Evaluation of the Hepa Wash®treatment in pigs with acute liver failure

Abstract

BackgroundMortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF.MethodsIn the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h.ResultsAll animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed.ConclusionsHepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

“…Total (complete) liver devascularization usually involves portacaval shunt together with hepatic artery blockage, and, in many situations, devascularization of the gastric and diaphragmatic branches and ligation of the common bile duct are needed [11, 31]. The animals in these models usually died rapidly due to irreversibility.…”

“…The partial hepatectomy model, usually also involving devascularization, is seldom used because currently there is no unified standard for the volume of removed liver [9]. Ischemic models (complete/transient devascularization) are the most commonly used surgical models at present [10, 11], usually involving a portacaval shunt followed by hepatic artery occlusion and, in many situations, also requiring devascularization of accessory hepatic vessels and occlusion of the common bile duct [9, 11]. In order to control hepatic ischemic time and prolong survival time of the experimental animals, surgical procedures to create this model normally are performed in two or three steps [12].…”

Extracorporeal liver support devices for listed patients

“…The albumin dialysate is recirculated via a “Hepa Wash” circuit, which contains 2 parallel conventional hemofilters, in which albumin‐bound toxins are released through exposure to an alkaline or acid environment and subsequently removed by filtration. This design aims to maintain clearances of protein‐bound toxins through the treatment period . This is contrary to MARS, where a decline in clearance of protein‐bound toxins is seen throughout the recommended 7‐hour treatment …”

“…In a pig liver ischemia ALF model, Hepa Wash resulted in improvement in survival, cerebral perfusion pressure, hemodynamic status, and kidney function. Moreover, Hepa Wash resulted in reduction in azotemia, hyperammonemia, and blood nitrate/nitrite levels . Clinical trials in humans with ALF and ACLF were initiated in 2010 but have since been terminated for unknown reasons (NCT01079104, NCT01079091).…”

Establishment of gene‐edited pigs expressing human blood‐coagulation factor VII and albumin for bioartificial liver use

“…On the contrary, porcine primary hepatocytes are abundant and close to human hepatocytes in terms of metabolism and detoxication activity. Moreover, porcine primary hepatocytes are the earliest and the most widely used cell source for clinical trials of BALs for they are easily accessible …”