Does a patient with acute on chronic liver failure, alcoholic hepatitis, or persistent hyperbilirubinemia require Plasma Exchange (PLEX)?

Plasma Exchange for ACLF/Alcoholic Hepatitis/Persistent Hyperbilirubinemia

Plasma exchange (PLEX) is NOT routinely recommended for acute-on-chronic liver failure, alcoholic hepatitis, or persistent hyperbilirubinemia outside of research protocols, according to the most recent EASL guidelines, though it may be considered in highly selected critically ill patients as a bridge to transplantation when standard therapies fail. 1, 2

Guideline-Based Recommendations

Current Consensus Position

The major hepatology societies have divergent positions on PLEX for ACLF:

• EASL (2023) explicitly advises against routine use of PLEX for ACLF outside of research trials 1, 2
• AASLD (2024) suggests PLEX only for acute liver failure (ALF) with hyperammonemia (ammonia >150 μmol/L), not for ACLF 1, 2
• Asian guidelines (APASL/Chinese) support PLEX as promising for ACLF patients awaiting transplant, but this represents regional practice patterns rather than Western consensus 2

Critical Distinction: ALF vs. ACLF

PLEX has conditional support only for ALF with hyperammonemia, NOT for ACLF. 1, 2 The AASLD guidelines specifically recommend PLEX when available for critically ill ALF patients with ammonia >150 μmol/L (conditional recommendation, low-quality evidence). 1 This does not extend to ACLF or isolated hyperbilirubinemia. 2

Evidence Base and Limitations

Research Findings vs. Guideline Recommendations

While recent meta-analyses show potential survival benefit with PLEX in ACLF:

• A 2025 meta-analysis (23 studies, 5,336 patients) demonstrated reduced 30-day mortality (RR 0.70) and 90-day mortality (RR 0.81) with PLEX versus standard medical therapy 3
• A 2021 propensity-matched study from the AARC database showed PLEX improved SIRS resolution and reduced multiorgan failure development 4

However, the EASL guidelines explicitly reject routine PLEX use despite this emerging data, citing insufficient high-quality evidence and the need for controlled trials. 1, 2 This represents the most authoritative and recent guideline position for Western practice.

Why Guidelines Remain Conservative

The evidence limitations include:

• Most studies are observational or small RCTs with heterogeneous ACLF definitions 3, 5
• Lack of standardized PLEX protocols (volume, frequency, replacement fluid) 5
• Unclear patient selection criteria for optimal benefit 6
• Regional variation in practice patterns (Asian vs. Western centers) 2

Priority Management Algorithm

Step 1: Confirm Diagnosis and Severity

Immediately assess ACLF grade using CLIF-SOFA scoring (evaluates liver, kidney, brain, coagulation, circulation, lungs). 7

• ACLF Grade 1: Single organ failure
• ACLF Grade 2: Two organ failures
• ACLF Grade 3: Three or more organ failures 7

Step 2: Standard Evidence-Based Interventions (NOT PLEX)

These interventions have stronger evidence and guideline support than PLEX:

• Identify and treat precipitants aggressively: bacterial/fungal infection, GI bleeding, viral hepatitis reactivation, alcohol-related hepatitis, drug-induced liver injury 7, 2
• Empirical broad-spectrum antibiotics if infection suspected—do not delay for cultures 7
• Hepatorenal syndrome management: Terlipressin plus albumin first-line; norepinephrine if terlipressin unavailable 7
• Vasopressor support for MAP <70 mmHg despite fluid resuscitation; avoid excessive crystalloids 7
• Renal replacement therapy for creatinine >440 μmol/L or refractory fluid overload 7

Step 3: Transplant Evaluation (Higher Priority Than PLEX)

Early transplant center referral is critical and takes precedence over experimental therapies. 7, 2

Immediate transplant evaluation indicated for:

• ACLF Grade 2-3 7
• King's College criteria met 7
• Wilson's disease with hemolysis and coagulopathy 7
• Autoimmune hepatitis not responding to corticosteroids after 2 weeks 7

Transplant outcomes far exceed PLEX outcomes: 1-year survival 78% with early transplant vs. <10% without transplant in ACLF. 7

Step 4: When to Consider PLEX (Exceptional Circumstances Only)

PLEX might be considered only in this narrow scenario:

A critically ill ACLF patient who is:

• Listed for transplant and deteriorating while awaiting organ availability (bridge to transplant) 2, 5
• Failing standard therapies including organ support 2
• At a center with PLEX expertise and ideally within a research protocol 1, 2

Do NOT use PLEX for:

• Isolated persistent hyperbilirubinemia without organ failures 1
• Stable ACLF Grade 1 7
• Patients not transplant candidates (futile intervention) 7
• Routine alcoholic hepatitis management 1

Critical Pitfalls to Avoid

• Delaying transplant evaluation while pursuing PLEX—transplant referral must occur first 7, 2
• Using PLEX as substitute for identifying/treating precipitants—infection control and precipitant management are evidence-based priorities 7, 2
• Prophylactic blood product transfusion before PLEX—this obscures disease progression monitoring 7
• Assuming PLEX recommendations for ALF apply to ACLF—these are distinct conditions with different evidence bases 1, 2
• Continuing experimental therapies beyond 2 weeks without improvement in autoimmune hepatitis—escalate to transplant evaluation instead 7

Prognostic Reassessment

Reassess ACLF grade at 3-7 days to guide ongoing management decisions. 7

• Improving organ function: Continue standard therapies, maintain transplant listing
• Stable or worsening multiorgan failure: Urgent transplant or palliative care discussion 7

Post-discharge prognosis without transplant is dismal (1-year survival <25%), so all ACLF survivors require transplant center referral. 7