Liver cell dysplasia in cirrhosis. A serologic and immunohistochemical study

Abstract

Liver cell dysplasia (LCD) was investigated for hepatitis B virus (HBV) markers, alpha-fetoprotein (AFP) and ferritin by serologic and immunohistochemical methods in 101 patients with cirrhosis. LCD was found in 30 cases (29.7%), with the highest incidence in cases of posthepatitic cirrhosis (67%). In the group of dysplastic cirrhosis (DC) 46.6% of the patients had active HBV infection (hepatitis B surface antigen [HBsAg] serum positivity) compared with 7% of the patients with nondysplastic cirrhosis (NDC) (P < 0.01). The mean serum AFP concentration was significantly raised in the DC group compared with that in the NDC group (P < 0.05). In seven patients with LCD at the initial biopsy, the histologic follow-up showed the persistence of LCD in all cases, and the development of hepatocellular carcinoma (HCC) in three cases. In serologic HBsAg-positive cases, dysplastic cells, at variance with the surrounding liver parenchyma, were almost always negative for tissue HBsAg, and always negative for tissue hepatitis B core antigens (HBcAg). AFP was never detected in either normal or dysplastic cells. Ferritin was found in all cases, but dysplastic foci displayed a lesser amount of this protein. These serologic and immuno-histochemical data strongly suggest a preneoplastic significance of LCD. The importance of monitoring cirrhotic patients with LCD and particularly those with HBV infection and/or increased AFP levels with more aggressive follow-up is also stressed. Cancer 57:1515-1521, 1986. IVER CELL DYSPLASIA (LCD) i S a well-known histologic L entity with preneoplastic significance in experimental hepatic onc~genesis.'-~ In humans, LCD was first described by Anthony et aL4 who proposed strict morpho-logic criteria for its identification. Since that study, other authors have reported the frequent association between LCD and hepatocellular carcinoma (HCC) so that, even in men, a preneoplastic role of LCD was Moreover, LCD was frequently found in association with chronic hepatitis B virus (HBV) infection, a condition predisposing to hepatic tumors mainly in those areas where there is a high incidence of viral i n f e ~ t i o n. ~ ~ ~ ~ ' ~-' ~ However, in white populations, this relationship is less evident, and a large number of HCC is preceeded by cir-rhosis, suggesting that chronic liver disease could be con

Large liver cell dysplasia: A controversial entity

“…This feature that is consistently reported in different studies, either on liver biopsies or on surgical resections, has been taken to support premalignancy, given the multifocal hepatic carcinogenesis, or to disclaim it as a simple bystander phenomenon [14]. Another interesting feature of dysplasia is its persistence over time, as reported in consecutive liver biopsies [10,15]. Such a feature is biologically consistent either with a lesion uncommitted to die or with an age-related change.…”

“…Some papers suggested that LCC is mostly negative for tissue HBsAg/HBcAg [15,29]. Given that loss of expression of viral proteins is a common feature of malignant hepatocytes, possibly due to HBV integration into the host DNA, more objective data on HBV physical status and protein expression should be provided to address putative similarities between dysplastic and malignant hepatocytes in HBV-related cirrhosis.…”

“…In contrast, the incidence is higher in studies on explanted cirrhotic livers, with rates of 71-85% in C viral cirrhosis and 100% in B viral cirrhosis (Table 1) [10][11][12][14][15][16][17][18][19][20]. The substantial increase of LCC in resected specimens may be due to either the occurrence of LCC in the liver adjacent to HCC or to the greater chance of recognizing LCC on larger size specimens as well as at the end-stage of the disease.…”

Liver cell dysplasia and risk of hepatocellular carcinoma in cirrhosis: a preliminary report.

“…This work was presented in part at the 25th meeting of the European Association for the Study of the Liver in Budapest, [3][4][5][6] October 1990.…”

Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Only a few prospective studies have ing intensive screening for HCC. Liver cell dysplasia 32,33,[37][38][39] has been considered prebeen performed to determine the predictive factors for the occurrence of HCC on cirrhotic liver. [27][28][29][30] However, cancerous.…”