Skip to main content

Advertisement

Log in

Mechanism of impaired hepatic regeneration in cholestatic liver

  • Review article
  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

The regenerative capacity of the liver is an important factor following liver surgery. The dramatic change in portal venous flow, due to either portal vein embolization or partial hepatectomy, induces a rapid change in liver volume. In response to these stresses, hepatocytes are primed, through the release of inflammatory cytokines, to increase the expression of immediate early genes and increase the activation of transcriptional factors. The primed hepatocytes then respond to growth factors, including hepatocyte growth factor, epidermal growth factor, and transforming growth factor-α. Several pathologic conditions have been shown to inhibit hepatic regeneration. These include diabetes mellitus, malnutrition, aging, infection, chronic ethanol consumption, and biliary obstruction. Impaired hepatic regeneration in the setting of biliary obstruction is an especially serious problem because it can be a major determinant in not considering surgical treatment. The mechanism responsible for impaired hepatic regeneration in patients with biliary obstruction includes decreased portal venous flow, attenuated production of liver proliferation-associated factors, an increased rate of apoptosis, and lack of enterohepatic circulation. Restoring these factors may lead to an improvement in regeneration in a cholestatic liver following portal vein embolization or partial hepatectomy. This review article summarizes the current understanding of the mechanism of hepatic regeneration, with particular emphasis on that in the cholestatic liver.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. T Takayama M Makuuchi (2004) ArticleTitlePreoperative portal vein embolization: is it useful? J Hepatobiliary Pancreat Surg 11 17–20 Occurrence Handle15747030 Occurrence Handle10.1007/s00534-002-0800-0

    Article  PubMed  Google Scholar 

  2. M Makuuchi BL Thai K Takayasu T Takayama T Kosuge P Gunven et al. (1990) ArticleTitlePreoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report Surgery 107 521–7 Occurrence Handle2333592 Occurrence Handle1:STN:280:DyaK3c3jvFOjsQ%3D%3D

    PubMed  CAS  Google Scholar 

  3. H Kinoshita K Sakai K Hirohashi S Igawa O Yamasaki S Kubo (1986) ArticleTitlePreoperative portal vein embolization for hepatocellular carcinoma World J Surg 10 803–8 Occurrence Handle3022488 Occurrence Handle10.1007/BF01655244 Occurrence Handle1:STN:280:DyaL2s%2FksVejtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. N Kokudo H Imamura Y Sugawara Y Sakamoto J Yamamoto M Seki et al. (2004) ArticleTitleSurgery for multiple hepatic colorectal metastases J Hepatobiliary Pancreat Surg 11 84–91 Occurrence Handle15127269 Occurrence Handle10.1007/s00534-002-0754-2

    Article  PubMed  Google Scholar 

  5. S Kawasaki M Makuuchi T Kakazu S Miyagawa T Takayama T Kosuge et al. (1994) ArticleTitleResection for multiple metastatic liver tumors after portal embolization Surgery 115 674–7 Occurrence Handle8197557 Occurrence Handle1:STN:280:DyaK2c3lsFyktg%3D%3D

    PubMed  CAS  Google Scholar 

  6. WW Lautt (1985) ArticleTitleMechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response Am J Physiol 249 G549–56 Occurrence Handle3904482 Occurrence Handle1:STN:280:DyaL28%2FkvVWkuw%3D%3D

    PubMed  CAS  Google Scholar 

  7. M Nagino Y Nimura J Kamiya M Kanai N Hayakawa H Yamamoto (1998) ArticleTitleImmediate increase in arterial blood flow in embolized hepatic segments after portal vein embolization: CT demonstration AJR Am J Roentgenol 171 1037–9 Occurrence Handle9762992 Occurrence Handle1:STN:280:DyaK1cvjtl2mtA%3D%3D

    PubMed  CAS  Google Scholar 

  8. Y Kito M Nagino Y Nimura (2001) ArticleTitleDoppler sonography of hepatic arterial blood flow velocity after percutaneous transhepatic portal vein embolization AJR Am J Roentgenol 176 909–12 Occurrence Handle11264076 Occurrence Handle1:STN:280:DC%2BD3M7msF2ltw%3D%3D

    PubMed  CAS  Google Scholar 

  9. E Takeuchi Y Nimura S Mizuno M Nagino M Shoji-Kawaguchi S Izuta et al. (1996) ArticleTitleLigation of portal vein branch induces DNA polymerases alpha, delta, and epsilon in nonligated lobes J Surg Res 65 15–24 Occurrence Handle8895601 Occurrence Handle10.1006/jsre.1996.0337 Occurrence Handle1:CAS:528:DyaK28XmvFOit70%3D

    Article  PubMed  CAS  Google Scholar 

  10. M Nagino Y Nimura J Kamiya S Kondo K Uesaka Y Kin et al. (1995) ArticleTitleChanges in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization Hepatology 21 434–9 Occurrence Handle7843717 Occurrence Handle1:STN:280:DyaK2M7ks1Snug%3D%3D

    PubMed  CAS  Google Scholar 

  11. M Nagino M Ando J Kamiya K Uesaka T Sano Y Nimura (2001) ArticleTitleLiver regeneration after major hepatectomy for biliary cancer Br J Surg 88 1084–91 Occurrence Handle11488794 Occurrence Handle10.1046/j.0007-1323.2001.01832.x Occurrence Handle1:STN:280:DC%2BD3MvktlWhuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  12. JK Westwick C Weitzel HL Leffert DA Brenner (1995) ArticleTitleActivation of Jun kinase is an early event in hepatic regeneration J Clin Invest 95 803–10 Occurrence Handle7860764 Occurrence Handle1:CAS:528:DyaK2MXjsV2rsLs%3D

    PubMed  CAS  Google Scholar 

  13. JK Westwick C Weitzel A Minden M Karin DA Brenner (1994) ArticleTitleTumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase J Biol Chem 269 26 396–401 Occurrence Handle1:CAS:528:DyaK2cXmt1ygu7g%3D

    CAS  Google Scholar 

  14. H Talarmin C Rescan S Cariou D Glaise G Zanninelli M Bilodeau et al. (1999) ArticleTitleThe mitogen-activated protein kinase kinase/extracellular signal-regulated kinase cascade activation is a key signalling pathway involved in the regulation of G(1) phase progression in proliferating hepatocytes Mol Cell Biol 19 6003–11 Occurrence Handle10454547 Occurrence Handle1:CAS:528:DyaK1MXlslSqu7k%3D

    PubMed  CAS  Google Scholar 

  15. NL Thompson JE Mead L Braun M Goyette PR Shank N Fausto (1986) ArticleTitleSequential protooncogene expression during rat liver regeneration Cancer Res 46 3111–7 Occurrence Handle3516391 Occurrence Handle1:CAS:528:DyaL28Xkt1aisLY%3D

    PubMed  CAS  Google Scholar 

  16. JA Alcorn SP Feitelberg DA Brenner (1990) ArticleTitleTransient induction of c-jun during hepatic regeneration Hepatology 11 909–15 Occurrence Handle2114348 Occurrence Handle10.1002/hep.1840110602 Occurrence Handle1:CAS:528:DyaK3cXlt12rt7w%3D

    Article  PubMed  CAS  Google Scholar 

  17. D Morello MJ Fitzgerald C BabInet N Fausto (1990) ArticleTitlec-myc, c-fos, and c-jun regulation In the regenerating livers of normal and H-2K/c-myc transgenic mice Mol Cell Biol 10 3185–93 Occurrence Handle2111449 Occurrence Handle1:CAS:528:DyaK3cXkt1WltL4%3D

    PubMed  CAS  Google Scholar 

  18. M Tewari P Dobrzanski KL Mohn DE Cressman JC Hsu R Bravo et al. (1992) ArticleTitleRapid 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 12 2898–908 Occurrence Handle1588976 Occurrence Handle1:CAS:528:DyaK3sXit1Krtb0%3D

    PubMed  CAS  Google Scholar 

  19. MJ FitzGerald EM Webber JR Donovan N Fausto (1995) ArticleTitleRapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration Cell Growth Differ 6 417–27 Occurrence Handle7794809 Occurrence Handle1:CAS:528:DyaK2MXkvFWksrs%3D

    PubMed  CAS  Google Scholar 

  20. DE Cressman RH Diamond R Taub (1995) ArticleTitleRapid activation of the Stat3 transcription complex in liver regeneration Hepatology 21 1443–9 Occurrence Handle7737651 Occurrence Handle1:CAS:528:DyaK2MXlvFCkt70%3D

    PubMed  CAS  Google Scholar 

  21. AM Diehl SQ Yang (1994) ArticleTitleRegenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to the C/EBP site in the c-fos promoter Hepatology 19 447–56 Occurrence Handle8294101 Occurrence Handle1:CAS:528:DyaK2cXlt1Kksb8%3D

    PubMed  CAS  Google Scholar 

  22. B Rana Y Xie D Mischoulon NL Bucher SR Farmer (1995) ArticleTitleThe DNA binding activity of C/EBP transcription factor is regulated in the G1 phase of the hepatocyte cell cycle J Biol Chem 270 18 123–32 Occurrence Handle1:CAS:528:DyaK2MXnt1Cqsrc%3D

    CAS  Google Scholar 

  23. KR Feingold M Soued C Grunfeld (1988) ArticleTitleTumor necrosis factor stimulates DNA synthesis in the liver of intact rats Biochem Biophys Res Commun 153 576–82 Occurrence Handle3132913 Occurrence Handle10.1016/S0006-291X(88)81134-3 Occurrence Handle1:CAS:528:DyaL1cXksFaqsbg%3D

    Article  PubMed  CAS  Google Scholar 

  24. M Koga H Ogasawara (1991) ArticleTitleInduction of hepatocyte mitosis in intact adult rat by interleukin-1 alpha and interleukin-6 Life Sci 49 1263–70 Occurrence Handle1943441 Occurrence Handle10.1016/0024-3205(91)90139-3 Occurrence Handle1:CAS:528:DyaK3MXmtVGksbg%3D

    Article  PubMed  CAS  Google Scholar 

  25. S Hortelano B Dewez AM Genaro MJ Diaz-Guerra L Bosca (1995) ArticleTitleNitric oxide is released in regenerating liver after partial hepatectomy Hepatology 21 776–86 Occurrence Handle7533126 Occurrence Handle1:CAS:528:DyaK2MXltlentL4%3D

    PubMed  CAS  Google Scholar 

  26. T Nakamura H Teramoto A Ichihara (1986) ArticleTitlePurification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures Proc Natl Acad Sci U S A 83 6489–93 Occurrence Handle3529086 Occurrence Handle10.1073/pnas.83.17.6489 Occurrence Handle1:CAS:528:DyaL28XlsVOjtL0%3D

    Article  PubMed  CAS  Google Scholar 

  27. E Draghi U Armato PG Andreis L Mengato (1980) ArticleTitleThe 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 103 129–47 Occurrence Handle7000798 Occurrence Handle10.1002/jcp.1041030118 Occurrence Handle1:CAS:528:DyaL3cXkvV2itb8%3D

    Article  PubMed  CAS  Google Scholar 

  28. GG Skouteris M McMenamin (1992) ArticleTitleTransforming growth factor-alpha-induced DNA synthesis and c-myc expression in primary rat hepatocyte cultures is modulated by indomethacin Biochem J 281 729–33 Occurrence Handle1531590 Occurrence Handle1:CAS:528:DyaK38XhtVSis7o%3D

    PubMed  CAS  Google Scholar 

  29. HL Leffert T Moran R Boorstein KS Koch (1977) ArticleTitleProcarcinogen activation and hormonal control of cell proliferation in differentiated primary adult rat liver cell cultures Nature 267 58–61 Occurrence Handle558527 Occurrence Handle10.1038/267058a0 Occurrence Handle1:CAS:528:DyaE2sXltFGhtrY%3D

    Article  PubMed  CAS  Google Scholar 

  30. A Francavilla L Polimeno A DiLeo M Barone P Ove M Coetzee et al. (1989) ArticleTitleThe effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro Hepatology 9 614–20 Occurrence Handle2784403 Occurrence Handle10.1002/hep.1840090417 Occurrence Handle1:CAS:528:DyaL1MXhs1Kgt74%3D

    Article  PubMed  CAS  Google Scholar 

  31. ML Bucher MN Swaffield (1975) ArticleTitleRegulation of hepatic regeneration in rats by synergistic action of insulin and glucagon Proc Natl Acad Sci U S A 72 1157–60 Occurrence Handle1055372 Occurrence Handle10.1073/pnas.72.3.1157 Occurrence Handle1:CAS:528:DyaE2MXktVWht7s%3D

    Article  PubMed  CAS  Google Scholar 

  32. L Braun JE Mead M Panzica R Mikumo GI Bell N Fausto (1988) ArticleTitleTransforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation Proc Natl Acad Sci U S A 85 1539–43 Occurrence Handle3422749 Occurrence Handle10.1073/pnas.85.5.1539 Occurrence Handle1:CAS:528:DyaL1cXhs1aitr8%3D

    Article  PubMed  CAS  Google Scholar 

  33. J Romero-Gallo EG Sozmen A Chytil WE Russell R Whitehead WT Parks et al. (2005) ArticleTitleInactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy Oncogene 24 3028–41 Occurrence Handle15735717 Occurrence Handle10.1038/sj.onc.1208475 Occurrence Handle1:CAS:528:DC%2BD2MXjsVeqtrg%3D

    Article  PubMed  CAS  Google Scholar 

  34. JA Ibdah Z Yang MJ Bennett (2000) ArticleTitleLiver disease in pregnancy and fetal fatty acid oxidation defects Mol Genet Metab 71 182–9 Occurrence Handle11001809 Occurrence Handle10.1006/mgme.2000.3065 Occurrence Handle1:CAS:528:DC%2BD3cXms1yju7o%3D

    Article  PubMed  CAS  Google Scholar 

  35. EM Webber J Bruix RH Pierce N Fausto (1998) ArticleTitleTumor necrosis factor primes hepatocytes for DNA replication in the rat Hepatology 28 1226–34 Occurrence Handle9794905 Occurrence Handle10.1002/hep.510280509 Occurrence Handle1:CAS:528:DyaK1cXntlSjs70%3D

    Article  PubMed  CAS  Google Scholar 

  36. T Matsumoto M Yamaguchi M Kuzume A Matsumiya K Kumada (2003) ArticleTitleInsulin gene transfer with adenovirus vector via the spleen safely and effectively improves posthepatectomized conditions in diabetic rats J Surg Res 110 228–34 Occurrence Handle12697406 Occurrence Handle10.1016/S0022-4804(03)00023-4 Occurrence Handle1:CAS:528:DC%2BD3sXivV2mtrg%3D

    Article  PubMed  CAS  Google Scholar 

  37. H Imamura R Shimada M Kubota Y Matsuyama A Nakayama S Miyagawa et al. (1999) ArticleTitlePreoperative portal vein embolization: an audit of 84 patients Hepatology 29 1099–105 Occurrence Handle10094953 Occurrence Handle10.1002/hep.510290415 Occurrence Handle1:STN:280:DyaK1M7pslSrug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  38. T Yamada M Yamamoto K Ozawa I Honjo (1977) ArticleTitleInsulin requirements for hepatic regeneration following hepatectomy Ann Surg 185 35–42 Occurrence Handle831634 Occurrence Handle10.1097/00000658-197701000-00006 Occurrence Handle1:CAS:528:DyaE2sXmvFKgtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  39. S Skullman I Ihse J Larsson (1990) ArticleTitleInfluence of malnutrition on regeneration and composition of the liver in rats Acta Chir Scand 156 717–22 Occurrence Handle2264430 Occurrence Handle1:STN:280:DyaK3M%2FovFOktA%3D%3D

    PubMed  CAS  Google Scholar 

  40. A Ito T Higashiguchi (1999) ArticleTitleEffects of glutamine administration on liver regeneration following hepatectomy Nutrition 15 23–8 Occurrence Handle9918058 Occurrence Handle10.1016/S0899-9007(98)00133-6 Occurrence Handle1:CAS:528:DyaK1MXmtVyhsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  41. S Yoshida T Yunoki K Aoyagi J Ohta N Ishibashi T Noake et al. (1995) ArticleTitleEffect of glutamine supplement and hepatectomy on DNA and protein synthesis in the remnant liver J Surg Res 59 475–81 Occurrence Handle7564320 Occurrence Handle10.1006/jsre.1995.1194 Occurrence Handle1:CAS:528:DyaK2MXpt12hsbw%3D

    Article  PubMed  CAS  Google Scholar 

  42. S Skullman M Wiren PJ Garlick MA McNurlan J Larsson (1994) ArticleTitleProtein synthesis in regenerating rat liver during malnutrition J Hepatol 21 174–81 Occurrence Handle7527436 Occurrence Handle10.1016/S0168-8278(05)80391-5 Occurrence Handle1:CAS:528:DyaK2MXhvVOjuro%3D

    Article  PubMed  CAS  Google Scholar 

  43. P Iakova SS Awad NA Timchenko (2003) ArticleTitleAging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest Cell 113 495–506 Occurrence Handle12757710 Occurrence Handle10.1016/S0092-8674(03)00318-0 Occurrence Handle1:CAS:528:DC%2BD3sXktVGmtbw%3D

    Article  PubMed  CAS  Google Scholar 

  44. A Marshall S Rushbrook SE Davies LS Morris IS Scott SL Vowler et al. (2005) ArticleTitleRelation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection Gastroenterology 128 33–42 Occurrence Handle15633121 Occurrence Handle10.1053/j.gastro.2004.09.076

    Article  PubMed  Google Scholar 

  45. R Sun B Gao (2004) ArticleTitleNegative regulation of liver regeneration by innate immunity (natural killer cells/interferon-gamma) Gastroenterology 127 1525–39 Occurrence Handle15521020 Occurrence Handle10.1053/j.gastro.2004.08.055 Occurrence Handle1:CAS:528:DC%2BD2cXhtVKisr3E

    Article  PubMed  CAS  Google Scholar 

  46. JG Tralhao J Roudier S Morosan C Giannini H Tu C Goulenok et al. (2002) ArticleTitleParacrine 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 U S A 99 6991–6 Occurrence Handle12011457 Occurrence Handle10.1073/pnas.092657699 Occurrence Handle1:CAS:528:DC%2BD38XjvFCqsbs%3D

    Article  PubMed  CAS  Google Scholar 

  47. J Chen G Kunos B Gao (1999) ArticleTitleEthanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocyts FEBS Lett 457 162–8 Occurrence Handle10486586 Occurrence Handle10.1016/S0014-5793(99)01031-5 Occurrence Handle1:CAS:528:DyaK1MXmtFejtbg%3D

    Article  PubMed  CAS  Google Scholar 

  48. J Chen EJ Ishac P Dent G Kunos B Gao (1998) ArticleTitleEffects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver Biochem J 334 669–76 Occurrence Handle9729476 Occurrence Handle1:CAS:528:DyaK1cXmsVKgsr0%3D

    PubMed  CAS  Google Scholar 

  49. Y Gong L Cui GY Minuk (1999) ArticleTitleEffects of acute and chronic ethanol exposure on the hepatic gamma-aminobutyric acid transport system in rats Alcohol 19 213–8 Occurrence Handle10580510 Occurrence Handle10.1016/S0741-8329(99)00049-X Occurrence Handle1:CAS:528:DyaK1MXntlelu74%3D

    Article  PubMed  CAS  Google Scholar 

  50. S Mizuno Y Nimura H Suzuki S Yoshida (1996) ArticleTitlePortal vein branch occlusion induces cell proliferation of cholestatic rat liver J Surg Res 60 249–57 Occurrence Handle8592423 Occurrence Handle10.1006/jsre.1996.0039 Occurrence Handle1:STN:280:DyaK287lsVWnsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  51. T Kaido A Yoshikawa S Seto S Yamaoka M Sato T Ishii et al. (1999) ArticleTitleHepatocyte growth factor supply accelerates compensatory hypertrophy caused by portal branch ligation in normal and jaundiced rats J Surg Res 85 115–9 Occurrence Handle10383847 Occurrence Handle10.1006/jsre.1999.5639 Occurrence Handle1:CAS:528:DyaK1MXktVSltLc%3D

    Article  PubMed  CAS  Google Scholar 

  52. TF Tracy SuffixJr PV Bailey ME Goerke C Sotelo-Avila TR Weber (1991) ArticleTitleCholestasis without cirrhosis alters regulatory liver gene expression and inhibits hepatic regeneration Surgery 110 176–82 Occurrence Handle1858028

    PubMed  Google Scholar 

  53. M Nagino M Tanaka M Nishikimi Y Nimura H Kubota M Kanai et al. (1989) ArticleTitleStimulated rat liver mitochondrial biogenesis after partial hepatectomy Cancer Res 49 4913–8 Occurrence Handle2758420 Occurrence Handle1:CAS:528:DyaL1MXlvFanurs%3D

    PubMed  CAS  Google Scholar 

  54. T Katoh M Tanaka Y Nimura M Kanai M Nagino T Ozawa (1991) ArticleTitleEnhancement of rat liver mitochondrial function by portal branch ligation secures subsequent extended hepatectomy Biochem Int 24 107–16 Occurrence Handle1768249 Occurrence Handle1:CAS:528:DyaK3MXltleiu7g%3D

    PubMed  CAS  Google Scholar 

  55. T Uemura M Miyazaki R Hirai H Matsumoto T Ota R Ohashi et al. (2000) ArticleTitleDifferent 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 5 173–9 Occurrence Handle10639597 Occurrence Handle1:CAS:528:DC%2BD3cXos1Kisg%3D%3D

    PubMed  CAS  Google Scholar 

  56. N Fausto (1999) ArticleTitleLessons from genetically engineered animal models. V. Knocking out genes to study liver regeneration: present and future Am J Physiol 277 G917–21 Occurrence Handle10564095 Occurrence Handle1:CAS:528:DyaK1MXns1Olu78%3D

    PubMed  CAS  Google Scholar 

  57. KL Streetz T Luedde MP Manns C Trautwein (2000) ArticleTitleInterleukin 6 and liver regeneration Gut 47 309–12 Occurrence Handle10896929 Occurrence Handle10.1136/gut.47.2.309 Occurrence Handle1:CAS:528:DC%2BD3cXlvVygu7k%3D

    Article  PubMed  CAS  Google Scholar 

  58. DE Cressman LE Greenbaum RA DeAngelis G Ciliberto EE Furth V Poli et al. (1996) ArticleTitleLiver failure and defective hepatocyte regeneration in interleukin-6-deficient mice Science 274 1379–83 Occurrence Handle8910279 Occurrence Handle10.1126/science.274.5291.1379 Occurrence Handle1:CAS:528:DyaK28XntFKlsrg%3D

    Article  PubMed  CAS  Google Scholar 

  59. Y Yamada I Kirillova JJ Peschon N Fausto (1997) ArticleTitleInitiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor Proc Natl Acad Sci U S A 94 1441–6 Occurrence Handle9037072 Occurrence Handle10.1073/pnas.94.4.1441 Occurrence Handle1:CAS:528:DyaK2sXhtl2is7s%3D

    Article  PubMed  CAS  Google Scholar 

  60. P Akerman P Cote SQ Yang C McClain S Nelson GJ Bagby et al. (1992) ArticleTitleAntibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy Am J Physiol 263 G579–85 Occurrence Handle1415718 Occurrence Handle1:CAS:528:DyaK3sXlsVSq

    PubMed  CAS  Google Scholar 

  61. M Kawai K Naruse S Komatsu S Kobayashi M Nagino Y Nimura et al. (2002) ArticleTitleMechanical stress-dependent secretion of interleukin 6 by endothelial cells after portal vein embolization: clinical and experimental studies J Hepatol 37 240–6 Occurrence Handle12127429 Occurrence Handle10.1016/S0168-8278(02)00171-X Occurrence Handle1:CAS:528:DC%2BD38XlsVKjsrs%3D

    Article  PubMed  CAS  Google Scholar 

  62. M Yamashita M Taniyama M Tamai (2002) ArticleTitleCellular localization of tumor necrosis factor-alpha mRNA and interleukin-6 mRNA in the rat liver after hemorrhagic shock Surg Today 32 701–6 Occurrence Handle12181720 Occurrence Handle10.1007/s005950200130 Occurrence Handle1:CAS:528:DC%2BD38Xns1enu78%3D

    Article  PubMed  CAS  Google Scholar 

  63. A Ayala MM Perrin W Ertel IH Chaudry (1992) ArticleTitleDifferential effects of haemorrhage on Kupffer cells: decreased antigen presentation despite increased inflammatory cytokine (IL-1, IL-6 and TNF) release Cytokine 4 66–75 Occurrence Handle1319764 Occurrence Handle10.1016/1043-4666(92)90039-T Occurrence Handle1:CAS:528:DyaK3sXmsVOluro%3D

    Article  PubMed  CAS  Google Scholar 

  64. X Aldeguer F Debonera A Shaked AM Krasinkas AE Gelman X Que et al. (2002) ArticleTitleInterleukin-6 from intrahepatic cells of bone marrow origin is required for normal murine liver regeneration Hepatology 35 40–8 Occurrence Handle11786958 Occurrence Handle10.1053/jhep.2002.30081 Occurrence Handle1:CAS:528:DC%2BD38XmvFarug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  65. RP Cornell BL Liljequist KF Bartizal (1990) ArticleTitleDepressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice Hepatology 11 916–22 Occurrence Handle2194922 Occurrence Handle10.1002/hep.1840110603 Occurrence Handle1:CAS:528:DyaK3MXkt1ek

    Article  PubMed  CAS  Google Scholar 

  66. E Seki H Tsutsui Y Iimuro T Naka G Son S Akira et al. (2005) ArticleTitleContribution of Toll-like receptor/myeloid differentiation factor 88 signaling to murine liver regeneration Hepatology 41 443–50 Occurrence Handle15723296 Occurrence Handle10.1002/hep.20603 Occurrence Handle1:CAS:528:DC%2BD2MXisFCku7k%3D

    Article  PubMed  CAS  Google Scholar 

  67. S Kobayashi M Nagino S Komatsu K Naruse Y Nimura M Nakanishi et al. (2003) ArticleTitleStretch-induced IL-6 secretion from endothelial cells requires NF-kappaB activation Biochem Biophys Res Commun 308 306–12 Occurrence Handle12901869 Occurrence Handle10.1016/S0006-291X(03)01362-7 Occurrence Handle1:CAS:528:DC%2BD3sXlvFGhurc%3D

    Article  PubMed  CAS  Google Scholar 

  68. A Sasamoto M Nagino S Kobayashi K Naruse Y Nimura M Sokabe (2005) ArticleTitleMechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch Am J Physiol Cell Physiol 288 C1012–22 Occurrence Handle15613495 Occurrence Handle10.1152/ajpcell.00314.2004 Occurrence Handle1:CAS:528:DC%2BD2MXktlSgtb8%3D

    Article  PubMed  CAS  Google Scholar 

  69. HJ Hsieh NQ Li JA Frangos (1993) ArticleTitlePulsatile and steady flow induces c-fos expression in human endothelial cells J Cell Physiol 154 143–51 Occurrence Handle8419400 Occurrence Handle10.1002/jcp.1041540118 Occurrence Handle1:CAS:528:DyaK3sXnsl2jug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  70. A Cucina AV Sterpetti V Borrelli S Pagliei A Cavallaro LS D'Angelo (1998) ArticleTitleShear stress induces transforming growth factor-beta 1 release by arterial endothelial cells Surgery 123 212–7 Occurrence Handle9481408 Occurrence Handle1:STN:280:DyaK1c7kt1CjtQ%3D%3D

    PubMed  CAS  Google Scholar 

  71. T Morita M Yoshizumi H Kurihara K Maemura R Nagai Y Yazaki (1993) ArticleTitleShear stress increases heparin-binding epidermal growth factor-like growth factor mRNA levels in human vascular endothelial cells Biochem Biophys Res Commun 197 256–62 Occurrence Handle8250932 Occurrence Handle10.1006/bbrc.1993.2469 Occurrence Handle1:CAS:528:DyaK2cXisVaqsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  72. K Nishida DG Harrison JP Navas AA Fisher SP Dockery M Uematsu et al. (1992) ArticleTitleMolecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase J Clin Invest 90 2092–6 Occurrence Handle1385480 Occurrence Handle1:CAS:528:DyaK3sXks1Knsb0%3D Occurrence Handle10.1172/JCI116092

    Article  PubMed  CAS  Google Scholar 

  73. T Niiya M Murakami T Aoki N Murai Y Shimizu M Kusano (1999) ArticleTitleImmediate increase of portal pressure, reflecting sinusoidal shear stress, induced liver regeneration after partial hepatectomy J Hepatobiliary Pancreat Surg 6 275–80 Occurrence Handle10526063 Occurrence Handle10.1007/s005340050118 Occurrence Handle1:STN:280:DyaK1Mvlslehtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  74. Y Sato S Koyama K Tsukada K Hatakeyama (1997) ArticleTitleAcute portal hypertension reflecting shear stress as a trigger of liver regeneration following partial hepatectomy Surg Today 27 518–26 Occurrence Handle9306545 Occurrence Handle10.1007/BF02385805 Occurrence Handle1:STN:280:DyaK2svltFKjsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  75. H Kanda Y Nimura A Yasui T Uematsu S Kamiya Y Machiki et al. (1996) ArticleTitleHepatic blood flow after acute biliary obstruction and drainage in conscious dogs Hepatogastroenterology 43 235–40 Occurrence Handle8682470 Occurrence Handle1:STN:280:DyaK283mvVOqsQ%3D%3D

    PubMed  CAS  Google Scholar 

  76. HU Baer T Guastella AM Wheatley A Zimmermann LH Blumgart (1993) ArticleTitleAcute effects of partial hepatectomy on liver blood flow in the jaundiced rat J Hepatol 19 377–82 Occurrence Handle8151097 Occurrence Handle10.1016/S0168-8278(05)80545-8 Occurrence Handle1:STN:280:DyaK2c3gtFGgtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  77. Y Goto M Nagino Y Nimura (1998) ArticleTitleDoppler estimation of portal blood flow after percutaneous transhepatic portal vein embolization Ann Surg 228 209–13 Occurrence Handle9712566 Occurrence Handle10.1097/00000658-199808000-00010 Occurrence Handle1:STN:280:DyaK1czns1Cisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  78. K Kusaka H Imamura T Tomiya M Makuuchi (2004) ArticleTitleFactors affecting liver regeneration after right portal vein embolization Hepatogastroenterology 51 532–5 Occurrence Handle15086196

    PubMed  Google Scholar 

  79. K Nakano K Chijiiwa M Tanaka (2001) ArticleTitleLower 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 280 640–5 Occurrence Handle11162569 Occurrence Handle10.1006/bbrc.2000.4185 Occurrence Handle1:CAS:528:DC%2BD3MXls1amtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  80. KD Bissig U Marti M Solioz M Forestier H Zimmermann M Luthi et al. (2000) ArticleTitleEpidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy J Hepatol 33 275–81 Occurrence Handle10952245 Occurrence Handle10.1016/S0168-8278(00)80368-2 Occurrence Handle1:CAS:528:DC%2BD3cXlvVylu7s%3D

    Article  PubMed  CAS  Google Scholar 

  81. Y Fujiwara M Shimada Y Yamashita E Adachi K Shirabe K Takenaka et al. (2001) ArticleTitleCytokine characteristics of jaundice in mouse liver Cytokine 13 188–91 Occurrence Handle11161464 Occurrence Handle10.1006/cyto.2000.0781 Occurrence Handle1:CAS:528:DC%2BD3MXhtVyktLk%3D

    Article  PubMed  CAS  Google Scholar 

  82. H Miyoshi C Rust PJ Roberts LJ Burgart GJ Gores (1999) ArticleTitleHepatocyte apoptosis after bile duct ligation in the mouse involves Fas Gastroenterology 117 669–77 Occurrence Handle10464144 Occurrence Handle10.1016/S0016-5085(99)70461-0 Occurrence Handle1:CAS:528:DyaK1MXmtFSht74%3D

    Article  PubMed  CAS  Google Scholar 

  83. A Ogawa T Tagawa H Nishimura T Yajima T Abe T Arai et al. (2005) ArticleTitleToll-like receptors 2 and 4 are differentially involved in Fas-dependent apoptosis in Peyers patch and liver at an early stage after bile duct ligation in mice Gut 55 105–13 Occurrence Handle16118350 Occurrence Handle10.1136/gut.2005.065318

    Article  PubMed  Google Scholar 

  84. Y Iimuro T Nishiura C Hellerbrand KE Behrns R Schoonhoven JW Grisham et al. (1998) ArticleTitleNFkappaB prevents apoptosis and liver dysfunction during liver regeneration J Clin Invest 101 802–11 Occurrence Handle9466975 Occurrence Handle1:CAS:528:DyaK1cXht1Wrtro%3D

    PubMed  CAS  Google Scholar 

  85. SP Tzung N Fausto DM Hockenbery (1997) ArticleTitleExpression of Bcl-2 family during liver regeneration and identification of Bcl-x as a delayed early response gene Am J Pathol 150 1985–95 Occurrence Handle9176392 Occurrence Handle1:CAS:528:DyaK2sXktFalu7Y%3D

    PubMed  CAS  Google Scholar 

  86. T Takehara N Hayashi E Mita T Kanto T Tatsumi Y Sasaki et al. (1998) ArticleTitleDelayed Fas-mediated hepatocyte apoptosis during liver regeneration in mice: hepatoprotective role of TNF alpha Hepatology 27 1643–51 Occurrence Handle9620338 Occurrence Handle10.1002/hep.510270625 Occurrence Handle1:CAS:528:DyaK1cXjvVCrsrg%3D

    Article  PubMed  CAS  Google Scholar 

  87. T Sakamoto Z Liu N Murase T Ezure S Yokomuro V Poli et al. (1999) ArticleTitleMitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy Hepatology 29 403–11 Occurrence Handle9918916 Occurrence Handle10.1002/hep.510290244 Occurrence Handle1:CAS:528:DyaK1MXhtFOksbY%3D

    Article  PubMed  CAS  Google Scholar 

  88. DS Wang KF Dou KZ Li ZQ Gao ZS Song ZC Liu (2003) ArticleTitleHepatocellular apoptosis after hepatectomy in obstructive jaundice in rats World J Gastroenterol 9 2737–41 Occurrence Handle14669324

    PubMed  Google Scholar 

  89. T Sano T Ajiki Y Takeyama Y Kuroda (2004) ArticleTitleInternal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats Surgery 136 693–9 Occurrence Handle15349120 Occurrence Handle10.1016/j.surg.2004.02.001

    Article  PubMed  Google Scholar 

  90. S Saiki K Chijiiwa M Komura K Yamaguchi S Kuroki M Tanaka (1999) ArticleTitlePreoperative internal biliary drainage is superior to external biliary drainage in liver regeneration and function after hepatectomy in obstructive jaundiced rats Ann Surg 230 655–62 Occurrence Handle10561089 Occurrence Handle10.1097/00000658-199911000-00007 Occurrence Handle1:STN:280:DC%2BD3c%2FitlOntw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  91. S Kamiya M Nagino H Kanazawa S Komatsu T Mayumi K Takagi et al. (2004) ArticleTitleThe value of bile replacement during external biliary drainage: an analysis of intestinal permeability, integrity, and microflora Ann Surg 239 510–7 Occurrence Handle15024312 Occurrence Handle10.1097/01.sla.0000118594.23874.89

    Article  PubMed  Google Scholar 

  92. Y Ogata M Nishi H Nakayama T Kuwahara Y Ohnishi S Tashiro (2003) ArticleTitleRole of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats J Surg Res 115 18–23 Occurrence Handle14572768 Occurrence Handle10.1016/S0022-4804(03)00308-1 Occurrence Handle1:CAS:528:DC%2BD3sXot1Gkuro%3D

    Article  PubMed  CAS  Google Scholar 

  93. S Iyomasa M Terasaki H Kuriki Y Nimura S Shionoya K Kojima et al. (1992) ArticleTitleDecrease in regeneration capacity of rat liver after external biliary drainage Eur Surg Res 24 265–72 Occurrence Handle1425823 Occurrence Handle1:STN:280:DyaK3s%2FkvFCqtg%3D%3D

    PubMed  CAS  Google Scholar 

  94. H Suzuki S Iyomasa Y Nimura S Yoshida (1994) ArticleTitleInternal biliary drainage, unlike external drainage, does not suppress the regeneration of cholestatic rat liver after partial hepatectomy Hepatology 20 1318–22 Occurrence Handle7927267 Occurrence Handle1:STN:280:DyaK2M%2Fht1Wmsw%3D%3D Occurrence Handle10.1002/hep.1840200532

    Article  PubMed  CAS  Google Scholar 

  95. A Mizuta K Chijiiwa S Saiki S Kuroki K Nakamura M Tanaka (2002) ArticleTitleDifferences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage Eur Surg Res 34 291–9 Occurrence Handle12145555 Occurrence Handle10.1159/000063068 Occurrence Handle1:CAS:528:DC%2BD38Xls1Oqs70%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Yokoyama, Y., Nagino, M. & Nimura, Y. Mechanism of impaired hepatic regeneration in cholestatic liver. J Hepatobiliary Pancreat Surg 14, 159–166 (2007). https://doi.org/10.1007/s00534-006-1125-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00534-006-1125-1

Key words

Navigation