Hepatomegaly, can you accurately diagnose this rare cause?

One case
of hepatomegaly due to a rare cause was reported here.

Hepatomegaly is a common clinical sign with many
causes.
Moderate hepatoma is mostly seen in viral hepatitis, chronic liver disease (all causes), chronic hepatitis, cirrhosis, common bile duct stones, extrahepatic bile duct obstruction and other liver diseases
.
Marked hepatitomegaly (> 10 cm below the costal margin) is rarely seen and includes: (1) primary and metastatic liver tumors, including lymphoma; (2) Alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis); (3) severe congestive heart failure; (4) Liver infiltrative diseases, such as amyloidosis, myelofibrosis; (5) Chronic myeloid leukemia
.
This article reports a case
of hepatomegaly caused by a rare cause, amyloidosis.

A 65-year-old male was referred to a liver centre
for progressive shortness of breath, unintentional weight loss (31 kg in the last 6 months), and night sweats.
Past medical history includes alcohol
abuse.
The patient is non-smoking and has no significant family history
.
Physical examination reveals cachexia with hepatomegaly
.
Patients have no ascites, jaundice, or any signs of
chronic liver disease.
Laboratory tests show γ-glutamyltransferase 219 IU/L (reference range 12-68 IU/L), alkaline phosphatase 194 IU/L (reference range 30-130 IU/L), and other liver function tests are normal
.
Patients present with coagulopathy [international normalized ratio (INR) 1.
58] and anaemia [hemoglobin 10.
8 g/dL (reference range 13-17 g/dL)] and elevated brain natriuretic peptide (BNP) to 6389 pg/mL (reference range< 250 pg/mL).

Renal function, tumor markers, lactate dehydrogenase (LDH), virus, and autoimmune screening were all negative
.

CT scan of the chest, abdomen, and pelvis shows hepatomegaly with significant abdominal and mediastinal lymph node pathology
.
PET shows massive hepatomegaly and multiple metabolically
active thoracic lymph nodes.
EBUS-guided lymph node sampling shows negative
for malignancy.
The patient then undergoes an ultrasound-guided liver biopsy
.

How should it be diagnosed?

Figure A shows coronary reconstruction during the portal vein phase of liver CT, showing that the liver extends below the costal margin with a maximum diameter of 27 cm
.
The liver morphology is normal, the liver attenuation index is normal, and there is no hepatic steatosis or focal lesion
of the liver.
Figure B shows H&E-stained liver biopsy specimens, showing eosinophilic amorphous deposition in the sinuses with little residual hepatocytes
.
Figure C shows Congo red stained specimens, showing the presence of amyloid.

Further immunohistochemical analysis confirmed amyloid staining and lambda light chain antibodies
.

Proteomic analysis supports the diagnosis of
amyloidosis.
Serum electrophoresis is positive for paraproteins, and serum and urine immunofixation electrophoresis reveals monoclonal IgA Lambda bands
.
Bone marrow biopsy shows excess bone marrow cells, 40% plasma cells, and amyloid deposition
.
Further cardiac MRI showed mild centripetal myocardial thickening of the left ventricle, diffuse subendocardial delayed gadolinium enhancement of preservation of the overall systolic function of the left ventricle, and suspected infiltrative cardiomyopathy
.
This is a highly sensitive and specific manifestation of
amyloidosis.

Diagnosis: hepatic amyloidosis
.

Amyloidosis is a type of disease caused by the deposition of various amyloids outside the cell, which is clinically rare and the course of the disease can be benign or malignant
.
Amyloid invades the liver and is called amyloidosis
of the liver when deposited between hepatocytes or in reticular fiber scaffolds.
The liver is one of the most frequently violated sites of
amyloidosis.

The clinical manifestations of hepatic amyloidosis are non-specific, and patients may present with weight loss, fatigue, and other organ-related symptoms such as heart failure
.
Physical examination reveals hepatomegaly
in most cases.
Elevated alkaline phosphatase on laboratory tests is a common finding
.

Patients with hepatic amyloidosis have a poor prognosis, so early diagnosis is essential
.
Clinically, the possibility of liver amyloidosis should be ruled out if the following conditions occur: (1) the liver is obviously enlarged and there is no obvious jaundice; (2) Serum alkaline phosphatase, glutamyl transpeptidase and other bile enzymes were significantly increased, but liver enzyme changes were not obvious; (3) Exclude common diseases that cause hepatomegaly such as primary liver cancer, schistosomiasis liver disease, primary biliary cirrhosis, and non-alcoholic fatty liver disease
.

Pathological examination is the only basis for confirming the diagnosis of hepatic amyloidosis, Congo red staining is the gold standard for diagnosing amyloidosis, and amyloids are apple-green
under polarized light microscopy.
For the treatment of liver amyloidosis, there is currently no specific treatment, based on the principle of symptomatic and supportive treatment, the purpose of treatment is to inhibit the production of amyloid and abnormal deposition
.
Predictors of poor prognosis include congestive heart failure, elevated bilirubin concentration, and platelet count > 500 x 109/L
.

References:

1.
WANG Fusheng, et al.
Schiff Hepatology (11th Edition)[M].
Peking University Medical Press.
2015.

2.
 Clifford C, Ryan R, Houlihan D, An interesting case of hepatomegaly, Gastroenterology (2022), doi:https://doi.
org/10.
1053/j.
gastro.
2022.
08.
019.

3.
QIU Xinyun, YU Chenggong, QIAN Cheng, et al.
A case of hepatic amyloidosis characterized by hepatomegaly[J].
Gastroenterology, 2011,16(02):127-128.

4.
WANG Huihui, TIAN Zibin, DING Xueli, et al.
Clinical features of Chinese liver amyloidosis[J].
World Chinese Journal of Digestion, 2013,21(13):1261-1265.