Granulomatous liver diseases

Abstract

A granuloma is a discrete collection of activated macrophages and other inflammatory cells. Hepatic granulomas can be a manifestation of localized liver disease or be a part of a systemic process, usually infectious or autoimmune. A liver biopsy is required for the detection and evaluation of granulomatous liver diseases. The prevalence of granulomas on liver biopsy varies from 1% to 15%. They may be an incidental finding in an asymptomatic individual, or they may represent granulomatous hepatitis with potential to progress to liver failure, or in chronic disease, to cirrhosis. This review focuses on pathogenesis, histological features of granulomatous liver diseases, and most common etiologies, knowledge that is essential for timely diagnosis and intervention.

FIGURE 1

Pathogenesis of granuloma formation. Bacteria or any foreign organism can be phagocytosed by macrophages as a part of the innate immune response. In the adaptive response, antigen is presented to the CD4+ T-cells through Ag-presenting cells: macrophages, dendritic cells, and B-cells. The Th1 pathway involves the release of TNF-α, INF-γ, IL-2, IL-12, and other pro-inflammatory cytokines and it is critical in sarcoidosis and tuberculosis. The Th2 response is mediated through IL-4, IL-5, and IL-13, and it plays a role in helminth infections such as schistosomiasis. Abbreviations: INF-γ, interferon-gamma; Th2, T helper type 2; TNF-α, tumor necrosis factor-alpha).

FIGURE 2

Histological features of hepatic granulomas. (A) Microgranuloma in metabolic dysfunction–associated steatohepatitis, H&E, ×600. (B) Lipogranuloma in metabolic dysfunction–associated steatohepatitis, H&E, ×400. (C) Fibrin-ring granuloma in drug-induced injury due to the ICIs ipilimumab and nivolumab, H&E, ×400. (D) Non-necrotizing epithelioid granuloma in autoimmune lymphoproliferative syndrome, H&E, ×400. (E) Necrotizing epithelioid granuloma in eosinophilic hepatitis, H&E, ×200. (F) Florid duct lesion of primary biliary cholangitis, H&E, ×400. (G) Mycobacterial granuloma, H&E, ×200. (H) Mycobacterium tuberculosis on acid-fast bacilli stain, ×600. (I) Granulomas in sarcoidosis, H&E, ×200. Abbreviations: H&E, hematoxylin and eosin; ICI, immune checkpoint inhibitors.

FIGURE 3

Workup of incidental granuloma on the liver biopsy. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; PBC, primary biliary cholangitis; TB, tuberculosis.