Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and histoplasmosis or it can be the sign of a serious and life-threatening lysosomal storage disease. Systemic venous hypertension can also increase the risk for developing hepatosplenomegaly, which may be seen in those patients with right-sided heart failure.

Are the following:^{[citation needed]}

• Lipoproteinlipase deficiency
• Multiple sulfatase deficiency
• Osteopetrosis
• Adult-onset Still's disease (AOSD)