The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

Abstract

The mammalian hepatic lobule is characterized by a Little is known about the alterations of metabolic ormarked functional heterogeneity. [1][2][3] According to their posiganization of the human liver tissue in chronic liver distion within the hepatic lobule, hepatocytes present signifieases. We therefore compared the distribution of the folcant differences in the level of many enzyme activities, such lowing zonal metabolic markers in 10 samples of normal as those involved in the carbohydrate, ammonia, lipid, and liver tissue, 10 samples of fibrotic tissue, and 22 samples xenobiotic metabolisms, 2-5 and in the expression of some seof cirrhotic tissue: (a) the enzymatic activities of glucosecreted products, such as plasma proteins. 6 The metabolic or-6-phosphatase (G6P), lactate dehydrogenase (LDH), ganization of the mammalian hepatic lobule is well exemplisuccinate dehydrogenase (SDH), nicotinamide-adeninefied in the rat. In this species, gluconeogenesis, fatty acid dinucleotide-phosphate [NADPH] dehydrogenase (ND), oxydation, ureagenesis, and albumin synthesis predominate b-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine in the periportal region of the hepatic lobule, while glycolysis, synthetase (GLS); and (c) albumin messenger RNA fatty acid synthesis, glutamine formation, and xenobiotic me-(mRNA). The normal human hepatic lobule was charac-tabolism predominate in the perivenous region.7 The metaterized by the periportal predominance of G6P and SDH bolic zonation of the mammalian hepatic lobule is thought to enzymatic activities and albumin mRNAs, the perive-play an important physiological role by enabling the liver to nous predominance of ND and GDH, the restriction of simultaneously perform anabolic and catabolic activities, and GLS to a small perivenous compartment, and the pre-by allowing quick responses of the hepatic parenchyma to dominance of b-HBDH at the contact of both portal changes in the physiological status. 2,3,8 It is currently tracts and centrilobular veins. In fibrosis, the overall thought 2,3,8 that the maintenance of the metabolic organizametabolic organization of the normal liver tissue was tion of the liver depends mainly on microenvironmental facretained. The expression of periportal markers predomi-tors, including: (a) blood-borne factors, such as the gradients nated around enlarged portal tracts and that of perive-in oxygen, substrates, and hormones determined by the uninous markers around residual centrilobular veins. GLS directional perfusion of the hepatic lobule by the portal blood was constantly detected at the contact of centrilobular flow, (b) pericellular factors, such as the zonal differences in veins. In cirrhotic nodules, no zonation was observed the pattern of innervation, the composition of the extracellufor most enzymatic activities or for albumin. Only G6P lar matrix, and the functional characteristics of nonparenchyusually predominated at the periphery of the nodules. mal liver cells; and possibly (c) paracrine interact...

Glutamine synthetase expression in activated hepatocyte progenitor cells and loss of hepatocellular expression in congestion and cirrhosis

“…Aetiology of active disease included acute or chronic viral hepatitis , autoimmune hepatitis , ischaemia , cholestasis , steatohepatitis and acute rejection . Aetiology of inactive disease included steatosis without ballooning , inactive autoimmune hepatitis , low activity chronic viral hepatitis , non‐cirrhotic portal hypertension and normal biopsies .…”

“…When regional differences in stage were encountered, two or more blocks from a liver were graded separately, so that 51 livers contained 63 regions of interest, enumerated as follows: Chronic non‐biliary disease (Group 6) ( N = 30) was represented by hepatitis C , alcoholic disease , non‐alcoholic steatohepatitis , autoimmune hepatitis , alpha‐1‐antitrypsin deficiency and hepatitis B . Chronic biliary disease (Group 7) ( N = 33) was represented by primary sclerosing cholangitis , primary biliary cirrhosis , cystic fibrosis , malignant biliary obstruction and chronic ductopenic rejection . The sections were staged using the Laennec Staging System .…”

“…In the normal human and rodent liver, glutamine synthetase (GS) is expressed in a rim of hepatocytes adjacent to hepatic veins . Perivenular expression has been reported to be decreased or lost in cirrhosis . Increased GS expression in non‐perivenular hepatocytes occurs in regenerative states such as chronic hepatitis B and C , focal nodular hyperplasia , peritumoural hyperplasia and in some neoplasms including hepatocellular adenoma and hepatocellular carcinoma .…”

Over‐expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology

“…This pattern is highly conserved. GS is a useful marker in tumour liver pathology, including the diagnosis of liver HCA and nodules in cirrhotic tissue (17,18). As a consequence, we tested this FNH marker in various clinical situations related to hepatocellular nodules.…”

A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis

“…Although annular fibrosis surrounding hepatocyte nodules is the hallmark of cirrhosis, this feature is only one part of the spectrum of the lesions observed in cirrhotic livers. Indeed, vascular remodeling, sinusoidal capillarization, perisinusoidal fibrosis,20, 21 and loss of lobular zonation22 also develop in advanced fibrosis with important functional consequences in liver physiology. To date, whether these important microscopic features may improve in parallel with the regression of liver fibrosis/cirrhosis after an SVR remains unexplored.…”