The immunopathogenesis of cirrhosis

Abstract

Fibrosis is a type of wound healing which occurs in most organs after repetitive acute or sustained chronic injury. With continued injury, fibrosis may progress to a complex set of changes which encompass matrix deposition, immunomodulation, and distortion of liver vasculature and gross architecture. Tremendous progress in understanding the pathophysiology of this wound-healing response has led to realistic expectations for treating fibrosis in patients with chronic liver disease owing to either viral hepatitis or metabolic or autoimmune diseases, among others. There have been continued clarification of the cellular source of ECM in hepatic fibrosis, major advances in understanding signaling and transcriptional events, and exciting insights into the biology of fibrosis progression and resolution [1]. The clarification of interactions between the immune system and fibrogenic response has been among the most exciting developments in fibrosis. In the liver, these advances include evidence of direct interactions between immune cell subsets and fibrogenic cells in liver, the emergence of natural killer (NK) cells as determinants of hepatic stellate apoptosis and thus fibrosis resolution, the establishment of hepatocellular apoptosis as an inflammatory and fibrogenic stimulus, and the growing recognition that HSCs contribute to the innate immune response and development of hepatocellular carcinoma (HCC). These and other observations underscore the prospect for eventually manipulating these interactions therapeutically. Whereas fibrosis accompanies progressive liver injury and may vary from mild to extensive, cirrhosis is the end stage of fibrosis of the hepatic parenchyma, resulting in nodule formation that can lead to altered hepatic function and blood flow which can be seen as a form of vascular remodeling.