Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma

Liu, Jessica; Yang, Hwai I.; Lee, Hsuan-Shu; Lu, Sheng; Jen, C.-L.; Batrla-Utermann, Richard; Wang, Li Yu; You, San–Lin; Hsiao, Chuhsing Kate; Chen, Pei‐Jer; Chen, Chien Jen

doi:10.1136/gutjnl-2013-305785

Cited by 163 publications

(156 citation statements)

References 38 publications

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“…Earlier HBeAg seroconversion with subsequent low viral load (,2000 IU/mL) usually confers a favorable clinical outcome (Liu et al 2013a), whereas late or absent HBeAg seroconversion after multiple hepatitis flares may accelerate the progression of chronic hepatitis leading to cirrhosis; it, therefore, has a poor clinical outcome Hsu et al 2002;Yang et al 2002;Chu and Liaw 2007;Liu et al 2013a). The pathogenic differences among various HBV genotypes have been partially clarified and influence the clinical outcomes of HBV infection (Table 2).…”

Section: Intergenotypic Recombinationmentioning

confidence: 99%

Hepatitis B Virus Genotypes and Variants

Lin

Kao

2015

Cold Spring Harbor Perspectives in Medicine

195

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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Section: Intergenotypic Recombinationmentioning

confidence: 99%

Hepatitis B Virus Genotypes and Variants

Lin

Kao

2015

Cold Spring Harbor Perspectives in Medicine

195

139

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“…The best patient outcome is seen with clearance of hepatitis B surface antigen (HBsAg) from the serum, with or without development of measurable antibodies to HBsAg (Yuen et al, 2004(Yuen et al, , 2008. For patients with HBsAg seroclearance, the risk of developing HCC is markedly reduced yet still modestly elevated relative to background levels in the general ''healthy'' population (Liu et al, 2014). For the 5-7% of HBV-infected adults who do not clear HBsAg, there is a substantially increased risk of developing cirrhosis, hepatic decompensation, and HCC (Fattovich et al, 2004;Ganem and Prince, 2004;Liaw et al, 1988;Marcellin et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent

et al. 2015

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Current therapies for chronic hepatitis B virus infection (CHB) - nucleos(t)ide analogue reverse transcriptase inhibitors and interferons - result in low rates of functional cure defined as sustained off-therapy seroclearance of hepatitis B surface antigen (HBsAg). One likely reason is the inability of these therapies to consistently and substantially reduce the levels of viral antigen production. Accumulated evidence suggests that high serum levels of HBsAg result in exhaustion of the host immune system, rendering it unable to mount the effective antiviral response required for HBsAg clearance. New mechanistic approaches are required to produce high rates of HBsAg seroclearance in order to greatly reduce off-treatment disease progression. Already shown to be a clinically viable means of reducing gene expression in a number of other diseases, therapies based on RNA interference (RNAi) can directly target hepatitis B virus transcripts with high specificity, profoundly reducing the production of viral proteins. The fact that the viral RNA transcripts contain overlapping sequences means that a single RNAi trigger can result in the degradation of all viral transcripts, including all messenger RNAs and pregenomic RNA. Advances in the design of RNAi triggers have increased resistance to degradation and reduced nonspecific innate immune stimulation. Additionally, new methods to effectively deliver the trigger to liver hepatocytes, and specifically to the cytoplasmic compartment, have resulted in increased efficacy and tolerability. An RNAi-based drug currently in clinical trials is ARC-520, a dynamic polyconjugate in which the RNAi trigger is conjugated to cholesterol, which is coinjected with a hepatocyte-targeted, membrane-active peptide. Phase 2a clinical trial results indicate that ARC-520 was well tolerated and resulted in significant, dose-dependent reduction in HBsAg for up to 57days in CHB patients. RNAi-based therapies may play an important role in future therapeutic regimes aimed at improving HBsAg seroclearance and eliminating the need for lifelong therapy. This paper forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."

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“…Various host, viral, and environmental risk factors for HBVrelated hepatocellular carcinoma have been identified, including family history, serum HBV DNA and HBsAg levels, viral genotype, environmental toxins, and alcohol consumption (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Alcohol consumption has been previously established as a risk factor for hepatocellular carcinoma even among individuals with chronic HBV infection (6,7,15,16).…”

Section: Introductionmentioning

confidence: 99%

Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B–Related Hepatocellular Carcinoma

Liu

Yang

Lee

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The role of polymorphisms on ADH1B and ALDH2 in patients with chronic hepatitis B is unclear. This study aims to examine whether alcohol drinking mediates the association between two ADH1B and ALDH2 polymorphisms and the risk of hepatocellular carcinoma among chronic hepatitis B patients.Methods: A total of 3,824 individuals were enrolled in this study. Two SNPs, rs1229984 (ADH1B) and rs671 (ALDH2), were genotyped using the Affymetrix Axiom Genome-Wide CHB1 Array (Affymetrix, Inc). Multivariate unconditional logistic regression and mediation analyses were used, comparing CT or TT with CC for rs1229984 and GA and AA with GG for rs671.Results: There were 602 cases of hepatocellular carcinoma and 3,222 controls. Frequencies of the rs1229984 (ADH1B) T allele and rs671 (ALDH2) A allele were 72.9% and 28.8%, respectively. Individuals who carried at least one deficient allele for both SNPs

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Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma

Abstract: Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.

Cited by 163 publications

References 38 publications

Hepatitis B Virus Genotypes and Variants

Hepatitis B Virus Genotypes and Variants

Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent

Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B–Related Hepatocellular Carcinoma

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