TY - JOUR
T1 - Long-term clinical outcomes in cirrhotic chronic hepatitis B patients treated with tenofovir disoproxil fumarate for up to 5 years
AU - Buti, Maria
AU - Fung, Scott
AU - Gane, Edward
AU - Afdhal, Nezam H.
AU - Flisiak, Robert
AU - Gurel, Selim
AU - Flaherty, John F.
AU - Martins, Eduardo B.
AU - Yee, Leland J.
AU - Dinh, Phillip
AU - Bornstein, Jeffrey D.
AU - Mani Subramanian, G.
AU - Janssen, Harry L.A.
AU - George, Jacob
AU - Marcellin, Patrick
N1 - Funding Information:
This study was supported by Gilead Sciences, Inc. The authors thank Anna Lau, PhD, of Percolation Communications LLC for medical editorial support, funded by Gilead Sciences, Inc. JG is supported by the Robert W. Storr bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant no. 1053206, and the Sydney West Translational Cancer Research Centre Partner Program funded by the Cancer Institute NSW.
Publisher Copyright:
© The Author(s) 2015.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Background: Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF. Methods: Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy–diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis. Results: After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0 % achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9 % had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2 % developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3 % of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss. Conclusions: This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.
AB - Background: Phase 3 clinical studies have shown that long-term treatment with tenofovir disoproxil fumarate (TDF) can suppress hepatitis B viral load and promote significant fibrosis regression and cirrhosis reversal in a majority of treated chronic hepatitis B (CHB) patients. This retrospective analysis investigated the impact of baseline cirrhosis status on virologic, serologic, and histologic outcomes in patients treated with TDF. Methods: Patients enrolled in studies GS-US-174-0102 and GS-US-174-0103 who had baseline liver biopsy–diagnosed cirrhosis and entered the open-label phase of the studies were included in the virologic and serologic analyses. Patients (both HBeAg positive and negative) with paired liver biopsies at baseline and 5 years (N = 348) were included in a histologic analysis. Results: After 5 years on study, comparing patients with and without baseline cirrhosis, respectively: 99.2 and 98.0 % achieved virologic response (hepatitis B viral load < 69 IU/ml) (p = 0.686); 79.7 and 81.9 % had normal serum levels of alanine aminotransferase (p = 0.586); 4.0 and 1.2 % developed hepatocellular carcinoma (p = 0.044). In HBeAg-positive patients with and without baseline cirrhosis, HBsAg loss occurred in 14.4 and 8.3 % of patients, respectively (p = 0.188). One HBeAg-negative patient had HBsAg loss. Conclusions: This represents the largest analyses to date of CHB patients with sequential liver biopsies demonstrating that treatment with TDF for up to 5 years is associated with favorable virologic, serologic, and histologic outcomes, regardless of baseline cirrhosis status. Notably, histologic improvement was observed in the majority of cirrhotic and noncirrhotic patients.
KW - Antiviral agent
KW - Chronic hepatitis B
KW - Cirrhosis
KW - Hepatitis B e antigen
KW - Hepatitis B surface antigen
KW - Tenofovir disoproxil
UR - http://www.scopus.com/inward/record.url?scp=84939983283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939983283&partnerID=8YFLogxK
U2 - 10.1007/s12072-015-9614-4
DO - 10.1007/s12072-015-9614-4
M3 - Article
C2 - 25788199
AN - SCOPUS:84939983283
SN - 1936-0533
VL - 9
SP - 243
EP - 250
JO - Hepatology International
JF - Hepatology International
IS - 2
ER -