Article
Case Report
Korean J Gastroenterol 2024; 84(6): 288-292
Published online December 25, 2024 https://doi.org/10.4166/kjg.2024.133
© The Korean Society of Gastroenterology.
Idiopathic Vanishing Bile Duct Syndrome in a Young Female: A Case Report
젊은 여성에서 발생한 특발성 담도 소실 증후군: 증례 보고
Min Ji Kim1,2,3, Hyun Myung Cho1,2,3, Young Mi Hong1,2,3, Ki Tae Yoon1,2,3
김민지1,2,3, 조현명1,2,3, 홍영미1,2,3, 윤기태1,2,3
Correspondence to: Ki Tae Yoon, Liver Center, Pusan National University of Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea. Tel: +82-55-360-2362, Fax: +82-55-360-1736, E-mail: ktyoon@pusan.ac.kr, ORCID: http://orcid.org/0000-0002-8580-0239
Financial support: This study was supported by a 2024 research grant from Pusan National University Yangsan Hospital.
This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Vanishing bile duct syndrome (VBDS) is characterized by the progressive loss and destruction of the intrahepatic bile ducts, leading to bile stasis and associated symptoms such as jaundice. This condition is commonly associated with drug side effects, infections, neoplasms, and autoimmune diseases, but the precise mechanism of its development is unclear. Although VBDS can be diagnosed based on the patient's symptoms and disease progression, a liver biopsy is essential for confirmation, and the prognosis can vary significantly. This paper presents a rare case of a young female patient diagnosed with idiopathic VBDS after undergoing a liver biopsy to investigate unexplained jaundice. The patient's liver function improved partially after an ursodeoxycholic acid and prednisolone treatment.
KeywordsJaundice; Cholestasis; Bile ducts
INTRODUCTION
Vanishing bile duct syndrome (VBDS) is a rare condition characterized by the progressive loss and obliteration of the intrahepatic bile ducts within the portal tract, leading to cholestasis and resulting in manifestations such as jaundice and liver failure.1 Despite the associations of VBDS with congenital and genetic anomalies, autoimmune disorders, malignancies, infections, and commonly used antibiotics, it can occur without any clear exposure to these factors.2 VBDS accounts for only 0.5% of small biliary duct pathologies and has a wide range of prognoses, from cholestasis and biliary cirrhosis to liver failure and death.3 Although a diagnosis depends primarily on patient-reported symptoms, a liver biopsy is essential.2 This paper presents a unique case of idiopathic VBDS in a young female with no prior history of antibiotic use or malignancies. The patient exhibited clinical and laboratory improvement after treatment with ursodeoxycholic acid (UDCA) and prednisolone.
CASE REPORT
A 20-year-old female patient with no significant medical history except for treated neonatal jaundice visited the hospital with the chief complaint of jaundice and itching that had started three weeks prior to presentation. She reported that her father had been receiving treatment for chronic hepatitis B (HBV), but she had received her vaccination for HBV and was an antibody carrier with no evidence of HBV infection. The patient denied any smoking or alcohol consumption and did not take any supplements for weight loss. Regarding her medication history, she had taken Cetirizine (10 mg) for five days because of itching that developed after the onset of jaundice. She had no recent travel history, nor had she engaged in any physical activities involving strenuous exercise. During the initial physical examination, the patient presented with scleral jaundice and reported lower abdominal discomfort. She denied the possibility of pregnancy. There was no tenderness upon palpation and no signs of organ enlargement. The chest x-ray revealed no infiltrates or abnormalities in the lung parenchyma. The laboratory tests revealed elevated liver enzymes, with aspartate aminotransferase and alanine aminotransferase levels of 68 IU/L (normal range, 0–50 IU/L) and 70 IU/L (normal range, 0–50 IU/L), respectively. Gamma-glutamyl transferase (GGT) was recorded at 14 U/L (normal range, 9–64 IU/L), and a slight increase in alkaline phosphatase at 139 U/L (normal range, 43–115 IU/L) was noted. The total bilirubin was significantly elevated at 19.6 mg/dL (normal range, 0.3–1.2 mg/dL), with direct bilirubin at 13.8 mg/dL (normal range, 0–0.2 mg/dL). The international normalized ratio (INR) was modestly elevated at 1.52 (normal range, 0.8–1.2), suggesting potential impairment of the liver function. An analysis of the complete blood count revealed a hemoglobin level of 13 g/dL (normal range, 13.5–17.5 g/dL), indicating no anemia, and the white blood cell and platelet counts were within the normal range. A serologic evaluation for viral hepatitis and autoimmune antibody analysis, including anti-mitochondrial, antinuclear, and anti-smooth muscle antibodies, were negative. The serum IgG 1,272 mg/dL (normal range, 700–1,600 mg/dL), IgM 131 mg/dL(normal range, 40–230 mg/dL), and ceruloplasmin 35.4 mg/dL (normal range, 16.0–45.0 mg/dL) levels were within the normal range. The total cholesterol, triglycerides, HDL cholesterol, and calculated LDL cholesterol were 254 mg/dL (normal range, 0–200 mg/dL), 509 mg/dL (normal range, 0– 150 mg/dL), 11 mg/dL (normal range, 40–60 mg/dL), and 141 mg/dL (normal range, 0–100 mg/dL), respectively. The blood culture showed no growth, with no evidence of any overt infection, including that of the Epstein–Barr Virus. Computed tomography showed no evidence of hepatomegaly or abnormal findings such as dilatation of the intrahepatic and extrahepatic bile ducts (Fig. 1). In addition, no indications of lymph node enlargement were observed around the liver or signs suggestive of infection. From the day of admission, the patient was started on 600 mg/day of UDCA to aid in liver function recovery. Despite this treatment, the direct bilirubin level continued to rise, reaching 19.6 mg/dL on the fourth day of hospitalization. Consequently, an ultrasound-guided liver biopsy was performed on the sixth day after admission. The histology examination revealed cholestatic hepatitis with more than 50% bile duct loss and moderate lobular activity. Bridging fibrosis was also observed, and immunohistochemistry revealed significant hepatocytic K7-positivity, indicating liver damage (Fig. 2). Primary Biliary Cholangitis (PBC) was evaluated as part of a differential diagnosis, and immunological tests were performed to exclude late-stage PBC. The anti-mitochondrial antibody (AMA) in the patient was negative, as were PBC-specific antibodies, including anti-glycoprotein 210 and anti-speckled 100. Based on the biopsy results, the patient was diagnosed with liver damage due to vanishing bile duct syndrome of an unknown origin.
-
Figure 1. Patient's computed tomography images. The liver and bile ducts showed no abnormalities. (A) Axial image, (B) Coronal image.
-
Figure 2. Pathologic findings of a liver biopsy. The hepatocytes exhibited a striking reaction with the K7 antibody through the biopsy specimen. The red arrow indicates an interlobular bile duct rarely seen in this sample, while the blue arrow indicates a portal area devoid of bile duct. (A) Hematoxylin and Eosin stain, ×200, (B) K7 stain, ×200, (C) K7 stain, ×40.
The administration of prednisolone 60 mg/day (1 mg/kg) and high-dose UDCA 900 mg/day was initiated. After seven days of treatment with prednisolone and high-dose UDCA, the bilirubin levels dropped from 20 mg/dL to 13.1 mg/dL. Two weeks into the treatment, her clinical symptoms improved, and the liver function tests allowed the prednisolone dose to be reduced to half the initial dose (30 mg/day). The dose was then gradually tapered every two weeks until it reached 20 mg/day. Subsequently, prednisolone was further reduced by 5 mg per month, and by the sixth month of treatment, the patient was stabilized on prednisolone 5 mg/day and UDCA 900 mg/day. Her bilirubin, INR, and albumin levels improved to 2.5 mg/dL, 0.91, and 3.8 g/dL, respectively (Fig. 3).
-
Figure 3. Changes in (A) AST, ALT, ALP, GGT (IU/L), (B) total bilirubin (mg/dL), and INR levels for 186 days. The liver biopsy was performed on the sixth day of hospitalization, and prednisolone administration was initiated on the 13th day of hospitalization. AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase.
1. Ethical statement
The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the Helsinki Declaration (as revised in 2013).
DISCUSSION
VBDS is a rare disease characterized by the progressive destruction and disappearance of the intrahepatic bile ducts, leading to cholestasis.1 Although the pathogenesis of VBDS is not completely understood, various causes and mechanisms contributing to bile duct damage and loss have been identified.4 In VBDS, hepatobiliary imaging cannot offer a definitive diagnosis as the condition predominantly affects the small canaliculi of the biliary tract, which are less than 15 mm in size.5 A liver biopsy is crucial for establishing a diagnosis and should be performed immediately if disease is suspected. A diagnosis of VBDS is made when a liver biopsy reveals less than 50% of the bile ducts, suggesting that the majority of the bile ducts have been destroyed.6 This condition can be associated with a multitude of factors, including drug use, infections, autoimmune diseases, neoplasms, and transplant rejection responses.2 The patient had previously taken Cetirizine (10 mg), but its consumption was assumed to be after the onset of pruritus caused by cholestasis, making it an unlikely direct cause of liver damage. Moreover, no evidence of viral hepatitis, autoimmune diseases, or alcohol consumption was observed, making it impossible to identify a specific cause. On the other hand, the disease was considered to be an idiopathic onset liver dysfunction because VBDS could be diagnosed based on a histological examination of the liver biopsy findings.
Idiopathic VBDS refers to cases of unexplained cholestatic liver disease and ductopenia despite comprehensive evaluations through laboratory tests, imaging studies, and a liver biopsy. In a study involving 2,082 adult patients with intrahepatic bile duct damage, cases of unknown etiology showed less than 1% of the instances, indicating a very low incidence.7 GGT is typically elevated in cases of VBDS, and it is rare for it to remain within the normal range in patients with significantly elevated bilirubin levels, as observed in this case. This patient consistently exhibited GGT levels within the normal range, but the precise reason is unclear. One study reported that individuals with genetic variants associated with reduced GGT activity may not show elevated GGT levels even in the presence of liver damage.8 On the other hand, it is unclear if the normal GGT levels are linked to the disease activity or prognosis in VBDS. In this patient's case, further evaluation is necessary to determine the precise reason for the normal GGT levels.
The prognosis of VBDS varies, and factors such as severity and degree of liver dysfunction, pre-existing liver disease, comorbidities, history of ethanol consumption, and histological characteristics can affect the prognosis. Although Ballonoff et al. reported that one-third of patients may experience a reversible disease course, the disease is often progressive, leading to long-term biliary cirrhosis, bile duct loss, liver failure, and death.9 Among the different types of VBDS, idiopathic VBDS often has the poorest outcomes, with up to 50% of cases progressing to liver failure, some requiring liver transplantation owing to extensive bile duct destruction.
The treatment of VBDS involves addressing the underlying cause. If a potential causative agent is identified, it must be discontinued as soon as possible. This is crucial for spontaneous recovery and is generally accompanied by clinical improvement.10 In addition, other potential causes of liver damage, including infections, alcohol consumption, autoimmune and ischemic hepatitis, and other metabolic liver diseases, must be excluded. Imaging studies such as computed tomography or magnetic resonance imaging are recommended to exclude extrahepatic biliary obstruction. To the best of the authors' knowledge, only three cases have been reported in Korea, highlighting the rarity of this condition (Table 1).11-13 No standardized treatment protocol exists because of its low incidence. The primary treatment primarily involves administering UDCA and steroids and managing the symptoms as they arise. UDCA stimulates bile secretion through the bile ducts, protects the epithelium from bile acid-induced cytotoxicity, and inhibits hepatocyte apoptosis.14 The use of steroids is controversial, but they have been used effectively in severe cholestasis and VBDS, offering beneficial effects in reducing potential inflammatory mechanisms.15 Medications such as antihistamines, rifampicin, phenobarbital, and opioid analogs can be used to manage severe itching, but their use should be based on the severity of symptoms and the patient's liver function.16
-
Table 1 Reported Cases of Vanishing Bile Duct Syndrome in Korean Adults
Author (yr) Age, sex Underlying disease Trigger factor Finding of liver biopsy Treatment (duration) Treatment results Bak et al.11 (2020) 20, female None Non-steroidal antiinflammatory drug (Pelubiprofen) Chronic cholestatic hepatitis with a biliary pattern, showing bile duct loss involving >50% of the portal areas examined, accompanied by hepatic arterioles. Methylprednisolone 30 mg/day (Reduced by half every week for a month) Liver transplant waiting status Choi et al.12 (2005) 60, male Type 2 diabetes mellitus, chronic kidney disease Allopurinol Diffuse intrahepatic bile duct loss, chronic cholestasis Steroid (19 days); Types and dosages of steroids are not specified Death (Hospital day 35) Han et al.13 (2005) 45, male Complete remission stage of Hodgkin's lymphoma Unknown Absence of interlobular bile duct loss involving >50% of the por tal areas examined, no Reed-Sternberg cell in the liver None Spontaneous resolution (Bilirubin level normalized but Hodgkin's lymphoma recurrence)
In conclusion, delays in diagnosis and treatment can increase morbidity and mortality. A better understanding of the disease and prompt diagnosis can lead to effective treatment. This case provides insights into the management of similar cases of patients with VBDS.
Financial support
This study was supported by a 2024 research grant from Pusan National University Yangsan Hospital.
Conflict of interest
None.
References
- Izzo P, Gallo G, Codacci Pisanelli M, et al. Vanishing bile duct syndrome in an adult patient: Case report and review of the literature. J Clin Med 2022;11:3253.
- Ludwig J, Wiesner RH, LaRusso NF. Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis. J Hepatol 1988;7:193-199.
- Björnsson ES, Jonasson JG. Idiosyncratic drug-induced liver injury associated with bile duct loss and vanishing bile duct syndrome: Rare but has severe consequences. Hepatology 2017;65:1091-1093.
- Zhao Z, Bao L, Yu X, et al. Acute vanishing bile duct syndrome after therapy with cephalosporin, metronidazole, and clotrimazole: A case report. Medicine (Baltimore) 2017;96:e8009.
- Geubel AP, Sempoux CL. Drug and toxin-induced bile duct disorders. J Gastroenterol Hepatol 2000;15:1232-1238.
- Nakanuma Y, Tsuneyama K, Harada K. Pathology and pathogenesis of intrahepatic bile duct loss. J Hepatobiliary Pancreat Surg 2001;8:303-315.
- Marchioni Beery RM, Vaziri H, Forouhar F. Primary biliary cirrhosis and primary sclerosing cholangitis: a review featuring a women's health perspective. J Clin Transl Hepatol 2014;2:266-284.
- van Beek JH, de Moor MH, de Geus EJ, et al. The genetic architecture of liver enzyme levels: GGT, ALT and AST. Behav Genet 2013;43:329-339.
- Ballonoff A, Kavanagh B, Nash R, et al. Hodgkin lymphoma-related vanishing bile duct syndrome and idiopathic cholestasis: statistical analysis of all published cases and literature review. Acta Oncol 2008;47:962-970.
- Greca RD, Cunha-Silva M, Costa LBE, et al. Vanishing bile duct syndrome related to DILI and Hodgkin lymphoma overlap: A rare and severe case. Ann Hepatol 2020;19:107-112.
- Bak H, Kim H, Lee S, Lee Y, Bang SM, Lee YS. A case of vanishing bile duct syndrome after drug-induced liver injury caused by pelubiprofen. Yonsei Med J 2020;61:1060-1063.
- Choi SH, Yang SH, Song YB, et al. A case of vanishing bile duct syndrome associated with hypersensitivity to allopurinol. Korean J Hepatol 2005;11:80-85.
- Han WS, Jung ES, Kim YH, et al. Spontaneous resolution of vanishing bile duct syndrome in Hodgkin's lymphoma. Korean J Hepatol 2005;11:164-168.
- Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009;50:1721-1734.
- Tajiri H, Etani Y, Mushiake S, Ozono K, Nakayama M. A favorable response to steroid therapy in a child with drug-associated acute vanishing bile duct syndrome and skin disorder. J Paediatr Child Health 2008;44:234-236.
- Imam MH, Gossard AA, Sinakos E, Lindor KD. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol 2012;27:1150-1158.
Article
Case Report
Korean J Gastroenterol 2024; 84(6): 288-292
Published online December 25, 2024 https://doi.org/10.4166/kjg.2024.133
Copyright © The Korean Society of Gastroenterology.
Idiopathic Vanishing Bile Duct Syndrome in a Young Female: A Case Report
Min Ji Kim1,2,3, Hyun Myung Cho1,2,3, Young Mi Hong1,2,3, Ki Tae Yoon1,2,3
1Department of Internal Medicine, Pusan National University College of Medicine; 2Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital; 3Liver Center, Pusan National University Yangsan Hospital, Yangsan, Korea
Correspondence to:Ki Tae Yoon, Liver Center, Pusan National University of Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan 50612, Korea. Tel: +82-55-360-2362, Fax: +82-55-360-1736, E-mail: ktyoon@pusan.ac.kr, ORCID: http://orcid.org/0000-0002-8580-0239
Financial support: This study was supported by a 2024 research grant from Pusan National University Yangsan Hospital.
This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Vanishing bile duct syndrome (VBDS) is characterized by the progressive loss and destruction of the intrahepatic bile ducts, leading to bile stasis and associated symptoms such as jaundice. This condition is commonly associated with drug side effects, infections, neoplasms, and autoimmune diseases, but the precise mechanism of its development is unclear. Although VBDS can be diagnosed based on the patient's symptoms and disease progression, a liver biopsy is essential for confirmation, and the prognosis can vary significantly. This paper presents a rare case of a young female patient diagnosed with idiopathic VBDS after undergoing a liver biopsy to investigate unexplained jaundice. The patient's liver function improved partially after an ursodeoxycholic acid and prednisolone treatment.
Keywords: Jaundice, Cholestasis, Bile ducts
INTRODUCTION
Vanishing bile duct syndrome (VBDS) is a rare condition characterized by the progressive loss and obliteration of the intrahepatic bile ducts within the portal tract, leading to cholestasis and resulting in manifestations such as jaundice and liver failure.1 Despite the associations of VBDS with congenital and genetic anomalies, autoimmune disorders, malignancies, infections, and commonly used antibiotics, it can occur without any clear exposure to these factors.2 VBDS accounts for only 0.5% of small biliary duct pathologies and has a wide range of prognoses, from cholestasis and biliary cirrhosis to liver failure and death.3 Although a diagnosis depends primarily on patient-reported symptoms, a liver biopsy is essential.2 This paper presents a unique case of idiopathic VBDS in a young female with no prior history of antibiotic use or malignancies. The patient exhibited clinical and laboratory improvement after treatment with ursodeoxycholic acid (UDCA) and prednisolone.
CASE REPORT
A 20-year-old female patient with no significant medical history except for treated neonatal jaundice visited the hospital with the chief complaint of jaundice and itching that had started three weeks prior to presentation. She reported that her father had been receiving treatment for chronic hepatitis B (HBV), but she had received her vaccination for HBV and was an antibody carrier with no evidence of HBV infection. The patient denied any smoking or alcohol consumption and did not take any supplements for weight loss. Regarding her medication history, she had taken Cetirizine (10 mg) for five days because of itching that developed after the onset of jaundice. She had no recent travel history, nor had she engaged in any physical activities involving strenuous exercise. During the initial physical examination, the patient presented with scleral jaundice and reported lower abdominal discomfort. She denied the possibility of pregnancy. There was no tenderness upon palpation and no signs of organ enlargement. The chest x-ray revealed no infiltrates or abnormalities in the lung parenchyma. The laboratory tests revealed elevated liver enzymes, with aspartate aminotransferase and alanine aminotransferase levels of 68 IU/L (normal range, 0–50 IU/L) and 70 IU/L (normal range, 0–50 IU/L), respectively. Gamma-glutamyl transferase (GGT) was recorded at 14 U/L (normal range, 9–64 IU/L), and a slight increase in alkaline phosphatase at 139 U/L (normal range, 43–115 IU/L) was noted. The total bilirubin was significantly elevated at 19.6 mg/dL (normal range, 0.3–1.2 mg/dL), with direct bilirubin at 13.8 mg/dL (normal range, 0–0.2 mg/dL). The international normalized ratio (INR) was modestly elevated at 1.52 (normal range, 0.8–1.2), suggesting potential impairment of the liver function. An analysis of the complete blood count revealed a hemoglobin level of 13 g/dL (normal range, 13.5–17.5 g/dL), indicating no anemia, and the white blood cell and platelet counts were within the normal range. A serologic evaluation for viral hepatitis and autoimmune antibody analysis, including anti-mitochondrial, antinuclear, and anti-smooth muscle antibodies, were negative. The serum IgG 1,272 mg/dL (normal range, 700–1,600 mg/dL), IgM 131 mg/dL(normal range, 40–230 mg/dL), and ceruloplasmin 35.4 mg/dL (normal range, 16.0–45.0 mg/dL) levels were within the normal range. The total cholesterol, triglycerides, HDL cholesterol, and calculated LDL cholesterol were 254 mg/dL (normal range, 0–200 mg/dL), 509 mg/dL (normal range, 0– 150 mg/dL), 11 mg/dL (normal range, 40–60 mg/dL), and 141 mg/dL (normal range, 0–100 mg/dL), respectively. The blood culture showed no growth, with no evidence of any overt infection, including that of the Epstein–Barr Virus. Computed tomography showed no evidence of hepatomegaly or abnormal findings such as dilatation of the intrahepatic and extrahepatic bile ducts (Fig. 1). In addition, no indications of lymph node enlargement were observed around the liver or signs suggestive of infection. From the day of admission, the patient was started on 600 mg/day of UDCA to aid in liver function recovery. Despite this treatment, the direct bilirubin level continued to rise, reaching 19.6 mg/dL on the fourth day of hospitalization. Consequently, an ultrasound-guided liver biopsy was performed on the sixth day after admission. The histology examination revealed cholestatic hepatitis with more than 50% bile duct loss and moderate lobular activity. Bridging fibrosis was also observed, and immunohistochemistry revealed significant hepatocytic K7-positivity, indicating liver damage (Fig. 2). Primary Biliary Cholangitis (PBC) was evaluated as part of a differential diagnosis, and immunological tests were performed to exclude late-stage PBC. The anti-mitochondrial antibody (AMA) in the patient was negative, as were PBC-specific antibodies, including anti-glycoprotein 210 and anti-speckled 100. Based on the biopsy results, the patient was diagnosed with liver damage due to vanishing bile duct syndrome of an unknown origin.
-
Figure 1. Patient's computed tomography images. The liver and bile ducts showed no abnormalities. (A) Axial image, (B) Coronal image.
-
Figure 2. Pathologic findings of a liver biopsy. The hepatocytes exhibited a striking reaction with the K7 antibody through the biopsy specimen. The red arrow indicates an interlobular bile duct rarely seen in this sample, while the blue arrow indicates a portal area devoid of bile duct. (A) Hematoxylin and Eosin stain, ×200, (B) K7 stain, ×200, (C) K7 stain, ×40.
The administration of prednisolone 60 mg/day (1 mg/kg) and high-dose UDCA 900 mg/day was initiated. After seven days of treatment with prednisolone and high-dose UDCA, the bilirubin levels dropped from 20 mg/dL to 13.1 mg/dL. Two weeks into the treatment, her clinical symptoms improved, and the liver function tests allowed the prednisolone dose to be reduced to half the initial dose (30 mg/day). The dose was then gradually tapered every two weeks until it reached 20 mg/day. Subsequently, prednisolone was further reduced by 5 mg per month, and by the sixth month of treatment, the patient was stabilized on prednisolone 5 mg/day and UDCA 900 mg/day. Her bilirubin, INR, and albumin levels improved to 2.5 mg/dL, 0.91, and 3.8 g/dL, respectively (Fig. 3).
-
Figure 3. Changes in (A) AST, ALT, ALP, GGT (IU/L), (B) total bilirubin (mg/dL), and INR levels for 186 days. The liver biopsy was performed on the sixth day of hospitalization, and prednisolone administration was initiated on the 13th day of hospitalization. AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase.
1. Ethical statement
The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the Helsinki Declaration (as revised in 2013).
DISCUSSION
VBDS is a rare disease characterized by the progressive destruction and disappearance of the intrahepatic bile ducts, leading to cholestasis.1 Although the pathogenesis of VBDS is not completely understood, various causes and mechanisms contributing to bile duct damage and loss have been identified.4 In VBDS, hepatobiliary imaging cannot offer a definitive diagnosis as the condition predominantly affects the small canaliculi of the biliary tract, which are less than 15 mm in size.5 A liver biopsy is crucial for establishing a diagnosis and should be performed immediately if disease is suspected. A diagnosis of VBDS is made when a liver biopsy reveals less than 50% of the bile ducts, suggesting that the majority of the bile ducts have been destroyed.6 This condition can be associated with a multitude of factors, including drug use, infections, autoimmune diseases, neoplasms, and transplant rejection responses.2 The patient had previously taken Cetirizine (10 mg), but its consumption was assumed to be after the onset of pruritus caused by cholestasis, making it an unlikely direct cause of liver damage. Moreover, no evidence of viral hepatitis, autoimmune diseases, or alcohol consumption was observed, making it impossible to identify a specific cause. On the other hand, the disease was considered to be an idiopathic onset liver dysfunction because VBDS could be diagnosed based on a histological examination of the liver biopsy findings.
Idiopathic VBDS refers to cases of unexplained cholestatic liver disease and ductopenia despite comprehensive evaluations through laboratory tests, imaging studies, and a liver biopsy. In a study involving 2,082 adult patients with intrahepatic bile duct damage, cases of unknown etiology showed less than 1% of the instances, indicating a very low incidence.7 GGT is typically elevated in cases of VBDS, and it is rare for it to remain within the normal range in patients with significantly elevated bilirubin levels, as observed in this case. This patient consistently exhibited GGT levels within the normal range, but the precise reason is unclear. One study reported that individuals with genetic variants associated with reduced GGT activity may not show elevated GGT levels even in the presence of liver damage.8 On the other hand, it is unclear if the normal GGT levels are linked to the disease activity or prognosis in VBDS. In this patient's case, further evaluation is necessary to determine the precise reason for the normal GGT levels.
The prognosis of VBDS varies, and factors such as severity and degree of liver dysfunction, pre-existing liver disease, comorbidities, history of ethanol consumption, and histological characteristics can affect the prognosis. Although Ballonoff et al. reported that one-third of patients may experience a reversible disease course, the disease is often progressive, leading to long-term biliary cirrhosis, bile duct loss, liver failure, and death.9 Among the different types of VBDS, idiopathic VBDS often has the poorest outcomes, with up to 50% of cases progressing to liver failure, some requiring liver transplantation owing to extensive bile duct destruction.
The treatment of VBDS involves addressing the underlying cause. If a potential causative agent is identified, it must be discontinued as soon as possible. This is crucial for spontaneous recovery and is generally accompanied by clinical improvement.10 In addition, other potential causes of liver damage, including infections, alcohol consumption, autoimmune and ischemic hepatitis, and other metabolic liver diseases, must be excluded. Imaging studies such as computed tomography or magnetic resonance imaging are recommended to exclude extrahepatic biliary obstruction. To the best of the authors' knowledge, only three cases have been reported in Korea, highlighting the rarity of this condition (Table 1).11-13 No standardized treatment protocol exists because of its low incidence. The primary treatment primarily involves administering UDCA and steroids and managing the symptoms as they arise. UDCA stimulates bile secretion through the bile ducts, protects the epithelium from bile acid-induced cytotoxicity, and inhibits hepatocyte apoptosis.14 The use of steroids is controversial, but they have been used effectively in severe cholestasis and VBDS, offering beneficial effects in reducing potential inflammatory mechanisms.15 Medications such as antihistamines, rifampicin, phenobarbital, and opioid analogs can be used to manage severe itching, but their use should be based on the severity of symptoms and the patient's liver function.16
-
Table 1 . Reported Cases of Vanishing Bile Duct Syndrome in Korean Adults.
Author (yr) Age, sex Underlying disease Trigger factor Finding of liver biopsy Treatment (duration) Treatment results Bak et al.11 (2020) 20, female None Non-steroidal antiinflammatory drug (Pelubiprofen) Chronic cholestatic hepatitis with a biliary pattern, showing bile duct loss involving >50% of the portal areas examined, accompanied by hepatic arterioles. Methylprednisolone 30 mg/day (Reduced by half every week for a month) Liver transplant waiting status Choi et al.12 (2005) 60, male Type 2 diabetes mellitus, chronic kidney disease Allopurinol Diffuse intrahepatic bile duct loss, chronic cholestasis Steroid (19 days); Types and dosages of steroids are not specified Death (Hospital day 35) Han et al.13 (2005) 45, male Complete remission stage of Hodgkin's lymphoma Unknown Absence of interlobular bile duct loss involving >50% of the por tal areas examined, no Reed-Sternberg cell in the liver None Spontaneous resolution (Bilirubin level normalized but Hodgkin's lymphoma recurrence)
In conclusion, delays in diagnosis and treatment can increase morbidity and mortality. A better understanding of the disease and prompt diagnosis can lead to effective treatment. This case provides insights into the management of similar cases of patients with VBDS.
Financial support
This study was supported by a 2024 research grant from Pusan National University Yangsan Hospital.
Conflict of interest
None.
Fig 1.

Fig 2.

Fig 3.

-
Table 1 Reported Cases of Vanishing Bile Duct Syndrome in Korean Adults
Author (yr) Age, sex Underlying disease Trigger factor Finding of liver biopsy Treatment (duration) Treatment results Bak et al.11 (2020) 20, female None Non-steroidal antiinflammatory drug (Pelubiprofen) Chronic cholestatic hepatitis with a biliary pattern, showing bile duct loss involving >50% of the portal areas examined, accompanied by hepatic arterioles. Methylprednisolone 30 mg/day (Reduced by half every week for a month) Liver transplant waiting status Choi et al.12 (2005) 60, male Type 2 diabetes mellitus, chronic kidney disease Allopurinol Diffuse intrahepatic bile duct loss, chronic cholestasis Steroid (19 days); Types and dosages of steroids are not specified Death (Hospital day 35) Han et al.13 (2005) 45, male Complete remission stage of Hodgkin's lymphoma Unknown Absence of interlobular bile duct loss involving >50% of the por tal areas examined, no Reed-Sternberg cell in the liver None Spontaneous resolution (Bilirubin level normalized but Hodgkin's lymphoma recurrence)
References
- Izzo P, Gallo G, Codacci Pisanelli M, et al. Vanishing bile duct syndrome in an adult patient: Case report and review of the literature. J Clin Med 2022;11:3253.
- Ludwig J, Wiesner RH, LaRusso NF. Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis. J Hepatol 1988;7:193-199.
- Björnsson ES, Jonasson JG. Idiosyncratic drug-induced liver injury associated with bile duct loss and vanishing bile duct syndrome: Rare but has severe consequences. Hepatology 2017;65:1091-1093.
- Zhao Z, Bao L, Yu X, et al. Acute vanishing bile duct syndrome after therapy with cephalosporin, metronidazole, and clotrimazole: A case report. Medicine (Baltimore) 2017;96:e8009.
- Geubel AP, Sempoux CL. Drug and toxin-induced bile duct disorders. J Gastroenterol Hepatol 2000;15:1232-1238.
- Nakanuma Y, Tsuneyama K, Harada K. Pathology and pathogenesis of intrahepatic bile duct loss. J Hepatobiliary Pancreat Surg 2001;8:303-315.
- Marchioni Beery RM, Vaziri H, Forouhar F. Primary biliary cirrhosis and primary sclerosing cholangitis: a review featuring a women's health perspective. J Clin Transl Hepatol 2014;2:266-284.
- van Beek JH, de Moor MH, de Geus EJ, et al. The genetic architecture of liver enzyme levels: GGT, ALT and AST. Behav Genet 2013;43:329-339.
- Ballonoff A, Kavanagh B, Nash R, et al. Hodgkin lymphoma-related vanishing bile duct syndrome and idiopathic cholestasis: statistical analysis of all published cases and literature review. Acta Oncol 2008;47:962-970.
- Greca RD, Cunha-Silva M, Costa LBE, et al. Vanishing bile duct syndrome related to DILI and Hodgkin lymphoma overlap: A rare and severe case. Ann Hepatol 2020;19:107-112.
- Bak H, Kim H, Lee S, Lee Y, Bang SM, Lee YS. A case of vanishing bile duct syndrome after drug-induced liver injury caused by pelubiprofen. Yonsei Med J 2020;61:1060-1063.
- Choi SH, Yang SH, Song YB, et al. A case of vanishing bile duct syndrome associated with hypersensitivity to allopurinol. Korean J Hepatol 2005;11:80-85.
- Han WS, Jung ES, Kim YH, et al. Spontaneous resolution of vanishing bile duct syndrome in Hodgkin's lymphoma. Korean J Hepatol 2005;11:164-168.
- Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res 2009;50:1721-1734.
- Tajiri H, Etani Y, Mushiake S, Ozono K, Nakayama M. A favorable response to steroid therapy in a child with drug-associated acute vanishing bile duct syndrome and skin disorder. J Paediatr Child Health 2008;44:234-236.
- Imam MH, Gossard AA, Sinakos E, Lindor KD. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol 2012;27:1150-1158.