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Background: Complement protein C4d has been used as a marker of antibody mediated rejection in kidney allografts. C4d has been shown to be deposited also in chronic kidney allograft rejection, and frequently in acute liver allograft rejection. In chronic liver allograft rejection there is limited data of C4d positivity., Methods: 7 liver allografts explanted at retransplantation due to chronic rejection were examined for expression of C4d. Immunoperoxidase technique on frozen sections was used. The "zero" biopsies of the same livers at the first transplantation served as controls., Results: Expression of C4d was significantly increased in portal and central veins as well as in the portal stroma of the grafts with chronic rejection when compared to the expression at implantation of the graft., Conclusion: The complement system and anti-donor antibodies may contribute to the process of chronic allograft rejection in the liver.

High mobility group box 1 protein (HMGB1), a cytokine actively secreted by phagocytes and passively released from necrotic cells, is an inflammatory mediator in experimental hepatic ischemia/reperfusion injury. We characterized its expression in human liver transplantation. In 20 patients, in addition to systemic samples, blood was drawn from portal and hepatic veins during and after reperfusion to assess changes within the graft. Plasma HMGB1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured, and HMGB1 immunohistochemistry was performed on biopsies taken before and after reperfusion. Plasma HMGB1 was undetectable before reperfusion, and levels in systemic circulation peaked after graft reperfusion. At portal declamping, HMGB1 levels were substantially higher in the caval effluent [188 (80-371) ng/mL] than in portal venous blood [0 (0-3) ng/mL, P < 0.001]. HMGB1 release from the graft continued thereafter. HMGB1 levels were not related to TNF-alpha or IL-6 levels. HMGB1 expression was up-regulated in biopsies taken after reperfusion (P = 0.020), with intense hepatocyte and weak neutrophil staining. HMGB1 levels in hepatic venous blood correlated with graft steatosis (r = 0.497, P = 0.03) and peak postoperative alanine aminotransferase levels (r = 0.588, P = 0.008). Our results indicate that HMGB1 originates from the graft and is a marker of hepatocellular injury in human liver transplantation., ((c) 2008 AASLD.)

Background: Acute liver failure (ALF) is a significant cause of liver transplantation. We have previously reported that human herpesvirus-6 (HHV-6) was found in most livers of patients with ALF of unknown origin ending up with liver transplantation. In this study, we investigated the posttransplant HHV-6 infection of the liver graft in these patients., Methods: Thirty-two patients transplanted due to ALF were included in this retrospective study. Twelve of the 15 patients with unknown cause and four of 17 patients with a known cause of ALF had HHV-6 antigens in the explanted liver. Altogether, 18 patients had some pretransplant evidence of HHV-6. After transplantation, the patients were frequently monitored for the viruses, and biopsy histology was performed in every case of graft dysfunction. HHV-6 was demonstrated in liver tissue by immunohistochemistry., Results: During the follow-up of 6 months, hepatic HHV-6 infection was demonstrated in 9 of the 18 patients, at a mean 19 days (6-38 days) after transplantation. All patients with posttransplant HHV-6 showed graft dysfunction. In biopsy histology, seven out of these nine patients demonstrated viral infection, one of them also having CMV antigens in the liver. None of those patients without evidence of pretransplant HHV-6 showed HHV-6 in the posttransplant biopsies. Posttransplant HHV-6 was not treated and the virus had no effect on 1-year patient or graft survivals., Conclusion: Pretransplant hepatic HHV-6 infection of patients with ALF is a risk factor for posttransplant HHV-6 infection and liver dysfunction, but has no effect on 1-year graft or patient survival.

Objective: Liver cirrhosis and its complications constitute a daily clinical challenge. The diagnosis of cirrhosis is traditionally established with the invasive method of liver biopsy. We undertook the present study in order to investigate the sensitivity and specificity of magnetic resonance imaging (MRI) in diagnosing cirrhosis., Material and Methods: A total of 56 patients were included in our retrospective study. The liver cirrhosis group comprised 30 patients and the control group 26 patients. All cases were histologically verified. A 1.5T MRI unit was used. Twelve radiological features of cirrhosis (enlargement of segment one, narrowing of hepatic veins, enlargement of spleen, fibrosis, nodular liver surface, ascites, regenerative nodules, enlargement of hilar periportal space, atrophy of right lobe, portosystemic collaterals, expanded gallbladder fossa, iron depositions) and tumour-load were evaluated by consensus reading. The ratio between segment one and right lobe was measured and the livers were classified as cirrhotic or non-cirrhotic. The chi2-test and t-test were used to indicate statistical difference., Results: The sensitivity of MRI in diagnosing liver cirrhosis was 87% and the specificity 92%. The most characteristic MRI features were enlargement of segment one (83%), narrowing of hepatic veins (83%), signs of portal hypertension (77%), fibrosis (77%), and nodular liver margin (67%). There were statistical differences in all MRI signs between the cirrhosis and control groups. The ratio between segment one and right lobe also showed statistical significance between the two groups. All occult hepatocellular carcinomas were detected in the cirrhosis group., Conclusion: MRI has high sensitivity and specificity in the diagnosis of liver cirrhosis.

Background: Hepatic lesions constitute a daily challenge to radiology in clinical settings, and non-invasive methods are valuable in the characterization of these liver tumours. We undertook our investigation to assess the lesion characterization potential of MRI by evaluating several unenhanced MR sequences and the dynamic gadolinium (Gd)-enhanced technique., Methods: A total of 116 focal liver lesions in 116 patients were included in our retrospective study, and histological verification was available for 107 lesions. Nine haemangiomas had a follow-up of 2 years. The 1.5-T MR system was used. T1- and T2-weighted sequences and dynamic Gd-enhanced studies were evaluated by two individual readers as separate sequences and also collectively. Lesions were classified into benign or malignant, and a specific diagnosis was proposed. The McNemar test was used in statistical analysis, and interobserver variation was measured using kappa statistics., Results: Lesion classification into benign and malignant tumours (by evaluating all images in concert) was assessed in 83% and 89% of cases by readers 1 and 2, respectively. From single sequences, best lesion classification was achieved with Gd-enhanced T1 by both readers. The difference in classification was statistically significant when all sequences were evaluated in comparison with any single sequence alone (P = 0.02). Specific diagnosis was correctly determined using all sequences together in 60% and 71% of cases by readers 1 and 2, respectively. For individual sequences, correct diagnosis was most frequently proposed with a Gd-enhanced T1-weighted sequence by both readers (59% and 65% for readers 1 and 2, respectively)., Conclusion: Multisequential MRI using Gd-enhanced imaging performs extremely well in liver lesion classification, and with moderate ability to determine a specific diagnosis.

We investigated whether determination in fine-needle aspiration biopsy (FNAB) specimens of cells expressing granzymes (Grs) and Fas ligand would provide a reliable, easy, and quantitative measure of rejection activity in the transplanted liver. Retrospectively, 13 FNAB specimens obtained during clinical acute rejection, 10 FNAB specimens obtained during subclinical rejection, 12 FNAB specimens obtained during cytomegalovirus (CMV) infection, and 26 FNAB specimens obtained in the absence of rejection or infection were included on the study. Cytospin preparations of FNAB and peripheral-blood specimens were immunocytochemically stained for Fas-ligand and Gr, and increments in the liver were calculated by subtracting frequencies of positive cells in blood from those in FNAB specimens. Only sporadically Fas ligand-expressing, but many Gr-expressing, cells were detected in FNAB specimens. Increments in Gr-positive (Gr(+)) cells were significantly greater in FNAB specimens obtained during clinical rejection (median, 70 Gr(+) cells; range, 0 to 312 Gr(+) cells; P = .006) and tended to be greater in FNAB specimens obtained during subclinical rejection (median, 62 Gr(+) cells; range, 5 to 113 Gr(+) cells; P = .09) compared with those obtained in the absence of rejection (median, 16 Gr(+) cells; range, 0 to 103 Gr(+) cells). Increments obtained during clinical or subclinical rejection did not differ from those obtained during CMV infection (median, 27 Gr(+) cells; range, 6 to 212 Gr(+) cells). With the exclusion of specimens obtained during CMV infection, the sensitivity of Gr determination in FNAB specimens for the diagnosis of acute rejection (either clinical or subclinical) was 70%, and specificity, 69%. In FNAB specimens obtained during clinical and subclinical acute rejection episodes after liver transplantation, increased numbers of Gr-expressing cells were present; in the absence of CMV infection, their quantification provides a measure for rejection activity with moderate accuracy.

Purpose: To evaluate the efficacy of combined (double contrast) use of superparamagnetic iron particles (SPIOs) and gadolinium (Gd) in liver MR imaging., Material and Methods: Unenhanced, Gd-enhanced, SPIO-enhanced, and both SPIO- and Gd-enhanced images were acquired at 1.5 T. Twenty patients with previously detected liver lesions were included. Fast SE-STIR, and breath-hold true FISP, fat-suppressed T1- and T2-weighted sequences were obtained with all techniques. Lesion count was assessed by consensus reading., Results: Collective evaluation of all MR sequences revealed 61 lesions in 16 patients; SPIO-enhanced MR detected lesions with a sensitivity of 95% (n=58). The sensitivity of unenhanced MR imaging was 90% (n=55). There was no statistical difference between SPIO-enhanced and unenhanced MR images. From single sequences, the greatest number of lesions was detected with the SPIO-enhanced fast SE-STIR sequence (n=56, sensitivity 92%). By using the fat-suppressed T1-weighted sequence, Gd-enhanced and both SPIO- and Gd-enhanced MR images demonstrated sensitivities of 77% (n=47) and 80% (n=49), respectively. Despite the combined use of both contrast media, this sequence was significantly less sensitive in lesion detection when compared to SPIO-enhanced imaging., Conclusion: SPIO-enhanced MR imaging was the most sensitive method in lesion detection. The benefit of the combined use of SPIO and Gd was negligible.

Background: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model., Method: One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined., Results: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells., Conclusions: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.

Objective: To evaluate hepatic and splanchnic oxygenation during liver transplantation., Design: Prospective study., Setting: University hospital., Patients: Ten adult patients undergoing liver transplantation., Interventions: Standardized surgery and anesthesia without venovenous bypass., Measurements and Main Results: Hepatic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in hepatic venous blood. Splanchnic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in portal venous blood and by gastric tonometry. Before reperfusion, the grafts were flushed with 1000 mL of acetated Ringer's solution and 400 mL of portal venous blood. The effluent blood from the graft was wasted and showed a mean pH of 6.86 and a lactate concentration of 9.4 mmol/L. Five minutes after portal reperfusion, most of the grafts produced lactate. Portal-hepatic venous P(CO2) difference ranged from 3 to 16 torr (0.4-2.1 kPa). By the time of restoration of the infrahepatic caval flow mean 24 mins later, eight of the grafts had stopped producing lactate. Mean hepatic venous oxygen tension was 47 torr (6.3 kPa), stabilizing to 41 torr (5.5 kPa) at the end of surgery. Acidosis resolved without pharmacologic interventions. Mean gastric mucosal pH was 7.29 during the anhepatic phase and 7.40 at the end of surgery. One of the patients developed hepatic arterial thrombosis intraoperatively. Her data were analyzed separately. Later, the other patients recovered with good liver function, whereas the patient with hepatic arterial thrombosis was successfully retransplanted., Conclusions: The liver grafts received well-oxygenated portal venous blood during reperfusion, despite the low values of gastric mucosal pH immediately before reperfusion. Hepatic oxygenation became adequate soon after reperfusion. In the patient with hepatic arterial thrombosis, the recovery of hepatic oxygenation was impaired and lactic acidosis persisted.

Background/aims: The pathogenesis of the inflammatory lesion in primary sclerosing cholangitis is unknown. The clinical picture is characterized by i.a. episodes of fever, the cause of which also remains speculative. Previous studies of bacterial isolates in the liver or bile ducts in primary sclerosing cholangitis have had the shortcoming of possible contamination associated with the sampling. The aim of this study was to investigate whether bile and bile duct tissue, obtained under sterile conditions in connection with liver transplantation, contain bacteria., Methods: We studied bile from bile duct walls and bile collected from the explanted livers of 36 patients with primary sclerosing cholangitis and 14 patients with primary biliary cirrhosis., Results: Positive cultures were obtained from 21 of 36 primary sclerosing cholangitis patients, but from none of the primary biliary cirrhosis patients. The number of bacterial strains was inversely related to the time after the last endoscopic retrograde cholangiography. Treatment with antibiotics or intraductal stent, or the occurrence of fever before liver transplantation did not seem to influence the culture results, whereas antibiotic treatment in connection with endoscopic retrograde cholangiography may possibly have reduced the number of isolates in the cultures. Alpha-haemolytic Streptococci were retrieved as late as 4 years after the last endoscopic retrograde cholangiography. Retrospective analysis of liver laboratory tests after endoscopic retrograde cholangiography did not indicate a deleterious effect of the investigation., Conclusions: The data suggest that antibiotics should be given routinely in connection with endoscopic retrograde cholangiography. They also raise the question of a possible role of alpha-haemolytic Streptococci in the progression of primary sclerosing cholangitis.

Objective: To evaluate the effects of dopexamine administration on hemodynamic variables and tissue oxygen tensions during crystalloid resuscitation from hemorrhagic shock., Design: Randomized, control trial., Setting: An animal laboratory at a university center., Subjects: Twelve piglets, mean weight 22 kg., Interventions: The animals were anesthetized and bled to a state of hemorrhagic shock and resuscitated, using a crystalloid solution infused at a rate of approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean arterial pressure (MAP were measured as indicators of volume filling during the 20- to 30-min resuscitation period and during the follow-up period until 80 mins from the start of resuscitation. Dopexamine was administered by infusion at 6 micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6). The rest of the animals (control group, n = 6) were given volume replacement only., Measurements and Main Results: Systemic oxygen transport variables were calculated. Tissue oxygen tensions were continuously recorded from the liver, conjunctival layer, and via subcutaneous and transcutaneous electrodes in the abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and cardiac output decreased by 77% during the shock period. During resuscitation, cardiac output was restored in both groups. MAP increased close to the baseline during the early resuscitation period and decreased slowly during follow-up. Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption was restored during resuscitation in both groups. Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group. After 60 mins of resuscitation, the liver oxygen tension decreased to control group values. None of the other tissue oxygen tensions showed any differences between groups., Conclusions: Dopexamine administration during crystalloid resuscitation from hemorrhagic shock was well tolerated and resulted in significant and specific, although transient, improvement in liver oxygenation.

Glutathione transferase Alpha (GSTA) is a sensitive indicator of hepatocellular integrity. Its reference range is low (0.7-14 microgram/L) and its half-life is short (1 hr) in serum. We evaluated the changes in GSTA concentration in 18 recipients during and after liver transplantation. The respective liver donors were also included in 13 cases. The baseline GSTA concentrations were normal or slightly elevated in all donors, 1.2-79 micrograms/L (median 5.1 micrograms/L) and recipients, 1.1-34 micrograms/L (median 6.4 micrograms/L). Surgical dissection of donor liver caused a moderate or even large increase in GSTA concentration, peak 80-6500 microgram/L (median 800 micrograms/L). In the recipients the peak of GSTA concentrations varied from 1400 to 47000 micrograms/L (median 5000 micrograms/L), and it was always observed within 45 min after reperfusion of the graft. The highest GSTA values were observed after long cold ischemia and in patients transplanted for acute liver failure. However, they were not associated with early graft dysfunction. There was a correlation between the AUC of GSTA and cold ischemia time in the recipients with chronic nonalcoholic liver failure (r=0.94). There was no correlation between GSTA values in the donors and recipients (r=0.14). The apparent half-life of GSTA in serum was 56 min (median). Perioperative GSTA concentrations in the donors had no obvious predictive value. In the recipients an exceptionally long apparent half-life of GSTA immediately after transplantation or a large second increase in GSTA were predictors of postoperative complications.

The concentration of group II phospholipase A2 was measured in blood plasma samples before and after liver transplantation in a 27-year-old woman who suffered from a massive epitheloid hemangioendothelioma of the liver. The pretransplantation concentration of group II phospholipase A2 was 830 microg/L, which is markedly above the upper limit of the reference interval (10.8 microg/L). After the transplantation, there was a dramatic decrease in the group II phospholipase A2 level (33 microg/L on the first posttransplantation day). In situ hybridization of mRNA and immunohistochemistry revealed synthesis of group II phospholipase A2 in hepatocytes in non-neoplastic areas of the liver. Tumor cells did not contain group II phospholipase A2. The results indicate that group II phospholipase A2 circulating in blood plasma originates in hepatocytes.

Of readily available methods to estimate the donor liver size, measurement of the body circumference at the xiphoid level (xiphoid measure) appeared to be the most accurate in the present prospective study of 60 donors and 57 recipients (r = 0.64, P = 0.0001). The estimated liver volume could be calculated using the equation: bloodless liver volume (1) = 1.44 x xiphoid measure (m). The difference between donor and recipient xiphoid measures was significantly higher in slowly recovering patients than in those recovering uneventfully (7 +/- 7 cm vs. - 5 +/- 8 cm, P < 0.001). The bloodless donor liver volume measured by water displacement averaged 1249 +/- 230 ml and had increased by 3 weeks posttransplant by 64 +/- 28% as determined using computed tomography. The volume of the liver graft seemed to adapt to the recipient as it correlated positively with body weight (r = 0.64, P < 0.01) and negatively with the age of the recipient (r = -0.42, P < 0.01). The liver graft volume seemed to increase less markedly in patients with a slow recovery than in those with an uncomplicated recovery (37% +/- 15% vs. 68% +/- 24%, P < 0.001). We conclude that a simple measurement of the body circumference at the xiphoid level can be used to estimate the donor liver volume. A gross mismatch of this parameter between the donor and the recipient seems to increase the risk of graft dysfunction. We also found that the change in the liver graft volume is influenced by the recipient's age and body weight.

An extensive liver rupture developed in a 50-year-old woman after she received severe blunt injuries in a criminal assault. Nonsurgical management of the liver injury led to recovery of the patient despite a serious blood loss and multiorgan failure. However, 3 months after the injury a complete left bile duct stenosis with liver dysfunction and two hepatic artery pseudoaneurysms were found. Biliodigestive bypass restored normal liver function.

Intercellular adhesion molecule-1 (ICAM-1) induction on hepatocytes was investigated in relation to acute liver allograft rejection, CMV infection, and systemic bacterial infections. Twenty-four liver transplant recipients underwent an episode of acute rejection, 13 developed a symptomatic clinical CMV infection, and 7 had bacterial sepsis. Seven recipients without rejection or infection complications were used as controls. All rejection episodes monitored by frequent FNABs were reversible, and lymphocyte and lymphoid blast-dominated with a with peak of inflammation (7.2 +/- 3.9 corrected increment units [CIU]). The rejections were treated with high-dose steroids, and the inflammation subsided within one week. ICAM-1 was demonstrated from fine needle aspiration biopsy (FNAB) preparations by a monoclonal antibody and immunoperoxidase staining. ICAM-1 was not detected on the hepatocytes immediately after transplantation or in control patients, but was always seen during rejection. ICAM-1 appeared 1-5 days before the onset of inflammation in FNAB. The intensity of ICAM-1 expression increased toward the peak of inflammation and subsided together with inflammation. During CMV infection a mild immune activation was seen in FNAB (peak 2.5 +/- 0.8 CIU) and in blood. An intense ICAM-1 induction also preceded the immune activation caused by CMV, and subsided slowly with successful antiviral treatment. In addition, a slight ICAM-1 induction on the hepatocytes was recorded during bacterial sepsis. ICAM-1 induction on hepatocytes appears to be linked with an early phase of immune response, and it even precedes the lymphoid activation of rejection. However, several infections, such as CMV and bacterial infections, raise an immune response and may also induce ICAM-1. In conclusion, ICAM-1 induction on hepatocytes can be considered an early, though unspecific, marker for acute liver allograft rejection.

Lipid extracts of biopsy samples from normal and non-alcohol-induced fatty human liver were studied by 1H-NMR at 200 MHz. Spectra of the lipid extracts from 10 mg samples were obtained in 6 min with routine acquisition parameters and allowed the calculation of the phosphatidylcholine to total fatty acyl chain ratio, the cholesterol to total fatty acyl chain ratio, the average fatty acyl chain length, the unsaturation ratio and the acylated glycerol to total fatty acyl chain ratio. The data suggest that lipids with a higher ratio of de novo synthesized fatty acyl chains are stored in non-alcohol-induced fatty liver. NMR lipid analysis appears to be a reliable method for the rapid assessment of hepatic lipid composition on bioptic specimens.

Background and Methods: Hepatic dysfunction after severe hemorrhagic shock is common and may be a consequence of visceral tissue hypoxia. Peripheral tissue PO2 has been suggested to correlate with the development of visceral hypoxia. To test the hypothesis that changes in peripheral tissue PO2 reflect changes in hepatic PO2, we measured subcutaneous PO2, transcutaneous PO2, transconjunctival PO2, and liver tissue PO2, and their relationship with changes in mean arterial blood pressure (MAP) and systemic oxygen transport (DO2), during progressive bleeding in pigs (n = 23). In addition to the tissue PO2, portal vein PO2 and circulating lactate concentrations were also measured in six of the animals. The animals were anesthetized and bled to an MAP of 50 mm Hg within 1 hr., Results: After an induced 10% reduction of MAP, only the DO2 decreased significantly (p less than .05). After a 20% reduction of MAP, the DO2 decreased further and was associated with a significant (p less than .05) reduction of all peripheral tissue PO2 values. A significant (p less than .05) reduction of liver tissue PO2 was observed later during bleeding, after induction of a 30% reduction in MAP. In the subgroup with portal venous PO2 and lactate measurements, reductions of all peripheral tissue PO2 and portal venous PO2 values occurred after a 20% reduction (p less than .05) of MAP. An increase (p less than .05) in the portal venous lactate concentration was observed after a 50% reduction of MAP, and a decrease (p less than .05) in liver tissue PO2 was noted after a 60% reduction of MAP., Conclusions: Reductions of both peripheral and portal venous PO2 values occur early during hemorrhage. The liver tissue PO2, though initially low, appears to be better defended, suggesting either redistribution of splanchnic blood flow or adaptation in hepatic oxygen demand.

The diagnosis of acute liver allograft rejection is difficult, as clinical signs or liver function tests are too unspecific. The diagnosis is mainly based on biopsy histology. However, the liver core biopsy may be associated with complications. The fine-needle aspiration biopsy (FNAB) method, originally developed for the monitoring of renal transplants, is a reliable and atraumatic technique to diagnose acute cellular rejection of liver allografts. FNAB makes it possible to quantity the inflammation associated with rejection, and to monitor the response to anti-rejection therapy. Additional information is received from changes in liver parenchymal cells indicating tissue damage and/or possible hepatotoxic effects of the drugs used. In addition, FNAB may be helpful in differential diagnosis of infections, cholestasis or other complications. A good correlation between FNAB findings of acute liver rejection and histology has been reported. However, histological examination is needed to diagnose chronic rejection. Several liver transplant centres now use FNAB technology as a routine diagnostic tool.

Fine-needle aspiration biopsies were used for clinical monitoring of liver allografts; 21 patients with an inflammatory episode of acute rejection (12.0 +/- 3.3 CIU at the peak) were studied; all episodes were reversible. The inflammatory infiltrate consisted mainly of lymphoid cells, including lymphoid blasts, with increased numbers of class II and IL-2-receptor expressing lymphocytes. No lymphoid activation was seen in corresponding blood specimens. A rapid response to antirejection therapy with high-dose steroids was recorded by FNAB. Another group of 7 recipients without rejection developed a severe CMV disease. The CMV disease was associated with mild inflammation in the FNAB (3.2 +/- 0.9 CIU at the peak), but fewer blast cells and activated cell types were recorded in the graft, and blast cells and lymphocyte activation were seen in the blood specimens, as well. The inflammation disappeared from the FNABs during successful antiviral treatment. The cellular findings of rejection and CMV infection were significantly different, and the presence or absence of rejection could be firmly established by FNAB.

It has been suspected that vasopressin infusion may cause small bowel necrosis and liver ischaemia. In this study a direct method of measuring the oxygen tension of these organs during intravenous vasopressin infusion was used for the first time. Vasopressin in a dose of 2.75 mU/kg/min was infused during a 45 minute period in ten dogs. Both intestinal and liver pO2 decreased to a hypoxic level. This level was observed within a mean time of 25 minutes in both organs. After discontinuing the vasopressin infusion the oxygen tension was noted to return to normal in 45 minutes. It is concluded that vasopressin causes definite ischaemia of the small bowel and the liver parenchyma, and consequently this vasoactive drug should be used with care. The exact time of onset and duration of intestinal hypoxia could be of great value in planning vasopressin induced hypoxia for radioprotection.

In an earlier study we found that intravenous vasopressin infusion caused a profound decrease in intestinal and liver pO2. As vasopressin has been reported to be more effective when infused directly into the superior mesenteric artery, we have now studied the effects of this type of administration. Intestinal pO2 and pCO2 and liver pO2 were continuously recorded using a silicone elastomer tube as a tonometer. Vasopressin was infused in a dose of 2.75 mU/kg/min in twelve dogs for 45 minutes. Intestinal tissue pO2 decreased during 45 minute infusion period from 35 +/- 0.9 mmHg to 19 +/- 0.7 mmHg (p less than 0.001) and liver pO2 from 38 +/- 1.9 mmHg to 19 +/- 1.1 mmHg (p less than 0.005). Both values obtained in this study did not differ from those noted when the same dose of vasopressin was administered intravenously.

A brief account of our present knowledge on the enterohepatic metabolism of estrogens and on the origin, metabolism and biological effects of mammalian lignans and phytoestrogens is undertaken. Furthermore, recently published results on the effects of dietary fiber, fat and carbohydrates on estrogen metabolism are reviewed. New preliminary results are presented on quantitative assays of lignans and phytoestrogens in urine of women belonging to various dietary and population groups and in a group of chimpanzees. The highest values of lignans and phytoestrogens were found in the non-human primates, and in macrobiotic, lactovegetarian and Japanese women, all groups considered having a low risk for the development of breast and other hormone-dependent cancer. New results on correlations between intake of various fibers, lignan and phytoestrogen excretion and plasma levels of estrogens, free testosterone and SHBG in women are presented. There is a significant positive correlation between the intake of fiber and urinary excretion of lignans and phytoestrogens, and the concentration of plasma SHBG. Fiber intake and urinary excretion of lignans and equol correlated negatively with plasma percentage free estradiol. Enterolactone excretion correlated negatively with plasma free testosterone. It is concluded that dietary macro- and micronutrients seem to play an important role in estrogen metabolism.

Liver histological and electron microscopical changes were studied in six dogs after liver hilus dearterialization and in two dogs after sham operation. All specimens were taken in vivo. In light microscopy a marked dilatation of the sinusoids was noted 90 minutes after dearterialization. After 24 hours it was even more pronounced. The hepatocytes were shrunken. On the seventh day these alterations persisted in the central area only. None of these changes were found in the sham-operated controls. In electron microscopy rounding and swelling of the mitochondria was observed on the first day after dearterialization. On the seventh day they looked normal. Damage of the endoplasmatic reticulum was found to persist even on the seventh day. The bile canaliculi membrane was damaged after dearterialization but not after sham operation. Dilatation of the sinusoids and widening of the space of Disse was observed on the first and seventh day after dearterialization. In the controls none of these changes were seen. In both dearterialized and sham-operated dogs a transient decrease in liver glycogen was noted. In conclusion, light and electron microscopical studies demonstrated reversible ischemic changes in the liver. These correlated well with our liver pO2 measurements which indicated transient hypoxia and our biochemical studies which indicated reversible damage of the liver.

Because it is difficult to verify the efficacy of hemorrhagic shock treatment, we compared subcutaneous O2 tension (PscO2) with liver oxygenation in efforts to correct shock in piglets with two different colloids, hydroxyethyl starch (HES-120) and dextran-70. Nineteen animals were bled to shock and the shed blood was retransfused in the control group. Liver oxygenation was measured directly by means of a silicone tube used as a tonometer, and indirectly by calculating liver O2 consumption (VO2). PscO2 was monitored with a needle electrode. The two colloid groups were compared by measuring plasma lactate, and the plasma colloid osmotic pressure (COPp). PscO2 followed closely the changes in liver tissue PO2 during the experiment; it seems to be a useful tool in estimating volume filling during the treatment of hemorrhagic shock. A wider variation was noted in calculated liver VO2 compared with hepatic venous PO2 or liver tissue PO2. Despite the fact that COPp increased to a higher level after the administration of dextran, HES proved to be at least as effective as dextran in restoring mean arterial pressure, cardiac output, liver oxygenation, PscO2, arterial pH, arterial plasma lactate, and liver lactate uptake.

Changes in liver blood flow immediately after and during one week after a standardized liver hilus dearterialization were studied in a series of 16 dogs. An additional six dogs were sham-operated and used as controls. The liver blood flow was measured using Xe133 injections administered by two methods in every animal: into the liver parenchyma, and into the portal vein. The measurements were taken immediately before, and 15, 30, 60 minutes, and one and seven days after the operation. Xe133 wash out from the liver was found to be reduced 15 minutes after the dearterialization, measured both by liver parenchymal and portal venous injection routes (p less than 0.05). Return to normal took place rapidly thereafter. On the next day some increase in the liver blood flow was observed in both dearterialized and sham-operated dogs. The aleration was significant in the dearterialized animals as measured by portal vein injections, and in the sham-operated dogs as measured by liver parenchymal injections (p less than 0.05). On the seventh day normal Xe133 liver wash out was recorded in all animals. It can be concluded that after liver hilus dearterialization in the dog liver blood flow was decreased for a very short period of time only. Increased flow was noted as early as the next day, not only in the dearterialized, but also in the sham-operated animals. The use of adequate controls is important.

Twenty-one harrier dogs underwent a standardized liver hilus dearterialization with (7) or without (14) cholecystectomy using six sham-operated dogs as controls. Seven dogs died, only one of which was in the dearterialization and cholecystectomy group. S-OCT and s-GDH were increased at 90 minutes after dearterialization. There was no statistical difference between the groups at 90 minutes. On the first day after dearterialization, the activity of s-OCT, s-GDH, s-ALAT rose significantly (p less than 0.005). The activity of s-ASAT was, however, increased to the same extent both in the dearterialized and the sham-operated animals. A normalization of the serum enzyme activities was usually seen after one week. S-ALP increased on the first day (p less than 0.005) and still higher values were noted on the seventh day after dearterialization. Cholecystectomy did not affect any of these results except mortality. Liver oxygen consumption, in vitro was unchanged throughout the experiment. The oxygen consumption of bile duct mucosal scrapings one week after dearterialization was similar to the corresponding values in the controls. The results indicate that the dearterialization leads to a definite but mild and reversible mitochondrial and cell membrane damage. The results indicate further the need of adequate controls when the effects of dearterialization on the liver are studied.

A standardized and angiographically controlled liver hilus dearterialization was performed in 21 harrier dogs with (7) or without (14) cholecystectomy. Six sham-operated dogs were used as controls. All dogs had repeat laporatomies performed on the first and seventh postoperative days. Seven dogs died, only one from the group with added cholecystectomy. If the gall bladder was left in place following dearterialization it was found to be gangrenous in all animals by the next day. On the seventh day gall bladder perforation and bile peritonitis occurred in four of the eight surviving dogs. Cholecystectomy associated with the dearterialization had a striking effect on the incidence of intra-abdominal complications. The basic microscopic structure of the liver was not affected by the operation. Selective hepatic angiograms before the dearterialization proved to be useful in detecting all tributaries from the hepatic artery. Angiograms immediately after the dearterialization effectively located possible unnoted arterial tributaries which could then be ligated. A method of control was thus achieved by angiograms before and after the liver hilus dearterialization.

Liver oxygenation was studied with hemorrhagic hypotension and corrected using whole blood, a synthetic colloid (hydroxyethyl starch or hetastarch, HES; mol. wt. 120,000), or a crystalloid solution. Measurements were performed directly by recording pig liver tissue oxygen tension with an implanted silicone elastomer (Silastic) tube, and indirectly by calculating blood oxygen contributions. The direct method seems fairly reliable and accurately reflects different levels of bleeding and shock and their correction. Liver tissue oxygen tension (PlO2) may thus be used as an indicator of central organ response to shock management. PlO2 decreased during bleeding from 33.5 +/- 0.5 to 16.0 +/- 0.5 torr, and normalized rapidly after retransfusion. The baseline values were significantly exceeded after hetastarch infusion but were never reached with Ringer's solution. The correction of liver oxygen consumption was less complete after crystalloid infusion as well. On the other hand, the difference in liver oxygenation was less marked after crystalloid infusion and retransfusion, which restored perfusion to the baseline. The total amount of Ringer's solution needed to keep the animals hemodynamically stable during the 2-h follow-up period was four times higher than with hetastarch and some five times the blood volume shed. The cause of defective correction of liver oxygenation seems to be the poor response of liver blood flow to refilling in the Ringer group, in addition to apparent tissue edema after crystalloid infusion. According to our study, hemorrhagic hypotension related to liver oxygenation is more promptly and completely corrected with the colloid hydroxyethyl starch than with a crystalloid solution in the early phase of treatment.

Purpose: To investigate prospectively multidetector computed tomography (CT) (MDCT) and magnetic resonance (MR) imaging (MRI) in the preoperative assessment of focal liver lesions.Material and Methods: Multiphasic MDCT and conventional gadolinium-enhanced MRI were performed on 31 consecutive patients prior to hepatic surgery. All images were blindly analyzed as consensus reading. Lesion counts and their relation to vascular structures and possible extrahepatic disease were determined. The data from the MDCT and MRI were compared with the results obtained by intraoperative ultrasound (IOUS) and palpation. Histopathologic verification was available.Results: At surgery, IOUS and palpation revealed 45 solid liver lesions. From these, preoperative MDCT detected 43 (96%) and MRI 35 (78%) deposits. MDCT performed statistically better than MRI in lesion detection (P=0.008). Assessment of lesion vascular proximity was correctly determined by MDCT in 98% of patients and by MRI in 87%. Statistical difference was found (P=0.002). IOUS and palpation changed the preoperative surgical plan as a result of extrahepatic disease in 8/31 (26%) cases. In MDCT as well in MRI extrahepatic involvement was suspected in two cases.Conclusion: MDCT was superior to MRI and nearly equal to IOUS in liver lesion detection and in the determination of lesion vascular proximity. However, both techniques fail to reliably detect extrahepatic disease. [ABSTRACT FROM AUTHOR]

Background: Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post-transplant survival. Methods: Data from two groups of patients receiving liver allografts during 1982-2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival. Results: A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of re-transplantation in PSC patients were an episode of early rejection and vascular thrombosis. Conclusion: In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re-transplantation compared to the comparison group. [ABSTRACT FROM AUTHOR]