Late histopathological findings in renal allografts with four immunosuppressive regimens

The histological changes in renal allografts are usually studied when graft function has already deteriorated. The early results of renal allografts have improved dramatically during the last two decades, but the half-life of renal cadaveric allografts has remained unchanged at approximately 7 years [1]. The mechanism of chronic rejection, and how to prevent it, is not known. We studied the histology of renal allografts under four different immunosuppressive regimens 2 years after transplantation. The aim of this study was to investigate whether histopathological changes exist in the renal allografts with relatively good and stable graft function. We also investigated whether there were differences in allograft histology between four immunosuppressive treatment groups 2 years after transplantation.     

A simple method for predicting bone fractures in PBC patients after liver transplantation

Abstract We introduce a simple serum test to predict which patients will have bone problems after liver transplantation. The crosslinked part of collagen I (s-ICTP) was measured in 21 patients with primary biliary cirrhosis before transplantation. Those with post-     

Non-invasive diagnosis of liver cirrhosis: magnetic resonance imaging presents special features

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.     

Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries

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.     

Sterol parameters as markers of liver function in primary biliary cirrhosis before and after liver transplantation

Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end-stage of primary biliary cirrhosis (PBC) - prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6-3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.     

Changes in liver graft rejections over time

Incidence and possible risk factors of acute rejection, time to acute rejection, graft rejection within 3 months, multiple rejections within 1 year, steroid-resistant rejection, and graft lost to chronic rejection or to chronic dysfunction were evaluated in 388 liver transplantations. HLA matches, anti-HLA class I antibodies, positive crossmatch test, or positive cytomegalovirus serology did not have an effect on the occurrence of acute or chronic rejection. Increased total bleeding diminished occurrence of acute rejection, lengthened the time to acute rejection, and reduced the risk of steroid-resistant rejection. Immunological pretransplant factors did not have a major effect on the occurrence of rejection after liver transplantation. Different types of rejections diminished over time and the time period to the first acute rejection increased, although the basic immunosuppression stayed mainly the same over 20 years in our center.     

Complement Activation During Liver Transplantation—Special Emphasis on Patients With Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy often caused by mutations in complement factor H (CFH), the main regulator of alternative complement pathway. Because CFH is produced mainly by the liver, combined liver–kidney transplantation is a reasonable option in treatment of patients with severe aHUS. We studied complement activation by monitoring activation markers during liver transplantation in two aHUS patients treated extensively with plasma exchange and nine other liver transplantation patients. After the reperfusion, a clear increase in all the activation markers except C4d was observed indicating that the activation occurs mainly through the alternative pathway. Concentration of SC5b‐9 was higher in the hepatic than the portal vein indicating complement activation in the graft. Preoperatively and early during the operation, the aHUS patients showed highest C3d concentrations but otherwise their activation markers were similar to the other patients. In the other patients, correlation was found between perioperative SC5b‐9 concentration and postoperative alanine aminotransferase and histological changes. This study explains why supply of normal CFH by extensive plasma exchange is beneficial before combined liver–kidney transplantation of aHUS patients. Also the results suggest that perioperative inhibition of the terminal complement cascade might be beneficial if enhanced complement activation is expected.     

Early Molecular Adsorbents Recirculating System Treatment of Amanita Mushroom Poisoning

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life‐threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin‐bound and water‐soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one‐year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first‐aid at a local hospital and to MARS treatment were 18 h (range 14–36 h) and 48 h (range 26–78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side‐effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.