Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients

the C-TEAM study group and the Taiwan Liver Diseases Consortium

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background & Aims: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. Methods: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. Results: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. Conclusions: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

Original languageEnglish
Pages (from-to)1755-1764
Number of pages10
JournalLiver International
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Chronic Hepatitis B
Hepatocellular Carcinoma
Mortality
Fibrosis
Therapeutics
Hepatitis B e Antigens
alpha-Fetoproteins
Risk Reduction Behavior
entecavir
Propensity Score
Peritonitis
Taiwan
Multicenter Studies
Antiviral Agents
Disease Progression
Cohort Studies
Confidence Intervals
Hemorrhage

Keywords

  • antiviral therapy
  • liver cancer
  • nucleos(t)ide analogue
  • spontaneous bacterial peritonitis
  • variceal bleeding

ASJC Scopus subject areas

  • Hepatology

Cite this

Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients. / the C-TEAM study group and the Taiwan Liver Diseases Consortium.

In: Liver International, Vol. 36, No. 12, 01.12.2016, p. 1755-1764.

Research output: Contribution to journalArticle

the C-TEAM study group and the Taiwan Liver Diseases Consortium. / Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients. In: Liver International. 2016 ; Vol. 36, No. 12. pp. 1755-1764.
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abstract = "Background & Aims: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. Methods: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment-na{\"i}ve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. Results: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60{\%} HCC risk reduction [hazard ratio (HR): 0.40, 95{\%} confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. Conclusions: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.",
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author = "{the C-TEAM study group and the Taiwan Liver Diseases Consortium} and Su, {Tung Hung} and Hu, {Tsung Hui} and Chen, {Chi Yi} and Huang, {Yi Hsiang} and Chuang, {Wan Long} and Lin, {Chun Che} and Wang, {Chia Chi} and Su, {Wei Wen} and Chen, {Ming Yao} and Peng, {Cheng Yuan} and Chien, {Rong Nan} and Huang, {Yi Wen} and Wang, {Horng Yuan} and Lin, {Chih Lin} and Yang, {Sheng Shun} and Chen, {Tsung Ming} and Mo, {Lein Ray} and Hsu, {Shih Jer} and Tseng, {Kuo Chih} and Hsieh, {Tsai Yuan} and Suk, {Fat Moon} and Hu, {Chi Tan} and Bair, {Ming Jong} and Liang, {Cheng Chao} and Lei, {Yung Chao} and Tseng, {Tai Chung} and Chen, {Chi Ling} and Kao, {Jia Horng}",
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AU - Su, Tung Hung

AU - Hu, Tsung Hui

AU - Chen, Chi Yi

AU - Huang, Yi Hsiang

AU - Chuang, Wan Long

AU - Lin, Chun Che

AU - Wang, Chia Chi

AU - Su, Wei Wen

AU - Chen, Ming Yao

AU - Peng, Cheng Yuan

AU - Chien, Rong Nan

AU - Huang, Yi Wen

AU - Wang, Horng Yuan

AU - Lin, Chih Lin

AU - Yang, Sheng Shun

AU - Chen, Tsung Ming

AU - Mo, Lein Ray

AU - Hsu, Shih Jer

AU - Tseng, Kuo Chih

AU - Hsieh, Tsai Yuan

AU - Suk, Fat Moon

AU - Hu, Chi Tan

AU - Bair, Ming Jong

AU - Liang, Cheng Chao

AU - Lei, Yung Chao

AU - Tseng, Tai Chung

AU - Chen, Chi Ling

AU - Kao, Jia Horng

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N2 - Background & Aims: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. Methods: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. Results: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. Conclusions: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

AB - Background & Aims: Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. Methods: The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. Results: In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. Conclusions: Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.

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KW - liver cancer

KW - nucleos(t)ide analogue

KW - spontaneous bacterial peritonitis

KW - variceal bleeding

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