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BARCELONA, Spain — Plasma exchange using 5% albumin improved medium-term survival in carefully selected patients with acute-on-chronic liver failure (ACLF), potentially buying time for some patients to become eligible for liver transplantation, according to results from the phase 3 APACHE trial.

Plasma exchange delivered early in the course of ACLF provided a survival benefit that persisted well beyond the treatment period — out to 90 days — addressing a major unmet need in a syndrome associated with high short-term mortality and few effective therapeutic options.

“We have seen many negative studies in this field. This is the first positive study demonstrating an improvement in survival in ACLF, and it is going to change clinical practice,” said lead investigator Javier Fernández, MD, PhD, hepatologist and head of the Liver Intensive Care Unit at Hospital Clínic de Barcelona in Barcelona, Spain.

Fernández presented the findings here at the European Association for the Study of the Liver (EASL) Congress 2026.

Long-Standing Need for Effective Liver Support

ACLF develops when patients with underlying cirrhosis experience an acute deterioration accompanied by organ failure, including liver dysfunction, renal failure, hepatic encephalopathy, and coagulation abnormalities. Mortality is high, particularly among patients requiring intensive care.

Until now, treatment has largely focused on managing precipitating events such as infection or severe alcohol-associated hepatitis and organ support, while liver transplantation remains the only definitive treatment. “We have lacked an effective liver support system capable of improving survival,” Fernández told Medscape News Europe.

Previous attempts to provide artificial liver support in ACLF, including albumin dialysis systems such as MARS and Prometheus, have generally improved biochemical parameters without demonstrating consistent survival benefits.

Investigators hypothesized that removing circulating inflammatory mediators might benefit patients with ACLF.

“In ACLF, plasma exchange removes harmful molecules that activate the immune system and contribute to multi-organ failure,” Fernández explained. “At the same time, it provides anti-inflammatory and immunomodulatory effects through replacement with albumin and plasma from healthy donors.”

APACHE Trial Design

The APACHE study was a phase 3, multicenter, open-label trial conducted across 29 centers in Europe, North America, and Canada.

Patients with cirrhosis and ACLF at high risk for hospital mortality were randomly assigned 1:1 to receive either standard medical treatment alone or standard medical treatment plus plasma exchange using 5% human serum albumin.

The treatment involved removal of approximately 1.2 plasma volumes (roughly 3 L per session) with replacement primarily using 5% albumin and smaller amounts of fresh frozen plasma. Patients received between four and nine treatment sessions over approximately 16 days.

Although the trial originally planned to enroll approximately 380 participants, recruitment stopped after 274 patients enrolled. According to Fernández, the study nevertheless retained adequate statistical power to demonstrate a treatment effect.

Importantly, investigators focused on patients early in the course of the disease. Around 80% had ACLF grade 2 or 1b, typically involving failure in two organs or one failure plus one dysfunction. Patients with advanced multi-organ failure were excluded.

“In critical care, timing is everything,” Fernández said. “If a patient is referred after 2 or 3 weeks, it becomes much harder for any intervention to work.”

Survival Benefit Extends Beyond Treatment

The study met its primary endpoint. By day 90, fewer patients treated with plasma exchange plus standard medical treatment had died before receiving a liver transplant than those treated with standard medical treatment alone: 37.8% vs 49.6%. This difference was statistically significant and corresponded to a 35% lower risk for death before transplant.

Patients in the plasma exchange group also began to show better survival early in follow-up, and that advantage was still seen at day 90. However, by 90 days, the overall proportion of patients who had either died or undergone a liver transplant was similar in the two groups. The findings suggest that plasma exchange may help keep some patients alive long enough to undergo transplantation, rather than eliminating the need for transplantation.

“This suggests that plasma exchange acts mainly as a bridge to a liver transplantation in ACLF,” said Fernández.

Notably, the benefit persisted long after active treatment ended. “Patients received four to nine plasma exchange sessions over about 16 days, yet the survival benefit extended to 90 days,” Fernández said. “That was not necessarily what we expected at the outset.”

Fernández emphasized that plasma exchange is not a cure for cirrhosis. Instead, he described it as a strategy to stabilize patients long enough to reach transplantation.

Many patients with ACLF are initially considered too ill for transplant listing because of severe organ dysfunction and poor expected outcomes. “Plasma exchange can stabilize these patients, improve brain function and other organ failures, and allow them to become transplant candidates,” he said. “The treatment gives these patients time; time to recover sufficiently to be listed and time to reach transplantation.”

Potential Practice-Changing Findings

Previous interventions had not convincingly improved survival in ACLF. “Everybody has been waiting for the APACHE results,” Fernández said. “Many clinicians already believed plasma exchange was beneficial based on smaller studies and clinical experience, but we needed definitive evidence.”

He believes the therapy will now become part of standard medical management for appropriately selected patients with ACLF.

Asked to comment for Medscape News Europe, Jan Stange, MD, PhD, of the University of Rostock in Rostock, Germany, a pioneer in extracorporeal liver support therapies, said, “This important trial finally confirms that extracorporeal liver support providing detoxification support is a lifesaving therapy in acute-on-chronic liver failure. It will inspire further development until liver support will be a standard to bridge to transplant or recovery in ACLF.”

“This was a rather complex therapy,” Stange added. “It does prove new extracorporeal therapies involving means of detoxification and immunomodulation and substitution are superior to current standards. It should be the new standard to base further developments on once we understand the mechanisms of action better.”

Also speaking with Medscape News Europe, Marina Berenguer, MD, PhD, of La Fe University Hospital in Valencia, Spain, said the findings are particularly notable because few therapies directly target the underlying pathophysiology of ACLF.

“Despite advances in prognostic stratification, the management of ACLF remains largely supportive,” Berenguer said, noting that current care focuses on treating precipitants, supporting organ function, and evaluating patients for transplantation.

“In this context, the APACHE results may represent a major step forward,” she added, suggesting that plasma exchange with 5% albumin could emerge as one of the first ACLF-directed therapies capable of dampening the systemic inflammation that drives multiorgan failure and improving short-term survival.

Future studies will focus on identifying which patients derive the greatest benefit and whether plasma exchange should be combined with other therapeutic approaches.

“There are still patients who do not respond,” Fernández said. “We need to understand why and how we can improve outcomes further. But this is a major step forward.”

The APACHE trial was sponsored by Grifols Therapeutics. Fernández reported receiving honoraria from Grifols for lectures and educational activities. Stange reported being an inventor of the Molecular Adsorbents Recirculating System and co-founder of Albutec. Berenguer reported participating in the multinational ACLF CHANCE study.