Albumin 5% Cut Mortality Rates in Sudden Liver Failure With Other Organ Failure

Plasma exchange with albumin 5% (Albutein 5%, PE-A5%) added to standard medical treatment (SMT) improved outcomes in patients with acute-on-chronic liver failure (ACLF), according to the randomized phase III APACHE trial.

Among 274 patients with liver failure plus one, two, or three other organ failures, those who received PE-A5% plus SMT saw significantly lower 90-day overall mortality rates without prior liver transplant than those receiving SMT alone (37.8% vs 49.6%, HR 0.65, P=0.021).

In an exploratory subgroup analysis by ACLF grade, PE-A5% was linked with lower mortality rates mainly in less severe forms of ACLF, reported Javier Fernández, MD, PhD, of the Hospital Clínic de Barcelona in Spain, at the European Association for the Study of the Liver annual meeting in Barcelona.

“I’m not saying that plasma exchange is a substitute for liver transplantation,” Fernández cautioned during his presentation. Instead, PE-A5% “is something that’s going to give you time for stabilizing the patient, to improve the clinical status of the patient, to bridge the patient to liver transplantation, if the patient is a candidate.”

ACLF is a severe condition in patients with chronic liver disease, in which sudden liver decompensation leads to multi-organ failure and high mortality rates. Triggers include alcohol-associated hepatitis, drug-induced liver injury, viral hepatitis, bacterial infections, and major surgical interventions. There are no FDA-approved therapies for ACLF, and the only lifesaving treatment is liver transplantation.

The open-label, active-controlled phase III APACHE trial enrolled 274 patients at 29 centers in nine European and North American countries in an intention-to-treat analysis. Patients were age 18 years or older with a liver cirrhosis diagnosis and hospitalized with ACLF-1b (one organ failure, not kidney or brain), ACLF-2 (two organ failures), or ACLF-3a (three organ failures). Key exclusionary criteria included having ACLF alone, ACLF-1a (kidney failure), or ACLF-3b (four to six organ failures).

Patients randomized to PE-A5% plus SMT received at least four and up to nine plasma-exchange sessions over the first 17 days, with follow-up at day 21, 28, 60, and 90. If patients didn’t respond, treatment was stopped after the fourth session. PE-A5% was also stopped in patients who worsened to ACLF-3b. SMT-alone patients received care over 17 days, with the same follow-up regimen as PE-A5% patients.

The study’s primary endpoint was 90-day overall survival without prior liver transplant.

Mean patient age was 50.7 years, 67.9% were male, 87.2% were white, 6.9% were Black or African American, 1.5% were Asian, and 0.4% were American Indian or Alaskan Native. More than half of patients (55.5%) were ACLF-2; 23% were ACLF-3a and 21.5% were ACLF-1b. Mean Chronic Liver Failure Consortium ACLF score at baseline was 51.4. Alcohol use was a factor in 90% of patients in both treatment arms, Fernández noted.

The exploratory analysis by ACLF grade showed that among ACLF-1b patients, 21.4% of PE-A5% patients and 32.3% of SMT-alone patients died at 90 days (HR 0.73). The mortality rates among ACLF-2 patients were 36.4% and 52.0%, respectively (HR 0.55), while rates among ACLF-3a patients were 56.7% and 60.6%, respectively (HR 0.83).

A mortality advantage was observed at day 28, though it was not significant, with 28.9% of PE-A5% patients dying without prior liver transplant compared with 36.7% of SMT-only patients (HR 0.67, P=0.06).

There were no significant differences in the percentages of patients who had a liver transplant or died at 90 days, at 64.4% for PE-A5% and 64% for SMT alone (HR 0.83, P=0.22). Those virtually identical rates are a reminder that “this plasma exchange is mainly a bridge to transplantation,” Fernández said. “You cannot compete with liver transplantation in ACLF.”

PE-A5% was linked to greater rates of any treatment-emergent adverse events (TEAE) than SMT alone (85.2% vs 71.9%), as well as greater rates of serious TEAEs (28.9% vs 20.1%). Those higher TEAE rates didn’t translate into higher rates of fatal TEAEs, however (7.0% and 7.2%, respectively).