Zakim and Boyer's Hepatology (Seventh Edition): 5 - The Liver's Response to Injury: Inflammation and Fibrosis

Elsevier, Zakim and Boyer's Hepatology (Seventh Edition), A Textbook of Liver Disease, 2018, Pages 77-83.e5
Min Cong, Jidong Jia, Tatiana Kisseleva, and David A. Brenner

Inflammation is a part of the immune response to infection and trauma, and under physiologic conditions is designed to facilitate wound healing. The traditional inflammatory response is characterized as a complex reaction to an injuring agent that involves the loss of vascular wall integrity, activation of leukocytes and their extravasations, and release of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. The liver functions to eliminate toxins and pathogens from the circulation, and has developed a unique mechanism of immunosurveillance. To avoid unnecessary activation of the immune system, the liver has a local immune response followed by induction of peripheral tolerance toward the antigen. When stressful agents such as pathogens or environmental insults challenge the liver for extended periods and their elimination is not possible, then inflammation follows.

Hepatic fibrosis and then cirrhosis commonly follows chronic inflammation.5, 6 Sustained suppression of inflammatory activity by elimination of the etiologic agent7, 8, 9, 10, 11, 12, 13 or by dampening of the immune response14, 15, 16, 17, 18 can halt and even reverse the fibrotic process. The success of current treatments of chronic liver inflammation in achieving antifibrotic effects can be measured by prolonged survival and possibly a reduced occurrence of hepatocellular carcinoma. Thus hepatic inflammation is one driver of fibrosis, cirrhosis, and hepatocellular carcinoma.