Publications by authors named "Arno Nordin"

44 Publications

Gallbladder cancer epidemiology, treatment and survival in Southern Finland - a population-based study.

Scand J Gastroenterol 2021 Aug 5;56(8):929-939. Epub 2021 Jul 5.

Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Introduction: Gallbladder cancer (GBC) is a rare malignancy in Western population with poor prognosis. This study aimed to investigate the trends in GBC incidence, treatment pattern, and survival in Finland.

Methods: Patients diagnosed with primary GBC in a geographically defined area (Southern Finland Regional Cancer Center) during 2006-2017 were identified.

Results: Final cohort included 270 patients with GBC. The incidence was 1.32/100,000 persons, and it decreased 6.8 cases per million personyears during the study period. One hundred fifty-one (56%) patients were diagnosed at Stage IV. Fifty-one patients (19%) underwent curative-intent resection with 96% R0-resection rate. The median overall survival was 7.1 months and 5-year overall survival 11.6% for all patients, and 67.7 months and 56.8% after curative-intent resection, respectively. No improvement was noted over time in overall survival in patients with GBC, or in subgroups of different stages of GBC.

Conclusions: The incidence of GBC is slightly decreasing in Southern Finland, but survival has not improved over time.
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http://dx.doi.org/10.1080/00365521.2021.1915373DOI Listing
August 2021

Salivary Biomarkers and Oral Health in Liver Transplant Recipients, with an Emphasis on Diabetes.

Diagnostics (Basel) 2021 Apr 7;11(4). Epub 2021 Apr 7.

Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, University of Helsinki, P.O. Box 220, 00100 Helsinki, Finland.

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels ( < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios ( < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health ( < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.
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http://dx.doi.org/10.3390/diagnostics11040662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067605PMC
April 2021

The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation.

Clin J Am Soc Nephrol 2021 03;16(3):427-436

Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Background And Objectives: Transplant centers in Europe aim to minimize the time from brain death to organ procurement (procurement delay), but evidence to justify this is scarce. In the United States, procurement times are significantly longer. Our objective was to analyze how procurement delay associates with kidney allograft outcomes.

Design, Setting, Participants, & Measurements: Kidney transplantations from brain-dead donors were retrospectively analyzed from the Finnish Kidney Transplant Registry and the Scientific Registry of Transplant Recipients in the United States. Multivariable models were adjusted with donor and recipient characteristics, and the relationship between procurement delay and outcomes was modeled with cubic spline functions.

Results: In total, 2388 and 101,474 kidney transplantations in Finland and the United States were included, respectively. The median procurement delay was 9.8 hours (interquartile range, 7.8-12.4) in Finland and 34.8 hours (interquartile range, 26.3-46.3) in the United States. A nonlinear association was observed between procurement delay and the risk of delayed graft function, with highest risk seen in short and very long procurement delays. In multivariable models, the lowest risk of delayed graft function was associated with procurement delay between 20 and 50 hours. In multivariable models, longer procurement delay was linearly associated with lower risk of graft loss (hazard ratio, 0.90/1 h longer; 95% confidence interval, 0.88 to 0.92; <0.001). Acute rejection rates, for which data were only available from Finland, were not associated with procurement delay.

Conclusions: Longer procurement delay was associated with noninferior or even better kidney allograft outcomes.
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http://dx.doi.org/10.2215/CJN.11420720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011019PMC
March 2021

First-day plasma amylase detects patients at risk of complications after simultaneous pancreas-kidney transplantation.

Clin Transplant 2021 04 4;35(4):e14233. Epub 2021 Feb 4.

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

Background: Simultaneous pancreas-kidney transplantation (SPK) carries a high risk of major postoperative complications, but knowledge on early warning signs and surrogate markers for postoperative complications is scarce.

Aims: Our aim was to analyze the complication-predictive value of different laboratory tests in pancreas transplantation.

Materials & Methods: All SPKs in Finland between January 2010 and February 2020 were retrospectively analyzed. Levels of first three-day plasma amylase, drain fluid amylase, C-reactive protein, C-peptide, plasma trypsinogen, and white blood cell count were assessed for their performance predicting cumulative postoperative complications (assessed using the Comprehensive Complication Index) within 90 days from transplantation by using ROC analyses.

Results: Of the 164 SPK patients included, 39 suffered at least one complication requiring laparotomy. First-day plasma amylase had the best value in predicting complications based on its high AUC value and easy clinical applicability, with an optimum cutoff of six times the upper normal limit. Negative predictive values (NPVs) and positive predictive values of this cutoff were 0.81 and 0.71 for any relaparotomy, and 0.91 and 0.71 for the Comprehensive Complication Index >47.7 (which equals the morbidity of two relaparotomies), respectively.

Conclusion: In conclusion, first-day plasma amylase could be able to detect patients at risk of complications after SPK.
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http://dx.doi.org/10.1111/ctr.14233DOI Listing
April 2021

Pre- vs. postoperative initiation of thromboprophylaxis in liver surgery.

HPB (Oxford) 2021 Jul 19;23(7):1016-1024. Epub 2020 Nov 19.

Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address:

Background: Thromboprophylaxis protocols in liver surgery vary greatly worldwide. Due to limited research, there is no consensus whether the administration of thromboprophylaxis should be initiated pre- or postoperatively.

Methods: Patients undergoing liver resection in Helsinki University Hospital between 2014 and 2017 were reviewed retrospectively. Initiation of thromboprophylaxis was changed in the institution in the beginning of 2016 from postoperative to preoperative. Patients were classified into two groups for analyses: thromboprophylaxis initiated preoperatively (Preop-group) or postoperatively (Postop-group). The incidences of VTE and haemorrhage within 30 days of surgery were compared between these groups. Patients with permanent anticoagulation were excluded.

Results: A total of 512 patients were included to the study (Preop, n = 253, Postop, n = 259). The incidence of VTE was significantly lower in the Preop-group compared to the Postop-group (3 (1.2%) vs. 25 (9.7%), P = <.0001), mainly due to a lower incidence of pulmonary embolisms in the Preop-group (3 (1.2%) vs. 24 (9.3%), P < .0001). The rates of posthepatectomy haemorrhage within 30 days of surgery were similar (Preop 38 (15.0%) vs. Postop 36 (13.9%), p = .719).

Conclusion: Initiating thromboprophylaxis preoperatively may reduce the incidence of postoperative VTE without affecting the incidence of posthepatectomy haemorrhage in patients undergoing liver resection.
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http://dx.doi.org/10.1016/j.hpb.2020.10.018DOI Listing
July 2021

Randomised sham-controlled double-blind trial evaluating remote ischaemic preconditioning in solid organ transplantation: a study protocol for the RIPTRANS trial.

BMJ Open 2020 11 16;10(11):e038340. Epub 2020 Nov 16.

Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Introduction: Remote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs.

Methods And Analyses: RIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients.

Ethics And Dissemination: This study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital's Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14-15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication.

Trial Registration Number: NCT03855722.
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http://dx.doi.org/10.1136/bmjopen-2020-038340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670950PMC
November 2020

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study.

Transpl Int 2020 12 25;33(12):1700-1710. Epub 2020 Sep 25.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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http://dx.doi.org/10.1111/tri.13734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756726PMC
December 2020

Outcomes and quality of life after major bile duct injury in long-term follow-up.

Surg Endosc 2021 Jun 22;35(6):2879-2888. Epub 2020 Jun 22.

Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Introduction: Recently new standards for reporting outcomes of bile duct injury (BDI) have been proposed. It is unclear how these treatment outcomes are reflected in quality of life (QOL). The aim of this study was to report outcomes and QOL after repair of major BDI and compare repairs by hepatobiliary surgeon to repairs by non-hepatobiliary surgeons.

Methods: This was a retrospective study of patients treated for major (Strasberg E-type) BDI after cholecystectomy at a tertiary hepatobiliary center. Outcomes were assessed using Cho-Strasberg proposed standards. QOL was assessed using Short Form Health Survey (SF-36) and the gastrointestinal QOL-index (GIQLI). Patients undergoing uneventful cholecystectomy matched by age, urgency, and duration of follow-up were used as controls.

Results: Fifty-two patients with major BDI treated between 2000 and 2016 were included (42% male, median age 53 years). Thirty-seven (71%) patients attained primary patency (29 (83%) if primarily operated by a hepatobiliary surgeon). Actuarial primary patency rate (grade A result) at 1, 3, and 5 years was 58%, 56%, and 53% in the whole cohort, and 83%, 80%, and 80% in patients primary treated by a hepatobiliary surgeon, respectively. At 3-year follow-up 6 (11.5%) patients obtained grade B, 10 (19.2%) grade C, and 7 (13.5%) grade D result. QOL was similar in patients with BDI and controls (median SF-36 physical component 51.7 and 53.6, p = 1.0, mental component 53.3 and 53.4, p = 1.0, GIQLI 109.0 and 123.0, p = 0.174, respectively) at median 90 (IQR 70-116) months from cholecystectomy. QOL was similar regardless of outcome grade.

Conclusion: First attempt to repair a severe BDI should be undertaken by a hepatobiliary surgeon. However, long-term QOL is not affected even by severe BDI, and QOL is not associated with the grade of the outcome.
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http://dx.doi.org/10.1007/s00464-020-07726-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116261PMC
June 2021

Cancer morbidity and mortality after pediatric solid organ transplantation-a nationwide register study.

Pediatr Nephrol 2020 09 11;35(9):1719-1728. Epub 2020 May 11.

Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The prevalence of malignancies after pediatric solid organ transplantation was evaluated in a nationwide study.

Methods: All patients who had undergone kidney, liver, or heart transplantation during childhood between the years 1982 and 2015 in Finland were identified. The inclusion criteria were age under 16 years at transplantation and age over 18 years at the last follow-up day. A total of 233 (137 kidney, 53 liver, and 43 heart) transplant recipients were enrolled. Controls (n = 1157) matched by the year of birth, gender, and hometown were identified using the Population Register Center registry. The cancer diagnoses were searched using the Finnish Cancer Registry.

Results: Altogether 26 individuals diagnosed with cancer were found, including 18 transplant recipients. Cancer was diagnosed at a median of 12.0 (IQR 7.8-17.8) years after the transplantation. The transplant recipients' risk for cancer was significantly higher when compared with the controls (HR 14.7; 95% CI 6.4-33.9). There was no difference for different graft types. Sixty-one percent of cancers among the transplant recipients were diagnosed at age older than 18 years.

Conclusion: The risk for cancer is significantly higher among young adults having undergone solid organ transplantation during childhood in comparison with population controls. Careful follow-up and attention to prevent cancers throughout adulthood are warranted.
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http://dx.doi.org/10.1007/s00467-020-04546-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385020PMC
September 2020

Enhanced recovery protocol in laparoscopic liver surgery.

Surg Endosc 2021 03 27;35(3):1058-1066. Epub 2020 Feb 27.

Department of Transplantation and Liver Surgery, HUS Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, 00029, Helsinki, Finland.

Introduction: Enhanced recovery protocols (ERP) accelerate recovery and shorten postoperative hospital stay. This increased knowledge of ERPs has also gradually implemented into liver surgery. However, in laparoscopic liver surgery (LLS), the experience of optimized perioperative care protocols is still limited.

Methods: We prospectively studied the implementation of multimodal ERP principles to LLS in the first 100 consecutive patients. Opioid-sparing multimodal pain management was applied together with early mobilization already in the postoperative care unit (PACU). Drains and catheters were avoided and per oral intake was initiated promptly. Primary pain control was achieved with iv NSAIDS, low-dose opioid and corticosteroids. Combination of per oral ibuprofen and long-acting tramadol was routinely administered shortly after operation. The multiprofessional adherence to the protocol was also evaluated.

Results: Investigated LLS was performed during Aug 2016-Apr 2019. Operations were done due to malignancy in 83 (83%) of cases, mostly for colorectal liver metastases (n = 52, 52%). Forty-eight (48%) of the operated patients were female. Median age was 65 years (range 17-91). The American Society of Anaesthesiologists Physical Status (ASA) classification median was three. Median postoperative hospital stay was 2 days (range 1-8 days). More than seventy percent of patients were discharged by the second postoperative day and nearly ninety percent by the third postoperative day. Complications after surgery were few. The new ERP elements were adopted in most of the cases.

Conclusions: ERP was introduced safely and effectively after LLS. The adherence to the ERP was good. Routine discharge 1-2 days after LLS is realistic and achievable.
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http://dx.doi.org/10.1007/s00464-020-07470-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886749PMC
March 2021

Role of Autoimmunity in Patients Transplanted for Acute Liver Failure of Unknown Origin: A Clinical and Graft Biopsy Analysis.

Liver Transpl 2020 06 11;26(6):764-773. Epub 2020 May 11.

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

The etiology and prognosis of acute liver failure (ALF) remains unknown in a significant proportion of cases. Signs of autoimmunity may be present, but no consistent pattern has been observed. We aimed to analyze if pretransplant immunological findings, human leukocyte antigen (HLA) haplotypes, and clinical features among patients with an unknown etiology differ from those of autoimmune or other known etiologies. We also analyzed whether such signs impact posttransplant biopsy findings or complications. All adult ALF patients undergoing liver transplantation (LT) in Finland during 1987-2015 were followed to 2016. Data were collected from the LT registry, pathology database, and patient records. A total of 124 patients were included in the analysis. Study subgroups were acute autoimmune hepatitis (AIH; n = 25), known non-AIH etiology (n = 54), and unknown etiology (n = 45). The unknown etiology group differed from the known non-AIH group with regard to the following pretransplant autoimmunity-associated features: positive perinuclear anti-neutrophil cytoplasmic antibodies (36% versus 8%; P = 0.02) and higher mean immunoglobulin A (IgA; 3.2 ± 1.7 versus 2.1 ± 1.4, P = 0.006) and immunoglobulin G (IgG; 12.7 ± 4.3 versus 8.5 ± 3.6, P = 0.001). AIH-associated HLA haplotypes B8, DR3, and B8DR3 were more common in the AIH group (40%, 44%, and 36%, respectively) and in the unknown group (29%, 33%, and 29%, respectively) than in the known non-AIH group (11%, 17%, and 11%, respectively) or in the Finnish general population (17%, 18%, and 8%, respectively). However, these findings had no association with protocol biopsies, extrahepatic autoimmune diseases, or survival. Patients with ≥ 1 rejection episode had higher pretransplant IgA (3.7 ± 2.3 versus 2.6 ± 1.2; P = 0.02) and IgG (16.4 ± 10.2 versus 12.4 ± 6.8; P = 0.03) than those without rejections. Autoimmunity-associated pretransplant laboratory findings and HLA haplotypes were common in ALF of unknown etiology, but they showed minimal predictive value for posttransplant biopsy findings, clinical complications, or survival.
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http://dx.doi.org/10.1002/lt.25729DOI Listing
June 2020

Long-term outcome after sequential liver and lung metastasectomy is comparable to outcome of isolated liver or lung metastasectomy in colorectal carcinoma.

Surg Oncol 2019 Sep 25;30:22-26. Epub 2019 May 25.

Department of Abdominal Center, Transplant and Liver Surgery, Helsinki University, Helsinki, Finland.

Background And Aims: Previously, colorectal cancer (CRC) metastasis of both liver and lungs was considered disseminated disease, which contraindicated surgical metastasectomies. Increasing evidence from studies on patient series have indicated that survival improved after resecting both liver and lung metastases. However, those results and long-term outcomes remain controversial. We aimed to compare surgical outcomes between patients treated for both liver and lung metastases to the patients who had only isolated liver or lung metastases.

Material And Methods: All patients (n = 105) underwent surgery for CRC metastases between July 2002 and September 2015. Three groups were compared: the sequentially operated group (n = 33 patients) underwent sequential liver and lung resections; the liver group (n = 38 patients) underwent liver resections; and the lung group (n = 34 patients) underwent lung resections. The main endpoints were long-term survival rates.

Results: The groups were not different in disease-free survival (P = 0.727) or overall survival (P = 0.218). Five-year survival rates were 69.7% in the sequentially operated group, 65.1% in the liver group, and 50.0% in the lung group.

Conclusion: Long-term outcomes after sequential liver and lung resections of CRC metastases were comparable to outcomes after isolated liver or lung metastasectomies. Therefore, aggressive surgical interventions should be considered for patients with both liver and lung metastases of CRC.
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http://dx.doi.org/10.1016/j.suronc.2019.05.015DOI Listing
September 2019

Graft glycocalyx degradation in human liver transplantation.

PLoS One 2019 15;14(8):e0221010. Epub 2019 Aug 15.

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objective: Ischaemia/reperfusion-injury degrades endothelial glycocalyx. Graft glycocalyx degradation was studied in human liver transplantation.

Methods: To assess changes within the graft, blood was drawn from portal and hepatic veins in addition to systemic samples in 10 patients. Plasma syndecan-1, heparan sulfate and chondroitin sulfate, were measured with enzyme-linked immunosorbent assay.

Results: During reperfusion, syndecan-1 levels were higher in graft caval effluent [3118 (934-6141) ng/ml, P = 0.005] than in portal venous blood [101 (75-121) ng/ml], indicating syndecan-1 release from the graft. Concomitantly, heparan sulfate levels were lower in graft caval effluent [96 (32-129) ng/ml, P = 0.037] than in portal venous blood [112 (98-128) ng/ml], indicating heparan sulfate uptake within the graft. Chondroitin sulfate levels were equal in portal and hepatic venous blood. After reperfusion arterial syndecan-1 levels increased 17-fold (P < 0.001) and heparan sulfate decreased to a third (P < 0.001) towards the end of surgery.

Conclusion: Syndecan-1 washout from the liver indicates extensive glycocalyx degradation within the graft during reperfusion. Surprisingly, heparan sulfate was taken up by the graft during reperfusion. Corroborating previous experimental reports, this suggests that endogenous heparan sulfate might be utilized within the graft in the repair of damaged glycocalyx.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695121PMC
March 2020

Effect of Pretransplant Dialysis Modality on Outcomes After Simultaneous Pancreas-Kidney Transplantation.

Ann Transplant 2019 Jul 19;24:426-431. Epub 2019 Jul 19.

Department of Transplantation and Liver Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

BACKGROUND Pretransplant dialysis modality may affect outcome after simultaneous pancreas-kidney transplantation (SPKT), and it has been suspected that peritoneal dialysis (PD) is associated with more postoperative complications compared to hemodialysis (HD). The aim of this study was to evaluate whether pretransplant dialysis modality affects the risk for postoperative complications in SPKT recipients. MATERIAL AND METHODS This was a retrospective longitudinal cohort study of all patients undergoing SPKT from 2010 to 2017, during which 99 simultaneous pancreas-kidney transplantations were performed. Three pre-emptive transplantations were excluded. Patient groups receiving PD (n=59) or HD (n=37) were similar regarding baseline characteristics. All complications occurring during the first 3 months after transplantation, as well as patient and graft survival, were analyzed. RESULTS There were no significant differences in postoperative complications between groups, with similar rates of intra-abdominal infections (8% in HD vs. 10% in PD), pancreatitis (16% in HD vs. 17% in PD), gastrointestinal bleedings (22% in HD vs. 10% in PD), and relaparotomies (27% in HD vs. 24% in PD). None of the patients had venous graft thrombosis. Past peritonitis was not associated with increased risk for postoperative complications in PD patients. Patient and graft survival were similar between PD and HD groups. CONCLUSIONS Peritoneal dialysis is not a risk factor for postoperative complications after SPKT.
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http://dx.doi.org/10.12659/AOT.916649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668491PMC
July 2019

Transcatheter arterial embolization in hepatic tumor hemorrhage.

Scand J Gastroenterol 2019 Jul 26;54(7):917-924. Epub 2019 Jun 26.

Department of Abdominal Surgery, Helsinki University Hospital, University of Helsinki , Helsinki , Finland.

Spontaneous hepatic tumor hemorrhage is a rare but challenging emergency especially among cirrhotic patients with poor hepatic function. This study aimed at analyzing the safety, efficacy and feasibility of transcatheter arterial embolization (TAE) in the treatment of hepatic tumor hemorrhage. This retrospective study included all patients undergoing embolization attempt for hepatic tumor hemorrhage in the Helsinki University Hospital during 2004-2017. Electronic medical records provided the study data. Outcomes included the 30-day rebleeding, complication and mortality rates, need for blood transfusions, durations of intensive care unit and hospital admissions, estimates of overall survival, and analysis of factors associated with 30-day mortality. During the study period, 49 patients underwent angiography for hepatic tumor hemorrhage. TAE was technically feasible in 45 patients (92%), and controlled the bleeding with the first attempt in 84%. The 30-day complication and mortality rates were 57 and 33%, respectively. Major complications occurred in 33% of patients. In-hospital mortality was higher among cirrhotic than non-cirrhotic patients (55 versus 7%,  < .001). Patients with bleeding hepatic metastases, but no cirrhosis, had an in-hospital mortality of 0% with no major complications. Patients with benign etiology had a good prognosis and no bleeding- or tumor-related mortality. TAE is an effective method in controlling the bleeding in spontaneous hepatic hemorrhage. Underlying pathology determines the prognosis that is poor especially in cirrhotic patients with bleeding hepatocellular carcinoma.
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http://dx.doi.org/10.1080/00365521.2019.1633566DOI Listing
July 2019

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

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

Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases.

Tumour Biol 2018 Jan;40(1):1010428317752944

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

Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland. The samples were taken before and 3 months after curative resection. Increased concentrations of CEA (>5 µg/L) and hCGβ (>1 pmol/L) 3 months after liver resection correlated with recurrence and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired overall survival, but postoperative TATI was not prognostic. Preoperatively elevated CEA and CA19-9 correlated with impaired overall survival, but not with recurrence. Neither preoperative hCGβ nor TATI was prognostic. In conclusion, CEA is a useful prognostic marker, when measured 3 months after resection of colorectal liver metastases. CA19-9 also has prognostic significance and may have additional value.
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http://dx.doi.org/10.1177/1010428317752944DOI Listing
January 2018

The risk of incidental gallbladder cancer is negligible in macroscopically normal cholecystectomy specimens.

HPB (Oxford) 2018 05 13;20(5):456-461. Epub 2017 Dec 13.

Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address:

Background: Cholecystectomy is usually carried out for benign indications. Most perform routine histopathologic examination to detect incidental gallbladder cancer (GBC).

Methods: Cholecystectomies performed at four hospitals in the Helsinki Metropolitan Area during 2010-2012 were analyzed retrospectively. Patients with preoperative suspicion of neoplasia, active malignancy, or in whom cholecystectomy was performed as a secondary procedure were excluded.

Results: A total of 2034 cholecystectomies were included. In ten patients (0.5%), GBC was identified, each with an associated macroscopic finding, including local hardness (n = 1), a thickened wall (n = 5), acute inflammation and necrosis (n = 1), or suspected neoplasia (n = 3). No GBC was found in macroscopically normal gallbladders (n = 1464). Of the ten patients with GBC, five underwent subsequent liver resection, four had metastatic disease, and one had locally advanced inoperable disease. Three of the five patients who underwent liver resection were alive and disease-free at final follow-up (median 48 months). The remaining seven patients with GBC died of the disease, with a median survival of 14 months (range 10-48 months).

Conclusions: Routine histopathologic examination of a macroscopically normal gallbladder does not improve diagnosis of GBC. A histopathological examination is, however, mandatory when a macroscopic abnormality is present.
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http://dx.doi.org/10.1016/j.hpb.2017.11.006DOI Listing
May 2018

When should a drain be left in the abdominal cavity upon surgery?

Duodecim 2017;133(11):1063-8

Passive or active drainage can be used after abdominal surgery. Drains aim at eradicating infected or inflammatory tissue fluids and to alarm of undesired events such as bile, pancreatic, or bowel leak. Drains may, however, occlude or be situated away from the postoperative dilemma. Furthermore, drains themselves are susceptible to cause or maintain infection by retrograde contamination, may irritate the peritoneum causing excess ascites formation, and cause pain. Recent scientific evidence suggests that drains are unnecessary after most abdominal operations. Thus, drains should be used only in certain specific operation types such as pancreatic and emergency surgery. In other operations drains can be omitted if no clear risk factors are present.
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January 2018

Living donor kidney transplantation.

Duodecim 2017;133(10):937-44

While the majority of kidney transplantations in Finland have been traditionally performed from deceased donors, the frequency of living donors should be increased. Kidney donation is a safe procedure for a carefully examined donor, and for the recipient living donation enables elective surgery and preemptive transplantation. Potential risks for the donor must be minimized, but according to current recommendations, mild hypertension or obesity are not absolute contraindications for donation. Guidelines for donor selection and examination have been updated to simplify the process for all parties. Legislation in Finland requires changes to optimize the use of all potential living donors.
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January 2018

Endoscopic Therapy of Biliary Injury After Cholecystectomy.

Dig Dis Sci 2018 02 25;63(2):474-480. Epub 2017 Sep 25.

Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki University, Haartmaninkatu 4, 00290, Helsinki, Finland.

Background: Iatrogenic bile duct injury (BDI) is a common complication after cholecystectomy. Patients are mainly treated endoscopically, but the optimal treatment method has remained unclear.

Aims: The aim was to analyze endoscopic treatment in BDI after cholecystectomy and to explore endoscopic sphincterotomy (ES), with or without stenting, as the primary treatment for an Amsterdam type A bile leak.

Methods: All patients referred to Helsinki University Hospital endoscopy unit due to a suspected BDI between the years 2004 and 2014 were included in this retrospective study. To collect the data, all ERC reports were reviewed.

Results: Of the 99 BDI patients, 94 (95%) had bile leak of whom 11 had concomitant stricture. Ninety-three percent of all patients were treated endoscopically. Seventy-one patients had native papillae and a leak in the cystic duct or peripheral radicals. They were treated with ES (ES group, n = 50) or with sphincterotomy and stenting (EST group, n = 21). There was no difference between the closure time of the fistula (p = 0.179), in the time of discharge from hospital (p = 0.298), or in the primary healing rate between the ES group and the EST group (45/50 vs 19/21 patients, p = 0.951).

Conclusion: After the right patient selection, the success rate of endoscopic treatment can approach 100% for Amsterdam type A bile leak. ES is an effective and cost-effective single procedure with success rate similar to EST. It may be considered as a first-line therapy for the management of Amsterdam type A leaks.
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http://dx.doi.org/10.1007/s10620-017-4768-7DOI Listing
February 2018

Oral surgery in liver transplant candidates: a retrospective study on delayed bleeding and other complications.

Oral Surg Oral Med Oral Pathol Oral Radiol 2016 May 13;121(5):490-5. Epub 2016 Feb 13.

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

Objective: Untreated dental infections pose a threat for immunocompromised liver transplant (LT) recipients. Therefore, pretransplant dental evaluations are recommended. However, risk of bleeding should be considered among patients with end-stage liver disease, and prophylactic blood transfusions may be used to prevent bleeding. We performed a retrospective study of the incidence of and risk factors for oral surgery-related bleeding in candidates for LT and hypothesized that complications may occur despite preoperative and perioperative hemostatic actions.

Study Design: One hundred thirty-four patients who had tooth extractions performed by oral and maxillofacial surgeons before LT were studied. The primary endpoint was bleeding between 24 hours and 2 weeks after extraction. Bleeding risk was analyzed by preoperative platelet (PLT) count and international normalized ratio (INR). Invasiveness of procedures, severity of liver disease, PLT, INR, prophylactic transfusions of PLT, fresh frozen plasma, and tranexamic acid (TA) were included in univariate and multivariate logistic regression analyses to further assess risk.

Results: Twelve patients exhibited minor bleeding; four despite PLT >100 × 10(9)/L and INR <1.5. Increased bleeding associated with INR and prophylactic transfusions by univariate analysis; by multivariate analyses, prophylactic TA (odds ratio [OR] = 8.0; 95% confidence interval [CI] 1.7-37.0), and PLT (OR = 8.3; 95% CI 1.1-62.7) remained significant.

Conclusions: Most extractions were safe, but prophylactic transfusions did not ensure adequate hemostasis. Local hemostatic measures and close follow-up are warranted.
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http://dx.doi.org/10.1016/j.oooo.2016.01.025DOI Listing
May 2016

Treatment of ascites and its complications.

Duodecim 2016;132(18):1719-25

The underlying cause of ascites should always be treated if possible. Adhering to a low-salt diet is most important in the treatment of ascites. Diuretics are used in the treatment of clinically established and abundant ascites. The first-line drug in diuretic therapy is spironolactone, when necessary in combination with furosemide. The most important complications of ascites are hepatorenal syndrome and spontaneous bacterial peritonitis. The development of ascites lowers the quality of life, and is associated with significant mortality. Although new groundbreaking therapies are not available, prognosis of the patients is expected to be improved through optimization of current therapies.
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January 2018

Early Predictors of Long-term Outcomes of HCV-negative Liver Transplant Recipients Having Survived the First Postoperative Year.

Transplantation 2016 Feb;100(2):382-90

1 Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland. 2 Clinic of Gastroenterology, Helsinki University Hospital, Helsinki University, Finland.

Background: The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV-negative recipients.

Methods: This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections.

Results: Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P < 0.001), glomerular filtration rate (HR 0.89, P = 0.002), hypertension (HR 0.44, P < 0.001), early posttransplant infections (HR 1.52-1.67, P = 0.007-0.03), and alkaline phosphatase (ALP) (HR 1.05, P < 0.001). Elevated ALP at 1 year, affecting 30% of patients, predicted both graft loss and rejection, independent of immunologic stability, etiology, and immunosuppression type. Area under the curve of ALP in predicting graft loss from rejection was 0.81 (95% CI 0.71-0.90) and 0.85 (95% CI 0.72-0.98, P = 0.001) among patients under 50. Among immunologically stable patients who underwent transplantation after 2000, antimetabolite use at 1 year was associated with improved survival (P = 0.04), specifically in the subgroup with native-liver hepatocellular or biliary cancer (P = 0.02).

Conclusions: Easily measurable, widely available, and noninvasive factors known at 1 year post-LT can help stratify patients according to their long-term risk of death or graft loss, and thus facilitate a personalization of long-term follow-up. ALP deserves routine monitoring, and the cause for an elevated ALP should be sought.
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http://dx.doi.org/10.1097/TP.0000000000001038DOI Listing
February 2016

Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013.

Scand J Gastroenterol 2015 Jun;50(6):797-808

Section for Transplantation Surgery, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital , Oslo , Norway.

Aim And Background: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013.

Materials And Methods: The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report.

Results: Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively.

Conclusion: The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).
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http://dx.doi.org/10.3109/00365521.2015.1036359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487534PMC
June 2015

Who is too healthy and who is too sick for liver transplantation: external validation of prognostic scores and survival-benefit estimation.

Scand J Gastroenterol 2015 11;50(9):1144-51. Epub 2015 Apr 11.

Clinic of Gastroenterology, Helsinki University Hospital, Helsinki University , Helsinki , Finland.

Objective: Thresholds for when a patient should be considered too healthy or too sick to undergo liver transplantation (LT) have been pursued, but have undergone little external validation and may differ between centers and countries.

Material And Methods: We investigated the ability of the Model for End-stage Liver Disease (MELD), D-MELD, Donor Risk Index (DRI) and Balance of Risk (BAR) scores to predict 1-year graft survival, and determined the 1-year survival-benefit of LT, compared with conservative management, according to MELD score and graft quality among 538 adult LT recipients with underlying chronic non-malignant liver disease.

Results: One-year graft survival rates showed small, but statistically significant variation according to MELD (p = 0.002) and D-MELD score (p = 0.04), and among LTs after year 2000 also according to BAR score (p = 0.01), but not according to DRI. Diagnostic accuracy of these scores was poor; area under the curve was 0.50-0.65 depending on the score. A 1-year survival-benefit of LT emerged at MELD scores ≥15, but also at lower MELD scores when using high-quality grafts (DRI <1.075).

Conclusions: The performance of various prognostic scores in the Finnish setting was poor. Careful clinical evaluation is imperative when deciding on the timing of LT in the course of chronic liver disease.
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http://dx.doi.org/10.3109/00365521.2015.1028992DOI Listing
March 2016

[Four years of simultaneous pancreas-kidney transplantations in Finland].

Duodecim 2014 ;130(20):2079-85

HYKS:n Operatiivinen tulosyksikkö.

The first simultaneous pancreas-kidney transplantation in Finland was performed in 2010. On a global scale, already more than 45,000 pancreatic transplantations have been performed. Pancreatic transplantation restores the blood glucose level to normal, but only at the cost of possible adverse effects due to surgery and anti-rejection drugs. Based on our experience with 24 patients, this operation has met the expectations and shown that simultaneous pancreas-kidney transplantation is a good alternative for selected type 1 diabetics instead of mere kidney transplantation. In the future we aim to conduct approximately 15 combined transplantations per year.
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January 2015

Differences in long-term survival among liver transplant recipients and the general population: a population-based Nordic study.

Hepatology 2015 Feb 5;61(2):668-77. Epub 2015 Jan 5.

Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland; Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.

Unlabelled: Dramatic improvement in first-year outcomes post-liver transplantation (LT) has shifted attention to long-term survival, where efforts are now needed to achieve improvement. Understanding the causes of premature death is a prerequisite for improving long-term outcome. Overall and cause-specific mortality of 3,299 Nordic LT patients (1985-2009) having survived 1 year post-LT were divided by expected rates in the general population, adjusted for age, sex, calendar date, and country to yield standardized mortality ratios (SMRs). Data came from the Nordic Liver-Transplant Registry and WHO mortality-indicator database. Stagnant patient survival rates >1 year post-LT were 21% lower at 10 years than expected survival for the general population. Overall SMR for death before age 75 (premature mortality) was 5.8 (95% confidence interval [CI] 5.4-6.3), with improvement from 1985-1999 to 2000-2010 in hepatitis C (HCV) (SMR change 23.1-9.2), hepatocellular carcinoma (HCC) (SMR 38.4-18.8), and primary sclerosing cholangitis (SMR 11.0-4.2), and deterioration in alcoholic liver disease (8.3-24.0) and acute liver failure (ALF) (5.9-7.6). SMRs for cancer and liver disease (recurrent or transplant-unrelated disease) were elevated in all indications except primary biliary cirrhosis (PBC). Absolute mortality rates underestimated the elevated premature mortality from infections (SMR 22-693) and kidney disease (SMR 13-45) across all indications, and from suicide in HCV and ALF. SMR for cardiovascular disease was significant only in PBC and alcoholic liver disease, owing to high mortality in the general population. Transplant-specific events caused 16% of deaths.

Conclusion: standardized premature mortality provided an improved picture of long-term post-LT outcome, showing improvement over time in some indications, not revealed by overall absolute mortality rates. Causes with high premature mortality (infections, cancer, kidney and liver disease, and suicide) merit increased attention in clinical patient follow-up and future research.
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http://dx.doi.org/10.1002/hep.27538DOI Listing
February 2015

[Acute hepatitis in a middle-aged woman].

Duodecim 2014 ;130(13):1329-33

In mild cases of hepatitis the patient may be completely symptomless or merely suffer from upper abdominal discomfort and lack of appetite, whereas in severe hepatitis the patient is seriously ill and may rapidly develop hepatic insufficiency requiring intensive care. The most common causative agents include hepatitis viruses A, B and C, alcohol and numerous pharmacologic agents. We describe acute hepatitis in a middle-aged, working woman, whose hepatic insufficiency led to thorough investigations in specialized care. Etiologic examinations necessitated a liver biopsy.
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September 2014
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