Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma

Sun, Hui‐Chuan; Zhang, Wei; Qin, Lun–Xiu; Zhang, Boheng; Ye, Qing–Hai; Wang, Lu; Ren, Ning; Zhuang, Peng–Yuan; Zhu, Xiao‐Dong; Fan, Jia; Tang, Zhao–You

doi:10.1016/j.jhep.2007.06.019

Cited by 155 publications

(146 citation statements)

References 36 publications

(52 reference statements)

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“…However, in HBV-associated HCC, only a limited number of studies have focused on this purpose, and only the HBV in the serum samples were used for correlation. [10][11][12] In this study, we assayed the virological factors directly from the noncancerous liver tissue adjacent to surgically removed HCCs. Our data clearly indicate that the viral load of HBV and the presence of BCP mutations were independently associated with postoperative prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…To date, several studies have demonstrated that serum HBV-DNA levels as well as other virological factors are closely associated with the development of HCC. 8,9 However, whereas there have been a few studies examining the prognostic value of these serological viral factors in HCC patients after surgical removal of the cancer, [10][11][12] no study has examined the prognostic value of the virological factors assayed directly from liver tissue.…”

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confidence: 99%

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Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Yeh

et al. 2010

Hepatology

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Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has never been investigated. To address this issue, 185 liver samples obtained from the noncancerous part of surgically removed HBV-associated HCC tissues were subjected to virological analysis. Assayed factors included the amount of HBV-DNA in the liver tissues; genotype; and the presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre-S deletions/stop codon mutation. All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival. It was found that an HBV-DNA level >3.0 3 10 7 copies/g of liver tissue and the presence of the basal core promoter mutation independently predicted disease-free (adjusted hazard ratio 1. Kaplan-Meier survival analysis indicated that in-frame, short stretch (<100 bp) pre-S deletions, but not large fragment (>100 bp) pre-S deletions, were significantly associated with poorer disease-free (P 5 0.005) and overall (P 5 0.020) survival. A hot deletion region located between codons 107 and 141 of the pre-S sequence was identified for the short stretch pre-S deletion mutants. Conclusion: The amount of HBV-DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. A short stretch pre-S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis. (HEPATOLOGY 2010;52:1922-1933 W orldwide, hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed solid cancer and the third most common cause of cancer-related death.1 HCC is multifactorial in origin. The three most important causes are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus infection, and alcoholic liver disease.2,3 Other risk factors include old age, male sex, underlying chronic liver diseases, and most importantly, liver cirrhosis. [4][5][6] Aflatoxin exposure and diabetes have also been linked to the development of HCC. 7In areas such as Southeast Asia, where chronic hepatitis B continues to be highly prevalent, a correspondingly high incidence of HCC is found. 4 Furthermore, despite a successful vaccination program in Taiwan, HBV remains the major etiological factor of HCC in patients over 25 years of age. Consequently, much

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Yeh

et al. 2010

Hepatology

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“…Patients were monitored every 2 months postsurgery as described. 17 A diagnosis of recurrence was based on typical appearance on computed tomography (CT) and/or magnetic resonance imaging (MRI). The recurrent tumors were treated as described in previous studies.…”

Section: Methodsmentioning

confidence: 99%

Thrombin is a therapeutic target for metastatic osteopontin-positive hepatocellular carcinoma

Xue¹,

Zhang²,

Dong³

et al. 2010

Hepatology

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We previously identified osteopontin (OPN) as a promoter and thus a potential therapeutic target for hepatocellular carcinoma (HCC) metastasis. The serine protease thrombin interacts with OPN and can modify its biological activity. To explore the role of thrombin alone or in conjunction with OPN in HCC, we studied the correlation of thrombin levels to HCC prognosis in patients with various OPN levels, and evaluated the effects of OPN fragments generated by thrombin cleavage on proliferation and adhesion of HCC cells. We found that the thrombin level was strongly associated with the metastatic potential of HCC cell lines, and that thrombin was remarkably overexpressed in HCC tissue compared with adjacent nontumor tissue. In addition, HCC tissue from patients with recurrent disease displayed much higher thrombin levels, particularly in those with elevated OPN levels. Only HCCs with elevated OPN levels had a significant correlation between high thrombin levels and overall survival (OS; P < 0.01), or time to recurrence (TTR; P < 0.0001) of HCC. Multivariate analysis revealed that thrombin was an independent prognostic indicator. In vitro assays demonstrated that thrombin promotes the proliferation and adhesion of OPN1 HCC cells. Furthermore, thrombin activated the focal adhesion kinase (FAK) pathway of OPN1 HCC cells, which was blocked by the inhibition of integrin b1. Conclusion: Thrombin plays an important role in OPN-mediated aggressive phenotype of HCC through activation of integrin b1-FAK signaling, and is an independent poor prognostic factor for HCC. Thus, thrombin may be a potential therapeutic target to inhibit HCC metastasis in OPN1 patients (HEPATOLOGY 2010;52:2012-2022 O steopontin (OPN) is an extracellular matrix (ECM) protein that binds to avb integrins and receptors of the CD44 family to propagate cellular signals and promotes induction of cell adhesion, chemotaxis, ECM degradation, angiogenesis, prevention of apoptosis, and indolent tumor growth. 1 , 2 Many studies have shown that increased OPN levels are associated with increased aggressiveness and metastatic potential of hepatocellular carcinoma (HCC) and are positively correlated with poor prognosis and early tumor recurrence in patients with HCC. 3-5 Thus, the molecules involved in the signaling pathways through which OPN mediates cancer metastasis, especially the portion of the pathway mediating the early stages of cellular invasion, may contain potential therapeutic targets for HCC metastasis. Thrombin is a serine protease that performs a multifaceted role in coagulation. Thrombin cleaves OPN at the cleavage site (RSK) into two fragments of approximately equivalent size, which changes the topological structure of OPN to display the integrin and CD44 binding domains. 7 This cleavage by thrombin improves the bioactivity of OPN and is necessary for efficient engagement with the integrin receptor. [8][9][10][11] Previous studies have demonstrated that thrombincleaved OPN is critically involved in the pathogenesis

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“…Various postoperative interventions, such as adjuvant therapy with interferon, Vitamin E or K2, or I 131 , are used to reduce the incidence of tumor recurrence after curative treatment (6,7). The adjuvant application of interferon (7)(8)(9)(10) and antiviral treatment (11,12) seems promising but should be confirmed in further multi-center phase III clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Adjuvant sorafenib reduced mortality and prolonged overall survival and post-recurrence survival in hepatocellular carcinoma patients after curative resection: A single-center experience

Zhang

Zhao

Wei

et al. 2014

BST

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Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma

Cited by 155 publications

References 36 publications

Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Thrombin is a therapeutic target for metastatic osteopontin-positive hepatocellular carcinoma

Adjuvant sorafenib reduced mortality and prolonged overall survival and post-recurrence survival in hepatocellular carcinoma patients after curative resection: A single-center experience

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