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Prediction model of hepatocellular carcinoma risk in Asian patients with chronic hepatitis B treated with entecavir.

ABSTRACT: Until now, no risk score could predict hepatocellular carcinoma (HCC) in nucleos(t)ide analog (NA)-treated Asian patients.We enrolled 1325 NA-naïve chronic hepatitis B patients with entecavir monotherapy for >12 months, with 883 and 442 patients randomly assigned to the development and validation groups, respectively, in the risk model.The cumulative probabilities of HCC were 2.4%, 4.1%, and 9.9% after 2, 3, and 5 years of treatment, respectively. In the development group, age, platelet counts, and alpha-fetoprotein levels after 12 months of treatment were the independent predictors of HCC. We converted the Cox proportional hazards regression coefficients for these predictors into risk scores and developed the APA-B model, with the total risk scores ranging from 0 to 15. The risk scores accurately categorized patients with low (0-5), medium (6-9), and high (10-15) risks in the validation group (P <0.001). The areas under the receiver operating characteristic curve for predicting HCC risk after 2, 3, and 5 years were 0.877, 0.842, and 0.827, respectively, in the development group and 0.939, 0.892, and 0.862, respectively, in the validation group.The proposed HCC risk prediction model exhibited excellent predictive accuracy in NA-naïve Asian patients receiving entecavir therapy.

SUBMITTER: Chen CH

PROVIDER: S-EPMC5696194 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Prediction model of hepatocellular carcinoma risk in Asian patients with chronic hepatitis B treated with entecavir.

Chen Chien-Hung CH Lee Chuan-Mo CM Lai Hsueh-Chou HC Hu Tsung-Hui TH Su Wen-Pang WP Lu Sheng-Nan SN Lin Chia-Hsin CH Hung Chao-Hung CH Wang Jing-Houng JH Lee Mei-Hsuan MH Peng Cheng-Yuan CY

Oncotarget 20170928 54

<h4>Background</h4>Until now, no risk score could predict hepatocellular carcinoma (HCC) in nucleos(t)ide analog (NA)-treated Asian patients.<h4>Methods</h4>We enrolled 1325 NA-naïve chronic hepatitis B patients with entecavir monotherapy for >12 months, with 883 and 442 patients randomly assigned to the development and validation groups, respectively, in the risk model.<h4>Results</h4>The cumulative probabilities of HCC were 2.4%, 4.1%, and 9.9% after 2, 3, and 5 years of treatment, respectivel ...[more]

PMID: 29190928

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Project description:Background & aimsRecently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC.MethodsWe included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively.ResultsHCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78-0.82). NPVs were always >99% (99.3-100%), whereas PPV ranged between 13% and 24%.ConclusionsIn NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease.Lay summarySeveral risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.

Project description:ImportanceEntecavir and tenofovir disoproxil fumarate have comparable efficacy in achieving surrogate end points, including virologic response, and are equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). However, it is unclear whether treatment with these drugs is associated with equivalent clinical outcomes, especially development of hepatocellular carcinoma (HCC).ObjectiveTo compare entecavir and tenofovir in terms of the risk of HCC and death or liver transplant in patients with CHB infection.Design, setting, and participantsA nationwide historical population cohort study involving treatment-naive adult patients with CHB who started treatment with entecavir (n = 11 464) or tenofovir disoproxil fumarate (n = 12 692) between January 1, 2012, and December 31, 2014, using data from the Korean National Health Insurance Service database. As validation, a hospital cohort of patients with CHB treated with entecavir (n = 1560) or tenofovir (n = 1141) in a tertiary referral center between January 1, 2010, and December 31, 2016, were analyzed. Nationwide cohort data were retrieved from January 1, 2010, to December 31, 2016, and hospital cohort data from January 1, 2010, to October 31, 2017.Main outcomes and measuresCumulative incidence rates of HCC and death and transplant rates.ResultsAmong the population cohort of 24 156, the mean (SD) age was 48.9 (9.8) years, and 15 120 patients (62.6%) were male. Among the hospital cohort of 2701, the mean (SD) age was 48.8 (10.5) years and 1657 patients (61.3%) were male. In the population cohort, the annual incidence rate of HCC was significantly lower in the tenofovir group (0.64 per 100 person-years [PY]) than in the entecavir group (1.06 per 100 PY). By multivariable-adjusted analysis, tenofovir therapy was associated with a significantly lower risk of HCC (hazard ratio [HR], 0.61; 95% CI, 0.54-0.70) and all-cause mortality or transplant (HR, 0.77; 95% CI, 0.65-0.92) compared with entecavir. The tenofovir group also showed a significantly lower risk of HCC in the 10 923-pair propensity score-matched population cohort (HR, 0.62; 95% CI, 0.54-0.70) and 869-pair propensity score-matched hospital cohort (HR, 0.68; 95% CI, 0.46-0.99) compared with the entecavir group.Conclusions and relevanceThis study suggests that tenofovir treatment was associated with a significantly lower risk of HCC compared with entecavir treatment in a population-based cohort of adults with CHB; these findings were validated in a hospital cohort. Given the poor prognosis of patients with HCC, these findings may have considerable clinical implications in prevention of this cancer in patients with CHB infection.

Project description:BackgroundLong-term antiviral treatments are associated with a significantly lower hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients by reducing HBV DNA concentrations. However, it is still controversial whether antiviral strategies affect HCC development in antiviral treatment-naïve CHB patients. This study aimed to estimate the incidence of HCC in antiviral treatment-naïve CHB patients who were treated with Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF) and compare the efficacy of two treatment regimens in HCC reduction.MethodsThe PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were systematically searched until June 24, 2021. The pooled incidence and 95% confidence interval of HCC were calculated by the Freeman-Tukey double arcsine transformation method. The efficacies of ETV and TDF treatments in HCC reduction were compared through a network meta-analysis.ResultsA total of 27 studies were identified as eligible for this systematic review. The incidence densities in the ETV and TDF treatment groups were 2.78 (95% CI: 2.21-3.40) and 2.59 (95% CI: 1.51-3.96) per 100 persons-year among patients with preexisting cirrhosis and 0.49 (95% CI: 0.32-0.68) and 0.30 (95% CI: 0.06-0.70) per 100 persons-year among patients without preexisting cirrhosis. As the proportion of CHB patients with preexisting cirrhosis increased, the incidence density of HCC also increased gradually. Compared with other Nucleos(t)ide analogs (NAs) treatments, ETV and TDF treatments significantly lowered the risk of HCC, with hazard ratios (HRs) of 0.60 (95% CI: 0.40-0.90) and 0.56 (95% CI: 0.35-0.89), respectively. However, there was no difference in the incidence density of HCC between ETV and TDF treatments (HR = 0.92, 95% CI: 0.71-1.20) regardless of preexisting cirrhosis.ConclusionETV and TDF treatments were associated with significantly lower risks of HCC than other NAs treatments. However, no difference was observed between ETV and TDF treatments in the risk of HCC development regardless of preexisting cirrhosis among treatment-naïve CHB patients.

Project description:Simple Summary Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B. Despite many meta-analyses being conducted, it is still not clear whether TDF is more effective than ETV at reducing the risk of HCC due to the inconsistent statistical methodologies employed in previous observational studies. To reduce heterogeneity, we analysed only hospital cohort data studies with anti-viral naive patients. Additionally, unlike previous studies, we conducted subgroup analyses with enrolment criteria and socioeconomic factors that could not be corrected with statistical techniques. There is no difference between the two drugs in terms of reducing the risk of HCC in a pooled analysis of PS-matched patients. In the subgroup analysis, if there was interval of over three years from the start point of patient enrolment, we found that TDF was associated with significantly lower HCC risk. This result will provide new perspectives for future research. Abstract Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B (CHB). However, the efficacy of these agents in reducing the incidence of hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to assess the efficacy of anti-viral agent on preventing HCC in CHB. Two investigators independently searched all relevant studies that examined the efficacy of anti-viral agent for preventing HCC using MEDLINE, Embase, and Cochrane Library databases through August 2021. The extracted data were analysed using a random-effects meta-analysis model based on the inverse-variance method (DerSimonian–Laird) and expressed as hazard ratio (HR) and 95% confidence interval (95% CI). We included 19 retrospective studies in the analysis. Although there was substantial heterogeneity between the studies, the overall pooled HR indicated that TDF significantly lowered the risk of HCC (HR: 0.72, 95% CI: 0.58–0.90, I2 = 66.29%). However, the pooled analysis of propensity score (PS)-matched subpopulations showed no significant differences (HR, 0.83; 95% CI, 0.65–1.06; I2 = 52.30%) between TDF and ETV. In a subgroup analysis, an interval of over three years in the start point of patient enrolment and excluding alcoholic liver disease patients significantly lowered the HCC risk associated with TDF. In conclusion, TDF may be more effective than ETV at reducing HCC incidence in treatment-naive CHB patients, but this effect was not consistent in the PS-matched subpopulation that reduced heterogeneity. As a result of subgroup analysis, the conflicting findings of previous studies may result from heterogeneous inclusion criteria. Further studies with standardised protocols are needed to reduce the residual heterogeneity.

Dataset Information

Prediction model of hepatocellular carcinoma risk in Asian patients with chronic hepatitis B treated with entecavir.

Publications

Prediction model of hepatocellular carcinoma risk in Asian patients with chronic hepatitis B treated with entecavir.

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