Clinicopathological differences between hepatitis B viral genotype B‐ and C‐related resectable hepatocellular carcinoma

Lin, Chun-Yao; Jd, Chen; Liu, Chun‐Jen; Lee, Po‐Huang; Pj, Chen; My, Lai; Kao, Jia‐Horng; Ds, Chen

doi:10.1111/j.1365-2893.2006.00776.x

Cited by 22 publications

(20 citation statements)

References 40 publications

(49 reference statements)

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“…All these possible mechanisms might explain why higher serum HBV-DNA level was associated with poor prognosis of HCC and became an important risk factor of metastasis or recurrence. Clinical and virological implications of HBV genotypes showed that HBV genotype C has a higher risk of HCC development than HBV genotype B, and genotype C HBV infection may be associated with more active and progressive liver disease [Lin et al, 2007]. A previous pathological study on HCC suggested that patients with genotype C HBV infection could be prone to the development of multiple tumors in cirrhosis liver, and liver cirrhosis and multiple tumors have been documented as important prognostic factors for patients with respectable HCC [Tobe et al, 1994].…”

Section: Discussionmentioning

confidence: 98%

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Huang

Wang

et al. 2008

Journal of Medical Virology

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Identification of risk factors for recurrence and metastasis of HCC is important for the prognosis of HCC surveillance in chronic HBV infection. In this article, 125 HCC patients recruited were followed up prospectively for tumor metastasis and recurrence for a median of 104 (10-130) weeks. HBV DNA level was detected by LightCycler-based real-time fluorescence quantitative polymerase chain reaction-restriction system. HBV genotypes were determined by using PCR restriction-fragment length polymorphism. BCP and PC mutations were performed by PCR and direct sequencing of amplified products. Among 125 HCC patients, 19 patients were excluded because of the lack of follow-up data and the remaining 106 patients were followed up of 2 years and entered into analysis. Sixty-nine patients had tumor metastasis or recurrence during the follow-up and the cumulative probability of HCC metastasis or recurrence was 65.1%. On multivariate analysis, genotype C and HBV DNA level were the risk factors for HCC recurrence or metastasis. The incidence of recurrence or metastasis increased with baseline HBV DNA level in a dose-response relationship ranging from 22% for HBV DNA level of less than 3 log10 copies/ml to 80% for HBV DNA level of 5 log10 copies/ml or greater (P = 0.012). Fifty-seven (74.0%) and 12 (41.4%) patients had metastasis or recurrence in patients with genotype C and B, respectively. The adjusted OR of recurrence or metastasis for genotype C compared with genotype B was 9.755 (P = 0.009). In conclusion, elevated HBV DNA level and genotype C are strong risk predictors of HCC metastasis or recurrence.

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Section: Discussionmentioning

confidence: 98%

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Huang

Wang

et al. 2008

Journal of Medical Virology

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“…Among our 193 patients with resectable HBV-related HCC, genotype B patients were less associated with cirrhosis compared with genotype C patients (33% vs. 51%, P = 0.01). Pathologically, genotype B patients had a higher rate of solitary tumor (94% vs. 86%, P = 0.048) and more satellite nodules (22% vs. 12%, P = 0.05) than genotype C patients [57]. These characteristics may contribute to the recurrence patterns and prognosis of HBV-related HCC patients with genotype B or C infection [58].…”

Section: Genotype and Subgenotypementioning

confidence: 97%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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“…In Taiwan, among 193 HBV-related HCC patients receiving surgery, genotype B patients had a higher rate of solitary tumor (94% vs. 86%, P ¼ 0.048) but more satellite nodules (22% vs. 12%, P ¼ 0.05) than genotype C patients (Chen et al 2004b;Lin et al 2007b). Wu et al (2009) also reported that in HCC patients, liver inflammation activity was higher in HBV genotype C patients than in genotype B patients (P ¼ 0.023), and more genotype C patients tended to have a higher viral load (.10 6 copies/ml) than genotype B patients (52.3% vs. 37.6%, P ¼ 0.067).…”

Section: Hbv Genotypes and Risk Of Hcc Developmentmentioning

confidence: 99%

Hepatitis B Virus Genotypes and Variants

Lin

Kao

2015

Cold Spring Harbor Perspectives in Medicine

201

139

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At least 10 hepatitis B virus (HBV) genotypes (A to J) with distinct geographic distributions and several HBV mutants, including precore/core promoter mutations and pre-S/S deletion mutations, have been recognized to be not only predictive of liver disease progression but also associated with response to antiviral therapy. HBV genotype -specific pathogenesis may contribute to heterogeneous clinical outcomes in chronic hepatitis B patients across the world. For example, patients with HBV genotypes C and D infection have a lower rate of spontaneous HBeAg seroconversion. In addition, HBV genotypes C and D have a higher frequency of core promoter and pre-S mutations than genotypes A and B. Genotypes C and D also carry a higher lifetime risk of cirrhosis and HCC development than genotypes A and B. Core promoter and pre-S mutations also correlate with an increased risk of hepatocellular carcinoma (HCC). Therapeutically, genotypes A and B patients have a better response to interferon-based therapy than genotypes C and D patients, but the response to nucleos(t)ide analogs is comparable across different HBV genotypes. In conclusion, HBV genotypes and variants may serve as viral genetic markers to predict disease progression as well as help practicing physicians optimize individualized antiviral therapy in clinical practice.

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Clinicopathological differences between hepatitis B viral genotype B‐ and C‐related resectable hepatocellular carcinoma

Cited by 22 publications

References 40 publications

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

Role of viral factors in the natural course and therapy of chronic hepatitis B

Hepatitis B Virus Genotypes and Variants

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