Bile Duct Occlusion Research Articles

Acute, Clinically Evident Hepatitis C Virus Infection and Liver Injury

Purpose: Clinically evident acute (or recent) hepatitis C virus (HCV) infection and liver injury is uncommon, in contrast to chronic HCV infection and associated liver disease. However, the clinical and laboratory features of overt recent HCV infection are not dissimilar to other etiologies of acute hepatitis, i.e. fatigue, anorexia, pale stools and dark urine; serum aminotransferase concentrations are typically elevated significantly. Therefore, because clinically overt acute HCV infection is uncommon and alternative diagnoses demand consideration, e.g. autoimmune hepatitis (AIH), liver biopsy may be undertaken. A recent report drew attention to the spectrum of observed histologic abnormalities, such as those concerning for large bile duct occlusion. Methods: We describe five patients with what we believe was clinically evident acute HCV infection and liver injury, all of whom required and underwent liver biopsy on clinical grounds. Results: Five adult patients (two men; median age 41 years [range 19–47]) presented for further evaluation of acute severe liver injury, either without (two patients) or with symptoms – malaise, anorexia, nausea, abdominal pain, pale stools and dark urine. The means of recent HCV exposure was as follows: sexual (two), intranasal (two), and intravenous (one). Pertinent data are contained in the table. Alternative causes of acute severe liver injury (viral, autoimmune, drug-induced, metabolic and alcoholic) were excluded as far as possible by history-taking and laboratory testing. However, because liver injury was so marked, and in three patients alternative or additional explanations existed (Wilson's disease, AIH) liver biopsy was undertaken. Unlike classic descriptions of morphologic changes in acute viral hepatitis, namely lobular hepatocyte swelling/ballooning and acidophil necrosis, pigment-laden macrophages, and/or canalicular cholestasis (all five biopsies revealed these changes), two of the biopsy specimens demonstrated portal tract expansion by edema, with many neutrophils and evidence of bile duct injury. Chronic inflammation was minimal. This raised concern for a primary biliary process, e.g. large duct obstruction. Furthermore, one of these two specimens revealed numerous portal eosinophils concerning for drug reaction. Conclusion: All five patients had laboratory evidence of acute severe liver injury. Symptomatic patients had lower serum albumin, but higher total serum bilirubin and alanine aminotransferase (ALT) concentrations than those without symptoms. Moreover, this difference distinguished those patients with histological changes concerning for an underlying biliary process from those who did not in two of three cases. Timing between infection and liver biopsy might explain these differences.Table

Endoscopic Management of Postcholecystectomy Bile Duct Strictures

Review of 1.6 million cholecystectomies, from 1992 to 1999, demonstrated a 0.5% incidence of bile duct injury, despite increasing experience with laparoscopy. The incidence has not decreased after the "learning curve." The management of major bile duct injuries has traditionally been by hepaticojejunostomy. Endoscopy has been increasingly used to treat these injuries. This study reviews the senior author's endoscopic treatment of bile duct injuries. This is a retrospective study, from 1991 to 2006, examining data on 292 patients who were referred for postcholecystectomy problems; 199 had cholecystectomy-related injuries and 93 had other pathologies. Sixty-seven patients had bile duct injuries (Amsterdam Academic Medical Center Classification, types B, C, and D). Nineteen patients underwent bilioenteric bypass for complete bile duct occlusion or transection. In the remaining 48, endoscopic retrograde cholangiopancreatography (ERCP) evaluation and treatment were possible. Our protocol called for biliary stenting for 11 to 14 months, with stent changes at 3-month intervals. Short- and longterm results were evaluated by clinical, radiologic, and laboratory studies. Forty-six patients were selected for endoscopic management by balloon dilation and biliary stent placement. The mean +/- SD duration of endoscopic stenting was 12+/-9.8 months and followup was 30+/-24 months after stent removal. During the followup period, 10 of 46 patients (22%) had recurrent stricture: 6 (13%) responded to endoscopic biliary stenting and 4 (9%) required hepaticojejunostomy. Complications included pancreatitis (8%). There were no deaths in the endoscopic group. ERCP intervention is a safe, effective, minimally invasive treatment for bile duct strictures after cholecystectomy and can be an alternative to hepaticojejunostomy.

Endoscopic intraductal radiotherapy of high bile-duct carcinoma

A new method for palliative intraductal radiotherapy of high malignant bile duct occlusion was used in three patients. It consists of insertion of a 4 cm x 0,6 mm iridium-192 wire into the stenosis caused by the tumour. It uses a modified nasobiliary probe which is guided endoscopically retrograde transpapillary. A radiation output of 0.85 Gy/min (85 rd/min) and a requested therapeutic dosage of 60 Gy (6000 rd) at a distance of 0.5 cm lead to in situ position of the wire for about 70 hours. During that time bile flow is effected via the nasobiliary probe. The advantage over previously described methods (percutaneous transhepatic, surgical after installation of U-drainage) lies in a smaller complication rate and improved follow-up treatment as change of the endoprosthesis or repeat irradiation is not associated with renewed tissue trauma.

Expression of Angiotensin II Receptor Type 1 Is Reduced in Advanced Rat Liver Fibrosis

In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil (CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced mRNA of profibrotic TGF-beta, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for the prevention of cirrhosis.

Significance of C4d Deposition in the Diagnosis of Rejection After Liver Transplantation

C4d immunohistochemical staining of liver allograft biopsies was performed to assess its relationship to other pathological changes in the liver. C4d deposition was detected in 69.2% of liver graft biopsies from patients under going rejection, 33.3% of liver graft biopsies from patients with hepatitis B relapse after transplantation, and 28.6% of liver biopsies from patients with hepatitis B. When rejection occurred C4d deposition was located in the vascular walls of portal areas and hepatic sinusoidal walls. Examination of biopsies from patients with hepatitis B relapse after transplantation or hepatitis B infection showed C4d deposition only in the vascular walls of the portal area. C4d deposition in both vascular walls of portal area and hepatic sinusoidal walls was detected in only one of 12 ischemia-reperfusion damage cases. Repeated biopsy of the same patient 1 month later revealed acute cellular rejection. No C4d deposition was found in biopsies from a patient with bile duct occlusion after liver transplantation. C4d might serve as a sensitive marker for the diagnosis of liver rejection.

Multislice helical CT in the diagnosis of hilar cholangiocarcinoma

目的 探讨肝门区胆管细胞癌直接征象的多层螺旋CT(MSCT)表现.方法应用MSCT对19例无痛性黄疸患者行上腹部常规平扫及静脉注射对比剂后25和60 s双期增强扫描,15例应用增强扫描数据行三维图像重组,以3级评分法,判断MSCT对肝门区胆管细胞癌直接征象的显示能力.分析病变胆管的形态学特征、胆管受累范围.19例均经手术病理(15例)或内镜逆行胰胆管造影(ERCP,4例)证实为胆管细胞癌.结果 15例行三维图像重组者有14例显示肿瘤直接征象和肿瘤累及范围,19例行25和60 s双期增强扫描者分别有8例和7例显示肿瘤直接征象和肿瘤累及范围,三者间差异具有统计学意义(P值均<0.05).注药25 s时肿瘤强化最明显,表现为肝总管管壁环行增强、增厚、管腔局部狭窄或完全闭塞,三维图像呈模拟染色体样表现,并可观察到病变远、近端胆管内播散结节.结论 MSCT在注射对比剂后25 s扫描,病变增强最明显;三维重组图像可观察胆管的直接征象和受累范围.

Acute Occlusion of Self-Expandable Metallic Stents of the Bile Duct

Background: Self-expandable metallic stents (SEMS) are useful for the treatment of malignant biliary obstruction.The endoscopic and percutaneous techniques are well established with a high success rate. However, SEMS are sometimes occluded within very short periods. Aim: To identify frequency and causes of acute occlusion of SEMS within ten days after insertion. Patients and Methods: The medical records of 170 patients with malignant obstruction of the bile duct since October 1993 to April 2004 were reviewed. 81 patients underwent transhepatic stent placement and 89 patients underwent stents placement endoscopically. In 123 patients, the cholangiograms were obtained via the transient external drainage catheter inserted in the SEMS. Occlusion was diagnosed when bile duct occlusion was revealed by cholangiogram or cholangitis was occurred. Results: In 16 patients (9.4%) of 170 patients, SEMS were occluded within 10 days after insertion. 15 patients was diagnosed by cholangiogram and one patient was diagnosed by cholangitis. Periods of acute obstruction from insertion were 2 to 9 days (median 5 days). Causes of acute obstruction were edema in 12 patients, debris in 2 patients, and coagula in 2 patients respectively. Mechanical cleaning or washing via nasobiliary tube were effective for obstructions due to debris or coagula. At the initial period of this study, the patient with edema underwent second stent insertion (n = 4) or balloon dilation (n = 1). However, at the late period of this study, the patients were treated conservatively and obstruction improved from 8 to 19 days. Balloon dilation before SEMS insertion could not prevent acute obstruction. Conclusion: Acute obstructions were occurred in 9.4% of SEMS. Although edema is the most common causes of acute obstruction, the conditions improved conservatively without inserting the second stents. Background: Self-expandable metallic stents (SEMS) are useful for the treatment of malignant biliary obstruction.The endoscopic and percutaneous techniques are well established with a high success rate. However, SEMS are sometimes occluded within very short periods. Aim: To identify frequency and causes of acute occlusion of SEMS within ten days after insertion. Patients and Methods: The medical records of 170 patients with malignant obstruction of the bile duct since October 1993 to April 2004 were reviewed. 81 patients underwent transhepatic stent placement and 89 patients underwent stents placement endoscopically. In 123 patients, the cholangiograms were obtained via the transient external drainage catheter inserted in the SEMS. Occlusion was diagnosed when bile duct occlusion was revealed by cholangiogram or cholangitis was occurred. Results: In 16 patients (9.4%) of 170 patients, SEMS were occluded within 10 days after insertion. 15 patients was diagnosed by cholangiogram and one patient was diagnosed by cholangitis. Periods of acute obstruction from insertion were 2 to 9 days (median 5 days). Causes of acute obstruction were edema in 12 patients, debris in 2 patients, and coagula in 2 patients respectively. Mechanical cleaning or washing via nasobiliary tube were effective for obstructions due to debris or coagula. At the initial period of this study, the patient with edema underwent second stent insertion (n = 4) or balloon dilation (n = 1). However, at the late period of this study, the patients were treated conservatively and obstruction improved from 8 to 19 days. Balloon dilation before SEMS insertion could not prevent acute obstruction. Conclusion: Acute obstructions were occurred in 9.4% of SEMS. Although edema is the most common causes of acute obstruction, the conditions improved conservatively without inserting the second stents.

Early Biliary Complications of Laparoscopic Cholecystectomy: Evaluation on T2-Weighted MR Cholangiography in Conjunction with Mangafodipir Trisodium-Enhanced T1-Weighted MR Cholangiography

Our aim was to assess preliminary experience with combined conventional T2-weighted and mangafodipir trisodium (MnDPDP)-enhanced T1-weighted MR cholangiography in evaluating early biliary complications of laparoscopic cholecystectomy. Conventional heavily T2-weighted MR cholangiography with MnDPDP-enhanced T1-weighted MR cholangiography and ERCP were performed in seven patients with high clinical suspicion of biliary complications after laparoscopic cholecystectomy. The final diagnoses of complications were classified according to the presence and degree of bile duct injury, bile leakage, and retained stones. The diagnoses on MR cholangiography were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 3), partial strictures of the common bile duct with bile leakage (n = 1), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). The final diagnoses at surgery (n = 2) and ERCP (n = 5) were as follows: complete transection and occlusion of the common bile duct with bile leakage (n = 2), partial strictures of the common bile duct with bile leakage (n = 2), cystic duct leakage (n = 1), partial ligation of an aberrant right hepatic duct (n = 1), and hemorrhage without biliary complication (n = 1). MR cholangiography accurately yielded the same findings as the final diagnoses, except in one case with partial stricture of the bile duct with bile leakage (overdiagnosed as complete occlusion on MR cholangiography). Combined conventional T2-weighted and MnDPDP-enhanced T1-weighted MR cholangiography may eliminate the use of other studies for the imaging of biliary complications after cholecystectomy if this preliminary data can be verified in a larger study.

Bilioenteric Reconstruction for Small Bile Ducts Without Mucosa-to-Mucosa Alignment

Biliary reconstruction of the small bile duct is difficult, and bilioenteric reconstruction without mucosa-to-mucosa alignment would be a simple and useful maneuver in this situation; however, the long-term results of this surgical technique remain to be evaluated. To evaluate the usefulness of bilioenteric reconstruction without mucosa-to-mucosa alignment from the standpoint of the long-term results. Retrospective review. University hospital. Bilioenteric reconstruction without mucosa-to-mucosa alignment was performed in 17 patients at our institution. Six patients had malignancy, and 11 were liver transplant recipients from a living donor. Clinical records, blood chemistry data, and findings from dynamic computed tomography. Among the 17 patients, 4 died of recurrent malignant disease, and 3 died of thrombosis, brain hemorrhage, and pneumonia, respectively. During the follow-up (median, 41.2 months) of the remaining 10 patients, cholangitis occurred in 2 (1 episode in each), and anastomotic leakage from the hepaticojejunostomy performed by the standard method for other thicker ducts developed in 1. There were no other anastomosis-related complications. Dynamic computed tomography performed 2.4 to 62.7 months (median, 34.4 months) after the operation showed no bile duct dilatation in any of the 10 cases. Long-term patency of the small bile ducts after bilioenteric reconstruction without mucosa-to-mucosa alignment was demonstrated. Thus, this technique is useful for the reconstruction of small bile ducts, especially in patients with poor liver function in whom even minimal additional reduction in the volume of functioning liver due to occlusion of a small bile duct would be acceptable.

Pathogenesis and outcome of biliary atresia: current concepts.

Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring within the first 3 months of life. Bile flow is impaired, and patients have conjugated hyperbilirubinemia, acholic stools, and hepatomegaly. Overall, 1 in 2,500 live births is affected with a neonatal cholestatic disorder (1). The two most common causes of neonatal cholestasis are biliary atresia and idiopathic neonatal hepatitis, accounting for up to 50% to 70% of cases. Other causes include a variety of neonatal infections (viral, toxoplasmosis, syphilis, bacterial), metabolic and genetic diseases, progressive familial intrahepatic cholestatic disorders (PFIC), paucity of interlobular bile duct disorders (e.g., Alagille syndrome), choledochal cyst, ischemia–reperfusion injury, association with parenteral nutrition administration, and other conditions (Table 1). Despite clinical improvement after the portoenterostomy procedure, approximately 70% to 80% of children with biliary atresia will eventually require liver transplantation; thus, biliary atresia alone accounts for almost 50% of all liver transplants performed in children (1). It should be noted that $77 million is spent each year in the United States on liver transplantation for children and the ensuing hospitalizations (2). This sum of money covers 0.2% of total health care expenditures related to children, even though these children represent 0.0006% of the total pediatric population. Importantly, this disproportionate expenditure for liver transplantation in children could be cut in half if improved therapies for biliary atresia were developed that could abrogate or further delay the need for liver transplantation. Remarkably, little is known about the etiopathogenesis of biliary atresia; consequently, there has been slow progress in developing improved therapies or preventative strategies during the past decade. The purpose of this review is to summarize recent advances in the diagnosis and management of biliary atresia, examine the clinical outcome, describe the evolving theories of the etiology and pathogenesis of this disorder, and highlight gaps in our current knowledge.

Unique reciprocal changes of hepatocellular membrane transporter expression and fluidity in rats with selective biliary obstruction

Background and aims: The localized occlusion of bile ducts by intrahepaticlithiasis and intrahepatic neoplasms dose not cause severe jaundice, although the reason is unclear. The aim of this study was to clarify the molecular change of the liver in partial cholestasis, especially with respect to transporter expression (Mrp2, Mrp3, Bsep, P-gps) and membrane fluidity. Methods and results: After 3 days of selective bile duct ligation in Sprague–Dawley rats, the obstructed lobe (OL) and non-OL were analyzed. Canalicular and sinusoidal membrane fluidity were decreased in the OL compared with the non-OL. Mrp2 protein expression was significantly lower in the OL (by 62.9±6.9%) when compared with the non-OL. Mdr1b and Mdr2 mRNA were up-regulated in the OL when compared with the non-OL. Interestingly, Mrp3 protein and mRNA were induced in both the non-OL and OL of rats without hyperbilirubinemia. Conclusions: It seems that the reduction of membrane fluidity in the OL is a local response to localized cholestasis, while the induction of Mrp3 observed in both the OL and non-OL may be a response of the whole liver to localized impairment of bile secretion, although the regulatory mechanism is yet to be established.

Liver glutathione concentrations in dogs and cats with naturally occurring liver disease.

To determine total glutathione (GSH) and glutathione disulfide (GSSG) concentrations in liver tissues from dogs and cats with spontaneous liver disease. Liver biopsy specimens from 63 dogs and 20 cats with liver disease and 12 healthy dogs and 15 healthy cats. GSH was measured by use of an enzymatic method; GSSG was measured after 2-vinylpyridine extraction of reduced GSH. Concentrations were expressed by use of wet liver weight and concentration of tissue protein and DNA. Disorders included necroinflammatory liver diseases (24 dogs, 10 cats), extrahepatic bile duct obstruction (8 dogs, 3 cats), vacuolar hepatopathy (16 dogs), hepatic lipidosis (4 cats), portosystemic vascular anomalies (15 dogs), and hepatic lymphosarcoma (3 cats). Significantly higher liver GSH and protein concentrations and a lower tissue DNA concentration and ratio of reduced GSH-to-GSSG were found in healthy cats, compared with healthy dogs. Of 63 dogs and 20 cats with liver disease, 22 and 14 had low liver concentrations of GSH (micromol) per gram of tissue; 10 and 10 had low liver concentrations of GSH (nmol) per milligram of tissue protein; and 26 and 18 had low liver concentrations of GSH (nmol) per microgram of tissue DNA, respectively. Low liver tissue concentrations of GSH were found in cats with necroinflammatory liver disease and hepatic lipidosis. Low liver concentrations of GSH per microgram of tissue DNA were found in dogs with necroinflammatory liver disease and cats with necroinflammatory liver disease, extrahepatic bile duct occlusion, and hepatic lipidosis. Low GSH values are common in necroinflammatory liver disorders, extrahepatic bile duct occlusion, and feline hepatic lipidosis. Cats may have higher risk than dogs for low liver GSH concentrations.

Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary biliary fibrosis.

The trisubstituted methylxanthine derivative pentoxifylline inhibits hepatic stellate cell proliferation and collagen synthesis in vitro. The antifibrotic effect of pentoxifylline in a suitable in vivo model of chronic liver fibrogenesis remains to be tested. Groups of adult rats (n=20-23) received oral pentoxifylline at a dose of 8 mg/kg/day from week 1 to week 6, and 16 mg/kg/day from week 1 to week 6 or week 4 to week 6 after complete bile duct occlusion. Animals who underwent sham operation that received 16 mg/kg/day pentoxifylline and untreated rats with bile duct occlusion alone served as controls. After six weeks, animals were sacrificed and parameters of fibrogenesis determined. Bile duct occlusion caused portal cirrhosis with a 10-fold increased hepatic collagen content in the absence of inflammation or necrosis. This was accompanied by an 11-fold elevated serum aminoterminal procollagen III peptide (PIIINP). The drug induced a dramatic eightfold downregulation of procollagen I mRNA, and suppression of the fibrogenic factors transforming growth factor beta1 and connective tissue growth factor by 60-70%. However, profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was increased twofold, resulting in only a moderate decrease in liver collagen, fibrosis score, and PIIINP. We conclude that targeting pentoxifylline to the fibrogenic cells, thereby avoiding upregulation of TIMP-1, could become a potent antifibrogenic tool in chronic liver disease.

Technical considerations to maintain a low frequency of postoperative biliary stent-associated infections.

In patients with malignant biliary obstruction, preoperative biliary tract manipulation and stent drainage has been associated with increased infectious complications and mortality. Between October 1996 and September 2000, 36 patients underwent bilioenteric anastomosis by a single surgeon. Diagnoses included pancreatic and other periampullary cancers (67%), benign obstruction (14%), hilar cholangiocarcinoma (8%), and other malignancies (11%). Preoperative bile duct manipulation had been done in 72%, and a biliary stent had been placed in 58%. Two-thirds of patients underwent major resection and the remainder were treated with internal biliary bypass. All patients had received preoperative bowel cleansing and perioperative antibiotics. Bile ducts were left clamped after incision until anastomotic completion to avoid biliary spillage, and drains were generally not placed. Intraoperative bile cultures were positive in 73%. This was strongly linked to the presence of a stent ( P = 0.0004), or prior duct manipulation ( P = 0.002). There were 3 postoperative, unrelated deaths in patients after palliative bypass (overall mortality rate, 8.3%). Postoperative infections occurred in 7 patients (19%), of which three were due to a similar organism. There was one biliary leak, no pancreatic leak, and no intraabdominal abscess. Appropriate preoperative antibiotic coverage, preventing intraoperative peritoneal bile contamination through temporary bile duct occlusion, and avoiding routine drain placement, are strongly suggested for patients in whom preoperative biliary manipulation has taken place.

Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment

Background / Aims : Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and/or extrahepatic bile ducts. Methods : In a prospective study of 106 patients treated for up to 13 years with ursodeoxycholic acid, the development of major bile duct stenoses and the efficacy of endoscopic measures have been evaluated. Results : Of 106 patients ten had major duct stenoses at entry, and during a median follow-up period of 5.0 years another 43 developed a dominant stenosis. Fifty-two patients with dominant stenoses were treated endoscopically by repeated balloon dilatations and five patients were temporarily stented. Complications of endoscopic procedures were pancreatitis (5.2%), bacterial cholangitis (3.3%) and bile duct perforation (0.5%). Five years after the first dilatation of a dominant stenosis the Kaplan–Meier survival rates free of liver transplantation were 100% in stage 2, 72% in stage 3 and 50% in stage 4 disease. The actuarial survival free of liver transplantation of the whole group at 3, 5 and 7 years were 0.987, 0.935 and 0.891 and the corresponding survival rates predicted with the Mayo multicenter survival model were 0.860, 0.775 and 0.737 ( P <0.001). Conclusions : In advanced disease, occlusion of major bile ducts with time occurs in the majority of patients. Endoscopic opening of dominant stenoses is effective and appears to be a valuable addition to the medical treatment of such patients.

Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen α1(I) and TIMP-1

Background/Aims : Silymarin reduces hepatic collagen accumulation by 35% in rats with secondary biliary cirrhosis. The aim of the present study was to explore its antifibrotic mechanism. Methods : Thirty female adult Wistar rats were allocated to (1) bile duct occlusion, (2) bile duct occlusion and oral silymarin at 50 mg/kg per day, and (3) sham operation and oral silymarin at 50 mg/kg per day. Steady-state mRNA levels for procollagen α1(I), tissue inhibitor of metalloproteinases-1 (TIMP-1), and transforming growth factor (TGF) β1 were determined by multi-probe ribonuclease protection assay. Results : After 6 weeks of bile duct occlusion, liver collagen content was increased 12-fold, when compared with the sham-operated controls. These animals displayed 17-, 6.5- and 16-fold higher transcript levels for procollagen α1(I), TIMP-1 and TGF β1 ( P <0.01). Silymarin downregulated elevated procollagen α1(I), TIMP-1 and TGF β1 mRNA levels by 40–60% ( P <0.01). These lowered hepatic profibrogenic transcript levels correlated with decreased serum levels of the aminoterminal propeptide of procollagen type III. Conclusions : Silymarin suppresses expression of profibrogenic procollagen α1(I) and TIMP-1 most likely via downregulation of TGF β1 mRNA in rats with biliary fibrosis. The serum procollagen type III propeptide level mirrors profibrogenic mRNA expression in the liver.

Interventional radiologic procedures in liver transplantation.

Postoperative biliary and vascular complications contribute significantly to morbidity and mortality in liver transplantation. Interventional radiologists are an integral part of the multidisciplinary team necessary for optimizing the management of these complications. During a 15-year period, 39 cadaveric and 25 living related liver transplantations were performed at the Chang Gung Memorial hospital, Taiwan. Of 64 liver transplant recipients, 9 (3 adult and 6 pediatric) underwent 13 interventional radiological procedures for the treatment of biliary sludge-casts (n = 2), bile duct occlusion or stenosis (n = 2), hepatic veins thrombosis (n = 1), hepatic veins stenosis (n = 1), portal vein stenosis with splenorenal shunting (n = 1), biloma (n = 1), and infected fluid collection or ascites (n = 4). Antegrade or retrograde interventional approach was used to successfully treat all biliary complications, and all percutaneous drainage procedures were effective in the control of intra-abdominal fluid collections. Portal vein stenosis was treated by balloon dilatation, and the associated splenorenal shunt was closed by metallic coil embolization via transhepatic catheterization of the portal vein. Hepatic vein stenosis was effectively treated by balloon dilatation and expandable metallic stent deployment via transfemoral and jugular venous approaches, respectively. Hepatic vein thrombosis was only partially lysed by transvenous streptokinase administration, and surgical thrombectomy was needed to achieve complete recanalization. The total success rate of the interventional procedures was 92 % with no procedure-related complications. The overall survival rate in this series is 89 %, and all patients who underwent living related liver transplantation maintain to date a 100 % survival rate. We can conclude that interventional radiological procedures are very useful for managing biliary and vascular complications after liver transplantation. These techniques provide a cure in most situations, thus obviating the need for further surgical intervention or re-transplantation.

Effects of blood volume restitution following a portal hypertensive–related bleeding in anesthetized cirrhotic rats

The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension–related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n = 17), moderate transfusion (50% of expected blood loss, 5 mL, n = 11), and total transfusion (100% of expected blood loss, 10 mL, n = 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group (↓12 ± 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP (↓65 ± 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 ± 1.5 g) than in groups given 5 mL (15.9 ± 2.8 g; P < .05) or no transfusion (13.2 ± 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival. (HEPATOLOGY 2001;33:821-825.)

Proliferating Bile Duct Epithelial Cells Are a Major Source of Connective Tissue Growth Factor in Rat Biliary Fibrosis

Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta1 (TGF-beta1) and thus a potential target for antifibrotic treatment strategies. CTGF is up-regulated in disorders such as atherosclerosis, scleroderma, and fibrosis of kidneys and lungs. We investigated the temporospatial expression patterns of CTGF and TGF-beta1 mRNA in rat livers with acute fibrogenesis (after a single dose of CCl(4)) and with advanced fibrosis (6 weeks after complete bile duct occlusion). Multiprobe ribonuclease protection assay revealed increasing TGF-beta1 and CTGF mRNA levels 6 hours after injection of CCl(4), with peak levels after 72 hours. In biliary fibrosis TGF-beta1 and CTGF mRNA levels increased fourfold and sevenfold, respectively (P: < 0.001). In situ hybridization combined with cell-specific markers revealed CTGF transcripts in desmin-positive cells after a single dose of carbon tetrachloride, whereas no transcripts were found in normal livers. In biliary fibrosis, however, proliferating bile duct epithelial cells were the predominant source of CTGF mRNA. We conclude that in rat liver fibrogenesis CTGF is up-regulated in close association with TGF-beta1 and that, contrary to a previous report, not solely hepatic stellate cells but activated bile duct epithelial cells are the main source of this profibrogenic factor.

Percutaneous transpapillary extraction of biliary calculi for symptomatic choledocholithiasisafter unsuccessful endoscopic treatment

Evaluation of a percutaneous transhepatic treatment of symptomatic choledocholithiasis in bile ducts that cannot be reached with the endoscope. From January 1996 to August 2000 a transhepatic extraction of biliary calculus was performed in four patients. Endoscopic retrograde cholangiography (ERC) was not successful in any of the cases. Clinical symptoms were icterus in four cases, additional cholangitis or colics in two cases. First, a balloon dilation of the papilla was performed by a percutaneous transhepatic approach. For removal of bile duct stones, occlusion catheters and Dormia baskets were used. Technical success was defined as complete removal of bile duct stones. Clinical success was defined as normalization of cholestasis and inflammation parameters. In the follow-up an ultrasound examination was performed and blood samples were taken for control of cholestasis parameters. In all four cases treatment was technically and clinically successful. For complete removal of biliary calculus a second intervention was necessary in two cases. In each case an internal to external drainage was left over a mean of 7 days (3-13 days). In the mean follow-up of 30.5 months (6-50 months) all patients had persistent relief of symptoms. No further interventions were necessary. No complications were present. Percutaneous transpapillary extraction of biliary calculus is an effective alternative to surgery in patients with bile ducts, that cannot be reached with the endoscope.