Introduction: Hepatobiliary disease is a common complication in primary hypogammaglobulinemia. In Bruton’s X-linked Agammaglobulinemia (BtAg), hepatitis virus infections acquired via intravenous immunoglobulin (IVIg) have been associated with the development of liver disease that may require liver transplantation. Hepatic veno-occlusive disease (VOD) is most commonly seen in association with patients following bone marrow transplantation but is also described in the setting of toxins, chemotherapeutic agents, radiation therapy, and metabolic disorders. We report an interesting case of progressive cirrhosis in a patient with BtAg who following liver transplantation was found to have VOD in the explanted liver. Methods: A 14 year old male with a history of BtAg was transferred to The Children’s Hospital in Denver, Colorado for evaluation of a two month history of cirrhosis, portal hypertension, and progressive ascites. BtAg was diagnosed in infancy and had been managed with monthly IVIg infusions. Two months prior to his transfer, he developed nausea, vomiting, fatigue and intermittent fevers. He was noted to have mildly elevated AST and ALT, and his clinical picture progressed to include jaundice and ascites. Protime was 25.4 seconds with an INR of 2.75. He underwent an extensive evaluation which included negative PCR testing for viral infections including hepatitis A, B, C, and E, EBV, CMV, parvovirus, enterovirus and adenovirus as well as negative metabolic and anatomic evaluations. Blood for human herpes virus 7 (HHV7) PCR was positive. Despite aggressive management, he developed intractable ascites and liver failure and underwent liver transplantation. Results: Evaluation of the explanted liver revealed advanced veno-occlusive lesions, including sinusoidal congestion, intimal fibroplasia, obliteration and recanalization of central venous lumina, and hepatocyte necrosis. There was an absence of giant cells, but portal inflammation and fibrosis were present, suggesting a possible infectious etiology. The patient is doing well fourteen months after liver transplantation on cyclosporin-based immunosuppression. Conclusion: This case demonstrates an interesting presentation in a boy with BtAg of subacute liver failure caused by hepatic VOD with HHV7 PCR positivity. Presumably the HHV7 was acquired through IVIg infusions. This unique case extends the spectrum of hepatic VOD and raises the possibility that HHV7 could be a hepatic pathogen in immunocompromised children.