Intestinal endotoxemia as a pathogenetic mechanism in liver failure.
Liver injury induced by various pathogenic factors (such as hepatitis virus, ethanol, drugs and hepatotoxicants, etc.) through their respective special pathogenesis is referred to as   primary liver injury   (PLI). Liver injury resulted from endotoxin (lipopolysaccharide, LPS) and the activation of Kupffer cells by LPS while intestinal endotoxemia (IETM) occurred during the occurrence and development of hepatitis is named the   secondary liver injury   (SLI). The latter which has lost their own specificities of primary pathogenic factors is ascribed to IETM. The   secondary liver injury   is of important action and impact on development and prognosis of hepatitis. More severe IETM commonly results in excessive inflammatory responses, with serious hepatic necrosis, further severe hepatitis and even induces acute liver failure. The milder IETM successively precipitates a cascade, including repeated and persistent hepatocytic impairment accompanied by infiltration of inflammatory cells, hepatic fibrosis, cirrhosis and hepatocarcinoma. Generally, the milder IETM ends with chronic hepatic failure. If PLI caused by various pathogenic factors through their independent specific mechanismis regarded as   the first hit   on liver, then SLI mediated by different chemical mediators from KCs activated by IETM in the course of hepatitis is   the second hit   on liver. Thus, fusing and overlapping of the primary and scondary liver injuries determine and influeuce the complexity of the illness and outcome of the patient with hepatitis. For this reason, the viewpoint of   SLI   induced by the   second hit   on liver inflicted by IETM suggests that medical professionals should attach great importance to both   PLI   and   SLI   caused by IETM. That is, try to adjust the function of KS(s) and eliminate endotoxemia of the patient.
Han
De-Wu
DW
Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China. smuhan@public.ty.sx.cn
D000818:Animals; D019446:Endotoxemia / Q000150:complications*; D006505:Hepatitis / Q000209:etiology; D006801:Humans; D007410:Intestinal Diseases / Q000150:complications*; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000293:injuries; D017093:Liver Failure / Q000209:etiology*; D008954:Models, Biological; D010587:Phagocytosis