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Abstract: Background: Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear. Methods: In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated. Results: Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7–1.0]; 1.4 [0.9–1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2–0.5]; 1.7 [1.3–3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation. Conclusions: Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury. [Copyright &y& Elsevier]

Abstract: Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values ± SD were 93 ± 58 IU/mL vs 17 ± 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 ± 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 ± 43 IU/mL vs 104 ± 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 ± 34 IU/mL in patients with rejection (P = .014) vs 69 ± 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients. [Copyright &y& Elsevier]

Background: Quantitative PCR assays have become the most common methods in the determination of viral load during cytomegalovirus (CMV) infection of transplant patients. However, usually these tests are still quite time-consuming and labor-intensive which diminishes their utility of these tests in routine diagnostic laboratories. Objectives: The objective of this study was to develop a quantitative CMV PCR test which is time-saving and easy to perform for the detection and monitoring of CMV infection of transplant patients. Study design: The quantitative real time CMV PCR assay using TaqMan chemistry and an automated sample preparation system, MagNA Pure LC, was developed. The designed quantitative CMV test was compared to commercial quantitative PCR test, Cobas Amplicor Monitor, in the determination of CMV DNA loads in plasma samples of liver and kidney transplant patients. The results were also correlated with the CMV pp65-antigenemia test. The clinical material of 270 blood specimens of transplant patients were tested using these two PCR methods and pp65-antigenemia test in parallel. Plasma samples were used for PCR assays and leucocytes for the antigenemia test. Results: The TaqMan assay described was easy to perform, it was rapid (3–4 h) and hands-on time needed for performing the test was short. The detection limit of the assay was 250 copies/ml (cps/ml) plasma and the linear range up to 25,000,000 cps/ml. TaqMan assay was the most sensitive test detecting 92% of the CMV positive findings. Cobas Monitor detected 80% and pp65 test 88% of the positive findings. The correlations between TaqMan and antigenemia assays, and between Cobas Amplicor and antigenemia were statistically significant and high, R=0.84 (P<0.0001) and R=0.80 (P<0.0001), respectively. Also correlation between two PCR tests was statistically significant (R=0.64, P<0.0001). Of the 27 patient studied, 19 demonstrated CMV antigenemia and DNAemia in their blood during the post transplant monitoring. Thirteen of these patients developed a symptomatic CMV infection and were treated with ganciclovir. The peak viral loads of symptomatic patients were statistically higher by all three methods than those of asymptomatic patients. Conclusions: The developed real time TaqMan assay was rapid and easily performed and could be the best alternative for the diagnosis of CMV infection and monitoring of liver and kidney transplant patients. [Copyright &y& Elsevier]

Background: The majority of patients with inherited haemochromatosis carry two mutant alleles of the recently discovered HFE gene. Individuals heterozygous for the HFE mutation could be predisposed to end-stage liver disease due to other causes. Methods: The frequencies of the HFE gene mutations C282Y and H63D were determined in DNA samples obtained from 189 liver transplant patients and 225 healthy Finnish blood donors. Results: 5% of the 189 liver transplant recipients were heterozygotes and 0.5% homozygotes for the C282Y mutation, while 16% were heterozygotes and 0.5% homozygotes for the H63D mutation. These figures were not increased in comparison to controls, of whom 11% were C282Y heterozygotes, 16% H63D heterozygotes and 0.9% H63D homozygotes. Among recipients with acute non-A-E hepatitis (n = 31), the frequency of the H63D allele was higher than in controls (21% versus 9.1%, P < 0.01). Perls' stain for iron in explanted liver specimens was positive in 28% of recipients with alcoholic cirrhosis, 26% of patients with acute non-A-E hepatitis and 14% in the rest of the recipients. The HFE genotypes did not correlate with the iron status. Conclusion: Individuals heterozygous for either the C282Y or H63D mutation of the HFE gene are not at increased risk of developing chronic endstage liver disease. However, subjects heterozygous for the H63D mutation may have an increased risk to develop fulminant non-A-E hepatitis. [ABSTRACT FROM AUTHOR]

Background: We have observed increased serum tumor markers, especially carbohydrate antigen 19-9 (CA 19-9) levels, in patients with acute liver failure (ALF) being evaluated for liver transplantation, raising the question of potential malignancy. In chronic liver disease increased serum alpha-fetoprotein (AFP) may be a sign of liver regeneration, but little is known of these markers in ALF. The aim of this study was to evaluate the causes of overexpression of tumor markers in patients with non-malignant ALF. Methods: The serum AFP, carcinoembryonic antigen (CEA), and CA 19-9 levels were compared with the liver function tests in 33 patients with acute liver failure and in 78 patients with chronic non-malignant liver disease being evaluated for liver transplantation. Immunohistochemical stainings of the tumor markers were performed on explanted liver specimens. Results: The AFP (1-218 U/ml) and CA 19-9 (10-6520 U/ml) levels were significantly higher in the patients with ALF than in the patients with chronic liver disease (P < 0.01). The AFP and CA 19-9 values also correlated with the total serm bilirubin level. In the patients with ALF the immunohistochemical staining for CA 19-9 was highly positive in periportal transformed ductular hepatocytes and correlated positively with the serum CA 19-9 values (P < 0.001). The stainings for AFP or CEA showed no or only slight positivity in the patients with increased serum values of the tumor markers. Conclusions: In patients with ALF increased serum levels of CA 19-9 reflect the amount of transformed ductular hepatocytes without any evidence of malignancy. Increased CA 19-9 values should not be the cause of delay when an ALF patient needs an urgent liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period. Methods: Data on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry. Results: A total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing. Conclusion: Results of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human colonic contents and many colonic microbes produce considerable amounts of acetaldehyde from ethanol in vitro. AIMS: To examine in piglets if acetaldehyde is produced in the colon also in vivo, and if so, what is the fate of intracolonically formed acetaldehyde. ANIMALS: Seventeen native, non-fasted female piglets (20-25 kg) were used. METHODS: Six piglets received either 1.5 g/kg bw or 2.5 g/kg bw of ethanol intravenously. In seven piglets, 0.7 g or 1.75 g of ethanol/kg bw was administered intravenously, followed by a subsequent intragastric ethanol infusion of 1.8 g/kg bw and 4.5 g/kg bw, respectively. The samples of colonic contents for the assessment of ethanol and acetaldehyde concentrations were obtained up to seven hours. In four additional piglets, the intracolonic values of ethanol, acetaldehyde, and acetate were observed for 60 minutes after an intracolonic infusion of acetaldehyde solution. RESULTS: A raised intracolonic, endogenous acetaldehyde concentration (mean (SEM); 36 (9) microM) was found in all piglets before ethanol infusion. After the infusion of ethanol, intracolonic ethanol and acetaldehyde values increased in parallel, reaching the peak values 57 (4) mM of ethanol and 271 (20) microM of acetaldehyde in the group that received the highest dose of ethanol. A positive correlation (r = 0.45; p < 0.001) was found between intracolonic ethanol and acetaldehyde values. Acetaldehyde administered intracolonically was mainly metabolised to acetate but also to ethanol in the colon. CONCLUSIONS: Significant endogenous intracolonic acetaldehyde values can be found in the normal porcine colon. Furthermore, our results suggest the existence of a bacteriocolonic pathway for ethanol oxidation. Increased amounts of acetaldehyde are formed intracolonically from ingested ethanol by this pathway. [ABSTRACT FROM PUBLISHER]

Acute fulminant pancreatitis is associated with significant morbidity and mortality. To examine the outcome of conservative and surgical treatment of this disorder, 36 patients who survived an initial episode were restudied after a mean of six years. Fifty three per cent had developed diabetes mellitus, half of whom required insulin therapy. Pancreatic resection was associated with a 100% frequency of diabetes, while only 26% of those treated with peritoneal lavage developed this (p less than 0.001). Insulin secretion and sensitivity were assessed using the hyperglycaemic glucose clamp technique. First phase insulin secretion was impaired in surgically treated patients (mean (SEM) 14 (5) microU/ml x 10 minutes) compared with conservatively treated patients and control subjects (144 (66) and 87 (12) microU/ml x 10 minutes, respectively; p less than 0.05). Second phase and 'maximal' insulin secretion were also impaired among the surgically treated patients compared with the conservatively treated patients and the controls. Insulin sensitivity was reduced among the surgically treated patients (2.88 (58) mg/kg.minute) when compared with conservatively treated patients and healthy control subjects (5.87 (1.02) and 6.45 (0.66) mg/kg.minute; p less than 0.05). Pancreatic resection is associated with a very high frequency of diabetes compared with peritoneal lavage, and these results favour conservative treatment of active fulminant pancreatitis whenever possible. [ABSTRACT FROM PUBLISHER]

ABSTRACT- We studied the sequential changes in the positive acute phase reactants orosomucoid, α1-antichymotrypsin, α1-antitrypsin, haptoglobin and C-reactive protein, and in the negative acute phase reactant, prealbumin, as well as in α2-macroglobulin and β2-microglobulin in serum following orthotopic liver transplantation in nine adult patients. Synchronous increases in all five positive acute phase reactants were observed in association with acute liver rejection episodes; the elevations were statistically significant for orosomucoid and α1-antichymotrypsin. In four out of nine well-documented rejection episodes C-reactive protein did not increase at all. Marked variations occurred in post-transplant prealbumin and α2-macroglobulin levels; both proteins tended to decrease 2-3 days after the rejection was diagnosed. The circulating levels of β2-microglobulin were raised during the post-transplant period and markedly increased in association with acute graft rejection episodes. The results demonstrate marked changes in plasma protein concentrations in association with acute liver allograft rejection episodes; the kinetics of serum acute phase reactants is very similar to that found in inflammation and tissue injury in general. [ABSTRACT FROM AUTHOR]