Researchers reported a rare case of a noncirrhotic patient with Alagille syndrome (ALGS) who later developed hepatocellular carcinoma (HCC), according to a letter to the editor in Medicina Clinica.

ALGS is a rare hereditary disorder that is usually diagnosed in childhood. The development of cirrhosis and HCC in a patient with ALGS is uncommon.

A 47-year-old man was diagnosed with ALGS at 12 years of age after displaying signs that fit the clinical criteria of the disease, such as pulmonary artery stenosis, arteriohepatic dysplasia, “butterfly” vertebrae, and chronic cholestasis. As the disease progressed, an increase in cholestasis was observed with the following liver function test results:

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  • Gamma-glutamyl transferase: 2738 U/L
  • Alkaline phosphatase: 186 U/L 
  • Total bilirubin: 1.26 mg/dL 
  • Alpha-fetoprotein (AFP): 200 ng/mL 

Read more about ALGS prognosis

The patient’s physicians spotted a 16 mm nonspecific lesion on segment 2 of the liver upon dynamic magnetic resonance imaging, which was classified as a hepatic hemangioma. Six months later, the lesion grew to 80 mm in size. A computerized tomography (CT) scan revealed it to have a heterogeneous appearance and a percutaneous ultrasound-guided biopsy was performed, which revealed evidence of fibrosis and ductopenia without cytological atypia.

“Given the growth, the radiological characteristics of the lesion and the increase in AFP, a left hepatic lobectomy was decided,” the researchers wrote. Histological studies revealed a well-differentiated HCC on a noncirrhotic liver with marked ductopenia. There was neither evidence of the involvement of the surgical margins, nor vascular or capsular infiltration.

Four months later, an abdominal CT scan revealed several peritoneal implants with no signs of hepatic tumor recurrence. The patient’s physicians decided to exclude the patient from the liver transplant waiting list and instead started on sorafenib 800 mg/day. 

The patient’s AFP managed to drop from 6000 ng/mL to 690 ng/mL within the first 2 months. However, there was still evidence of tumor progression on imaging studies and subsequent follow-up revealed a new rise in AFP. The patient died from respiratory infection 5 months after treatment.

“We report the exceptional case of a patient with [ALGS] who developed HCC in a non-cirrhotic liver, with development of peritoneal metastases after tumour resection and who was treated with sorafenib as an off-label indication, without clear benefit,” the authors concluded.


Vázquez Rodríguez JA, Molina Villalba C, Estévez Escobar M. Alagille syndrome and hepatocellular carcinoma in a non-cirrhotic adultMed Clin (Barc). 2021;21:00358-4. doi:10.1016/j.medcli.2021.06.010