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A multinational phase 3 clinical trial presented at the EASL Congress 2026 has shown that plasma exchange using 5% human serum albumin significantly improves short-term survival in selected patients with acute-on-chronic liver failure (ACLF). The APACHE study demonstrated a 35% reduction in the risk of death without liver transplantation at 90 days, providing the first robust evidence that an extracorporeal liver support strategy can improve survival in this high-risk population. The findings may represent an important advance for a syndrome characterized by high mortality and limited treatment options.
Acute-on-chronic liver failure is one of the most severe complications of cirrhosis. The syndrome develops when patients experience an acute deterioration accompanied by failure of one or more organs, including the liver, kidneys, brain, circulatory system, respiratory system, or coagulation system. Mortality is high, particularly among patients requiring intensive care.
Despite major advances in the understanding of ACLF over the past decade, treatment remains largely supportive and focuses on managing precipitating events such as bacterial infections or severe alcohol-related hepatitis. Liver transplantation remains the only definitive treatment for many patients.
Clinicians have long sought effective organ support strategies capable of improving survival while patients recover or await transplantation. Previous extracorporeal organ support systems showed improvements in biochemical parameters but failed to consistently demonstrate a survival benefit.
The APACHE study was a phase 3, multicenter, open-label trial conducted across 29 centers in Europe and North America. The study enrolled 274 patients with cirrhosis and ACLF who were considered at high risk of hospital mortality.
Participants were randomly assigned to receive either standard medical treatment alone or standard medical treatment combined with plasma exchange using 5% human serum albumin. The treatment involved removing approximately 1.2 plasma volumes per session and replacing them primarily with albumin together with smaller amounts of fresh frozen plasma.
Patients received between four and nine treatment sessions over a period of approximately 16 days. Importantly, the study focused on patients early in the course of ACLF. Most participants had ACLF grade 1b or grade 2, while patients with advanced multiorgan failure were excluded.
At 90 days, the proportion of patients who died before receiving a liver transplant was significantly lower in the plasma exchange group than in the standard treatment group (37.8% versus 49.6%). This corresponded to a 35% reduction in the risk of death without liver transplantation.
“Our results suggest that plasma exchange with 5% albumin should be part of the standard of care of patients with early ACLF. This treatment can safely bridge these patients to liver transplantation and less frequently to recompensation”, said Javier Fernández, Principal Investigator of the APACHE trial, Head of the Liver Intensive Care Unit at Hospital Clínic de Barcelona, and Head of Clinical Operations at EF CLIF.
Notably, the survival benefit persisted well beyond the active treatment period, suggesting that plasma exchange may alter the trajectory of the disease rather than simply providing temporary physiological support.
According to the researchers, plasma exchange appears to act through multiple mechanisms, including the removal of harmful inflammatory mediators and the replacement of protective factors present in albumin and plasma from healthy donors. Together, these effects may help attenuate the systemic inflammation and immune dysregulation that drive organ systems failure in ACLF.
The findings are particularly relevant because many patients with ACLF are initially considered unsuitable candidates for liver transplantation due to severe organ dysfunction and poor short-term prognosis.
By stabilizing organ function and improving clinical status, plasma exchange may provide a critical window of opportunity during which patients can recover sufficiently to become eligible for transplantation.
This concept of “bridging” patients to transplant has long been a goal of liver support therapies, but until now evidence demonstrating a clear survival benefit has remained elusive.
The APACHE trial is the first large, randomized study to demonstrate a significant survival advantage for a therapeutic intervention specifically targeting ACLF. Experts attending the EASL Congress 2026 in Barcelona, Spain, highlighted the importance of the findings, noting that current management of ACLF remains largely supportive despite major advances in risk stratification and disease characterization.
Plasma exchange could become part of standard management for carefully selected patients with early-stage ACLF who remain at high risk of death despite optimal medical treatment.
While the results represent a major advance, important questions remain. Not all patients responded to treatment, and future research will need to determine which patient subgroups derive the greatest benefit and whether plasma exchange could be combined with other therapeutic approaches.
Nevertheless, the APACHE study provides the strongest evidence to date that targeted extracorporeal support can improve survival in ACLF and offers new hope for patients facing one of the most life-threatening complications of advanced liver disease.
The APACHE trial was conducted in collaboration with Grifols.
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