Therapeutic Plasma Exchange for Acute and Acute‐on‐Chronic Liver Failure: A Randomized Pilot Study Comparing Standard‐ and High‐Volume Protocols in a Resource‐Limited Setting

BACKGROUND: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) carry substantial short-term mortality. While liver transplantation is the definitive therapy, access is often delayed in settings reliant on living-donor transplantation, such as Egypt. Therapeutic plasma exchange (TPE) has emerged as a potential bridging strategy, but evidence from resource-limited health systems remains scarce. METHODS: We conducted a prospective randomized pilot study including 46 adults with ALF or ACLF at a tertiary center in Egypt. Participants were assigned to standard medical therapy (SMT; n = 15), standard-volume plasma exchange (SVPE; n = 16), or high-volume plasma exchange (HVPE; n = 15). SVPE involved exchange of 1.5-2.0 plasma volumes per session, whereas HVPE delivered 8-12 L/day for 3 consecutive days. All patients received guideline-based SMT. Changes in alanine aminotransferase (ALT), total bilirubin, international normalized ratio (INR), and MELD-Na score were evaluated alongside procedure-related complications and 90-day mortality. RESULTS: Both TPE strategies produced greater improvements in ALT, total bilirubin, INR, and MELD-Na compared with SMT alone. HVPE achieved the largest reduction in MELD-Na but was associated with higher rates of catheter-related infection and neurological complications. SVPE demonstrated a more favorable safety-effectiveness profile. Ninety-day mortality was highest with SMT and lower in both TPE groups. CONCLUSIONS: In a resource-limited tertiary setting, protocolized TPE is feasible and may improve short-term outcomes in ALF and ACLF. SVPE may represent a safer and more scalable bridging strategy when immediate access to liver transplantation is limited.