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A multi‐centre study of trends in hepatitis B virus‐related hepatocellular carcinoma risk over time during long‐term entecavir therapy

Kim, Seung Up ; Chon, Yong Eun ; Seo, Yeon Seok ; [et al.]

Wiley ; 2020

In: Journal of Viral Hepatitis Vol. 27, No. 12 ( 2020-12), p. 1352-1358

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In: Journal of Viral Hepatitis, Wiley, Vol. 27, No. 12 ( 2020-12), p. 1352-1358

Abstract: The risk of developing hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment‐naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007‐2010), middle (2011‐2012) and late (2013‐2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P 〉 .05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child‐Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis ( P 〈 .001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development ( P = .457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR = 2.069), liver cirrhosis (aHR = 3.771) and Child‐Pugh class B (vs A, aHR = 1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR = 0.993; all P 〈 .05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.

Type of Medium: Online Resource

ISSN: 1352-0504 , 1365-2893

URL: Issue

URL: Article

DOI: 10.1111/jvh.v27.12

DOI: 10.1111/jvh.13384

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 2007924-2

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A machine learning model for predicting hepatocellular carcinoma risk in patients with chronic hepatitis B

Lee, Hye Won ; Kim, Hwiyoung ; Park, Taeyun ; [et al.]

Wiley ; 2023

In: Liver International Vol. 43, No. 8 ( 2023-08), p. 1813-1821

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In: Liver International, Wiley, Vol. 43, No. 8 ( 2023-08), p. 1813-1821

Abstract: Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an ML‐based HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT). Methods Treatment‐naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort ( n = 960) to develop a novel ML model that predicted HCC development within 5 years and validated the model using an independent external cohort ( n = 1937). ML algorithms consider all potential interactions and do not use predefined hypotheses. Results The mean age of the patients in the training cohort was 48 years, and most patients (68.9%) were men. During the median 59.3 (interquartile range 45.8–72.3) months of follow‐up, 69 (7.2%) patients developed HCC. Our ML‐based HCC risk prediction model had an area under the receiver‐operating characteristic curve (AUC) of 0.900, which was better than the AUCs of CAMD (0.778) and REAL B (0.772) (both p 〈 .05). The better performance of our model was maintained (AUC = 0.872 vs. 0.788 for CAMD and 0.801 for REAL B) in the validation cohort. Using cut‐off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development differed significantly among the three risk groups ( p 〈 .001). Conclusions Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.

Type of Medium: Online Resource

ISSN: 1478-3223 , 1478-3231

URL: Issue

URL: Article

DOI: 10.1111/liv.v43.8

DOI: 10.1111/liv.15597

Language: English

Publisher: Wiley

Publication Date: 2023

detail.hit.zdb_id: 2124684-1

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Validation of risk prediction scores for hepatocellular carcinoma in patients with chronic hepatitis B treated with entecavir or tenofovir

Chang, Jin Won ; Lee, Jae Seung ; Lee, Hye Won ; [et al.]

Wiley ; 2021

In: Journal of Viral Hepatitis Vol. 28, No. 1 ( 2021-01), p. 95-104

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In: Journal of Viral Hepatitis, Wiley, Vol. 28, No. 1 ( 2021-01), p. 95-104

Abstract: Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE‐B, PAGE‐B and modified PAGE‐B (mPAGE‐B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow‐up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P 〈 .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P 〈 .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC ( P 〈 .05). The predictive accuracy of AASL score was the highest for 3‐ and 5‐year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE‐B, PAGE‐B and mPAGE‐B scores (AUC = 0.780‐0.815 and 0.769‐0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy.

Type of Medium: Online Resource

ISSN: 1352-0504 , 1365-2893

URL: Issue

URL: Article

DOI: 10.1111/jvh.v28.1

DOI: 10.1111/jvh.13411

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2007924-2

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Long‐term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B

Chon, Young Eun ; Kim, Seung Up ; Seo, Yeon Seok ; [et al.]

Wiley ; 2022

In: Journal of Gastroenterology and Hepatology Vol. 37, No. 1 ( 2022-01), p. 200-207

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In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 37, No. 1 ( 2022-01), p. 200-207

Abstract: Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long‐term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. Methods Treatment‐naïve chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase‐to‐platelet ratio index (APRI) and fibrosis index based on four factors (FIB‐4) were used to determine fibrotic burden. Results In the entire population ( n = 3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P 〈 0.001) and FIB‐4 (3.60 vs 2.80, P 〈 0.001) than those treated with TDF, significant fibrosis regression was identified during 6 years of AVT in both ETV (APRI, mean 1.71 → 0.48, P 〈 0.001; FIB‐4, mean 3.60 → 2.21, P 〈 0.001) and TDF groups (APRI, mean 1.07 → 0.43, P 〈 0.001; FIB‐4, mean 2.80 → 2.19, P 〈 0.001). In patients without cirrhosis ( n = 2366), baseline APRI was significantly higher in ETV group than in TDF group (1.72 vs 0.97, P 〈 0.001); however, they became similar after 6 months. Similarly, baseline FIB‐4 was significantly higher in ETV group than in TDF group (3.25 vs 2.35, P 〈 0.001), but became similar from 4 to 6 years. In patients with cirrhosis ( n = 911), baseline APRI (1.70 vs 1.34, P 〈 0.001) and FIB‐4 (4.62 vs 3.91, P = 0.005) were higher in ETV group than in TDF, however, both parameters became statistically similar from 6 months to 6 years. Conclusion Significant regression of APRI and FIB‐4 was observed during long‐term ETV and TDF treatment. Despite higher baseline fibrotic burden in ETV group, fibrotic burden between the groups eventually converged through significant fibrosis regression after 1 to 4 years of AVT.

Type of Medium: Online Resource

ISSN: 0815-9319 , 1440-1746

URL: Issue

URL: Article

DOI: 10.1111/jgh.v37.1

DOI: 10.1111/jgh.15678

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2006782-3

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The clinical effect of antiviral therapy in patients with hepatitis B virus‐related decompensated cirrhosis and undetectable DNA

Lee, Han Ah ; Lee, Young‐Sun ; Jung, Young Kul ; [et al.]

Wiley ; 2023

In: Journal of Gastroenterology and Hepatology Vol. 38, No. 5 ( 2023-05), p. 716-723

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In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 38, No. 5 ( 2023-05), p. 716-723

Abstract: Antiviral therapy (AVT) is the mainstay of hepatitis B virus (HBV) management. We investigated whether AVT improves the outcomes of HBV‐related decompensated cirrhosis and undetectable HBV‐DNA. Methods Between 2000 and 2017, treatment‐naïve patients with HBV‐related decompensated cirrhosis and undetectable HBV‐DNA were recruited from two tertiary hospitals. The endpoints included death and hepatocellular carcinoma (HCC). Results A total of 429 patients were analyzed (50 and 379 patients in the AVT and non‐AVT groups, respectively). Patients in the AVT group were significantly younger and had higher alanine aminotransferase and alpha‐fetoprotein levels than those in the non‐AVT group (all P 〈 0.05). During follow‐up (median 49.6 months), 98 patients died and 105 developed HCC. The cumulative incidence rates of death (2.0%, 4.1%, and 6.4%, and 4.9%, 7.2%, and 10.2% at 6 months, 1 year, and 2 years, respectively) and HCC (8.6%, 15.8%, and 26.4% vs 1.6%, 7.7%, and 24.4% at 1, 2, and 5 years, respectively) were statistically comparable between the AVT and non‐AVT groups (all P 〉 0.05). Using Cox regression analysis, AVT was not significantly associated with death nor HCC (all P 〉 0.05). Similar results were observed after balancing baseline characteristics with inverse probability of treatment weighting. In the non‐AVT group, the cumulative incidence rates of HBV‐DNA detection at 6 months, 1 year, and 2 years were 2.0%, 3.1%, and 6.4%, respectively. Conclusions Antiviral therapy did not attenuate the risk of death nor HCC in patients with HBV‐related decompensated cirrhosis and undetectable HBV‐DNA.

Type of Medium: Online Resource

ISSN: 0815-9319 , 1440-1746

URL: Issue

URL: Article

DOI: 10.1111/jgh.v38.5

DOI: 10.1111/jgh.16132

Language: English

Publisher: Wiley

Publication Date: 2023

detail.hit.zdb_id: 2006782-3

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