A previously healthy 56-year-old man presented with progressive jaundice for 6 weeks and abdominal distension with swelling of feet for 4 weeks. He also had symptoms of fatigue and mild generalized itching. His past medical history was unremarkable, with no prior history of liver disease. On physical examination, he was deeply icteric, had bilateral pitting lower-limb edema, a left-sided pleural effusion, a short apical systolic murmur, and a flapping tremor. His abdominal examination revealed massive hepatosplenomegaly with moderate ascites. His clinical presentation was akin to acute-on-chronic liver failure (ACLF) with the appearance of ascites and encephalopathy within 2 weeks of presentation with jaundice. His primary physician referred the case to our center after he developed signs of liver decompensation. Hence his initial diagnostic work-up focused on identifying the underlying etiology. Complete blood count and serum electrolytes were within normal limits. Laboratory studies showed blood urea 45 mg/dL, creatinine 0.9 mg/dL, total bilirubin 22 mg/dL, serum albumin 24 g/L, international normalized ratio 3.2, alkaline phosphatase 1,496 IU/L, gamma-glutamyltransferase 136 IU/L, alanine aminotransferase 128 IU/L, and aspartate aminotransferase 170 IU/L. C-reactive protein was elevated, and immunoglobulin (Ig) levels were normal with IgG 12 g/L, IgA 3.15 g/L, and IgM 0.52 g/L. Serum protein electrophoresis and beta2 microglobulin were within normal limits, and urinalysis was negative for Bence-Jones proteinuria. Alpha-fetoprotein was within the normal range. Serologies for hepatitis were all unremarkable. Autoimmune work-up, including antinuclear, anti-smooth muscle, and anti-DNA antibodies, were negative. The 24-hour urinary protein excretion was 0.068 g/L.
Abdominal ultrasonography revealed hepatosplenomegaly with no focal liver lesions and normal intra- and extrahepatic bile ducts. Computed tomography of the abdomen showed the liver measured 16.6-cm in craniocaudal span, with a subtle lobulated outline and widened interlobar fissures. The main portal vein was mildly dilated with thin collaterals, suggestive of portal hypertension. There was no evidence of retroperitoneal or mesenteric lymphadenopathy (Figure 1). Transthoracic echocardiography showed normal chambers with diastolic dysfunction, normal systolic function with ejection fraction of >60%, and no pericardial effusion. Ascitic fluid analysis showed 500 cells, 90% lymphocytes, high serum albumin ascitic gradient (2.1), low protein (2.4 g/L), and low adenosine deaminase (5.7 IU/L). Polymerase chain reaction was negative for tuberculosis and there were no malignant cells on cytology. These findings were consistent with portal hypertension.
Transjugular liver biopsy was performed. Hepatic venous pressure gradient was 14 mm Hg, confirming the clinical diagnosis of portal hypertension. Liver biopsy showed near complete effacement of acinar architecture by sinusoidal and portal deposits of extracellular, pale eosinophilic, hyaline, amorphous, acellular material. Hepatocytes showed pressure atrophy and focal presence of canalicular bile. Portal tracts showed no significant inflammation with F1 fibrosis (Figure 2). The material stained positive with Congo red and displayed green birefringence when viewed under polarized light, confirming amyloid deposition. Stains for iron and copper deposition were not remarkable. Immunohistochemistry revealed that the amyloid deposits consisted largely of light chains, with lambda being stronger than kappa (Figure 3). Bone marrow aspiration showed erythroid hyperplasia with normoblastic to mild megaloblastic erythropoiesis. Plasma cells were 9%. No evidence of myeloma was seen. Serum free light chains were negative. Skeletal survey did not reveal any lytic lesions. Rectal biopsy showed maintained crypt architecture. There were focal deposits of acellular eosinophilic amorphous material in the wall of blood vessels in submucosa. These deposits also showed apple green birefringence on staining with Congo red under polarization. This confirmed extrahepatic deposition of amyloid (Figure 4).
The patient's clinical condition rapidly deteriorated over the next few days, and he developed fulminant liver failure and sepsis. He could not be offered chemotherapy due to liver failure, and was deemed unfit for liver transplantation. He died within 12 days of presentation at our center.