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Salum GM, el Meguid MA, Abelhafez TH, Medhat E, Abdel Aziz AO, Dawood R. Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation. J Genet Eng Biotechnol 2021; 19:174. [PMID: 34757522 PMCID: PMC8581076 DOI: 10.1186/s43141-021-00266-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 10/05/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Orthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. RESULTS Seven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02-1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5-1407.8]. CONCLUSIONS Accordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.
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Affiliation(s)
- Ghada M. Salum
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Mai Abd el Meguid
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Tawfeek H. Abelhafez
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Eman Medhat
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf O. Abdel Aziz
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Reham Dawood
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
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Resino S, Fernández-Rodríguez A, Pineda-Tenor D, Gómez-Moreno AZ, Sánchez-Ruano JJ, Artaza-Varasa T, Muñoz-Gómez MJ, Virseda-Berdices A, Martín-Vicente M, Martínez I, Jiménez-Sousa MA. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients. J Clin Med 2021; 10:483. [PMID: 33525598 PMCID: PMC7865714 DOI: 10.3390/jcm10030483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/23/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. METHODS We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. RESULTS The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). CONCLUSIONS TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.
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Affiliation(s)
- Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Daniel Pineda-Tenor
- Servicio de Laboratorio Clínico, Hospital de Antequera, 29200 Málaga, Spain;
| | - Ana Zaida Gómez-Moreno
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - Juan José Sánchez-Ruano
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - Tomas Artaza-Varasa
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - María José Muñoz-Gómez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - María Martín-Vicente
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - María A. Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
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Frias M, Rivero-Juárez A, López-López P, Rivero A. Pharmacogenetics and the treatment of HIV-/HCV-coinfected patients. Pharmacogenomics 2018; 19:979-995. [PMID: 29992850 DOI: 10.2217/pgs-2018-0046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
This review will summarize the role of pharmacogenetics in the natural history of hepatitis C, particularly in patients with HIV/HCV and will take the perspective of pharmacogenetics and its influence on the response to antiviral therapy and the susceptibility to develop adverse effects. This review will also devote a section to host genetics in other clinical situations, such as disease progression and acute HCV infection, which may determine whether treatment of HIV-/HCV-coinfected patients is implemented or deferred.
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Affiliation(s)
- Mario Frias
- Department of Clinical Virology & Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba. Córdoba, 14004, Spain
| | - Antonio Rivero-Juárez
- Department of Clinical Virology & Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba. Córdoba, 14004, Spain
| | - Pedro López-López
- Department of Clinical Virology & Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba. Córdoba, 14004, Spain
| | - Antonio Rivero
- Department of Clinical Virology & Zooneses, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba. Córdoba, 14004, Spain
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Eslam M, Hashem AM, Romero-Gomez M, Berg T, Dore GJ, Mangia A, Chan HLY, Irving WL, Sheridan D, Abate ML, Adams LA, Weltman M, Bugianesi E, Spengler U, Shaker O, Fischer J, Mollison L, Cheng W, Nattermann J, Riordan S, Miele L, Kelaeng KS, Ampuero J, Ahlenstiel G, McLeod D, Powell E, Liddle C, Douglas MW, Booth DR, George J. FibroGENE: A gene-based model for staging liver fibrosis. J Hepatol 2016; 64:390-398. [PMID: 26592354 DOI: 10.1016/j.jhep.2015.11.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 11/02/2015] [Accepted: 11/09/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The extent of liver fibrosis predicts long-term outcomes, and hence impacts management and therapy. We developed a non-invasive algorithm to stage fibrosis using non-parametric, machine learning methods designed for predictive modeling, and incorporated an invariant genetic marker of liver fibrosis risk. METHODS Of 4277 patients with chronic liver disease, 1992 with chronic hepatitis C (derivation cohort) were analyzed to develop the model, and subsequently validated in an independent cohort of 1242 patients. The model was assessed in cohorts with chronic hepatitis B (CHB) (n=555) and non-alcoholic fatty liver disease (NAFLD) (n=488). Model performance was compared to FIB-4 and APRI, and also to the NAFLD fibrosis score (NFS) and Forns' index, in those with NAFLD. RESULTS Significant fibrosis (⩾F2) was similar in the derivation (48.4%) and validation (47.4%) cohorts. The FibroGENE-DT yielded the area under the receiver operating characteristic curve (AUROCs) of 0.87, 0.85 and 0.804 for the prediction of fast fibrosis progression, cirrhosis and significant fibrosis risk, respectively, with comparable results in the validation cohort. The model performed well in NAFLD and CHB with AUROCs of 0.791, and 0.726, respectively. The negative predictive value to exclude cirrhosis was>0.96 in all three liver diseases. The AUROC of the FibroGENE-DT performed better than FIB-4, APRI, and NFS and Forns' index in most comparisons. CONCLUSION A non-invasive decision tree model can predict liver fibrosis risk and aid decision making.
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia
| | - Ahmed M Hashem
- Department of Systems and Biomedical Engineering, Faculty of Engineering, Minia University, Minia, Egypt
| | - Manuel Romero-Gomez
- Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
| | - Thomas Berg
- Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany; Department of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Gregory J Dore
- Kirby Institute, The University of New South Wales, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia
| | - Alessandra Mangia
- Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy
| | - Henry Lik Yuen Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - William L Irving
- NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, United Kingdom
| | - David Sheridan
- Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Translational and Stratified Medicine, Plymouth University, United Kingdom
| | - Maria Lorena Abate
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Leon A Adams
- School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, WA, Australia
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, NSW, Australia
| | - Elisabetta Bugianesi
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Olfat Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Janett Fischer
- Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany
| | - Lindsay Mollison
- School of Medicine and Pharmacology, Fremantle Hospital, UWA, Fremantle, WA, Australia
| | - Wendy Cheng
- Department of Gastroenterology & Hepatology, Royal Perth Hospital, WA, Australia
| | - Jacob Nattermann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Stephen Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia
| | - Luca Miele
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Kebitsaone Simon Kelaeng
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia
| | - Javier Ampuero
- Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
| | - Golo Ahlenstiel
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia
| | - Duncan McLeod
- Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, Australia
| | - Elizabeth Powell
- Princess Alexandra Hospital, Department of Gastroenterology and Hepatology, Woolloongabba, QLD, Australia; The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Christopher Liddle
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia
| | - Mark W Douglas
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia
| | - David R Booth
- Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Millennium Institute for Medical Research and Westmead Hospital, The University of Sydney, NSW, Australia.
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