Cirrhosis and autoimmune liver disease: Current understanding

Abstract

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.

Keywords: Autoimmune hepatitis; Cirrhosis; Hepatic fibrosis; Liver transplantation; Myofibroblasts; Primary biliary cirrhosis; Primary sclerosing cholangitis.

Figure 1

“Multiple hit hypothesis” accounting for the development of autoimmune disease. Interplay between immunological, genetic, epigenetic and environmental factors is thought to account for the loss of tolerance to self constituents in AILD. AILD: Autoimmune liver disease.

Figure 2

Development of fibrosis and cirrhosis in autoimmune liver disease. Persistent autoimmune-mediated inflammation and liver cell injury leads to the activation and differentiation of quiescent hepatic stellate cells (HSC) and portal fibroblasts (PF) into activated myofibroblasts. These proliferative, pro-inflammatory and pro-fibrogenic myofibroblasts increase collagen synthesis and deposit extracellular matrix proteins (ECM), leading to the development of fibrous scar tissue. Cirrhosis, characterised by significant fibrosis and nodular regeneration, eventually ensues, with the resultant loss of liver function and eventually liver failure.