Pathogenesis of Precirrhotic Portal Hypertension in Alcohol-Fed Baboons

Happei Miyakawa, Shinji Iida, Maria A. Leo, Robert J. Greenstein, David S. Zimmon, Charles S. Lieber

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

To study mechanisms and anatomic correlates of precirrhotic portal hypertension, we measured portal pressure either at laparotomy (in the portal vein) or by hepatic vein catheterization (wedge pressure) in 24 pairs of baboons fed 50% of energy either as ethanol or isocaloric carbohydrate (controls) for 4 mo–9 yr. On liver biopsy 7 had simple fatty liver; none had portal pressure exceeding the control range (2.7–13.0 cmH2O). The remaining 17 alcoholfed baboons had fibrous tissue deposition around the terminal hepatic venules and adjacent sinusoids. The mean portal pressure was significantly increased (15.0 ± 1.4 cmH2O) compared with the value in baboons with fatty liver (9.6 ± 0.9 cmH2O) and in controls (8.0 ± 0.6 cmH2O), with 8 animals exceeding the control range. Estimated hepatic blood flow was unchanged. Alcohol feeding resulted in increased hepatocyte size in both the fatty liver and fatty liver with fibrosis group; however, portal pressure did not correlate with alterations of cell size, liver volume, hepatic triacylglycerol, and protein contents. By contrast, for veins of comparable size, there was a significant correlation (r = 0.6666, p < 0.01) between the thickness of the perivenular fibrous rim and portal pressure. Perivenular fibrosis was commonly associated with adjacent perisinusoidal fibrosis and this lesion also correlated with portal pressure. Furthermore, i f one postulates that increased cell size causes enhanced pressure with secondary fibrosis, the latter should have first occurred “upstream,” in the mid and portal zones. Sequential biopsy specimens, however, showed that fibrosis first appeared in the perivenular areas, suggesting that, in most instances, increased pressure is in fact secondary to the perivenular fibrosis.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalGastroenterology
Volume88
Issue number1
DOIs
StatePublished - 1985

Keywords

  • CAB
  • NS
  • THV
  • chromotrope aniline blue
  • not significant
  • terminal hepatic venules

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