Abstract
BackgroundAcute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival.MethodsMEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model.DiscussionWe present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned.Systematic review registration(PROSPERO) CRD42019122520, registered April 16, 2019.
Highlights
Acute liver failure is a rare syndrome with significant morbidity and mortality, in absence of transplantation as a rescue therapy
Its defining characteristic is the absence of premorbid liver disease [4] and the complications of long-term portal hypertension
One current rescue therapy exists in the form of liver transplantation
Summary
Acute liver failure is a rare syndrome with significant morbidity and mortality, in absence of transplantation as a rescue therapy. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival. Acute liver failure (ALF) is defined by the American Association for the Study of Liver Disease (AASLD) as a new coagulopathy (with International Normalized Ratio [INR] ≥ 1.5) and any degree of encephalopathy in a patient with new onset liver failure (< 26 weeks) [1]. It is a rare entity with an estimated incidence of between 1 and 6 cases per million people per year [2]. Given this survival discrepancy of nearly 25%, there is a need for a deeper understanding of the pathophysiology of acute liver failure and therapies that will help bridge to transplantation or obviate the need for transplantation
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