Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease

[Guest guest]

Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in

patients with decompensated chronic hepatitis B liver disease.

Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F,

Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K,

Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER.

Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College

of Medicine, Taipei, Taiwan.

Abstract

Data are limited on the safety and effectiveness of oral antivirals other than

lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in

patients with decompensated liver disease. This Phase 2, double-blind study

randomized 112 patients with CHB and decompensated liver disease to receive

either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF

(fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary

endpoint was safety; more specifically, tolerability failure (adverse events

resulting in permanent treatment discontinuation) and confirmed serum creatinine

increase ™0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL.

Patients with insufficient viral suppression (e.g., confirmed HBV DNA ™400

copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered

failures in this interim week 48 analysis for efficacy endpoints. Tolerability

failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P =

0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5%

(P = 1.000), respectively. Six patients died (none considered related to study

drug) and six received liver transplants (none had HBV recurrence). The adverse

event and laboratory profiles were consistent with advanced liver disease and

complications, with no unexpected safety signals. At week 48, HBV DNA was <400

copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of

patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76%

(FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion

occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV).

Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved

in all groups. Conclusion: All treatments were well tolerated in patients with

decompensated liver disease due to CHB with improvement in virologic,

biochemical, and clinical parameters. (HEPATOLOGY 2011.).Copyright ¿ 2010

American Association for the Study of Liver Diseases.

PMID: 21254162 [PubMed - in process]

[Guest guest]

Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in

patients with decompensated chronic hepatitis B liver disease.

Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F,

Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K,

Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER.

Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College

of Medicine, Taipei, Taiwan.

Abstract

Data are limited on the safety and effectiveness of oral antivirals other than

lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in

patients with decompensated liver disease. This Phase 2, double-blind study

randomized 112 patients with CHB and decompensated liver disease to receive

either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF

(fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary

endpoint was safety; more specifically, tolerability failure (adverse events

resulting in permanent treatment discontinuation) and confirmed serum creatinine

increase ™0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL.

Patients with insufficient viral suppression (e.g., confirmed HBV DNA ™400

copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered

failures in this interim week 48 analysis for efficacy endpoints. Tolerability

failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P =

0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5%

(P = 1.000), respectively. Six patients died (none considered related to study

drug) and six received liver transplants (none had HBV recurrence). The adverse

event and laboratory profiles were consistent with advanced liver disease and

complications, with no unexpected safety signals. At week 48, HBV DNA was <400

copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of

patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76%

(FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion

occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV).

Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved

in all groups. Conclusion: All treatments were well tolerated in patients with

decompensated liver disease due to CHB with improvement in virologic,

biochemical, and clinical parameters. (HEPATOLOGY 2011.).Copyright ¿ 2010

American Association for the Study of Liver Diseases.

PMID: 21254162 [PubMed - in process]

[Guest guest]

Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in

patients with decompensated chronic hepatitis B liver disease.

Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F,

Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K,

Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER.

Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College

of Medicine, Taipei, Taiwan.

Abstract

Data are limited on the safety and effectiveness of oral antivirals other than

lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in

patients with decompensated liver disease. This Phase 2, double-blind study

randomized 112 patients with CHB and decompensated liver disease to receive

either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF

(fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary

endpoint was safety; more specifically, tolerability failure (adverse events

resulting in permanent treatment discontinuation) and confirmed serum creatinine

increase ™0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL.

Patients with insufficient viral suppression (e.g., confirmed HBV DNA ™400

copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered

failures in this interim week 48 analysis for efficacy endpoints. Tolerability

failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P =

0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5%

(P = 1.000), respectively. Six patients died (none considered related to study

drug) and six received liver transplants (none had HBV recurrence). The adverse

event and laboratory profiles were consistent with advanced liver disease and

complications, with no unexpected safety signals. At week 48, HBV DNA was <400

copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of

patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76%

(FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion

occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV).

Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved

in all groups. Conclusion: All treatments were well tolerated in patients with

decompensated liver disease due to CHB with improvement in virologic,

biochemical, and clinical parameters. (HEPATOLOGY 2011.).Copyright ¿ 2010

American Association for the Study of Liver Diseases.

PMID: 21254162 [PubMed - in process]

[Guest guest]

Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.

Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in

patients with decompensated chronic hepatitis B liver disease.

Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F,

Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K,

Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER.

Liver Research unit, Chang Gung Memorial Hospital, Chang Gung University College

of Medicine, Taipei, Taiwan.

Abstract

Data are limited on the safety and effectiveness of oral antivirals other than

lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in

patients with decompensated liver disease. This Phase 2, double-blind study

randomized 112 patients with CHB and decompensated liver disease to receive

either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF

(fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary

endpoint was safety; more specifically, tolerability failure (adverse events

resulting in permanent treatment discontinuation) and confirmed serum creatinine

increase ™0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL.

Patients with insufficient viral suppression (e.g., confirmed HBV DNA ™400

copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered

failures in this interim week 48 analysis for efficacy endpoints. Tolerability

failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P =

0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5%

(P = 1.000), respectively. Six patients died (none considered related to study

drug) and six received liver transplants (none had HBV recurrence). The adverse

event and laboratory profiles were consistent with advanced liver disease and

complications, with no unexpected safety signals. At week 48, HBV DNA was <400

copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of

patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76%

(FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion

occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV).

Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved

in all groups. Conclusion: All treatments were well tolerated in patients with

decompensated liver disease due to CHB with improvement in virologic,

biochemical, and clinical parameters. (HEPATOLOGY 2011.).Copyright ¿ 2010

American Association for the Study of Liver Diseases.

PMID: 21254162 [PubMed - in process]