亚急性重症肝炎与淤胆性肝炎黄疸成因的组织学差别

对29例亚急性重症肝炎及13例次淤胆性肝炎肝穿刺标本的光、电镜检查,测算了18例亚急性重症肝炎,9例淤胆性肝炎肝细胞内淤胆的容积百分比、胆汁凝固性坏死的容积百分比与临床资料进行统计学处理,指出这两类肝炎都有肝细胞内淤胆和胆汁凝固性坏死,但淤胆性肝炎肝小叶结构完整,胆汁流出道不破坏,亚急性重症肝炎肝小叶破坏。认为除肝细胞大量坏死外,胆汁流出道破坏是影响预后的另一个重要因素。本文详细描述了胆计凝固性坏死的超微结构改变。     

Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production

We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.     

肝尾状叶的外科解剖及其临床应用

在42例成人肝脏标本上，研究了肝尾状叶的形态，动脉、静脉和肝管的分布特征；尾状叶常有3个突起，即尾状突、乳头突和下腔静脉后突，且变异较大；尾状叶有两个恒定的蒂，其结构排列由浅入深分别是门静脉支、肝动脉支和肝管。尾状叶静脉有2～5支，其中以3支居多，主要汇入下腔静脉肝后段的中、下1／3部的左前壁。中结合解剖学研究总结了施行肝尾状叶肿瘤切除术的方法和经验。     

High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease

An increase in bile ductular structures is observed in diverse human liver diseases. These structures harbour the progenitor cell compartment of the liver. Since ATP-binding cassette (ABC) transporters may have a cytoprotective role in liver disease, an immunohistochemical study was performed on human liver specimens from patients with primary biliary cirrhosis (PBC), chronic hepatitis C virus (HCV) infection, submassive cell necrosis, and normal liver. The expression of MDR1, MDR3, BSEP, MRP1, MRP2, and MRP3 was determined using specific antibodies. Dilution series were constructed to determine the critical staining level in order to estimate the factor of up-regulation. In normal liver, hepatocytes showed canalicular staining for MDR3, BSEP, and MRP2. MDR1 stained the canalicular membrane of hepatocytes as well as that of cholangiocytes. MRP3 showed low immunoreactivity of bile duct epithelial cells and centrilobular hepatocytes only. Normal liver showed no immunoreactivity for MRP1. In diseased liver, the expression of MDR3, BSEP, and MRP2 was relatively stable. In PBC, HCV, and submassive necrosis, the expression levels of MDR1, MRP1, and MRP3 were increased. The strongest immunoreactivity was seen after submassive necrosis, where remaining islands of hepatocytes showed strong canalicular staining for MDR1 and MRP3. Regenerating bile ductules at the interface of portal tracts and necrotic areas stained intensely for MDR1, MRP1, and MRP3. In conclusion, MDR1, MRP1, and MRP3 are up-regulated in hepatocytes in severe human liver disease. Strong MDR1, MRP1, and MRP3 reactivity is seen in regenerating human bile ductules.     

Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.     

Primary biliary cirrhosis and coronary atherosclerosis: Protective antioxidant effect of bilirubin

Increased concentration of lipid peroxidation products in patients with primary biliary cirrhosis is related to elevation of serum lipid content, but not to activation of lipid peroxidation. Hyperbilirubinemia in patients with primary biliary cirrhosis is accompanied by a decrease in the concentration of lipid peroxidation products and increase in antioxidant activity of blood serum. Antioxidants play a major role in the prevention of atherosclerosis. We hypothesized that the absence of increased risk of atherosclerosis in patients with primary biliary cirrhosis is due to inhibition of lipid peroxidation in blood serum by antioxidant compound bilirubin. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 23–28, January, 2008     

Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.     

Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss

The pathogenesis of progressive bile duct loss in primary biliary cirrhosis remains unclear. In this study, the involvement of cellular senescence of biliary epithelial cells was examined in liver tissue samples from patients with primary biliary cirrhosis (n = 33), and compared with control diseased and normal livers (n = 83). In addition, cellular senescence was induced by oxidative stress in cultured mouse biliary epithelial cells. Biliary epithelial cells in small bile ducts in primary biliary cirrhosis, especially those in patients presenting with chronic non-suppurative cholangitis, frequently expressed senescence-associated beta-galactosidase, and senescence-associated p16(INK4) and p21(WAF1/CIP). In contrast, senescence-associated markers were rarely expressed in small bile ducts in control livers. The infiltration of myeloperoxidase-positive inflammatory cells into biliary epithelial cell layers was closely associated with the cellular senescence of biliary epithelial cells in early-stage PBC. Cellular senescence of cultured mouse biliary epithelial cells was induced by treatment with H2O2 via the p38MAPK-dependent pathway and nitric oxide-augmented H2O2-induced cellular senescence. Oxidative stress- and nitric oxide-mediated cellular senescence may be involved in bile duct lesions, which are followed by progressive bile duct loss in primary biliary cirrhosis.     

Peripheral hepatolithiasis incidentally found at autopsy

Summary Hepatolithiasis is a common disease in East Asia though very rare in the West. Four cases of hepatolithiasis in which calculi were incidentally found in the peripheral branches of the intrahepatic biliary tree at autopsy are described and compared with hepatolithiasis involving the major branches of the intrahepatic biliary tree. These four cases were all elderly, three patients were male and one female. The calculi were brown pigment stones in each case, as seen in the major branch type. The stone-containing ducts showed mild fibrosis and glandular proliferation with inflammatory changes in three cases; these changes were marked in the fourth case. The hepatic parenchyma around the stone-containing ducts was atrophic or collapsed in all four cases. The major branches of the intrahepatic biliary tree as well as the extrahepatic tree failed to show findings suggestive of bacterial infections or biliary anomalies. These data suggest that brown pigment stones develop primarily in the peripheral ducts in the liver. It remains uncertain whether the peripheral type eventually progresses to the major type or not.     

Expression of alpha-amylase isoenzymes and trypsin by the proliferating epithelium of large intrahepatic bile ducts and intrahepatic peribiliary glands in hepatolithiasis

The expression of alpha-amylase isoenzymes (pancreatic and salivary) and trypsin by the epithelium of large intrahepatic bile ducts and peribiliary glands was examined immunohistochemically in hepatolithiasis ( n = 22), extrahepatic biliary obstruction ( n = 20) and normal liver ( n = 22). Hepatolithiasis was associated with marked proliferation of bile duct cells and peribiliary glands. Expression of pancreatic and salivary amylase was observed in the proliferating bile duct cells and peribiliary glands of all livers, and trypsin was found in 68% of the livers. In extrahepatic biliary obstruction, proliferation of the biliary epithelium was less marked, but expression of amylase isoenzymes was observed in all livers and trypsin was found in 50%. All normal livers showed expression of amylase isoenzymes in large intrahepatic bile ducts, septal bile ducts and peribiliary glands, and trypsin was found in 73%. The density of enzyme-containing acini was highest in hepatolithiasis, intermediate in extrahepatic biliary obstruction and lowest in normal liver. These results show that the proliferating biliary epithelium in hepatolithiasis contains amylase isoenzymes and trypsin and that biliary epithelium retains the ability to produce these enzymes after proliferation, suggesting that a large amount of amylase isoenzymes and trypsin may be secreted into the bile ducts in hepatolithiasis. These enzymes may play an important role in the pathophysiology of hepatolithiasis.