Cirrhosis of the liver
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The ancient story of Prometheus, chained to a rock for defying Zeus by stealing fire from Mount Olympus and subjected to daily tearing at his liver by an eagle, attests to the early recognition of the extraordinary regenerative capacity of the human liver. This process had remained an intriguing mystery over the millennia. In the last 20 years, following the pioneering work of Bucher (1) and Moolten et al (2), there has been an explosion of research that has clarified some of the mechanisms underlying the process of hepatic regeneration.
Regeneration implies proliferation and regeneration. After the fetal and postnatal growth of the liver is completed, hepatocytes no longer proliferate actively, but they can proliferate in response to cell death or loss (3). Hepatocyte growth responses are of particular research interest because they occurin vivo and involve cells that are normally quiescent.
Hepatic regeneration constitutes a highly regulated process that is best shown by the arrest of liver growth following a partial hepatectomy precisely at the moment the hepatic mass reaches the mass of the original intact liver (3). This suggests that hepatic regeneration after a partial hepatectomy is a strictly regulated nonautonomous growth process that is controlled by the same factors that are responsible for the determination and maintenance of hepatic mass in a normal individual. In response to a partial hepatectomy, hepatocytes enter the cell cycle and progress to DNA synthesis and replication but only in number sufficient to restore the hepatic mass. The regeneration response is both synchronized and universal in that it affects all intrahepatic cell lines, including nonparenchymal cells.
The first part of the present paper deals with a review of the concepts related to the regulation of growth and regeneration following liver injury. This is followed by discussion of the process of hyperplasia and neoplasia seen in cirrhosis. The second part of this work deals with a new histopathological method used to identify hepatocellular carcinoma (HCC), which is based upon a consideration of dynamic criteria and the lessons learned from a human disease process, alpha-1-antitrypsin (AAT) deficiency.
Key Wordshepatic regeneration hyperplastic nodules cirrhosis hepatocellular carcinoma alpha-1-antitrypsin deficiency
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- 1.Bucher NLR: Experimental aspects of hepatic regeneration. N Engl J Med 277:686–696, 738–746, 1967Google Scholar
- 2.Moolten FL, Oakman NJ, Bucher NLR: Accelerated response of hepatic DNA synthesis to partial hepatectomy in rats pretreated with growth hormone or surgical stress. Cancer Res 30:2353–2357, 1970Google Scholar
- 3.Bucher NLR, Malt RA: Regeneration of Liver and Kidney. Boston, Little Brown, 1971, pp 17–176Google Scholar
- 4.Fausto N, Mead JE: Biology of disease. Regulation of liver growth: Protooncogenes and transforming growth factor. Lab Invest 60:4–13, 1989Google Scholar
- 5.Wisse E, De Zanger RB, Charles K: The liver sieve: Considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology 5:683–692, 1985Google Scholar
- 6.Rappaport AM: The microcirculatory acinar concept of normal and pathological hepatic structure. Beitz Pathol 157:215–243, 1976Google Scholar
- 7.Popper H: Regulatory mechanisms in hepatology. Hepatology 7:586–590, 1987Google Scholar
- 8.Rappaport AM, MacPhee PJ, Fisher MM, Philips MJ: The scarring of the liver acini (cirrhosis). Virchows Arch A (Pathol Anat) 402:107–137, 1983Google Scholar
- 9.Popper H, Acs G: Regulatory factors in pathologic processes of the liver. Modulators and interacting metabolic networks. Sem Liver Dis 5:191–207, 1985Google Scholar
- 10.Sherman M, Shafritz DA: Hepatitis B virus and hepatocellular carcinoma: Molecular biology and mechanistic considerations. Sem Liver Dis 4:98–112, 1984Google Scholar
- 11.Van Eyken P, Sciot R, Callea F, Desmet VT: A cytokeratin-immunohistochemical study of focal nodular hyperplasia of the liver: further evidence that ductural metaplasia of hepatocytes contributes to ductural “proliferation”. Liver 9:372–377, 1989Google Scholar
- 12.Ryoo TW, Bushmann RJ: A morphometric analysis of the hypertrophy of experimental liver cirrhosis. Virchows Arch (Pathol Anat) 400:173–186, 1983Google Scholar
- 13.Medline A, Farber E: The multi-step theory of neoplasia. Rec Adv Histopathol 11:19–34, 1981Google Scholar
- 14.Sciot R, Paterson A, Van Eyken P, Callea F, Desmet VT: Transferrin receptor expression in human hepatocellular carcinoma. Histopathology 12:53–63, 1988Google Scholar
- 15.Van Eyken P, Sciot R, Paterson A, Callea F, Kew MC, Desmet VT: Cytokeratin expression in hepatocellular carcinoma. Hum Pathol 19:562–568, 1988Google Scholar
- 16.Bannash P: Cytology and cytogenesis of neoplastic (hyperplastic) hepatic nodules. Cancer Res 36:2555–2562, 1976Google Scholar
- 17.Nakanuma Y, Ohta G: Expression of Mallory bodies in hepatocellular carcinoma in man and its significance. Cancer 57:81–86, 1986Google Scholar
- 18.Callea F: Natural history of hepatocellular carcinoma as viewed by the pathologist. Appl Pathol 6:105–116, 1988Google Scholar
- 19.Kew MC, Popper H: Relationship between hepatocellular carcinoma and cirrhosis. Sem Liver Dis 4:136–146, 1984Google Scholar
- 20.Popper H: Cell necrosis in cirrhosis.In Liver Cirrhosis. JL Boyer, et al (eds.). Lancaster, UK, MTP Press, 1987, pp 9–18Google Scholar
- 21.MacSween RNM: A clinico-pathological review of 100 cases of primary malignant tumors of the liver. J Clin Pathol 27:669–682, 1974Google Scholar
- 22.Eriksson S, Carlson J, Veler R: Risk of cirrhosis and primary liver cancer in alpha-1-antitrypsin deficiency. N Engl J Med 314:736–739, 1986Google Scholar
- 23.Callea F, Fevery J, DeGroote T, Desmet VT: Detection of PiZ phenotype individuals by AAT immunohistochemistry in paraffin-embedded liver tissue specimens. J Hepatol 2:389–401, 1986Google Scholar
- 24.Callea F, Fevery J, Massi G, Lievens C, De Groote J, Desmet VT: AAT and its stimulation in the liver of Pi MZ phenotype individuals. A “recruitment-secretory block” (“R-SB”) phenomenon. Liver 4:325–337, 1984Google Scholar
- 25.Edmondson HA: Tumors of the liver and intrahepatic bile ducts.In Atlas of Tumor Pathology; Section VII, Fasc. 25 37–80 (AFIP), 1958Google Scholar
- 26.Histological typing of liver tumors of the rat. J Nat Cancer Inst 64:193, 1980Google Scholar
- 27.Callea F, Brisigotti M, Faa G, Lucini L, Eriksson S: Identification of PiZ gene products in liver tissue by a monoclonal antibody specific for the Z mutant of alpha-1-antitrypsin. J Hepatol (in press)Google Scholar