Melvin Lau, MD Series Editor: Richard W. Goodgame, MD


April 09, 2008


The liver can be involved in many systemic diseases, including infectious, neoplastic, immunologic, metabolic, and vascular diseases.[4] Amyloidosis encompasses a group of systemic diseases caused by deposition of extracellular proteins that are rendered relatively insoluble and undigestable by misfolding.[13,15] The misfolding causes self-aggregation and fibril formation. The source of the precursor proteins can be chronic inflammatory diseases (AA "secondary" amyloidosis), plasma cell disorders (AL "primary" amyloidosis), or an array of inherited genetic defects in isolated proteins.[15] AL "primary" amyloidosis is the most common type of amyloidosis, having a similar frequency as Hodgkin's lymphoma or chronic myelogenous leukemia.[13] The precursor protein is a fragment of an Ig light chain produced by a clonal population of plasma cells in the bone marrow. AL amyloidosis frequently involves the liver, but clinical liver disease is uncommon. However, in some patients with AL amyloidosis, there is massive involvement of the liver. This condition has been called "primary hepatic amyloidosis."[7,8,9,16] This disease has a characteristic collection of symptoms, signs, and laboratory features. It is well represented by our patient. Unfortunately, it is associated with diffuse organ involvement and very short survival.

Patients with primary hepatic amyloidosis typically complain of involuntary weight loss, fatigue, abdominal pain, edema, and anorexia.[7,8,9,16] On examination, 1 series reported hepatomegaly in 81% of patients, followed by ascites (42%), purpura (15%), splenomegaly (10%), and spider angiomata (7%).[16] Primary hepatic amyloidosis is frequently associated with syndromes common in AL amyloidosis: nephrotic syndrome, congestive heart failure, peripheral neuropathy, orthostatic hypotension, and carpal tunnel syndrome.[13,16] The most frequently abnormal laboratory value in primary hepatic amyloidosis is an elevated serum alkaline phosphatase. More than half of the patients have values > 500 U/L.[7,8,9,16] Although serum creatinine is typically normal, there is marked proteinuria.[16] The severe cholestatic disease is associated with liver biopsy findings similar to our patient's: massive nodular deposition of amyloid in the portal tracts (Figure 4).

Amyloid deposition is not evident on CT scans or ultrasound examination. Diagnosis of AL amyloidosis relies on pathologic demonstration of amyloid in the tissues and evidence of plasma cell dyscrasia by one of the following: clonal plasma cells in the bone marrow; monoclonal light chain in the serum or urine; or positive free-light-chain assay in the serum.[13] Most patients with AL amyloidosis die within 1 year, usually of cardiac or renal disease.[7] Liver disease is rarely the cause of death. Until recently, 5-year and 10-year survival rates for patients with hepatic amyloidosis were 13% and 1%, with a median survival of 9 months.[16] Newer treatment regimens rely on high-dose melphalan and stem-cell transplantation. [13,17,18] Skinner and colleagues[18] enrolled 701 patients with primary amyloidosis in an 8-year longitudinal analysis; 312 underwent high-dose melphalan treatment and stem-cell transplantation. Forty percent achieved remission in 1 year, and median survival was 4.6 years. Sanchorawala and colleagues[17] showed that the 10-year survival of selected patients with primary amyloidosis who were treated with melphalan and stem-cell transplantation was 23%.[17]


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