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Mechanisms of Hepatic Regeneration Following Portal Vein Embolization and Partial Hepatectomy: A Review

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Abstract

Background

Portal vein embolization (PVE) improves outcome following major hepatectomy, and basic studies have presented evidence related to the mechanisms responsible for hepatic regeneration. Hemodynamic changes following PVE are similar to, but slightly different from, those of partial hepatectomy (PH) because arterial flow to the embolized lobe is preserved. However, the process of hepatic regeneration is essentially the same after both PVE and PH. A number of mediators are involved in PVE or PH-induced hepatic regeneration. These include inflammatory cytokines, vasoregulators, growth factors, eicosanoids, and various hormones. These mediators activate a complex network of signal transduction that promotes hepatic regeneration. A variety of conditions have been shown to modulate the function of these mediators and inhibit regeneration. These include biliary obstruction, diabetes, chronic ethanol consumption, malnutrition, gender, aging, and infection.

Conclusion

Optimizing these factors, where possible, before PVE or PH, is essential to maximize hypertrophy of the liver. A fuller understanding of hepatic physiology and pathophysiology following PVE or PH may lead to greater functional capacity of the remaining liver and extend the indications for hepatectomy in patients who require large liver volume resection.

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References

  1. Makuuchi M, Takayasu K, Takuma T, et al. Preoperative transcatheter embolization of the portal venous branch for patients receiving extended lobectomy due to the bile duct carcinoma. J Jpn Soc Clin Surg 1984;45:14–20

    Google Scholar 

  2. Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 1990;107(5):521–527

    PubMed  CAS  Google Scholar 

  3. Kinoshita H, Sakai K, Hirohashi K, et al. Preoperative portal vein embolization for hepatocellular carcinoma. World J Surg 1986;10(5):803–808

    Article  PubMed  CAS  Google Scholar 

  4. Kawasaki S, Makuuchi M, Kakazu T, et al. Resection for multiple metastatic liver tumors after portal embolization. Surgery 1994;115(6):674–677

    PubMed  CAS  Google Scholar 

  5. Lautt WW. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol 1985;249(5 Pt 1):G549–G556

    PubMed  CAS  Google Scholar 

  6. Koga M, Ogasawara H. Induction of hepatocyte mitosis in intact adult rat by interleukin-1 alpha and interleukin-6. Life Sci 1991;49(17):1263–1270

    Article  PubMed  CAS  Google Scholar 

  7. Feingold KR, Soued M, Grunfeld C. Tumor necrosis factor stimulates DNA synthesis in the liver of intact rats. Biochem Biophys Res Commun 1988;153(2):576–582

    Article  PubMed  CAS  Google Scholar 

  8. Nakamura T, Teramoto H, Ichihara A. Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci USA 1986;83(17):6489–6493

    Article  PubMed  CAS  Google Scholar 

  9. Skouteris GG, McMenamin M. Transforming growth factor-alpha-induced DNA synthesis and c-myc expression in primary rat hepatocyte cultures is modulated by indomethacin. Biochem J 1992;281(Pt 3):729–733

    PubMed  CAS  Google Scholar 

  10. Draghi E, Armato U, Andreis PG, et al. The stimulation by epidermal growth factor (urogastrone) of the growth of neonatal rat hepatocytes in primary tissue culture and its modulation by serum and associated pancreatic hormones. J Cell Physiol 1980;103(1):129–147

    Article  PubMed  CAS  Google Scholar 

  11. Tewari M, Dobrzanski P, Mohn KL, et al. Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex. Mol Cell Biol 1992;12(6):2898–2908

    PubMed  CAS  Google Scholar 

  12. FitzGerald MJ, Webber EM, Donovan JR, et al. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration. Cell Growth Differ 1995;6(4):417–427

    PubMed  CAS  Google Scholar 

  13. Cressman DE, Diamond RH, Taub R. Rapid activation of the Stat3 transcription complex in liver regeneration. Hepatology 1995;21(5):1443–1449

    Article  PubMed  CAS  Google Scholar 

  14. Diehl AM, Yang SQ. Regenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to the C/EBP site in the c-fos promoter. Hepatology 1994;19(2):447–456

    Article  PubMed  CAS  Google Scholar 

  15. Rana B, Xie Y, Mischoulon D, et al. The DNA binding activity of C/EBP transcription factor is regulated in the G1 phase of the hepatocyte cell cycle. J Biol Chem 1995;270(30):18123–18132

    Article  PubMed  CAS  Google Scholar 

  16. Thompson NL, Mead JE, Braun L, et al. Sequential protooncogene expression during rat liver regeneration. Cancer Res 1986;46(6):3111–3117

    PubMed  CAS  Google Scholar 

  17. Alcorn JA, Feitelberg SP, Brenner DA. Transient induction of c-jun during hepatic regeneration. Hepatology 1990;11(6):909–915

    PubMed  Google Scholar 

  18. Morello D, Fitzgerald MJ, Babinet C, et al. c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H-2K/c-myc transgenic mice. Mol Cell Biol 1990;10(6):3185–3193

    PubMed  CAS  Google Scholar 

  19. Hortelano S, Dewez B, Genaro AM, Diaz-Guerra MJ, Bosca L. Nitric oxide is released in regenerating liver after partial hepatectomy. Hepatology 1995;21(3):776–786

    Article  PubMed  CAS  Google Scholar 

  20. Tsujii H, Okamoto Y, Kikuchi E, et al. Prostaglandin E2 and rat liver regeneration. Gastroenterology 1993;105(2):495–499

    PubMed  CAS  Google Scholar 

  21. Leffert HL, Moran T, Boorstein R, et al. Procarcinogen activation and hormonal control of cell proliferation in differentiated primary adult rat liver cell cultures. Nature 1977;267(5607):58–61

    Article  PubMed  CAS  Google Scholar 

  22. Francavilla A, Polimeno L, DiLeo A, et al. The effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro. Hepatology 1989;9(4):614–620

    PubMed  CAS  Google Scholar 

  23. Bucher ML, Swaffield MN. Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Proc Natl Acad Sci USA 1975;72(3):1157–1160

    Article  PubMed  CAS  Google Scholar 

  24. Braun L, Mead JE, Panzica M, et al. Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation. Proc Natl Acad Sci USA 1988;85(5):1539–1543

    Article  PubMed  CAS  Google Scholar 

  25. Romero-Gallo J, Sozmen EG, Chytil A, et al. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Oncogene 2005;24(18):3028–3041

    Article  PubMed  CAS  Google Scholar 

  26. Ibdah JA, Yang Z, Bennett MJ. Liver disease in pregnancy and fetal fatty acid oxidation defects. Mol Genet Metab 2000;71(1–2):182–189

    Article  PubMed  CAS  Google Scholar 

  27. Kardon RH, Kessel RG. Three-dimensional organization of the hepatic microcirculation in the rodent as observed by scanning electron microscopy of corrosion casts. Gastroenterology 1980;79(1):72–81

    PubMed  CAS  Google Scholar 

  28. Ohtani O, Kikuta A, Ohtsuka A, et al. Microvasculature as studied by the microvascular corrosion casting/scanning electron microscope method. I. Endocrine and digestive system. Arch Histol Jpn 1983;46(1):1–42

    PubMed  CAS  Google Scholar 

  29. Haratake J, Hisaoka M, Furuta A, et al. A scanning electron microscopic study of postnatal development of rat peribiliary plexus. Hepatology 1991;14(6):1196–1200

    Article  PubMed  CAS  Google Scholar 

  30. Yamamoto K, Phillips MJ. A hitherto unrecognized bile ductular plexus in normal rat liver. Hepatology 1984;4(3):381–385

    PubMed  CAS  Google Scholar 

  31. Sherman IA, Dlugosz JA, Barker F, et al. Dynamics of arterial and portal venous flow interactions in perfused rat liver: an intravital microscopic study. Am J Physiol 1996;271(1 Pt 1):G201–G210

    PubMed  CAS  Google Scholar 

  32. Lautt WW, Legare DJ, d’Almeida MS. Adenosine as putative regulator of hepatic arterial flow (the buffer response). Am J Physiol 1985;248(3 Pt 2):H331–H338

    PubMed  CAS  Google Scholar 

  33. Ezzat WR, Lautt WW. Hepatic arterial pressure-flow autoregulation is adenosine mediated. Am J Physiol 1987;252(4 Pt 2):H836–H845

    PubMed  Google Scholar 

  34. Nagino M, Nimura Y, Kamiya J, et al. Immediate increase in arterial blood flow in embolized hepatic segments after portal vein embolization: CT demonstration. AJR Am J Roentgenol 1998;171(4):1037–1039

    PubMed  CAS  Google Scholar 

  35. Kito Y, Nagino M, Nimura Y. Doppler sonography of hepatic arterial blood flow velocity after percutaneous transhepatic portal vein embolization. AJR Am J Roentgenol 2001;176(4):909–912

    PubMed  CAS  Google Scholar 

  36. Rocheleau B, Ethier C, Houle R, Huet PM, Bilodeau M. Hepatic artery buffer response following left portal vein ligation: its role in liver tissue homeostasis. Am J Physiol 1999;277(5 Pt 1):G1000–G1007

    PubMed  CAS  Google Scholar 

  37. Nagino M, Kanai M, Morioka A, et al. Portal and arterial embolization before extensive liver resection in patients with markedly poor functional reserve. J Vasc Interv Radiol 2000;11(8):1063–1068

    PubMed  CAS  Google Scholar 

  38. Aoki T, Imamura H, Hasegawa K, et al. Sequential preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma. Arch Surg 2004;139(7):766–774

    Article  PubMed  Google Scholar 

  39. Nagino M, Tanaka M, Nishikimi M, et al. Stimulated rat liver mitochondrial biogenesis after partial hepatectomy. Cancer Res 1989;49(17):4913–4918

    PubMed  CAS  Google Scholar 

  40. Katoh T, Tanaka M, Nimura Y, et al. Enhancement of rat liver mitochondrial function by portal branch ligation secures subsequent extended hepatectomy. Biochem Int 1991;24(1):107–116

    PubMed  Google Scholar 

  41. Takeuchi E, Nimura Y, Mizuno S, et al. Ligation of portal vein branch induces DNA polymerases alpha, delta, and epsilon in nonligated lobes. J Surg Res 1996;65(1):15–24

    Article  PubMed  CAS  Google Scholar 

  42. Mueller L, Broering DC, Meyer J, et al. The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow. J Hepatol 2002;37(5):606–612

    Article  PubMed  CAS  Google Scholar 

  43. Takamura K, Tsuchida K, Miyake H, et al. Activin and activin receptor expression changes in liver regeneration in rat. J Surg Res 2005;126(1):3–11

    Article  PubMed  CAS  Google Scholar 

  44. Mueller L, Grotelueschen R, Meyer J, et al. Sustained function in atrophying liver tissue after portal branch ligation in the rat. J Surg Res 2003;114(2):146–155

    Article  PubMed  CAS  Google Scholar 

  45. Uemura T, Miyazaki M, Hirai R, et al. Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats. Int J Mol Med 2000;5(2):173–179

    PubMed  CAS  Google Scholar 

  46. Mizuno S, Nimura Y, Suzuki H, et al. Portal vein branch occlusion induces cell proliferation of cholestatic rat liver. J Surg Res 1996;60(1):249–257

    Article  PubMed  CAS  Google Scholar 

  47. Suzuki H, Iyomasa S, Nimura Y, et al. Internal biliary drainage, unlike external drainage, does not suppress the regeneration of cholestatic rat liver after partial hepatectomy. Hepatology 1994;20(5):1318–1322

    Article  PubMed  CAS  Google Scholar 

  48. Imamura H, Shimada R, Kubota M, et al. Preoperative portal vein embolization: an audit of 84 patients. Hepatology 1999;29(4):1099–1105

    Article  PubMed  CAS  Google Scholar 

  49. Tracy TF Jr, Bailey PV, Goerke ME, et al. Cholestasis without cirrhosis alters regulatory liver gene expression and inhibits hepatic regeneration. Surgery 1991;110(2):176–182; discussion 182–183

    PubMed  Google Scholar 

  50. Kanda H, Nimura Y, Yasui A, et al. Hepatic blood flow after acute biliary obstruction and drainage in conscious dogs. Hepatogastroenterology 1996;43(7):235–240

    PubMed  CAS  Google Scholar 

  51. Baer HU, Guastella T, Wheatley AM, et al. Acute effects of partial hepatectomy on liver blood flow in the jaundiced rat. J Hepatol 1993;19(3):377–382

    Article  PubMed  CAS  Google Scholar 

  52. Goto Y, Nagino M, Nimura Y. Doppler estimation of portal blood flow after percutaneous transhepatic portal vein embolization. Ann Surg 1998;228(2):209–213

    Article  PubMed  CAS  Google Scholar 

  53. Kusaka K, Imamura H, Tomiya T, et al. Factors affecting liver regeneration after right portal vein embolization. Hepatogastroenterology 2004;51(56):532–535

    PubMed  Google Scholar 

  54. Nakano K, Chijiiwa K, Tanaka M. Lower activity of CCAAT/enhancer-binding protein and expression of cyclin E, but not cyclin D1, activating protein-1 and p21(WAF1), after partial hepatectomy in obstructive jaundice. Biochem Biophys Res Commun 2001;280(3):640–645

    Article  PubMed  CAS  Google Scholar 

  55. Hu RH, Lee PH, Yu SC, et al. Profile of hepatocyte growth factor in patients with obstructive jaundice. Hepatogastroenterology 2003;50(54):1987–1990

    PubMed  CAS  Google Scholar 

  56. Bissig KD, Marti U, Solioz M, et al. Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy. J Hepatol 2000;33(2):275–281

    Article  PubMed  CAS  Google Scholar 

  57. Fujiwara Y, Shimada M, Yamashita Y, et al. Cytokine characteristics of jaundice in mouse liver. Cytokine 2001;13(3):188–191

    Article  PubMed  CAS  Google Scholar 

  58. Abe T, Arai T, Ogawa A, et al. Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice. Hepatology 2004;40(2):414–423

    Article  PubMed  CAS  Google Scholar 

  59. Iyomasa S, Terasaki M ,Kuriki H, et al. Decrease in regeneration capacity of rat liver after external biliary drainage. Eur Surg Res 1992;24(5):265–272

    PubMed  CAS  Google Scholar 

  60. Saiki S, Chijiiwa K, Komura M, et al. Preoperative internal biliary drainage is superior to external biliary drainage in liver regeneration and function after hepatectomy in obstructive jaundiced rats. Ann Surg 1999;230(5):655–662

    Article  PubMed  CAS  Google Scholar 

  61. Starzl TE, Porter KA, Kashiwagi N. Portal hepatotrophic factors, diabetes mellitus and acute liver atrophy, hypertrophy and regeneration. Surg Gynecol Obstet 1975;141(6):843–858

    PubMed  CAS  Google Scholar 

  62. Demori I, Balocco S, Voci A, et al. Increased insulin-like growth factor binding protein-4 expression after partial hepatectomy in the rat. Am J Physiol Gastrointest Liver Physiol 2000;278(3):G384–G389

    PubMed  CAS  Google Scholar 

  63. Ghahary A, Minuk GY, Luo J, et al. Effects of partial hepatectomy on hepatic insulinlike growth factor binding protein-1 expression. Hepatology 1992;15(6):1125–1131

    PubMed  CAS  Google Scholar 

  64. Barra R, Hall JC. Liver regeneration in normal and alloxan-induced diabetic rats. J Exp Zool 1977;201(1):93–99

    Article  PubMed  CAS  Google Scholar 

  65. Yamada T, Yamamoto M, Ozawa K, et al. Insulin requirements for hepatic regeneration following hepatectomy. Ann Surg 1977;185(1):35–42

    Article  PubMed  CAS  Google Scholar 

  66. Matsumoto T, Yamaguchi M, Kuzume M, et al. Insulin gene transfer with adenovirus vector via the spleen safely and effectively improves posthepatectomized conditions in diabetic rats. J Surg Res 2003;110(1):228–234

    Article  PubMed  CAS  Google Scholar 

  67. Kawarada Y, Sanda M, Kawamura K, et al. Simultaneous extensive resection of the liver and the pancreas in dogs. Gastroenterol Jpn 1991;26(6):747–756

    PubMed  CAS  Google Scholar 

  68. Liatsos GD, Mykoniatis MG, Margeli A, et al. Effect of acute ethanol exposure on hepatic stimulator substance (HSS) levels during liver regeneration: protective function of HSS. Dig Dis Sci 2003;48(10):1929–1938

    Article  PubMed  CAS  Google Scholar 

  69. Koteish A, Yang S, Lin H, et al. Ethanol induces redox-sensitive cell-cycle inhibitors and inhibits liver regeneration after partial hepatectomy. Alcohol Clin Exp Res 2002;26(11):1710–1718

    PubMed  CAS  Google Scholar 

  70. Chen J, Kunos G, Gao B. Ethanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocytes. FEBS Lett 1999;457(1):162–168

    Article  PubMed  CAS  Google Scholar 

  71. Chen J, Ishac EJ, Dent P, et al. Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver. Biochem J 1998;334 ( Pt 3):669–676

    PubMed  CAS  Google Scholar 

  72. Gong Y, Cui L, Minuk GY. Effects of acute and chronic ethanol exposure on the hepatic gamma-aminobutyric acid transport system in rats. Alcohol 1999;19(3):213–218

    Article  PubMed  CAS  Google Scholar 

  73. Skullman S, Ihse I, Larsson J. Influence of malnutrition on regeneration and composition of the liver in rats. Acta Chir Scand 1990;156(10):717–722

    PubMed  CAS  Google Scholar 

  74. Ito A, Higashiguchi T. Effects of glutamine administration on liver regeneration following hepatectomy. Nutrition 1999;15(1):23–28

    Article  PubMed  CAS  Google Scholar 

  75. Yoshida S, Yunoki T, Aoyagi K, et al. Effect of glutamine supplement and hepatectomy on DNA and protein synthesis in the remnant liver. J Surg Res 1995;59(4):475–481

    Article  PubMed  CAS  Google Scholar 

  76. Nakagawa M, Hiramatsu Y, Furubayashi H, et al. Comparison of effects of long-chain and medium-chain triglyceride emulsions during hepatic regeneration in rats. Nutrition 1991;7(1):23–27

    PubMed  CAS  Google Scholar 

  77. Delany HM, John J, The EL, et al. Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy. Am J Surg 1994;167(1):135–143; discussion 143–144

    Article  PubMed  CAS  Google Scholar 

  78. Zhang K, Sun WB, Wang HF, et al. Early enteral and parenteral nutritional support in patients with cirrhotic portal hypertension after pericardial devascularization. Hepatobiliary Pancreat Dis Int 2005;4(1):55–59

    PubMed  Google Scholar 

  79. Hussein O, Szvalb S, Van den Akker-Berman LM, et al. Liver regeneration is not altered in patients with nonalcoholic steatohepatitis (NASH) when compared to chronic hepatitis C infection with similar grade of inflammation. Dig Dis Sci 2002;47(9):1926–1931

    Article  PubMed  Google Scholar 

  80. Zhang BH, Weltman M, Farrell GC. Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats. J Gastroenterol Hepatol 1999;14(2):133–137

    Article  PubMed  CAS  Google Scholar 

  81. Francavilla A, Gavaler JS, Makowka L, et al. Estradiol and testosterone levels in patients undergoing partial hepatectomy. A possible signal for hepatic regeneration? Dig Dis Sci 1989;34(6):818–822

    Article  PubMed  CAS  Google Scholar 

  82. Eagon PK, Porter LE, Francavilla A, et al. Estrogen and androgen receptors in liver: their role in liver disease and regeneration. Semin Liver Dis 1985;5(1):59–69

    Article  PubMed  CAS  Google Scholar 

  83. Shan YS, Hsieh YH, Sy ED, et al. The influence of spleen size on liver regeneration after major hepatectomy in normal and early cirrhotic liver. Liver Int 2005;25(1):96–100

    Article  PubMed  Google Scholar 

  84. Iakova P, Awad SS, Timchenko NA. Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell 2003;113(4):495–506

    Article  PubMed  CAS  Google Scholar 

  85. Marshall A, Rushbrook S, Davies SE, et al. Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology 2005;128(1):33–42

    Article  PubMed  Google Scholar 

  86. Tralhao JG, Roudier J, Morosan S, et al. Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: an alternative mechanism of HBx-related pathogenesis. Proc Natl Acad Sci USA 2002;99(10):6991–6996

    Article  PubMed  CAS  Google Scholar 

  87. Sun R, Gao B. Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-gamma). Gastroenterology 2004;127(5):1525–1539

    Article  PubMed  CAS  Google Scholar 

  88. Masson S, Daveau M, Francois A, et al. Up-regulated expression of HGF in rat liver cells after experimental endotoxemia: a potential pathway for enhancement of liver regeneration. Growth Factors 2001;18(4):237–250

    Article  PubMed  CAS  Google Scholar 

  89. Nagino M, Kamiya J, Nishio H, et al. Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up. Ann Surg 2006;243(3):364–372

    Article  PubMed  Google Scholar 

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  1. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Y. Yokoyama, M. Nagino & Y. Nimura

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  1. Y. Yokoyama
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  2. M. Nagino
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Yokoyama, Y., Nagino, M. & Nimura, Y. Mechanisms of Hepatic Regeneration Following Portal Vein Embolization and Partial Hepatectomy: A Review. World J. Surg. 31, 367–374 (2007). https://doi.org/10.1007/s00268-006-0526-2

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