Semin Liver Dis 2010; 30(3): 211-214
DOI: 10.1055/s-0030-1255350
FOREWORD

© Thieme Medical Publishers

Inflammation and Hepatic Fibrosis

D. Montgomery Bissell1
  • 1Division of Gastroenterology and Liver Center, University of California San Francisco, San Francisco, California
Further Information

Publication History

Publication Date:
21 July 2010 (online)

The modern era of fibrosis research was initiated by pathologists who, through careful study of histological sections, were able to relate excess connective tissue in the liver (fibrosis) to clinical disease. They pointed out that not only is the amount of fibrosis important, but also its localization.[1] This was useful for prognosis and led to formal systems for fibrosis staging.[2] A subject of debate was the way in which the observed fibrous strands or bands formed. Some argued that the process was a passive result of hepatocyte dropout and apposition of preexisting layers of extracellular matrix (ECM, or “ground substance”). Others believed that fibrogenesis was an active process involving the elaboration of scar by specialized fibrogenic cells from within or outside the liver. Starting in the 1950s, Toshio Ito performed morphological studies of lipid-storing cells in the perisinusoidal space of the liver, establishing that this population differed from the liver macrophages named for Kupffer. Calling them “fat-storing” cells, he also showed an association of this cell type with collagen fibrils.[3] In 1976, Kent and colleagues provided ultrastructural evidence for active fibrogenesis by Ito's cells.[4] This was an influential work, confirmed by others,[5] which stimulated further efforts to define the cellular source(s) of excess ECM in injury. Proof of the fibrogenic capability of Ito/fat-storing cells/lipocytes (now known as hepatic stellate cells [HSCs]) came in the mid-1980s when HSCs were isolated, placed in culture,[6] and shown directly to undergo activation and produce ECM proteins.[7] Studies in vivo followed, confirming that this cell type is quantitatively the preeminent producer of collagen and other ECM constituents during injury and repair.[8] Given the implications for intervening in fibrosis progression and liver failure, HSCs became a focus of intensive study.

REFERENCES

  • 1 Popper H, Uenfriend S. Hepatic fibrosis. Correlation of biochemical and morphologic investigations.  Am J Med. 1970;  49 707-721
  • 2 Brunt E M. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond.  Hepatology. 2000;  31 241-246
  • 3 Suematsu M, Aiso S. Professor Toshio Ito: a clairvoyant in pericyte biology.  Keio J Med. 2001;  50 66-71
  • 4 Kent G, Gay S, Inouye T, Bahu R, Minick O T, Popper H. Vitamin A-containing lipocytes and formation of type III collagen in liver injury.  Proc Natl Acad Sci U S A. 1976;  73 3719-3722
  • 5 Okanoue T, Burbige E J, French S W. The role of the Ito cell in perivenular and intralobular fibrosis in alcoholic hepatitis.  Arch Pathol Lab Med. 1983;  107 459-463
  • 6 de Leeuw A M, McCarthy S P, Geerts A, Knook D L. Purified rat liver fat-storing cells in culture divide and contain collagen.  Hepatology. 1984;  4 392-403
  • 7 Friedman S L, Roll F J, Boyles J, Bissell D M. Hepatic lipocytes: the principal collagen-producing cells of normal rat liver.  Proc Natl Acad Sci U S A. 1985;  82 8681-8685
  • 8 Maher J J, McGuire R F. Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo.  J Clin Invest. 1990;  86 1641-1648
  • 9 Bissell D M, Arenson D M, Maher J J, Roll F J. Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver.  J Clin Invest. 1987;  79 801-812
  • 10 Homeida M A, el Tom I, Nash T, Bennett J L. Association of the therapeutic activity of praziquantel with the reversal of Symmers' fibrosis induced by Schistosoma mansoni.  Am J Trop Med Hyg. 1991;  45 360-365
  • 11 Dienstag J L, Goldin R D, Heathcote E J et al.. Histological outcome during long-term lamivudine therapy.  Gastroenterology. 2003;  124 105-117
  • 12 Yao F Y, Terrault N A, Freise C, Maslow L, Bass N M. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort.  Hepatology. 2001;  34 411-416
  • 13 Issa R, Zhou X, Constandinou C M et al.. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking.  Gastroenterology. 2004;  126 1795-1808

D. Montgomery BissellM.D. 

Division of Gastroenterology and Liver Center, University of California

513 Parnassus Avenue, Box 0538, San Francisco, CA 94143-0538

Email: montgomery.bissell@ucsf.edu

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