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Chang YP, Huang CB, Kao JH, Su TH, Huang SC, Tseng TC, Chen PJ, Liu CJ, Liu CH. Long-term serum ferritin dynamics in patients receiving antiviral treatment for hepatitis C virus infection. J Formos Med Assoc 2025:S0929-6646(25)00012-9. [PMID: 39848863 DOI: 10.1016/j.jfma.2025.01.012] [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: 07/26/2024] [Revised: 11/03/2024] [Accepted: 01/16/2025] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND Limited data exists regarding the long-term serum ferritin dynamics following sustained virologic response (SVR12) and factors associated with trends in changes among patients undergoing treatment for hepatitis C virus (HCV). METHODS Serum ferritin levels were assessed biannually in 1538 participants undergoing direct-acting antivirals (DAAs) or peginterferon plus ribavirin (PR) with a median of follow-up of 5.0 years after off-treatment week 12. We compared the differences in time-dependent slope coefficients of serum ferritin levels for factors of interest using the generalized estimating equations to identify predictors associated with favorable serum ferritin evolution. RESULTS Using univariable analysis, SVR12, aged ≤50 year, absence of metabolic dysfunction-associated steatotic liver disease (MASLD), and pre-treatment HCV RNA level ≤2,000,000 IU/mL were associated with favorable ferritin evolution. Multivariable analysis showed that SVR12 (adjusted slope coefficient difference: 7.50 ng/mL/year [95% CI: 3.37 to -11.63], p < 0.001) and absence of MASLD (adjusted slope coefficient difference: 4.16 ng/mL/year [95% CI: 7.91 to -0.41], p = 0.022) predicted favorable ferritin evolution. Among participants achieving SVR12, the ferritin evolution was not affected by DAA or PR treatment (crude slope coefficient difference: 3.33 ng/mL/year [95% CI: 12.78 to 6.12], p = 0.49). Absence of MASLD was associated with favorable ferritin evolution (adjusted slope coefficient difference: 2.86 ng/mL/year [95% CI: 5.39 to -0.33], p = 0.021). CONCLUSIONS Patients achieving SVR12, irrespective of types of treatment, exhibited more favorable long-term ferritin dynamics compared to those not achieving SVR12. Absence of MASLD may help improve long-term ferritin dynamics among patients achieving SVR12.
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Affiliation(s)
- Yu-Ping Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chiuan-Bo Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan.
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Bagheri S, Fard GB, Talkhi N, Rashidi Zadeh D, Mobarra N, Mousavinezhad S, Khamse FM, Hosseini Bafghi M. Laboratory Biochemical and Hematological Parameters: Early Predictive Biomarkers for Diagnosing Hepatitis C Virus Infection. J Clin Lab Anal 2024; 38:e25127. [PMID: 39569979 DOI: 10.1002/jcla.25127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/20/2024] [Accepted: 11/09/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a worldwide concern, causing liver damage and necessitating early detection to prevent its spread. Studies indicate that evaluating changes in biochemical and hematological parameters, which serve as suitable predictors of inflammation, can be a reasonable method for diagnosing hepatitis C infection. METHODS This study analyzed 100 samples from high-risk patients positively identified via quantitative real-time PCR (qPCR). Anti-HCV titers, biochemical and inflammatory tests, and complete blood cell counts (CBCs) were performed for these individuals. Additionally, 100 HCV-negative individuals with normal laboratory results were selected as the control group. Receiver operating characteristic (ROC) curves were plotted to determine the cutoff values of the laboratory parameters. RESULTS According to the findings, the age, average white blood cell (WBC) count, platelet-to-lymphocyte ratio (PLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and ferritin levels were significantly higher in HCV patients. On the other hand, red blood cell (RBC) counts, neutrophils, lymphocytes, hemoglobin-to-platelet ratio (HPR), and iron (Fe) levels were significantly lower in the case group compared to those in the control group (p < 0.05). Furthermore, the ROC curve analysis revealed that lymphocyte count, neutrophil count, and PLR were very strong predictors for hepatitis C infection (p < 0.0001, AUC = 1). CONCLUSION The study highlights significant biochemical and hematological differences between HCV patients and healthy subjects. These biomarkers are crucial for early diagnosis, potentially preventing liver damage and reducing HCV transmission.
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Affiliation(s)
- Saeede Bagheri
- Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ghazaleh Behrouzian Fard
- Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nasrin Talkhi
- Department of Biostatistics, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davoud Rashidi Zadeh
- Department of Microbiology, Faculty of Basic Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Naser Mobarra
- Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedmahdi Mousavinezhad
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Fatemeh Mirzaeian Khamse
- Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Hosseini Bafghi
- Department of Laboratory Sciences, School of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
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Zheng X, Zhang Y, Zhang L, Yang T, Zhang F, Wang X, Zhu SJ, Cui N, Lv H, Zhang X, Li H, Liu W. Taurolithocholic acid protects against viral haemorrhagic fever via inhibition of ferroptosis. Nat Microbiol 2024; 9:2583-2599. [PMID: 39294459 DOI: 10.1038/s41564-024-01801-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 07/31/2024] [Indexed: 09/20/2024]
Abstract
Bile acids are microbial metabolites that can impact infection of enteric and hepatitis viruses, but their functions during systemic viral infection remain unclear. Here we show that elevated levels of the secondary bile acid taurolithocholic acid (TLCA) are associated with reduced fatality rates and suppressed viraemia in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne haemorrhagic fever virus. TLCA inhibits viral replication and mitigates host inflammation during SFTSV infection in vitro, and indirectly suppresses SFTSV-mediated induction of ferroptosis by upregulating fatty acid desaturase 2 via the TGR5-PI3K/AKT-SREBP2 axis. High iron and ferritin serum levels during early infection were correlated with decreased TLCA levels and fatal outcomes in SFTSV-infected patients, indicating potential biomarkers. Furthermore, treatment with either ferroptosis inhibitors or TLCA protected mice from lethal SFTSV infection. Our findings highlight the therapeutic potential of bile acids to treat haemorrhagic fever viral infection.
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Affiliation(s)
- Xiaojie Zheng
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
| | - Yunfa Zhang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
| | - Lingyu Zhang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
| | - Tong Yang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
| | - Faxue Zhang
- School of Public Health, Wuhan University, Wuhan, People's Republic of China
| | - Xi Wang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
- Graduate School of Anhui Medical University, Hefei, People's Republic of China
| | - Shu Jeffrey Zhu
- Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China
| | - Ning Cui
- The 154th Hospital, Xinyang, People's Republic of China
| | - Hongdi Lv
- The 154th Hospital, Xinyang, People's Republic of China
| | - Xiaoai Zhang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China
| | - Hao Li
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
- School of Public Health, Wuhan University, Wuhan, People's Republic of China.
- Graduate School of Anhui Medical University, Hefei, People's Republic of China.
| | - Wei Liu
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, People's Republic of China.
- School of Public Health, Wuhan University, Wuhan, People's Republic of China.
- Graduate School of Anhui Medical University, Hefei, People's Republic of China.
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Castiella A, José Sánchez-Iturri M, Urreta I, Torrente S, Alcorta A, Zapata E. Effect of viral eradication with direct-acting antiviral agents on iron parameters in patients with chronic hepatitis c and hyperferritinemia. CANADIAN LIVER JOURNAL 2023; 6:412-416. [PMID: 38152323 PMCID: PMC10751007 DOI: 10.3138/canlivj-2022-0042] [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: 11/06/2022] [Accepted: 01/01/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Patients with chronic hepatitis C are at increased risk for hyperferritinemia (HF). Abnormalities of serum iron parameters are frequently observed in patients with chronic hepatitis C (CHC). About a third of patients have increased iron parameters. Recently, studies on the effect of direct-acting antiviral agents (DAAs) in HCV eradication in patients with increased serum iron has been published, demonstrating the restoration of normal iron status. The aim of this study was to evaluate the effect of viral eradication with DDAs in patients with CHC and HF. METHODS Retrospective study conducted from January 2018 to December 2020 including patients treated with DAAs for HCV. Pre-treatment (PreT) and post-treatment (PostT) serum ferritin values were evaluated in all patients. Inclusion criteria: Pret HF (>400 μg/L); CHC patients treated with DAA achieving sustained viral response (SVR). Exclusion criteria: No PreT or PostT HF available; no SVR; lost patients. RESULTS From 621 patients treated with DAAs for CHC, 77 presented HF (12.40%), and 74 were included in the study. Fifty nine were men (79.73%) with a mean age 58.33, SD 8.68; PreT mean ferritin: 893.20 (SD 1037.09); PostT: 264.17 (SD 161.33); PreT mean transferrin saturation: 40.96 (SD 15.71); PostT: 29.82 (SD 11.17); PreT mean serum iron 152.32 (SD 62.07), PostT: 109.32 (SD 39.49). When we compared PreT and PostT iron parameters, significant statistical differences were present considering ferritin (p = 0.0000), transferrin saturation (p = 0.0000), and iron (p = 0.0002) determinations. CONCLUSIONS SVR after DAAs for CHC induces a statistically significant reduction on iron parameters.
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Affiliation(s)
- Agustin Castiella
- Department of Gastroenterology, Donostia University Hospital, Donostia, Spain
| | | | - Iratxe Urreta
- Epidemiology Unit, Donostia University Hospital, Donostia, Spain
| | - Silvia Torrente
- Department of Gastroenterology, Donostia University Hospital, Donostia, Spain
| | - Ana Alcorta
- Department of Gastroenterology, Donostia University Hospital, Donostia, Spain
| | - Eva Zapata
- Department of Gastroenterology, Donostia University Hospital, Donostia, Spain
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Wróblewska A, Woziwodzka A, Rybicka M, Bielawski KP, Sikorska K. Polymorphisms Related to Iron Homeostasis Associate with Liver Disease in Chronic Hepatitis C. Viruses 2023; 15:1710. [PMID: 37632052 PMCID: PMC10457817 DOI: 10.3390/v15081710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/01/2023] [Accepted: 08/05/2023] [Indexed: 08/27/2023] Open
Abstract
Dysregulation of iron metabolism in chronic hepatitis C (CHC) is a significant risk factor for hepatic cirrhosis and cancer. We studied if known genetic variants related to iron homeostasis associate with liver disease progression in CHC. Retrospective analysis included 249 CHC patients qualified for antiviral therapy between 2004 and 2014. For all patients, nine SNPs within HFE, TFR2, HDAC2, HDAC3, HDAC5, TMPRSS6, and CYBRD1 genes were genotyped. Expression of selected iron-related genes, was determined with qRT-PCR in 124 liver biopsies, and mRNA expression of co-inhibitory receptors (PD-1, Tim3, CTLA4) was measured in 79 liver samples. CYBRD1 rs884409, HDAC5 rs368328, TFR2 rs7385804, and TMPRSS6 rs855791 associated with histopathological changes in liver tissue at baseline. The combination of minor allele in HDAC3 rs976552 and CYBRD1 rs884409 linked with higher prevalence of hepatocellular carcinoma (HCC) during follow up (OR 8.1 CI 2.2-29.2; p = 0.001). Minor allele in HDAC3 rs976552 associated with lower hepatic expression of CTLA4. Tested polymorphisms related to iron homeostasis associate with histopathological changes in the liver. The presence of both HDAC3 rs976552 G and CYBRD1 rs884409 G alleles correlates with HCC occurrence, especially in the group of patients with elevated AST (>129 IU/L). rs976552 in HDAC3 could impact immunological processes associated with carcinogenesis in CHC.
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Affiliation(s)
- Anna Wróblewska
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Anna Woziwodzka
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Magda Rybicka
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Krzysztof P. Bielawski
- Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland; (A.W.); (A.W.); (M.R.); (K.P.B.)
| | - Katarzyna Sikorska
- Division of Tropical Medicine and Epidemiology, Faculty of Health Sciences, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, 81-519 Gdynia, Poland
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Zhu L, Luo S, Zhu Y, Tang S, Li C, Jin X, Wu F, Jiang H, Wu L, Xu Y. The Emerging Role of Ferroptosis in Various Chronic Liver Diseases: Opportunity or Challenge. J Inflamm Res 2023; 16:381-389. [PMID: 36748023 PMCID: PMC9899014 DOI: 10.2147/jir.s385977] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 01/06/2023] [Indexed: 02/01/2023] Open
Abstract
Ferroptosis is a recently identified iron-dependent form of intracellular lipid peroxide accumulation-mediated cell death. Different from other types of cell death mechanisms, it exhibits distinct biological and morphological features characterized by the loss of lipid peroxidase repair activity caused by glutathione peroxidase 4, the presence of redox-active iron, and the oxidation of phospholipids-containing polyunsaturated fatty acids. In recent years, studies have shown that ferroptosis plays a key role in various liver diseases such as alcoholic liver injury, non-alcoholic steatohepatitis, liver cirrhosis, and liver cancer. However, the mechanism of ferroptosis and its regulation on chronic liver disease are controversial among different types of cells in the liver. Herein, we summarize the current studies on mechanism of ferroptosis in chronic liver disease, aiming to outline the blueprint of ferroptosis as an effective option for chronic liver disease therapy.
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Affiliation(s)
- Lujian Zhu
- Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, People’s Republic of China
| | - Shengnan Luo
- Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, People’s Republic of China
| | - Yin Zhu
- Department of Infectious Diseases, Taizhou Enze Medical Center (Group), Enze Hospital, Taizhou, People’s Republic of China
| | - Shiyue Tang
- Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, People’s Republic of China
| | - Chenge Li
- College of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Xiaozhi Jin
- Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Faling Wu
- Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Huimian Jiang
- Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Lina Wu
- Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China
| | - Yejin Xu
- Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, People’s Republic of China,Correspondence: Yejin Xu, Department of Infectious Diseases, Jinhua Municipal Central Hospital, Jinhua, People’s Republic of China, Email
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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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Dufrusine B, Valentinuzzi S, Bibbò S, Damiani V, Lanuti P, Pieragostino D, Del Boccio P, D’Alessandro E, Rabottini A, Berghella A, Allocati N, Falasca K, Ucciferri C, Mucedola F, Di Perna M, Martino L, Vecchiet J, De Laurenzi V, Dainese E. Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation. Int J Mol Sci 2022; 24:15. [PMID: 36613462 PMCID: PMC9819889 DOI: 10.3390/ijms24010015] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.
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Affiliation(s)
- Beatrice Dufrusine
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Silvia Valentinuzzi
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Sandra Bibbò
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Verena Damiani
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Paola Lanuti
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Damiana Pieragostino
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Piero Del Boccio
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Ersilia D’Alessandro
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Alberto Rabottini
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Alessandro Berghella
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
| | - Nerino Allocati
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Katia Falasca
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Claudio Ucciferri
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Francesco Mucedola
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Marco Di Perna
- Pneumology Department, “SS Annunziata” Hospital, 66100 Chieti, Italy
| | - Laura Martino
- Pneumology Department, “SS Annunziata” Hospital, 66100 Chieti, Italy
| | - Jacopo Vecchiet
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Vincenzo De Laurenzi
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Enrico Dainese
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
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Mokgalaboni K, Phoswa W. Cross-link between type 2 diabetes mellitus and iron deficiency anemia. A mini-review. CLINICAL NUTRITION OPEN SCIENCE 2022. [DOI: 10.1016/j.nutos.2022.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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El-Kassas M, Awad A. Metabolic aspects of hepatitis C virus. World J Gastroenterol 2022; 28:2429-2436. [PMID: 35979265 PMCID: PMC9258278 DOI: 10.3748/wjg.v28.i22.2429] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/18/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
Many metabolic factors are associated with chronic hepatitis C virus (HCV) infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions. Several of these factors impact the course of chronic HCV (CHC) and result in the conceptual translation of CHC from a localized to systemic disease. Besides the traditional liver manifestations associated with CHC infection, such as cirrhosis and hepatocellular carcinoma, various extrahepatic disorders are associated with HCV infection, including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases. The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma. Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC. Therefore, there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors. Furthermore, patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism, but the exact evidence still requires further studies with long-term follow-up. This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.
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Affiliation(s)
- Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| | - Abeer Awad
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
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11
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Toma L, Dodot M, Zgura A, Bacalbasa N, Silaghi A, Simu R, Isac T, Mercan-Stanciu A. Calprotectin in viral systemic infections-COVID-19 versus hepatitis C virus. Clin Exp Med 2022; 22:311-317. [PMID: 34254197 PMCID: PMC8274470 DOI: 10.1007/s10238-021-00743-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 07/05/2021] [Indexed: 01/09/2023]
Abstract
This study aims to evaluate differences in serum and fecal calprotectin in patients with HCV chronic hepatitis and COVID-19 infection and compare them to a control group. This observational study was performed between April 2020 and October 2020 in a single Internal Medicine center. We determined serum and fecal calprotectin, as well as levels of transaminases, C-reactive protein, ferritin, in 25 patients with COVID-19 infection, 30 patients with active HCV chronic infection and 38 patients with cured HCV infection. Serum levels of ALT, AST, C-reactive protein and ferritin were significantly higher in patients with COVID-19 infection (mean values of 127 IU/mL, 135 IU/mL, 123 mg/L and 1034 ng/mL, respectively) than in patients with active HCV infection (mean values of 68 IU/mL, 51 IU/mL, 17 mg/L and 528 ng/mL, respectively) or in patients with cured HCV infection (37 IU/mL, 29 IU/mL, 3.4 mg/L and 274 ng/mL, respectively). Also, serum and fecal calprotectin had increased concentrations in patients with COVID-19 (7.3 µg/mL and 394 µg/mg) versus patients with active hepatitis (2.4 µg/mL and 217 µg/mg) and patients with cured hepatitis (1.2 µg/mL and 38 µg/mg). Values were significantly higher in patients with digestive symptoms related to COVID-19. Serum and fecal calprotectin can be used as inflammatory markers in patients with active viral infections. In COVID-19, calprotectin concentrations can be correlated to the severity of disease, particularly in patients with digestive symptoms.
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Affiliation(s)
- Letitia Toma
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania.
| | - Mihai Dodot
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Anca Zgura
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Nicolae Bacalbasa
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Andrei Silaghi
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Simu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Teodora Isac
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Adriana Mercan-Stanciu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
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12
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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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13
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Monitoring of Iron, Lipid and Liver Profiles in Egyptian Hepatitis C Virus Patients on Sofosbuvir Therapy. J Infect Public Health 2022; 15:277-281. [DOI: 10.1016/j.jiph.2022.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/11/2021] [Accepted: 01/09/2022] [Indexed: 11/22/2022] Open
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14
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Chang ML, Hu JH, Pao LH, Lin MS, Kuo CJ, Chen SC, Fan CM, Chang MY, Chien RN. Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice. BMC Immunol 2021; 22:54. [PMID: 34380427 PMCID: PMC8359585 DOI: 10.1186/s12865-021-00445-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/29/2021] [Indexed: 11/19/2022] Open
Abstract
Background Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides. Supplementary Information The online version contains supplementary material available at 10.1186/s12865-021-00445-5.
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Affiliation(s)
- Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Jing-Hong Hu
- Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Li-Heng Pao
- Graduate Institute of Health-Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
| | - Ming-Shyan Lin
- Department of Cardiology, Heart Failure Center, Chang Gung Memorial Hospital, Yunlin, Taiwan
| | - Chia-Jung Kuo
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shiang-Chi Chen
- Department of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Chun-Ming Fan
- Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Yu Chang
- Division of Pediatric Neurologic Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan.,Division of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. .,Liver Research Unit, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.
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Chaudhari R, Fouda S, Sainu A, Pappachan JM. Metabolic complications of hepatitis C virus infection. World J Gastroenterol 2021; 27:1267-1282. [PMID: 33833481 PMCID: PMC8015302 DOI: 10.3748/wjg.v27.i13.1267] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/10/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
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Affiliation(s)
- Rahul Chaudhari
- Department of Medicine, Pennsylvania Hospital of the University of Pennsylvania, Pennsylvania, PA 19104, United States
| | - Sherouk Fouda
- School of Health and Biomedical Sciences, RMIT University, Melbourne VIC 3000, Australia
| | - Ashik Sainu
- Department of Gastroenterology and Hepatology, Aster Oman Hospital, Al Ghubra, Muscat OM 133, Oman
| | - Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, United Kingdom
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