Metastatic Hepatocellular Carcinoma in a Patient with Crohn’s Disease Treated with Azathioprine and Infliximab: A Case Report and Literature Review

Abstract

Hepatocellular carcinoma most commonly occurs in patients with underlying liver disease or cirrhosis. We describe a case of hepatocellular carcinoma in a 34-year-old man with Crohn's disease treated with azathioprine and infliximab. The patient had no history of liver disease and a complete autoimmune and viral workup was unremarkable. Unfortunately, the patient developed widespread metastatic disease and passed away 5 months after his initial diagnosis. The mechanism of hepatocellular carcinoma in patients' with Crohn's disease is poorly understood and may include both autoimmunity and treatment-related complications. Previous case reports suggest the possibility of a concerning association between azathioprine therapy and the development of hepatocellular carcinoma in patients with Crohn's disease. Clinicians may consider early imaging in patients with Crohn's disease presenting with concerning symptomatology or abnormal liver enzymes, especially in those being treated with azathioprine alone or in combination with infliximab. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population.

Hepatocellular Carcinoma in a Patient With Crohn’s Disease

“…This case presents important clinical issues that HCC can occur in patients with CD, even without underlying liver diseases for HCC. The occurrence of HCC among patients with CD is extremely rare, with only 15 cases, including our case, published as case reports in the literature [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

“…This report represents only the twelfth case of HCC in a patient with CD [ 4 , 5 ]. Azathioprine therapy has been reported in 9 of the previous 11 cases and has been proposed as a potential trigger in the occurrence of HCC [ 5 ].…”

“…This report represents only the twelfth case of HCC in a patient with CD [ 4 , 5 ]. Azathioprine therapy has been reported in 9 of the previous 11 cases and has been proposed as a potential trigger in the occurrence of HCC [ 5 ]. It is important to note that azathioprine has never been directly linked to the development of HCC in several large-scale studies [ 7 , 8 ].…”

“…Inflammatory bowel disease, though associated with certain hepatobiliary conditions including steatosis, drug-induced hepatitis, cholelithiasis, primary sclerosing cholangitis and portal vein thrombosis [ 3 ], as well as with certain malignancies such as lymphoma and colon cancer, has never been directly associated with HCC. Over the past few years, however, a number of cases have emerged in the literature reporting HCC in patients with Crohn's disease (CD) in the absence of cirrhosis [ 4 , 5 ], particularly in those treated with azathioprine [ 5 ]. Though azathioprine, which is commonly used in the treatment of CD, has never been conclusively linked to HCC, adverse events attributed to this immunosuppressant agent include hepatotoxicity and increased incidence of lymphoma.…”

Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease

“…In some of these patients, there was a decrease or disappearance of autoantibodies with no need of further treatment which suggests an immune-mediated DILI rather than a drug-induced AIH[ 89 , 91 , 92 , 94 ]. Of note, there are also cases of malignancies described in patients treated with anti-TNF agents, notably case reports of hepatocellular carcinoma in non-cirrhotic patients[ 114 - 116 ] and of hepatosplenic T cell lymphoma[ 117 - 121 ]. All these patients were in combination treatment with an anti-TNF and a thiopurine, making it difficult to establish the specific role of the anti-TNF agent.…”