A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection

Obata, Hiroshi; Hayashi, Naoaki; Motoike, Yoji; Hisamitsu, T; Okuda, Hiroyuki; Kobayashi, Seiichiro; Nishioka, Kusuya

doi:10.1002/ijc.2910250609

Cited by 128 publications

(38 citation statements)

References 19 publications

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“…These observations were supported by the lowest final survival rate in the hepatitis B group and by the generally high survival rates in the discontinued alcoholic group. The high incidence of hepatoma in HBsAg-positive cirrhotic patients is in accordance with the report of Obata et al (1980). The prognosis of liver cirrhosis in the present study is fairly improved as compared with our results of cirrhotic patients who were admitted in 1951-1957 (Nakamura et al 1959).…”

Section: Results and Commentssupporting

confidence: 92%

Survival of and hepatoma development in patients with liver cirrhosis.

Nakamura

Takezawa

Kera³

et al. 1982

Tohoku J. Exp. Med.

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A follow-up study was made on 75 patients with liver cirrhosis. The patients were divided into 5 groups (discontinued alcoholic group, continued alcoholic group, hepatitis B group, male non-alcoholic non-hepatitis B group, and female non-alcoholic nonhepatitis B group). Hepatoma developed in 50% of the hepatitis B group, but in 1-9% of the other 4 groups. Abstinence did not accelerate the development of hepatoma. As for survival after onset of liver cirrhosis, the 1-4-year survival of the female non-alcoholic non-hepatitis B group and the final (8-year) survival of the hepatitis B group appeared to be lower than that of the other groups. Though the survival of the discontinued alcoholic group was seemingly higher than that of the continued alcoholic group, the difference was small and not significant. liver cirrhosis; hepatoma; survival; hepatitis B; alcoholismRecently Unuma et al. (1981) noted a high incidence of hepatoma in autopsied patients with alcoholic liver cirrhosis who had given up alcohol. Similar report was made by Lee (1966). These views were, however, not in accord with our clinical experiences. This problem was accordingly investigated by a follow-up study of cirrhotic patients. SUBJECTSSubjects studied included 92 cirrhotic patients who had been diagnosed at the First Department of Internal Medicine, Tohoku University Hospital, or referred hospitals in 1971 to 1976. Patients who were diagnosed as having complicating hepatoma during the admission were excluded. Follow-up information was available on 75 of the 92 patients. The interval between the discharge and the follow-up study averaged 6.8 years, and that between the onset of liver cirrhosis and the study 7.9 years.The patients were etiologically divided into 5 groups : 1) discontinued alcoholic group (10 cases) who gave up drinking, 2) continued alcoholic group (23 cases) who continued drinking, 3) hepatitis B group (8 cases), 4) male non-alcoholic non-hepatitis B group (15 cases,) and 5) female non-alcoholic non-hepatitis B group (19 cases). Alcoholic cirrhosis

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Section: Results and Commentssupporting

confidence: 92%

Survival of and hepatoma development in patients with liver cirrhosis.

Nakamura

Takezawa

Kera³

et al. 1982

Tohoku J. Exp. Med.

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“…However, only a few cases without cirrhosis were detected in >500 HBV-associated HCC cases, and therefore these were not included in the present study. A similar observation was identified by Obata et al, reporting that HCC was developed only in 23% of patients who were HBsAg-positive and suffered from cirrhosis and in only 5.9% of patients who were HBsAg-negative and presented liver cirrhosis (34).…”

Section: Discussionsupporting

confidence: 84%

Increased glyceraldehyde-3-phosphate dehydrogenase expression indicates higher survival rates in male patients with hepatitis B virus-accociated hepatocellular carcinoma and cirrhosis

Liu

Zhu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported in different human malignancies. To understand its role in hepatitis B virus (HBV) infection-associated hepatocellular carcinoma (HCC), the expression of GAPDH was quantitatively measured in a cohort of 72 male HCC patients without preoperative treatment, all with evidence of chronic HBV infection. Using C-terminal banding protein 1 (CTBP1) or hypoxanthine phosphori bosyltransferase 1 (HPRT1) as reference genes, the level of GAPDH mRNA in tumor tissue was found to be significantly higher compared with that in paired non tumor tissues (P=0.0087 for CTBP1; P=0.0116 for HPRT1). Accordingly, compared with the non-tumor tissue, 37.5% (27/72) of patients' tumor tissues had a more than 2-fold increase of GAPDH expression. Furthermore, following knockdown GAPDH expression via siRNA transient transfection, HepG2 cells exhibited enhanced resistance to cytosine arabinoside (IC 50 , 308.28 µM vs. 67.68 µM in the control; P=0.01). Notably, higher GAPDH expression was significantly associated with lower liver fibrosis score (P= 0.0394) and a tendency towards higher survival rates for patients with HCC. To the best of our knowledge, the present study is the first study to report that the elevated expression levels of GAPDH in HCC tumor tissue may be relevant to an improved fibrosis score and survival probability in male patients with HBV infection; however, the underlying mechanism requires further investigation. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality in males and the sixth leading cause in females worldwide (1). In addition, HCC is ranked as the second leading cause of cancer-related mortality in China (2). Over 50% of the annual HCC cases reported worldwide are diagnosed in the Chinese population (3), while hepatitis B virus (HBV) infection is responsible for 80% of all HCC causes in China (4). While a number of studies have revealed that HBV infection is the key pathogenic factor for the development of HCC, male gender and cirrhosis have also been found to be independent risk factors for the occurrence of HCC (5-7). However, few studies exist on patients presenting all these risk factors.Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was initially considered to be an essential glycolytic enzyme that is expressed in all prokaryotic and eukaryotic organisms. GADPH plays a major role in cellular metabolism, converting glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate (8). In addition, studies have demonstrated that GAPDH is involved in certain important physiological functions, including the transport of transfer RNA (9), translational control (10)

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“…Group II included patients with chronic hepatitis, without apparent tumor. Liver tissue samples from patients 14,15,17,18,19,20,21,22,23,25, and 26 were obtained by a surgical biopsy and liver tissue samples from patients 16,24,27,28,29, and 30 by a needle biopsy (=15 mg). Group III included two patients with acute hepatitis.…”

Section: Methodsmentioning

confidence: 99%

State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases.

Bréchot¹,

Hadchouel²,

Scotto³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

313

131

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Using the Southern blot technique and cloned hepatitis B virus (HBV) DNA as a probe, we studied the state of HBV DNA in the liver of 13 patients with hepatocellular carcinoma, 17 patients with chronic hepatitis, and 2 patients with acute hepatitis. The hybridization results were compared with the serological and immunohistological data. Integration of HBV DNA in cellular DNA of the liver from patients with hepatocellular carcinoma was demonstrated. In two patients from which tumorous and nontumorous liver tissue samples were available the integration patterns were different. In one patient with hepatitis B e antigen (HBeAg)-positive early hepatocellular carcinoma, free viral DNA was present in the liver. In some patients with HBeAg-negative chronic hepatitis, without tumor, integration of HBV DNA in cellular DNA was also demonstrated. This suggests that HBV is not the only factor involved in the development of a tumor. In patients with HBeAg-positive chronic hepatitis, free viral DNA was detected in the liver. In the two acute hepatitis patients analyzed, the restriction endonuclease patterns strongly suggested HBV DNA integration. Therefore, viral DNA integration seems to occur early in infection. Whatever the form of the disease, discrete bands were observed, suggesting the existence oflimited and specific integration sites in host cellular DNA. The presence of integrated or free DNA sequences has implications for antiviral therapy. In addition, detection ofHBV DNA in the liver is another sensitive viral marker that could be useful for diagnostic purposes.Exposure to hepatitis B virus (HBV) can be followed by acute and chronic hepatitis (1). In addition, human HBV chronic carriers have a significantly increased risk of developing hepatocellular carcinoma (2). The Southern blot technique (3) using cloned HBV DNA as a probe (4) provides another approach to investigating the relationship between HBV and these pathological conditions. Presence and integration of HBV DNA sequences in the cellular DNA of hepatocellular carcinomas and of a hepatoma cell line (5-8) have been demonstrated. This observation is an additional argument for HBV as a factor in this human cancer. Thus, it is important to investigate the state of the viral DNA in chronic hepatitis and acute hepatitis. Additionally, the results of the hybridization technique should be compared to the serological and histological tests of HBV infection to evaluate its diagnostic usefulness. In this report, we present evidence for integration of HBV DNA in tumorous and nontumorous parts of the liver of patients with hepatocellular carcinoma and in the liver of patients with chronic and acute hepatitis B.

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A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection

Cited by 128 publications

References 19 publications

Survival of and hepatoma development in patients with liver cirrhosis.

Survival of and hepatoma development in patients with liver cirrhosis.

Increased glyceraldehyde-3-phosphate dehydrogenase expression indicates higher survival rates in male patients with hepatitis B virus-accociated hepatocellular carcinoma and cirrhosis

State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and -negative liver diseases.

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