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World J Gastroenterol. Mar 14, 2014; 20(10): 2515-2532
Published online Mar 14, 2014. doi: 10.3748/wjg.v20.i10.2515
Hepatic inflammation and progressive liver fibrosis in chronic liver disease
Albert J Czaja
Albert J Czaja, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, United States
Author contributions: Czaja AJ determined the theme of this manuscript, designed its format, reviewed the literature, selected the pertinent studies, drafted the manuscript, critically reviewed and revised its content, developed the tables, designed the figure, typed the document, approved the final version, and submitted the manuscript for review.
Correspondence to: Albert J Czaja, MD, Professor Emeritus of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 1st St SW, Rochester, MN 55905, United States.
Telephone: +1-507-2848118 Fax: +1-507-2840538
Received: September 27, 2013
Revised: October 24, 2013
Accepted: November 12, 2013
Published online: March 14, 2014

Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease.

Keywords: Inflammation, Fibrosis, Cirrhosis, Treatment, Anti-oxidants, Angiotensin receptors, Investigational drugs

Core tip: The prevention of hepatic fibrosis and the reversal of cirrhosis are now achievable objectives in the management of chronic liver disease. Conventional immunosuppressive, anti-inflammatory, and anti-viral therapies can accomplish these outcomes by reducing liver damage, suppressing hepatic inflammation, and eliminating etiological agents, but they do so inconsistently and indirectly. The continuing clarification of pro-fibrotic mechanisms affords opportunities to design site-specific, anti-fibrotic interventions. Anti-oxidants and angiotensin inhibitors have shown promise as adjunctive anti-fibrotic agents in preliminary human studies, and they exemplify a genre of interventions that are likely to influence future management strategies.