COVID-19 Exposure Unmasking Systemic Amyloidosis With Hepatic Predominance

Abstract

Amyloidosis is characterized by depositing insoluble fibrillar proteins that misfold into beta-pleated sheets. This phenomenon occurs on a systemic or local level and may interfere with the function of various organs, including the heart, kidneys, and liver. Among those presenting with amyloidosis, hepatic, gastrointestinal, renal, cardiac, vitreous, and immunological involvement may occur. These manifestations are linked to several clinical presentations, varying from abdominal pain and hepatomegaly to restrictive cardiomyopathy and chronic renal failure. The two most common types of amyloid proteins are amyloid light chain (AL) and serum amyloid A (AA) proteins. AL produced by immunoglobulin light chains kappa and lambda (κ, λ) circulate systemically and accumulate in organs. At the same time, serum AA proteins are acute-phase reactants seen in infectious, chronic inflammatory states. In an immune-mediated infection such as COVID-19, serum AA levels may be a predictive factor of disease severity and a valuable biomarker to monitor the clinical course of COVID-19 patients. This report highlights a case in which infection with COVID-19 provoked an effective immune response that may have contributed to the accelerated progression of systemic amyloidosis with hepatic involvement. The study further investigates the involvement of AL and AA proteins in COVID-19 infections, including their role in synergistically exacerbating an already grueling clinical course.

Keywords: amyloid plaques; clinical infectious medicine; covid-19; gastrointestinal amyloid; hepatology; liver function.

Figure 1. A graph summarizing the liver-related tests during the hospital course of the patient.

ALT: Alanine transaminase (Normal 7-40U/L), AST: Aspartate aminotransferase (Normal 13-40U/L), ALP: Alkaline phosphatase (Normal 46-116U/L), T.Bili: Total bilirubin (Normal 0.3-1.2mg/dL), and D.Bili: Direct bilirubin (Normal 0-0.3mg/dL)

Figure 2. Abdominal ultrasound (US) findings: The visualized portions of the liver are homogeneous. There is hepatomegaly measuring 20.68cm and subtle hepatic surface nodularity suggestive of cirrhosis with a moderate volume of ascites (prior to conservative therapy).

Figure 3. Abdominal computer tomography (CT) findings: hepatomegaly with diffuse hepatic steatosis.

Figure 4. Abdominal magnetic resonance imaging (MRI) findings: (A) There is hepatomegaly with the liver measuring 20.5cm in the craniocaudal dimension (after conservative therapy). (B) A trace amount of perihepatic ascites is present with hepatic and portal veins patent. There is no biliary ductal dilatation, and the gallbladder, spleen, adrenals, and kidneys are within normal limits.

Figure 5. Magnetic resonance cholangiopancreatography (MRCP) findings: The liver is mildly enlarged but homogeneous. No hepatic parenchymal signal loss is demonstrated to suggest hepatic steatosis. The portal veins are patent. The volume of perihepatic ascites is slightly increased. The gallbladder is contracted, but the gallbladder wall does not appear disproportionately thickened, and no gallbladder calculi are identified. There is a small amount of pericholecystic ascites.

Figure 6. Cardiac transthoracic echocardiogram (TTE) showing infiltrative cardiomyopathy without decreased ejection fraction.

Figure 7. Liver biopsy demonstrating diffusely expanded sinusoids by amorphous eosinophilic deposits infiltrating the portal vessel walls on hematoxylin and eosin stain.

Figure 8. Liver biopsy demonstrating amyloidosis deposition: (A) Patchy apple-green birefringence by congo red stain with a polarizing light filter. (B) Patchy apple-green birefringence by congo red stain with a nonpolarizing light filter.

Figure 9. Liver biopsy demonstrating liver parenchyma negative for fibrosis on trichrome stain.

Figure 10. Liver biopsy demonstrating staining of amyloid light-chain (kappa and lambda) and amyloid A protein deposition on immunohistochemical staining. (A) Positive staining of kappa-type amyloid light-chain deposition. (B) Positive staining of lambda-type amyloid light-chain deposition. (C) Positive staining of amyloid A protein deposition.

Figure 11. Abdominal computer tomographic angiography (CTA) after liver biopsy findings: (A) Status post-ultrasound-guided core liver biopsy showing the development of new large volume complex attenuating perihepatic ascites fluid tracking along the paracolic gutters into the lower pelvis. This finding may represent blood products. (B) There is an enhancing focal area not seen elsewhere in the liver with a surrounding slight lucency at the periphery of the liver anteriorly suspicious for a site of active extravasation of contrast, likely active bleeding. (C) Diffuse hepatic steatosis with extensive volume complex ascites with centralization of the bowel loops and hematocrit levels in the right paracolic gutter and lower pelvis indicate hemorrhagic ascites or ascites with a hemorrhagic component.

Figure 12. Liver biopsy demonstrating prominent bile ductular proliferation and pressure atrophy of hepatocytes forming cord-like islands on hematoxylin and eosin stain.

Figure 13. Liver biopsy demonstrating focal canalicular cholestasis and interference with the passage of bile resulting from pressure atrophy of hepatocytes on hematoxylin and eosin stain.