Hepatosplenomegaly — a condition where both the liver and spleen are enlarged — is an early and the most common symptom of Gaucher disease. An enlarged spleen is observed in more than 90% of patients and is often the first sign of the disease. In some cases, spleen size may be as much as 15 times larger than normal. This enlargement generally causes abdominal distension and pain. An enlarged liver is seen in 60%–80% of Gaucher disease patients.

Causes of hepatosplenomegaly

Hepatosplenomegaly occurs when Gaucher cells accumulate in the liver and spleen, resulting in an abnormal increase in their size. Gaucher cells contain large amounts of glucocerebroside, a complex lipid molecule that accumulates inside cells due to the beta-glucocerebrosidase enzyme not functioning properly in Gaucher disease patients.

Gaucher cells are predominantly immune cells called macrophages because they engulf and ingest old red and white blood cells, which are sources for large amounts of glucocerebroside.

Management of hepatosplenomegaly

Several treatments for Gaucher disease to help manage hepatosplenomegaly are summarized below.

Enzyme replacement therapy

The most effective treatment that decreases the size of the liver and spleen in Gaucher disease patients is enzyme replacement therapy (ERT). Such therapies approved by the U.S. Food and Drug Administration (FDA) include Cerezyme (imiglucerase), Elelyso (taliglucerase alfa), and VPRIV (velaglucerase alfa). When infused into a patient, the recombinant beta-glucocerebrosidase enzyme enters the patient’s cells and metabolizes glucocerebroside. ERT thus helps to alleviate disease symptoms, including hepatosplenomegaly.

Substrate reduction therapy

When enzyme replacement therapy is ineffective, substrate reduction therapy can be used. These small molecule inhibitors reduce the production of the substrate of the faulty enzyme, glucocerebroside, thus alleviating disease symptoms including hepatosplenomegaly. FDA-approved substrate reduction therapeutics include Cerdelga (eliglustat) and Zavesca (miglustat).


Before the development of ERT, splenectomy or the surgical removal of the spleen was the main treatment for splenomegaly and severe hypersplenism (overactive spleen). However, splenectomy is now rarely performed in Gaucher disease patients because it may lead to substantial worsening of the disease in other organs. The operation is only performed if patients have severe cytopenia (reduction in the number of mature blood cells) due to splenomegaly and are not responding to ERT.

Liver transplant

A liver transplant can be performed to treat Gaucher disease patients who have complications caused by an enlarged liver such as portal hypertension, where blood flow through the portal vein (the blood vessel that carries blood to the liver) is obstructed because of massive infiltration of Gaucher cells.


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