BackgroundCommon variable Immunodeficiency (CVID) is a primary immunodeficiency disorder and the most common form of severe antibody deficiency. Both children and adults are affected and clinical manifestations vary widely. Often, CVID manifests with infections, autoimmune phenomena or chronic lung disease, but it also frequently affects the liver. The differential diagnoses of hepatopathies in CVID patients are diverse and the characteristics of CVID patients often make it difficult to determine the correct diagnosis.Case presentationWe present the case of a 39-year-old patient with CVID and elevated liver enzymes, nausea and unintended weight loss, who was referred to our clinic with the suspected diagnose of autoimmune hepatitis or immunoglobulin-induced hepatopathy. Prior, the patient had undergone an extensive diagnostic work-up including liver biopsy but viral hepatitides had only been investigated serologically – with negative antibody results. We searched for viral nucleic acid by polymerase chain reaction and detected hepatitis E virus-RNA. Antiviral therapy was started and the patient recovered quickly.ConclusionHepatopathies in CVID patients are common with a broad spectrum of possible causes. While treating CVID patients, the distinct diagnostic and therapeutic requirements of the CVID patients should be closely considered and diagnosed by the appropriate measures.