Features of liver damage in Niemann — Pick disease type A, A/B and B (deficiency of acidic sphingomyelinase)

Background. Acid sphingomyelinase deficiency (Niemann – Pick disease) leads to the intracellular accumulation of sphingomyelin within the mononuclear phagocyte system, including liver, spleen, lungs and bone marrow. Liver involvement represents one of the earliest and persistent visceral manifestations of the disease. Foamy macrophages featuring prominent cytoplasmic vacuolation are generated within the liver. Intracellular accumulation of pathological substrates in hepatocytes results in several pathological changes, including inflammation and cytokine release, remodeling of the sinusoidal network, periportal and bridging fibrosis and progressive portal hypertension. Dyslipidemia, associated with Niemann – Pick disease, is characterised by elevated levels of various lipid fractions. Gradual lipid accumulation leads to the liver enlargement (hepatomegaly) and the development of hepatic steatosis. Hepatomegaly, biochemical abnormalities and progressive fibrosis significantly impair the patients' quality of life and adversely affect the prognosis of the disease.

Objective. To analyze current data on the pathogenesis, clinical manifestations, morphological features, and treatment of liver damage in Niemann – Pick disease types A, A/B, and B.

Materials and methods. A systematic review of publications from 2013-2025 on the clinical presentation, histopathology, and treatment of acid sphingomyelinase deficiency was conducted, including the impact of enzyme replacement therapy on liver pathology.

Results. The liver is a key target organ in Niemann – Pick disease types A, A/B, and B. The spectrum of liver changes includes hepatomegaly, parenchymal infiltration with foamy macrophages, progressive fibrosis, cirrhosis, hepatic steatosis, and the possible development of portal hypertension and liver failure requiring transplantation. The severity of liver damage and the age at onset of changes depend on the disease phenotype. Liver failure, in addition to respiratory disease, is the leading cause of death in chronic forms of Niemann – Pick disease. Modern enzyme replacement therapy can reduce liver volume, improve biochemical parameters, and slow the progression of fibrosis.

Conclusion. Early diagnosis and pathogenetic therapy are key to slowing the progression of liver disease in acid sphingomyelinase deficiency.

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