Vanishing Bile Duct Syndrome in Hodgkin’s Lymphoma: Successful Remission through Early Chemotherapy

Vanishing Bile Duct Syndrome in Hodgkin’s Lymphoma: Successful Remission through Early Chemotherapy | 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 Case Report Vanishing Bile Duct Syndrome in Hodgkin’s Lymphoma: Successful Remission through Early Chemotherapy Omer Riyadh, Victor Chang, Priya Kumaravelu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7553024/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 Vanishing bile duct syndrome (VBDS) is a rare complication associated with Hodgkin's Lymphoma (HL), characterized by cholestasis and jaundice due to bile duct destruction. We report the case of a 78-year-old male with HL and VBDS, who presented with obstructive jaundice, severe cholestasis, and pancytopenia. Initial imaging showed no biliary obstruction, and the diagnosis of HL was confirmed by a lymph node biopsy. The patient was treated with a reduced dose of cyclophosphamide and prednisone, resulting in a normalization of hepatic and hematologic parameters. Following this, the patient underwent ABVD chemotherapy and achieved remission. This case emphasizes the potential for VBDS reversal with early treatment of HL, highlighting the importance of distinguishing cholestatic patterns related to malignancy from primary liver disease. Early intervention with chemotherapy targeting the underlying malignancy can restore liver function and improve patient outcomes. Categories : Internal Medicine, Oncology, Gastroenterology chemotherapy response general internal medicine oncology invisible bile duct syndrome hodgkin's Introduction VBDS (Vanishing Bile Duct Syndrome) is a rare, acquired form of chronic cholestatic liver disease. Several different causes of ductopenia exist, ranging from drug-induced liver injury, immune-mediated disorders like Primary Biliary Cholangitis and Primary Sclerosing Cholangitis, infectious causes such as CMV or chronic viral hepatitis, idiopathic adulthood ductopenia, and malignancies [ 1 ]. Acquired bile duct loss has an unpredictable prognosis, potentially leading either to gradual recovery through regeneration and proliferation of biliary epithelium, or to irreversible bile duct loss, causing biliary obstruction and ultimately cirrhosis. VBDS is an irreversible complication that may be associated with Hodgkin’s Lymphoma (HL). This disorder results in cholestasis and jaundice due to intrahepatic bile duct destruction. Although the relationship between VBDS and HL is not scientifically proven, theories suggest that ductal destruction may be caused by CD8 T lymphocytes or harmful cytokines released from lymphoma cells in the form of antibodies or hepatotoxic molecules [ 1 ]. VBDS has been shown to manifest as severe jaundice and hepatic laboratory abnormalities, reflecting an obstructive pattern. The clinical course of VBDS is not well-defined, though recent studies have shown reversibility and remission in a subgroup of patients [ 2 ]. Treatment for VBDS is challenging due to limited published data on outcomes, poor treatment tolerance, and the risk of fulminant liver failure. Here, we report the case of a 78-year-old male with HL and VBDS who was treated with an alternative immunosuppressive chemotherapy regimen, resulting in the resolution of hepatic obstruction through the reduction of lymphocytes. Case Presentation A 78-year-old man with an unremarkable past medical history was seen in Mexico in December 2017 with complaints of fever and cough. A physical exam at that time revealed several mediastinal lymph nodes and bronchitis. When the patient returned to the United States for follow-up in March 2018, he denied any night sweats, loss of appetite, or weight loss, and no additional lymph nodes were found in the neck or armpit regions. He was later admitted for hypokalemia and fever of unknown origin. A mediastinal lymph node biopsy performed in April 2018 during his admission confirmed Hodgkin’s Lymphoma (HL), nodular sclerosing type, positive for CD15, CD30, and PAX. The patient continued to experience low-grade fevers and Staphylococcus aureus infection was identified in the biopsy sample. Approximately two weeks after the HL diagnosis, he developed severe cholestasis with jaundice, with a total bilirubin level reaching a high of 17.4 mg/dL, direct bilirubin of 10.5 mg/dL, AST of 190 U/L, ALT of 106 U/L, How to cite this article alkaline phosphatase of 1293 U/L, and LDH of 1195 U/L. Physical exam revealed bilateral leg swelling. An ERCP for causes of obstructive jaundice was negative, while a bone marrow biopsy was positive for HL. CBC showed pancytopenia, with hemoglobin dropping to 6.5 g/dL and an absolute neutrophil count (ANC) of 1.4. The patient was started on a 75% reduced dose of cyclophosphamide (1250 mg/m²) and prednisone (100 mg po daily) for 14 days. He also received pRBC, and by the end of the cycle, his CBC and biochemical lab values normalized. However, the treatment course was complicated by neutropenic ESBL E. coli sepsis, hypernatremic metabolic encephalopathy, and anasarca, which responded to neupogen and meropenem. One month after the cyclophosphamide and prednisone treatment, the patient was started on ABVD (C1D1) treatment for his HL. The patient is now in remission after eight cycles of ABVD therapy. Discussion VBDS was once thought to be an irreversible and progressive diagnosis associated with HL, curable only through liver transplantation. The immune-mediated damage caused by autoreactive T cells ultimately leads to epithelial cell apoptosis and ductopenia [ 3 , 4 ]. Patients with HL and hepatic involvement should be referred for biopsy and definitive therapy, as early detection and treatment with curative intent have shown reversal of VBDS and clinical remission in select cases. Given the rapid deterioration of our patient’s condition, there was insufficient time to perform a liver biopsy. A liver biopsy is important in patients presenting with hepatic dysfunction and a cholestatic pattern to differentiate between paraneoplastic syndrome and VBDS. Paraneoplastic syndrome in HL patients presents with jaundice, hyperbilirubinemia, and a normal liver, whereas VBDS presents with jaundice, hyperbilirubinemia, and ductopenia. Patients with paraneoplastic syndrome tend to improve once the HL is treated, while VBDS patients typically experience intrahepatic ductal destruction too severe to regenerate on its own [ 5 ]. Treating HL patients with a cholestatic presentation is particularly complex due to the challenge of minimizing hepatotoxicity during chemotherapy. Studies have shown that modified MOPP-ABV chemotherapy regimens can be introduced without a significant worsening of cholestasis [ 1 ]. Extrahepatic biliary obstruction caused by HL requires dose reductions in standard chemotherapy, but adding radiotherapy to treatment does not compromise liver function. Our case is remarkable because a known HL patient presented with an obstructive jaundice pattern without strictures or visible blockages seen on ERCP. VBDS has been associated with a variety of diseases, including biliary atresia, primary biliary cirrhosis, primary sclerosing cholangitis, Langerhans cell histiocytosis, viral infections, and drug-induced injury. The strongest neoplastic correlation with VBDS has been with HL. In this case, the obstructive jaundice seen in our VBDS patient was also coupled with acute pancytopenia. An analysis of recent cases published articles in Table 1 identifies the diverse presentation and age range of this disease. Table 1 Summary of findings in patients diagnosed with Vanishing Bile Duct syndrome Category Summary of Findings Patient Ages Cases spanned patients aged 9 to 75 years, with a majority of cases involving patients in their 20s. MRCP/ERCP Findings Most cases reported unremarkable findings or did not perform imaging. Some exceptions included sclerosing cholangitis and intrahepatic bile duct atrophy. Treatment Approaches Treatment varied, including chemotherapy regimens (Brentuximab or ABVD), corticosteroids (Dexamethasone), and UDCA (Ursodeoxycholic acid) for liver-related symptoms. In several cases, treatment shifted after initial approaches. Outcomes A majority of patients achieved remission, while some experienced liver failure or death. Notably, younger patients tended to have better outcomes. The patient qualified for a single dose of 75% reduced cyclophosphamide, which is not commonly used in HL patients, in an attempt to reverse the presumed obstruction as it does not require hepatic metabolism. After the personalized cyclophosphamide dose and a 14-day course of prednisone, the patient’s bilirubin and hepatic enzyme levels began to normalize. Once the patient’s lab values stabilized, and he was ready for discharge one month later, he transitioned to the expected ABVD treatment protocol. The patient is now in remission after eight cycles of ABVD. Conclusions In conclusion, the cyclophosphamide treatment eliminated the remaining lymphocytes causing the cholestatic presentation, highlighting the importance of early treatment of HL to allow liver regeneration once the autoimmune process is halted. Treating the underlying HL with cyclophosphamide also reversed the acute cytopenia, illustrating that bone marrow infiltration by lymphoma cells was the primary cause of both the abnormal CBC results and the obstructive pattern. This case underscores the importance of keeping VBDS in the differential diagnosis, as early detection and prompt treatment can be life-saving for certain HL patients. In cancer patients, it is crucial to remember that a cholestatic presentation does not necessarily indicate a primary liver disease, but may instead reflect a manifestation of malignancy. Identifying the obstruction as a result of malignant lymphocytes rather than bile duct disease, and treating it with chemotherapy, led this patient to remission. Declarations Human subjects : Informed consent for treatment and open access publication was obtained or waived by all participants in this study. KCU IRB Committe issued approval none. Consent was received from the patient. Conflicts of interest : In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info : All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships : All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships : All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. References Pass AK, McLin VA, Rushton JR, Kearney DL, Hastings CA, Margolin JF (2008) Vanishing bile duct syndrome and Hodgkin disease: a case series and review of the literature. J Pediatr Hematol Oncol Dec 30:976–980. 1097/MPH 0b013e31818b37c4 Ballonoff A, Kavanagh B, Nash R et al (2008) Hodgkin lymphoma-related vanishing bile duct syndrome and idiopathic cholestasis: statistical analysis of all published cases and literature review. Acta Oncol 47:962–970. 10.1080/02841860701644078 de Medeiros BC, Lacerda MA, Telles JE, da Silva JA, de Medeiros CR (1998) Cholestasis secondary to Hodgkin's disease: report of 2 cases of vanishing bile duct syndrome. Haematol Nov 83:1038–1040 Gonzalez R, Parmar P, Hardee S et al Hodgkin Lymphoma-related Vanishing Bile Duct Syndrome Cholestasis Resolved After Chemotherapy. J Pediatr Hematol Oncol. Apr 01. 1097/MPH.000000000000222 Barta SK, Yahalom J, Shia J, Hamlin PA Idiopathic cholestasis as a paraneoplastic phenomenon in Hodgkin's lymphoma (2006) Clin Lymphoma Myeloma 7:77–82. 10.3816/CLM.2006.n.044 Additional Declarations The authors declare no competing interests. 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-7553024","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":511269100,"identity":"4d93c91a-d0f7-4a0e-a973-7fa2ef6ed675","order_by":0,"name":"Omer Riyadh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYPACCSDOYXzYAOUeQCLxamE2hGs5QFgLCOSwScK0MODTwi92+NgHxj0Wif3tuccqZ9TcsefvP/zw8Mc2Bjm+GwlYtUjOTkuewfBMInHGmXdpNzcce5Y440aawYGDbQzGkji0GNzOMQY6QSKx4UaO2c0HbIcTGG7wMIC0JG7AqSX/M1jLfKCWwgf/DtvLnz8D1lKPW0sOM1jLBqAWxo1thxk3HMgBa0kwwO0XY4aEAxLGG8+8MZac2Xc4cSPIL2fOSRjOPPMAe4hJJz9m+HCgTnbe8RzDjz3fDtvLnT/8+ENFmY0833HstoABUMqxAUWEkU0Ct3IosEfj/yGoYxSMglEwCkYOAABdynCeUOpoeAAAAABJRU5ErkJggg==","orcid":"","institution":"Kansas City Univeristy","correspondingAuthor":true,"prefix":"","firstName":"Omer","middleName":"","lastName":"Riyadh","suffix":""},{"id":511269101,"identity":"636e1914-1192-41c0-8c4b-0705c1b0e9e5","order_by":1,"name":"Victor Chang","email":"","orcid":"","institution":"Kansas City Univeristy","correspondingAuthor":false,"prefix":"","firstName":"Victor","middleName":"","lastName":"Chang","suffix":""},{"id":511269102,"identity":"11739d93-031a-4bff-a5ee-79ec79ecf807","order_by":2,"name":"Priya Kumaravelu","email":"","orcid":"","institution":"Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Priya","middleName":"","lastName":"Kumaravelu","suffix":""}],"badges":[],"createdAt":"2025-09-06 21:12:50","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7553024/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7553024/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90918448,"identity":"cdacdbb0-23c1-44af-a8e5-0f81dbc740e4","added_by":"auto","created_at":"2025-09-09 14:29:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":576489,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7553024/v1/f79ea06b-f67d-4a0c-9548-0c5ce1cb9aaf.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eVanishing Bile Duct Syndrome in Hodgkin’s Lymphoma: Successful Remission through Early Chemotherapy\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eVBDS (Vanishing Bile Duct Syndrome) is a rare, acquired form of chronic cholestatic liver disease. Several different causes of ductopenia exist, ranging from drug-induced liver injury, immune-mediated disorders like Primary Biliary Cholangitis and Primary Sclerosing Cholangitis, infectious causes such as CMV or chronic viral hepatitis, idiopathic adulthood ductopenia, and malignancies [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Acquired bile duct loss has an unpredictable prognosis, potentially leading either to gradual recovery through regeneration and proliferation of biliary epithelium, or to irreversible bile duct loss, causing biliary obstruction and ultimately cirrhosis.\u003c/p\u003e\u003cp\u003eVBDS is an irreversible complication that may be associated with Hodgkin\u0026rsquo;s Lymphoma (HL). This disorder results in cholestasis and jaundice due to intrahepatic bile duct destruction. Although the relationship between VBDS and HL is not scientifically proven, theories suggest that ductal destruction may be caused by CD8 T lymphocytes or harmful cytokines released from lymphoma cells in the form of antibodies or hepatotoxic molecules [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. VBDS has been shown to manifest as severe jaundice and hepatic laboratory abnormalities, reflecting an obstructive pattern. The clinical course of VBDS is not well-defined, though recent studies have shown reversibility and remission in a subgroup of patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Treatment for VBDS is challenging due to limited published data on outcomes, poor treatment tolerance, and the risk of fulminant liver failure.\u003c/p\u003e\u003cp\u003eHere, we report the case of a 78-year-old male with HL and VBDS who was treated with an alternative immunosuppressive chemotherapy regimen, resulting in the resolution of hepatic obstruction through the reduction of lymphocytes.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eA 78-year-old man with an unremarkable past medical history was seen in Mexico in December 2017 with complaints of fever and cough. A physical exam at that time revealed several mediastinal lymph nodes and bronchitis. When the patient returned to the United States for follow-up in March 2018, he denied any night sweats, loss of appetite, or weight loss, and no additional lymph nodes were found in the neck or armpit regions. He was later admitted for hypokalemia and fever of unknown origin. A mediastinal lymph node biopsy performed in April 2018 during his admission confirmed Hodgkin\u0026rsquo;s Lymphoma (HL), nodular sclerosing type, positive for CD15, CD30, and PAX. The patient continued to experience low-grade fevers and Staphylococcus aureus infection was identified in the biopsy sample.\u003c/p\u003e\u003cp\u003eApproximately two weeks after the HL diagnosis, he developed severe cholestasis with jaundice, with a total bilirubin level reaching a high of 17.4 mg/dL, direct bilirubin of 10.5 mg/dL, AST of 190 U/L, ALT of 106 U/L,\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eHow to cite this article\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003ealkaline phosphatase of 1293 U/L, and LDH of 1195 U/L. Physical exam revealed bilateral leg swelling. An ERCP for causes of obstructive jaundice was negative, while a bone marrow biopsy was positive for HL. CBC showed pancytopenia, with hemoglobin dropping to 6.5 g/dL and an absolute neutrophil count (ANC) of 1.4.\u003c/p\u003e\u003cp\u003eThe patient was started on a 75% reduced dose of cyclophosphamide (1250 mg/m\u0026sup2;) and prednisone (100 mg po daily) for 14 days. He also received pRBC, and by the end of the cycle, his CBC and biochemical lab values normalized. However, the treatment course was complicated by neutropenic ESBL E. coli sepsis, hypernatremic metabolic encephalopathy, and anasarca, which responded to neupogen and meropenem. One month after the cyclophosphamide and prednisone treatment, the patient was started on ABVD (C1D1) treatment for his HL. The patient is now in remission after eight cycles of ABVD therapy.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eVBDS was once thought to be an irreversible and progressive diagnosis associated with HL, curable only through liver transplantation. The immune-mediated damage caused by autoreactive T cells ultimately leads to epithelial cell apoptosis and ductopenia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Patients with HL and hepatic involvement should be referred for biopsy and definitive therapy, as early detection and treatment with curative intent have shown reversal of VBDS and clinical remission in select cases. Given the rapid deterioration of our patient\u0026rsquo;s condition, there was insufficient time to perform a liver biopsy. A liver biopsy is important in patients presenting with hepatic dysfunction and a cholestatic pattern to differentiate between paraneoplastic syndrome and VBDS. Paraneoplastic syndrome in HL patients presents with jaundice, hyperbilirubinemia, and a normal liver, whereas VBDS presents with jaundice, hyperbilirubinemia, and ductopenia. Patients with paraneoplastic syndrome tend to improve once the HL is treated, while VBDS patients typically experience intrahepatic ductal destruction too severe to regenerate on its own [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTreating HL patients with a cholestatic presentation is particularly complex due to the challenge of minimizing hepatotoxicity during chemotherapy. Studies have shown that modified MOPP-ABV chemotherapy regimens can be introduced without a significant worsening of cholestasis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Extrahepatic biliary obstruction caused by HL requires dose reductions in standard chemotherapy, but adding radiotherapy to treatment does not compromise liver function.\u003c/p\u003e\u003cp\u003eOur case is remarkable because a known HL patient presented with an obstructive jaundice pattern without strictures or visible blockages seen on ERCP. VBDS has been associated with a variety of diseases, including biliary atresia, primary biliary cirrhosis, primary sclerosing cholangitis, Langerhans cell histiocytosis, viral infections, and drug-induced injury. The strongest neoplastic correlation with VBDS has been with HL. In this case, the obstructive jaundice seen in our VBDS patient was also coupled with acute pancytopenia. An analysis of recent cases published articles in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e identifies the diverse presentation and age range of this disease.\u003c/p\u003e\u003c/div\u003e\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\u003eSummary of findings in patients diagnosed with Vanishing Bile Duct syndrome\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"1\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSummary of Findings\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatient Ages\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCases spanned patients aged 9 to 75 years, with a majority of cases involving patients in their 20s.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMRCP/ERCP\u003c/p\u003e\u003cp\u003eFindings\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMost cases reported unremarkable findings or did not perform imaging. Some exceptions included sclerosing cholangitis and intrahepatic bile duct atrophy.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003cp\u003eApproaches\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTreatment varied, including chemotherapy regimens (Brentuximab or ABVD), corticosteroids (Dexamethasone), and UDCA (Ursodeoxycholic acid) for liver-related symptoms. In several cases, treatment shifted after initial approaches.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA majority of patients achieved remission, while some experienced liver failure or death. Notably, younger patients tended to have better outcomes.\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/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe patient qualified for a single dose of 75% reduced cyclophosphamide, which is not commonly used in HL patients, in an attempt to reverse the presumed obstruction as it does not require hepatic metabolism. After the personalized cyclophosphamide dose and a 14-day course of prednisone, the patient\u0026rsquo;s bilirubin and hepatic enzyme levels began to normalize. Once the patient\u0026rsquo;s lab values stabilized, and he was ready for discharge one month later, he transitioned to the expected ABVD treatment protocol. The patient is now in remission after eight cycles of ABVD.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn conclusion, the cyclophosphamide treatment eliminated the remaining lymphocytes causing the cholestatic presentation, highlighting the importance of early treatment of HL to allow liver regeneration once the autoimmune process is halted. Treating the underlying HL with cyclophosphamide also reversed the acute cytopenia, illustrating that bone marrow infiltration by lymphoma cells was the primary cause of both the abnormal CBC results and the obstructive pattern. This case underscores the importance of keeping VBDS in the differential diagnosis, as early detection and prompt treatment can be life-saving for certain HL patients. In cancer patients, it is crucial to remember that a cholestatic presentation does not necessarily indicate a primary liver disease, but may instead reflect a manifestation of malignancy. Identifying the obstruction as a result of malignant lymphocytes rather than bile duct disease, and treating it with chemotherapy, led this patient to remission.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003eHuman subjects\u003c/b\u003e: Informed consent for treatment and open access publication was obtained or waived by all participants in this study. KCU IRB Committe issued approval none. Consent was received from the patient. \u003cb\u003eConflicts of interest\u003c/b\u003e: In compliance with the ICMJE uniform disclosure form, all authors declare the following: \u003cb\u003ePayment/services info\u003c/b\u003e: All authors have declared that no financial support was received from any organization for the submitted work. \u003cb\u003eFinancial relationships\u003c/b\u003e: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. \u003cb\u003eOther relationships\u003c/b\u003e: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.\u003c/p\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003ePass AK, McLin VA, Rushton JR, Kearney DL, Hastings CA, Margolin JF (2008) Vanishing bile duct syndrome and Hodgkin disease: a case series and review of the literature. J Pediatr Hematol Oncol Dec 30:976\u0026ndash;980.\u0026nbsp;\u003c/span\u003e\u003cspan\u003e1097/MPH 0b013e31818b37c4\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBallonoff A, Kavanagh B, Nash R et al (2008) Hodgkin lymphoma-related vanishing bile duct syndrome and idiopathic cholestasis: statistical analysis of all published cases and literature review. Acta Oncol 47:962\u0026ndash;970. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/02841860701644078\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ede Medeiros BC, Lacerda MA, Telles JE, da Silva JA, de Medeiros CR (1998) Cholestasis secondary to Hodgkin\u0026apos;s disease: report of 2 cases of vanishing bile duct syndrome. Haematol Nov 83:1038\u0026ndash;1040\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eGonzalez R, Parmar P, Hardee S et al Hodgkin Lymphoma-related Vanishing Bile Duct Syndrome Cholestasis Resolved After Chemotherapy. J Pediatr Hematol Oncol. Apr 01.\u0026nbsp;\u003c/span\u003e\u003cspan\u003e1097/MPH.000000000000222\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBarta SK, Yahalom J, Shia J, Hamlin PA Idiopathic cholestasis as a paraneoplastic phenomenon in\u0026nbsp;\u003c/span\u003e\u003cspan\u003eHodgkin\u0026apos;s lymphoma (2006) Clin Lymphoma Myeloma 7:77\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3816/CLM.2006.n.044\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Hematology and Medical Oncology, Regional Medical Center, ","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":"chemotherapy response, general internal medicine, oncology, invisible bile duct syndrome, hodgkin's","lastPublishedDoi":"10.21203/rs.3.rs-7553024/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7553024/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eVanishing bile duct syndrome (VBDS) is a rare complication associated with Hodgkin's Lymphoma (HL), characterized by cholestasis and jaundice due to bile duct destruction. We report the case of a 78-year-old male with HL and VBDS, who presented with obstructive jaundice, severe cholestasis, and pancytopenia. Initial imaging showed no biliary obstruction, and the diagnosis of HL was confirmed by a lymph node biopsy. The patient was treated with a reduced dose of cyclophosphamide and prednisone, resulting in a normalization of hepatic and hematologic parameters. Following this, the patient underwent ABVD chemotherapy and achieved remission. This case emphasizes the potential for VBDS reversal with early treatment of HL, highlighting the importance of distinguishing cholestatic patterns related to malignancy from primary liver disease. Early intervention with chemotherapy targeting the underlying malignancy can restore liver function and improve patient outcomes.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCategories\u003c/b\u003e: Internal Medicine, Oncology, Gastroenterology\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","manuscriptTitle":"Vanishing Bile Duct Syndrome in Hodgkin’s Lymphoma: Successful Remission through Early Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 14:13:32","doi":"10.21203/rs.3.rs-7553024/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"e631a009-6588-4e0d-83c6-c9e8e2111df5","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-09T14:13:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 14:13:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7553024","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7553024","identity":"rs-7553024","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}