On-Treatment Changes in FIB-4 and 1-Year FIB-4 Values Help Identify Patients with Chronic Hepatitis B Receiving Entecavir Therapy Who Have the Lowest Risk of Hepatocellular Carcinoma

Wang, Hung‐Wei; Lai, Hsueh Chou; Hu, Tsung Hui; Su, Wen Pang; Lu, Sheng; Lin, Chia Hsin; Hung, Chao Hung; Chuang, Po‐Heng; Wang, Jing Houng; Lee, Hsuan-Shu; Chen, Chien Hung; Peng, Cheng Yuan

doi:10.3390/cancers12051177

Cited by 11 publications

(16 citation statements)

References 40 publications

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“…Although ALT normalization did not significantly affect HCC occurrence (HR 0.771; p = 0.339) in the current study, multivariate analysis showed that FIB‐4 reduction after 1 year of ETV therapy was strongly associated with HCC incidence (HR 0.491; p = 0.013) (Table 4). In addition, a previous study 17 showed on‐treatment change in the FIB‐4 index helped to identify patients with CHB who have the lowest risk of HCC, as we suggested in the current study. The authors of the previous study suggest an algorithm for HCC prediction in CHB patients treated with ETV according to cut‐off value of 12 months (noncirrhosis 1.58 vs. cirrhosis 2.88) and the presence of on‐treatment FIB‐4 index after 1 year of ETV therapy.…”

Section: Discussionsupporting

confidence: 53%

“…Another study of 539 patients with nucleoside/nucleotide therapy reported that a FIB‐4 index of more than 2.65 had predictive power for HCC incidence 13 . In addition, recently, Wang et al 17 . suggested a predictive algorithm for HCC risk estimation using a specific value of FIB‐4 index and on‐treatment change in the FIB‐4 index after 1 year of ETV treatment for CHB patients with or without LC.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a study using the mFIB‐4 index showed satisfactory predictability of HCC development 16 . However, only one study 17 has recently shown that the risk estimation of HCC incidence correlated with a change in the FIB‐4 index after antiviral therapy. Thus, the purpose of the current study was to validate the clinical usefulness of well‐known noninvasive fibrosis indices such as FIB‐4, mFIB‐4, or APRI in predicting treatment responses and the incidence of HCC in the early stages of ETV treatment.…”

Section: Introductionmentioning

confidence: 99%

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Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment‐naïve patients with chronic hepatitis B following entecavir therapy

Jeong

Shin

Jung

et al. 2021

Hepatology Research

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Aims This study aimed to evaluate the clinical usefulness of the aminotransferase to platelet ratio index (APRI), fibrosis‐4 (FIB‐4), and modified FIB‐4 (mFIB‐4) indices in predicting hepatocellular carcinoma (HCC) in patients receiving entecavir (ETV) treatment. Methods Among 1955 patients treated with ETV, a total of 857 treatment‐naive chronic hepatitis B patients (424 with liver cirrhosis [LC], 433 without cirrhosis) treated with ETV for more than 1 year were analyzed. Results Of the 857 patients, 85 (9.9%) patients (77 in the LC group and 8 in the non‐LC group) developed HCC during the follow‐up period. The median observation period was 6.9 years. Multivariate regression analysis of HCC incidence revealed that the initial mFIB‐4 index (hazard ratio [HR] 1.058; 95% confidence interval [CI], 1.007–1.112; p = 0.027) and improvement in the FIB‐4 index after 1 year of ETV treatment (HR 0.531; 95% CI, 0.339–0.831; p = 0.006) were independent prognostic factors in the entire cohort. In the LC group, the improvement of the FIB‐4 index following ETV treatment (HR 0.491; 95% CI, 0.280–0.861; p = 0.013) was negatively correlated with incidence of HCC. However, the area under the receiver operating characteristic curve of specific cut‐off values of the FIB‐4 index at baseline and 1 year after ETV treatment were 0.572 (95% CI, 0.504–0.640) and 0.615 (95% CI, 0.546–0.684), respectively. In the non‐LC group, none of the invasive fibrosis indices could predict HCC incidence. Conclusions The specific cut‐off value of the FIB‐4 index was not suitable for predicting HCC. However, the improvement in the FIB‐4 index after 1 year of ETV therapy could be a predictor of HCC development in cirrhotic patients.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment‐naïve patients with chronic hepatitis B following entecavir therapy

Jeong

Shin

Jung

et al. 2021

Hepatology Research

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“…First, the present study was conducted solely based on a retrospective, single-center cohort in a large tertiary referral university hospital, and its results are potentially subject to selection bias. Second, although we validated the predictive performance of the initial aMAP score and the 1-year aMAP score, the predictive role of the combination of aMAP and on-treatment changes in aMAP (ΔaMAP) during NA therapy and their optimal time point requires further investigation, as in the case of the fibrosis index based on four factors (FIB-4) ( 32 ). Third, given that metabolic risk factors, including diabetes, obesity, high blood pressure, and hypercholesterolemia, are associated with an increased HCC risk in patients with CHB ( 33 ), other metabolic risk factors should be incorporated in future studies as such models will have higher discriminatory power.…”

Section: Discussionmentioning

confidence: 99%

External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy

et al. 2021

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Background and Aim: A prediction model of hepatocellular carcinoma (HCC) risk in patients with chronic liver diseases, based on age, male sex, albumin-bilirubin, and platelets (aMAP), has been previously reported. We validated the aMAP score and compared its performance to those of other risk scores in an independent at-risk cohort.Methods: Treatment-naïve patients with chronic hepatitis B-related compensated cirrhosis who received entecavir or tenofovir monotherapy for at least 12 months were enrolled in this study. The performances of the aMAP and other HCC risk scores were assessed using Harrell's c-index, and predefined cut-off values were evaluated using survival analysis.Results: Of the 1,042 patients, 131 (12.6%) developed HCC during a median follow-up of 41 months. The aMAP score provided the highest Harrell's c-index (0.724), followed by CAMD (0.719), mPAGE-B (0.719), and PAGE-B (0.695). The 5-year cumulative HCC probabilities were 2.9% for patients with a low aMAP score (<50), 11.2% for patients with an intermediate aMAP score (50–60), and 27.9% for patients with a high aMAP score (>60). Using both aMAP and mPAGE-B, 11.6% of patients were identified as low risk with a negative predictive value of 98.2% for not developing HCC within 5 years. Patients with aMAP >60 and diabetes exhibited an extremely high risk of HCC, with a cumulative incidence of 49.3% at 5 years. The predictive performance of aMAP with a reassessment at 1 year after the initiation of antiviral therapy outperformed the predictive performance of aMAP at enrollment.Conclusions: The aMAP score accurately predicted the risk of HCC in at-risk patients with compensated cirrhosis undergoing antiviral therapy. A combination of the aMAP score and diabetes status could further stratify the risk of HCC.

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“…Previous studies have revealed determinants of liver-related events; however, the reported predictors have not been consistent. 14 , 16 , 27 In this retrospective study, we determined independent risk predictors for liver-related events, liver-related mortality, and HCC from widely validated models developed with routinely available laboratory parameters.…”

Section: Discussionmentioning

confidence: 99%

Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy

Cheng¹,

Xu²,

Tan³

et al. 2021

IDR

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Objective: Many scores have been constructed to predict liver-related events in chronic hepatitis B, while most of them are based on baseline clinical parameters. The objective of this study was to develop nomograms based on on-treatment improvement in established scores to predict clinical outcomes in patients with hepatitis B virus (HBV)-related cirrhosis who are receiving antiviral therapy. Methods: The Cox proportional hazards regression model was used. Nomograms were constructed for the prediction of liver-related events, hepatocellular carcinoma (HCC), and liver-related mortality risk during long-term antiviral therapy. Results: A total of 277 treatment-naive patients with HBV-associated cirrhosis were enrolled from January 2010 to December 2013. After a median follow-up of 63.3 months, 95 patients developed liver-related events, including 59 patients with liver-related death. Multivariate Cox analysis showed that the albumin-bilirubin score at year 1 was an independent predictor of liver-related events, liver-related mortality, and HCC. Age, decompensation, and delayed virological remission were independent factors for liver-related mortality. Age was also a risk factor for liver-related events. The concordance index values of eventnomogram, mortality-nomogram, and HCC-nomogram were 0.742 (95% confidence interval [CI], 0.691~0.793), 0.799 (95% CI, 0.748~0.850), and 0.613 (95% CI, 0.540~0.686), respectively. The calibration plots showed an agreement between the predicted and observed incidences, which indicates good calibration of the model of event-nomogram and mortalitynomogram. Conclusion:The nomograms achieved an optimal preoperative prediction of liver-related events, mortality, and HCC development in patients with HBV-related cirrhosis receiving antiviral therapy. These findings may help to identify high-risk patients for further optimal surveillance and intervention strategies.

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On-Treatment Changes in FIB-4 and 1-Year FIB-4 Values Help Identify Patients with Chronic Hepatitis B Receiving Entecavir Therapy Who Have the Lowest Risk of Hepatocellular Carcinoma

Cited by 11 publications

References 40 publications

Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment‐naïve patients with chronic hepatitis B following entecavir therapy

Clinical usefulness of noninvasive fibrosis indices for predicting hepatocellular carcinoma in treatment‐naïve patients with chronic hepatitis B following entecavir therapy

External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy

Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy

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