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Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver disease of unknown etiology characterized by highly specific anti-mitochondrial antibody in serum and immune-mediated non-pyogenic destructive infection in the small intrahepatic bile ducts,which can lead to portal inflammation and fibrosis and finally progress to liver cirrhosis and liver failure.At present,ursodeoxycholic acid (UDCA) is the only drug approved for the treatment of PBC with a recommended dose of 13-15 mg · kg-1 · d-1.There are significant improvements in the survival rate of patients achieving biochemical response after UDCA treatment.However,about 40％ of PBC patients do not respond to UDCA,and such patients have a risk of disease progression and are in urgent need of other drugs.With reference to recent clinical studies and guidelines,this article summarizes the basic concepts and latest advances in pharmacotherapy for PBC,as well as the perspectives of new drugs in clinical trials,in order to bring new hopes to PBC patients with poor response to UDCA.
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Background:The clinical presentation of eosinophilic gastroenteritis( EG)is nonspecific and has not received much concern by physicians and pathologists. The diagnosis of EG was delayed in many cases. Aims:To explore the clinical features of EG. Methods:The clinical,laboratory,endoscopic and radiologic features and treatment in patients who were diagnosed as EG from October 2011 to September 2013 in Zhongshan Hospital, Fudan University were analyzed retrospectively. Results:Median age of 10 EG patients was 41. 9 years. Four patients had a history of allergy or asthma. The time from onset to diagnose was 25 days on average. The most common symptoms were abdominal pain with bloating, diarrhea or vomiting. Eight patients had hypereosinophilia. Abdominal CT revealed uniform edema or stratified thickness of intestinal wall or ascites in 7 patients. Endoscopy revealed erythema,edema and erosion in antrum,duodenum or jejunum in 6 patients. All cases were confirmed as having eosinophilic infiltration by mucosal biopsy or examination of ascites. Seven patients were successfully treated with corticosteroid. One patients experienced relapse after discontinuing corticosteroids during following up. Conclusions:EG may be more common than previously recognized and should be considered in the differential diagnosis of unexplained abdominal pain with peripheral eosinophilia or uniform edema or stratified thickness of intestinal wall. Multiple biopsies in multiple sites including descending duodenum and pathological examination for finding eosinophil infiltration are the keys to confirm the diagnosis. Corticosteroids are effective in relieving symptoms and improving eosinophilia.
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Objective To comprehensively evaluate the clinical and radiological features of patients with Klebsiella pneumonia liver abscess (KLA) in order to improve treatment. Methods Data of 197 patients with KLA (n=106) or non-KLA (n=56) between March 2001 and January 2009 were collected and retrospectively analyzed on the aspects of underlying diseases, clinical manifestations, laboratory tests, pathogenic and imaging examinations. Results In comparison with non-KLA patients, the underlying diseases such as diabetes (53. 77% vs 25.00%, P = 0. 001) and hepatic adipose infiltration (16. 04% vs 5, 36%, P<0.05) were more common in KLA patients.Whereas the clinical presentations including abdominal pain (57. 14% vs 40. 57%, P<0. 05),hypodynamia (46.43% vs 19.81%, P=0. 001) and hepatomegaly (14.29% vs 4.72%, P<0. 05)were more severe in non-KLA patients than in KLA patients, however, the fasting blood glucose was higher in KLA patients than in non-KLA patients [(7.84±0.36) mmol/L vs (5.76±0.30) mmol/L,P=0. 001] on the admission. In addition, the abscess of KLA often appeared alone in the right lobe of the liver and was liable to generate air cavity (32. 88% vs 13.51%, P<0.05), un-smooth rim (71.23% vs 40.54% ,P<0.05) and dynamic septum enhancement (41.10% vs 16.22% ,P<0.01) in comparison with non-KLA. Conclusions Klebsiella pneumonia has emerged as the main pathogen of pyogenic liver abscess. The patients with KLA are often complicated with diabetes and fatty liver, as well as high prevalence of air cavity. The CT findings may be helpful for prompt treatment of Klebsiella pneumonia liver abscess.
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Objective To investigate the role of cyclooxygenase-2 (COX-2) in sinusoidal capillarization in liver cirrhotic rats. Methods The SD rats were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 8 weeks to induce liver cirrhosis. The rats were randomly divided into three groups: normal control group (n= 10), model control group (n= 15) and rofecoxib treated group (received 10 mg/kg of rofecoxib daily, n = 15). Liver histopathology was examined by light microscopy, and sinusoidal ultrastructure was observed by transmission electron microscopy. Furthermore, the level of basement membrane proteins (collagen type Ⅳ, laminin) and their localizations in liver were determined by Western blotting and immunohistochemistry, respectively, and the microvessel density was detected following vWF (yon Willebrand factor) immunolabeling on liver tissue sections. Results Fibrotic areas were reduced in rofecoxib treated group compared with that in model group (30.7±8.9 vs 23.5±6.5,P<0. 05). The light and electron microscopy showed that the pathologic changes including loss or reduction in number of sinusoidal endothelial fenestrate, the accumulation of extracellular matrix in the Disse's space and development of subendothelial basal lamina (basement membrane formation) were more severe in model group than those in rofecoxib treated group. Compared with model group, administration of rofecoxib resulted in significant decrease in microvessel density (11.3 ± 1.6 vs. 6.4 ±0. 7, P<0. 01). Rofecoxib could significantly decrease the expression of type Ⅳ collagen and laminin at protein levels (3.0±0.5 and 3.0±0.5, respectively) when compared with model group (3.8±0.4 and 3.7±0. 5, respectively). Conclusion The results indicate that early administration of rofecoxib may reduce sinusoidal capillarization.
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Objective To investigate the expression of integrin avβ3 in both of hepatic stellate cell (HSC)and fibrotic liver tissue,and to demonstrate whether integrin avβ3 is a phenotypical receptor of activated HSC.Methods HSC were isolated from Sprague-Dawley rats and activated by prolonged cultural.The rats were injected with 175 mg of thioacetamide twice a week for 12 weeks to induce liver fibosis.The expressions of avβ3 and a-SMA were identified by immunocytochemical staining.The expression of avβ3 in HSC,normal and fibrotic tissues were examined by real-time PCR and Western blot.Results The expression of avβ3 in activated HSC were up regulated and levels of mRNA and protein were increased to 18 and 5.2 folds on day 14 compared with day 1 and were also higher than control(t=2.39,P＜0.05;t=2.74,P＜0.05).The immunochemistry staining showed that integrin avβ3 was expressed on membrane of activated HSCs.The avβ3 and a-SMA were expressed in portal vein in normal liver,but were also expressed in portal and fibrotic.Conclusions The integrin avβ3 is up-regulated in activated HSC both in vitro and in vivo.It is a phenotypical receptor of activated HSC which involved in liver fibrosis.
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Objective To investigate the preventive effect of inactive schistosome ova on trinitrobenzesulfonic acid(TNBS)-induced colitis in mice and its mechanism.Methods Murine colitis was induced by administration of 3 mg of TNBS.Sixty mice were divided into control group(n=20),treatment group(n=20)and model group(n=20).Ten thousand frozen inactive schistosome ova were intraperitoneal injected at 14th and third day before TNBS induction in treatment group.The mice in model group were intraperitoneaUy injected with saline. All survival mice were killed at 7th day and mortality rate was calculated and morphological and pathological changes were eveluated.Expression of interleukin-10 and interferon-γ at colon tissue and serum were measured by real-time PCR and ELISA,respectively.Results The mortality rate in treatment group was lower than that in model group(20%vs 50%,P＜0.05)and the colonic inflammation alleviated(Ameho-criteria score:1.58±0.5 vs 4.18±0.8,P＜0.05)compared with the model group.Meanwhile,compared with model group,the expression of interferon-γ was decreased[serum:(48.33±16.59)pg/ml vs(29.79±6.97)pg/ml,colon tissue:2.31±1.08 vs 7.23±3.52 P＜0.05]and interleukin-10 was increased significantly[serum:(28.87±5.74)pg/ml vs(38.22±9.96)pg/ml,colon tissue:3.68±1.58 vs 7.44±3.04 P＜0.05]in treatment group.Conclusions IntraDeritonealy injection of inactive schistosome ova can alleviate inflammation of TNBS-induced colitis in mice,which may be the result of increased IL-10 and decreased IFN-γ expression in colon and serum.
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Objective To investigate the role of cyclooxygenase 2 (COX 2) in the forming of portal hypertension and whether a selective COX 2 inhibitor can reduce the portal hypertension or not. Methods Cirrhotic Sprague Dawley rat was induced by carbon tetrachloride (CCl 4) intraperitoneally for 8 weeks. The animals were divided into three groups: 10 normal rats served as control group; the other 15 rats, which received CCl 4 intraperitoneally twice a week and rofecoxib (10 mg/kg) by gavages daily, served as treatment group; another 15 rats, which were induced cirrhosis by CCl 4 but given placebo (saline solution ) instead of rofecoxib, served as placebo group. After 8 weeks of CCl 4 induction, portal pressure was measured, and the levels of thromboxane B 2 (TXB 2), and prostaglandin (PG)E 2 in the liver tissues were determined by enzyme immunoassay. Furthermore, liver histopathological analysis was performed in H E and Masson's trichrome staining sections. Results Portal pressure in the rats of rofecoxib group was significantly decreased compared to that in the placebo group [(11.95?1.05) mm Hg vs. (13.45?1.15) mm Hg; P