Cirrhosis and hepatocellular neoplasia: More like cousins than like parent and child

Theise, N

doi:10.1053/gast.1996.v111.agast961110526

Cited by 27 publications

(17 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have indicated that at least in a subset of cases, MRN and DN are indeed monoclonal (Paradis et al, 1998) and that their clonal expansion may be initiated before the full development of cirrhosis (Theise, 1995(Theise, , 1996. Results of other molecular studies Roncalli et al, 1999;Zondervan et al, 2000) are in keeping with the concept of a multistep process in hepatic carcinogenesis from cirrhosis to well-developed HCC.…”

mentioning

confidence: 60%

“…Cirrhosis has been considered in itself a preneoplastic condition (Okuda, 1992), while it has been shown that at least a subset of cirrhotic nodules may be monoclonal in origin (Aihara et al, 1994). Monoclonal neoplastic expansion could be initiated before the full development of cirrhosis (Theise, 1996). Therefore it could be speculated that cirrhosis progresses to cancer through a molecular pathway marked by sequential and additional genetic changes towards malignancy .…”

Section: Tornillo Et Almentioning

confidence: 99%

See 1 more Smart Citation

Chromosomal Alterations in Hepatocellular Nodules by Comparative Genomic Hybridization: High-Grade Dysplastic Nodules Represent Early Stages of Hepatocellular Carcinoma

Tornillo

Carafa

Sauter

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Data from experimental hepatocarcinogenesis and recent studies in humans have suggested that the emergence of hepatocellular carcinoma (HCC) is a stepwise process. However, despite abundant experimental data, the precise molecular mechanisms and genetic alterations involved in human liver carcinogenesis are still unclear. Comparative genomic hybridization was used to analyze 26 hepatocellular nodules obtained from patients undergoing liver transplantation or surgical resection for HCC. According to the criteria proposed by the International Working Party, 16 nodules were classified as multiacinar regenerative nodules (MRN), 4 as low-grade dysplastic nodules (LG-DN), and 6 as high-grade dysplastic nodules (HG-DN). Our aim was to investigate the possible genetic differences between MRN, LG-DN, and HG-DN. The whole group of nodules showed only a few aberrations (mean 1.1/case), without any significant pattern. This finding is comparable to what happens in non-neoplastic tissue. On the contrary, in three of six HG-DN, we found deletions of 8p and gains of 1q.LG-DN and MRN did not show these chromosomal imbalances. These results confirm the important role of allelic losses on 8p as well as of gains of 1q in HCC. We conclude that the genes that are important in early stages of hepatocarcinogenesis are probably located on these chromosomal arms. (Lab Invest 2002, 82:547-553).

show abstract

mentioning

confidence: 60%

Section: Tornillo Et Almentioning

confidence: 99%

Chromosomal Alterations in Hepatocellular Nodules by Comparative Genomic Hybridization: High-Grade Dysplastic Nodules Represent Early Stages of Hepatocellular Carcinoma

Tornillo

Carafa

Sauter

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…46 As such, early estrogen exposure resulting from the early onset of menarche could potentially influence the replication activity of HBV at early ages, causing various degrees of hepatic lesions, including chronic hepatitis and cirrhosis, which are closely associated with the subsequent risk of developing HCC. 38,44 However, estrogen might suppress the growth of HCC and/or the regenerative nodule, which is the most important preneoplastic lesion of HCC, 47 in cirrhotic patients. 43 In conclusion, our observations of a relation between HCC and several reproductive events that are thought to reflect cumulative exposure to estrogen provide indirect evidence supporting a role for estrogen in HCC development.…”

Section: Discussionmentioning

confidence: 99%

Role of Reproductive Factors in Hepatocellular Carcinoma: Impact on Hepatitis B- and C-Related Risk

Chang

et al. 2003

Hepatology

106

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is more prevalent in men than in women. Estrogen may play some role in the development of HCC. We conducted a multicenter case-control study to evaluate the effects of reproductive factors on HCC risk, and to assess whether the association between each factor and HCC differs between hepatitis B surface antigen (HBsAg)-positive and -negative women, in which hepatitis C virus (HCV) is the major cause of HCC. The study included 218 women with HCC and 729 control women selected from nonbiological and firstdegree female relatives of patients with HCC. The risk of HCC was inversely related to the number of full-term pregnancies (FTP) (P trend ‫؍‬ .0216) and age at natural menopause (P trend ‫؍‬ .0251 among women aged 45-55 without prior surgical menopause). Oophorectomy at age <50 during premenopausal years was also a risk factor (multivariate-adjusted OR, 2.57; 95% CI, H epatocellular carcinoma (HCC) is a highly malignant disease characterized by a striking male predominance; the male-to-female ratios in the incidence of HCC range from 2 to 4 in geographically diverse populations. 1,2 This gender difference may be, at least in part, attributable to differences in exposure to lifestyle risk factors for HCC, such as alcohol consumption and cigarette smoking. 3,4 However, sex hormone and X-linked genetic factors may also be important.Estrogen receptors exist in both mammalian and human livers. [5][6][7][8] In experimental rats and mice, there is also a greater preponderance of HCC in male subjects compared with female subjects. This sex difference has been observed in various animal models, including transgenic mice expressing hepatitis B or C viral proteins. [9][10][11][12][13][14][15] In addition, ovariectomy in mice increased susceptibility to chemically induced hepatocarcinogenesis. 11,16 Although these observations may suggest some role for endogenous estrogen in the etiology of HCC in humans, these aspects received relatively scant attention. [17][18][19] Exogenous estrogen use may also be associated with the risk of HCC. Several case reports have described the occurrence of liver adenomas or focal nodular hyperplasia in women taking oral contraceptives, 20 and the possible association between use of oral contraceptives and the risk of HCC has been assessed in several studies. 3,17,[21][22][23][24][25][26][27] However, most of these studies were based on a very limited number of case subjects, and the results have been incon-

show abstract

“…The concept that cirrhosis itself is premalignant is probably incorrect; rather, it develops in parallel with neoplasia in a chronically diseased liver. 35,36 Coinfection with HIV During the early years of hepatitis C recognition, there was also very little that could yet be done for HIV infection. Successful anti-retroviral therapy was still more than half a decade away.…”

Section: Neoplasia-related Changesmentioning

confidence: 99%

Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach

2007

View full text Add to dashboard Cite

The terminology for assessment of chronic viral hepatitis in liver biopsy specimens has become confusing with the proliferation of grading and staging schemes that have paralleled the rise of the hepatitis C epidemic and the importance of mixed viral infections. This review represents a personal approach to the interpretation of these biopsy specimens, aiming at clarifying and simplifying the important points for the general pathologist confronted by these diagnostic dilemmas. The most commonly used schemes-Ishak modification of the Knodell 'hepatic activity index', Scheuer, Metavir, Batts-Ludwig classifications-are presented with evaluation of their pros and cons. Which scheme is selected is less important than the consistent use of a single scheme and the clear naming of that scheme in pathology reports. The importance and clinical implications of identifying severe necroinflammatory activity in the form of 'confluent necrosis' is discussed. Pathologists must also be clear about assessing concomitant diseases, in particular, alcoholic or non-alcoholic fatty liver disease, and be aware that grading/staging schemes for chronic hepatitis do not apply to mixed disease conditions. Other important features to be evaluated in all chronic hepatitis biopsy specimens include iron (which may represent hereditary hemochromatosis or secondary uptake) and neoplasia-associated changes, namely large cell change and small cell change; these findings and their clinical import are updated and reviewed. Sample approaches to composing useful diagnostic reports are also presented. Modern Pathology (2007) 20, S3-S14. doi:10.1038/modpathol.3800693Keywords: grading; staging; chronic hepatitis; viral hepatitis; liver biopsy Once upon a time, the assessment of liver biopsy specimens from patients with chronic viral hepatitis was very simple. There were three categories created for us by the Gnomes (not fairytale, mythical, woodland folk, but 'an International Working Group' of liver pathologists): chronic persistent, active, and lobular hepatitis (CPH, CAH, and CLH, respectively).1 In addition, one would describe the scarring and the progression toward cirrhosis. These categories were sufficient because there were only three likely diseases to be dealt with: autoimmune hepatitis, hepatitis B, and non-A-non-B hepatitis. For the first two, these categories of histopathology were reasonably prognostic. Also, only autoimmune hepatitis had a treatment, which was immune suppression. As for non-A, non-B hepatitis, welly there wasn't much to be said for that beyond describing the histologic changes, knowing that CPH, CAH, and CLH were not predictive in those cases.Then things changed. Hepatitis C was discovered and the true extent of the epidemic was made clear. Antiviral treatments were developed that required assessments in clinical trials and detailed comparison between pre-and post-treatment biopsies. Continuing intravenous drug use in urban centers made mixed viral infections more common. Most liver biopsies were not performed for autoimmu...

show abstract

Cirrhosis and hepatocellular neoplasia: More like cousins than like parent and child

Cited by 27 publications

References 1 publication

Chromosomal Alterations in Hepatocellular Nodules by Comparative Genomic Hybridization: High-Grade Dysplastic Nodules Represent Early Stages of Hepatocellular Carcinoma

Chromosomal Alterations in Hepatocellular Nodules by Comparative Genomic Hybridization: High-Grade Dysplastic Nodules Represent Early Stages of Hepatocellular Carcinoma

Role of Reproductive Factors in Hepatocellular Carcinoma: Impact on Hepatitis B- and C-Related Risk

Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach

Contact Info

Product

Resources

About