|Year : 2021 | Volume
| Issue : 4 | Page : 459-462
Hepatic amyloidosis: A rare entity
Charusheela R Gore, Namrata Patro, Banyameen Iqbal, Tushar Kambale
Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India
|Date of Submission||15-Feb-2020|
|Date of Decision||15-Feb-2020|
|Date of Acceptance||07-Jul-2020|
|Date of Web Publication||17-Jun-2021|
E-406, Mahindra Royale Co. Housing Society, Kharalwadi, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Hepatic amyloidosis is a unique and uncommon disease which shows its presentation in the form of an infiltrative disease involving the liver. Amyloidosis is a systemic disease entity which is characterized by deposition of amyloid protein in the extracellular tissues of multiple organs. A 45-year-old female was admitted with complaints of yellowish discoloration of sclera and decreased appetite since 1 month. Liver enzymes were raised with a significantly high serum alkaline phosphatase. Microscopy showed linear sinusoidal deposition of an amorphous eosinophilic material which was also causing atrophy of liver cell plates. The portal tracts as well showed similar eosinophilic deposits. There was no significant lobular or portal inflammation. The material was found to be congophilic on congo red stain and it also showed apple green birefringence on polarizing microscopy. A diagnosis of hepatic amyloidosis was made. Amyloidosis of the liver is a rare disease entity that often presents with vague, nonspecific findings and has a poor prognosis. Prompt diagnosis and management are required to improve outcomes for this patient population. Further investigation and research are needed to elucidate the risks and effectiveness of hepatic amyloidosis treatment regimens. Liver involvement of amyloidosis presents with nonspecific clinical symptoms such as weight loss and fatigue. The prompt diagnosis is however very critical as liver-biopsy-proven amyloidosis has a poor prognosis as the median survival is only 8.5 months. Progressive organ involvement most often leads to organ malfunction and subsequently death due to renal and/or cardiac involvement.
Keywords: Amyloidosis, congo red, hepatic amyloidosis
|How to cite this article:|
Gore CR, Patro N, Iqbal B, Kambale T. Hepatic amyloidosis: A rare entity. Med J DY Patil Vidyapeeth 2021;14:459-62
| Introduction|| |
Hepatic amyloidosis is a unique and uncommon disease which shows its presentation in the form of an infiltrative disease involving the liver. Amyloidosis is a systemic disease entity which is characterized by deposition of amyloid protein extracellularly in multiple organs.,,, These proteins are insoluble, fibril-forming proteins and their deposition in excess may lead to end-organ dysfunction., The most common type of amyloidosis is systemic light chain amyloidosis (AL) type. It results from plasma cell dyscrasias producing abnormal amounts of immunoglobulin (Ig) light chains. These get deposited in organs such as the heart, kidney, peripheral nerves, and liver. Liver involvement presents with nonspecific clinical symptoms such as weight loss and fatigue. Prompt diagnosis is however very critical as liver-biopsy-proven amyloidosis has a poor prognosis as the median survival is only 8.5 months. Progressive organ involvement most often leads to organ malfunction and subsequently death due to renal and/or cardiac involvement. The wide range of presenting symptoms in cases of hepatic amyloidosis makes rapid clinical diagnosis quite difficult. None of the known present imaging techniques today is capable of specifically demonstrating the presence of amyloid. Even when suspected clinically and radiologically, the diagnosis depends solely on a tissue biopsy for the confirmation of the presence of amyloid deposits.
| Case Report|| |
A 45-year-old female was admitted with complaints of yellowish discoloration of sclera and decreased appetite since 1 month. She also had a history of right hypochondriac fullness since 15 days. She presented with physical examination findings which included icterus, hepatomegaly and pitting edema. There was no significant past or family history.
The laboratory findings showed leukocyte count of 16,000/mm3 with 60% lymphocytosis, hemoglobin level of 8.3 g/dL and platelet count of 520,000/mm3. Biochemical tests showed that the serum level of alanine aminotransferase was 26 IU/L, aspartate aminotransferase (AST) was 64 IU/L, and alkaline phosphatase elevated up to 2217 IU/L. The patient had direct hyperbilirubinemia with a total bilirubin level of 4.21 mg/dL and direct bilirubin being 4.09 mg/dL. Creatinine was 1.21 mg/dL. Prothrombin time international normalized ratio was 1.8. triglycerides, cholestrol, low-density lipoprotein were elevated with maximum increase in the level of serum cholestrol level being 726 mg/dL. Alpha fetoprotein was within normal limits. Antimitochondrial antibody was also negative. The results for hepatitis B surface antigen (HBs) and anti-HBs were negative thus viral hepatitis, primary biliary cirrhosis and autoimmune hepatitis were ruled out. Total proteins, albumin, globulin, A: G ratio were within normal limits. Ascitic fluid showed a transudative picture. On abdominal ultrasonography liver showed diffuse coarse echo and hypoechoic pattern with hepatomegaly. Contrast-enhanced computed tomography additionally showed hepatic vein thrombosis. Two-dimensional (2D) echo showed a thickened anterior mitral valve. Liver biopsy was performed for a definitive diagnosis.
We received adequate liver biopsy strands which were processed and stained. The H and E stained sections showed linear sinusoidal deposition of an amorphous eosinophilic material which was causing significant atrophy of hepatocytes [Figure 1]a and [Figure 1]b. The portal tracts also showed similar extracellular eosinophilic deposits. There was no significant lobular or portal inflammation. Amyloidosis was suspected and the biopsy was subjected to other stains. The material was found to be congophilic on congo red stain and it also showed apple green birefringence on polarizing microscopy [Figure 2]a and [Figure 2]b. The material was variably positive for periodic acid-Schiff. It stained positive with toluidine blue and Masson's trichrome [Figure 3]a, [Figure 3]b, [Figure 3]c. A diagnosis of massive hepatic amyloidosis was made. The patient unfortunately succumbed before the diagnosis. The cause of death was speculated to be either liver cell failure or cardiac failure to the probable involvement of the cardiac valves by amyloidosis as evident on 2D echo.
|Figure 1: (a and b) Amyloid deposits in liver parenchyma (H and E, ×100, ×400)|
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|Figure 2: (a and b) Congo red staining × 100, apple green birefringence on polarized microscopy|
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| Discussion|| |
Amyloidosis is a well-known multisystemic disease which is diffusely infiltrating in nature. This is due to deposition of fibrils of protein-mucopolysaccharide complexes. The type of protein getting deposited defines the subgroup of amyloid. In cases of primary amyloidosis, light chain Ig (AL) is deposited. Therefore, primary amyloidosis is associated with multiple myeloma, lymphoplasmacytic lymphoma, and Waldenstrom macroglobulinemia. Bone marrow biopsy is mandatory for all patients diagnosed with AL amyloidosis to exclude a cause of overt multiple myeloma. We could not evaluate the bone marrow picture of our patient as she succumbed before the biopsy report could be given. In primary AL amyloidosis, there is presence of light chain Ig in the patient's serum without the associated heavy chain. It is more common than those accompanying an Ig M heavy chain which was found in about 4.4% cases.
Secondary amyloidosis (AA type), shows evidence of protein deposition secondary to inflammation. Thus, secondary amyloidosis occurs in patient's suffering from chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, bronchiectasis, tuberculosis, and chronic osteomyelitis.
There is a third subtype, known as hereditary or senile type of amyloid (ATTR) which occurs due to mutant and wild type of transthyretin. In cases of localized or organ-limited type, amyloid material is found to be confined to an organ, most commonly the respiratory tract, urinary tract, skin, and liver. Localized amyloidosis is known to be usually a primary (AL type) and it rarely presents as a secondary type (AA type). Localized amyloidosis is diagnosed mainly by excluding other systemic involvement. In systemic or secondary amyloidosis, abnormal proteins get deposited in multiple organs, most commonly the gastrointestinal tract with colon being more frequently involved; other tissues which may show involvement are myocardium, striated muscle, and adipose tissue. The mitral valves were thickened in our patient which could have been due to cardiac amyloidosis.
Amyloidosis is typically observed as a systemic form although 10%–20% may be localized. Systemic amyloidosis is a progressive and fatal condition with death usually occurring as a result of renal or heart failure. The management of localized amyloidosis is usually supportive and it does not require any systemic therapy. Due to the varying therapeutic and prognostic implications, distinction between the primary and secondary type of amyloidosis becomes clinically vital.
In hepatic amyloidosis, amyloid gets deposited in the hepatic parenchyma, usually within the space of Disse along the sinusoids and/or along the blood vessel walls. Hepatocytes get severely compressed by the accumulating amyloid material. This results in atrophy or near disappearance of the hepatocytes. In advanced cases of amyloid infiltration, there occurs hepatomegaly with liver showing rubbery elastic consistency and may progress to a show “lardaceous liver” appearance over the cut surface. Hepatic involvement in amyloidosis is a common feature, although with mild clinical manifestations. Hepatomegaly with borderline abnormal liver function tests (LFTs) is a more frequent finding which is seen with hepatic amyloidosis. Symptomatic presentations occur due to hepatic failure, portal hypertension, and very rarely due to organ rupture.
There has been reports suggesting the fact that 77% of hepatic amyloidosis is associated with nephrotic syndrome, congestive heart failure, peripheral neuropathy, or orthostatic hypotension. Other signs of hepatic amyloidosis may include proteinuria (88%), elevated serum alkaline phosphatase (ALP) (86%), abnormal serum protein electrophoresis (64%), hyposplenism on peripheral blood smear defined by the presence of Howell–Jolly bodies (62%), hepatomegaly disproportionate to abnormal liver enzymes (81%). Serum ALP was significantly high in our patient as well. LFTs are not sensitive or specific, with a normal level of bilirubin and AST seen in 32% of cases. The median survival of patients with hepatic amyloidosis was 9 months.,
Definitive diagnosis undoubtedly requires histopathological evaluation as diagnostic imaging findings are nonspecific. Histologically, amyloid is recognized as a homogeneous extracellular material displaying apple green birefringence after positive Congo red staining. It shows aggregation of approximately 10 nm wide fibrils on electron microscopy, exhibits a beta-pleated sheet configuration on radiographic analysis and show resistance to proteases other than pronase.
| Conclusion|| |
Amyloidosis of the liver is a rare disease entity that often presents with vague, nonspecific findings and has a poor prognosis. Prompt diagnosis and management are required to improve outcomes for this patient population. Further investigation and research are needed to elucidate the risks and effectiveness of hepatic amyloidosis treatment regimens.
Liver transplant could play a role. We would like to conclude that one should suspect this condition if all other causes of hepatomegaly and deranged LFTs are ruled out.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]