Mitochondrial antibodies in extrahepatic biliary obstruction

Sera from 732 patients were screened for mitochondrial antibodies by immunofluorescence. Such antibodies were not found in any of the 36 patients of this series with extrahepatic biliary obstruction, 14 of whom had obstruction lasting more than 3 months. Mitochondrial antibodies were found in all 5 patients with primary biliary cirrhosis, in 3 patients with chronic hepatitis, and in 1 patient with alcoholic cirrhosis. It is concluded that the presence of mitochondrial antibodies remains a useful diagnostic tool in the differential diagnosis between primary biliary cirrhosis and extrahepatic biliary obstruction.     

Role of the gut in the pathophysiology of extrahepatic biliary obstruction.

BACKGROUND: Gram negative septic events are the commonest source of morbidity and mortality as a result of surgery in jaundiced patients. The large intestine provides the major source of Gram negative bacteria in mammals and is implicated in the pathogenesis of systemic endotoxaemia in obstructive jaundice. Bile salts have an important part in maintaining indigenous microecological homeostasis through their emulsifying properties. AIMS: The aim was to investigate the effects of biliary obstruction and isolated external biliary diversion on gastro-intestinal structure and caecal bacterial flora in relation to bacterial translocation. METHOD: Six groups of adult male Wistar rats were studied (no operation, sham operated, and bile duct ligated (BDL) for one and three weeks and a choledocho-vesical fistula (CDVF) for one week). At the end of the study period plasma was assayed for evidence of endotoxaemia and the animals were tested for bacterial translocation to the mesenteric lymph node complex (MLNC), liver, lungs, and spleen. Quantitative and qualitative bacteriological studies were performed on the caecal contents and segments of colon and terminal ileum were washed and prepared for histological assessment. RESULTS: Bacterial translocation was significantly increased in the BDL1 (68.8%) and BDL3 (60%) groups compared with the sham1 (6.3%), sham3 (9.1%), No operation (0%), and CDVF1 (16.7%) groups. Although translocation was more pronounced in the BDL1 group, this was almost exclusively to the MLNC compared with the more widespread translocation to other organs in the BDL3 group. The BDL3 group was the only group with significantly raised concentrations of endotoxin and anticore glycolipid. The caecal Gram negative aerobic counts were significantly increased in the BDL1 and CDVF1 groups compared with all other groups. There was evidence of structural abnormalities in the terminal ileum of rats jaundiced for three weeks, but not in the other groups. CONCLUSIONS: Biliary obstruction for one and three weeks promotes bacterial translocation although the mechanisms may be different. Absence of intralumenal bile results in a significant but self limiting increase in the Gram negative aerobic population, which may account for translocation in the early stages of biliary obstruction. As the duration of biliary obstruction increases systemic endotoxaemia is a consistent feature which, combined with factors such as immunological depression and physical disruption of gut barrier function, may promote bacterial translocation perpetuating systemic sepsis.     

Mechanism of neutrophil accumulation in sinusoids after extrahepatic biliary obstruction

BACKGROUND/AIMS: Polymorphonuclear neutrophil (PMN) infiltration represents a potential source of liver injury, but the precise mechanisms of PMN infiltration in cholestatic liver are not fully understood. METHODOLOGY: This study investigated hepatic expression of cytokine-induced neutrophil chemoattractant (CINC) 14 days after bile duct ligation, as well as the number of infiltrated PMNs in livers. Portal venous endotoxin levels were also evaluated. Furthermore, in vitro CINC production by isolated liver cells from obstructive jaundice (OJ) liver or sham-treated liver was evaluated after stimulation with tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta) or LPS. RESULTS: The number of infiltrated PMNs in sinusoids significantly increased in OJ liver, as compared to sham-treated liver. CINC mRNA expression was also increased in OJ liver. Immunohistochemical study revealed that the majority of the CINC-positive cells were hepatocytes. In vitro study proved that CINC production by isolated hepatocytes was markedly enhanced by IL-1beta stimulation in OJ liver. Furthermore, IL-1beta production by LPS-stimulated Kupffer cells isolated from OJ liver was significantly increased, compared to those from sham-treated liver. Portal venous endotoxin was detectable only in OJ rats. CONCLUSIONS: Excessive production of IL-1beta by activated Kupffer cells, as a result of portal endotoxemia, may play an important role for increased CINC release from hepatocytes in cholestatic liver, leading to PMN infiltration.     

Initial site of bile regurgitation following extrahepatic biliary obstruction in living rats

BACKGROUND AND AIM: The precise mechanism of bile regurgitation from the biliary system to the blood stream still remains to be elucidated. The aim of this study was to examine the initial site of bile regurgitation in vivo after common bile duct (CBD) obstruction by digitally enhanced fluorescence microscopy. METHODS: The fluorescence excreted into bile canaliculi after the administration of sodium fluorescein was continuously observed in CBD obstruction, using video-enhanced contrast (VEC) microscopy equipped with a silicon intensified target (SIT) camera. The liver histology and the localization of Mg(2+)-ATPase were examined by light and electron microscopy. RESULTS: By the continuous recording of canalicular fluorescence, the sequential regurgitation of the fluorescence from the canaliculi to the hepatocyte cytoplasm to the sinusoids was distinctively recognized after CBD obstruction. Bile canalicular fluorescence was enhanced, and then the fluorescence of the hepatocyte cytoplasm increased in intensity, followed by regurgitation of the fluorescence to the sinusoids. These in vivo sequences closely correlated with changes in CBD pressure. In zone 1, canalicular fluorescence focally burst into hepatocyte cytoplasm, thus resulting in the formation of fluorescent cells. By light and electron microscopy, the fluorescent cells were found to correspond to the liver cell injury. The reaction products of Mg(2+)-ATPase were incorporated into vesicles with a decreased canalicular activity, and then were transported to the sinusoidal surface after CBD obstruction. CONCLUSIONS: The initial site of bile regurgitation may be transcellular, and partly involves liver cell injury in zone 1 in extrahepatic biliary obstruction, associated with increased pressure of the biliary system.     

Liver transplantation for alcoholic liver disease

Alcoholism is a disease of remission and relapse. A lapse in abstinence tends to be viewed as a failure to commit to abstinence, and an acknowledged relapse may lead to the patient's removal from the liver transplant list; however, such a relapse may actually offer insight into alcoholism. Liver transplant physicians should consider recognizing lapses in abstinence as slips that indicate a need for treatment of alcoholism. Further research should address which alcoholic liver patients suffer relapses and how alcohol relapse affects the ability to maintain abstinence before or after transplantation.     

Liver transplantation for alcoholic liver disease

Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease.Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft.There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores....     

Liver transplantation for alcoholic liver disease

Patients with end-stage alcoholic liver disease should be considered for liver transplantation. A careful pretransplant evaluation must be undertaken to assess for both medical and psychiatric factors that will continue to require attention following transplantation. Although most programs require at least 6 months of ethanol abstinence before consideration of liver transplantation, there is little evidence that this conclusively predicts a reduction in recidivism. Most programs continue to exclude those with alcoholic hepatitis. Postoperatively, attention to psychiatric issues, recidivism, compliance, and assessment for tumors, especially squamous cell carcinomas, should be undertaken.     

经ERCP置入胆道金属支架与PTCD治疗老年肝外胆道恶性梗阻患者临床疗效比较*

目的 观察比较经内镜逆行胰胆管造影（ERCP）放置胆道金属支架与经皮肝穿刺胆管引流术（PTCD）治疗老年肝外胆道恶性梗阻患者的临床效果。方法 2014年10月~2017年10月我院收治的60例老年肝外胆道恶性梗阻患者,30接受PTCD治疗（对照组）,另30例接受经ERCP胆道金属支架置入治疗（观察组）。随访1年。结果 术后,观察组支架通畅时间为（225.4±52.6） d,显著长于对照组【（156.7±44.2） d,P<0.05】,住院时间为（12.3±2.4）d,显著短于对照组【（19.9±4.1） d,P<0.05】;观察组血清总胆红素为（110.2±60.1） μmol/L,显著低于对照组【（149.8±64.5） μmol/L,P<0.05】,碱性磷酸酶为（216.8±127.6）IU/L,显著低于对照组【（312.9±149.5） IU/L,P<0.05】,谷氨酰转肽酶为（196.5±100.5） IU/L,显著低于对照组【（269.8±121.3） IU/L,P<0.05】;观察组并发症发生率为10.0%,显著低于对照组的33.3%（P<0.05）;1 a生存率为30.0%,显著高于对照组的10.0%（x²=3.922,P=0.045）。结论 老年肝外胆道恶性梗阻患者接受经ERCP胆道金属支架置入治疗能短期降低黄疸,改善患者的肝功能指标,延长生存期。     

Failure to induce selective cholestasis in the rat after long-term extrahepatic selective biliary obstruction

Forty-eight hours after extra-hepatic selective biliary obstruction (SBO), there is evidence of cholestasis in the obstructed lobes (OL). However, some major ultrastructural features of cholestasis are missing. The aim of this work was to investigate the long-term effect of SBO. One month after surgery, and in comparison with sham-operated rats, bile flow, liver weight, and liver weight ratio of obstructed/nonobstructed lobes were normal. Furthermore, there was no evidence of cholestasis in OL by light and electron microscopy. Bile duct communications between obstructed and non-obstructed lobes were evidenced by Indian ink injection. In sham-operated rats, bile duct communications between ducts of the different lobes were involved in bile drainage. It appears, therefore, that the main reason for the lack of cholestasis 1 month after SBO is the drainage of bile from OL through accessory bile ducts.     

Susceptibility of the liver and biliary tract to anaerobic infection in extrahepatic biliary tract obstruction. II. Liver function and morphology of the liver and biliary tract--an experimental study in rabbits.

Biliary tract infection with anaerobic bacteria (B. fragilis or Fusobacterium mortiferum) was produced in rabbits by common duct ligation (c.d.l.) 3 days prior to intravenous bacterial inoculation. Animals were investigated 1, 4 or 7 days after inoculation. Histopathological investigations included the liver, the common duct, and the gallbladder, while liver function was evaluated by bilirubin, alkaline phosphatase (AP), and L-alanine aminotransferase (GPT) in serum. Rabbits with c.d.l. and biliary tract infection were compared to rabbits with c.d.l. in which bacterial inoculation failed to produce infection, to inoculated rabbits without c.d.l., and to uninoculated rabbits with c.d.l. Anaerobic biliary tract infection in rabbits with c.d.l. caused a significant increase in liver abscesses, a significant increased infiltration with granulocytes in the gallbladder, and a significant increase in serum levels of bilirubin, AP, and GPT, but failed to produce signs of cholangitis in the liver and intramural abscesses in the gallbladder. A material is presented of normal values for bilirubin, AP, and GPT in serum in rabbits.