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1
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Ye YQ, Li PH, Wu Q, Yang SL, Zhuang BD, Cao YW, Xiao ZY, Wen SQ. Evolution of surgical treatment for hepatolithiasis. World J Gastrointest Surg 2024; 16:3666-3674. [PMID: 39734463 PMCID: PMC11650219 DOI: 10.4240/wjgs.v16.i12.3666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/27/2024] [Accepted: 10/11/2024] [Indexed: 11/27/2024] Open
Abstract
Hepatolithiasis is a common disease where stones are located in the intrahepatic bile duct. Hepatolithiasis is a disease with regional characteristics. The complication and postoperative recurrence rates of the disease are high. The intrahepatic cholangiocarcinoma and the incidence of liver cirrhosisare the main causes of death in patients with hepatolithiasis. Thus, it is difficult to treat. The majority of biliary stones are readily removed endoscopically, however complex intrahepatic or large refractory extrahepatic stones often require surgical or percutaneous interventions when standard endoscopic methods fail. At present, the main clinical treatment for hepatolithiasis is surgery, of which there are different methods depending on the patient's condition. With the continuous updates and development of medical technology, the treatment of hepatolithiasis has improved. In this paper, several mainstream surgical methods including partial hepatectomy, choledochojejunostomy, biliary tract exploration and lithotomy, percutaneous transhepatic chledochoscopic lithotripsy and liver transplantation used in the clinic are reviewed for clinicians' reference. Depending on the characteristics of each case, a suitable surgical method is chosen to obtain the best treatment effect.
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Affiliation(s)
- Yong-Qing Ye
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
| | - Pei-Heng Li
- Department of Oncology, Foshan Nanhai District Fifth People's Hospital, Foshan 528000, Guangdong Province, China
| | - Qing Wu
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
| | - Shang-Lin Yang
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
| | - Bao-Ding Zhuang
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
| | - Ya-Wen Cao
- Department of Emergency Medicine, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Zhan-Yi Xiao
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
| | - Shun-Qian Wen
- Department of Hepatobiliary Surgery, The Second People's Hospital of Foshan, Foshan 528000, Guangdong Province, China
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2
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Kakos CD, Ziogas IA, Demiri CD, Esagian SM, Economopoulos KP, Moris D, Tsoulfas G, Alexopoulos SP. Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review. Cancers (Basel) 2022; 14:1294. [PMID: 35267604 PMCID: PMC8908995 DOI: 10.3390/cancers14051294] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/23/2022] [Accepted: 02/28/2022] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative option for children with unresectable hepatocellular carcinoma (HCC). We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases (end-of-search date: 31 July 2020). Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of clinically relevant variables on outcomes using the Kaplan-Meier method and log-rank test. Sixty-seven studies reporting on 245 children undergoing LT for HCC were included. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the two hundred and thirty-eight patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. Although no difference was observed between children transplanted within vs. beyond Milan criteria (p = 0.15), superior OS was observed in children transplanted within vs. beyond UCSF criteria (p = 0.02). LT can yield favorable outcomes for pediatric HCC beyond Milan but not beyond UCSF criteria. Further research is required to determine appropriate LT selection criteria for pediatric HCC.
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Affiliation(s)
- Christos D. Kakos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
| | - Ioannis A. Ziogas
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Charikleia D. Demiri
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- 2nd Department of Pediatric Surgery, “Papageorgiou” General Hospital, Aristotle University School of Medicine, 54124 Thessaloniki, Greece
| | - Stepan M. Esagian
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
| | - Konstantinos P. Economopoulos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece; (C.D.K.); (I.A.Z.); (C.D.D.); (S.M.E.); (K.P.E.)
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, 54124 Thessaloniki, Greece;
| | - Sophoclis P. Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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3
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Bakır A, Topçu V, Çavdarlı B. The molecular landscape of progressive familial intrahepatic cholestasis in Turkey: Defining the molecular profiles and expanding the variant spectrum. Ann Hum Genet 2021; 86:119-126. [PMID: 34961929 DOI: 10.1111/ahg.12456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/02/2021] [Accepted: 12/08/2021] [Indexed: 11/29/2022]
Abstract
Progressive familial intrahepatic cholestasis (PFIC) is a rare genetically heterogeneous group of autosomal recessive liver disorders that manifests as intrahepatic cholestasis during the neonatal period. ATP8B1, ABCB11, and ABCB4 genes are responsible for PFIC type 1, PFIC type 2, and PFIC type 3, respectively. To determine the underlying molecular etiology of PFIC, 80 patients from 77 families were investigated. The molecular genetic diagnosis was applied by using next-generation sequencing (NGS) and revealed 29 different variants from 32 patients. In this study, we evaluated these variants according to mechanisms, clinical sub-groups, and genotype-phenotype correlation.
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Affiliation(s)
- Abdullatif Bakır
- Department of Medical Genetics, AnkaraTraining and Research Hospital, Ankara, Turkey.,Department of Medical Genetics, University of Health Sciences, Dr. Sami Ulus Maternity and Children's Education and Research Hospital, Ankara, Turkey
| | - Vehap Topçu
- Department of Medical Genetics, Ankara Numune Training and Research Hospital, Ankara, Turkey.,Department of Medical Genetics, Ankara Cıty Hospıtal, Ankara, Turkey
| | - Büşranur Çavdarlı
- Department of Medical Genetics, Ankara Numune Training and Research Hospital, Ankara, Turkey.,Department of Medical Genetics, Ankara Cıty Hospıtal, Ankara, Turkey
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4
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Zhang W, Lin R, Lu Z, Sheng H, Xu Y, Li X, Cheng J, Cai Y, Mao X, Liu L. Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China. Pediatr Gastroenterol Hepatol Nutr 2020; 23:558-566. [PMID: 33215027 PMCID: PMC7667226 DOI: 10.5223/pghn.2020.23.6.558] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 05/21/2020] [Accepted: 06/23/2020] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. METHODS We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. RESULTS Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. CONCLUSION The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.
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Affiliation(s)
- Wen Zhang
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Ruizhu Lin
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Zhikun Lu
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Huiying Sheng
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Yi Xu
- Department of Infectious Disease, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Xiuzhen Li
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Jing Cheng
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Yanna Cai
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Xiaojian Mao
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Li Liu
- Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China
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Aguiar TFM, Rivas MP, Costa S, Maschietto M, Rodrigues T, Sobral de Barros J, Barbosa AC, Valieris R, Fernandes GR, Bertola DR, Cypriano M, Caminada de Toledo SR, Major A, Tojal I, Apezzato MLDP, Carraro DM, Rosenberg C, Lima da Costa CM, Cunha IW, Sarabia SF, Terrada DL, Krepischi ACV. Insights Into the Somatic Mutation Burden of Hepatoblastomas From Brazilian Patients. Front Oncol 2020; 10:556. [PMID: 32432034 PMCID: PMC7214543 DOI: 10.3389/fonc.2020.00556] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/27/2020] [Indexed: 12/23/2022] Open
Abstract
Hepatoblastoma is a very rare embryonal liver cancer supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. In this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case. Our data disclosed a low mutational background and pointed out to a novel set of candidate genes for hepatoblastoma biology, which were shown to impact gene expression levels. Only three recurrently mutated genes were detected: CTNNB1 and two novel candidates, CX3CL1 and CEP164. A relevant finding was the identification of a recurrent mutation (A235G) in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed upregulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas. In inflammatory regions of hepatoblastomas, CX3CL1/CX3CR1 were not detected in the infiltrated lymphocytes, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative labeling in tumor cells, but strongly positive infiltrated lymphocytes. Altogether, these data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, mostly related to tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations. Overall, we present here novel candidate genes for hepatoblastoma, with evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with progression, besides reporting specific mutational signatures.
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Affiliation(s)
- Talita Ferreira Marques Aguiar
- International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil.,Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Maria Prates Rivas
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Silvia Costa
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | | | - Tatiane Rodrigues
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Juliana Sobral de Barros
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Anne Caroline Barbosa
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Renan Valieris
- International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Gustavo R Fernandes
- Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil
| | - Debora R Bertola
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | - Monica Cypriano
- Adolescent and Child With Cancer Support Group (GRAACC), Department of Pediatric, Federal University of São Paulo, São Paulo, Brazil
| | - Silvia Regina Caminada de Toledo
- Adolescent and Child With Cancer Support Group (GRAACC), Department of Pediatric, Federal University of São Paulo, São Paulo, Brazil
| | - Angela Major
- Department of Pathology and Immunology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, United States
| | - Israel Tojal
- International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil
| | | | - Dirce Maria Carraro
- International Center for Research, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Carla Rosenberg
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
| | | | - Isabela W Cunha
- Department of Pathology, Rede D'OR-São Luiz, São Paulo, Brazil.,Department of Pathology, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Stephen Frederick Sarabia
- Department of Pathology and Immunology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, United States
| | - Dolores-López Terrada
- Department of Pathology and Immunology, Texas Children's Hospital and Baylor College of Medicine, Houston, TX, United States.,Department of Pediatrics, Texas Children's Cancer Center, Houston, TX, United States.,Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
| | - Ana Cristina Victorino Krepischi
- Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo, São Paulo, Brazil
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6
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Lu X, Liu L, Shan W, Kong L, Chen N, Lou Y, Zeng S. The Role of the Sodium-taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) in Related Liver Disease. Curr Drug Metab 2019; 20:377-389. [PMID: 31258056 DOI: 10.2174/1389200220666190426152830] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 03/10/2019] [Accepted: 03/26/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease. METHODS We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP. RESULTS This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases. CONCLUSION NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.
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Affiliation(s)
- Xiaoyang Lu
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Lin Liu
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Wenya Shan
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Limin Kong
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Na Chen
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Yan Lou
- The First Affiliated Hospital, Zhejiang University, Zhejiang, China
| | - Su Zeng
- Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Zhejiang, China
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7
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M. Z, S.M. D, F. E, M.R. F, M. M, S.M.B. T. In-silico Evaluation of Rare Codons and their Positions in the Structure of ATP8b1 Gene. J Biomed Phys Eng 2019; 9:105-120. [PMID: 30881940 PMCID: PMC6409373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/18/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND Progressive familial intrahepatic cholestases (PFIC) are a spectrum of autosomal progressive liver diseases developing to end-stage liver disease. ATP8B1 deficiency caused by mutations in ATP8B1 gene encoding a P-type ATPase leads to PFIC1. The gene for PFIC1 has been mapped on a 19-cM region of 18q21-q22, and a gene defect in ATP8B1 can cause deregulations in bile salt transporters through decreased expression and/or activity of FXR. Point mutations are the most common, with the majority being missense or nonsense mutations. In addition, approximately 15% of disease-causing ATP8B1 mutations are annotated as splicing disrupting alteration given that they are located at exon-intron borders. OBJECTIVE Here, we describe the hidden layer of computational biology information of rare codons in ATP8B1, which can help us for drug design. METHODS Some rare codons in different locations of ATP8b1 gene were identified using several web servers and by in-silico modelling of ATP8b1 in Phyre2 and I-TASSER server, some rare codons were evaluated. RESULTS Some of these rare codons were located at special positions which seem to have a critical role in proper folding of ATP8b1 protein. Structural analysis showed that some of rare codons are related to mutations in ATP8B1 that are responsible for PFIC1 disease, which may have a critical role in ensuring the correct folding. CONCLUSION Investigation of such hidden information can enhance our understanding of ATP8b1 folding. Moreover, studies of these rare codons help us to clarify their role in rational design of new and effective drugs.
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Affiliation(s)
- Zarenezhad M.
- MD, PhD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,MD, PhD, legal medicine research center, legal medicine organization, Tehran , iran
| | - Dehghani S.M.
- MD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ejtehadi F.
- MD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fattahi M.R.
- MD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mortazavi M.
- PhD, Department of Biotechnology, Institute of Science and High Technology and Environmental Science, Graduate University of Advanced Technology, Kerman, Iran
| | - Tabei S.M.B.
- MD, Genetic Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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8
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Pandita A, Gupta V, Gupta G. Neonatal Cholestasis: A Pandora's Box. CLINICAL MEDICINE INSIGHTS-PEDIATRICS 2018; 12:1179556518805412. [PMID: 30574003 PMCID: PMC6295748 DOI: 10.1177/1179556518805412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 08/29/2018] [Indexed: 12/15/2022]
Abstract
Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition–associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.
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Affiliation(s)
- Aakash Pandita
- Department of Neonatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Vishal Gupta
- Department of Neonatology, Max Hospital, New Delhi, India
| | - Girish Gupta
- Department of Neonatology, Max Hospital, New Delhi, India
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9
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Gan L, Pan S, Cui J, Bai J, Jiang P, He Y. Functional analysis of the correlation between ABCB11 gene mutation and primary intrahepatic stone. Mol Med Rep 2018; 19:195-204. [PMID: 30431138 PMCID: PMC6297787 DOI: 10.3892/mmr.2018.9661] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 10/22/2018] [Indexed: 12/16/2022] Open
Abstract
The adenosine 5'‑triphosphate binding cassette subfamily B member (ABCB)11 gene is involved in bile transport, and mutations in this gene are associated with cholestasis and cholelithiasis. Therefore, the aim of the present study was to investigate the association between ABCB11 gene mutation and primary intrahepatic stone (PIS)s and to investigate the mechanism through which ABCB11 gene mutations affect the expression of the corresponding protein. Mutations of the ABCB11 gene in 443 PIS patients and 560 healthy participants were detected by exon sequencing. The expression levels of ABCB11 mRNA and bile salt export pump (BSEP) protein in the liver tissues of patients with PISs were measured by quantitative polymerase chain reaction and western blot analysis. The mutant plasmids constructed by site‑directed mutagenesis of the human BSEP gene were transfected into human embryonic kidney 293 (293) cells and Madin‑Darby canine kidney (MDCK) cells, and the expression and distribution of rs118109635 of BSEP was measured. There were two significant mutations in the ABCB11 gene of the PIS patients compared with the healthy population; a missense mutation, rs118109635 (P=0.025), and a synonymous mutation, rs497692 (P=0.006). The two mutations were associated with the occurrence of preoperative jaundice (P=0.026, and P=0.011, respectively). The expression levels of BSEP in PIS patients with the missense mutation rs118109635 was decreased, whereas its mRNA expression levels remained unchanged. In PIS patients with the synonymous mutation rs497692, the expression levels of ABCB11 were decreased at both the mRNA and protein level. It was also found that mutation A865V reduced the expression levels of BSEP in 293 cells at the cellular level; its distribution in MDCK cell membranes was decreased, whereas its mRNA levels remained unchanged. The mutated loci at rs118109635 and rs497692 of the ABCB11 gene were correlated with PISs, causing a decreased expression of BSEP and reduced distribution of the protein in the cell membrane. Therefore, mutations at rs118109635 and rs497692 of the ABCB11 gene may be risk factors for PISs.
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Affiliation(s)
- Lang Gan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
| | - Shuguang Pan
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
| | - Jinchi Cui
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
| | - Jie Bai
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
| | - Peng Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
| | - Yu He
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China
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10
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Imagawa K, Hayashi H, Sabu Y, Tanikawa K, Fujishiro J, Kajikawa D, Wada H, Kudo T, Kage M, Kusuhara H, Sumazaki R. Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis. J Hum Genet 2018; 63:569-577. [PMID: 29507376 DOI: 10.1038/s10038-018-0431-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 02/02/2018] [Accepted: 02/07/2018] [Indexed: 01/26/2023]
Abstract
The bile salt export pump (BSEP) plays an important role in biliary secretion. Mutations in ABCB11, the gene encoding BSEP, induce progressive familial intrahepatic cholestasis type 2 (PFIC2), which presents with severe jaundice and liver dysfunction. A less severe phenotype, called benign recurrent intrahepatic cholestasis type 2, is also known. About 200 missense mutations in ABCB11 have been reported. However, the phenotype-genotype correlation has not been clarified. Furthermore, the frequencies of ABCB11 mutations differ between Asian and European populations. We report a patient with PFIC2 carrying a homozygous ABCB11 mutation c.386G>A (p.C129Y) that is most frequently reported in Japan. The pathogenicity of BSEPC129Y has not been investigated. In this study, we performed the molecular analysis of this ABCB11 mutation using cells expressing BSEPC129Y. We found that trafficking of BSEPC129Y to the plasma membrane was impaired and that the expression of BSEPC129Y on the cell surface was significantly lower than that in the control. The amount of bile acids transported via BSEPC129Y was also significantly lower than that via BSEPWT. The transport activity of BSEPC129Y may be conserved because the amount of membrane BSEPC129Y corresponded to the uptake of taurocholate into membrane vesicles. In conclusion, we demonstrated that c.386G>A (p.C129Y) in ABCB11 was a causative mutation correlating with the phenotype of patients with PFIC2, impairment of biliary excretion from hepatocytes, and the absence of canalicular BSEP expression in liver histological assessments. Mutational analysis in ABCB11 could facilitate the elucidation of the molecular mechanisms underlying the development of intrahepatic cholestasis.
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Affiliation(s)
- Kazuo Imagawa
- Department of Pediatrics, University of Tsukuba Hospital, Ibaraki, Japan. .,Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
| | - Hisamitsu Hayashi
- Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
| | - Yusuke Sabu
- Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Ken Tanikawa
- Department of Diagnostic Pathology, Kurume University Hospital, Fukuoka, Japan
| | - Jun Fujishiro
- Department of Pediatric Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Daigo Kajikawa
- Department of Pediatrics, University of Tsukuba Hospital, Ibaraki, Japan
| | - Hiroki Wada
- Department of Pediatrics, University of Tsukuba Hospital, Ibaraki, Japan
| | - Toyoichiro Kudo
- Department of Pediatrics, Mito Saiseikai General Hospital, Ibaraki, Japan
| | - Masayoshi Kage
- Department of Diagnostic Pathology, Kurume University Hospital, Fukuoka, Japan
| | - Hiroyuki Kusuhara
- Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| | - Ryo Sumazaki
- Department of Child Health, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
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