What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis of Liver
• Amyloidosis-Associated Liver Disease
• Liver Amyloidosis

What is Hepatic Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ, or may occur throughout the body. The deposition of amyloid proteins in the liver leads to Hepatic Amyloidosis, which may result in enlarged liver and abdominal discomfort
• There are 5 major types of amyloidosis, which can lead to Liver Amyloidosis:
  • AL amyloidosis that occurs when bone marrow produces too much amyloid protein, creating light (L) chains
  • AA amyloidosis, when amyloid proteins build up secondary to a chronic disease
  • Hereditary amyloidosis: It is an inherited form of the disease; the amyloid build-up primarily affects the kidneys and nerves
  • Wild-type ATTR amyloidosis: This form leads to amyloid protein deposits in elderly adults, particularly in the heart and tendons
  • Dialysis-related amyloidosis: This occurs in individuals who have undergone dialysis for a long time. The amyloid protein tends to get deposited in the tendons and joints
• Hepatic Amyloidosis is more common in AA- and AL- amyloidosis. However, heritable mutations in certain genes, such as ApoA1, LYZ and B2M (which are causative genes for inherited type of amyloidosis) may very rarely lead to Hepatic Amyloidosis as well
• The signs and symptoms depend on the type of amyloidosis the affected individual is observed with. Hepatic Amyloidosis occurs in older adults; men are more susceptible to the condition than women
• The treatment involves an effective management of amyloidosis and the underlying condition causing it. The outcome of Hepatic Amyloidosis depends on the underlying condition causing it, the severity of liver symptoms, and the response of the individual to treatment

Who gets Hepatic Amyloidosis? (Age and Sex Distribution)

• The overall prevalence of Hepatic Amyloidosis is not clearly known. It occurs primarily in AA and AL subtypes of amyloidosis. In AL amyloidosis, approximately 15% of the affected individuals exhibit Amyloidosis-Associated Liver Disease
• Some individuals with the inherited form of amyloidosis may rarely develop this liver condition
• Hepatic Amyloidosis is more frequent in older adults and may occur worldwide. Typically, men are more susceptible to the condition than women

What are the Risk Factors for Hepatic Amyloidosis? (Predisposing Factors)

The following are some known risk factors for developing Hepatic Amyloidosis:

• Advancing age
• Male gender
• A family history of amyloidosis, specifically involving mutation(s) in the ApoA1, LYZ and B2M genes
• Any condition that affects the antibody-producing cells in the body, including benign monoclonal gammopathy, malignant lymphoma, and multiple myeloma
• Chronic infections or inflammatory disease, including rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, and tuberculosis
• Long-term kidney dialysis
• Chronic inflammatory conditions such as:
  • Arthritis, including rheumatoid arthritis, juvenile inflammatory arthritis, psoriatic arthritis and ankylosing spondylitis
  • Inflammatory bowel disease (IBD) such as ulcerative colitis
• Chronic infections that include:
  • Tuberculosis
  • Leprosy
  • Bronchiectasis
  • Osteomyelitis
  • Skin infections (especially in drug abusers, who use needles to inject themselves)
  • Chronic infection in skin with burns
  • Chronic kidney infections (pyelonephritis)
  • Whipple’s disease
• Poorly-controlled diabetes
• Infectious diseases such as HIV/AIDS
• Cystic fibrosis; individuals with this condition are prone to repeat infections
• Certain cancers such as Hodgkin’s lymphoma and renal cell carcinoma
• Family history of certain hereditary disorders that may include:
  • Familial Mediterranean fever (FMF)
  • Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
  • Hyperimmunoglobulin D syndrome and periodic fever syndrome (HIDS)
  • Cryopyrin-associated periodic syndrome (CAPS)
  • Majeed syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hepatic Amyloidosis? (Etiology)

• Hepatic Amyloidosis is caused primarily due to AA- and AL- subtypes of amyloidosis. And, occasionally due to the inherited form of amyloidosis (mutations in the ApoA1, LYZ, and B2M genes are responsible)
• Irrespective of the subtype of amyloidosis, abnormal proteins are generated that undergo misfolding to form amyloid proteins. The amyloid protein fibrils circulate in the bloodstream and get deposited in the liver
• However, clinically significant manifestation of symptoms is rare in Hepatic Amyloidosis

What are the Signs and Symptoms of Hepatic Amyloidosis?

The signs and symptoms of Hepatic Amyloidosis may vary among affected individuals in severity. Some individuals may have amyloid deposits in their liver without any adverse effect on the organ, and others may exhibit clinically significant symptoms.

The following are some signs and symptoms reported for Hepatic Amyloidosis:

• Enlarged liver (hepatomegaly)
• Enlarged spleen (splenomegaly)
• Upper abdominal pain; abdominal swelling
• Possible changes in the levels and function of liver enzymes

Since Hepatic Amyloidosis does not occur in isolation but as part of systemic Amyloidosis, additional signs and symptoms may be present that may include:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Skin rashes, which may be purple or red spots
• Rash around eyes
• Eyes that appear puffy
• Tingling sensation and numbness
• Anemia
• Clay-colored stools
• Carpal tunnel syndrome (resulting in weak grip)
• Bleeding disorders; problems with proper clotting of blood

How is Hepatic Amyloidosis Diagnosed?

The diagnosis of Hepatic Amyloidosis may include general tests to ascertain the subtype of amyloidosis (and its underlying cause), as well as specific tests to assess damage to the structure and function of liver.

The following methods may be used to diagnose Amyloidosis of Liver:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests to assess:
  • Complete blood count (CBC)
  • Perform “Freelite assay”, a measurement of light chain immunoglobulins
  • Measure immunoglobulin by immunofixation electrophoresis
  • Assess liver function by measuring liver enzymes
• Urine tests to check for presence of bilirubin, which may be indicative of abnormal liver function
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Tissue biopsy: A biopsy of an affected organ or tissue (in this case, the liver) is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In Hepatic Amyloidosis, 
  • Immunohistochemical analysis of tissue samples using anti-AA serum may be performed, to identify the type of amyloidosis an individual has
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
• Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains
• Molecular genetic testing to check for mutation(s) in genes known to cause various types of amyloidosis
• Molecular testing to check the type of proteins in amyloid deposits through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hepatic Amyloidosis?

The potential complications of Hepatic Amyloidosis include:

• Portal vein hypertension
• Liver failure
• Spontaneous liver rupture

How is Hepatic Amyloidosis Treated?

The following are some treatment options for Hepatic Amyloidosis, where symptoms are present:

• A combination of boretezomib and dexamethasone
• Rarely, liver transplantation may be necessary in severe cases, where liver function is compromised

Hepatic Amyloidosis generally does not occur in isolation, and is associated with involvement of many other organs in systemic AA- and AL- type of amyloidosis. Therefore, additional treatments pertaining to these subtypes and their underlying cause are often necessary.

How can Hepatic Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Hepatic Amyloidosis
• Seeking prompt medical attention for pre-existing conditions that can lead to amyloidosis, which consequently causes Liver Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Hepatic Amyloidosis? (Outcomes/Resolutions)

• The prognosis for Hepatic Amyloidosis may be determined by a number of factors, such as the extent of disease, overall health of the affected individual, and his/her response to treatment
• In general, Hepatic Amyloidosis is a rare condition and many individuals with amyloid deposition in the liver are not known to exhibit any significant symptoms
• However, if severe symptoms are noted that are indicative of liver malfunction or damage, immediate treatment is necessary. If left untreated, liver failure may occur that may even necessitate a liver transplantation

Additional and Relevant Useful information for Hepatic Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum