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.