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  1. Article ; Online: Defining the natural history of rare genetic liver diseases: Lessons learned from the NAPPED initiative.

    van Wessel, Daan B E / Gonzales, Emmanuel / Hansen, Bettina E / Verkade, Henkjan J

    European journal of medical genetics

    2021  Volume 64, Issue 7, Page(s) 104245

    Abstract: While rare diseases collectively affect ~300 million people worldwide, the prevalence of each disease concerns a relatively small number of patients. Usually, only limited data with regard to natural history are available. Multicenter initiatives are ... ...

    Abstract While rare diseases collectively affect ~300 million people worldwide, the prevalence of each disease concerns a relatively small number of patients. Usually, only limited data with regard to natural history are available. Multicenter initiatives are needed to aggregate data and answer clinically relevant research questions. In 2017, we launched the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) consortium. In three years, NAPPED created a global network focused on rare genetic liver diseases in the Progressive Familial Intrahepatic Cholestasis (PFIC) spectrum. During these years, we have learned important lessons which we feel should be taken into account when initiating and leading a global consortium. First, it is essential to 'keep it simple' from the start. Research questions, case report forms (CRFs) and data acquisition should be limited and clear to stay focused and keep the workload low for new participants. Secondly, early rewards and research output are needed to keep momentum and motivation. Quick output can only follow a clean and simple design. Thirdly, the leading team should be in touch and accessible. Ideally, an involved PhD-candidate is appointed as primary contact person. Lastly, be inclusive and actively involve all participants the consortium's course. Global consortia are critical for personalized medicine in rare diseases. Also, they are essential for setting up trials to investigate generic drugs and personalized therapies. We hope to herewith stimulate others that are starting (or are planning to start) a global consortium, ultimately to help improve the care for patients with a rare disease.
    MeSH term(s) Cholestasis, Intrahepatic/diagnosis ; Cholestasis, Intrahepatic/genetics ; Cholestasis, Intrahepatic/therapy ; Consensus ; Databases, Factual ; Genetic Diseases, Inborn/diagnosis ; Genetic Diseases, Inborn/genetics ; Genetic Diseases, Inborn/therapy ; Humans ; Practice Guidelines as Topic ; Rare Diseases/diagnosis ; Rare Diseases/genetics ; Rare Diseases/therapy
    Language English
    Publishing date 2021-05-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2184135-4
    ISSN 1878-0849 ; 1769-7212
    ISSN (online) 1878-0849
    ISSN 1769-7212
    DOI 10.1016/j.ejmg.2021.104245
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  2. Article ; Online: Prognosis of Biliary Atresia After 2-year Survival With Native Liver: A Nationwide Cohort Analysis.

    Witt, Mauri / van Wessel, Daan B E / de Kleine, Ruben H J / Bruggink, Janneke L M / Hulscher, Jan B F / Verkade, Henkjan J

    Journal of pediatric gastroenterology and nutrition

    2018  Volume 67, Issue 6, Page(s) 689–694

    Abstract: Objectives: The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age.: Methods: We retrospectively ... ...

    Abstract Objectives: The aim of the study is to determine the prognosis of patients with biliary atresia after 2 years of native liver survival (NLS) and to identify prognostic factors for continued NLS after 2 years of age.
    Methods: We retrospectively analyzed perioperative, laboratory, and outcome parameters of all biliary atresia patients in The Netherlands between January 1987 and June 2015 with NLS of at least 2 years. We compared parameters between patients who continued to have their native liver (NLS+) to those who did not, either by transplant or death (NLS-).
    Results: We included 100 patients. Upon a median follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in 6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were 89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%, 90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher clearance of jaundice (COJ) rate, significantly lower total and direct serum bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared with NLS- patients (each P < 0.05). Cox regression could only assess a significant effect of COJ on continued NLS. Main indications for LTx after the age of 2 were irreversible jaundice and portal hypertension.
    Conclusions: Eighty-seven percent of patients with 2-year NLS reach adult age and more than 50% with their native liver. A pre-transplant mortality of 6%, however, exists among patients who reach the age of 2 years with their native livers. Early life parameters, other than COJ, did not have a significant effect on continued NLS after 2 years of age.
    MeSH term(s) Adolescent ; Adult ; Biliary Atresia/mortality ; Biliary Atresia/physiopathology ; Biliary Atresia/surgery ; Child ; Child, Preschool ; Databases, Factual ; Female ; Follow-Up Studies ; Humans ; Liver/physiopathology ; Male ; Netherlands ; Portoenterostomy, Hepatic/mortality ; Prognosis ; Registries ; Retrospective Studies ; Survival Rate ; Time Factors ; Young Adult
    Language English
    Publishing date 2018-09-03
    Publishing country United States
    Document type Evaluation Studies ; Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1097/MPG.0000000000002130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1728: Show issues Location:
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  3. Article ; Online: A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results From an Epidemiological Study in The Netherlands.

    Nomden, Mark / van Wessel, Daan B E / Ioannou, Solomon / Verkade, Henkjan J / de Kleine, Ruben H / Alizadeh, Behrooz Z / Bruggink, Janneke L M / Hulscher, Jan B F

    Journal of pediatric gastroenterology and nutrition

    2020  Volume 72, Issue 2, Page(s) 202–209

    Abstract: Objectives: Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and ... ...

    Abstract Objectives: Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and population density, and geographical and temporal clustering of BA in the Netherlands.
    Study design: Correlations between the monthly incidence of BA and the number of confirmed infections were assessed. BA incidence per province was calculated and compared to the province with highest population density. Birthplaces were classified as rural or urban. Temporal clustering of month of birth and month of conception were analyzed. We performed analyses for isolated BA (IBA) and syndromic BA (SBA) separately. Chi2, logistic regression, and Walter and Elwood test were used.
    Results: A total of 262 IBA and 49 SBA patients, born between 1987 and 2018, were included. IBA incidence correlated to the number of confirmed infections of, for example, Chlamydia trachomatis (R = 0.14; P = 0.02) and adenovirus (R = 0.22; P = 0.005). We observed a higher incidence of IBA (0.75/10,000; odds ratio [OR] = 1.86; P = 0.04) and SBA (0.27/10,000; OR = 6.91; P = 0.001) in Groningen and a higher incidence of SBA in Gelderland (0.13/10,000; OR = 3.35; P = 0.03). IBA incidence was 68% higher in rural (0.67/10,000) versus urban areas (0.40/10,000) (P = 0.02). The estimated month of conception of patients with SBA clustered in November (85% increase compared to average SBA incidence [0.09/10,000; P = 0.04]).
    Conclusions: IBA incidence correlated weakly with national confirmed infections. IBA and SBA incidence varied geographically in the Netherlands. IBA incidence was higher in rural than in urban areas, which may be explained decreased exposure to pathogens. Our results provide support for a role of environmental factors in the pathogenesis of IBA.
    MeSH term(s) Biliary Atresia/epidemiology ; Biliary Atresia/etiology ; Epidemiologic Studies ; Humans ; Incidence ; Netherlands/epidemiology ; Rural Population
    Language English
    Publishing date 2020-09-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1097/MPG.0000000000002916
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  4. Article ; Online: Preterm Infants With Biliary Atresia: A Nationwide Cohort Analysis From The Netherlands.

    van Wessel, Daan B E / Boere, Thomas / Hulzebos, Christian V / de Kleine, Ruben H J / Verkade, Henkjan J / Hulscher, Jan B F

    Journal of pediatric gastroenterology and nutrition

    2017  Volume 65, Issue 4, Page(s) 370–374

    Abstract: Objectives: Biliary atresia (BA) occurs in 0.54 of 10.000 of overall live births in the Netherlands. BA has an unfavorable prognosis: <40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% ...

    Abstract Objectives: Biliary atresia (BA) occurs in 0.54 of 10.000 of overall live births in the Netherlands. BA has an unfavorable prognosis: <40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% and the 4-year survival rate is ∼75%. Little is known on difficulties in diagnosis and the outcome of BA in preterm infants. We aimed to analyze the incidence and outcome of BA in preterm infants in the Netherlands.
    Methods: Retrospective study including Dutch preterm infants treated for BA. Parameters included gestational age, congenital anomalies, age at KPE, days between first symptoms, and KPE and referral interval (first hospital to KPE). Outcome parameters were clearance of jaundice (COJ) and (transplant-free) survival. Data are presented as medians (ranges).
    Results: Included 28 preterm infants (13 boys/15 girls) between March 1988 and December 2015. The incidence of BA was 1.06 of 10.000 preterm live births. Gestational age was 34.8 (27.3-36.9) weeks. Congenital anomalies were present in 11 of 28 (39%) infants. Time between first symptoms and KPE was 57 (9-138) days. Referral interval was 28 (8-86) days. Age at KPE was 70 (35-145) days. COJ was achieved in 23% of cases. Four-year transplant-free survival rate was 21%. Four-year overall survival was 61%.
    Conclusions: BA has a higher incidence in the preterm population compared to the overall BA population. The outcome of BA in preterm infants is poor, regarding COJ and (transplant-free) survival. We speculate that timely recognition of BA-related signs and symptoms in preterm infants will improve prognosis.
    MeSH term(s) Biliary Atresia/epidemiology ; Biliary Atresia/surgery ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology ; Infant, Premature, Diseases/surgery ; Liver Transplantation ; Male ; Netherlands/epidemiology ; Portoenterostomy, Hepatic ; Prognosis ; Retrospective Studies ; Survival Rate
    Language English
    Publishing date 2017-09-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1097/MPG.0000000000001692
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  5. Article ; Online: Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

    Felzen, Antonia / van Wessel, Daan B E / Gonzales, Emmanuel / Thompson, Richard J / Jankowska, Irena / Shneider, Benjamin L / Sokal, Etienne / Grammatikopoulos, Tassos / Kadaristiana, Agustina / Jacquemin, Emmanuel / Spraul, Anne / Lipiński, Patryk / Czubkowski, Piotr / Rock, Nathalie / Shagrani, Mohammad / Broering, Dieter / Nicastro, Emanuele / Kelly, Deirdre / Nebbia, Gabriella /
    Arnell, Henrik / Fischler, Björn / Hulscher, Jan B F / Serranti, Daniele / Arikan, Cigdem / Polat, Esra / Debray, Dominique / Lacaille, Florence / Goncalves, Cristina / Hierro, Loreto / Muñoz Bartolo, Gema / Mozer-Glassberg, Yael / Azaz, Amer / Brecelj, Jernej / Dezsőfi, Antal / Calvo, Pier Luigi / Grabhorn, Enke / Hartleif, Steffen / van der Woerd, Wendy J / Kamath, Binita M / Wang, Jian-She / Li, Liting / Durmaz, Özlem / Kerkar, Nanda / Jørgensen, Marianne Hørby / Fischer, Ryan / Jimenez-Rivera, Carolina / Alam, Seema / Cananzi, Mara / Laverdure, Noemie / Ferreira, Cristina Targa / Guerrero, Felipe Ordoñez / Wang, Heng / Sency, Valerie / Kim, Kyung Mo / Chen, Huey-Ling / de Carvalho, Elisa / Fabre, Alexandre / Bernabeu, Jesus Quintero / Zellos, Aglaia / Alonso, Estella M / Sokol, Ronald J / Suchy, Frederick J / Loomes, Kathleen M / McKiernan, Patrick J / Rosenthal, Philip / Turmelle, Yumirle / Horslen, Simon / Schwarz, Kathleen / Bezerra, Jorge A / Wang, Kasper / Hansen, Bettina E / Verkade, Henkjan J

    JHEP reports : innovation in hepatology

    2022  Volume 5, Issue 2, Page(s) 100626

    Abstract: Background & aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with ... ...

    Abstract Background & aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship.
    Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS.
    Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3
    Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment.
    Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.
    Language English
    Publishing date 2022-11-16
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2589-5559
    ISSN (online) 2589-5559
    DOI 10.1016/j.jhepr.2022.100626
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  6. Article ; Online: Genotype correlates with the natural history of severe bile salt export pump deficiency.

    van Wessel, Daan B E / Thompson, Richard J / Gonzales, Emmanuel / Jankowska, Irena / Sokal, Etienne / Grammatikopoulos, Tassos / Kadaristiana, Agustina / Jacquemin, Emmanuel / Spraul, Anne / Lipiński, Patryk / Czubkowski, Piotr / Rock, Nathalie / Shagrani, Mohammad / Broering, Dieter / Algoufi, Talal / Mazhar, Nejat / Nicastro, Emanuele / Kelly, Deirdre A / Nebbia, Gabriella /
    Arnell, Henrik / Björn Fischler / Hulscher, Jan B F / Serranti, Daniele / Arikan, Cigdem / Polat, Esra / Debray, Dominique / Lacaille, Florence / Goncalves, Cristina / Hierro, Loreto / Muñoz Bartolo, Gema / Mozer-Glassberg, Yael / Azaz, Amer / Brecelj, Jernej / Dezsőfi, Antal / Calvo, Pier Luigi / Grabhorn, Enke / Sturm, Ekkehard / van der Woerd, Wendy J / Kamath, Binita M / Wang, Jian-She / Li, Liting / Durmaz, Özlem / Onal, Zerrin / Bunt, Ton M G / Hansen, Bettina E / Verkade, Henkjan J

    Journal of hepatology

    2020  Volume 73, Issue 1, Page(s) 84–93

    Abstract: Background & aims: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes ... ...

    Abstract Background & aims: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date.
    Methods: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category.
    Results: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 μmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001).
    Conclusions: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS.
    Lay summary: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily B, Member 11/deficiency ; ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics ; Adult ; Bile Acids and Salts/blood ; Bile Acids and Salts/metabolism ; Biliary Tract Surgical Procedures/methods ; Biliary Tract Surgical Procedures/statistics & numerical data ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/prevention & control ; Child, Preschool ; Cholestasis, Intrahepatic/diagnosis ; Cholestasis, Intrahepatic/genetics ; Cholestasis, Intrahepatic/physiopathology ; Cholestasis, Intrahepatic/surgery ; Female ; Genetic Testing/methods ; Humans ; Liver Neoplasms/diagnosis ; Liver Neoplasms/prevention & control ; Male ; Mutation ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Survival Analysis ; Time
    Chemical Substances ABCB11 protein, human ; ATP Binding Cassette Transporter, Subfamily B, Member 11 ; Bile Acids and Salts
    Language English
    Publishing date 2020-02-20
    Publishing country Netherlands
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2020.02.007
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  7. Article ; Online: Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

    van Wessel, Daan B E / Thompson, Richard J / Gonzales, Emmanuel / Jankowska, Irena / Shneider, Benjamin L / Sokal, Etienne / Grammatikopoulos, Tassos / Kadaristiana, Agustina / Jacquemin, Emmanuel / Spraul, Anne / Lipiński, Patryk / Czubkowski, Piotr / Rock, Nathalie / Shagrani, Mohammad / Broering, Dieter / Algoufi, Talal / Mazhar, Nejat / Nicastro, Emanuele / Kelly, Deirdre /
    Nebbia, Gabriella / Arnell, Henrik / Fischler, Björn / Hulscher, Jan B F / Serranti, Daniele / Arikan, Cigdem / Debray, Dominique / Lacaille, Florence / Goncalves, Cristina / Hierro, Loreto / Muñoz Bartolo, Gema / Mozer-Glassberg, Yael / Azaz, Amer / Brecelj, Jernej / Dezsőfi, Antal / Luigi Calvo, Pier / Krebs-Schmitt, Dorothee / Hartleif, Steffen / van der Woerd, Wendy L / Wang, Jian-She / Li, Li-Ting / Durmaz, Özlem / Kerkar, Nanda / Hørby Jørgensen, Marianne / Fischer, Ryan / Jimenez-Rivera, Carolina / Alam, Seema / Cananzi, Mara / Laverdure, Noémie / Targa Ferreira, Cristina / Ordonez, Felipe / Wang, Heng / Sency, Valerie / Mo Kim, Kyung / Chen, Huey-Ling / Carvalho, Elisa / Fabre, Alexandre / Quintero Bernabeu, Jesus / Alonso, Estella M / Sokol, Ronald J / Suchy, Frederick J / Loomes, Kathleen M / McKiernan, Patrick J / Rosenthal, Philip / Turmelle, Yumirle / Rao, Girish S / Horslen, Simon / Kamath, Binita M / Rogalidou, Maria / Karnsakul, Wikrom W / Hansen, Bettina / Verkade, Henkjan J

    Hepatology (Baltimore, Md.)

    2021  Volume 74, Issue 2, Page(s) 892–906

    Abstract: Background and aims: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely ... ...

    Abstract Background and aims: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date.
    Approach and results: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS.
    Conclusions: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.
    MeSH term(s) Adenosine Triphosphatases/deficiency ; Adenosine Triphosphatases/genetics ; Adolescent ; Bile Acids and Salts/blood ; Bile Ducts, Intrahepatic/surgery ; Child ; Child, Preschool ; Cholestasis, Intrahepatic/blood ; Cholestasis, Intrahepatic/genetics ; Cholestasis, Intrahepatic/mortality ; Cholestasis, Intrahepatic/surgery ; Codon, Nonsense ; Female ; Follow-Up Studies ; Humans ; Infant ; Liver Transplantation/statistics & numerical data ; Male ; Prognosis ; Prospective Studies ; Retrospective Studies ; Risk Assessment/methods ; Risk Assessment/statistics & numerical data ; Survival Analysis ; Treatment Outcome ; Young Adult
    Chemical Substances Bile Acids and Salts ; Codon, Nonsense ; Adenosine Triphosphatases (EC 3.6.1.-) ; ATP8B1 protein, human (EC 3.6.1.3.)
    Language English
    Publishing date 2021-07-13
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.31787
    Database MEDical Literature Analysis and Retrieval System OnLINE

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