Amoebic liver abscess pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Ameoebic liver abscess is caused by a protozoan Entamoeba histolytica. It is the most common extraintestinal manifestation of amoebiasis. The mode of transmission of Entamoeba histolytica include fecal-oral route (ingestion of food and water contaminated with feces containing cysts), sexual transmission via oral-rectal route in homosexuals, vector transmission via flies, cockroaches, and rodents.^[1][2] Hepatocyte programmed cell death induced by Entamoeba histolytica causes amoebic liver abscess. The infection is transmitted to liver by portal venous system.^[3]

• Amoebic liver abscess is the most common extraintestinal manifestation of amoebiasis.
• There are two genetically different species of entamoeba.^[4] They are

• Entamoeba histolytica (the pathogen)
• Entamoeba dispar (a commensal)

• The mode of transmission of Entamoeba histolytica include:^[1][2]

• Fecal-oral route (ingestion of food and water contaminated with feces containing cysts)
• Sexual transmission via oral-rectal route in homosexuals
• Vector transmission via flies, cockroaches, and rodents.

• Hepatocyte programmed cell death induced by Entamoeba histolytica causes amoebic liver abscess.
• The infection is transmitted to liver by portal venous system.^[3]
• Clinical syndromes associated with Entamoeba histolytica infection

• After ingestion of contaminated food and water, Entamoeba histolytica trophozoites adhere to epithelial cells of colon, through the galactose/N-acetylgalactosamine specific lectin.^[5]
• After adhesion, the parasite releases cysteine proteinases which digest extracellular matrix proteins. This facilitate trophozoite invasion into submucosal tissue through amoebapore leading to activation of amoebic virulence program.^[6][7]
• The extracellular amoebic cysteine proteinase converts pIL-1β (precursor interleukin 1β) to active IL-1β. The chemokines and cytokines released from epithelial cells attract macrophages and neutrophils to the site of infection.^[8]
• Neutrophils transmigrating to the epithelial surface facilitate E histolytica invasion by creating channels. Cysteine proteinases digest extracellular matrix protein, causing epithelial cells to break from the villi, which also aid in the parasite’s direct invasion into submucosal tissues.^[9]
• The mediators released by the neutrophils cause more damage to adjacent intestinal epithelial cells.^[10]
• The trophozoites penetrate the mucosa, submucosal tissues and even into the portal circulation where they encounter additional host defenses, including complement system.
• E. histolytica are covered by highly glycosylated and phosphorylated lipophosphoglycan which may serve as a physical barrier to complement components. The amoebic Gal/GalNAc lectin has a region with antigenic cross reactivity with CD59 which protect trophozoites against lysis.^[11]
• The cysteine proteinases cleave and inactivate the anaphylatoxins C3a and C5a along with human IgA and IgG which provides further defense against host immune response.^[12][13]
• The trophozoites which enter the liver through portal circulation leading to apoptosis of liver cells and abscess formation.
• Stages of abscess formation include:

• Acute inflammation
• Granuloma formation
• Necrosis with necrotic abscess or periportal fibrosis

• Solitary lesions (30%-70%) are more common amoebic liver abscesses and most commonly seen in right lobe of the liver.
• The right hepatic lobule is most commonly effected due to portal circulatory system of the right colon.

• The amoebic liver abscesses are well circumscribed regions which contain necrotic material (dead hepatocytes, liquefied cells and cellular debris) and the surrounding fibrinous border.
• The adjacent liver parenchyma is usually normal.
• The abscesses are single or multiple.
• The abscess cavity may be filled with chocolate colored pasty material (anchovy sauce-like).

• Multiple neutrophilic abscess with areas of necrosis are seen in the liver parenchyma.
• A rim of connective tissue, with few inflammatory cells and amoebic trophozoites are clustered in the fibrin at the junction of viable and necrotic tissue.