Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients

Liu, Matt; Tseng, Tai Chung; Jun, Dae Won; Yeh, Ming Lun; Trinh, Huy N.; Wong, Grace Lai–Hung; Chen, Chien Hung; Peng, Cheng Yuan; Kim, Sung Eun; Oh, Hongseob; Kwak, Min Sun; Cheung, Michael C.; Toyoda, Hidenori; Hsu, Yao Chun; Jeong, Jae Yoon; Yoon, Eileen L.; Ungtrakul, Teerapat; Zhang, Jian; Xie, Qing; Ahn, Sang Bong; Enomoto, Masaru; Shim, Jae Jun; Cunningham, Chris; Jeong, Soung Won; Cho, Yong Kyun; Ogawa, Eiichi; Huang, Rui; Lee, Dong Hoon; Takahashi, Hirokazu; Tsai, Pei‐Chien; Huang, Chung Feng; Dai, Chia Yen; Tseng, Cheng Hao; Yasuda, Satoshi; Kozuka, Ritsuzo; Li, Jiayi; Wong, Christopher; Wong, Clifford; Zhao, Changqing; Hoang, Joseph; Eguchi, Yuichiro; Wu, Chao; Tanaka, Yasuhito; Gane, Ed; Tanwandee, Tawesak; Cheung, Ramsey; Yuen, Man Fung; Lee, Hyo Suk; Yu, Ming; Yang, Hwai I.; Nguyen, Mindie H.

doi:10.1007/s12072-020-10113-2

Cited by 17 publications

(9 citation statements)

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“…The development of novel biomarkers may also represent a cost-effective way to expand HCC screening to other groups that are not included in current HCC surveillance recommendations but have been found to have increased risk, such as men under age 40 or women under age 50 with chronic HBV infection but not cirrhosis. [38] The findings of this study also augment a large body of existing evidence that surveillance is underused among multiple subgroups of patients at high risk for HCC. [9,12,14,21,33] Interestingly, adherence to surveillance guidelines in the present study was similar to that observed in our previous analysis conducted among patients with cirrhosis, in which 34% had received an abdominal ultrasound at 6 months.…”

Section: Discussionsupporting

confidence: 65%

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Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States

et al. 2022

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Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high‐risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow‐up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53–2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26–13.07, p < 0.001). Mean total and patient‐paid daily surveillance‐related costs ranged from $99 (ultrasound) to $334 (magnetic resonance imaging), and mean annual patient costs due to lost productivity for surveillance‐related outpatient visits ranged from $93 (using the federal minimum wage) to $321 (using the Bureau of Labor Statistics wage). Conclusion: Use of current HCC surveillance strategies was low across patients with HBV infection, and surveillance was associated with substantial patient financial burden. These data highlight an urgent need for accessible and easy‐to‐implement surveillance strategies with sufficient sensitivity and specificity for early HCC detection.

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Section: Discussionsupporting

confidence: 65%

“…The development of novel biomarkers may also represent a cost‐effective way to expand HCC screening to other groups that are not included in current HCC surveillance recommendations but have been found to have increased risk, such as men under age 40 or women under age 50 with chronic HBV infection but not cirrhosis. [ 38 ]…”

Section: Discussionmentioning

confidence: 99%

Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States

et al. 2022

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“…Meanwhile, CHB patients can also develop HCC without cirrhosis. The new data show that annual HCC rates ranged 0.03%–1.57% among non-LC Asian CHB male patients ( 4 ). In involving 34,952 patients, the study suggested that 2.29% of CHB patients would develop HCC despite hepatitis B surface antigen (HBsAg) seroclearance ( 5 ).…”

Section: Introductionmentioning

confidence: 97%

A CpG Methylation Signature as a Potential Marker for Early Diagnosis of Hepatocellular Carcinoma From HBV-Related Liver Disease Using Multiplex Bisulfite Sequencing

Song

Qin

et al. 2021

Front. Oncol.

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BackgroundAberrant methylation of CpG sites served as an epigenetic marker for building diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC).MethodsUsing Illumina 450K and EPIC Beadchip, we identified 34 CpG sites in peripheral blood mononuclear cell (PBMC) DNA that were differentially methylated in early HCC versus HBV-related liver diseases (HBVLD). We employed multiplex bisulfite sequencing (MBS) based on next-generation sequencing (NGS) to measure methylation of 34 CpG sites in PBMC DNA from 654 patients that were divided into a training set (n = 442) and a test set (n = 212). Using the training set, we selected and built a six-CpG-scorer (namely, cg14171514, cg07721852, cg05166871, cg18087306, cg05213896, and cg18772205), applying least absolute shrinkage and selection operator (LASSO) regression. We performed multivariable analyses of four candidate risk predictors (namely, six-CpG-scorer, age, sex, and AFP level), using 20 times imputation of missing data, non-linearly transformed, and backwards feature selection with logistic regression. The final model’s regression coefficients were calculated according to “Rubin’s Rules”. The diagnostic accuracy of the model was internally validated with a 10,000 bootstrap validation dataset and then applied to the test set for validation.ResultsThe area under the receiver operating characteristic curve (AUROC) of the model was 0.81 (95% CI, 0.77–0.85) and it showed good calibration and decision curve analysis. Using enhanced bootstrap validation, adjusted C-statistics and adjusted Brier score were 0.809 and 0.199, respectively. The model also showed an AUROC value of 0.84 (95% CI 0.79–0.88) of diagnosis for early HCC in the test set.ConclusionsOur model based on the six-CpG-scorer was a reliable diagnosis tool for early HCC from HBVLD. The usage of the MBS method can realize large-scale detection of CpG sites in clinical diagnosis of early HCC and benefit the majority of patients.

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“…Meanwhile, CHB patients can also develop HCC without cirrhosis. The new data shows that annual HCC rates ranged 0.03-1.57% among non-LC Asian CHB male patients [4]. In involving 34952 patients study suggested that 2.29% CHB patients would develop HCC despite hepatitis B surface antigen (HBsAg) seroclearance [5].…”

Section: Introductionmentioning

confidence: 98%

A CpGs Methylation Signature as Potential Marker for Early Diagnosis of Hepatocellular Carcinoma from HBV-Related Liver Disease using Multiplex Bisulfite Sequencing

Song

Qin

et al. 2021

Preprint

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Background: Aberrant methylation of CpG sites severed as epigenetic marker for building diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC). Methods:Using Illumina 450K and EPIC Beadchip, we identified 34 CpG sites in peripheral blood mononuclear cell(PBMC) DNA that were differentially methylatedin early HCCversusHBV-related liver diseases (HBVLD). We employed multiplex bisulfite sequencing (MBS) based onnext-generation sequencing (NGS) to measure methylation of 34 CpG sites in PBMC DNA from 654 patients that were divided into a training set (n = 442), a test set (n = 212). Using training set, we selected and built a six-CpG-scorer (including cg14171514, cg07721852, cg05166871, cg18087306, cg05213896, and cg18772205), applying least absolute shrinkage and selection operator (LASSO) regression. We performed multivariable analyses of four candidate risk predictors (including six-CpG-scorer, age, sex, AFP level), using 20 times imputation of missing data, non-linearly transformed and backwards feature selection with logistic regression. The final model’s regression coefficients were calculated according to “Rubin's Rules”. The diagnostic accuracy of model was internally validated with10000 bootstrap validation dataset, and then applied to thetest set for validation.Results:The area under the receiver operating characteristic curve (AUROC) of the model was 0.81(95%CI, 0.77-0.85) and it showed good calibration, decision curve analysis. Using enhanced bootstrap validation, adjusted C-statistics and adjusted brier score was 0.809 and 0.199, respectively. The model also showed AUROC value of 0.84 (95% CI 0.79-0.88) of diagnosis for early HCC in test set.Conclusions:Our model basing onsix-CpG-scorer was a reliable diagnosis tool for early HCC from HBVLD.The usage of MBS method can realize large-scale detection of CpGsites in clinical diagnosis of early HCCand benefit the majority of patients.

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Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients

Cited by 17 publications

References 17 publications

Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States

Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States

A CpG Methylation Signature as a Potential Marker for Early Diagnosis of Hepatocellular Carcinoma From HBV-Related Liver Disease Using Multiplex Bisulfite Sequencing

A CpGs Methylation Signature as Potential Marker for Early Diagnosis of Hepatocellular Carcinoma from HBV-Related Liver Disease using Multiplex Bisulfite Sequencing

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