Refractory Hepatocellular Carcinoma in a Patient with CVID

We report the case of a 47-year-old female with common variable immunodeficiency (CVID) who developed refractory and fatal hepatocellular carcinoma (HCC). She was diagnosed with CVID at age 32 and maintained on subcutaneous IgG replacement. Her medical history was complicated with chronic giardia-induced enteropathy and chronic atrophic gastritis leading to gastric cancer at age 42, for which she underwent a distal gastrectomy. A commercial genetic panel test for inborn errors of immunity involving 207 genes was not diagnostic at the time of her initial CVID diagnosis. Attempts for whole-exome sequencing were unsuccessful due to insurance limitations. At age 47, she presented with a suspected liver hematoma bleed, which was managed by embolization. Subsequent imaging revealed a liver mass, confirmed as HCC via biopsy. Histological analysis ruled out metastasis from her previous gastric cancer. She had no history of elevated liver functions tests, negative testing for hepatitis B and C, and no evidence of nodular regenerative hyperplasia. She received immunotherapy with druvalumab and tremelimumab followed by Y-90 radio embolization. She did not respond well; lenvatinib was trialed, but she developed malignant ascites, hepatic encephalopathy, and passed away at the age of 48. HCC in the context of CVID has been reported only once before, in a 50-year-old male with no previously known liver disease and no hepatitis. He also experienced rapid progression and death. This case highlights the aggressive nature of HCC in patients with CVID and underscores the need for further research to understand the underlying mechanisms and develop effective treatments.