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  • 101.
    Okamoto, Sadahisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ericzon, B-G
    Friman, S
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Prognostic value of pre-transplant cardiomyopathy in Swedish liver transplanted patients for familial amyloidotic polyneuropathy2011In: Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, ISSN 1744-2818, Vol. 18 Suppl 1, p. 166-8Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LTx) for familial amyloidotic polyneuropathy (FAP) is a recognized treatment for halting disease progression. Since cardiac complications are the main cause of postoperative death in FAP patients, we studied the potential relationship between pre-LTx amyloid heart disease and post-LTx mortality. Seventy-five Swedish patients who underwent LTx (72 Val30Met and 3 non-Val30Met patients) were available for the study. An intra-ventricular septal (IVS) thickness more than 15 mm at the pre-LTx evaluation was defined as cardiomyopathy. Nine patients out of 75 patients died, all were males and all belonged to the late onset group (age at onset ≥50 years). Four had cardiomyopathy at the pre-LTx evaluation. Survival rate was significantly higher in patients without cardiomyopathy at LTx compared to those with cardiomyopathy. Our results suggest that cardiomyopathy at LTx has an impact on the outcome of LTx for FAP.Read More: http://informahealthcare.com/doi/full/10.3109/13506129.2011.574354064

  • 102.
    Okamoto, Sadahisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Obayashi, Konen
    Ando, Yukio
    Ericzon, Bo-Göran
    Friman, Styrbjörn
    Uchino, Makoto
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liver transplantation for familial amyloidotic polyneuropathy: impact on Swedish patients' survival2009In: Liver transplantation, ISSN 1527-6465, E-ISSN 1527-6473, Vol. 15, no 10, p. 1229-1235Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LTx) for familial amyloidotic polyneuropathy (FAP) is an accepted treatment for this fatal disease. However, the long-term outcome with respect to that of nontransplanted patients has not been fully elucidated. The aim of this study was to compare the long-term survival of Swedish LTx FAP patients with that of historical controls, especially with respect to the age at onset of the disease and gender. In order to evaluate the outcome of LTx as a treatment for FAP, survival was calculated from the onset of disease. One hundred forty-one FAP patients, 108 transplanted and 33 not transplanted, were included in the study. Significantly increased survival was noted for LTx patients in comparison with controls. The outcome was especially favorable for those with an early onset of the disease (age at onset < 50 years) in comparison with early-onset controls (P < 0.001). In contrast, no significant difference for late-onset cases (> or = 50 years) was found. Transplanted late-onset females had significantly improved survival in comparison with transplanted late-onset males (P = 0.02). We were unable to find significant differences in survival between patients with long (> or = 7 years) or short (<7 years) disease duration at transplantation. The survival of male patients with late-onset disease appeared not to improve with LTx. LTx is an efficacious treatment for improving the survival of early-onset FAP patients. Further studies are needed to analyze the cause of the poorer outcome for late-onset male patients.

  • 103.
    Okamoto, Sadahisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Backman, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Ericzon, Bo-Göran
    Center for Surgical Sciences, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden.
    Wijayatunga, Priyantha
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Development of cardiomyopathy after liver transplantation in Swedish hereditary transthyretin amyloidosis (ATTR) patients2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no 4, p. 200-205Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies of liver transplanted (LTx) familial amyloidotic polyneuropathy (FAP) patients have shown a progression of cardiomyopathy in some patients after LTx, but knowledge of the underlying factors remains limited.

    Methods: Seventy-five patients, who had undergone LTx from 1996 to 2008, were included. They had all been examined by echocardiography 1-16 months before LTx. Fifty-four had been re-examined 7-34 months, and forty-two 36-137 months after LTx.

    Results: A significant increase in interventricular septum (IVS) thickness occurred after LTx (p < 0.01), particularly in males (p = 0.002) and late onset patients (p = 0.003). The development of post-LTx cardiomyopathy was related to patient's age at onset of the disease, male gender and pre-LTx IVS thickness. On multivariate regression analysis, however, age at onset was the only significant predictor for the development of cardiomyopathy (odds ratio = 1.14, 95% confident interval 1.01-1.30, p = 0.04).

    Conclusion: An increase of IVS thickness can be observed in FAP patients after LTx. Age at onset of the disease is the main predictor for increased IVS thickness and for the development of cardiomyopathy after liver transplantation.

  • 104.
    Olsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Planté-Bordeneuve, V
    Jonasson, J
    Lång, K
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mitochondrial haplogroup is associated with the phenotype of familial amyloidosis with polyneuropathy in Swedish and French patients2009In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 75, no 2, p. 163-168Article in journal (Refereed)
    Abstract [en]

    Familial amyloidotic polyneuropathy (FAP) is a monogenic disease caused by mutations in the transthyretin (TTR) gene. The phenotype of the most common TTR mutation, V30M, varies within and between populations. Oxidative stress and protein misfolding are cellular processes involved in the development of FAP. Because the mitochondria are important for both these processes, we investigated if mitochondrial haplogroups are related to age at onset of the disease in Swedish and French FAP patients. Mitochondrial haplogroup analysis was performed on 25 early-onset (below 40 years) and 29 late-onset (above 51 years) Swedish FAP patients. DNA from 249 Swedish individuals served as controls. In addition, 6 early-onset and 17 late-onset French FAP patients were examined with 25 French controls. The haplogroup distribution among late-onset Swedish and French cases was similar to that found in the general populations, whereas among early-onset cases a different haplogroup distribution was seen. The relatively rare haplogroup K was significantly more common among early-onset cases. Our findings substantiate the suggestion that a genetic component, still to be found, affecting mitochondrial function has an impact on the amyloid generating process in transthyretin amyloidosis.

  • 105.
    Olsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Frequency of the transthyretin Val30Met mutation in the northern Swedish population2014In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 21, no 1, p. 18-20Article in journal (Other academic)
    Abstract [en]

    By genotyping a large number of samples from the Northern Sweden Health and Disease Study cohort, a carrier frequency could be determined for the Skelleftea and Lycksele populations. A previous study of the amyloidogenic transthyretin mutation TTRV30M in Northern Sweden's endemic area has shown a large variation in carrier frequency and penetrance of the trait within the area. However, the estimations have been based on a small sample size within the different regions in the area and therefore, the wide variation in TTRV30M carrier frequency observed between the Lycksele and Skelleftea populations are uncertain. Based on a total of 3460 samples, the estimated overall carrier frequency in the two regions was 1.82% with a carrier frequency in the Skelleftea and Lycksele population of 1.63% and 2.02%, respectively. Thus, the previously reported extremely high frequency in the Lycksele region compared to that of the Skelleftea region could not be substantiated. However, it does not change the previous finding of a surprisingly higher carrier frequency in the population from endemic area of Northern Sweden compared to that reported from endemic areas in Portugal.

  • 106.
    Olsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norgren, Nina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Obayashi, Konen
    Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
    Plante-Bordeneuve, Violaine
    Service de Neurologie, CHU Henri Mondor, Créteil, France.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers2010In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 11, p. 130-Article in journal (Refereed)
    Abstract [en]

    Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population.

  • 107.
    Olsson, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norgren, Nina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Saraiva, Maria J
    Cederquist, Kristina
    Jonasson, Jenni
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Distribution of mitochondrial DNA haplogroups in Portuguese familial amyloidosis with polyneuropathy (FAP) patientsManuscript (preprint) (Other academic)
  • 108. Pagoldh, Maria
    et al.
    Eriksson, Anders
    Heimtun, Erling
    Kvifors, Eva
    Sternby, Berit
    Blomquist, Lars
    Lapidus, Annika
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lange, Stefan
    Karlbom, Urban
    Nordström, Daniel
    Rettrup, Björn
    Effects of a supplementary diet with specially processed cereals in patients with short bowel syndrome.2008In: European journal of gastroenterology & hepatology, ISSN 1473-5687, Vol. 20, no 11, p. 1085-93Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Short bowel syndrome patients frequently experience impaired health-related quality of life. This syndrome is also associated with increased costs for the individuals concerned and the community. Intake of specially processed cereals has been demonstrated to decrease intestinal secretion. This study evaluates the effect of a supplementary diet with specially processed cereals compared with nonprocessed cereals. METHODS: This investigation is a randomized double-blind, cross-over multicentre prospective study of 26 intestinal resected out patients, considered as short bowel syndrome patients. The patients were divided into groups A or B, in accordance with the first allocated treatment. Subgroup analyses of the underlying diagnoses and type of surgical procedure were performed. The studied parameters were faecal volume, nocturnal stools, abdominal pain/discomfort, health-related quality of life, peripheral blood tests and anthropometric data. RESULTS: In both groups, intake of nonprocessed cereals significantly decreased the faecal volume. The subgroup analyses of patients with a history of ulcerative colitis (compared with Crohn's disease) and nonileostomy-operated procedure (compared with ileostomi-operated procedure) showed significantly decreased faecal volume during nonprocessed cereals intake. Peripheral blood tests, quality of life and anthropometry were not affected. CONCLUSION: In this study, nonprocessed cereals seemed to be as effective as specially processed cereals in decreasing faecal volume in general and especially in ulcerative colitis patients (mainly operated with nonileostomy techniques). Our results indicate that use of supplementary cereals is safe for this group of patients, but should optimally include evaluation of the underlying diagnosis and the surgical method used.

  • 109. Parman, Yesim
    et al.
    Adams, David
    Obici, Laura
    Galan, Lucia
    Guergueltcheva, Velina
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Coelho, Teresa
    Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP2016In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 29, p. S3-S13Article in journal (Refereed)
    Abstract [en]

    Purpose of review Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present. Recent findings The incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment. Summary The article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework - a networked approach to disease management with an emphasis on collaboration and sharing of best practice.

  • 110.
    Pilebro, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Arvidsson, Sandra
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Westermark, Per
    Antoni, Gunnar
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sörensen, Jens
    Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)2018In: Journal of Nuclear Cardiology, ISSN 1071-3581, E-ISSN 1532-6551, Vol. 25, no 1, p. 240-248Article in journal (Refereed)
    Abstract [en]

    Background: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing 11C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer’s disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.

    Methods: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.

    Results: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min−1, P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.

    Conclusion: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.

  • 111.
    Pilebro, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Westermark, Per
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    99mTC-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Aims In transthyretin amyloid (ATTR) amyloidosis various principal phenotypes have been described: cardiac, neuropathic, or a mixed cardiac and neuropathic. In addition, two different types of amyloid fibrils have been identified (type A and type B). Type B fibrils have thus far only been found in predominantly early-onset V30M and in patients carrying the Y114C mutation, whereas type A is noted in all other mutations currently examined as well as in wild-type ATTR amyloidosis. The fibril type is a determinant of the ATTR V30M disease phenotype. Tc-99m-DPD scintigraphy is a highly sensitive method for diagnosing heart involvement in ATTR amyloidosis. The objective of this study was to determine the relationship between ATTR fibril composition and Tc-99m-DPD scintigraphy outcome in patients with biopsy-proven ATTR amyloidosis. Methods Altogether 55 patients with biopsy-proven diagnosis of ATTR amyloidosis and amyloid fibril composition determined were examined by Tc-99m-DPD scintigraphy. The patients were grouped and compared according to their type of amyloid fibrils. Cardiovascular evaluation included ECG, echocardiography, and cardiac biomarkers. The medical records were scrutinized to identify subjects with hypertension or other diseases that have an impact on cardiac dimensions. Results A total of 97% with type A and none of the patients with type B fibrils displayed Tc-99m-DPD uptake at scintigraphy (p < 0.001). Findings from analyses of cardiac biomarkers, ECG, and echocardiography, though significantly different, could not differentiate between type A and B fibrils in individual patients. Conclusion In ATTR amyloidosis, the outcome of Tc-99m-DPD scintigraphy is strongly related to the patients' transthyretin amyloid fibril composition.

  • 112. Plante-Bordeneuve, Violaine
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Maurer, Mathew S.
    White, Barbara
    Grogan, Donna R.
    Coelho, Teresa
    The Transthyretin Amyloidosis Outcomes Survey (THAOS) registry: design and methodology2013In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 29, no 1, p. 77-84Article in journal (Refereed)
    Abstract [en]

    Background: Transthyretin (TTR) amyloidosis - the most common type of hereditary amyloidosis - also has an acquired form and is observed in geographically dispersed populations. TTR amyloidosis is marked by considerable clinical heterogeneity, and the main phenotypes are neurologic and cardiovascular. Methods: THAOS is an international, noninterventional, longitudinal, observational registry designed to evaluate overall survival in patients, better understand genotype-phenotype relationships and the natural history of TTR amyloidosis, and evaluate the effects of liver transplantation and other treatments on disease progression in TTR amyloidosis. All individuals with a confirmed TTR mutation with or without a diagnosis of TTR amyloidosis and patients with wild-type TTR amyloidosis are eligible to be enrolled in the registry. Purpose: To describe the design and methodology of the recently established registry. Procedures for data collection are outlined and a minimum set of assessments for the standard evaluation of all subjects with TTR amyloidosis is described. Demographic information, TTR genotype, medical history, family history of the disease, and transplant history are assessed at baseline. On return visits, signs and symptoms of the disease are evaluated, general examinations are conducted, and laboratory data, measures of neurologic and cardiovascular function, and quality of life are assessed according to the standard of care for patients. Visits on at least a biannual basis are recommended. The registry will remain open for a period of at least 10 years. Results: The initial experience suggests that the registry is characterized by a comprehensive set of data elements which can be completed by providers from the various clinical backgrounds who administer care to individuals with TTR amyloidosis. Conclusion: As of September 2011, 30 centers in 15 of the 19 countries participating in the THAOS registry have enrolled 975 patients. Such data provide a representative sample of the global TTR amyloidosis patient population, including asymptomatic TTR variant carriers, which can inform the natural history of the disease and offer the potential to evaluate novel therapeutic modalities in diverse patient subpopulations.

  • 113. Polydefkis, M.
    et al.
    Ebenezer, G.
    Adams, D.
    Coelho, T.
    Conceicao, I.
    Waddington Cruz, M.
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Partisano, A.
    Chen, J.
    Gollob, J.
    Suhr, O.
    Umeå University.
    EFFECT OF PATISIRAN ON NERVE FIBER DENSITY AND AMYLOID CONTENT IN SKIN: RESULTS FROM PHASE 2 OPEN LABEL EXTENSION (OLE) STUDY IN HATTR AMYLOIDOSIS2017In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 22, no 3, p. 360-360Article in journal (Other academic)
  • 114. Polydefkis, Michael
    et al.
    Adams, David
    Coelho, Teresa
    Kristen, Arnt
    Gonzalez-Duarte, Alejandra
    Berk, John
    Quan, Dianna
    Partisano, Angela
    Gollob, Jared
    Sweester, Marianne
    Chen, Jihong
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Infusion related reactions in patients with hATTR amyloidosis treated with patisiran2018In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 23, no 4, p. 352-352Article in journal (Other academic)
  • 115.
    Rydh, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hietala, Sven-Ola
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Pepys, M B
    Hawkins, P N
    Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation.1998In: European Journal of Nuclear Medicine, ISSN 0340-6997, E-ISSN 1432-105X, Vol. 25, no 7, p. 709-713Article in journal (Refereed)
    Abstract [en]

    Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1-5 years beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1-5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome.

  • 116. Sah, Dinah WY
    et al.
    Chen, Qingmin
    Costelha, Susete
    Butler, Jim
    Fishman, Shannon
    Rossomando, Anthony
    Nechev, Lubomir
    Saraiva, Maria Joao
    Coelho, Teresa
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adams, David
    Lozeron, Pierre
    Hawkins, Philip
    Mant, Timothy
    Hutabarat, Renta
    Falzone, Rick
    Cehelsky, Jeff
    Figueroa, Yaysie
    Vaishnaw, Akshay
    Gollob, Jared
    ALN-TTR, an RNAI therapeutic for the treatment of transthyretin amyloidosis2011In: Nucleic acid therapeutics, ISSN 2159-3337, Vol. 21, no 5, p. A55-A56Article in journal (Refereed)
  • 117.
    Sandgren, Ola
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Kjellgren, Daniel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ocular manifestations in liver transplant recipients with familial amyloid polyneuropathy.2008In: Acta ophthalmologica, ISSN 1755-3768, Vol. 86, no 5, p. 520-4Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate postoperative ocular involvement in Swedish liver transplant (LT) recipients with familial amyloid polyneuropathy (FAP). METHODS: Routine ophthalmological examinations were performed in 48 LT recipients, with particular attention given to amyloid deposition in the anterior segment and the vitreous body. Medical records were scrutinized for information regarding neurological impairment at the time of the LT. The diagnosis was secured in all cases by examining for amyloid deposits in biopsy specimens and positive genetic testing for amyloidogenic transthyretin (ATTR) Val30Met mutation. RESULTS: Six patients (12.5%) developed vitreous opacities within the post-LT observation period. The first opacities were seen 40 months after transplantation, 8 years after the onset of systemic disease. Four patients (8%) developed secondary glaucoma, the first of which was observed 18 months after the procedure and 6.5 years after the onset of disease. Sixteen patients (33%) developed deposits on the anterior surface of the lens. Scalloped pupillary margins were noted in 10 patients (21%). CONCLUSION: The prevalence of eye complications increases with time after LT and regular follow-up is necessary, especially to disclose the development of glaucoma--a complication with insidious symptoms of which patients are normally unaware.

  • 118. Sato, Takashi
    et al.
    Ando, Yukio
    Susuki, Seiko
    Mikami, Fumi
    Ikemizu, Shinji
    Nakamura, Masaaki
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anraku, Makoto
    Kai, Toshiya
    Suico, Mary Ann
    Shuto, Tsuyoshi
    Mizuguchi, Mineyuki
    Yamagata, Yuriko
    Kai, Hirofumi
    Chromium(III) ion and thyroxine cooperate to stabilize the transthyretin tetramer and suppress in vitro amyloid fibril formation.2006In: FEBS Lett, ISSN 0014-5793, Vol. 580, no 2, p. 491-6Article in journal (Refereed)
  • 119. Schmidt, Hartmut
    et al.
    Adams, David
    Coelho, Teresa
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Gollob, Jared
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Patisiran ph 2 open-label extension study in Familial Amyloidotic Polyneuropathy2016In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, no 12Article in journal (Other academic)
    Abstract [en]

    Background: Familial Amyloid Polyneuropathy (FAP) is a progressive disease caused by deposition of transthyretin (TTR). Patisiran is an investigational, small interfering RNA (siRNA) inhibiting TTR. This abstract highlights patisiran's long-term safety. Methods: Phase 2 OLE study to evaluate patisiran's safety. Patisiran's effect on serum TTR levels, impact on neuropathy impairment scores and QOL were assessed. Results: 27 patients with FAP enrolled; median age 64 years. Patisiran was generally well tolerated out to 23-months. Five patients experienced SAEs (unrelated) including one discontinuation (gastroesophageal cancer); patient subsequently died. Flushing (25.9%) and infusion-related reactions (18.5%) were mild in severity; no discontinuations resulted. Approximately 80% sustained mean serum TTR lowering resulted with a mean nadir of up to 93% between doses. Among the 20 evaluable patients, neuropathy impairment scores were stable through 18-months; mean change in mNIS+7 and NIS of 1.7 and 4.2 points, respectively. This compares favorably to 17–26 point mNIS+7/NIS increase estimated at 18-months from prior FAP studies. Stabilization of QOL measures and improvement of distal thigh sweat gland nerve fiber density observed. Conclusion: Data demonstrates that 18-months of patisiran administration was generally well tolerated, resulted in sustained mean serum TTR lowering, supporting the hypothesis that TTR knockdown potentially halts neuropathy progression.

  • 120. Solomon, Scott D.
    et al.
    Adams, David
    Kristen, Arnt
    Grogan, Martha
    Gonzalez-Duarte, Alejandra
    Maurer, Mathew S.
    Merlini, Giampaolo
    Damy, Thibaud
    Slama, Michel S.
    Brannagan, Thomas H., III
    Dispenzieri, Angela
    Berk, John L.
    Shah, Amil M.
    Garg, Pushkal
    Vaishnaw, Akshay
    Karsten, Verena
    Chen, Jihong
    Gollob, Jared
    Vest, John
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 4, p. 431-443Article in journal (Refereed)
    Abstract [en]

    Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed.

    Methods: APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness 13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis.

    Results: In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference SEM: -0.90.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3 +/- 3.9 mL, P=0.036), decreased global longitudinal strain (-1.4 +/- 0.6%, P=0.015), and increased cardiac output (0.38 +/- 0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01).

    Conclusions: Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis.

  • 121. Stangou, Arie J
    et al.
    Lobato, Luisa
    Zeldenrust, Steven
    Rela, Mohamed
    Portmann, Bernard
    Linke, Reinhold P
    Conceicao, Isabel
    Otto, Gerd
    Wilczek, Henryk
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Azoulay, Daniel
    Grateau, Gilles
    Picken, Maria
    O'Grady, John
    Heaton, Nigel
    Ericzon, Bo-Göran
    Benson, Merrill D
    Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 81-84Article in journal (Refereed)
    Abstract [en]

    Fibrinogen A alpha-chain (AFib) and apolipoprotein AI (AApoAI) amyloidosis due to variants in the AFib and ApoAI genes are the most common types of hereditary amyloidosis in Europe and the United States. Liver is the exclusive source of the aberrant amyloidogenic protein in AFib and responsible for supplying approximately half of the circulating variant ApoAI. Nephrotic syndrome and renal impairment due to renal amyloidosis are common disease manifestations; however, recent research provides evidence to support a more diverse and systemic disease phenotype, which in turn has implications in the management of the hereditary amyloidoses with solid organ transplantation and, in particular, liver transplantation.

  • 122. Stangou, Arie
    et al.
    Larsson, Marie E.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wilczek, Henryk E.
    Ericzon, Bo-Göran
    Domino liver transplantation (DLT) using familial amyloid polyneuropathy (FAP) grafts: report from the FAP world transplant registry (FAPWTR) and call for an international collaborative study to assess the risk of de novo FAP in domino recipients2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, p. 259A-260A, article id 123Article in journal (Other academic)
  • 123. Stål, P
    et al.
    Befrits, R
    Rönnblom, A
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ståhlberg, D
    Brinkberg Lapidus, A
    Löfberg, R
    Clinical trial: the safety and short-term efficacy of recombinant cholera toxin B subunit in the treatment of active Crohn's disease.2010In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 31, no 3, p. 387-395Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cholera toxin B subunit ameliorates experimentally induced colitis in mice. In humans, cholera toxin B subunit has never been tested in the treatment of Crohn's disease (CD). AIM: To evaluate the safety and efficacy of treatment with recombinant cholera toxin B subunit of patients with CD. METHODS: An open-label, multicentre, nonrandomized trial including 15 patients with mild/moderate CD. Patients received an oral solution of 5 mg recombinant cholera toxin B subunit three times weekly for 2 weeks. Reduction in CD Activity Index (CDAI) with >100 between baseline and days 15, 29, 42 and 70 defined clinical response. Patients with CDAI score < or = 150 were defined as being in remission. RESULTS: A significant decrease in CDAI score was observed. Response rates were 40% in the full analysis set and 42% in the per protocol analysis. Two patients receiving adjuvant treatment after day 29 were excluded, after which 40% were in remission at 4 weeks and 30% at 8 weeks post-treatment. Mild side effects (arthralgia, headache and pruritus) were seen in 33% of patients. CONCLUSIONS: Treatment with recombinant cholera toxin B subunit was safe. Approximately 40% of patients with active CD responded to treatment. Randomized studies are needed to establish the clinical efficacy of recombinant cholera toxin B subunit.

  • 124.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Commentary to Isabel Conceicao et al. early diagnosis through targeted follow-up of identified carriers of TTR gene mutations2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, no 1, p. 1-2Article in journal (Other academic)
  • 125.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Response: concerning “late early and late onset” ATTR Val30Met patients2019In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 26, no 4, p. 250-250Article in journal (Refereed)
  • 126.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    "Skelleftesjukan", en sjukdom med många ansikten2010In: Kungliga Skytteanska Samfundets årsbok 2010, Thule , 2010Chapter in book (Other academic)
  • 127.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Backman, Clas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Karlsson, A
    Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Do troponin and B-natriuretic peptide detect cardiomyopathy in transthyretin amyloidosis?2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 3, p. 294-301Article in journal (Refereed)
  • 128.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Gastric emptying before and after liver transplantation for familial amyloidotic polyneuropathy, Portuguese type (Val30Met).2003In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 10, no 2, p. 121-6Article in journal (Refereed)
    Abstract [en]

    Liver transplantation is an accepted treatment of familial amyloidotic polyneuropathy (FAP), Portuguese type (Val30Met), and the outcome so far seems promising. Gastric retention with nausea and vomiting are common complications of the disease, and may interfere with immuno-suppression therapy and prolong recovery after liver transplantation. The aim of this study was to assess the frequency of gastric retention in FAP patients and to evaluate the impact liver transplantation has on gastric emptying. Twenty-two patients, who had undergone liver transplantation, and had been re-examined for gastric retention after the procedure, were included in the study. Gastric emptying was recorded by scintigraphy after the ingestion of a 99m-technetium (99mTc)-labelled meal (omelette). The half-time (T50) of the emptying phase was calculated. Gastrointestinal symptoms before and after transplantation were recorded, and the majority of patients were also subjected to an upper endoscopic examination, where the presence of solid residual in the stomach was regarded as consistent with gastric retention. A high frequency of gastric retention was noted among the patients both before and after transplantation, and no significant improvement for the group was noted, even though decreased gastric emptying was noted for patients with a duration of the disease for less that 4 years. Patients who improved their nutritional status after transplantation had a faster gastric emptying than those who deteriorated. From our findings it can be concluded that gastric retention is a common complication of FAP and that gastric emptying in patients with longstanding disease (> or = 4 years) is unchanged after liver transplantation.

  • 129.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersen, Oluf
    Aronsson, Thomas
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Kalimo, Hannu
    Lundahl, Christer
    Lundgren, Hans-Eric
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Melberg, Atle
    Nyberg, Johan
    Olsson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Sandberg, Arne
    Westermark, Per
    Report of five rare or previously unknown amyloidogenic transthyretin mutations disclosed in Sweden.2009In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 16, no 4, p. 208-214Article in journal (Refereed)
    Abstract [en]

    The number of amyloidogenic transthyretin (TTR) mutations described in the literature is more than 100. However, for several mutations, the phenotype has been described in a few individuals only; thus, the knowledge of the clinical course and the outcome after therapeutical interventions such as liver transplantation is limited. We describe the phenotype associated with five rare amyloidogenic TTR mutations that lately were discovered in Sweden: ATTR Val30Leu, Ala45Ser, Leu55Gln, Gly57Arg and Tyr69His of which ATTR Gly57Arg is previously unknown. The symptoms at onset differed, but cardiomyopathy and peripheral neuropathy were observed in all except the ATTR Tyr69His mutation. Likewise, carpal tunnel syndrome was found or had been present in all cases except the case with the ATTR Val30Leu mutation. The phenotype of the ATTR Tyr69His mutation was characterised by oculo-meningeal symptoms with seizures and a steadily progressing dementia, symptoms rarely found in ATTR amyloidosis, but similar to those previously described for this mutation, where all cases appear to originate from one Swedish family. Two patients with the ATTR Leu55Gln and Ala45Ser mutations have been subjected to liver transplantation, but echocardiographic examination has revealed an increasing cardiomyopathy after transplantation in both cases, the ATTR Leu55Gln patient succumbed 2 years after transplantation from progressive disease.

  • 130.
    Suhr, Ole B.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Coelho, Teresa
    Buades, Juan
    Pouget, Jean
    Conceicao, Isabel
    Berk, John
    Schmidt, Hartmut
    Waddington-Cruz, Marcia
    Campistol, Josep M.
    Bettencourt, Brian R.
    Vaishnaw, Akshay
    Gollob, Jared
    Adams, David
    Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study2015In: Orphanet Journal of Rare Diseases, ISSN 1750-1172, E-ISSN 1750-1172, Vol. 10, article id 109Article in journal (Refereed)
    Abstract [en]

    Background: Transthyretin-mediated amyloidosis is an inherited, progressively debilitating disease caused by mutations in the transthyretin gene. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of patisiran (ALN-TTR02), a small interfering RNA encapsulated within lipid nanoparticles, in patients with transthyretin-mediated familial amyloid polyneuropathy (FAP). Methods: In this phase II study, patients with FAP were administered 2 intravenous infusions of patisiran at one of the following doses: 0.01 (n = 4), 0.05 (n = 3), 0.15 (n = 3), or 0.3 (n = 7) mg/kg every 4 weeks (Q4W), or 0.3 mg/kg (n = 12) every 3 weeks (Q3W). Results: Of 29 patients in the intent-to-treat population, 26 completed the study. Administration of patisiran led to rapid, dose-dependent, and durable knockdown of transthyretin, with the maximum effect seen with patisiran 0.3 mg/kg; levels of mutant and wild-type transthyretin were reduced to a similar extent in Val30Met patients. A mean level of knockdown exceeding 85 % after the second dose, with maximum knockdown of 96 %, was observed for the Q3W dose. The most common treatment-related adverse event (AE) was mild-to-moderate infusion-related reactions in 10.3 % of patients. Four serious AEs (SAEs) were reported in 1 patient administered 0.3 mg/kg Q3W (urinary tract infection, sepsis, nausea, vomiting), and 1 patient administered 0.3 mg/kg Q4W had 1 SAE (extravasation-related cellulitis). Conclusions: Patisiran was generally well tolerated and resulted in significant dose-dependent knockdown of transthyretin protein in patients with FAP. Patisiran 0.3 mg/kg Q3W is currently in phase III development.

  • 131.
    Suhr, Ole B.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Karayal, O.
    Ericzon, B-G
    Nutritional status and autonomic function in clinical trials of tafamidis for transthyretin familial polyneuropathy2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 775-775Article in journal (Other academic)
  • 132.
    Suhr, Ole B.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceição, Isabel M.
    Karayal, Onur N.
    Mandel, Francine S.
    Huertas, Pedro E.
    Ericzon, Bo-Göran
    Post hoc analysis of nutritional status in patients with transthyretin familial amyloid polyneuropathy: impact of tafamidis2014In: Neurology and therapy, ISSN 2193-8253, Vol. 3, no 2, p. 101-112Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Gastrointestinal symptoms are common among patients with transthyretin familial amyloid polyneuropathy (TTR-FAP). This post hoc analysis evaluated the nutritional status of TTR-FAP patients treated with tafamidis while enrolled in clinical trials.

    METHODS: Nutritional status was measured by the modified body mass index (mBMI = BMI × albumin level). Treatment-related changes in mBMI were reported for 71 Val30Met TTR-FAP patients who completed an 18-month, randomized, double-blind, placebo-controlled trial and who continued into its open-label, 12-month extension.

    RESULTS: At month 18, mBMI worsened in the placebo group (n = 33) (-33 ± 16 kg/m(2) g/l, P = 0.04 versus baseline) but improved in the tafamidis group (n = 38) (+37 ± 14 kg/m(2) g/l, P = 0.01 versus baseline) such that the effect size between the groups was statistically significant (P = 0.001). By month 30 (completion of the open-label extension), placebo patients with 12 months of tafamidis treatment and tafamidis-treated patients with 30 months of treatment both tended to increase their mBMI (28 ± 19 kg/m(2) g/l and 16 ± 18 kg/m(2) g/l, respectively). Increase in BMI was most pronounced in patients with low BMI at entry into the studies.

    CONCLUSIONS: mBMI is well suited to monitor disease progression in TTR-FAP patients. The delay in neurological deterioration brought about by tafamidis treatment in clinical trials is associated with improvements in, or maintenance of, mBMI.

  • 133.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Cronborg, O
    Sjukdomar i matstrupe, magsäck och tolvfingertarm2006In: Läkemedelsboken 2005/2006, Apoteket AB , 2006Chapter in book (Other (popular science, discussion, etc.))
  • 134.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ericzon, B-G
    Lundgren, E
    Liver transplantation for transthyretin amyloidosis.2009In: Recent advances in transthyretin evolution, structure and biological function. / [ed] Richardson SJ, Cody V, Berlin-Heidelberg: Springer-Verlag , 2009Chapter in book (Other academic)
  • 135.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ericzon, Bo-Göran
    Selection of hereditary transthyretin amyloid patients for liver transplantation: the Swedish experience2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no S1, p. 78-80Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LTx) is currently an accepted treatment for hereditary transthyretin amyloidosis (h-ATTR). However, to optimize the outcome, careful selection of patients is required, since increased mortality compared with that found for nontransplanted historical controls are observed for several groups of h-ATTR patients. We have noted that malnourished patients and patients with a late onset of the disease especially in combination with findings of cardiomyopathy are at risk for an increased mortality and morbidity. Recently detection of different types of amyloid fibrils that appears to be related to the phenotype of the patient may facilitate patient selection for LTx.

  • 136.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Friman, Styrbjörn
    Ericzon, Bo-Göran
    Early liver transplantation improves familial amyloidotic polyneuropathy patients' survival.2005In: Amyloid, ISSN 1350-6129, Vol. 12, no 4, p. 233-8Article in journal (Refereed)
  • 137.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Holmgren, Gösta
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Lundgren, Erik
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Gene therapy: lessons learned from liver transplantation for transthyretin-amyloidosis.2004In: Liver Transpl, ISSN 1527-6465, Vol. 10, no 12, p. 1551-3Article in journal (Refereed)
  • 138.
    Suhr, Ole B
    et al.
    Umeå University Hospital.
    Larsson, Marie
    Ericzon, Bo-Göran
    Wilczek, Henryk E
    Survival After Transplantation in Patients With Mutations Other Than Val30Met: Extracts From the FAP World Transplant Registry2016In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 100, no 2, p. 373-381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Liver transplantation (LTx) has been performed for hereditary transthyretin amyloidosis (ATTR) since 1990. Outcomes for a relatively large series of LTx ATTR patients with the Val30Met (mutation are available, but for non-Val30Met patients, only a few reports with a small number of patients exist. Here, we present outcomes for non-Val30Met ATTR patients after LTx, as reported to the Familial Amyloid Polyneuropathy World Transplant Registry (FAPWTR).

    METHODS: Data regarding outcome were extracted for all non-Val30Met patients reported to the registry. Survival rates were analyzed by the Kaplan-Meier method and log-rank test.

    RESULTS: The total number of patients with a non-Val30Met mutation in the registry was 264 (174 men and 90 women), representing 57 mutations. The 10-year survival varied markedly for the 9 most common mutations, ranging from 21% for Ser50Arg to 85% for Val71Ala. Poor survival was noted for all mutations with leptomeningeal complications except for those with the Tyr114Cys mutation.

    CONCLUSIONS: Large differences in survival were observed relative to different mutations and between mutations with similar phenotypes. Excellent survival was noted for mutations, such as Leu111Met, Val71Ala, and Leu58His. Patients with mutations other than Val30Met are not a homogeneous group, and the term non-Val30Met should be used with caution or avoided. Moreover, for several mutations, data are too limited to allow evaluation of the efficacy of LTx, and continuous international collaboration is important for obtaining treatment guidance.

  • 139.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Backman, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Myocardial hypertrophy and function are related to age at onset in familial amyloidotic polyneuropathy.2006In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 13, no 3, p. 154-159Article in journal (Refereed)
  • 140.
    Suhr, Ole B.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, Erik
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Westermark, P
    One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 4, p. 337-347Article, review/survey (Refereed)
    Abstract [en]

    Although hereditary transthyretin (h-ATTR) amyloidosis is a monogenetic disease, a large variation in its phenotype has been observed. The common hypothesis of amyloid fibril formation involves dissociation of the transthyretin (TTR) tetramer into monomers that after misfolding reassemble into amyloid fibrils. This notion is partly challenged by the finding of two distinct types of amyloid fibrils. One of these, type A, consists of C-terminal ATTR fragments and full-length TTR, whereas the other, type B, consists only of full-length TTR. All organs of an individual patient contain ATTR deposits of either type A or type B fibrils, and the composition in each individual remains unchanged over time. The finding of two distinct types of ATTR fibrils suggests that there are at least two different pathways in operation for ATTR fibril formation. For the most common European mutation, TTR Val30Met, ATTR fibril composition is related to the outcome of liver transplantation, which is the first successful treatment for the disease, and the penetrance of the trait. In addition, the presence of C-terminal ATTR fragments has an impact on the affinity for various tracers used for noninvasive imaging of amyloid depositions such as 99 m-technetium-diphosphono-propanodicarboxylic acid scintigraphy and positron emission tomography utilizing Pittsburgh component B, and even for the gold standard diagnostic procedure, tissue biopsy stained by Congo red and examined under polarized light. The importance of amyloid fibril composition needs to be taken into consideration when designing clinical trials of treatment modalities, and also in the evaluation of diagnostic methods such as imaging techniques.

  • 141.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, Erik
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Westermark, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Transthyretin amyloidoses: new strategies for therapeutic intervention2010In: Drugs of the future, ISSN 0377-8282, E-ISSN 2013-0368, Vol. 35, no 4, p. 325-332Article in journal (Refereed)
    Abstract [en]

    Liver transplantation as a treatment for transthyretin amyloidosis (ATTR) was introduced 20 years ago and is currently the only available treatment for the disease. Although the procedure has been proven to halt the progression of the disease for most patients, several unexpected complications have emerged, and it is obvious that for several mutations liver transplantation has no impact on the progression of the disease. Heart complications, especially in elderly patients, have been a cause of concern for many patients, including those with the most widespread neuropathic mutation, transthyretin (TTR)Val30Met. These drawbacks and the risk involved with transplantation, together with the need for life-long immunosuppressive therapy, have demonstrated the need for an effective medical treatment. From the experience with liver transplant patients, it appears that the amyloidogenic properties of wild-type TTR are enhanced once amyloid formation has started, and that elimination of the mutated TTR is not sufficient to prevent further amyloid formation in all cases. The development of animal models for the disease has further increased our understanding of factors involved in amyloid formation, and offers the possibility to test new medical treatment modalities. From our experience with liver transplantation, it appears that treatment directed towards stabilizing the TTR tetramer, eliminating misfolded TTR, decreasing TTR serum concentrations, decreasing toxicity and removing amyloid deposits are the most attractive modalities for treatment. Several studies are currently planned or ongoing to explore these possibilities, and promising results are already being reported.

  • 142.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lång, K
    Wikström, L
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, G
    Tashima, K
    Scavenger treatment of free radical injury in familial amyloidotic polyneuropathy: a study on Swedish transplanted and non-transplanted patients.2001In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 61, no 1, p. 11-8Article in journal (Refereed)
    Abstract [en]

    Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.

  • 143.
    Suhr, Ole B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    The Swedish landscape of hereditary ATTR amyloidosis2017In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, no 1, p. 93-94Article in journal (Refereed)
    Abstract [en]

    Northern Sweden is a well-known clustering area for hereditary transthyretin (TTR) amyloid (ATTR) amyloidosis caused by the Val30Met mutation. However, several additional mutations have been found in the Swedish population, of which many, such as the Ala45Ser, Gly57Arg and His88Arg mutations, have not been reported outside of Sweden to the best of our knowledge. We aim to give an overview of the various mutations found in the Swedish population.

  • 144.
    Suhr, Ole Bernt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wijayatunga, Priyantha
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Westermark, Per
    Ihse, Elisabet
    Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0211983Article in journal (Refereed)
    Abstract [en]

    Background: The amyloid fibril in hereditary transthyretin (TTR) Val30Met (pVal50Met) amyloid (ATTR Val30Met) amyloidosis is composed of either a mixture of full-length and TTR fragments (Type A) or of only full-length TTR (Type B). The type of amyloid fibril exerts an impact on the phenotype of the disease, and on the outcome of diagnostic procedures and therapy. The aim of the present study was to investigate if the type of amyloid fibril remains the same within ATTR Val30Met amyloidosis families. Methods: Fifteen families were identified in whom at least two first-degree relatives had their amyloid fibril composition determined. The type of ATTR was determined by Western blot in all but two patients. For these two patients a positive 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy indicated ATTR Type A. Results: In 14 of the 15 families, the same amyloid fibril composition was noted irrespective of differences in age at onset. In the one family, different ATTR fibril types was found in two brothers with similar ages at onset. Conclusions: Family predisposition appears to have an impact on amyloid fibril composition in members of the family irrespective of their age at onset of disease, but if genetically determined, the gene/genes are likely to be situated at another location than the TTR gene in the genome.

  • 145.
    Suhr, Ole
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Larsson, Marie
    Ericzon, Bo-Goran
    Wilczek, Henryk
    PATIENTS WITH NON-V30MET TRANSTHYRETIN MUTATIONS: DATA FROM THE FAP WORLD TRANSPLANT REGISTRY (FAPWTR) SHOW LARGE VARIATION IN OUTCOME FOLLOWING LIVER OR LIVER/HEART TRANSPLANTATION2015In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 171-171Article in journal (Other academic)
  • 146. Tysk, Curt
    et al.
    Almer, Sven
    Andersson, Magnus V
    Befrits, Ragnar
    Hertervig, Erik
    Kilander, Anders
    Lindgren, Stefan
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    [Management of severe attack of ulcerative colitis]2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 2994-8Article in journal (Refereed)
  • 147. Ueda, Mitsuharu
    et al.
    Misumi, Yohei
    Mizuguchi, Mineyuki
    Nakamura, Masaaki
    Yamashita, Taro
    Sekijima, Yoshiki
    Ota, Kazutoshi
    Shinriki, Satoru
    Jono, Hirofumi
    Ikeda, Shu-ichi
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Yukio
    SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.2009In: Clinical chemistry, ISSN 1530-8561, Vol. 55, no 6, p. 1223-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mass spectrometric analyses are valuable for detection of transthyretin (TTR) variants, which cause familial amyloidotic polyneuropathy (FAP). However, those methods require an immunoprecipitation step with an anti-TTR antibody and are not suitable for quantitative detection. We investigated the usefulness of SELDI-TOF mass spectrometry (MS) without an immunoprecipitation step. METHODS: We used ProteinChips with chromatographic capture formats to detect TTRs. We attempted to correlate the intensity of mixed samples of amyloidogenic TTR (ATTR) V30M to wild-type (WT) TTR. We analyzed the proportion of ATTR V30M in amyloid-laden cardiac tissues from FAP patients, and also evaluated samples from FAP patients with 16 other TTR mutations. RESULTS: Detection of ATTR required only 3 h of SELDI-TOF MS analysis. We determined that SELDI-TOF MS was suitable for quantitative detection of ATTR V30M and demonstrated that the proportion of ATTR V30M to WT TTR was 46.6% in amyloid-laden cardiac tissue from an FAP patient who died 10 years after liver transplantation. With this method, we identified 12 of 17 TTR variants. Small mass shifts and low concentrations of variants prevented ATTR detection. By changing the analytical conditions, we achieved detection of low concentrations of ATTR Y114C in serum. CONCLUSIONS: SELDI-TOF MS is a reliable tool for quantitative evaluation of TTR variants, in both tissue amyloid deposits and body fluids. This method is useful for the diagnosis and investigation of the pathogenesis of FAP.

  • 148.
    Unéus, Erica
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wilhelmsson, Christer
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Visualisation of amyloid deposition within the brain of long-term hereditary transthyretin amyloidosis survivors by 18F-flutemetamol positron emission tomography2019In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no S1, p. 287-287, article id EPR3027Article in journal (Other academic)
    Abstract [en]

    Background and aims: Hereditary transthyretin amyloid (ATTRv) amyloidosis caused by the transthyretin (TTR) Val30Met (p.V50M) mutation is characterised by peripheral neuropathy, and central nervous (CNS) complications has rarely been reported. However, liver transplantation has prolonged the patients’ survival, and CNS complications attributed to amyloid angiopathy caused by CNS synthesis of variant TTR have been reported. The aim of the study was to ascertain CNS amyloid deposition in long-term ATTRv survivors.

    Methods: 20 ATTR Val30Met patients with symptoms from the CNS and a median disease duration of 16 years (9-25 years) together with five Alzheimer (AD) patients, who served as positive controls were included in the study. Amyloid CNS deposits were assessed by 18F- flutemetamol PET/CT examination utilising relative z scores with pons as reference.

    Results: Expectedly, all Alzheimer patients had an clearly increased global composite z score above 2.0 compared with 55% of the ATTRv patients. There was an increased local uptake corresponding to cerebellum in 12 ATTRv patients compared to only one in the AD group (fig 1). Four of these ATTRv patients had a global composite z score within the normal range. No correlation between duration after 9 years and amyloid CNS deposition was noted.

    Conclusion: Amyloid deposition within the brain after long-standing ATTRv amyloidosis is increased and is often noted in the cerebellum. However, not all patient display amyloid CNS deposition, thus, additional causes for CNS complications should always be considered.

  • 149. Waddington Cruz, M
    et al.
    Coelho, T
    Conceicao, I
    Plante-Bordeneuve, V
    Ericzon, B-G
    Falk, RH
    Ikeda, S-I
    Mauer, M
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Mazzeo, A
    Grogan, D
    Baseline nutritional status in symptomatic patients in the transthyretin amyloidosis outcomes survey (thaos)2011In: Special Issue: Abstracts of the 15th Congress of the EFNS, Budapest, Hungary, 2011, Oxford: Rapid Communications , 2011, Vol. 18, p. 322-322Conference paper (Refereed)
  • 150.
    Wange, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Ericzon, Bo-Göran
    Pennlert, Johanna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Atrial Fibrillation and Central Nervous Complications in Liver Transplanted Hereditary Transthyretin Amyloidosis Patients2018In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, no 2, p. e59-e66Article in journal (Refereed)
    Abstract [en]

    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 Vasterbotten, 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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