AIMTo investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODST...AIMTo investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODSThis is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of RESULTSA total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B (P value P value P value P value P value P value P value CONCLUSIONThe 6-wk and 5-d mortality and rebleeding rate were significantly higher in patients with liver cirrhosis compared to patients with schistosomal periportal fibrosis.展开更多
AIM:To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS:Aloe vera high molecular weight fractions(AHM) were processed by patented hyper-dry system in combin...AIM:To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS:Aloe vera high molecular weight fractions(AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation.Fifteen healthy volunteers as the control group and 40 patients were included.The patients were randomly subdivided into two equal groups:the conventional group was treated with placebo(starch),and AHM group was treated with 0.15 gm/d AHM,both for 12 consecutive weeks.The patients were investigated before and after treatment.Serum activity of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),hyaluronic acid(HA),transforming growth factor-β(TGF-β) and matrixmetalloproteinase-2(MMP-2) were determined.The reduced glutathione(GSH) and malondialdehyde(MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin(α-SMA) was identified by immunohistochemistry.RESULTS:At the start of the study,the hematoxylin and eosin staining revealed fibro-proliferated bile ductules,thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment.The use of AHM for 12 wk significantly ameliorated the fibrosis,inhibited the inflammation,and resulted in minimal infiltration and minimal fibrosis compared to the conventional group.The enzyme activities of the liver(ALT,AST and ALP) were attenuated after treatment in both groups,and the decrease in the AHM group was more significant as compared with the conventional group.Similar to the AST,the MDA levels were significantly higher before treatment,and were attenuated after treatment in both groups.In contrast,the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls.The serum levels of the fibrosis markers(HA,TGF-β and MMP-2) were also reduced significantly after treatment.The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls.In the conventional group,there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins,while in the AHM group,few α-SMA positive cells were present in sinusoid and lobule after treatment.CONCLUSION:Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients.展开更多
The microvascular supply of the biliary tree, the peribiliary plexus （PBP）, stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been perform...The microvascular supply of the biliary tree, the peribiliary plexus （PBP）, stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts （SEMvcc） technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra-and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a morecomplex vascular network. After common duct ligation （BDL）, progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor （VEGF） is evaluated. VEGF-A,VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand,the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.展开更多
The liver has a complex vascular anatomy with a unique dual blood supply.Clinical conditions of the liver vary widely and include disorders originating in the vascular and biliary systems as well as the parenchyma.In ...The liver has a complex vascular anatomy with a unique dual blood supply.Clinical conditions of the liver vary widely and include disorders originating in the vascular and biliary systems as well as the parenchyma.In most vascular disorders,the effects on the liver are generally subclinical because of its abundant blood supply.However,early diagnosis of such vascular diseases can significantly reduce patient morbidity and mortality.Because imaging findings of vascular disease are not always readily apparent,diagnosis can be difficult.Computed tomography angiography is an excellent imaging modality for visualizing the vascular anatomy of patients for treatment planning.In this review article,we focus on the vascular anatomy of the liver and the imaging findings in some acute hepatic vascular diseases.展开更多
A recent publication highlights the importance of high yes-associated protein(YAP) expressing cells in liver regeneration following partial hepatectomy.Although the names of the cell populations described in these art...A recent publication highlights the importance of high yes-associated protein(YAP) expressing cells in liver regeneration following partial hepatectomy.Although the names of the cell populations described in these articles [hybrid periportal hepatocytes(HybHP) or epithelial-mesenchymal transition(EMT)-reprogrammed hepatocytes] are not identical, they all express high levels of YAP.We hypothesize that the HybHP and EMT-reprogrammed hepatocytes might be a similar cell population. Hippo signaling is the primary pathway that regulates YAP activity. According to the contribution of these two types of cells to liver regeneration and the high YAP expression, Hippo-YAP signaling activation may be a common regulatory pathway experienced by cells undergoing dedifferentiation and reactivating proliferative activity during liver regeneration.Although no evidence has shown that HybHP cells contribute to hepatocellular carcinoma in mouse models, we can not rule out the possibility that these highly regenerative cells can further develop into tumor cells when they acquire mutations caused by viral infection or other risk factors like alcohol. The detailed mechanistic insight of the regulation of YAP expression and activity in HybHP(or other types of cells contributing to liver regeneration) is unknown. We hypothesize that liver regeneration under various conditions will eventually lead to divergent consequences, likely due to the duration of YAP activation regulated by Hippo-large tumor suppressor 1 and 2 pathway in a context-and cell typedependent manner.展开更多
Background: Liver fibrosis is the presence of excess collagen due to new fibers formation. It is classified as a component of many forms of liver disease and injury rather than a disease by itself. To-date, there is n...Background: Liver fibrosis is the presence of excess collagen due to new fibers formation. It is classified as a component of many forms of liver disease and injury rather than a disease by itself. To-date, there is no effective treatment for liver fibrosis. The only known way for patients suffering from advanced liver fibrosis is liver transplantation. Aim: The study was conducted to prove safety of Regehep (DAH04) as a novel treatment for treatment of advanced liver fibrosis in both of healthy adult volunteers. In addition, effectiveness and tolerability of Regehep (DAH04) in patients with advanced liver fibrosis. Method: Fourteen adult volunteers were enrolled for part A and B. Part A, twelve adult healthy volunteers were randomly assigned into four groups (n = 3) as section of safety. Part B, two patients were enrolled to asses tolerability and effectiveness of Regehep in case of advanced liver fibrosis. Single ascending dose was used to asses safety in part A while therapeutic dose was used to achieve primary and secondary end point in part B. Results: There were no serious side effects as well as no serious biochemical changes after administration of single ascending doses of Regehep (DAH04) up to 25 folds of therapeutic dose. While part B, two cases of advanced liver fibrosis showed improvement of biochemical profile and ultrasound images of the liver till curing of periportal fibrosis as secondary end point. Conclusion: Regehep (DAH04) appears to be safe in doses up to 25 folds of therapeutic dose as well as effective in treatment of periportal fibrosis in late stages.展开更多
文摘AIMTo investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODSThis is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of RESULTSA total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B (P value P value P value P value P value P value P value CONCLUSIONThe 6-wk and 5-d mortality and rebleeding rate were significantly higher in patients with liver cirrhosis compared to patients with schistosomal periportal fibrosis.
文摘AIM:To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis.METHODS:Aloe vera high molecular weight fractions(AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation.Fifteen healthy volunteers as the control group and 40 patients were included.The patients were randomly subdivided into two equal groups:the conventional group was treated with placebo(starch),and AHM group was treated with 0.15 gm/d AHM,both for 12 consecutive weeks.The patients were investigated before and after treatment.Serum activity of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),hyaluronic acid(HA),transforming growth factor-β(TGF-β) and matrixmetalloproteinase-2(MMP-2) were determined.The reduced glutathione(GSH) and malondialdehyde(MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin(α-SMA) was identified by immunohistochemistry.RESULTS:At the start of the study,the hematoxylin and eosin staining revealed fibro-proliferated bile ductules,thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment.The use of AHM for 12 wk significantly ameliorated the fibrosis,inhibited the inflammation,and resulted in minimal infiltration and minimal fibrosis compared to the conventional group.The enzyme activities of the liver(ALT,AST and ALP) were attenuated after treatment in both groups,and the decrease in the AHM group was more significant as compared with the conventional group.Similar to the AST,the MDA levels were significantly higher before treatment,and were attenuated after treatment in both groups.In contrast,the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls.The serum levels of the fibrosis markers(HA,TGF-β and MMP-2) were also reduced significantly after treatment.The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls.In the conventional group,there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins,while in the AHM group,few α-SMA positive cells were present in sinusoid and lobule after treatment.CONCLUSION:Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients.
基金MIUR grants PRIN 2005 (prot. 2005067975_001) to E. Gaudio and Biomedicina, Cluster C04, Progetto n. 5 to E.Gaudio-P.Onori MIUR grants PRIN 2005 (prot.No: 2005067975_002) to D. Alvaro and a VA Research Scholar Award, a VA Merit Award and the NIH grants DK58411 and DK062975 to Gianfranco Alpini
文摘The microvascular supply of the biliary tree, the peribiliary plexus （PBP）, stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts （SEMvcc） technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra-and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a morecomplex vascular network. After common duct ligation （BDL）, progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor （VEGF） is evaluated. VEGF-A,VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand,the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.
文摘The liver has a complex vascular anatomy with a unique dual blood supply.Clinical conditions of the liver vary widely and include disorders originating in the vascular and biliary systems as well as the parenchyma.In most vascular disorders,the effects on the liver are generally subclinical because of its abundant blood supply.However,early diagnosis of such vascular diseases can significantly reduce patient morbidity and mortality.Because imaging findings of vascular disease are not always readily apparent,diagnosis can be difficult.Computed tomography angiography is an excellent imaging modality for visualizing the vascular anatomy of patients for treatment planning.In this review article,we focus on the vascular anatomy of the liver and the imaging findings in some acute hepatic vascular diseases.
基金National Natural Science Foundation of China,No.81502304Science and Technology Projects of Quzhou,No.2018K20Suitable Technology Promotion Center New Technology and Product Research and Development Projects,No.2019329288
文摘A recent publication highlights the importance of high yes-associated protein(YAP) expressing cells in liver regeneration following partial hepatectomy.Although the names of the cell populations described in these articles [hybrid periportal hepatocytes(HybHP) or epithelial-mesenchymal transition(EMT)-reprogrammed hepatocytes] are not identical, they all express high levels of YAP.We hypothesize that the HybHP and EMT-reprogrammed hepatocytes might be a similar cell population. Hippo signaling is the primary pathway that regulates YAP activity. According to the contribution of these two types of cells to liver regeneration and the high YAP expression, Hippo-YAP signaling activation may be a common regulatory pathway experienced by cells undergoing dedifferentiation and reactivating proliferative activity during liver regeneration.Although no evidence has shown that HybHP cells contribute to hepatocellular carcinoma in mouse models, we can not rule out the possibility that these highly regenerative cells can further develop into tumor cells when they acquire mutations caused by viral infection or other risk factors like alcohol. The detailed mechanistic insight of the regulation of YAP expression and activity in HybHP(or other types of cells contributing to liver regeneration) is unknown. We hypothesize that liver regeneration under various conditions will eventually lead to divergent consequences, likely due to the duration of YAP activation regulated by Hippo-large tumor suppressor 1 and 2 pathway in a context-and cell typedependent manner.
文摘Background: Liver fibrosis is the presence of excess collagen due to new fibers formation. It is classified as a component of many forms of liver disease and injury rather than a disease by itself. To-date, there is no effective treatment for liver fibrosis. The only known way for patients suffering from advanced liver fibrosis is liver transplantation. Aim: The study was conducted to prove safety of Regehep (DAH04) as a novel treatment for treatment of advanced liver fibrosis in both of healthy adult volunteers. In addition, effectiveness and tolerability of Regehep (DAH04) in patients with advanced liver fibrosis. Method: Fourteen adult volunteers were enrolled for part A and B. Part A, twelve adult healthy volunteers were randomly assigned into four groups (n = 3) as section of safety. Part B, two patients were enrolled to asses tolerability and effectiveness of Regehep in case of advanced liver fibrosis. Single ascending dose was used to asses safety in part A while therapeutic dose was used to achieve primary and secondary end point in part B. Results: There were no serious side effects as well as no serious biochemical changes after administration of single ascending doses of Regehep (DAH04) up to 25 folds of therapeutic dose. While part B, two cases of advanced liver fibrosis showed improvement of biochemical profile and ultrasound images of the liver till curing of periportal fibrosis as secondary end point. Conclusion: Regehep (DAH04) appears to be safe in doses up to 25 folds of therapeutic dose as well as effective in treatment of periportal fibrosis in late stages.
