Study Of The Pathology And The Hepatocyte Heterogeneity Of Liver Atrophic Tissue In The Atrophy-hypertrophy Complex

BackgroudLiver atrophy-hypertrophy complex(AHC) is due to obstruction of the portalvein, hepatic vein or bile duct, causing atrophy of the affected hepatic lobes/segmentsand compensatory hypertrophy of the contralateral hepatic lobes/segments. AHC isoften associated with hepatolithiasis and hilar cholangiocarcinomar. Some patients ofcomplicated hepatolithiasis can’t undergo the liver resection because of small residualhepatic tissue and the atrophic hepatic tissue has an important role in maintaining thenormal liver function. Portal vein embolization(PVE) is often needed before extendedhemiheatectomy for hilar cholangiocarcinomar, causing the atrophy of the affectedliver lobes/segments and compensatory hypertrophy of the contralateral liverlobes/segments. In the course of the compensation of the contralateral liver, theatrophic hepatic tissue also has an important role in maintaining the normal liverfunction. Hepatic acinus was recognized as the fundamental unit of liver structure andfunction with the hepatocyte heterogeneity. However, the study in the pathology andfunction of the atrophic liver is rare. In this study, the atrophic hepatic tissue andhypertrophic hepatic tissue was researched by using the self-control open test and theaim to this study is to explore the pathology and function of the atrophic liver inAHC.Methods28patients with AHC were enrolled from Jan2008to Dec2013with the approvalof ethics committee and informed consent of the patients,24hepatolithiasis and4 hilar cholangiocarcinomar. After the liver resection, morphology of the atrophic tissuewas observed, and the pathology was observed by light microscope, cellularultrastructure by scanning electron microscope. Some proteins were selected asindicators, such as albumin(ALB) associated with nutrient metabolism anddetoxification, triosephosphate isomerase(TPI) and glyceraldehyde-3-phosphatedehydrogenase (GAPDH) associated with glycolysis, phosphoenolpyruvatecarboxykinase(PEPCK) associated with aerobic oxidation and gluconeogenesis,apolipoprotein A-1(Apo A-1) associated with cholesterol metabolism, glutamatedehydrogenase(GDH) associated with amino acid metabolism, liver fatty acid bindingprotein(L-FABP) associated with fatty acid metabolism and chromogenesis, andglutathione S-transferase(GST) associated with biotransformation and carriage ofbilirubin. The location and expression of these proteins in hepatic acinus wereobserved by immunohistochemistry, enzyme-linked immuno sorbent assay (ELISA)and proteomics, and the pathology and hepatocyte heterogeneity of liver atrophictissue were discussed.Results1. Morphological changes: the volue of the atrophic lobes/segments decreases andthe surface of the affected hepatic lobes/segments is fibrotic but the surface of thehypertrophic lobes/segments appears “bulbous”; Liver rotates along with the hepatichilar axes with the majority of rotation to the right, the bottom of the gallbladder tothe posterior, portal vein to the left of the common bile duct.2. Hepatocyte ultrastruture: hepatosyte mitochondria, rough endoplasmidreticulum，Golgi apparatus and smooth endoplasmic reticulum all reduce, and themicrovilli of the bile capillary is scare, swelling and disintegrative, with thecollagenous fiber around the bile capillary, in the atrophic tissue. But the liver cell inthe hypertrophic tissue is rich in those cellular organelles, and the microvilli of the bile capillary proliferate and gather.3. Distribution of the proteins: ALB and PEPCK expressed mostly in the1zoneof acinus, L-FABP, GST and TPI in the3zone andApo A-1in the2zone.4. Expression of the proteins: it was observed by immunohistochemistry andELISA that all the proteins were expressed in the atrophic tissue, less than those inthe hypertrophy, and ALB, PEPCK, L-FABP and Apo A-1significantly decreased, butGST and TPI decreased unremarkably. Proteomics indicated that ALB, GDH, TPI,GAPDH andApo A-1reduced, but GST reduced unremarkably.Conclusions1. AHC is the course of gradually atrophying and functional weakening in theaffected hepatic lobes/segments and compensatory hypertrophying and functionalenhancing in the contralateral hepatic lobes/segments.2. Liver atrophic lobes/segments remains part of the function of nutrientmatebolism and biotransformation.3. Hepatic acinus possesses the hepatocyte heterogeneity in liver atrophiclobes/segments too.4. The residual functions of nutrient matebolism and biotransformation in atrophiclobes/segments play an important transitional role in maintaining the normal hepaticfunction.5. Due to the residual functions of nutrient matebolism and biotransformation,excision of the affected bile duct for some of complicated hepatolithiasis, reservingthe atrophic lobes/segments, perhaps not only can cure the etiology but also canreserve enough liver tissue to maintain the normal hepatic function.