Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level

Chen, Chien-Jen; Yang, Hwai I.; Su, Jun; Jen, C.-L.; You, San–Lin; Lu, Sheng–Nan; Huang, Guan-Tarn; Iloeje, Uchenna H.

doi:10.1001/jama.295.1.65

Cited by 2,781 publications

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“…Genotype C virus has been associated with high rates of progression to the complications of CHB, including cirrhosis and HCC [7][8][9][10][11]. In addition to genotype, the level of HBV DNA in the serum is strongly associated with liver disease progression [12,13]. Persistently detectable and elevated viral loads predict the highest risk of progression to cirrhosis and HCC [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to genotype, the level of HBV DNA in the serum is strongly associated with liver disease progression [12,13]. Persistently detectable and elevated viral loads predict the highest risk of progression to cirrhosis and HCC [12][13][14]. Suppression of HBV replication with antiviral therapy may reduce the risk of complications and improve the long-term outcomes of CHB patients [15].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

et al. 2010

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Purpose Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudinerefractory Japanese patients treated with entecavir for 3 years. Methods Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples.Results After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55% (36/65) of patients had hepatitis B virus (HBV) DNA of [400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of C1 9 upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion. A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of [400 copies/mL, 84% (27/32) had ALT of C1 9 ULN, and 15% (4/27) achieved HBe seroconversion. Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed 123Hepatol Int (2010) 4:414-422 DOI 10.1007/s12072-009-9162-x improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares. Conclusions Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

et al. 2010

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“…How-ever, evidence is now available concerning direct effects of HBV in this process; indeed, recent data demonstrate that serum HBV DNA level is a strong risk predictor of HCC independent of HBeAg, serum alanine aminotransferase level and liver cirrhosis (Chen et al, 2006). Thus, HBV should be considered as having synergistic effects with chronic inflammation (Figure 1).…”

Section: The Role Of Hepatitis B Virus In Liver Cell Carcinogenesismentioning

confidence: 99%

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

et al. 2006

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As discussed in detail in other chapters of this review, chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated with the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarize the current knowledge on the mechanisms involved in HBVrelated liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus, as well as between viral infections and other environmental factors, such as alcohol.

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“…2,3 The current gold standard in monitoring viral loads is real-time polymerase chain reaction (PCR), which offers high sensitivity and accuracy. 4 Data from these assays reflect the disease status and are employed by most clinical studies.…”

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confidence: 99%

“…4 Data from these assays reflect the disease status and are employed by most clinical studies. 2,3 The shortcomings of PCR, however, are its relatively high cost and unavailability in some areas. Moreover, viral activity can still be monitored in patients with undetectable HBV DNA through the measurement of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) titers.…”

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Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

et al. 2011

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Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(1)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/ mL), and 1.71 Paul Ehrlich (PE) IU/mL (20.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(1) patients, baseline alanine aminotransferase (P 5 0.013), HBV DNA (P 5 0.040), and qHBsAg levels (P 5 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(1) group versus the SR(2) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(1) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(1) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (HEPATOLOGY 2011;53:1486-1493 C hronic infection with hepatitis B virus (HBV) is a worldwide health problem, with more than 400 million people thought to be infected.Moreover, these patients are at increased risk for disease progression to cirrhosis and hepatocellular carcinoma. 1 Large cohort studies have shown that elevated levels of Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; AUC, area under the curve; AUROC, area under the receiver operating characteristic

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Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level

Abstract: Elevated serum HBV DNA level (> or =10,000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.

Cited by 2,781 publications

References 21 publications

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

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