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In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

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In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

 

In light of apparently conflicting results from two recent major studies, it may be too early to consider outpatient albumin administration in patients with decompensated cirrhosis, according to Vijay Shah, MD, chair of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

Andrew D. Bowser/MDedge News
Dr. Vijay Shah

“These are interesting studies, but I don’t think we’re ready yet to use this broadly,” Dr. Shah said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.

Current guidelines do describe the use of albumin for large-volume paracentesis and other specific inpatient situations; however, extrapolating its long-term use has been explored in two major studies that recently came out with contradictory findings.

In the ANSWER trial, as reported in the Lancet, investigators at 33 centers randomized patients with cirrhosis and uncomplicated ascites to either standard medical treatment with or without human albumin, at 40 g twice weekly for 2 weeks, followed by 40 g weekly for up to 18 months.

Those investigators found that long-term albumin prolonged overall survival, with a 38% reduction in the mortality hazard ratio, with similar rates of serious, nonliver adverse events, leading them to conclude that this intervention may act as a disease-modifying treatment in decompensated cirrhosis patients.

By contrast, however, a recent randomized, placebo-controlled trial reported in the Journal of Hepatology showed that albumin plus midodrine, an alpha-adrenergic vasoconstrictor, did not improve survival among patients with decompensated cirrhosis on the liver transplant waiting list, at least at the doses administered (midodrine 15-30 mg/day and albumin 40 g every 15 days for a year).

While this particular combination of albumin plus midodrine did decrease renin and aldosterone levels, the intervention did not prevent complications or improve survival, investigators said at the time. Complication rates were 37% and 43% for treatment and placebo, respectively (P = .402), with low rates of death in both groups and no significant difference in mortality at 1 year (P = .527).

Dr. Shah said the discrepant results may be attributable to specific differences in study design or enrollment.

“It’s just hand waving, but it may be related to the dose of albumin, or may be related to the types of patients – the second study was in patients who are waiting for liver transplantation,” he told attendees. “But I don’t think that there’s currently enough evidence to use albumin in your patients in the outpatient setting.”

There is a third study, recently published in the American Journal of Gastroenterology, looking at data for a large end-stage liver disease cohort with hyponatremia. Investigators observed a higher rate of hyponatremia resolution and improved 30-day survival in those who had received albumin (total mean amount, 225 g) versus those who had not.

Considering all of this evidence taken together, Dr. Shah said he would not favor using outpatient albumin at this point – though he advised attendees to watch for a currently recruiting phase 3 randomized study, known as PRECIOSA, which is evaluating long-term administration of human albumin 20% injectable solution, dosed by body weight, in patients with decompensated cirrhosis and ascites.

Dr. Shah indicated that he is a consultant for Afimmune, Durect Corporation, Enterome, GRI Bio, Merck Research Laboratories, Novartis Pharma, and Vital Therapeutics. Global Academy and this news organization are owned by the same company.

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