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Reversibility of hepatic fibrosis and cirrhosis—is it all hype?

Nature Clinical Practice Gastroenterology & Hepatology volume 4, pages 236–237 (2007)Cite this article

Now that the idea that hepatic fibrosis is reversible is taking root, many clinicians are beginning to ask why, if fibrosis is reversible, is there so little progress in the clinical setting, and will patients ever really benefit from antifibrotic therapies? Underlying such questions is a subtle cynicism that the reversibility of fibrosis and cirrhosis has been overhyped—yet another example of the medical media 'spin machine' giving false hope to desperate patients. The situation has been fueled by the actions of ambitious institutional press relations officers. One such example is the worldwide media focus on the use of sulfasalazine to treat hepatic fibrosis, with claims that half of all liver deaths could be avoided1 even though the drug's reported efficacy was based on a single study in rodents.

So what is the truth, and how do we maintain perspective? First of all, progress has been tremendous. The mere idea that fibrosis can regress when the initial disease is controlled or cured is exciting, given the decades of dogma that suggested scar formation was a unidirectional pathway. Ample evidence that fibrosis regresses with control of hepatitis B, hepatitis C, or other chronic liver diseases2 attests to the tremendous regenerative power of the liver, and the rapid progress made in the development of targeted antiviral and disease-specific treatments. Without such advances a discussion of reversibility would have been moot, but this discussion has raised some semantic issues that sow controversy and obscure continued progress. Specifically, use of the term 'reversal' implies a complete return to normal histology, whereas a better term would be 'regression'—a more accurate and relevant term that indicates improvement in fibrosis without necessarily a return to normal histology. Of equal importance, stasis of disease or delayed progression are clinically meaningful, as they might prevent the development of cirrhosis, which is the only stage of chronic liver disease associated with significant and predictable complications.3 A related issue is the failure of some clinical studies to distinguish between cirrhosis, which connotes distinct architectural and structural changes (including nodules of fibrosis that encapsulate hepatocytes), and advanced fibrosis, which lacks these features.

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  1. Box 1123, Mount Sinai School of Medicine, Room 11-70C, 1425 Madison Avenue, New York, NY 10029-6574, USA scott.friedman@mssm.edu

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  1. SL Friedman is Fishberg Professor and Chief of the Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.,

    Scott L Friedman

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The author has declared associations with the following companies/organizations: Angion Biomedica, Intercept, Conatus, XTL, Stromedix, Breath ID, Biogen Idec, Genzyme, Gilead, Glaxo Smith Kline, Novartis and Pro-Pharmaceuticals.

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Friedman, S. Reversibility of hepatic fibrosis and cirrhosis—is it all hype?. Nat Rev Gastroenterol Hepatol 4, 236–237 (2007). https://doi.org/10.1038/ncpgasthep0813

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