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Fragkou N, Vlachaki E, Goulis I, Sinakos E. Liver disease in patients with transfusion-dependent β-thalassemia: The emerging role of metabolism dysfunction-associated steatotic liver disease. World J Hepatol 2024; 16:671-677. [PMID: 38818299 PMCID: PMC11135276 DOI: 10.4254/wjh.v16.i5.671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/02/2024] [Accepted: 04/17/2024] [Indexed: 05/22/2024] Open
Abstract
In this Editorial, we highlight the possible role that metabolism dysfunction-associated steatotic liver disease (MASLD) may play in the future, regarding liver disease in patients with transfusion-dependent β-thalassemia (TDBT). MASLD is characterized by excessive accumulation of fat in the liver (hepatic steatosis), in the presence of cardiometabolic factors. There is a strong correlation between the occurrence of MASLD and insulin resistance, while its increased prevalence parallels the global epidemic of diabetes mellitus (DM) and obesity. Patients with TDBT need regular transfusions for life to ensure their survival. Through these transfusions, a large amount of iron is accumulated, which causes saturation of transferrin and leads to the circulation of free iron molecules, which cause damage to vital organs (primarily the liver and myocardium). Over the past, the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C, for which modern and effective treatments have been found, resulting in successful treatment. Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths, and an increase in their life expectancy. This increased survival makes them vulnerable to the onset of diseases, which until recently were mainly related to the non-thalassemic general population, such as obesity and DM. There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence. However, it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia (Padeniya et al, BJH), that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis. These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence, the risk factors, and the effect of MASLD on these patients.
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Affiliation(s)
- Nikolaos Fragkou
- 4 Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Efthimia Vlachaki
- 2 Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Ioannis Goulis
- 4 Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Emmanouil Sinakos
- 4 Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece.
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2
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Kouroumalis E, Tsomidis I, Voumvouraki A. Iron as a therapeutic target in chronic liver disease. World J Gastroenterol 2023; 29:616-655. [PMID: 36742167 PMCID: PMC9896614 DOI: 10.3748/wjg.v29.i4.616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 11/03/2022] [Accepted: 12/31/2022] [Indexed: 01/20/2023] Open
Abstract
It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor in the development and progression of liver disease. The recent clarification of ferroptosis as a specific form of regulated hepatocyte death different from apoptosis and the description of ferritinophagy as a specific variation of autophagy prompted detailed investigations on the association of iron and the liver. In this review, we will present a brief discussion of iron absorption and handling by the liver with emphasis on the role of liver macrophages and the significance of the iron regulators hepcidin, transferrin, and ferritin in iron homeostasis. The regulation of ferroptosis by endogenous and exogenous mod-ulators will be examined. Furthermore, the involvement of iron and ferroptosis in various liver diseases including alcoholic and non-alcoholic liver disease, chronic hepatitis B and C, liver fibrosis, and hepatocellular carcinoma (HCC) will be analyzed. Finally, experimental and clinical results following interventions to reduce iron deposition and the promising manipulation of ferroptosis will be presented. Most liver diseases will be benefited by ferroptosis inhibition using exogenous inhibitors with the notable exception of HCC, where induction of ferroptosis is the desired effect. Current evidence mostly stems from in vitro and in vivo experimental studies and the need for well-designed future clinical trials is warranted.
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Affiliation(s)
- Elias Kouroumalis
- Liver Research Laboratory, University of Crete Medical School, Heraklion 71003, Greece
| | - Ioannis Tsomidis
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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3
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Kouroumalis E, Voumvouraki A. Hepatitis C virus: A critical approach to who really needs treatment. World J Hepatol 2022; 14:1-44. [PMID: 35126838 PMCID: PMC8790391 DOI: 10.4254/wjh.v14.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/14/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.
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Affiliation(s)
- Elias Kouroumalis
- Department of Gastroenterology, University of Crete Medical School, Heraklion 71500, Crete, Greece
| | - Argyro Voumvouraki
- First Department of Internal Medicine, AHEPA University Hospital, Thessaloniki 54621, Greece
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Elbedewy TA, Abd-Elsalam S, Mostafa SM, Abdellatif RS, Fouad A, Youssef M, Abo-Amer YEE, Elsebaey MA. Sofosbuvir/Ledipasvir for Treatment of Chronic Hepatitis C Infection in Adult Patients with β- Thalassemia Major: A Real-Life Study. Endocr Metab Immune Disord Drug Targets 2022; 22:290-296. [PMID: 33530921 DOI: 10.2174/1871530321666210202150538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 12/06/2020] [Accepted: 12/14/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND & AIMS Patients with thalassemia have a lifelong need for blood transfusion, which makes them more risky to hepatitis C virus (HCV). Iron overload and chronic HCV are considered risk factors for patients with thalassemia to develop liver insults. The aim of the present study is to investigate the safety and efficacy of sofosbuvir/ledipasvir in the treatment of chronic HCV infection in Egyptian adult patients with β- thalassemia major. METHODS A retrospective study included 53 patients with β-thalassemia major with chronic HCV treated with sofosbuvir (400 mg) and ledipasvir (90 mg) as a single pill fixed-dose combination once daily for 12 weeks. The effectiveness of the treatment was assessed by the sustained virologic response (SVR) at 12 weeks after the end of the treatment. RESULTS SVR was achieved in 96.23% of patients. 47.17% of patients had minor side effects. There was a significant reduction in ALT, AST, and serum ferritin 12 weeks post-therapy. There was an insignificant change in hemoglobin level or blood transfusion requirement 12 weeks posttherapy. There was no change in iron chelators doses throughout the study period. CONCLUSION Sofosbuvir/ledipasvir regimen seems to be safe and highly effective in the treatment of chronic HCV in patients with β-thalassemia major.
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Affiliation(s)
- Tamer A Elbedewy
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Sherief Abd-Elsalam
- Tropical Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Sahar Mohamed Mostafa
- Hepato-gastroentrology and Infectious Diseases Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Raghda Samir Abdellatif
- Clinical pathology department, National hepatolgy and tropical medicine research institute, Cairo, Egypt
| | - Amina Fouad
- Clinical pathology department, National hepatolgy and tropical medicine research institute, Cairo,Egypt
| | - Mona Youssef
- Department of Hepatology, Gastroenterology and Infectious Diseases, Benha Teaching Hospital, Benha, Egypt
| | - Yousry Esam-Eldin Abo-Amer
- Hepatology, Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Gharbia, Egypt
| | - Mohamed A Elsebaey
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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Safety and efficacy of direct-acting antiviral drugs in the treatment of chronic hepatitis C virus infection in patients with thalassemia: a prospective study. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00124-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassemic patients. Direct-acting antiviral agents (DAAs) are highly effective and well-tolerated by chronic HCV patients.
Results
The mean age of our patients was 29 years. Sustained virologic response (SVR) at 12 and 24 weeks was achieved in all patients (100%). The most common side effects were fatigue (18%), anemia (13.63%), and headache (4.5%). There was no statistically significant difference in the hemoglobin level before and after treatment (p = 0.48). There was a significant improvement in serum bilirubin and mean ALT levels after treatment compared to baseline data (p < 0.0005 each).
Conclusions
DAAs, namely, sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir, are effective and well-tolerated regimens in thalassemic patients with chronic HCV.
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Baronciani D, Casale M, De Franceschi L, Graziadei G, Longo F, Origa R, Rigano P, Pinto V, Marchetti M, Gigante A, Iolascon A, Forni GL. Selecting β-thalassemia Patients for Gene Therapy: A Decision-making Algorithm. Hemasphere 2021; 5:e555. [PMID: 33969274 PMCID: PMC8096466 DOI: 10.1097/hs9.0000000000000555] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 03/09/2021] [Indexed: 12/27/2022] Open
Abstract
This expert opinion originally developed by a panel of the Italian Society of Thalassemias and Hemoglobinopathies (SITE), reviewed and adopted by the European Hematology Association (EHA) through the EHA Scientific Working Group on Red Cells and Iron, has been developed as priority decision-making algorithm on evidence and consensus with the aim to identify which patients with transfusion-dependent beta-thalassemia (TDT) could benefit from a gene therapy (GT) approach. Even if the wide utilized and high successful allogeneic hematopoietic stem-cell transplantation provides the possibility to cure several patients a new scenario has been opened by GT. Therefore, it is important to establish the patients setting for whom it is priority indicated, particularly in the early phase of the diffuse use outside experimental trials conducted in high selected centers. Moreover, actual price, limited availability, and resources disposal constitute a further indication to a rational and progressive approach to this innovative treatment. To elaborate this algorithm, the experience with allogeneic transplantation has been used has a predictive model. In this large worldwide experience, it has been clearly demonstrated that key for the optimal transplant outcome is optimal transfusion and chelation therapy in the years before the procedure and consequently optimal patient's clinical condition. In the document, different clinical scenarios have been considered and analyzed for the possible impact on treatment outcome. According to the European Medicine Agency (EMA) for the GT product, this expert opinion must be considered as a dynamic, updatable, priority-based indications for physicians taking care of TDT patients.
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Affiliation(s)
| | - Maddalena Casale
- Università degli Studi della Campania «Luigi Vanvitelli», Napoli, Italy
| | | | - Giovanna Graziadei
- Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Malattie Rare, Milano, Italy
| | - Filomena Longo
- Centro Microcitemie-Pediatria, AOU San Luigi Gonzaga, Orbassano (TO), Italy
| | - Raffaella Origa
- Ospedale Pediatrico Microcitemico “A.Cao,” A.O. “G.Brotzu,” Cagliari, Italy
| | - Paolo Rigano
- Divisione di Malattie Rare del Sangue e degli Organi Emopoietici, Ospedale V. Cervello, Palermo, Italy
| | - Valeria Pinto
- Centro della Microcitemia e Anemie Congenite, E.O. Ospedali Galliera, Genova, Italy
| | - Monia Marchetti
- Hematology Day Service, SOC Oncologia, Ospedale Cardinal Massaia, Asti, Italy
| | - Antonia Gigante
- Società Italiana Talassemie ed Emoglobinopatie (SITE), Roma, Italy
| | - Achille Iolascon
- Dept. of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
- CEINGE Biotecnologie Avanzate, Naples, Italy
| | - Gian Luca Forni
- Centro della Microcitemia e Anemie Congenite, E.O. Ospedali Galliera, Genova, Italy
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El-Sayed MH, Indolfi G. Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination. Semin Liver Dis 2020; 40:213-224. [PMID: 32526785 DOI: 10.1055/s-0040-1708812] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Hepatitis C is a global public health threat. The introduction of direct-acting antivirals (DAAs) brings the prospect of curing the 71 million people living with the disease, dramatically changing the landscape of hepatitis C. The World Health Organization developed a roadmap for the elimination and cure of hepatitis C by 2030 with a clear goal with measurable targets. However, there is a lack of a well-defined strategy to tackle the hepatitis C virus (HCV) problem in children and adolescents vis-à-vis the adult population. Hepatitis C in children and adolescents can be addressed as part of a national policy for elimination in the whole population, namely macroelimination, or could be fragmented into a microelimination approach targeting the high-risk population groups. Children born to HCV-infected mothers, adolescents who are injecting drugs, migrants, and those suffering from inherited blood diseases are important target populations. After the U.S. Food and Drug Administration approval for the use of DAAs in children aged 3 years and above, evidence from clinical trials and real-world experience was accumulated using brand and generic medicines, with sustained virological response rates exceeding 95%. The evidence created should guide policies on the management of hepatitis C in children and adolescents. There are many challenges in managing HCV in this left-behind marginalized population. The lack of awareness and epidemiological data, consent age, prohibitive prices of medicines, and absence of policies on access to diagnostics, treatment, and linkage to care are among the many barriers to service delivery that should be addressed to achieve the elimination goal by 2030.
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Affiliation(s)
- Manal H El-Sayed
- Department of Pediatrics, Faculty of Medicine, Clinical Research Center, Ain Shams University, Cairo, Egypt
| | - Giuseppe Indolfi
- Pediatric and Liver Unit, Meyer Children's University Hospital and Department NEUROFARBA, University of Florence, Florence, Italy
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations. J Formos Med Assoc 2020; 119:1135-1157. [PMID: 32354689 DOI: 10.1016/j.jfma.2020.04.002] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug-drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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A Concise Review on the Frequency, Major Risk Factors and Surveillance of Hepatocellular Carcinoma (HCC) in β-Thalassemias: Past, Present and Future Perspectives and the ICET-A Experience. Mediterr J Hematol Infect Dis 2020; 12:e2020006. [PMID: 31934316 PMCID: PMC6951357 DOI: 10.4084/mjhid.2020.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 12/03/2019] [Indexed: 02/07/2023] Open
Abstract
Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the present report reviews briefly the frequency, the major risk factors, and the surveillance of HCC in β-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy and Greece. Among HCV-infected patients, additional factors promoting the development of HCC included: advanced age, male sex, chronic hepatitis B (CHB) co-infection, and iron overload. For early diagnosis of HCC, sequential ultrasound screening is recommended especially for thalassemia patients with chronic hepatitis C (CHC), which coincides with (one or more) additional risk factors for HCC. Here we report also the preliminary data from thalassemic patients, above the age of 30 years, followed in 13 ICET-A centers. The total number of enrolled patients was 1,327 (males: 624 and 703 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.66 % and 1.96 %, respectively. The lowest age at diagnosis of HCC was 36 years for TDT and 47 years for NTDT patients. We hope that this review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia and to define specific international guidelines to support clinicians for early diagnosis and treatment of HCC in thalassemic patients.
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10
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Bou Daher H, Sharara AI. Treatment of Chronic HCV Infection in Patients With Thalassemia. Clin Liver Dis (Hoboken) 2019; 14:199-202. [PMID: 32015868 PMCID: PMC6988433 DOI: 10.1002/cld.853] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 06/07/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Halim Bou Daher
- Division of Gastroenterology, Department of Internal MedicineAmerican University of Beirut Medical CenterBeirutLebanon
| | - Ala I. Sharara
- Division of Gastroenterology, Department of Internal MedicineAmerican University of Beirut Medical CenterBeirutLebanon
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11
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A nanocellulose-based colorimetric assay kit for smartphone sensing of iron and iron-chelating deferoxamine drug in biofluids. Anal Chim Acta 2019; 1087:104-112. [DOI: 10.1016/j.aca.2019.08.056] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Revised: 08/19/2019] [Accepted: 08/20/2019] [Indexed: 12/28/2022]
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12
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Ramgopal A, Lauko A, Rotz S, Hanna R. Safety of allogeneic hematopoietic stem cell transplantation in beta-thalassemia patients with chronic hepatitis C infections treated at a pediatric center. Pediatr Transplant 2019; 23:e13520. [PMID: 31209983 DOI: 10.1111/petr.13520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 04/30/2019] [Accepted: 05/23/2019] [Indexed: 12/11/2022]
Abstract
The outcome of allogeneic HCT in patients previously infected with HCV is a widely debated topic and rarely reported in the pediatric and young adult age group given the small population of affected patients. New medications directly targeting HCV have induced virologic cures for over 90% of patients, and their use in the pretransplant setting may improve outcomes for patients infected with HCV. We describe two patients with transfusion-dependent beta-thalassemia major who underwent matched sibling donor bone marrow transplantation, one with a myeloablative regimen and one with a reduced-intensity conditioning regimen. Allogeneic HCT appears feasible in patients with HCV infection that clear viremia prior to conditioning therapy and with a reduced-intensity conditioning regimen. Further investigation is warranted to better define transplant risks in this population.
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Affiliation(s)
- Archana Ramgopal
- Department of Hematology Oncology, Cleveland Clinic Children's Hospital, Cleveland, Ohio
| | - Adam Lauko
- Department of Hematology Oncology, Cleveland Clinic Children's Hospital, Cleveland, Ohio
| | - Seth Rotz
- Department of Hematology Oncology, Cleveland Clinic Children's Hospital, Cleveland, Ohio
| | - Rabi Hanna
- Department of Hematology Oncology, Cleveland Clinic Children's Hospital, Cleveland, Ohio
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13
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Papatheodoridis GV, Goulis J, Sypsa V, Lionis C, Manolakopoulos S, Elefsiniotis I, Anagnostou O, Tsoulas C, Hatzakis A, Dalekos GN. Aiming towards hepatitis C virus elimination in Greece. Ann Gastroenterol 2019; 32:321-329. [PMID: 31263353 PMCID: PMC6595935 DOI: 10.20524/aog.2019.0375] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 03/12/2019] [Indexed: 02/06/2023] Open
Abstract
There are estimated to be 74,000-134,000 patients living with chronic hepatitis C in Greece, but only 20-30% of them are aware of their disease status. In July 2017, the Hellenic National Plan for Hepatitis C was announced in alignment with the World Health Organization goals for the eradication of hepatitis C virus (HCV) by the year 2030. This article discusses the epidemiology and current treatment of chronic hepatitis C in Greece. Additionally the authors propose actions on how to bring back to care diagnosed patients lost to follow up, optimize access to care for HCV-infected people who inject drugs, and increase HCV screening in the general population. The medical community in Greece can play a pivotal role in the implementation of the HCV National Plan and in the efforts to reach the goal of HCV elimination.
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital (George V. Papatheodoridis)
| | - John Goulis
- 4 Department of Internal Medicine, Αristotle University of Thessaloniki Medical School (John Goulis)
| | - Vana Sypsa
- Department of Hygiene, Medical School of National and Kapodistrian, University of Athens, Epidemiology and Medical Statistics, Athens (Vana Sypsa, Angelos Hatzakis)
| | - Christos Lionis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion-Crete (Christos Lionis)
| | - Spilios Manolakopoulos
- 2 Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens (Spilios Manolakopoulos)
| | - Ioannis Elefsiniotis
- Academic Department of Internal Medicine-Hepatogastroenterology, "Agioi Anargyroi" General and Oncology Hospital, Athens (Ioannis Elefsiniotis)
| | - Olga Anagnostou
- Greek Organisation Against Drugs (OKANA), Athens (Olga Anagnostou)
| | - Christos Tsoulas
- Medical Department, Gilead Sciences Hellas, Athens (Christos Tsoulas)
| | - Angelos Hatzakis
- Department of Hygiene, Medical School of National and Kapodistrian, University of Athens, Epidemiology and Medical Statistics, Athens (Vana Sypsa, Angelos Hatzakis)
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly Medical School, Larissa (George N. Dalekos), Greece
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14
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Ponti ML, Comitini F, Murgia D, Ganga R, Canu R, Dessì C, Foschini ML, Leoni G, Morittu M, Perra M, Pilia MP, Casini MR, Zappu A, Origa R. Impact of the direct-acting antiviral agents (DAAs) on chronic hepatitis C in Sardinian patients with transfusion-dependent Thalassemia major. Dig Liver Dis 2019; 51:561-567. [PMID: 30658940 DOI: 10.1016/j.dld.2018.12.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 12/19/2018] [Accepted: 12/20/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Direct antiviral agents (DAAs) have revolutionised the standard of care for the treatment of hepatitis even in patients with hemoglobinopathies. The aim of this study is to show how, thanks to DAAs, HCV infection has been substantially eradicated in one of the biggest Centres for the management of Thalassemia in Europe. METHODS Thalassemia major patients regularly transfused and iron chelated in Cagliari (Italy) who were HCV-RNA positive were evaluated for the potential prescription of antiviral therapy. RESULTS A total of 99 patients, 26 of whom had been diagnosed with cirrhosis, were treated with at least one dose of DAAs, which proved to be safe and well tolerated. Two of the patients died during the treatment after becoming HCV-RNA negative while another voluntarily interrupted the therapy. The final SVR in the patients who completed the treatment was 100%, while measuring 97% (96/99) in the Intention-to-Treat analysis. After DAAs, no new cases of hepatocellular carcinoma have been reported. CONCLUSIONS The use of DAAs in patients suffering from beta-Thalassemia major with chronic hepatitis C or cirrhosis can be considered safe and effective. Close monitoring for hepatocellular carcinoma development is, in any case, recommended indefinitely post-SVR.
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Affiliation(s)
| | | | | | | | - Roberto Canu
- Medicine I, 'G.Brotzu' Hospital, Cagliari, Italy
| | - Carlo Dessì
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy
| | | | | | - Maddalena Morittu
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy
| | - Maria Perra
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy
| | - Maria Paola Pilia
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy
| | | | - Antonietta Zappu
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy
| | - Raffaella Origa
- Thalassemia Unit, 'A. Cao' Hospital, A.O. 'G. Brotzu', Cagliari, Italy.
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15
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Sharara AI, Rustom LBO, Marrache M, Rimmani HH, Bou Daher H, Koussa S, Taher A. Sofosbuvir/velpatasvir for chronic hepatitis C infection in patients with transfusion-dependent thalassemia. Am J Hematol 2019; 94:E43-E45. [PMID: 30394575 DOI: 10.1002/ajh.25339] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 11/01/2018] [Indexed: 02/06/2023]
Affiliation(s)
- Ala I Sharara
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Luma Basma O Rustom
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Majd Marrache
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Hussein H Rimmani
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Halim Bou Daher
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | | | - Ali Taher
- Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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16
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How I manage medical complications of β-thalassemia in adults. Blood 2018; 132:1781-1791. [PMID: 30206117 DOI: 10.1182/blood-2018-06-818187] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 09/09/2018] [Indexed: 02/06/2023] Open
Abstract
The complex pathophysiology in β-thalassemia can translate to multiple morbidities that affect every organ system. Improved survival due to advances in management means that patients are exposed to the harmful effects of ineffective erythropoiesis, anemia, and iron overload for a longer duration, and we started seeing new or more frequent complications in adult compared with younger patients. In this article, we highlight particular aspects of managing adult patients with β-thalassemia, using our own experience in treating such patients. We cover both transfusion-dependent and nontransfusion-dependent forms of the disease and tackle specific morbidities of highest interest.
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17
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Marcon A, Motta I, Taher AT, Cappellini MD. Clinical Complications and Their Management. Hematol Oncol Clin North Am 2018; 32:223-236. [DOI: 10.1016/j.hoc.2017.11.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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18
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Affiliation(s)
- Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Radha K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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19
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Safety and Efficacy of Direct-Acting Antivirals in Transfusion-Dependent Thalassemic Patients with Chronic Hepatitis C. HEPATITIS MONTHLY 2018. [DOI: 10.5812/hepatmon.61453] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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