Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure

Shinn, Brianna; Martin, Aaron; Coben, Robert; Conn, Mitchell; Prieto, J.; Kroop, Howard; DiMarino, Anthony J.; Hann, Hie‐Won

doi:10.4254/wjh.v11.i1.65

Cited by 16 publications

(18 citation statements)

References 32 publications

(50 reference statements)

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“…Existing treatments can treat chronic viral hepatitis, and some research has been performed previously to domenstrate the influence of antiviral treatment on disease progression as well as HCC development[13]. Moreover, many studies suggest that the survival of virus-related HCC patients can be prolonged through curative hepatectomy and/or local tumor ablation combined with adjuvant antiviral therapy[14-16]. On the other hand, virus and non-virus HCCs have been recognized to have apparently different outcomes, and different therapeutic strategies were recommended for them.…”

Section: Discussionmentioning

confidence: 99%

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

Huang

Chen

et al. 2019

WJGO

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BACKGROUNDHepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain.AIMTo construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODSThe expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes.RESULTSA total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank P = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways.CONCLUSIONAn eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC.

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Section: Discussionmentioning

confidence: 99%

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

Huang

Chen

et al. 2019

WJGO

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“…It is important to recognize that "undetectable" is a relative term given the variation in measurements conducted by different laboratory assays. At the Liver Disease Prevention Center, Division of Gastroenterology and Hepatology of Thomas Jefferson University Hospital, long-term follow-up data has demonstrated HCC recurrence in patients even after a decade of successful viral suppression (54,55) In our observational cohort, as of October 2020, 17 patients developed HCC despite having been treated for 9-19 years (median 13 years) with undetectable HBV DNA for 3-12 years (median 8 years) (Table 1). This is among the longest known follow up studies on the development of HCC in patients taking antiviral therapy.…”

Section: Persistent Risk For Hcc Despite Successful Hbv Suppressionmentioning

confidence: 87%

Achieving a Cure: The Next Frontier in Hepatitis B Treatment

et al. 2021

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Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, significant progress has been made in understanding the pathogenesis of the virus and creating an effective vaccine. In the past two decades, several antiviral therapies have reduced the incidence of HBV-related hepatocellular carcinoma. The nucleos(t)ide analogues have succeeded in decreasing the viral load to undetectable levels but have been unable to eradicate the virus due to the persistence of covalently closed circular DNA in the hepatocyte nucleus. Despite being on successful antiviral therapy for multiple years, patients are still at risk of developing hepatocellular carcinoma. Recently, a number of different drug targets have been identified that intervene on the viral replication cycle or host immune system. This chapter discusses the immunopathogenesis of the virus, the effectiveness of nucleos(t)ide analogues, and recent therapeutic developments. In light of robust progress achieved in antiviral therapy, the cure for hepatitis B is likely on the horizon.

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“…Second, homogeneity in the case cohort was largely enhanced through pre-analysis case selection. Viral and non-viral HCC were suggested to be associated with different prognoses, and different treatment strategies were recommended; therefore, they must be distinctively analyzed to develop the models for prognosis[17-20]. In contrast to previous studies that combined viral and non-viral related HCC, the current study was conducted in HBV-positive patients only.…”

Section: Discussionmentioning

confidence: 99%

Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma

Chen

et al. 2019

WJG

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BACKGROUNDHepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes.AIMTo establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis.METHODSRNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted.RESULTSA total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR) = 66.007, 95% confidence interval (CI): 8.361-521.105; P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA.CONCLUSIONThe established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

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Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure

Cited by 16 publications

References 32 publications

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

Achieving a Cure: The Next Frontier in Hepatitis B Treatment

Significance of tumor-infiltrating immunocytes for predicting prognosis of hepatitis B virus-related hepatocellular carcinoma

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