Chemotherapy-induced secondary sclerosing cholangitis mimicking primary sclerosing cholangitis: a case report

Abstract

Secondary sclerosing cholangitis (SSC) is a rare condition that may mimic primary sclerosing cholangitis. Chemotherapy-related biliary injury is an emerging cause. We present a 72-year-old male with gastric carcinoma who developed cholestatic liver injury following oxaliplatin-based chemotherapy. Imaging revealed intrahepatic biliary dilatation without an obstructing lesion. Percutaneous transhepatic cholangiography confirmed biliary abnormalities. The patient was managed with biliary drainage and supportive care, resulting in gradual clinical and biochemical improvement. Chemotherapy-induced SSC should be considered in patients with cholestatic liver injury after oxaliplatin-based regimens, and early recognition is essential.

Introduction

Secondary sclerosing cholangitis (SSC) is an uncommon but clinically significant condition characterized by inflammation, fibrosis, and multifocal strictures of the biliary tree. It can closely mimic primary sclerosing cholangitis (PSC) in both clinical presentation and imaging findings. However, unlike PSC, SSC develops secondary to identifiable etiological factors such as ischemia, infection, surgical interventions, or drug-induced hepatobiliary toxicity [1, 2].

In recent years, chemotherapy-related hepatobiliary injury has gained increasing attention. Oxaliplatin- and fluoropyrimidine-based regimens have been associated with various forms of liver injury, including sinusoidal obstruction syndrome and cholangiopathy [3, 4]. In rare cases, these agents may lead to SSC, which may radiologically resemble PSC with a characteristic ‘beaded’ appearance of the bile ducts.

Herein, we present a case of chemotherapy-induced SSC mimicking PSC in a patient with gastric cancer, highlighting the importance of differential diagnosis and appropriate management.

Case report

A 72-year-old male patient with a diagnosis of gastric carcinoma received neoadjuvant chemotherapy followed by total gastrectomy with D2 lymph node dissection. Postoperatively, the patient was initiated on a fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)-based chemotherapy regimen including 5-fluorouracil (3400 mg), leucovorin (330 mg), oxaliplatin (110 mg), and docetaxel (50 mg) administered every 15 days.

Approximately 12 weeks after the fifth chemotherapy cycle, the patient presented with abdominal pain, jaundice, nausea, and vomiting, and was admitted to our clinic. On physical examination, the patient was conscious but cachectic, with icteric sclera and tenderness in the right upper quadrant without rebound or guarding. Vital signs were stable, and body temperature was 36.9°C.

Laboratory investigations revealed a cholestatic pattern of liver injury, including elevated aspartate aminotransferase (166.5 IU/L), alanine aminotransferase (189 IU/L), gamma-glutamyl transferase (288 IU/L), and alkaline phosphatase (823 IU/L). Total bilirubin was 10.07 mg/dL with direct bilirubin of 9.8 mg/dL. C-reactive protein was elevated (39 mg/dL), while leukocyte count was within normal limits.

Abdominal ultrasonography demonstrated intrahepatic bile duct dilatation, predominantly in the central regions and both lobes, along with a distended gallbladder containing sludge and millimetric calculi.

A contrast-enhanced abdominal computed tomography (CT) performed on 08 July 2025, prior to the initiation of chemotherapy, demonstrated mild intrahepatic biliary dilatation without evidence of an obstructing lesion (Fig. 1). The patient subsequently received the first cycle of chemotherapy on 25 August 2025. After completion of the fifth chemotherapy cycle, he developed progressive jaundice and cholestatic liver enzyme elevation requiring hospitalization. A repeat contrast-enhanced CT obtained during this admission demonstrated progressive intrahepatic biliary dilatation and suspicious enhancement in the distal common bile duct (Fig. 2), supporting a temporal relationship between chemotherapy exposure and biliary injury.

The patient was initially treated with intravenous fluids, ceftriaxone and metronidazole, and ursodeoxycholic acid. Due to persistent cholestasis, interventional radiology was consulted. Percutaneous cholangiography demonstrated irregular, tortuous intrahepatic bile ducts with multifocal strictures showing a characteristic ‘beaded’ appearance (Fig. 2).

Endoscopic retrograde cholangiopancreatography (ERCP) was not feasible due to altered anatomy following esophagojejunostomy. Therefore, percutaneous transhepatic cholangiography (PTC) was performed, confirming diffuse biliary strictures and distal obstruction. An 8F external biliary drainage catheter was placed successfully (Fig. 3).

Following drainage, the patient showed marked clinical improvement. Daily bile drainage reached ~600 mL. Within 4 days, liver enzymes and bilirubin levels significantly decreased. At the 15-day follow-up, jaundice had resolved and laboratory values normalized (Table 1).

Autoimmune markers (ANA, ANCA) and IgG4 levels were negative, supporting the diagnosis of chemotherapy-induced SSC.

Magnetic resonance cholangiopancreatography was performed on 19 December 2025 during the evaluation of jaundice and cholestatic liver enzyme elevation after the fifth cycle of chemotherapy. Although image quality was limited by motion artifacts, the findings were reviewed in conjunction with CT imaging and discussed with radiology specialists. No radiological evidence of hepatic metastasis or malignant biliary obstruction was identified. Furthermore, tumor markers remained stable during follow-up. Considering the temporal relationship with chemotherapy exposure, the absence of obstructive malignant findings, negative autoimmune markers, lack of inflammatory bowel disease history, and atypical demographic characteristics for PSC, chemotherapy-induced SSC was considered the most likely diagnosis.

Discussion

SSC is a rare but clinically important condition that can closely mimic PSC in both clinical and radiological features. Differentiating SSC from PSC is essential, as their etiologies, management strategies, and prognoses differ significantly. PSC is typically a chronic, progressive disease frequently associated with inflammatory bowel disease, whereas SSC results from an identifiable insult and may demonstrate reversibility if the underlying cause is addressed [1, 2].

In the present case, the development of cholestatic liver injury following FLOT-based chemotherapy is particularly notable. The absence of autoimmune markers, including ANA, ANCA, and IgG4, along with the lack of inflammatory bowel disease and normal pre-chemotherapy imaging strongly supports a diagnosis of SSC rather than PSC.

Chemotherapy-associated hepatobiliary injury has increasingly been recognized, particularly with oxaliplatin- and fluoropyrimidine-based regimens. Proposed mechanisms include direct toxicity to biliary epithelial cells, sinusoidal endothelial injury, and microvascular ischemia, which collectively may lead to bile duct strictures and cholangiopathy [3–5].

Radiologically, the presence of multifocal intrahepatic strictures with a ‘beaded’ appearance can strongly suggest PSC; however, this finding is not pathognomonic and must be interpreted in the appropriate clinical context. In patients with recent chemotherapy exposure, SSC should be considered as a key differential diagnosis.

Another important aspect of this case is the management strategy. ERCP was not feasible due to altered anatomy. In such cases, PTC provides both diagnostic and therapeutic benefit. In our patient, PTC enabled effective biliary drainage, resulting in rapid biochemical and clinical improvement, which is consistent with previously reported outcomes in SSC [2, 5].

The favorable response to biliary drainage further supports SSC, as PSC typically does not demonstrate such reversibility. This highlights the importance of early recognition and timely intervention to prevent irreversible liver damage.

To our knowledge, this case represents a rare presentation of chemotherapy-induced SSC mimicking PSC following FLOT-based therapy.

Conclusion

Chemotherapy-induced SSC is a rare but important differential diagnosis in patients presenting with cholestatic liver injury following chemotherapy. This case underscores the importance of considering drug-induced biliary injury, particularly in patients receiving oxaliplatin-based regimens. Early diagnosis and appropriate biliary drainage can result in significant clinical improvement and may prevent irreversible liver damage.

Author contributions

N.D. managed the case and wrote the manuscript. K.Ç. supervised and critically revised the manuscript.

Conflicts of interest

The authors declare no conflict of interest.

Funding

No funding was received for this study.

Patient consent

Written informed consent was obtained from the patient for publication.

References