Role of ischemia in causing apoptosis, atrophy, and nodular hyperplasia in human liver

Abstract

of apoptosis such as portal vein thrombosis (PVT). Portal Ischemia is known to be a cause of hepatocellular apoptosis vein ligation is well-known to cause apoptosis in an experiand atrophy in experimental animals, but the effect of vascular mental model, 1,2 but the association of ischemia and obstruction on such lesions in the normal or cirrhotic human apoptosis has not been reported in human livers.3 liver has not been studied. ity, and acute and healed portal vein thrombosis (PVT). LargeThe effect of portal vein obstruction on the cirrhotic liver numbers of apoptotic cells were found in livers with acute has not been studied. PVT (17.2/medium-power field [MPF]) and in infarcts of ZahnThe aim of the present study was to examine the role of caused by obstruction of portal veins (PVs) by tumor (16.4/ ischemia in the pathogenesis of apoptosis and atrophy in the MPF). Smaller numbers of apoptotic cells were found in cirhuman liver. Explants, segmental resections, and autopsies rhosis of various etiologies (3.8-10.0/MPF) and rarely in norwere reviewed to establish the prevalence and histological mal livers (0.16/MPF). Evidence of healed PVT was found features of apoptosis, atrophy, and nodular hyperplasia, and in 47% of cirrhotic livers and was associated with nodular to correlate these features with portal vein disease, disease hyperplasia (58% vs. 32%, P õ .01) and focal atrophy (79% activity, and cirrhosis. vs. 49%, P õ .002). Apoptotic cells were found equally in those with and without healed PVT (40% vs. 38%, not signifi- MATERIALS AND METHODS cant). These observations suggest that apoptosis is a transient response to acute ischemia and that atrophy and nodularTwo sets of liver specimens were studied. The first was a series hyperplasia are chronic responses to ischemia. Vascular ob-of 100 large specimens selected to include a range of diagnoses, struction may be an important cause of the apoptosis and with or without cirrhosis, to be correlated with apoptotic cells and atrophy. The second set was composed of 118 consecutive explants atrophy, which are found in nodular regenerative hyperplasia with cirrhosis, for correlation of healed PVT with apoptosis, atro-(NRH), infarct of Zahn, chronic hepatitis, and cirrhosis. (HEPphy, and nodular hyperplasia.

The Potential of Angiogenesis Soluble Markers in Chronic Hepatitis C *

“…Previous studies have indicated that liver angiogenesis is stimulated by inflammation-derived mediators 6,15,23 and by fibrosis-associated hypoxia. 24 Our results showing a significant correlation between the grade of inflammation and serum levels of VEGF also support this concept. Based on this evidence, it seems logical that therapy-induced improvement of the hepatic lesion (that is, resolution of inflammation and regression of fibrosis) could result in inhibition of angiogenesis.…”

Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

“…The results may have direct clinical implications in liver diseases involving portal vein obliteration. Ischemia caused by this condition has been shown to cause hepatocellular apoptosis and liver atrophy in the absence of chronic inflammation [57] …”

Nodular regenerative hyperplasia of the liver: An under‐recognized cause of portal hypertension in hematological disorders

“…In rabbits, it has been demonstrated that ligation of one branch of the portal vein leads to atrophy of the ischemic portion and hypertrophy of the vascularized region of the liver [11]. In human livers obtained at explant, segmental resection, or autopsy, it has been shown that apoptosis, focal atrophy, and nodular hyperplasia of the liver are associated with acute and healed portal vein thrombosis [12]. The ensuing microcirculatory disturbances at the level of the liver sinusoid appear to occur either due to a mechanical obstruction or functionally due to local hemodynamic changes.…”