This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced through CCl4 administration in a swine model.
Methods
20 swines with AHF induced by intraperitoneal injection of carbon tetrachloride (CCl4) in oil solution, were randomly divided into two groups: animals receiving L.E.O2 NARDO treatment 48 h after the intoxication (study group); animals sham operated 48 h after the intoxication (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 h. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different time points and liver biopsies were collected 48 h after intoxication and at sacrifice.
Results
We observed decreased transaminases levels and a more rapid INR recovery in the study group, as compared to the control group. Eight animals of the study group vs. two animals of the control group survived at five days after surgery with a statistically significant difference (p<0.05). Liver biopsies performed at sacrifice showed a reduction of the damaged hepatic areas in the study group as compared to the control group.
Conclusions
Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.
RingeB., PichlmayrR., ZieglerH.Management of severe hepatic trauma by two-stage total hepatectomy and subsequent liver transplantation. Surgery.1991; 109(6): 792–795.
O'GradyJ.G., GimsonA.E., O'BrienC.J., PucknellA., HughesR.D., WilliamsR.Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology.1988; 94(5 Pt 1): 1186–1192.
5.
HughesR.D., PucknellA., RoutleyD., LangleyP.G., WendonJ.A., WilliamsR.Evaluation of the BioLogic-DT sorbent-suspension dialyser in patients with fulminant hepatic failure. Int J Artif Organs.1994; 17(12): 657–662.
6.
StangeJ., MitznerS.R., RislerT.Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support. Artif Organs.1999; 23(4): 319–330.
7.
RittlerP., KetscherC., InthornD., JauchK.W., HartlW.H.Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction—preliminary results. Liver Int.2004; 24(2): 136–141.
8.
SchmidtL.E., WangL.P., HansenB.A., LarsenF.S.Systemic haemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: a prospective controlled trial. Liver Transpl.2003; 9(3): 290–297.
9.
RifaiK., ErnstT., KretschmerU.Prometheus—a new extracorporeal system for the treatment of liver failure. J Hepatol.2003; 39(6): 984–990.
10.
EllisA.J., HughesR.D., WendonJ.A.Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure. Hepatology.1996; 24(6): 1446–1451.
11.
DemetriouA.A., BrownR.S.Jr., BusuttilR.W.Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg.2004; 239(5): 660–667, discussion 667-670.
12.
van de KerkhoveM.P., Di FlorioE., ScuderiV.Phase I clinical trial with the AMC-bioartificial liver. Int J Artif Organs.2002; 25(10): 950–959.
13.
SauerI.M., ZeilingerK., ObermayerN.Primary human liver cells as source for modular extracorporeal liver support—a preliminary report. Int J Artif Organs.2002; 25(10): 1001–1005.
14.
BaccaraniU., DoniniA., SannaA.First report of cryopreserved human hepatocytes based bioartificial liver successfully used as a bridge to liver transplantation. Am J Transplant.2004; 4(2): 286–289.
15.
StrainA.J., NeubergerJ.M.A bioartificial liver—state of the art. Science.2002; 295(5557): 1005–1009.
16.
KjaergardL.L., LiuJ., Als-NielsenB., GluudC.Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA.2003; 289(2): 217–222.
17.
O'BeirneJ.P., WendonJ.A.Liver support. Int J Artif Organs.2005; 28(5): 477–481.
18.
OgataA., MiyazakiM., OhtawaS., OhtsukaM., NakajimaN.Short-term effect of portal vein arterialization on hepatic protein synthesis and endotoxaemia after extended hepatectomy in dogs. J Gastroenterol Hepatol.1997; 12(9-10): 633–638.
19.
ShimizuY., MiyazakiM., ShimizuH.Beneficial effects of arterialization of the portal vein on extended hepatectomy. Br J Surg.2000; 87(6): 784–789.
20.
FanY-D, PraetM., Van HuysseJ., LelieB., De HemptinneB.Effects of portal vein arterialization on liver regeneration after partial hepatectomy in the rat. Liver Transpl.2002; 8(2): 146–152.
21.
NardoB., CaraceniP., PuvianiL.Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat. J Surg Res.2006; 135(2): 394–401.
22.
IsekiJ., TouyamaK., NoieT.Partial portal arterialization for the prevention of massive liver necrosis following extended pancreatobiliary surgery: experience of two cases. Surg Today.1992; 22(6): 568–571.
23.
OzekiY., UmemotoT., TateyamaK., KatagiriY., KatayamaM., SugiyamaA.Partial portal arterialization for dearterialized liver after hepatectomy. Br J Surg.1997; 84(7): 1011.
24.
TanabeG., KawaidaK., HamanoueM.Treatment for accidental occlusion of the hepatic artery after hepatic resection: report of two cases. Surg Today.1999; 29(3): 268–272.
25.
KondoS., HiranoS., AmboY., TanakaE., KubotaT., KatohH.Arterioportal shunting as an alternative to microvascular reconstruction after hepatic artery resection. Br J Surg.2004; 91(2): 248–251.
26.
YoungA.L., PrasadK.R., AdairR., Abu HilalM., GuthrieJ.A., LodgeJ.P.A.Portal vein arterialization as a salvage procedure during left hepatic trisectionectomy for hilar cholangiocarcinoma. J Am Coll Surg.2008; 207(5): e1–e6.
27.
QiuJ., WuH., PrasoonP., ZengY.Portal vein arterialization in hilar cholangiocarcinoma: one case report and literature review. Eur J Gastroenterol Hepatol.2012; 24(3): 229–232.
28.
CavallariA., NardoB., CaraceniP.Arterialization of the portal vein in a patient with a dearterialized liver graft and massive necrosis. N Engl J Med.2001; 345(18): 1352–1353.
29.
ShimizuK., TaniT., TakamuraH.Partial portal arterialization in living-donor liver transplantation for hepatic artery occlusion. Transplantation.2004; 77(6): 954–955.
30.
MaggiU., CamagniS., ReggianiP.Portal vein arterialization for hepatic artery thrombosis in liver transplantation: a case report, Doppler-ultrasound aspects, and review of the literature. Transplant Proc.2010; 42(4): 1369–1374.
31.
MelandroF., LaiQ., Levi SandriG.B.A case of portal vein arterialization after a liver transplant. Exp Clin Transplant.2013; 11(3): 287–289.
32.
NardoB., MontaltiR., PuvianiL.Portal vein arterialization in a patient with acute liver failure. Transplantation.2005; 79(7): 851–852.
33.
NardoB., CaraceniP., MontaltiR.Portal vein arterialization: a new surgical option against acute liver failure?Transplant Proc.2005; 37(6): 2544–2546.
34.
TsivianM., NeriF., PrezziD.Portal vein arterialization in hepatobiliary surgery and liver transplantation. Transplant Proc.2007; 39(6): 1877–1878.
NardoB., MontaltiR., PuvianiL.An experimental pilot study on controlled portal vein arterialization with an extracorporeal device in the swine model of partial liver resection and ischemia. Int J Artif Organs.2006; 29(9): 912–918.
37.
NardoB., VaccarisiS., PellegrinoV., CannistràM., BarcellonaE., CavallariG.Extracorporeal portal vein arterialization in man after extended hepatectomy to prevent acute liver failure: a case report. Transplant Proc.2011; 43(4): 1193–1195.
38.
NardoB., CaraceniP., PuvianiL.Successful treatment of CCl4-induced acute liver failure with portal vein arterialization in the rat. J Surg Res.2006; 135(2): 394–401.
39.
PiecuchJ., OrkiszW., GabrielA.Liver regeneration following portal blood arterialization and splenectomy in acute hepatic failure. Hepatogastroenterology.2007; 54(77): 1546–1550.
40.
NardoB., TsivianM., NeriF.Extracorporeal portal vein oxygenation improves outcome of acute liver failure in swine. Transplant Proc.2008; 40(6): 2046–2048.
41.
NardoB., PuvianiL., CaraceniP.Portal vein arterialization for the treatment of post resection acute liver failure in the rat. Transplant Proc.2006; 38(4): 1185–1186.
42.
YoshiokaS., MiyazakiM., ShimizuH.Hepatic venous hemoglobin oxygen saturation predicts regenerative status of remnant liver after partial hepatectomy in rats. Hepatology.1998; 27(5): 1349–1353.
43.
NewsomeP.N., PlevrisJ.N., NelsonL.J., HayesP.C.Animal models of fulminant hepatic failure: a critical evaluation. Liver Transpl.2000; 6(1): 21–31.
44.
BrownG.C.Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J.1992; 284(Pt 1): 1–13.
45.
YoshiokaS., MiyazakiM., ShimizuH.Hepatic venous hemoglobin oxygen saturation predicts regenerative status of remnant liver after partial hepatectomy in rats. Hepatology.1998; 27(5): 1349–1353.
46.
OzawaK., TakedaH., YamaokaY., NambuH., KamiyamaY.Adenine nucleotide metabolism in regenerative, atrophic, and necrotizing processes of the liver. Gastroenterology.1974; 67(6): 1225–1230.
47.
YamaokaY., OhsawaT., TakasanH., OzawaK.Energy requirement in regenerative and atrophic processes of the liver in man and other mammals. Surg Gynecol Obstet.1974; 139(2): 234–240.
48.
KamiyamaY., OzawaK., HonjoI.Changes in mitochondrial phosphorylative activity and adenylate energy charge of regenerating rabbit liver. J Biochem.1976; 80(4): 875–881.
49.
RozgaJ., JeppssonB., BengmarkS.Hepatotrophic factors in liver growth and atrophy. Br J Exp Pathol.1985; 66(6): 669–678.
