholangiography is also recommended for patients with highly suspected IgG4-SC, as its greatest clinical value lies in the dynamic observation of changes in biliary strictures following glucocorticoid therapy. Compared with MRCP, cholangiography provides clearer and more accurate imaging of the biliary lumen and is characterized by cost-effectiveness and low susceptibility to technical interference. Nevertheless, the clinical diagnosis of IgG4-SC in the absence of pathological confirmation remains a major challenge, and further optimization of imaging diagnostic modalities for this disease is still needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIgG4-SC, IgG4-related sclerosing cholangitis; PTC, Percutaneous transhepatic cholangiography; CC, cholangiocarcinoma\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThe authors declare that no funding was received for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor StatementResearch funding: The authors declare that no funding was received for this study.Conflict of interest: The authors declare no potential conflicts of interest.Informed consent: Written informed consent was obtained from all individual participants included in this study.Ethical approval: Ethical approval was not applicable for this study.Author ContributionsConceptualization: Cheng Wang, Ziman Zhu, Lin Zhang, Chengli Liu.Data curation: Cheng Wang, Chengli Liu, Yalin Kong.Formal analysis: Cheng Wang, Ziman Zhu, Lin Zhang.Methodology: Cheng Wang, Lin Zhang, Chengli Liu.Supervision: Chengli Liu.Writing \u0026ndash; original draft: Cheng Wang.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Medjaden Inc. for their valuable suggestions on revision.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analyzed during this study are included in this published article and its supplement.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSuxing, Y. 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(2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsaia, I., Natoli, G., Colaci, M., Stancanelli, B. \u0026amp; Malatino, L. Sclerosing cholangitis may mimic radiological pattern of cholangiocarcinoma: Differential diagnosis and review of literature. \u003cem\u003eAm. J. Med. Sci. 2022 Sep.\u003c/em\u003e, \u003cb\u003e364\u003c/b\u003e(3):359\u0026ndash;365 .\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHwang, J. A. et al. Total Bilirubin Level as a Predictor of Suboptimal Image Quality of the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI in Patients with Extrahepatic Bile Duct Cancer. \u003cem\u003eKorean J. Radiol.\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e (4), 389\u0026ndash;401 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang, C., Chen, C., Du, J., Zhang, S. \u0026amp; Song, J. Mass-forming immunoglobulin G4-related cholangitis with atypical pancreatic lesions: a case report of difficult diagnosis. \u003cem\u003eAm. J. Transl Res.\u003c/em\u003e \u003cb\u003e15\u003c/b\u003e (3), 2090\u0026ndash;2097 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKunlayawutipong, T. et al. IgG4-related cholangitis-distinguishing from other benign biliary strictures: clinical features, imaging, and response to treatment: a retrospective study. \u003cem\u003eBMC Gastroenterol.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (1), 514 (2025 Jul).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakazawa, T. et al. Clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2020: (revision of the clinical diagnostic criteria for IgG4-related sclerosing cholangitis 2012. \u003cem\u003eJ. Hepatobiliary Pancreat. Sci.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 235\u0026ndash;242 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaverenne, L., Weichselbaum, L., Van Hoof, M. \u0026amp; Deltenre, P. An unusual cause of extrahepatic cholestasis associated with solid liver lesions: a case report. \u003cem\u003eActa Gastroenterol. Belg.\u003c/em\u003e \u003cb\u003e86\u003c/b\u003e (3), 490\u0026ndash;492 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026ouml;hr, J. M., Vujasinovic, M., Rosendahl, J., Stone, J. H. \u0026amp; Beuers, U. IgG4-related diseases of the digestive tract. \u003cem\u003eNat. Rev. Gastroenterol. Hepatol.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e (3), 185\u0026ndash;197 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKamisawa, T. et al. Clinical practice guidelines for IgG4-related sclerosing cholangitis. \u003cem\u003eJ. Hepatobiliary Pancreat. 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Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis. \u003cem\u003eDig. Endosc\u003c/em\u003e. \u003cb\u003e31\u003c/b\u003e (4), 422\u0026ndash;430 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"IgG4-related sclerosing cholangitis (IgG4-SC), Percutaneous transhepatic cholangiography (PTC), Cholangiocarcinoma (CC), Bile duct wall elasticity, Differential diagnosis","lastPublishedDoi":"10.21203/rs.3.rs-9095183/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9095183/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eAlthough IgG4-associated sclerosing cholangitis (IgG4-SC) has been widely recognized, distinguishing it from cholangiocarcinoma remains challenging when MRI demonstrates biliary obstruction or abrupt cutoff. Moreover, conventional CT and MRI often fail to fully delineate the intraluminal morphology of stenotic bile ducts.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAims\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eTo evaluate the diagnostic value of percutaneous transhepatic cholangiography (PTC) versus CT and MRI in depicting intraluminal morphology and identifying features suggestive of benign, compliant strictures in patients with IgG4-SC.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eWe conducted a retrospective review of 20 patients diagnosed with IgG4-SC from our medical center. PTC findings were compared with contemporaneous CT and MRI images. In addition, PTC features of IgG4-SC were contrasted with those of classic cholangiocarcinoma. The utility of PTC for initial diagnosis and serial assessment of steroid response was analyzed.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eIn cases where CT/MRI showed biliary obstruction or cutoff, PTC more frequently demonstrated the typical features of IgG4-SC, with a higher diagnostic yield. PTC clearly identified long-segment, smooth, symmetric, and compliant strictures, which were distinctly different from the abrupt, irregular, and rigid strictures characteristic of malignant biliary tumors. Furthermore, PTC allows repeatable cholangiographic evaluation, enabling serial and timely monitoring of stricture changes in response to steroid therapy.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eFor patients with IgG4-SC, injecting a contrast agent through a biliary drainage tube can clearly show the internal morphological characteristics of the bile duct lumen by virtue of the physiological elasticity of the bile duct wall. PTC can identify IgG4-SC earlier in suspected cases and is a very valuable supplementary diagnostic method in the diagnosis of this disease.\u003c/p\u003e","manuscriptTitle":"Percutaneous transhepatic cholangiography can improve the detection rate of biliary lesion characteristics in IgG4-related sclerosing cholangitis and is a necessary method for early diagnosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 06:23:47","doi":"10.21203/rs.3.rs-9095183/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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