A microcholangiographic study of liver disease models in rats

RATIONALE AND OBJECTIVES: Rats develop hepatobiliary injury due to small bowel bacterial overgrowth (SBBO) that, at specimen, resembles cholangiography sclerosing cholangitis. To better visualize the smaller bile ducts, we used microcholangiography to determine the spectrum of biliary lesions in this and five other models of liver disease. METHODS: The models studied were as follows: (1) Surgically created jejunal, self-filling blind loops induce SBBO. (2) Intraperitoneal injection of a bacterial cell wall polymer, peptidoglycan-polysaccharide (PG-PS), causes granulomatous hepatitis. (3) Intraperitoneal injection of endotoxin (lipopolysaccharide) causes sinusoidal congestion and shock. (4) Bile duct ligation induces bile duct proliferation. (5) Alpha-naphthyl-isothiocyanate (ANIT) induces bile duct proliferation. (6) Carbon tetrachloride (CCl4) causes fibrosis and cirrhosis. Warmed barium sulfate, gelatin, and saline were injected in the extrahepatic bile duct. Liver slices (2 mm) underwent microradiographic techniques, and images were correlated with histology. RESULTS: Rats with SBBO had irregular and dilated extrahepatic bile ducts with thickened walls. Rats treated with endotoxin and CCl4 had normal microcholangiograms. Bile duct proliferation was identified following ANIT and bile duct ligation. Rats given PG-PS demonstrated irregular intrahepatic bile ducts. Microcholangiograms following SBBO and PG-PS showed similarities including focal ductal dilatation, narrowing, proliferation, and destruction. CONCLUSION: Various models of liver injury induce characteristic cholangiographic appearances. Microcholangiography is useful in examining biliary tract lesions and complements histology.     

Circulating activated endothelial cells in sickle cell anemia

BACKGROUND: The vascular wall participates in the pathogenesis of sickle cell disease. To determine whether the endothelium is activated in this disease, we studied the number, origin, and surface phenotype of circulating endothelial cells in patients with sickle cell anemia. METHODS: We used immunohistochemical examination of buffy-coat smears to enumerate circulating endothelial cells, and we evaluated the surface phenotype by applying preparations of circulating endothelial cells. An immunofluorescence microscopy panel of antibodies was used, including a specific anti-endothelial-cell antibody, P1H12. RESULTS: Mean (+/-SD) numbers of circulating endothelial cells in normal blood donors, patients with sickle cell trait, and patients with hemolytic anemias not due to hemoglobin S were 2.6+/-1.6, 3.0+/-2.6, and 2.0+/-0.8 per milliliter of whole blood, respectively. Patients with sickle cell anemia who presented with acute painful episodes had 22.8+/-18.2 circulating endothelial cells per milliliter of blood (P<0.001 for the comparison with normal donors), and patients with no such events within one month before or after blood sampling had 13.2+/-11.8 circulating endothelial cells per milliliter of blood (P=0.002 for the comparison with normal donors and P=0.019 for the comparison with patients with acute events). Serial observations of three patients showed a tendency toward higher levels of circulating endothelial cells at the onset of acute painful crises. The average viability of circulating endothelial cells was 66+/-30 percent. In patients with sickle cell anemia, regardless of clinical status, the circulating endothelial cells were predominantly microvascular in origin (CD36-positive), and most of the cells expressed four markers of endothelial-cell activation: intercellular adhesion molecule 1, vascular-cell adhesion molecule 1, E-selectin, and P-selectin. CONCLUSIONS: Our studies suggest that the vascular endothelium is activated in patients with sickle cell anemia, regardless of the patients' clinical status. Adhesion proteins on activated endothelial cells may have a role in the vascular pathology of sickle cell disease.     

Clinical evaluation of 99mTc-pyridoxylideneglutamate for hepatobiliary scanning

Clinical evaluation of hepatobiliary scanning using 99mTc-PG was done in twenty normal volunteers and eighty-three patients with liver and biliary tract disease. Satisfactory images of the biliary tract were obtained using small dosages of this agent. In normal humans, the agent reached the liver in 5 minutes, and the common bile duct, gallbladder, and duodenum in 10 to 20 minutes. The gallbladder was not visualized when the cystic duct was obstructed in patients with acute and chronic cholecystitis. In patients with partial common bile duct obstruction, a distended duct was visualized and there was delay in transit of radioactivity into the duodenum. With complete common bile duct obstruction, no radioactivity was seen in the biliary or gastrointestinal tracts up to 24 hours after injection. Hepatocellular disease was characterized by delayed liver clearance and delayed visualization of the biliary and gastrointestinal tracts. There were no toxic or other untoward effects in any patients.     

An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer

Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.     

Immunohistochemical localization of hepatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia

Nitric oxide (NO) generated from L-arginine and molecular oxygen by nitric oxide synthase (NOS) has been shown to influence hepatocellular function and pathology in response to ischemia and certain hepatotoxins. In the present study, we examined the liver of a transgenic line of sickle cell mice for hepatocellular injury and localization of two isoforms of NOS, the endothelial constitutively expressed isoform (EcNOS) and the inducible isoform (iNOS) by immunohistochemistry. Diffuse expression of EcNOS was observed in hepatocytes of control and sickle cell animals maintained under room air conditions. In contrast, iNOS was observed only in the sickle cell mice, well-localized to hepatocytes surrounding the central veins of the lobules. When normal mice were exposed to hypoxic conditions for 4 to 5 days, iNOS immunostaining appeared de novo in a patchy distribution throughout the liver lobules. In the sickle cell mice, hypoxia appeared to increase the subjective intensity of pericentral staining of iNOS. Liver histology was normal in the sickle cell mice maintained under room air conditions, but showed multifocal areas of necrosis when sickling was exacerbated by chronic hypoxic conditions. However, a pericentral zone of preserved architecture was present, corresponding to the region of iNOS staining. We postulate that pericentral induction of iNOS under ambient conditions occurs in transgenic sickle cell mice in response to particularly intense hypoxic conditions near the central veins of the liver. Increases in NO synthesis may occur in this region, which would serve to protect these cells from ischemic damage either directly or by maintaining blood flow. These findings could be relevant to liver pathophysiology in patients with sickle cell disease.     

Endoscopic biliary manometry in cholecystectomized patients with and without choledocholithiasis

BACKGROUND/AIMS: Direct study of the function of the sphincter of Oddi became possible recently with the advent of endoscopic manometry. A dysfunction of the bilio-pancreatic sphincter apparatus has been implicated in some bilio-pancreatic disorders. The purpose of this study was to examine the relation between dysfunction of the sphincter of Oddi and the formation of common bile duct stones. METHODOLOGY: Endoscopic biliary manometry was performed on 45 cholecystectomized patients. Endoscopic retrograde cholangiography showed choledocholithiasis in 26 patients while 19 patients were free of common bile duct stones. Nine healthy subjects served as controls. RESULTS: Manometric investigation showed a significant increase in the percentage of retrograde phasic contractions of the sphincter of Oddi (SO) in patients with choledocholithiasis compared to the control group (p < 0.05). Also, a significantly higher frequency of SO phasic contractions was found in the group of patients with choledocholithiasis when compared to the cholecystectomized group without common bile duct stones (p < 0.05), but there was no difference when compared with the control group. Markedly increased SO basal pressure was found in 5 patients with choledocholithiasis as well as in one cholecystectomized patient without choledocholithiasis (greater than x + 3SD). However, the SO basal pressure, phasic SO pressure, amplitude and duration of the phasic contractions as well as the choledochal pressure did not differ significantly between the groups. CONCLUSIONS: This study demonstrates manometric abnormalities in the SO of patients with choledocholithiasis which suggests that SO dysfunction and pathophysiological mechanisms are related to the formation of common bile duct stones.     

Surgical treatment of cicatricial biliary strictures

BACKGROUND/AIMS: Cicatricial biliary strictures are usually associated with high morbidity and mortality rates, frequently related to technical difficulties of their surgical repair, mainly in hilar lesions. Interference with bile duct blood supply during surgical attempts for correction is a major factor for unsuccessful results. The aim of this study is to evaluate, after an extended follow-up period, the results obtained with a modified technique for surgical correction of cicatricial biliary strictures. METHODOLOGY: The medical records of 57 patients surgically treated for cicatricial biliary strictures between January 1984 and July 1995 were reviewed and the immediate and long term results retrospectively analyzed. Patients consisted of 46 females and 11 males. The average age was 43 years. The etiology of the biliary lesion was: cholecystectomy alone (23); cholecystectomy with duct exploration (8); T tube CBD drainage (6); Biliary-enteric anastomosis stricture (16); choledochoplasty (2) and trauma (2). In 28 cases (49.1%) the stricture was located in the upper third of the bile duct, in 28 (49.1%) in the middle third and in one case (1.7%) it was low. All patients were submitted to longitudinal Roux-en-Y hepaticojejunostomy with mucosa apposition after dissection of the anterior aspect of the biliary tract. No transanastomotic stents were used. RESULTS: Ten patients (17.5%) presented 11 postoperative complications: biliary fistula (4), duodenal fistula (1), wound infection (5), and acute pancreatitis (1). Average hospital stay was 11 days and there were no postoperative mortalities. The follow-up study was possible in 54 patients and ranged from one to ten years, with an average of 2.9 years. Four patients of 28 (14%) with hilar lesions developed stricture recurrence and cholangitis episodes, whereas no patients bearing lesions below the biliary junction had such complications. CONCLUSION: Roux-en-Y hepaticojejunostomy with mucosa apposition without transanastomotic stent performed after minimal dissection of the biliary duct, thus avoiding major interference with the bile duct blood supply, is a safe and efficient method for the surgical repair of cicatricial biliary strictures. Using this technique excellent results can be obtained in the lesions below the biliary junction and acceptable results may be achieved in patients with hilar lesions.     

Cytotoxicity to isolated rabbit hepatocytes by lymphocytes from children with liver disease

A test of lymphocyte cytotoxicity for isolated adult rabbit hepatocytes has been performed using lymphocytes from 40 children with acute or chronic liver disease. Positive cytotoxicity was not observed in 26 children without liver disease and rarely in 13 children with disease affecting primarily the biliary tract. Temporarily positive tests were found in those with acute hepatocellular disease, but tests remained positive in patients with chronic active hepatitis, while liver function tests remained abnormal. Persistently positive test occurred in those with liver disease associated with alpha-antitrypsin deficiency. Such altered immunoresponsiveness could be an important pathogenic mechanism leading to chronic liver disease in childhood.     

Intra-bile duct growth of hepatocellular carcinoma: value of biliary dilatation on CT

In order to evaluate the usefulness of CT in demonstrating biliary invasion by hepatocellular carcinoma, 191 surgically proved cases were studied. Among 191 CT scans performed before surgery, six (3%) showed biliary dilatation. Pathological biliary invasion was found in eight cases (4%). Of these eight cases, four cases (50%) showed biliary dilatation on CT. In six cases with biliary dilatation on CT, pathological biliary invasion was revealed in four cases (67%). In two cases, the large (> or = 6cm) encapsulated tumors located in the hepatic hilum dilated the intrahepatic bile duct without intraductal tumor growth. We concluded that biliary dilatation on CT cannot be a sign of biliary invasion by hepatocellular carcinoma.     

Current problems with intrahepatic bile duct stones in Japan--congenital biliary malformations as a cause

BACKGROUND/AIMS: In patients with primary intrahepatic bile duct stones, strictures of the biliary duct are often present, but the relationship between these strictures and the formation of the stones remains controversial. Intrahepatic bile duct carcinoma in association with intrahepatic bile duct stones has recently been reported. The present study attempted to ascertain whether bile stasis induced by congenital biliary strictures is the basis for the formation of stones and occurrence of carcinoma. MATERIALS AND METHODS: We analyzed the location of strictures in 58 patients with strictures in the upper portion of the biliary tract including 38 patients with intrahepatic bile duct stones and 9 with intrahepatic bile duct carcinoma. The cell cycle of epithelial cells from the intrahepatic bile duct were analyzed with using proliferating cell nuclear antigen, which is a immunohistochemical staining method. RESULTS: Fifty six of 58 patients had congenital cystic dilatation of the common bile duct (two infant type and 54 adult type). Thirty eight patients had intrahepatic bile duct stones proximal to the strictures at the hepatic hilum. The location of the strictures were classified into four types. Nine patients had intrahepatic bile duct carcinoma and eight of the 9 carcinomas coexisted with intrahepatic bile duct stones. In the nine patients with intrahepatic bile duct carcinoma, the expression of proliferating cellular nuclear antigen (PCNA) in the carcinoma and the normal bile duct epithelium adjacent to the carcinoma was higher than that of patients with hepatocellular carcinoma without anomaly of the biliary duct. CONCLUSION: Considering the location of the strictures and clinical features, the strictures may have been formed congenitally. Furthermore, adult type cysts of the common bile duct with strictures in the upper portion of the biliary tract are thought to be the basis for the formation of primary intrahepatic bile duct stones. The most appropriate treatment for intrahepatic bile duct stones is thus suggested to be removal of the affected hepatic segment including the region of strictures, combined eventually with hepaticoenterostomy.     

Correlative imaging of the liver and hepatobiliary system

Many imaging techniques can be used to assess the liver and hepatobiliary system. Each modality has individual strengths and limitations, which usually vary depending on the specific clinical situation. This review discusses several specific common clinical situations where imaging of the liver and biliary system is necessary and describes the various imaging options. Space-occupying liver lesions are discussed, and particular attention is paid to the assessment of liver metastasis, hepatoma, and incidentally discovered liver lesions such as hemangioma, adenoma, and focal nodular hyperplasia. The value of ultrasound, computed tomography, magnetic resonance imaging, and scintigraphic techniques in this patient population is described. Isolated sulfur colloid hepatic scintigraphy is not of great value in the evaluation of these patients. Therefore, this review describes in some detail the value of physiological liver scintigraphy, including gallium and iminodiacetic acid (IDA) scanning as well as dynamic flow imaging of the liver such as hepatic artery perfusion scintigraphy and tagged red cell scintigraphy. Imaging of the biliary tree also is described. The roles of ultrasound and scintigraphy are compared and contrasted as related to the diagnosis of acute cholecystitis, common duct obstruction, and postoperative complications.     

Screening patients with celiac disease for primary biliary cirrhosis and vice versa

BACKGROUND: An association between celiac disease and primary biliary cirrhosis has been reported in a few cases, mainly as individual case reports. OBJECTIVES: To screen adult patients with celiac disease for primary biliary cirrhosis and patients with primary biliary cirrhosis for intestinal celiac involvement. METHODS: The celiac group consisted of 336 adults (218 women and 118 men; mean age, 36 yr; range 18-74 yr) with celiac disease diagnosed by serological and histological tests, 38 with newly diagnosed celiac disease and 298 with previously diagnosed celiac disease who were consuming a gluten-free diet. The mean follow-up period was 6 yr (range, 1-16 yr). Liver function parameters and autoantibody levels were determined, and, when indicated, histological tests were performed. The biliary cirrhosis group consisted of 65 subjects (58 women and seven men) (mean age, 59 yr; range, 35-67 yr) with primary biliary cirrhosis diagnosed 1-17 years previously (mean, 7 yr) on the basis of the usual biochemical, serological, and histological criteria. Antigliadin and antiendomysium antibody levels were determined, and two biopsy specimens from the distal duodenum obtained during endoscopy were evaluated. RESULTS: In patients with celiac disease, impairment of liver function was frequently found at diagnosis (16 of 38, or 44%), but primary biliary cirrhosis was diagnosed in only one case. In patients with primary biliary cirrhosis, no cases of celiac disease, as currently defined, were found. CONCLUSIONS: Our findings indicate that celiac disease and primary biliary cirrhosis are rarely associated and support the hypothesis that the intestinal lesions per se are not responsible for the liver disease.     

Therapy of hepatocellular carcinoma

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patient. In patients with small and solitary lesions, resection, liver transplantation and in some cases percutaneous ethanol injection (PEI) can be curative. In more advanced stages of the disease with larger or multiple lesions, PEI and/or transarterial chemotherapy with or without embolization (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radiotherapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs should be individualized, frequently involving a combination of therapeutic modalities. In contrast to the earlier dismal prognosis, for most HCC patients there is today a therapeutic strategy that results in prolongation of life and in some cases even cure.     

Traumatic neuroma with biliary duct obstruction after orthotopic liver transplantation

BACKGROUND: Traumatic neuromas may develop after injury to nerve fibers encased in Schwann cells. The incidence of symptomatic neural tumors appears to be low after orthotopic liver transplantation (OLT). Only two cases of biliary stricture caused by infiltrating traumatic neuroma have been described previously. METHODS: We report two new cases of biliary tract obstruction after OLT that failed to respond to percutaneous balloon dilatation and were corrected by a resection of the bile duct stricture followed by biliary reconstruction with a Roux-en-Y jejunal loop. RESULTS: The first patient (17 months after OLT) had a traumatic neuroma appearing as a distinct mass with nerve bundles confirmed histologically; the traumatic neuroma in the second patient (5 months after OLT) was a nerve stump with infiltration of nervous elements in the bile duct. Both patients recovered without complications. CONCLUSIONS: Traumatic neuromas should be considered in the differential diagnosis of late biliary stricture after OLT, in particular when not responding to percutaneous dilatation or stenting.     

Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma

In an attempt to clarify the role of oval cells in the emergence of hepatocellular carcinoma, we fed rats a choline-free diet containing 0%, 0.05% or 0.1% ethionine. The incidence and nature of premalignant and malignant hepatic lesions were then related to the degree of oval cell proliferation. Intake of choline-free diet alone for up to 12 mo was associated with minimal oval cell proliferation; cholangiofibrosis, hepatocellular nodules and hepatocellular carcinoma were observed in 55%, 23% and 14% of the animals, respectively. When rats were given the choline-free diet with 0.05% ethionine, proliferation of oval cells was more pronounced; after a 6- to 12 mo feeding period, cholangiofibrosis (57%) was again observed. However, hepatocellular nodules (91%) and hepatocellular carcinoma (74%) were the most common lesions seen with this feeding regimen. Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue. Most of these animals died before they had consumed the choline-free diet with 0.1% ethionine for 12 mo. Rats in this group (96%) exhibited large and numerous cholangiofibrotic lesions, but hepatocellular nodules and carcinoma were not detected. In all animals of each experimental group, hyperplastic bile duct cells in areas of cholangiofibrosis and oval cells were positive for cytokeratin 19, an intermediate filament protein present only in bile duct cells in normal liver. Hepatocellular nodules and hepatocellular carcinoma were invariably negative for cytokeratin 19. We interpret these findings to suggest that oval cells are not involved in the histogenesis of hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

What is the association of primary sclerosing cholangitis with sex and inflammatory bowel disease in Turkish patients?

BACKGROUND/AIMS: In the Western world, primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with inflammatory bowel disease (IBD), particularly chronic ulcerative colitis and, to a lesser degree, Crohn's disease. The goal of this study was to determine the prevalence of PSC in Turkish patients with IBD and chronic amebic colitis, a disease that is endemic in Turkey. METHODOLOGY: During a 10-year period, between 1986 and 1996, a total of 81 IBD (64 ulcerative colitis and 17 Crohn's disease) patients and 127 patients with chronic amebic colitis were seen and evaluated with radiologic, serologic, immunologic and pathologic tests. Whenever a clinical or biochemical finding suggested the presence of co-existent hepatic and/or biliary disease, the patient was further evaluated by liver biopsy, auto-antibodies and endoscopic retrograde cholangiopancreatography (ERCP) to determine whether they also had PSC or some other form of liver disease. As a disease control group, a total of 752 patients with clinical and/or laboratory evidence of pancreaticobiliary disease were also studied. In 86 of these 752 patients (10%), a primary disorder of the biliary tree was diagnosed by ultrasonography, computed tomography, peritoneoscopy, liver biopsy, ERCP and abdominal laparotomy. In addition, all 86 patients of the control group were evaluated endoscopically in order to determine whether they had any associated gastrointestinal condition of the upper or lower gastrointestinal tracts. After establishing final diagnoses of IBD, amebic colitis and PSC, these patients were evaluated with respect to their socio-economic status. A high protein diet (1.8 gram/kg/day) was administered to those patients with chronic amebic colitis and IBD during the active period of the disease. RESULTS: Of the 208 patients (81 with IBD and 127 with chronic amebic colitis), no cases of PSC were identified. Of the 86 patients in the control group with primary biliary tract disease, 45 had a biliary system malignancy, 14 had primary biliary cirrhosis (PBC), 16 had PSC, 3 had Caroli's disease, 6 had a common bile duct cyst, and 2 had gallbladder adenomatosis. All but 1 of the 16 patients with PSC were female. CONCLUSIONS: These data suggest that, in contrast to findings in Western Europe and the USA, in Turkey: 1) PSC is not regularly associated with idiopathic IBD; 2) most patients with PSC are female; 3) PSC accounts for only 18% of patients with a primary disorder of the biliary tree; 4) the incidence of small-duct primary sclerosing cholangitis is greater than that reported in the literature; and, 5) the incidence of IBD and PSC in Turkey is relatively lower than in other countries.     

Bile duct lesions in laparoscopic cholecystectomy--methods of reconstruction and results

From 1/1991 to 1/1997 a total of 18 patients with major biliary lesions after laparoscopic cholecystectomy were treated. Besides 4 biliary strictures (Bismuth III, Siewert II), which were found between 20 and 180 days after laparoscopic cholecystectomy, large defects (Siewert III, IV) of the proximal parts of the hepatic duct (Bismuth III, IV) occurred in the majority of cases (n = 14). Except for 3 intraoperatively realized lesions, diagnosis was made during the first 3 weeks. Subsequent reinterventions resulted in a high morbidity rate and the need of further procedures to establish definitive biliary reconstruction. Selection criteria of the technique used for repair were the extension of the biliary lesion and the exposure of the distal stump of the common bile duct. A small defect was treated by direct suturing protected by a t-tube (n = 1). Large defects and biliary strictures were reconstructed using either a Roux-en-Y bilio-digestive anastomosis (n = 7) or jejunal interposition (n = 10). The results suggest, that early repair of biliary lesions after laparoscopic cholecystectomy should be achieved. Besides the standard procedure of bilio-digestive anastomosis, reconstruction of major biliary lesions should be performed by jejunal interposition in selected cases.     

Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver

BACKGROUND/AIMS: Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown. METHODS: We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired. RESULTS: Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage. CONCLUSIONS: We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.     

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.     

Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion

BACKGROUND: Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion. METHODS: Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration. RESULTS: Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02). CONCLUSIONS: Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.