Issues in Hepatic Pathology

This issue of Seminars in Liver Disease is devoted to recent advances in hepatopathology. The articles provide insights into the pathophysiology, pathogenesis, and clinical and histological presentation of topics that are being embraced more and more by clinicians and pathologists alike in their daily practice.

The article by Brunt on nonalcoholic steatohepatitis (NASH) raises the theme of this issue. What was once an obscure diagnosis has now become a well-recognized entity that has reached almost epidemic proportions in North America. Her careful and extensive review demonstrates strong evidence for insulin resistance as one of the major bases for the development of steatohepatitis. The histopathologic criteria for NASH are without a doubt an invaluable diagnostic tool for both those familiar and those not too familiar with this entity.

Li and Crawford provide an in-depth and exhaustive look at the anatomy of the biliary tree and the pathophysiology of cholestasis. This article is an excellent reference for pathologists and clinicians. Complementing this article is one by Saxena and Theise on the newly revitalized topic of the Canal of Hering. That this previously obscure structure, described more than a century ago, is now recognized as a major player in hepatic injury and repair is intriguing and interesting. These two articles are written with great clarity and both provide explicit descriptions of these ductular structures and their significance in various liver diseases.

Dhillon and colleagues provide an in-depth review of the sequence of events in liver cell regeneration. They examine the possible roles of circulating and bone marrow-derived stem cells and bipotential liver progenitor cells in the regeneration process and discuss the identification of lymphoid blastlike cells in the inflammatory cell population as putative progenitor cells in massive hepatic necrosis. Isolation and expansion of these progenitor cells in vitro, and their procurement may have future therapeutic purposes.

Hytiroglou writes an excellent article on the morphologic changes of early human hepatocarcinogenesis. Precancerous lesions, in the form of small cell changes, dysplastic foci, or high-grade dysplastic nodules, frequently difficult to differentiate from a well-differentiated hepatocellular carcinoma (HCC), are carefully described. The article by Suriawinata and Xu on the molecular genetics of HCC summarizes the myriad complex and heterogeneous genetic alterations occurring in HCC and its precursors. Gene expression profiling can complement morphological alterations in distinguishing HCCs from normal or preneoplastic lesions, can identify molecular markers that help predict prognosis and responsiveness to therapy, and can help determine whether a separate tumor nodule in the liver represents intrahepatic metastasis or a newly developed HCC.

Guido and Rugge's article on the adequacy of liver biopsy specimens addresses the long-standing concern that pathologists have on how much liver tissue is needed to assess stage and grade of chronic hepatitis. In general, the more tissue there is, the better. As documented in this critical article, the problem of adequacy has been addressed in numerous publications without much agreement as to what the minimum number of portal tracts or the minimum length of the specimen should be. The authors also compare “sampling errors” as the result of using different biopsy techniques and different sizes of the needle bore.

Finally, Wanless, one of the authorities on fibrosis and its reversibility, and Shiota propose a four-step model, including the role of lipid release and hepatic venular obstruction in the progression of NASH to cirrhosis.

We would like to thank all the contributors for sharing their knowledge and expertise in assembling this issue. We hope that the information provided will further highlight and elucidate topics being covered.