Rating fibrosis progression in chronic liver diseases

Abstract

Much of the morbidity and almost all of the mortality due to chronic liver disease can be attributed to advanced liver fibrosis, i.e. cirrhosis. A wide range of hepatic insults are associated with the accumulation of new extra-cellular matrix frequently accompanied by infiltration of the liver by immunocytes. Progressive accumulation of matrix causes changes in the cellular morphology of all components of the hepatic acinus, disruption of their inter-cellular interactions, impairment of blood flow and a loss of functioning liver cell mass. Eventually this process gives rise to cirrhosis. It has become apparent that liver fibrosis results from a dynamic process in which the accumulation of scar tissue is accompanied by matrix degradation and remodelling [1x[1]Friedman, S.L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000; 275: 2247–2250Crossref | PubMed | Scopus (1719) | Google ScholarSee all References][1] in a finely balanced process that can be driven towards cirrhosis or reversed to restore normal hepatic structure and function. It is now recognized that even cirrhotic changes can be remodelled in response to removal of an hepatic insult [2x[2]Powell, L.W. and Kerr, J.F. Reversal of “cirrhosis” in idiopathic haemochromatosis following long-term intensive venesection therapy. Australas Ann Med. 1970; 19: 54–57PubMed | Google ScholarSee all References, 3x[3]Hammel, P., Couvelard, A., O'Toole, D., Ratouis, A., Sauvanet, A., Flejou, J.F. et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med. 2001; 344: 418–423Crossref | PubMed | Scopus (325) | Google ScholarSee all References], treatment of immune mediated liver diseases [4x[4]Dufour, J.F., DeLellis, R., and Kaplan, M.M. Reversibility of hepatic fibrosis in autoimmune hepatitis. Ann Intern Med. 1997; 127: 981–985Crossref | PubMed | Scopus (247) | Google ScholarSee all References, 5x[5]Wanless, I.R. Use of corticosteroid therapy in autoimmune hepatitis resulting in the resolution of cirrhosis. J Clin Gastroenterol. 2001; 32: 371–372Crossref | PubMed | Scopus (28) | Google ScholarSee all References, 6x[6]Kaplan, M.M., DeLellis, R.A., and Wolfe, H.J. Sustained biochemical and histologic remission of primary biliary cirrhosis in response to medical treatment. Ann Intern Med. 1997; 126: 682–688Crossref | PubMed | Scopus (113) | Google ScholarSee all References] or antiviral therapy [7x[7]Kweon, Y.O., Goodman, Z.D., Dienstag, J.L., Schiff, E.R., Brown, N.A., Burkhardt, E. et al. Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J Hepatol. 2001; 35: 749–755Abstract | Full Text | Full Text PDF | PubMed | Scopus (153) | Google ScholarSee all References, 8x[8]Lau, D.T., Kleiner, D.E., Park, Y., Di Bisceglie, A.M., and Hoofnagle, J.H. Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. Gastroenterology. 1999; 117: 1229–1233Abstract | Full Text | Full Text PDF | PubMed | Scopus (108) | Google ScholarSee all References, 9x[9]Poynard, T., McHutchison, J., Manns, M.P., Trepo, C., Lindsay, K.L., Goodman, Z. et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. 2002; 122: 1303–1313Abstract | Full Text | Full Text PDF | PubMed | Scopus (892) | Google ScholarSee all References]. Despite increasing knowledge of how fibrosis develops and regresses surprisingly little is know about the kinetics of this process, particularly in human disease.