Multiple immunosuppressants for immune-related acholia in a patient with metastatic colorectal cancer

Abstract

Immunotherapy-related adverse events (irAEs) such as hepatitis or cholestasis have been well recognized. In contrast, acholia was not previously reported as an irAE with a lack of standard treatment. We presented a case of a 68-year-old man with metastatic colon cancer that progressed after several chemotherapy sessions with targeted agents. He received nivolumab plus regorafenib (REGONIVO) as salvage treatment. However, he reported clay-colored stools and jaundice after 3 months of REGONIVO treatment. Computed tomography (CT) revealed no significant biliary tract dilation. Laboratory tests ruled out viral hepatitis or autoimmune hepatitis. Endoscopic retrograde cholangiopancreatography showed multiple filling defects of blood clot formation, and endoscopic retrograde biliary drainage was ineffective. An irAE presenting as acholia and hyperbilirubinemia was diagnosed. Subsequently, the patient was initially administered a corticosteroid only, with an equivalent dose of prednisone (1 mg/kg/day); however, this treatment had only limited effect. After the addition of multiple immunosuppressants, including mycophenolate mofetil and tacrolimus, the severity of hyperbilirubinemia declined and acholia was resolved. This case demonstrated that irAEs can present as acholia and hyperbilirubinemia without significant biliary obstruction. Although the mechanism of such an unusual irAE remains unclear, it seems to be refractory to corticosteroid treatment alone. A more aggressive strategy, such as multiple immunosuppressants, may be advisable.