Adefovir lowers MELD scores in patients with lamivudine-resistant hepatitis B waiting for transplantation

[Guest guest]

EASL 2005

http://clinicaloptions.com/hep/news/news_EASL2005_7.asp

Adefovir lowers MELD scores in patients with lamivudine-resistant hepatitis

B waiting for transplantation

By Jillian L. Lokere, MS

April 15, 2005 - Adefovir dipivoxil lowered MELD scores in patients with

lamivudine-resistent HBV infection who were on the waiting list for liver

transplantation, according to a multicenter study presented by Eugene Schiff

from the University of Miami, Florida at the 40th Annual Meeting of the

European Association for the Study of the Liver. Many of these patients were

then able to be removed from the waiting list.

Orthotopic liver transplantation (OLT) is in high demand for patients with

severe liver disease due to chronic hepatitis B, but there are too few

avaliable donor organs. Therefore, effective treatment for patients on the

waiting list for OLT at high-risk of liver failure and death are urgently

needed. Adefovir, a nucleotide analogue, is effective in patients with both

wild-type and lamivudine-resistant HBV infection. In this study, Schiff and

colleagues determined the efficacy of adefovir in patients with HBV

infection who were wait-listed for OLT.

A total of 226 patients from 88 centers who were on the OLT waiting list and

had lamivudine-resistant HBV infection were enrolled in the study. All

patients received 10 mg/day of adefovir along with continued lamivudine

treatment in a majority of patients. The majority of the patients were white

and male, with a median age of 52 years. The median Child-Turcotte-Pugh

score was 7.0, and the median MELD score was 12. Patients had been taking

lamivudine for a median of 74 weeks before study entry.

After enrollment, 61 patients underwent OLT and were not included in the

efficacy analysis, and 32 patients died while on the waiting list. A large

number of these deaths occurred within 30 days of beginning adefovir. Eight

patients died after OLT.

Among the wait-listed patients avaliable for the efficacy analysis, adefovir

treatment improved both clinical and laboratory findings. After 96 weeks of

adefovir treatment, serum HBV DNA fell below 1000 copies/mL in 65% of

patients, and ALT levels were normalized in 77%. The MELD score dropped by a

mean of 3.8 points at week 48 and 5.1 points at week 96. The cumulative

survival was 77% at 96 weeks by Kaplan-Meier estimates.

Adefovir was generally well tolerated. Among the 226 patients included in

the safety analysis, the most common adverse events were asthenia (4%),

abdominal pain (2%), and diarrhea (2%). Only 2% of patients discontinued

treatment because of renal events, and all these patients had renal risk

factors at the beginning of the study. Resistance muations to adefovir

(N236T) developed in 3 patients, all of whom had discontinued lamivudine

during the study and were taking only adefovir. None of the patients who

continued lamivudine developed resistance muations.

Schiff noted that adefovir treatment allowed downgrading or removal from the

OLT list in many patients, and therefore he believes that adefovir treatment

should be started as soon as possible in this population. In response to a

question from the audience, he suggested that all lamivudine-resistent

patients who begin taking adefovir should continue lamivudine treatment to

protect against the development of adefovir resistence mutations.

Reference

Schiff E, Lai CL, Neuhaus P, et al. Adefovir dipivoxil provides significant

clinical benefit, reduces MELD score and prevents transplantation in chronic

hepatitis B patients wait-listed for liver transplantation with

lamivudine-resistance. Program and abstracts of the 40th Annual Meeting of

the European Association for the Study of the Liver. Abstract 7.

[Guest guest]

EASL 2005

http://clinicaloptions.com/hep/news/news_EASL2005_7.asp

Adefovir lowers MELD scores in patients with lamivudine-resistant hepatitis

B waiting for transplantation

By Jillian L. Lokere, MS

April 15, 2005 - Adefovir dipivoxil lowered MELD scores in patients with

lamivudine-resistent HBV infection who were on the waiting list for liver

transplantation, according to a multicenter study presented by Eugene Schiff

from the University of Miami, Florida at the 40th Annual Meeting of the

European Association for the Study of the Liver. Many of these patients were

then able to be removed from the waiting list.

Orthotopic liver transplantation (OLT) is in high demand for patients with

severe liver disease due to chronic hepatitis B, but there are too few

avaliable donor organs. Therefore, effective treatment for patients on the

waiting list for OLT at high-risk of liver failure and death are urgently

needed. Adefovir, a nucleotide analogue, is effective in patients with both

wild-type and lamivudine-resistant HBV infection. In this study, Schiff and

colleagues determined the efficacy of adefovir in patients with HBV

infection who were wait-listed for OLT.

A total of 226 patients from 88 centers who were on the OLT waiting list and

had lamivudine-resistant HBV infection were enrolled in the study. All

patients received 10 mg/day of adefovir along with continued lamivudine

treatment in a majority of patients. The majority of the patients were white

and male, with a median age of 52 years. The median Child-Turcotte-Pugh

score was 7.0, and the median MELD score was 12. Patients had been taking

lamivudine for a median of 74 weeks before study entry.

After enrollment, 61 patients underwent OLT and were not included in the

efficacy analysis, and 32 patients died while on the waiting list. A large

number of these deaths occurred within 30 days of beginning adefovir. Eight

patients died after OLT.

Among the wait-listed patients avaliable for the efficacy analysis, adefovir

treatment improved both clinical and laboratory findings. After 96 weeks of

adefovir treatment, serum HBV DNA fell below 1000 copies/mL in 65% of

patients, and ALT levels were normalized in 77%. The MELD score dropped by a

mean of 3.8 points at week 48 and 5.1 points at week 96. The cumulative

survival was 77% at 96 weeks by Kaplan-Meier estimates.

Adefovir was generally well tolerated. Among the 226 patients included in

the safety analysis, the most common adverse events were asthenia (4%),

abdominal pain (2%), and diarrhea (2%). Only 2% of patients discontinued

treatment because of renal events, and all these patients had renal risk

factors at the beginning of the study. Resistance muations to adefovir

(N236T) developed in 3 patients, all of whom had discontinued lamivudine

during the study and were taking only adefovir. None of the patients who

continued lamivudine developed resistance muations.

Schiff noted that adefovir treatment allowed downgrading or removal from the

OLT list in many patients, and therefore he believes that adefovir treatment

should be started as soon as possible in this population. In response to a

question from the audience, he suggested that all lamivudine-resistent

patients who begin taking adefovir should continue lamivudine treatment to

protect against the development of adefovir resistence mutations.

Reference

Schiff E, Lai CL, Neuhaus P, et al. Adefovir dipivoxil provides significant

clinical benefit, reduces MELD score and prevents transplantation in chronic

hepatitis B patients wait-listed for liver transplantation with

lamivudine-resistance. Program and abstracts of the 40th Annual Meeting of

the European Association for the Study of the Liver. Abstract 7.

[Guest guest]

EASL 2005

http://clinicaloptions.com/hep/news/news_EASL2005_7.asp

Adefovir lowers MELD scores in patients with lamivudine-resistant hepatitis

B waiting for transplantation

By Jillian L. Lokere, MS

April 15, 2005 - Adefovir dipivoxil lowered MELD scores in patients with

lamivudine-resistent HBV infection who were on the waiting list for liver

transplantation, according to a multicenter study presented by Eugene Schiff

from the University of Miami, Florida at the 40th Annual Meeting of the

European Association for the Study of the Liver. Many of these patients were

then able to be removed from the waiting list.

Orthotopic liver transplantation (OLT) is in high demand for patients with

severe liver disease due to chronic hepatitis B, but there are too few

avaliable donor organs. Therefore, effective treatment for patients on the

waiting list for OLT at high-risk of liver failure and death are urgently

needed. Adefovir, a nucleotide analogue, is effective in patients with both

wild-type and lamivudine-resistant HBV infection. In this study, Schiff and

colleagues determined the efficacy of adefovir in patients with HBV

infection who were wait-listed for OLT.

A total of 226 patients from 88 centers who were on the OLT waiting list and

had lamivudine-resistant HBV infection were enrolled in the study. All

patients received 10 mg/day of adefovir along with continued lamivudine

treatment in a majority of patients. The majority of the patients were white

and male, with a median age of 52 years. The median Child-Turcotte-Pugh

score was 7.0, and the median MELD score was 12. Patients had been taking

lamivudine for a median of 74 weeks before study entry.

After enrollment, 61 patients underwent OLT and were not included in the

efficacy analysis, and 32 patients died while on the waiting list. A large

number of these deaths occurred within 30 days of beginning adefovir. Eight

patients died after OLT.

Among the wait-listed patients avaliable for the efficacy analysis, adefovir

treatment improved both clinical and laboratory findings. After 96 weeks of

adefovir treatment, serum HBV DNA fell below 1000 copies/mL in 65% of

patients, and ALT levels were normalized in 77%. The MELD score dropped by a

mean of 3.8 points at week 48 and 5.1 points at week 96. The cumulative

survival was 77% at 96 weeks by Kaplan-Meier estimates.

Adefovir was generally well tolerated. Among the 226 patients included in

the safety analysis, the most common adverse events were asthenia (4%),

abdominal pain (2%), and diarrhea (2%). Only 2% of patients discontinued

treatment because of renal events, and all these patients had renal risk

factors at the beginning of the study. Resistance muations to adefovir

(N236T) developed in 3 patients, all of whom had discontinued lamivudine

during the study and were taking only adefovir. None of the patients who

continued lamivudine developed resistance muations.

Schiff noted that adefovir treatment allowed downgrading or removal from the

OLT list in many patients, and therefore he believes that adefovir treatment

should be started as soon as possible in this population. In response to a

question from the audience, he suggested that all lamivudine-resistent

patients who begin taking adefovir should continue lamivudine treatment to

protect against the development of adefovir resistence mutations.

Reference

Schiff E, Lai CL, Neuhaus P, et al. Adefovir dipivoxil provides significant

clinical benefit, reduces MELD score and prevents transplantation in chronic

hepatitis B patients wait-listed for liver transplantation with

lamivudine-resistance. Program and abstracts of the 40th Annual Meeting of

the European Association for the Study of the Liver. Abstract 7.

[Guest guest]

EASL 2005

http://clinicaloptions.com/hep/news/news_EASL2005_7.asp

Adefovir lowers MELD scores in patients with lamivudine-resistant hepatitis

B waiting for transplantation

By Jillian L. Lokere, MS

April 15, 2005 - Adefovir dipivoxil lowered MELD scores in patients with

lamivudine-resistent HBV infection who were on the waiting list for liver

transplantation, according to a multicenter study presented by Eugene Schiff

from the University of Miami, Florida at the 40th Annual Meeting of the

European Association for the Study of the Liver. Many of these patients were

then able to be removed from the waiting list.

Orthotopic liver transplantation (OLT) is in high demand for patients with

severe liver disease due to chronic hepatitis B, but there are too few

avaliable donor organs. Therefore, effective treatment for patients on the

waiting list for OLT at high-risk of liver failure and death are urgently

needed. Adefovir, a nucleotide analogue, is effective in patients with both

wild-type and lamivudine-resistant HBV infection. In this study, Schiff and

colleagues determined the efficacy of adefovir in patients with HBV

infection who were wait-listed for OLT.

A total of 226 patients from 88 centers who were on the OLT waiting list and

had lamivudine-resistant HBV infection were enrolled in the study. All

patients received 10 mg/day of adefovir along with continued lamivudine

treatment in a majority of patients. The majority of the patients were white

and male, with a median age of 52 years. The median Child-Turcotte-Pugh

score was 7.0, and the median MELD score was 12. Patients had been taking

lamivudine for a median of 74 weeks before study entry.

After enrollment, 61 patients underwent OLT and were not included in the

efficacy analysis, and 32 patients died while on the waiting list. A large

number of these deaths occurred within 30 days of beginning adefovir. Eight

patients died after OLT.

Among the wait-listed patients avaliable for the efficacy analysis, adefovir

treatment improved both clinical and laboratory findings. After 96 weeks of

adefovir treatment, serum HBV DNA fell below 1000 copies/mL in 65% of

patients, and ALT levels were normalized in 77%. The MELD score dropped by a

mean of 3.8 points at week 48 and 5.1 points at week 96. The cumulative

survival was 77% at 96 weeks by Kaplan-Meier estimates.

Adefovir was generally well tolerated. Among the 226 patients included in

the safety analysis, the most common adverse events were asthenia (4%),

abdominal pain (2%), and diarrhea (2%). Only 2% of patients discontinued

treatment because of renal events, and all these patients had renal risk

factors at the beginning of the study. Resistance muations to adefovir

(N236T) developed in 3 patients, all of whom had discontinued lamivudine

during the study and were taking only adefovir. None of the patients who

continued lamivudine developed resistance muations.

Schiff noted that adefovir treatment allowed downgrading or removal from the

OLT list in many patients, and therefore he believes that adefovir treatment

should be started as soon as possible in this population. In response to a

question from the audience, he suggested that all lamivudine-resistent

patients who begin taking adefovir should continue lamivudine treatment to

protect against the development of adefovir resistence mutations.

Reference

Schiff E, Lai CL, Neuhaus P, et al. Adefovir dipivoxil provides significant

clinical benefit, reduces MELD score and prevents transplantation in chronic

hepatitis B patients wait-listed for liver transplantation with

lamivudine-resistance. Program and abstracts of the 40th Annual Meeting of

the European Association for the Study of the Liver. Abstract 7.