Detoxification of bilirubin and bile acids with intermittent coupled plasmafiltration and adsorption in liver failure (HERCOLE study)

Abstract

Background CPFA is an extracorporeal treatment used in severe sepsis to remove circulating proinflammatory cytokines. Limited evidence exists on the effectiveness of bilirubin adsorption by the hydrophobic styrenic resin, the distinctive part of CPFA. The aim of this study is to validate CPFA effectiveness in liver detoxification. Methods In this prospective observational study, we enrolled patients with acute or acute-on-chronic liver failure (serum total bilirubin > 20 mg/dL or MELD Score > 20) hospitalized from June 2013 to November 2017. CPFA was performed using the Lynda (Bellco/MedTronic, Mirandola, Italy) or the Amplya (Bellco/MedTronic, Mirandola, Italy) machines. Anticoagulation was provided with unfractionated heparin or citrate. Bilirubin and bile acids reduction ratios per session (RRs) were the main parameters for hepatic detoxification. Results Twelve patients with acute (n = 3) or acute-on-chronic (n = 9) liver failure were enrolled. Alcohol was the main cause of liver disease. Thirty-one CPFA treatments of 6 h each were performed, 19 with heparin and 12 with citrate. RRs was 28.8% (range 2.2–40.5) for total bilirubin, 32.7% (range 8.3–48.9) for direct bilirubin, 29.5% (range 6.5–65.4) for indirect bilirubin and 28.9% (16.7- 59.7) for bile acids. One patient received liver transplantation and 8/9 were alive at 1 year of follow-up. Three patients (25%) died: 2 during hospitalization and 1 for a cardiac event at 4 months of follow up with restored liver function. Conclusions CPFA resulted to be effective in liver detoxification. Thus, it may be considered as a “bridge technique” both to the liver transplant and to the recovery of the basal liver function.

Clinical use of plasmafiltration coupled with adsorption

“…[7] Various studies have shown that besides effectively removing water-soluble and protein binding toxins, CPFA can also reduce bilirubin levels by 30% to 50% in each cycle. [57][58] The HERCOLE study [59] showed that CPFA was effective in the "detoxification" of patients with liver failure and is now considered a good "bridging technique" to liver transplantation or until recovery of baseline liver function. The regional citrate assisted anticoagulation mode and corresponding protocol monitoring (Table 2) provided by Amplya TM allow the safe use of CPFA under these clinical conditions.…”

“…The regional citrate assisted anticoagulation mode and corresponding protocol monitoring (Table 2) provided by Amplya TM allow the safe use of CPFA under these clinical conditions. [32,59] Sodium, potassium, chlorine, magnesium (*) In the "free citrate" mode, the management of citrate and calcium solution is controlled by the operator. The machine does not monitor or adjust any parameters related to anticoagulation, and the treatment team needs to perform protocol monitoring and control.…”

Continuous renal replacement therapy and extended indications

“…A recent trial, the HERCOLE study, demonstrated the feasibility and practicality of applying CPFA in patients with liver failure. 89 Importantly, liver failure per se is not a contraindication for regional citrate anticoagulation (RCA) since citrate metabolization also takes place in the myocytes and the renal cortex, [90][91][92][93] in both CPFA and PAP citrate can be used. 94 A retrospective analysis compared the bilirubin removal capacity of PAP versus MARS.…”

Liver failure—future challenges and remaining questions

“…The evidence for plasma exchange is rather limited and a clinical benefit is in question. Liver dialysis can reduce serum bilirubin and bile acid concentrations (25), however, it is unclear if some bile acid species might be required for liver regeneration. Thus, liver dialysis may on the one hand remove harmful bile acids while on the other hand also reducing signals for regeneration.…”