Natural history of chronic hepatitis B REVEALed

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06695.x/abstract

Natural history of chronic hepatitis B REVEALed

Chien-Jen Chen1,2,*, Hwai-I Yang3Article first published online: 21 MAR 2011

DOI: 10.1111/j.1440-1746.2011.06695.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Volume 26, Issue 4, pages 628–638, April 2011

The REVEAL-HBV Study was supported by grants from the Academia Sinica, National

Health Research Institutes, and Bristol-Myers Squibb Co., USA

Abstract

Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural

history of chronic hepatitis B is important for the management of the disease. A

community-based prospective cohort study was carried out to evaluate the risk

predictors of progression of chronic hepatitis B in Taiwan. A total of 23 820

participants were enrolled in 1991–1992 from seven townships in Taiwan. Their

serum samples were collected at study entry and tested for hepatitis B surface

antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus

(anti-HCV), alanine aminotransferase (ALT), and α-fetoprotein (AFP). A

subcohort of 3653 male and female participants who were seropositive for HBsAg

and seronegative for anti-HCV was included in the Risk Evaluation of Viral Load

Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV)

study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC)

were ascertained through follow-up examination and data linkage with profiles of

the National Cancer Registry, National Health Insurance Database and Death

Certification System. The incidence of both HCC and cirrhosis were significantly

associated with serum HBV DNA levels in a dose-response relationship from < 300

(undetectable) to ≥ 1 000 000 copies/mL. The biological gradients remained

significant (P < 0.001) after adjustment for age, sex, habits of cigarette

smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort

entry. A significant association with risk of cirrhosis and HCC was also

observed for HBV genotype, precore G1896A mutant and basal core promoter

A1762T/G1764A double mutant. Nomograms have been developed for the long-term

risk prediction of cirrhosis and HCC for patients with chronic hepatitis B.

Inactive carriers of HBV have an increased HCC incidence and liver-related

mortality than HBsAg-seronegative controls. Serum HBV DNA level at study entry

is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg.

These findings may inform the effective and efficient management of chronic

hepatitis B.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06695.x/abstract

Natural history of chronic hepatitis B REVEALed

Chien-Jen Chen1,2,*, Hwai-I Yang3Article first published online: 21 MAR 2011

DOI: 10.1111/j.1440-1746.2011.06695.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Volume 26, Issue 4, pages 628–638, April 2011

The REVEAL-HBV Study was supported by grants from the Academia Sinica, National

Health Research Institutes, and Bristol-Myers Squibb Co., USA

Abstract

Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural

history of chronic hepatitis B is important for the management of the disease. A

community-based prospective cohort study was carried out to evaluate the risk

predictors of progression of chronic hepatitis B in Taiwan. A total of 23 820

participants were enrolled in 1991–1992 from seven townships in Taiwan. Their

serum samples were collected at study entry and tested for hepatitis B surface

antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus

(anti-HCV), alanine aminotransferase (ALT), and α-fetoprotein (AFP). A

subcohort of 3653 male and female participants who were seropositive for HBsAg

and seronegative for anti-HCV was included in the Risk Evaluation of Viral Load

Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV)

study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC)

were ascertained through follow-up examination and data linkage with profiles of

the National Cancer Registry, National Health Insurance Database and Death

Certification System. The incidence of both HCC and cirrhosis were significantly

associated with serum HBV DNA levels in a dose-response relationship from < 300

(undetectable) to ≥ 1 000 000 copies/mL. The biological gradients remained

significant (P < 0.001) after adjustment for age, sex, habits of cigarette

smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort

entry. A significant association with risk of cirrhosis and HCC was also

observed for HBV genotype, precore G1896A mutant and basal core promoter

A1762T/G1764A double mutant. Nomograms have been developed for the long-term

risk prediction of cirrhosis and HCC for patients with chronic hepatitis B.

Inactive carriers of HBV have an increased HCC incidence and liver-related

mortality than HBsAg-seronegative controls. Serum HBV DNA level at study entry

is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg.

These findings may inform the effective and efficient management of chronic

hepatitis B.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06695.x/abstract

Natural history of chronic hepatitis B REVEALed

Chien-Jen Chen1,2,*, Hwai-I Yang3Article first published online: 21 MAR 2011

DOI: 10.1111/j.1440-1746.2011.06695.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Volume 26, Issue 4, pages 628–638, April 2011

The REVEAL-HBV Study was supported by grants from the Academia Sinica, National

Health Research Institutes, and Bristol-Myers Squibb Co., USA

Abstract

Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural

history of chronic hepatitis B is important for the management of the disease. A

community-based prospective cohort study was carried out to evaluate the risk

predictors of progression of chronic hepatitis B in Taiwan. A total of 23 820

participants were enrolled in 1991–1992 from seven townships in Taiwan. Their

serum samples were collected at study entry and tested for hepatitis B surface

antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus

(anti-HCV), alanine aminotransferase (ALT), and α-fetoprotein (AFP). A

subcohort of 3653 male and female participants who were seropositive for HBsAg

and seronegative for anti-HCV was included in the Risk Evaluation of Viral Load

Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV)

study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC)

were ascertained through follow-up examination and data linkage with profiles of

the National Cancer Registry, National Health Insurance Database and Death

Certification System. The incidence of both HCC and cirrhosis were significantly

associated with serum HBV DNA levels in a dose-response relationship from < 300

(undetectable) to ≥ 1 000 000 copies/mL. The biological gradients remained

significant (P < 0.001) after adjustment for age, sex, habits of cigarette

smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort

entry. A significant association with risk of cirrhosis and HCC was also

observed for HBV genotype, precore G1896A mutant and basal core promoter

A1762T/G1764A double mutant. Nomograms have been developed for the long-term

risk prediction of cirrhosis and HCC for patients with chronic hepatitis B.

Inactive carriers of HBV have an increased HCC incidence and liver-related

mortality than HBsAg-seronegative controls. Serum HBV DNA level at study entry

is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg.

These findings may inform the effective and efficient management of chronic

hepatitis B.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06695.x/abstract

Natural history of chronic hepatitis B REVEALed

Chien-Jen Chen1,2,*, Hwai-I Yang3Article first published online: 21 MAR 2011

DOI: 10.1111/j.1440-1746.2011.06695.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Volume 26, Issue 4, pages 628–638, April 2011

The REVEAL-HBV Study was supported by grants from the Academia Sinica, National

Health Research Institutes, and Bristol-Myers Squibb Co., USA

Abstract

Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural

history of chronic hepatitis B is important for the management of the disease. A

community-based prospective cohort study was carried out to evaluate the risk

predictors of progression of chronic hepatitis B in Taiwan. A total of 23 820

participants were enrolled in 1991–1992 from seven townships in Taiwan. Their

serum samples were collected at study entry and tested for hepatitis B surface

antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus

(anti-HCV), alanine aminotransferase (ALT), and α-fetoprotein (AFP). A

subcohort of 3653 male and female participants who were seropositive for HBsAg

and seronegative for anti-HCV was included in the Risk Evaluation of Viral Load

Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV)

study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC)

were ascertained through follow-up examination and data linkage with profiles of

the National Cancer Registry, National Health Insurance Database and Death

Certification System. The incidence of both HCC and cirrhosis were significantly

associated with serum HBV DNA levels in a dose-response relationship from < 300

(undetectable) to ≥ 1 000 000 copies/mL. The biological gradients remained

significant (P < 0.001) after adjustment for age, sex, habits of cigarette

smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort

entry. A significant association with risk of cirrhosis and HCC was also

observed for HBV genotype, precore G1896A mutant and basal core promoter

A1762T/G1764A double mutant. Nomograms have been developed for the long-term

risk prediction of cirrhosis and HCC for patients with chronic hepatitis B.

Inactive carriers of HBV have an increased HCC incidence and liver-related

mortality than HBsAg-seronegative controls. Serum HBV DNA level at study entry

is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg.

These findings may inform the effective and efficient management of chronic

hepatitis B.