Publications by authors named "Bo-Göran Ericzon"

101 Publications

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden.

Am J Transplant 2021 Apr 3. Epub 2021 Apr 3.

The Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.
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http://dx.doi.org/10.1111/ajt.16596DOI Listing
April 2021

Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.

Gastroenterology 2021 03 9;160(4):1151-1163.e3. Epub 2020 Dec 9.

Department of Hepatology and Medical Liver Transplant Unit, Henri Mondor Hospital Assistance Publique-Hôpitaux de Paris, Paris-Est University, Creteil, France.

Background And Aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking.

Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis.

Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose.
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http://dx.doi.org/10.1053/j.gastro.2020.11.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724463PMC
March 2021

Characteristics, trends and Outcomes of Liver Transplantation for Primary sclerosing cholangitis in female vs male patients: An analysis from the European Liver Transplant Registry.

Transplantation 2020 Nov 13. Epub 2020 Nov 13.

Background: The influence of sex on primary sclerosing cholangitis (PSC), pre and post-liver transplantation (LT) is unclear.

Aims: to assess whether there have been changes in incidence, profile and outcome in LT- PSC patients in Europe with specific emphasis on sex.

Methods: Analysis of the ELTR database (PSC patients registered before 2018), including baseline demographics, donor, biochemical and clinical data at LT, immunosuppression (IS) and outcome.

Results: ELTR analysis (n=6463, 32% female) demonstrated an increasing number by cohort (1980-89, n=159; 1990-99, n=1282; 2000-09, n=2316; 2010-17, n=2549) representing on average 4% of all transplant indications. This increase was more pronounced in women (from 1.8% in the first cohort to 4.3% in the last cohort). Graft survival rate at 1, 5, 10, 15, 20 and 30 years was 83.6%, 70.8%, 57.7%, 44.9%, 30.8% and 11.6%, respectively. Variables independently associated with worse survival were male sex, donor and recipient age, cholangiocarcinoma (CC) at LT, non-DBD donor and reduced size of the graft. These findings were confirmed using a more recent LT population closer to the current standard of care (LT after the year 2000).

Conclusion: an increasing number of PSC patients, particularly women, are being transplanted in European countries with better graft outcome in female recipients. Other variables impacting outcome include donor and recipient age, CC, non-DBD donor and reduced graft size.
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http://dx.doi.org/10.1097/TP.0000000000003542DOI Listing
November 2020

The role of the comprehensive complication index for the prediction of survival after liver transplantation.

Updates Surg 2021 Feb 6;73(1):209-221. Epub 2020 Sep 6.

Starzl Unit of Abdominal Transplantation, Pôle de Chirurgie Expérimentale et Transplantation, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.

In the last years, several scoring systems based on pre- and post-transplant parameters have been developed to predict early post-LT graft function. However, some of them showed poor diagnostic abilities. This study aims to evaluate the role of the comprehensive complication index (CCI) as a useful scoring system for accurately predicting 90-day and 1-year graft loss after liver transplantation. A training set (n = 1262) and a validation set (n = 520) were obtained. The study was registered at https://www.ClinicalTrials.gov (ID: NCT03723317). CCI exhibited the best diagnostic performance for 90 days in the training (AUC = 0.94; p < 0.001) and Validation Sets (AUC = 0.77; p < 0.001) when compared to the BAR, D-MELD, MELD, and EAD scores. The cut-off value of 47.3 (third quartile) showed a diagnostic odds ratio of 48.3 and 7.0 in the two sets, respectively. As for 1-year graft loss, CCI showed good performances in the training (AUC = 0.88; p < 0.001) and validation sets (AUC = 0.75; p < 0.001). The threshold of 47.3 showed a diagnostic odds ratio of 21.0 and 5.4 in the two sets, respectively. All the other tested scores always showed AUCs < 0.70 in both the sets. CCI showed a good stratification ability in terms of graft loss rates in both the sets (log-rank p < 0.001). In the patients exceeding the CCI ninth decile, 1-year graft survival rates were only 0.7% and 23.1% in training and validation sets, respectively. CCI shows a very good diagnostic power for 90-day and 1-year graft loss in different sets of patients, indicating better accuracy with respect to other pre- and post-LT scores.Clinical Trial Notification: NCT03723317.
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http://dx.doi.org/10.1007/s13304-020-00878-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889667PMC
February 2021

Improvement of Islet Allograft Function Using Cibinetide, an Innate Repair Receptor Ligand.

Transplantation 2020 10;104(10):2048-2058

Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden.

Background: During intraportal pancreatic islet transplantation (PITx), early inflammatory reactions cause an immediate loss of more than half of the transplanted graft and potentiate subsequent allograft rejection. Previous findings suggest that cibinetide, a selective innate repair receptor agonist, exerts islet protective and antiinflammatory properties and improved transplant efficacy in syngeneic mouse PITx model. In a stepwise approach toward a clinical application, we have here investigated the short- and long-term effects of cibinetide in an allogeneic mouse PITx model.

Methods: Streptozotocin-induced diabetic C57BL/6N (H-2) mice were transplanted with 320 (marginal) or 450 (standard) islets from BALB/c (H-2) mice via the portal vein. Recipients were treated perioperative and thereafter daily during 14 d with cibinetide (120 µg/kg), with or without tacrolimus injection (0.4 mg/kg/d) during days 4-14 after transplantation. Graft function was assessed using nonfasting glucose measurements. Relative gene expressions of proinflammatory cytokines and proinsulin of the graft-bearing liver were assessed by quantitative polymerase chain reaction. Cibinetide's effects on dendritic cell maturation were investigated in vitro.

Results: Cibinetide ameliorated the local inflammatory responses in the liver and improved glycemic control immediately after allogeneic PITx and significantly delayed the onset of allograft loss. Combination treatment with cibinetide and low-dose tacrolimus significantly improved long-term graft survival following allogeneic PITx. In vitro experiments indicated that cibinetide lowered bone-marrow-derived-immature-dendritic cell maturation and subsequently reduced allogeneic T-cell response.

Conclusions: Cibinetide reduced the initial transplantation-related severe inflammation and delayed the subsequent alloreactivity. Cibinetide, in combination with low-dose tacrolimus, could significantly improve long-term graft survival in allogeneic PITx.
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http://dx.doi.org/10.1097/TP.0000000000003284DOI Listing
October 2020

Blood Group Antigen Expression in Isolated Human Liver Cells in Preparation for Implementing Clinical ABO-Incompatible Hepatocyte Transplantation.

J Clin Exp Hepatol 2020 Mar-Apr;10(2):106-113. Epub 2019 Jul 11.

Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden.

Background: ABO blood group antigens in the liver are expressed mainly on endothelial cells or biliary epithelial cells but not on hepatocytes. This suggests that ABO-incompatible hepatocyte transplantation (ABOi-HTx) is theoretically feasible. However, the effects of stress on ABO blood group antigen expression caused by isolation and intraportal infusion require thorough investigation before ABOi-HTx can be implemented in clinical settings.

Methods: Human hepatocytes were isolated from liver tissue obtained from liver resection or deceased donor livers. The expression of blood group antigens on cryopreserved human liver tissues and isolated hepatocyte smear specimens were examined by immunofluorescent staining. The effect of proinflammatory cytokines on blood group antigen expression of hepatocytes was evaluated by flow cytometry. Instant blood-mediated inflammatory reaction after hepatocyte incubation with ABO-incompatible whole blood was examined using the tubing loop model.

Results: Blood group antigens were mainly expressed on vessels in the portal area. In hepatocyte smear specimens, isolated hepatocytes did not express blood group antigens. In contrast, a subset of cells in the smear specimens of nonparenchymal liver cells stained positive. In the flow cytometry analysis, isolated hepatocytes were negative for blood group antigens, even after 4-h incubation with cytokines. Platelet counts and complement activation were not significantly different in ABO-identical versus ABO-incompatible settings in the tubing loop model.

Conclusion: Our study showed that blood group antigens were not expressed on hepatocytes, even after isolation procedures or subsequent incubation with cytokines. This finding is an important step toward removing the restriction of ABO matching in hepatocyte transplantation. Our results suggest that ABOi-HTx is a feasible therapeutic option, especially in patients who require urgent treatment with freshly isolated hepatocytes, such as those with acute liver failure.
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http://dx.doi.org/10.1016/j.jceh.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068001PMC
July 2019

Transfer of Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome by a Liver Graft From a Pregnant Female Donor to a Male Recipient: A Case Report.

Transplant Proc 2020 Mar 5;52(2):644-646. Epub 2020 Feb 5.

Division of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.

Eclampsia with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is a rare complication of pregnancy. HELLP syndrome may occur up to a week postpartum in women with eclampsia. CASE REPORT: We report a case of liver transplantation with the organ procured from a pregnant (gestation week 28) female donor who suffered brain death after cerebellar hemorrhage owing to eclampsia. Liver function tests were normal at the time of liver procurement. The liver graft was matched to a 62-year-old man with primary sclerosing cholangitis. On day 7 after an uneventful transplantation, the recipient presented with increased aminotransferases and severe thrombocytopenia. The recipient also developed hypertension and hyperthermia and a clinical picture of HELLP syndrome. The patient underwent emergency liver retransplantation on day 12 after the first transplantation. Intraoperatively, massive necrosis of the liver graft with diffuse subcapsular hematomas was seen. CONCLUSIONS: It appears that in our case, HELLP syndrome was transferred to and occurred in a male recipient. Eclampsia in the donor without overt HELLP syndrome may persist and be transferred by liver graft, developing into HELLP syndrome even in a male recipient. Therefore, liver grafts from female donors with eclampsia should be used with caution. Emergency retransplantation may be necessary.
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http://dx.doi.org/10.1016/j.transproceed.2019.10.037DOI Listing
March 2020

Impact of Hepatic Artery Variations and Reconstructions on the Outcome of Orthotopic Liver Transplantation.

World J Surg 2020 06;44(6):1954-1965

Division of Transplantation Surgery, CLINTEC, Karolinska University Hospital, Huddinge, 141 86, Stockholm, Sweden.

Background: Donor variational arteries often require complex reconstruction.

Methods: We analysed the incidence of different variations, types of arterial reconstructions and their impact on post-operative results from 409 patients undergoing liver transplantation at Karolinska Institute between 2007 and 2015.

Results: A total of 292 (71.4%) liver grafts had a standard hepatic artery (SHA), and 117 (28.6%) showed hepatic artery variants (HAV). 58% of HAV needed reconstruction. The main variations were variant left hepatic artery (45.3%) from the gastric artery; variant right hepatic artery (38.5%); and a triple combination of variant right and left hepatic artery and the proper hepatic artery from the common hepatic artery (12.8%); other 3.4%. Patients/graft survival and arterial complications were not different between SHA and HAV. Incidence of biliary stricture was numerically higher in left hepatic artery variants (p = 0.058) and in variants where no arterial reconstruction was performed (p = 0.001). Operation and arterial warm ischaemia time were longer in the HAV group. The need for intraoperative re-reconstruction was higher in the HAV group (p = 0.04). Intraoperative bleeding was larger after back-table reconstruction than with intraoperative reconstruction (p = 0.04).

Conclusion: No overall differences were found between the HAV and the SHA groups. Occurrence of a variant left hepatic artery and HAV with no reconstruction seems to increase the risk of biliary strictures.
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http://dx.doi.org/10.1007/s00268-020-05406-4DOI Listing
June 2020

Association of post-reperfusion syndrome and ischemia-reperfusion injury with acute kidney injury after liver transplantation.

Acta Anaesthesiol Scand 2020 07 20;64(6):742-750. Epub 2020 Feb 20.

Department of Clinical Science, Intervention and Technology, Division of Transplantation Surgery, Karolinska Institutet, Huddinge, Sweden.

Background: Acute kidney injury (AKI) is frequently observed after orthotopic liver transplantation (OLT) even in patients with previously normal renal function. In this study, we investigated the impact of factors such graft steatosis, post-reperfusion syndrome (PRS), and hepatic ischemia reperfusion injury (HIRI) on the development of AKI after OLT in adult patients.

Methods: We retrospectively examined consecutive adult patients who underwent OLT at our institution between July 2011 and June 2017. AKI was diagnosed based on the criteria proposed by the International Kidney Disease Improving Global Outcomes (KDIGO) workgroup. Peak aspartate aminotransferase (AST) level within 72 hours after OLT was used as a surrogate marker for HIRI. Graft steatosis was diagnosed by histopathological examination using specimens biopsied intraoperatively at the end of transplantation procedure and categorized as <10%, 10%-20%, 20%-30%, and ≥30% of hepatic steatosis.

Results: Out of 386 patients, 141 (37%) developed AKI (KDIGO stage 1:71 patients; stage 2:29 patients; stage 3:41 patients). Multivariable logistic regression analysis revealed that cold ischemic time (P = .012) and HIRI (P = .007) were independent risk factors for post-OLT AKI. Multivariable analysis also revealed that graft steatosis was associated with HIRI but not directly with AKI. PRS was not associated with HIRI or AKI in the multivariable analyses.

Conclusion: Our results indicate that greater severity of liver graft injury during transplantation negatively affects renal function after OLT. As expected, the severity of liver graft steatosis contributes to accelerated liver injury occurring during the transplantation procedure.
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http://dx.doi.org/10.1111/aas.13556DOI Listing
July 2020

Type of Preservation Solution, UW or HTK, Has an Impact on the Incidence of Biliary Stricture following Liver Transplantation: A Retrospective Study.

J Transplant 2019 21;2019:8150736. Epub 2019 Dec 21.

Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Organ preservation plays a crucial role in the outcome following solid organ transplantation. The aim of this study was to perform a retrospective outcome analysis following liver transplantation using histidine tryptophan ketoglutarate (HTK) or the University of Wisconsin (UW) solutions for liver graft preservation. We retrospectively reviewed data on adult patients who were liver-transplanted at Karolinska University Hospital between 2007 and 2015. There was evaluation of donor and recipient characteristics, pre- and post-transplant blood chemistry tests, biliary and vascular complications, graft dysfunction and nonfunction, and patient and graft survivals. A total of 433 patients were included in the analyses, with 230 and 203 patients having received livers preserved with HTK and UW, respectively. Mean follow-up was 45 ± 29 months for the HTK group and 42.4 ± 26 for the UW group. There was no difference between the two groups either in terms of patient and graft survival, or of results of postoperative blood chemistry, or incidence of arterial complications, early allograft dysfunction, or primary graft nonfunction. However, the incidence of biliary stricture was higher in the UW group (22.7%) versus the HTK group (13.5%; =0.013). Use of UW and HTK preservation solution in liver transplantation has no impact on patient and graft survival. However, use of HTK solution results in a lower incidence of posttransplant biliary stricture.
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http://dx.doi.org/10.1155/2019/8150736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942894PMC
December 2019

A Regional Report on the Evolution of Organ Transplantation in Estonia.

Transplantation 2019 10;103(10):1965-1967

Scandiatransplant, Aarhus, Denmark.

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http://dx.doi.org/10.1097/TP.0000000000002730DOI Listing
October 2019

Alcohol and drug use prior to liver transplantation: more common than expected in patients with non-alcoholic liver disease.

Scand J Gastroenterol 2019 Sep 27;54(9):1146-1154. Epub 2019 Aug 27.

The Transplant Institute, Sahlgrenska University Hospital , Gothenburg , Sweden.

Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease, acute liver failure or hepatocellular carcinoma (HCC). Patients with known alcoholic liver cirrhosis (ALC) are usually assessed by an addiction specialist, but patients with other liver diseases may also exhibit harmful drinking. This study aims to assess the drinking habits in LT-recipients with or without a diagnosis of ALC. Between April 2012 and December 2015, 190 LT-recipients were interviewed using the Lifetime Drinking History (LDH) and the Addiction Severity Index (ASI). Patients were categorized according to their diagnoses: ALC (group A,  = 39), HCC or hepatitis C (group B,  = 56) or other liver diseases (group C,  = 95). Data were analysed using descriptive statistic methods. Fifteen of 95 patients (15.8%) in group C - a cohort without suspected addiction problems - had either alcohol consumption or binge drinking within the upper quartile of the overall cohort. The aetiology of liver disease in this subgroup included mainly cholestatic and cryptogenic liver disease. Illicit drugs had been used by 35% of all patients. Cannabis and amphetamine were the most common drugs and had the longest duration of regular use. LT candidates without known alcohol or drug use may have a clinically significant consumption of alcohol and previous illicit drug use. Efforts should be put on identification of these patients during LT evaluation. The use of structured questionnaires such as the ASI and the LDH could facilitate detection of alcohol and drug problems.
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http://dx.doi.org/10.1080/00365521.2019.1656772DOI Listing
September 2019

Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study.

Transplantation 2019 09;103(9):1844-1862

Department of Hepatology and Gastroenterology, University Hospital of Henri-Mondor, Creteil, France.

Background: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study.

Methods: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004).

Results: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T.

Conclusions: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
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http://dx.doi.org/10.1097/TP.0000000000002700DOI Listing
September 2019

Characteristics and risk factors for recurrence of nonalcoholic steatohepatitis following liver transplantation.

Scand J Gastroenterol 2019 Feb 18;54(2):233-239. Epub 2019 Apr 18.

a Department of Clinical Science, Intervention and Technology, Division of Transplantation Surgery , Karolinska Institutet , Stockholm , Sweden.

Objectives: Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), is known to recur after LT. Since the recurrence of NASH can lead to graft failure, the identification of predictive factors is needed and preventive strategies should be implemented.

Methods: We retrospectively examined 95 patients who had undergone LT for NASH or alcoholic liver disease (ALD) as a primary indication. We evaluated peritransplant characteristics and histological findings 1-year post LT among liver transplant patients due to NASH or ALD.

Results: Pre-LT body mass index (BMI) was higher and pre-LT diabetes was more prevalent in NASH patients than in ALD patients (p < .01). The difference of BMI persisted at 3 months and 1 year after LT. There were no differences between the groups regarding histopathological findings including the degree of steatosis and fibrosis in 1-year biopsy. In multivariate analysis, recipient age and 1-year BMI were independent risk factors for post-LT fatty liver disease development. Regarding predictive factors of NASH recurrence, the prevalence of pre-LT insulin-dependent diabetes was significantly higher in patients who developed NASH recurrence than those who did not. The increase of HbA1c at 1-year post-LT checkup was higher in patients who developed recurrence than those who did not, although the difference did not reach statistical significance.

Conclusions: The results of this study suggest that insulin-dependent diabetes has detrimental effects on NASH recurrence following LT. Optimal glycemic control should be recommended, but studies are needed to prove its preventive effect on NASH recurrence.
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http://dx.doi.org/10.1080/00365521.2019.1577484DOI Listing
February 2019

Long-term Outcome of Endoscopic and Percutaneous Transhepatic Approaches for Biliary Complications in Liver Transplant Recipients.

Transplant Direct 2019 Mar 25;5(3):e432. Epub 2019 Feb 25.

Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Background: Biliary complications occur in 6% to 34% of liver transplant recipients, for which endoscopic retrograde cholangiopancreatography has become widely accepted as the first-line therapy. We evaluated long-term outcome of biliary complications in patients liver transplanted between 2004 and 2014 at Karolinska University Hospital, Stockholm.

Methods: Data were retrospectively collected, radiological images were analyzed for type of biliary complication, and graft and patient survivals were calculated.

Results: In 110 (18.5%) of 596 transplantations, there were a total of 153 cases of biliary complications: 68 (44.4%) anastomotic strictures, 43 (28.1%) nonanastomotic strictures, 24 (15.7%) bile leaks, 11 (7.2%) cases of stone- and/or sludge-related problems, and 7 (4.6%) cases of mixed biliary complications. Treatment success rates for each complication were 90%, 73%, 100%, 82% and 80%, respectively. When the endoscopic approach was unsatisfactory or failed, percutaneous transhepatic cholangiography or a combination of treatments was often successful (in 18 of 24 cases). No procedure-related mortality was observed. Procedure-related complications were reported in 7.7% of endoscopic retrograde cholangiopancreatography and 3.8% of percutaneous transhepatic cholangiography procedures. Patient survival rates, 1, 3, 5, and 10 years posttransplant in patients with biliary complications were 92.7%, 80%, 74.7%, and 54.1%, respectively, compared with 92%, 86.6%, 83.7%, and 72.8% in patients free from biliary complications ( < 0.01). Similarly, long-term graft survival was lower in the group experiencing biliary complications ( < 0.0001).

Conclusions: Endoscopic and percutaneous approaches for treating biliary complications are safe and efficient and should be considered complementing techniques. Despite a high treatment success rate of biliary complications, their occurrence still has a significant negative impact on patient and graft long-term survivals.
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http://dx.doi.org/10.1097/TXD.0000000000000869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411220PMC
March 2019

2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation.

Transpl Int 2018 12;31(12):1293-1317

Hôpital Henri Mondor, Créteil, France.

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.
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http://dx.doi.org/10.1111/tri.13358DOI Listing
December 2018

Cancer After Liver Transplantation in Children and Young Adults: A Population-Based Study From 4 Nordic Countries.

Liver Transpl 2018 09;24(9):1252-1259

Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.

Cancer after liver transplantation (LT) constitutes a threat also for young recipients, but cancer risk factors are usually absent in children and large studies on the cancer risk profile in young LT recipients are scarce. Data of patients younger than 30 years who underwent LT during the period 1982-2013 in the Nordic countries were linked with respective national cancer registries to calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were observed in 923 patients with 7846 person-years of follow-up. The SIR for all cancer types, compared with the matched general population, was 9.8 (12.4 for males and 7.8 for females). Cumulative incidence of cancer adjusted for the competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant risk factor for cancer, and the absolute risk of most cancers (except for lymphoma) increased considerably in young adults older than 20 years. The cancer risk pattern is different in pediatric and young LT patients compared with adult recipients. The striking increase in cancer incidence in young adulthood after the second decade of life deserves further consideration in transition programs.
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http://dx.doi.org/10.1002/lt.25305DOI Listing
September 2018

Technical Aspects of Orthotopic Liver Transplantation-a Survey-Based Study Within the Eurotransplant, Swisstransplant, Scandiatransplant, and British Transplantation Society Networks.

J Gastrointest Surg 2019 03 10;23(3):529-537. Epub 2018 Aug 10.

Department of Surgery and Transplantation, University Hospital RWTH Aachen, Pauwelsstrasse 30, Aachen, 52074, Germany.

Background: Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. However, technical aspects of OLT are still subject of ongoing debate and are widely based on personal experience and local institutional protocols.

Methods: An international online survey was sent out to all liver transplant centers (n = 52) within the Eurotransplant, Swisstransplant, Scandiatransplant, and British Transplant Society networks. The survey sought information on center-specific OLT caseload, vascular and biliary reconstruction, graft reperfusion, intraoperative control of hemodynamics, and drain policies.

Results: Forty-two centers gave a valid response (81%). Out of these, 50% reported piggy-back and 40.5% total caval replacement as their standard technique. While 48% of all centers generally do not apply veno-venous bypass (vvBP) or temporary portocaval shunt (PCS) during OLT, vvBP/PCS are routinely used in six centers (14%). Portal vein first reperfusion is used in 64%, followed by simultaneous (17%), and retrograde reperfusion (12%). End-to-end duct-to-duct anastomosis without biliary drain (67%) is the most frequently performed method of biliary reconstruction. No significant associations were found between the center caseload and the surgical approach used. The predominant part of the centers (88%) stated that techniques of OLT are not evidence-based and 98% would participate in multicenter clinical trials on these topics.

Conclusion: Technical aspects of OLT vary widely among European centers. The extent to which center-specific variation of techniques affect transplant outcomes in Europe should be elucidated further in prospective multicenter trials.
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http://dx.doi.org/10.1007/s11605-018-3915-6DOI Listing
March 2019

Circulating Fibroblast Growth Factor 19 in Portal and Systemic Blood.

J Clin Exp Hepatol 2018 Jun 28;8(2):162-168. Epub 2017 Jul 28.

Division of Transplantation Surgery, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.

Background: Bile acid homeostasis is essential and imbalance may lead to liver damage and liver failure. The bile acid induced intestinal factor fibroblast growth factor 19 (FGF19) has been identified as a key protein for mediating negative feedback inhibition of bile acid synthesis. The aim of the study was to define FGF19 and bile acid concentrations in portal and systemic blood in the fasted and postprandial state. We also addressed the question if physiological portal levels of FGF19 can be extrapolated from the concentration in systemic blood.

Methods: Portal and systemic blood was collected from 75 fasted patients undergoing liver surgery and from three organ donors before and after enteral nutrition. Serum concentration of FGF19 was determined with ELISA and bile acid concentration with gas chromatography-mass spectrometry.

Results: Concentration of bile acids was twice as high in portal compared to systemic blood in the fasted group and 3-5 times higher in the postprandial group. FGF19 increased after enteral nutrition but did not differ between portal and systemic blood, in either group. In addition, a strong, positive correlation between bile acids and FGF19 was found.

Conclusion: Our results confirm that bile acids drive the postprandial increase of circulating FGF19 but a hepatic clearance of FGF19 is unlikely. We conclude that systemic concentrations of FGF19 reflect portal concentrations of FGF19.
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http://dx.doi.org/10.1016/j.jceh.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992265PMC
June 2018

Liver transplantation for acute liver failure - a 30-year single center experience.

Scand J Gastroenterol 2018 Jun - Jul;53(7):876-882. Epub 2018 May 30.

a Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden and Department of Transplantation Surgery , Karolinska University Hospital , Stockholm , Sweden.

Objective: To determine overall long-term patient and graft survival rates among the recipients liver transplanted due to acute liver failure (ALF). Secondary aims included assessment of whether diagnosis, donor-recipient blood group compatibility and time-era of transplantation affected the outcome, and whether prescription-free availability of acetaminophen increased the need for liver transplantation (LTx).

Materials And Methods: A Retrospective cohort study of 78 patients who underwent LTx for ALF at Karolinska University Hospital 1984-2014. Patients were divided into two cohorts according to two 15-year periods: early cohort transplanted 1984-1999 (n = 40) and late cohort transplanted 2000-2014 (n = 38). Survival rates were established using Kaplan-Meier analyses.

Results: ALF patient survival rates for 1-year, 5-years, 10-years and 20-years were 71%, 63%, 52% and 40%, respectively. Survival for the late cohort at 1, 5 and 10 years was 82%, 76% and 71%, respectively. A high early mortality rate was noted during the first three months after transplantation when compared to LTx patients with chronic disease. Long-term survival rates were comparable between patients with ALF and chronic liver disease. Prescription-free access to acetaminophen did not increase the need for LTx. There was a strong trend towards improved survival in blood group identical donor-recipient pairs and blood group O recipients may have benefitted from this.

Conclusions: The high early mortality rate most likely reflects the critical pre-transplant condition in these patients and the urgent need to sometimes accept a marginal donor liver. Long-term survival improved significantly over time and variation in patient access to acetaminophen did not influence the rate of LTx in our region.
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http://dx.doi.org/10.1080/00365521.2018.1477986DOI Listing
November 2018

Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries.

Liver Int 2018 11 2;38(11):2082-2090. Epub 2018 May 2.

Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.

Background & Aims: Nonalcoholic fatty liver disease(NAFLD) is the second most common cause of liver transplantation in the US. Data on NAFLD as a liver transplantation indication from countries with lower prevalences of obesity are lacking. We studied the temporal trends of NAFLD as an indication for liver transplantation in the Nordic countries, and compared outcomes for patients with NAFLD to patients with other indications for liver transplantation.

Method: Population-based cohort study using data from the Nordic Liver Transplant Registry on adults listed for liver transplantation between 1994 and 2015. NAFLD as the underlying indication for liver transplantation was defined as a listing diagnosis of NAFLD/nonalcoholic steatohepatitis, or cryptogenic cirrhosis with a body mass index ≥25 kg/m and absence of other liver diseases. Waiting time for liver transplantation, mortality and withdrawal from the transplant waiting list were registered. Survival after liver transplantation was calculated using multivariable Cox regression, adjusted for age, sex, body mass index and model for end-stage liver disease.

Results: A total of 4609 patients listed for liver transplantation were included. NAFLD as the underlying indication for liver transplantation increased from 2.0% in 1994-1995 to 6.2% in 2011-2015 (P = .01) and was the second most rapidly increasing indication. NAFLD patients had higher age, model for end-stage liver disease and body mass index when listed for liver transplantation, but overall survival after liver transplantation was comparable to non--NAFLD patients (aHR 1.03, 95% CI 0.70-1.53 P = .87).

Conclusion: NAFLD is an increasing indication for liver transplantation in the Nordic countries. Despite more advanced liver disease, NAFLD patients have a comparable survival to other patients listed for liver transplantation.
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http://dx.doi.org/10.1111/liv.13751DOI Listing
November 2018

Survival of children after liver transplantation for hepatocellular carcinoma.

Liver Transpl 2018 02;24(2):246-255

Research Group Epidemiological and Statistical Methods, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.
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http://dx.doi.org/10.1002/lt.24994DOI Listing
February 2018

Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients.

Transplantation 2018 02;102(2):e59-e66

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Background: Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients.

Methods: The medical records of all LTx ATTRm amyloidosis patients in the county of Västerbotten, Sweden, were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status.

Results: Sixty-three patients that had survived for 3 years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P < 0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P = 0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P = 0.029).

Conclusions: AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However, the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.
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http://dx.doi.org/10.1097/TP.0000000000001975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802266PMC
February 2018

Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue.

Oncotarget 2017 Sep 24;8(36):60257-60269. Epub 2017 Jul 24.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC ( = 5), benign prostatic hyperplasia (BPH) ( = 27), BPH with concurrent PC ( = 4) and controls ( = 7). The majority of T-cells were CD8 and had a CCR7CD45RO effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostate-infiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD-1 T-cells in PC, the concomitant demonstration of high percentage of PD-1 T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.
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http://dx.doi.org/10.18632/oncotarget.19528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601136PMC
September 2017

Defining Benchmarks in Liver Transplantation: A Multicenter Outcome Analysis Determining Best Achievable Results.

Ann Surg 2018 03;267(3):419-425

Department of Surgery and Transplantation, Swiss HPB Center Zurich, University Hospital Zurich, Zurich, Switzerland.

: This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.

Objective: To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.

Background: Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.

Methods: Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.

Results: Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.

Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.
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http://dx.doi.org/10.1097/SLA.0000000000002477DOI Listing
March 2018

Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: Results from a multicenter, prospective study.

Pediatr Transplant 2017 Nov 17;21(7). Epub 2017 Jul 17.

Novartis Pharma AG, Basel, Switzerland.

In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard-of-care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2-5 ng/mL) until after month 6 post-enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m . Two patients experienced treated biopsy-proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2-18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.
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http://dx.doi.org/10.1111/petr.13024DOI Listing
November 2017

Exogenous alpha 1-antitrypsin down-regulates SERPINA1 expression.

PLoS One 2017 9;12(5):e0177279. Epub 2017 May 9.

Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

The main goal of the therapy with purified human plasma alpha1-antitrypsin (A1AT) is to increase A1AT levels and to prevent lungs from elastolytic activity in patients with PiZZ (Glu342Lys) A1AT deficiency-related emphysema. Potential hepatic gains of this therapy are unknown. Herein, we investigated the effect of A1AT therapy on SERPINA1 (gene encoding A1AT) expression. The expression of SERPINA1 was determined in A1AT or A1AT plus Oncostatin M (OSM) treated primary human hepatocytes isolated from liver tissues from A1AT deficient patients and control liver tissues. In addition, SERPINA1 mRNA was assessed in lung tissues from PiZZ emphysema patients with and without A1AT therapy, and in adherent human peripheral blood mononuclear cells (PBMC) isolated from healthy PiMM donors. In a dose-dependent manner purified A1AT lowered SERPINA1 expression in hepatocytes. This latter effect was more prominent in hepatocytes stimulated with OSM. Although it did not reach statistical significance (P = 0.0539)-analysis of lung tissues showed lower SERPINA1 expression in PiZZ emphysema patients receiving augmentation therapy relative to those without therapy. Finally, exogenously added purified A1AT (1mg/ml) reduced SERPINA1 expression in naïve as well as in lipopolysaccharide (LPS)-stimulated human adherent PBMCs. Exogenous A1AT protein reduces its own endogenous expression. Hence, augmentation with native M-A1AT protein and a parallel reduction in expression of dysfunctional mutant Z-A1AT may be beneficial for PiZZ liver, and this motivates further studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177279PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423693PMC
September 2017

Domino liver transplantation: full-length transthyretin in donor and recipient patients with ATTR Val30Met amyloidosis.

Amyloid 2017 Mar;24(sup1):128-129

b Division of Transplantation Surgery , CLINTEC, Karolinska Institutet and Karolinska University Hospital , Stockholm , Sweden , and.

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http://dx.doi.org/10.1080/13506129.2017.1294058DOI Listing
March 2017

Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy.

Clin Transplant 2017 06 27;31(6). Epub 2017 Apr 27.

Medical affairs, Astellas Pharma Europe Ltd, Chertsey, UK.

Background: With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged-release tacrolimus compared with immediate-release tacrolimus, prompting investigation of differing initial doses.

Methods: This substudy of a double-blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once-daily prolonged-release tacrolimus (initial dose: 0.2 mg/kg/day) versus twice-daily immediate-release tacrolimus (initial dose: 0.1 mg/kg/day) during the first 2 weeks post-transplant.

Results: Pharmacokinetic data were analyzed from patients receiving prolonged-release tacrolimus (n=13) and immediate-release tacrolimus (n=12). Mean systemic exposure (AUC ) was higher with prolonged-release versus immediate-release tacrolimus. Dose-normalized AUC (normalized to 0.1 mg/kg/day) showed generally lower exposure with prolonged-release tacrolimus versus immediate-release tacrolimus. There was good correlation between AUC and concentration at 24 hours after the morning dose (r=.96 and r=.86, respectively), and the slope of the line of best fit was similar for both formulations.

Conclusions: Doubling the initial starting dose of prolonged-release tacrolimus compared with immediate-release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged-release tacrolimus than immediate-release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough-level monitoring system. (ClinicalTrials.gov number: NCT00189826).
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http://dx.doi.org/10.1111/ctr.12958DOI Listing
June 2017

Advancing Transplantation: New Questions, New Possibilities in Kidney and Liver Transplantation.

Transplantation 2017 02;101 Suppl 2S:S1-S41

1 Karolinska University Hospital, Stockholm, Sweden. 2 Karolinska Institutet, Stockholm, Sweden. 3 Alberta Transplant Applied Genomics Centre, Edmonton, Canada. 4 Frankfurt University Hospital and Clinics, Frankfurt, Germany. 5 University of Heidelberg, Heidelberg, Germany. 6 Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. 7 Red de Investigación Renal (REDinREN), Instituto Carlos III, Madrid, Spain. 8 Hospital Universitari de Bellvitge, University of Barcelona, Spain. 9 Service de Néphrologie-Transplantation, Hôpital Necker, Paris, France. 10 University Hospitals Leuven, Leuven, Belgium. 11 University Hospital of Saint-Etienne, Jean Monnet University, France. 12 Western Infirmary, Glasgow, United Kingdom. 13 Fundació Puigvert, Barcelona, Spain. 14 University of Uppsala, Uppsala, Sweden. 15 King's College Hospital, London, United Kingdom. 16 Baylor University Medical Center Dallas, Dallas, TX. 17 Transplantcenter, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. 18 Department of Medical and Biological Sciences, University Hospital of Udine, Udine, Italy. 19 Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. 20 Directorate of Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, United Kingdom. 21 Department of Pathology, University of Pittsburgh, Pittsburgh, PA. 22 Experimental Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany. 23 Ahead of Time GmbH, Starnberg, Germany. 24 Better Value Healthcare, Oxford, United Kingdom.

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http://dx.doi.org/10.1097/TP.0000000000001563DOI Listing
February 2017