Metabolic alterations in obstructive jaundice: effect of duration of jaundice and bile-duct decompression.
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We examined the effect of prolonged bile duct obstruction, and subsequent biliary decompression, on biochemical and metabolic parameters, using a reversible jaundice model in male Fischer 344 rats. The animals were studied after biliary obstruction for varying periods (4 days, one week, and two weeks) and following decompression. They were sacrificed one or two weeks following decompression. All the rats were compared to sham operated, pair-fed, controls. Obstructive jaundice rapidly increased bilirubin, liver enzymes, serum free fatty acid, and triglyceride levels. Glucose levels were significantly decreased in the jaundice rats compared to their pair-fed controls. Only after two weeks of jaundice was significant hypoalbuminemia observed. Following decompression, all biochemical and metabolic values gradually returned to normal levels, except for albumin. Hypoalbuminemia was not reversed within the two-week post-decompression period. The rats jaundiced for two weeks had significantly higher mortality, compared to the other groups. We conclude that prolonged jaundice adversely affects the metabolic capacity of the rats, with albumin concentration being markedly decreased, and that biliary decompression could not reverse completely all the alterations seen with cholestasis, especially following two weeks of bile duct obstruction. (+info)
Obstructive cholestasis induces TNF-alpha- and IL-1 -mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2.
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Inverse acinar regulation of Mrp2 and 3 represents an adaptive response to hepatocellular cholestatic injury. We studied whether obstructive cholestasis (bile duct ligation) and LPS treatment affect the zonal expression of Bsep (Abcb11), Mrp4 (Abcc4), Ntcp (Slc10a1), and Oatp isoforms (Slco1a1, Slco1a4, and slco1b2) in rat liver, as analyzed by semiquantitative immunofluorescence. Contribution of TNF-alpha and IL-1beta to transporter zonation in obstructive cholestasis was studied by cytokine inactivation. In normal liver Bsep, Mrp4, Ntcp, and Oatp1a1 were homogeneously distributed in the acinus, whereas Oatp1a4 and Oatp1b2 expression increased from zone 1 to 3. Glutamine synthetase-positive pericentral hepatocytes exhibited markedly lower Oatp1a4 expression than the remaining zone 3 hepatocytes. In cholestatic liver Bsep and Ntcp immunofluorescence in periportal hepatocytes significantly decreased to 66 +/- 4% (P < 0.01) and 67 +/- 7% (P < 0.05), whereas it was not altered in pericentral hepatocytes. Oatp1a4 was significantly induced in hepatocytes with a primarily low expression, i.e., in periportal hepatocytes and in glutamine synthetase-positive pericentral hepatocytes. Likewise, Oatp1b2 was upregulated in periportal hepatocytes. Mrp4 zonal induction was homogeneous. Inactivation of TNF-alpha and IL-1beta prevented periportal downregulation of Bsep. Recruitment of neutrophils and polymorphonuclear cells mainly occurred in the periportal zone. Likewise, IL-1beta induction was largely found periportally. No significant transporter zonation was seen following LPS treatment. In conclusion, zonal downregulation of Bsep in obstructive cholestasis is associated with portal inflammation and is mediated by TNF-alpha and IL-1beta. Periportal downregulation of Ntcp and induction of Oatp1a4 and Oatp1b2 may represent adaptive mechanisms to reduce cholestatic injury in hepatocytes with profound downregulation of Bsep and Mrp2. (+info)
Treatment of malignant biliary obstruction with a PTFE-covered self-expandable nitinol stent.
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OBJECTIVE: We wanted to determine the technical and clinical efficacy of using a PTFE-covered self-expandable nitinol stent for the palliative treatment of malignant biliary obstruction. MATERIALS AND METHODS: Thirty-seven patients with common bile duct strictures caused by malignant disease were treated by placing a total of 37 nitinol PTFE stents. These stents were covered with PTFE with the exception of the last 5 mm at each end; the stent had an unconstrained diameter of 10 mm and a total length of 50-80 mm. The patient survival rate and stent patency rate were calculated by performing Kaplan-Meier survival analysis. The bilirubin, serum amylase and lipase levels before and after stent placement were measured and then compared using a Wilcoxon signed-rank test. The average follow-up duration was 27.9 weeks (range: 2-81 weeks). RESULTS: Placement was successful in all cases. Seventy-six percent of the patients (28/37) experienced adequate palliative drainage for the remainder of their lives. There were no immediate complications. Three patients demonstrated stent sludge occlusion that required PTBD (percutaneous transhepatic biliary drainage) irrigation. Two patients experienced delayed stent migration with stone formation at 7 and 27 weeks of follow-up, respectively. Stent insertion resulted in acute elevations of the amylase and lipase levels one day after stent insertion in 11 patients in spite of performing endoscopic sphincterotomy (4/6). The bilirubin levels were significantly reduced one week after stent insertion (p < 0.01). The 30-day mortality rate was 8% (3/37), and the survival rates were 49% and 27% at 20 and 50 weeks, respectively. The primary stent patency rates were 85%, and 78% at 20 and 50 weeks, respectively. CONCLUSION: The PTFE-covered self-expandable nitinol stent is safe to use with acceptable complication rates. This study is similar to the previous studies with regard to comparing the patency rates and survival rates. (+info)
Distal common bile duct stricture and secondary biliary cirrhosis due to choledocholithiasis.
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This case report documents a patient who presented with retained common bile duct (CBD) stones, recurrent attacks of cholangitis, CBD stricture, and secondary biliary cirrhosis. Endoscopic or surgical treatment of choledocholithiasis must be considered early in treatment. (+info)
TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse.
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Transcriptional activation by growth hormone of HNF-6-regulated hepatic genes, a potential mechanism for improved liver repair during biliary injury in mice.
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Liver histological, portal flow and plasmatic nitric oxide alterations caused by biliary obstruction and drainage in rats.
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PURPOSE: To evaluate liver alterations caused by biliary obstruction and drainage. METHODS: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB. RESULTS: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow. CONCLUSION: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing. (+info)
Bilioduodenal anastomosis in rats with extra-hepatic biliary obstruction is followed by lesions ischemia and reperfusion-induced.
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PURPOSE: The aim of this study was to investigate alterations compatible with hepatic ischemia-reperfusion after bilioduodenal shunt (BD) in rats with obstructive jaundice (OB) . METHODS: Thirty six animals were divided into 6 experimental groups: CO1 and CO2--control groups, sham-operated (SO) and evaluated 6 and 24 hours after, respectively; OB1 and OB2,--obstructive jaundice groups, sham-operated 15 days after bile duct ligature and evaluated 6 and 24 hours after SO, respectively; DBD1 and DBD2--obstructive jaundice groups evaluated ,respectively, 6 and 24 hours after BD performed 15 days after bile duct ligature. The parameters evaluated were serum total bilirubin, aminotransferase activity (AST, ALT), TNFalpha, liver mitochondrial functions and parenchymatous injury. RESULTS: Bilirubin decreased while aminotransferase activity increased 6 hours after BD (p<0.01); TNFalpha determination at the 6th hour after BD was higher than the one at the 24th hour (p<0.05); oxygen consumption in states 3 and 4 remained elevated in the BD initial phase , and liver cell damage worsened 24 hours after BD. CONCLUSION: The results demonstrated that surgical biliary decompression in obstructive jaundice is followed by alterations related to hepatic ischemia- reperfusion. (+info)