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Spera AM, Pagliano P, Conti V. Hepatitis C virus eradication in people living with human immunodeficiency virus: Where are we now? World J Hepatol 2024; 16:661-666. [PMID: 38818300 PMCID: PMC11135269 DOI: 10.4254/wjh.v16.i5.661] [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: 12/26/2023] [Revised: 03/06/2024] [Accepted: 04/15/2024] [Indexed: 05/22/2024] Open
Abstract
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
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Affiliation(s)
- Anna Maria Spera
- Infectious Disease Unit, Universitary Hospital OORR San Giovanni di Dio e Ruggi d'Aragona, Salerno 84131, Italy.
| | - Pasquale Pagliano
- Department of Infectious Diseases, University of Salerno, Salerno 84131, Italy
| | - Valeria Conti
- Clinical Pharmacology and Pharmacogenetics Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno 84131, Italy
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Kalia V, Sarkar S. Vitamin D and antiviral immunity. FELDMAN AND PIKE'S VITAMIN D 2024:1011-1034. [DOI: 10.1016/b978-0-323-91338-6.00045-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Qurban R, Saeed S, Kanwal W, Junaid K, Rehman A. Potential immune modulatory effect of vitamin D in HIV infection: A review. Clin Nutr ESPEN 2022; 47:1-8. [DOI: 10.1016/j.clnesp.2021.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 11/08/2021] [Accepted: 12/03/2021] [Indexed: 11/28/2022]
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Udaya Kumar V, Pavan G, Murti K, Kumar R, Dhingra S, Haque M, Ravichandiran V. Rays of immunity: Role of sunshine vitamin in management of COVID-19 infection and associated comorbidities. Clin Nutr ESPEN 2021; 46:21-32. [PMID: 34857198 PMCID: PMC8474796 DOI: 10.1016/j.clnesp.2021.09.727] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 09/10/2021] [Accepted: 09/20/2021] [Indexed: 02/06/2023]
Abstract
The catastrophic pandemic engendered due to the Novel coronavirus (COVID-19) outbreak which causes severe clinical afflictions on the respiratory system has severely high morbidity and mortality rates. The requirement of novel compounds is at utmost importance due to lack of targeted drug molecule to treat the afflictions and restrict the viral infection and for the usage of prophylactic treatment to avoid the spread of the infection is of utmost importance. Vitamin D is one such naturally available multifunctional molecule, which plays an eminent role in the immune system and instigation of numerous cellular pathways further promoting health benefits and enhancing the human quality of life. This article reviews the current standpoint scenario and future prevalence of vitamin D supplementation in the management of covid-19 patients. Novel findings of Vitamin D suggest that along with regulation of cell growth, neuroprotective and mood-stabilizing effects, it regulates the immune response also modulate cytokine Interleukin-6 (IL-6) by inducing progesterone-induced blocking factor (PIBF), given the IL-6 levels are considerably high in COVID-19 patients which increases the further complications. Vitamin D also have its effect on angiotensin converting enzyme (ACEII) inhibitor through which the COVID-19 virus makes cell entry. Numerous research data elucidate the play of Vitamin D, in complications of COVID-19 including the most common comorbid conditions, neurological manifestations and immunological aspects makes it an ideal molecule for adjuvant therapy. Including Vitamin D as add-on therapy in the management of COVID-19 might aid the arrest of infection and helps fight this arduous epidemic.
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Affiliation(s)
- V Udaya Kumar
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
| | - Garapati Pavan
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
| | - Krishna Murti
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India.
| | - Rahul Kumar
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
| | - Sameer Dhingra
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
| | - Mainul Haque
- The Unit of Pharmacology, Faculty of Medicine and Defence Health Universiti Pertahanan, Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, Kem Perdana Sungai Besi, Malaysia
| | - V Ravichandiran
- Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
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Akimbekov NS, Ortoski RA, Razzaque MS. Effects of sunlight exposure and vitamin D supplementation on HIV patients. J Steroid Biochem Mol Biol 2020; 200:105664. [PMID: 32229174 DOI: 10.1016/j.jsbmb.2020.105664] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 10/02/2019] [Accepted: 03/21/2020] [Indexed: 02/08/2023]
Abstract
Unlike many vitamins derived predominantly from food sources, vitamin D is produced endogenously in the skin upon exposure to sunlight. Ethnicity, skin pigmentation, socioeconomic status, geographic location, climate and sunscreen; all of these factors contribute to the amount of insolation for any given individual. Insufficient insolation creates the prerequisites for vitamin D deficiency. This is particularly true in HIV-infected individuals, who are highly vulnerable to vitamin D insufficiency/deficiency, as it plays a huge role in the musculoskeletal and cardiovascular systems. Antiretroviral therapy may also be a factor in vitamin D deficiency. Today, as the issues of preventing common skeletal and non-skeletal diseases with HIV-infected people are becoming highly relevant, the maintenance of vitamin D levels through exposure to sunlight or supplementation appears to be an effective and safe solution. This review focuses on studies concerning the potential role of vitamin D supplementation through adequate sunlight exposure or dietary intake in HIV-infected people. The biology and epidemiology of HIV infection, as well as the issues related to vitamin D deficiency, its status on immune function, the effect of vitamin D against HIV disease progression and other health aspects of this vitamin, are briefly explained.
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Affiliation(s)
- Nuraly S Akimbekov
- Department of Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan.
| | - Richard A Ortoski
- Department of Primary Care Education, Lake Erie College of Osteopathic Medicine, Erie, PA, USA
| | - Mohammed S Razzaque
- Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, PA, USA.
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Schmidbauer C, Chromy D, Schmidbauer V, Bauer D, Apata M, Nguyen D, Mandorfer M, Simbrunner B, Rieger A, Mayer F, Schmidt R, Holzmann H, Trauner M, Gschwantler M, Reiberger T. Epidemiological trends in HCV transmission and prevalence in the Viennese HIV+ population. Liver Int 2020; 40:787-796. [PMID: 32017359 PMCID: PMC7187177 DOI: 10.1111/liv.14399] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 01/11/2020] [Accepted: 01/26/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection is common in people who inject drugs (PWIDs). Recently, 'high-risk' behaviour among men who have sex with men (MSM) has emerged as another main route of HCV transmission. We analysed temporal trends in HCV epidemiology in a cohort of Viennese HIV+ patients. METHODS Hepatitis C virus parameters were recorded at HIV diagnosis (baseline [BL]) and last visit (follow-up [FU]) for all HIV+ patients attending our HIV clinic between January 2014 and December 2016. Proportions of HIV+ patients with anti-HCV(+) and HCV viraemia (HCV-RNA(+)) at BL/FU were assessed and stratified by route of transmission. RESULTS In all, 1806/1874 (96.4%) HIV+ patients were tested for HCV at BL. Anti-HCV(+) was detected in 93.2% (276/296) of PWIDs and in 3.7% (31/839) of MSM. After a median FU of 6.9 years, 1644 (91.0%) patients underwent FU HCV-testing: 167 (90.3%) of PWIDs and 49 (6.7%) of MSM showed anti-HCV(+). Among 208 viraemic HCV-RNA(+) patients at BL, 30 (14.4%) had spontaneously cleared HCV, 76 (36.5%) achieved treatment-induced eradication and 89 (42.8%) remained HCV-RNA(+) at last FU. Among 1433 initially HCV-naive patients, 45 (3.5%) acquired de-novo HCV infection (11.1% PWIDs/80.0% MSM; incidence rate (IR) 0.004%; 95% confidence interval [CI] 0.0%-0.022%) and 14 had HCV reinfections (85.7% PWIDs/14.3% other; IR 0.001%; 95% CI 0.0%-0.018%) during a median FU of 6.7 years (interquartile range 7.4). CONCLUSION Hepatitis C virus testing was successfully implemented in the Viennese HIV(+) patients. Anti-HCV(+) prevalence remained stable in HIV+ PWIDs but almost doubled in HIV+ MSM. De-novo HCV infection occurred mostly in MSM, while HCV reinfections were mainly observed in PWIDs. HCV treatment uptake was suboptimal with 42.8% remaining HCV-RNA(+) at FU.
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Affiliation(s)
- Caroline Schmidbauer
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Department of Internal Medicine IVWilhelminenspitalViennaAustria
| | - David Chromy
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Department of DermatologyMedical University of ViennaViennaAustria
| | - Victor Schmidbauer
- Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
| | - David Bauer
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Apata
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Dung Nguyen
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Armin Rieger
- Department of DermatologyMedical University of ViennaViennaAustria
| | - Florian Mayer
- Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | - Ralf Schmidt
- Department of Laboratory MedicineMedical University of ViennaViennaAustria
| | | | - Michael Trauner
- Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | | | - Thomas Reiberger
- Vienna HIV & Liver Study GroupViennaAustria,Division of Gastroenterology & HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
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Lee C. Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes. Nutrients 2020; 12:nu12040962. [PMID: 32235600 PMCID: PMC7230640 DOI: 10.3390/nu12040962] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 03/23/2020] [Accepted: 03/26/2020] [Indexed: 12/11/2022] Open
Abstract
Vitamin D (VD) plays an essential role in mineral homeostasis and bone remodeling. A number of different VD-related genes (VDRG) are required for the metabolic activation of VD and the subsequent induction of its target genes. They include a set of genes that encode for VD-binding protein, metabolic enzymes, and the VD receptor. In addition to its well-characterized skeletal function, the immunoregulatory activities of VD and the related polymorphisms of VDRG have been reported and linked to its therapeutic and preventive actions for the control of several viral diseases. However, in regards to their roles in the progression of viral diseases, inconsistent and, in some cases, contradictory results also exist. To resolve this discrepancy, I conducted an extensive literature search by using relevant keywords on the PubMed website. Based on the volume of hit papers related to a certain viral infection, I summarized and compared the effects of VD and VDRG polymorphism on the infection, pathogenesis, and treatment outcomes of clinically important viral diseases. They include viral hepatitis, respiratory viral infections, acquired immunodeficiency syndrome (AIDS), and other viral diseases, which are caused by herpesviruses, dengue virus, rotavirus, and human papillomavirus. This review will provide the most current information on the nutritional and clinical utilization of VD and VDRG in the management of the key viral diseases. This information should be valuable not only to nutritionists but also to clinicians who wish to provide evidence-based recommendations on the use of VD to virally infected patients.
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Affiliation(s)
- Choongho Lee
- College of Pharmacy, Dongguk University, Goyang 10326, Korea
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Chokuda E, Reynolds C, Das S. Association of Low Vitamin D with Complications of HIV and AIDS: A literature Review. Infect Disord Drug Targets 2020; 20:122-142. [PMID: 30574856 DOI: 10.2174/1871526519666181221122731] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/13/2018] [Accepted: 12/14/2018] [Indexed: 06/09/2023]
Abstract
With the advent of combination antiretroviral therapy (cART), the survival of HIV patients has improved dramatically, but the complications of the disease and treatment have become an important issue in the management of HIV patients. Vitamin-D deficiency is common in HIV patients. Low vitamin-D is associated with different comorbidities in the HIV uninfected general population. In this review, we first briefly describe vitamin D synthesis and mechanism of action and we focus on the epidemiological and clinical data dealing with the relationship between vitamin D deficiency in HIV infection with several comorbidities which has been found to be increasingly common in patients living with HIV infection. We searched the PubMed database using the keywords "HIV," "vitamin D" and other common disorders or conditions that are relatively common in HIV infection. The other conditions included in the search were osteoporosis and fracture, cardiovascular disease, diabetes and insulin resistance, active tuberculosis, hepatitis-C co-infection, and HIV disease progression. Articles presenting original data as well as systematic reviews and met analysis related to HIV population were included in our analysis. Vitamin-D deficiency seems to be associated with several adverse outcomes in HIV patients but a definite cause and effect relationship with vitamin-D is yet to be confirmed in most of the cases. However, the literature supporting the efficacy of vitamin-D supplementation is lacking.
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Affiliation(s)
- Evelyn Chokuda
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
| | - Chris Reynolds
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
| | - Satyajit Das
- Department of HIV Medicine, Coventry & Warwickshire Partnership Trust, Coventry, United Kingdom
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Hu YC, Wang WW, Jiang WY, Li CQ, Guo JC, Xun YH. Low vitamin D levels are associated with high viral loads in patients with chronic hepatitis B: a systematic review and meta-analysis. BMC Gastroenterol 2019; 19:84. [PMID: 31185932 PMCID: PMC6558894 DOI: 10.1186/s12876-019-1004-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 05/30/2019] [Indexed: 12/13/2022] Open
Abstract
Background Previous studies have investigated the vitamin D status in patients with chronic hepatitis B virus (HBV) infection and its relationship with HBV replication, the results however were inconsistent. The present meta-analysis was carried out to compare the vitamin D levels between patients with chronic hepatitis B (CHB) and healthy controls, and to determine whether vitamin D levels were correlated with HBV viral loads significantly. Methods A systematic search was conducted via PubMed, Web of Science, EMBASE and the Cochrane Library to identify eligible studies until September 28, 2017. We calculated pooled mean difference (MD) and 95% confidence intervals (CI) to quantitatively estimate the difference of vitamin D levels between CHB patients and controls. In addition, correlation between serum vitamin D levels and HBV viral loads was defined by summary correlation coefficient (r value) and the corresponding 95% CI. Results A total of 7 studies involving 814 CHB patients and 696 healthy controls were included. A significantly decreased vitamin D levels was found in CHB patients compared with healthy controls: pooled MD (95% CI) was − 2.03 ng/mL (− 2.60, − 1.46). Latitude-stratified subgroup analysis indicated this difference was more obvious in low latitude areas, with a bigger pooled MD (95% CI) of − 2.72 ng/mL (− 4.57, − 0.87). In addition, we observed an inverse correlation between serum vitamin D levels and HBV viral loads: pooled r (95% CI) was − 0.41(− 0.54, − 0.27). Conclusions Our results showed that vitamin D levels were lower in CHB patients than that of healthy controls and inversely correlated with HBV viral loads, although future comprehensive studies are needed to clarify the underlying mechanisms. Electronic supplementary material The online version of this article (10.1186/s12876-019-1004-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ye-Chao Hu
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China.,The First People's Hospital of Xiaoshan District, 199 Shixin South Road, Hangzhou, 311200, China
| | - Wei-Wei Wang
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China
| | - Wei-Yun Jiang
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China
| | - Chun-Qing Li
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China
| | - Jian-Chun Guo
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China
| | - Yun-Hao Xun
- Department of Liver Diseases, Hangzhou Sixth People's Hospital/Xixi Hospital of Hangzhou, Zhejiang University of Traditional Chinese Medicine, 2 Hengbu Road, Hangzhou, 310023, China.
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Teymoori-Rad M, Shokri F, Salimi V, Marashi SM. The interplay between vitamin D and viral infections. Rev Med Virol 2019; 29:e2032. [PMID: 30614127 DOI: 10.1002/rmv.2032] [Citation(s) in RCA: 174] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 11/28/2018] [Accepted: 12/03/2018] [Indexed: 02/06/2023]
Abstract
The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti-viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti-viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.
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Affiliation(s)
- Majid Teymoori-Rad
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Fazel Shokri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahid Salimi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Sayed Mahdi Marashi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Warraich S, Sidhu A, Hou M, Alenezi O. The impact of Middle Eastern Origin, HIV, HCV, and HIV/HCV co-infection in the development of hypovitaminosis D in adults. Mol Genet Genomic Med 2018; 6:1010-1014. [PMID: 30209895 PMCID: PMC6305679 DOI: 10.1002/mgg3.475] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 08/22/2018] [Accepted: 08/24/2018] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A relationship between hypovitaminosis D and infection with HIV and HCV has been established in the scientific literature. Studies comparing these illnesses to other risk factors for development of hypovitaminosis D, such as being of Middle Eastern origin, have been lacking. The goals of this study were: (a) to document vitamin D levels in groups of individuals at high risk of developing its deficiency, (b) analyze the data collected to numerically determine which group had the lowest average vitamin D levels, and (c) discuss the impact of the findings and offer possible explanations. METHODS This retrospective observational study involved reviewing medical charts and documenting recent vitamin D levels. Our subgroups were: (a) individuals infected with HIV, (b) individuals infected with HCV, (c) individuals co-infected with HIV/HCV, and (d) people of Middle Eastern origin. The gathered data was subsequently subjected to statistical analysis. RESULTS People of Middle Eastern origin were found more likely to be vitamin D deficient as compared to those infected with HIV, HCV, or co-infected with both HIV and HCV. CONCLUSION This suggests that genetic and environmental factors unique to otherwise healthy Middle Eastern people are more detrimental, in terms of developing hypovitaminosis D, than being chronically infected with the aforementioned illnesses.
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Affiliation(s)
| | - Aven Sidhu
- Vancouver Virology Centre, Vancouver, BC, Canada
| | - Michelle Hou
- Vancouver Virology Centre, Vancouver, BC, Canada
| | - Osamah Alenezi
- Vancouver Virology Centre, Vancouver, BC, Canada.,CIHR HIV Clinical Trials Network, Vancouver, BC, Canada
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12
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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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Hoan NX, Tong HV, Song LH, Meyer CG, Velavan TP. Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review. World J Gastroenterol 2018; 24:445-460. [PMID: 29398866 PMCID: PMC5787780 DOI: 10.3748/wjg.v24.i4.445] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 01/08/2018] [Accepted: 01/16/2018] [Indexed: 02/06/2023] Open
Abstract
The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses (HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response (SVR) to interferon (IFN) plus ribavirin (RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBV- and HCV-related chronic liver diseases. Furthermore, current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.
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Affiliation(s)
- Nghiem Xuan Hoan
- Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi 10004, Vietnam
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
| | - Hoang Van Tong
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi 10004, Vietnam
| | - Le Huu Song
- Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi 10004, Vietnam
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
| | - Christian G Meyer
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Medical Faculty, Duy Tan University, Da Nang, Vietnam
| | - Thirumalaisamy P Velavan
- Molecular Genetics of Infectious Diseases, Institute of Tropical Medicine, University of Tübingen, Tübingen 72074, Germany
- Vietnamese-German Center of Medical Research (VG-CARE), Hanoi 10004, Vietnam
- Medical Faculty, Duy Tan University, Da Nang, Vietnam
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Dadabhai AS, Saberi B, Lobner K, Shinohara RT, Mullin GE. Influence of vitamin D on liver fibrosis in chronic hepatitis C: A systematic review and meta-analysis of the pooled clinical trials data. World J Hepatol 2017; 9:278-287. [PMID: 28261385 PMCID: PMC5316848 DOI: 10.4254/wjh.v9.i5.278] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 12/14/2016] [Accepted: 01/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the relationship between vitamin D and liver fibrosis in hepatitis C-monoinfected or hepatitis C virus (HCV)-human immunodeficiency virus (HIV) co-infected patients. METHODS Pertinent studies were located by a library literature search in PubMed/Embase/Cochrane/Scopus/LILACS by two individual reviewers. Inclusion criteria: (1) studies with patients with HCV or co-infected HCV/HIV; (2) studies with patients ≥ 18 years old; (3) studies that evaluated liver fibrosis stage, only based on liver biopsy; and (4) studies that reported serum or plasma 25(OH)D levels. Studies that included pediatric patients, other etiologies of liver disease, or did not use liver biopsy for fibrosis evaluation, or studies with inadequate data were excluded. Estimated measures of association reported in the literature, as well as corresponding measures of uncertainty, were recorded and corresponding odds ratios with 95%CI were included in a meta-analysis. RESULTS The pooled data of this systematic review showed that 9 of the 12 studies correlated advanced liver disease defined as a Metavir value of F3/4 with 25(OH) D level insufficiency. The meta-analysis indicated a significant association across studies. CONCLUSION Low vitamin D status is common in chronic Hepatitis C patients and is associated with advanced liver fibrosis.
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Affiliation(s)
- Alia S Dadabhai
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Behnam Saberi
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Katie Lobner
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Russell T Shinohara
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
| | - Gerard E Mullin
- Alia S Dadabhai, Behnam Saberi, Katie Lobner, Gerard E Mullin, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States
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15
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Yamamoto K, Iwagami M, Seki T, Kano S, Ota N, Ato M. Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms. Parasitol Int 2016; 66:89-99. [PMID: 27919743 DOI: 10.1016/j.parint.2016.11.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 08/08/2016] [Accepted: 11/22/2016] [Indexed: 12/01/2022]
Abstract
Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.
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Affiliation(s)
- Kiichi Yamamoto
- Section of Environmental Parasitology, Tokyo Medical and Dental University, Japan; Department of Immunology, National Institute of Infectious Diseases, Japan.
| | - Moritoshi Iwagami
- Department of Tropical Medicine and Malaria Research Institute, National Center for Global Health and Medicine, Japan
| | - Takenori Seki
- Section of Environmental Parasitology, Tokyo Medical and Dental University, Japan
| | - Shigeyuki Kano
- Department of Tropical Medicine and Malaria Research Institute, National Center for Global Health and Medicine, Japan
| | - Nobuo Ota
- Section of Environmental Parasitology, Tokyo Medical and Dental University, Japan
| | - Manabu Ato
- Department of Immunology, National Institute of Infectious Diseases, Japan
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16
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Abstract
HCV coinfection has emerged as a major cause of non-AIDS-related morbidity and mortality in HIV-positive patients. As a consequence of the availability of modern combined antiretroviral therapy regimens, for optimally managed HIV/HCV-coinfected patients, the rates of liver fibrosis progression and the risk of liver-related events are increasingly similar to those of HCV-monoinfected patients. Moreover, our understanding of modulators of liver disease progression has greatly improved. In addition to immune status, endocrine, metabolic, genetic and viral factors are closely interrelated and might be important determinants of liver disease progression. In the last decade, a variety of serologic and radiographic tests for noninvasive liver disease staging have been extensively validated and are commonly used in HIV/HCV-coinfected patients. Sustained virologic response prevents end-stage liver disease, hepatocellular carcinoma, and death, with an even greater effect size in HIV-positive compared to HIV-negative patients. As interferon-free regimens achieve comparable rates of sustained virologic response in HIV-negative and HIV-positive patients, HIV/HCV-coinfected patients should from now on be referred to as a special, rather than a difficult-to-treat, population. Our comprehensive review covers all relevant aspects of HIV/HCV coinfection. Beginning with the changing epidemiology, it also provides new insights into the natural history of this condition and gives an overview on non-invasive techniques for the staging of liver disease. Furthermore, it outlines current recommendations for the treatment of acute hepatitis C and summarizes the unprecedented advances in the field of chronic hepatitis C therapy.
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Scheiner B, Mandorfer M, Schwabl P, Payer BA, Bucsics T, Bota S, Aichelburg MC, Grabmeier-Pfistershammer K, Stättermayer A, Ferenci P, Trauner M, Peck-Radosavljevic M, Reiberger T. The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection. PLoS One 2015; 10:e0143429. [PMID: 26599080 PMCID: PMC4658167 DOI: 10.1371/journal.pone.0143429] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 11/04/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear. METHODS In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes. RESULTS 75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes. CONCLUSIONS The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.
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Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Berit Anna Payer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Simona Bota
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Maximilian C. Aichelburg
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Katharina Grabmeier-Pfistershammer
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
- Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Albert Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- Vienna HIV & Liver Study Group, Medical University of Vienna, Vienna, Austria
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Chao CT, Chiang CK, Huang JW, Hung KY. Vitamin D is closely linked to the clinical courses of herpes zoster: From pathogenesis to complications. Med Hypotheses 2015; 85:452-7. [DOI: 10.1016/j.mehy.2015.06.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Accepted: 06/29/2015] [Indexed: 12/18/2022]
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Di Carlo P, Siracusa L, Mazzola G, Colletti P, Soresi M, Giannitrapani L, Li Vecchi V, Montalto G. Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review. Int J Endocrinol 2015; 2015:969040. [PMID: 26273302 PMCID: PMC4530270 DOI: 10.1155/2015/969040] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2014] [Revised: 01/23/2015] [Accepted: 02/10/2015] [Indexed: 02/06/2023] Open
Abstract
Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression.
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Affiliation(s)
- Paola Di Carlo
- Department of Sciences for Health Promotion and Mother-Child Care “G. D'Alessandro”, University of Palermo, Via del Vespro 127, 90127 Palermo, Italy
| | - Lucia Siracusa
- Department of Sciences for Health Promotion and Mother-Child Care “G. D'Alessandro”, University of Palermo, Via del Vespro 127, 90127 Palermo, Italy
| | - Giovanni Mazzola
- Biomedical Department of Internal Medicine and Specialities, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
| | - Piero Colletti
- Biomedical Department of Internal Medicine and Specialities, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
| | - Maurizio Soresi
- Biomedical Department of Internal Medicine and Specialities, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
| | - Lydia Giannitrapani
- Department of Sciences for Health Promotion and Mother-Child Care “G. D'Alessandro”, University of Palermo, Via del Vespro 127, 90127 Palermo, Italy
| | - Valentina Li Vecchi
- Biomedical Department of Internal Medicine and Specialities, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
| | - Giuseppe Montalto
- Biomedical Department of Internal Medicine and Specialities, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy
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20
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Vitamin D Deficiency in HIV Infection: Not Only a Bone Disorder. BIOMED RESEARCH INTERNATIONAL 2015; 2015:735615. [PMID: 26000302 PMCID: PMC4426898 DOI: 10.1155/2015/735615] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 02/18/2015] [Accepted: 03/02/2015] [Indexed: 01/01/2023]
Abstract
Hypovitaminosis D is a worldwide disorder, with a high prevalence in the general population of both Western and developing countries. In HIV patients, several studies have linked vitamin D status with bone disease, neurocognitive impairment, depression, cardiovascular disease, high blood pressure, metabolic syndrome, type 2 diabetes mellitus, infections, autoimmune diseases like type 1 diabetes mellitus, and cancer. In this review, we focus on the most recent epidemiological and experimental data dealing with the relationship between vitamin D deficiency and HIV infection. We analysed the extent of the problem, pathogenic mechanisms, clinical implications, and potential benefits of vitamin D supplementation in HIV-infected subjects.
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21
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Mandorfer M, Payer BA, Schwabl P, Steiner S, Ferlitsch A, Aichelburg MC, Stättermayer AF, Ferenci P, Obermayer-Pietsch B, Grabmeier-Pfistershammer K, Trauner M, Peck-Radosavljevic M, Reiberger T. Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3. Liver Int 2015; 35:876-85. [PMID: 24905495 DOI: 10.1111/liv.12615] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 05/22/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × μl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. RESULTS Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria
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Eltayeb AA, Abdou MAA, Abdel-aal AM, Othman MH. Vitamin D status and viral response to therapy in hepatitis C infected children. World J Gastroenterol 2015; 21:1284-1291. [PMID: 25632203 PMCID: PMC4306174 DOI: 10.3748/wjg.v21.i4.1284] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 08/20/2014] [Accepted: 09/30/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the frequency of vitamin D deficiency in patients with hepatitis C virus (HCV) infection and to evaluate the role of vitamin D supplementation in improving antiviral therapy.
METHODS: Sixty-six children aged from 7-14 years (mean ± SD, 11.17 ± 2.293) diagnosed with HCV infection were matched to 28 healthy controls. Serum levels of 25 (OH) D3, calcium, phosphorus, alkaline phosphatase and plasma level of parathormone were measured. Quantitative PCR for HCV was performed Bone density was determined by dual energy X-ray absorptiometry. All cases received conventional therapy, and only 33 patients received vitamin D supplementation.
RESULTS: Children with HCV showed significantly increased levels of HCV RNA (P < 0.001), parathormone (P < 0.01) and decreased vitamin D levels (P < 0.05) (33.3% deficient and 43.3% insufficient) compared with controls. Abnormal bone status (Z score -1.98 ± 0.75) was found in ribs, L-spine, pelvis and total body. Cases treated with vitamin D showed significant higher early (P < 0.04) and sustained (P < 0.05) virological response. There was a high frequency of vitamin D deficiency among the Egyptian HCV children, with significant decrease in bone density. The vitamin D level should be assessed before the start of antiviral treatment with the correction of any detected deficiency.
CONCLUSION: Adding vitamin D to conventional Peg/RBV therapy significantly improved the virological response and helped to prevent the risk of emerging bone fragility.
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23
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Anadol E, Schierwagen R, Elfimova N, Tack K, Schwarze-Zander C, Eischeid H, Noetel A, Boesecke C, Jansen C, Dold L, Wasmuth JC, Strassburg CP, Spengler U, Rockstroh JK, Odenthal M, Trebicka J. Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients. Hepatology 2015; 61:46-55. [PMID: 25125218 DOI: 10.1002/hep.27369] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 08/13/2014] [Indexed: 12/13/2022]
Abstract
UNLABELLED Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption. CONCLUSION Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients.
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Affiliation(s)
- Evrim Anadol
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
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Abstract
BACKGROUND Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chronic liver diseases are associated with serum vitamin D levels. DATA SOURCES A PubMed and Google Scholar search using terms: "vitamin D", "25(OH)D", "liver disease", "viral hepatitis", "non-alcoholic fatty liver disease", "liver fibrosis", "cirrhosis", "hepatocellular carcinoma" and "autoimmune liver disease" was performed, and relevant articles published in English between January 2000 and March 2014 were reviewed. Full-text publications relevant to the field were selected and relevant articles from reference lists were also included. RESULTS The insufficiency or deficiency of vitamin D is common in various kinds of chronic liver diseases including viral hepatitis B and C. Serum 25-hydroxyvitamin D and vitamin D receptors are possibly interrelated with the incidence, treatment and prognosis of diseases. Though the evidence of vitamin D supplementation in viral hepatitis and associated liver diseases is still limited, there is great potential to apply this adjuvant therapy to improve the treatments. CONCLUSIONS Although the exact role and mechanisms of vitamin D have not been fully elucidated in chronic liver diseases, it is potentially beneficial in the treatment of chronic liver diseases. Further mechanistic studies are needed to validate its clinical application.
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Affiliation(s)
- En-Qiang Chen
- Center of Infectious Diseases, West China Hospital; and Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China.
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García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S. Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis. Hepatology 2014; 60:1541-50. [PMID: 24975775 DOI: 10.1002/hep.27281] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 06/21/2014] [Indexed: 12/12/2022]
Abstract
UNLABELLED There is growing evidence that vitamin D is related to chronic hepatitis C (CHC) pathogenicity. We analyzed the relationship of vitamin D status with advanced liver fibrosis (ALF) in CHC treatment-naïve patients and sustained virologic response (SVR) in CHC patients on pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) therapy. We performed a meta-analysis of all eligible studies published to date (April, 2014) in PubMed, SCOPUS, LILACS, and the Cochrane Library, assessing plasma/serum vitamin D levels related to ALF and/or SVR. Pooled odds ratios (ORs) were estimated by either fixed or random effects models. Fourteen studies were selected from the literature search, seven for ALF (1,083 patients) and 11 for SVR (2,672 patients). For liver fibrosis, low vitamin D status was related to a diagnosis of ALF, with the cutoffs of 10 ng/mL (OR=2.37, 95% confidence interval [CI]=1.20, 4.72) and 30 ng/mL (OR=2.22, 95% CI=1.24, 3.97) being significant, and a near-significance for 20 ng/mL (OR=1.44, 95% CI=0.99, 2.12). Regarding SVR, a significant heterogeneity among studies was found (P<0.001), and we only found a significant association with SVR for a vitamin D cutoff of 20 ng/mL (OR=0.53, 95% CI=0.31, 0.91). When meta-analysis was performed excluding the outliers, significant pooled ORs were found for all patients (10 ng/mL [OR=0.48, 95% CI=0.34, 0.67] and 20 ng/mL [OR=0.58, 95% CI=0.45, 0.76]) and GT1/4 patients (10 ng/mL [OR=0.53, 95% CI=0.34, 0.81] and 20 ng/mL [OR=0.54, 95% CI=0.39, 0.74]). CONCLUSION Low vitamin D status in CHC patients is associated with a higher likelihood of having ALF and lower odds of achieving SVR following pegIFNα/ribavirin therapy.
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Affiliation(s)
- Mónica García-Álvarez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
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Escota GV, Cross S, Powderly WG. Vitamin D and calcium abnormalities in the HIV-infected population. Endocrinol Metab Clin North Am 2014; 43:743-67. [PMID: 25169565 DOI: 10.1016/j.ecl.2014.05.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The prevalence of vitamin D deficiency among HIV-infected persons is substantial and comparable to the general population. The factors associated with vitamin D deficiency are similar for both populations but additional factors (ie, use of certain antiretroviral agents) also contribute to vitamin D deficiency among HIV-infected persons. The adverse outcomes associated with vitamin D deficiency considerably overlap with non-AIDS defining illnesses (NADIs) that are increasingly becoming widespread in the aging HIV-infected population. However, there is scant evidence to support any causal inference. Further studies are warranted as efforts to identify and address modifiable risk factors contributing to NADIs continue.
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Affiliation(s)
- Gerome V Escota
- Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
| | - Sara Cross
- Division of Infectious Diseases, University of Tennessee Health Sciences Center, 956 Court Avenue, E336 Coleman Building, Memphis, TN 38163, USA
| | - William G Powderly
- Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA.
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Avihingsanon A, Jitmitraparp S, Tangkijvanich P, Ramautarsing RA, Apornpong T, Jirajariyavej S, Putcharoen O, Treeprasertsuk S, Akkarathamrongsin S, Poovorawan Y, Matthews GV, Lange JMA, Ruxrungtham K. Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: role of vitamin D levels. J Gastroenterol Hepatol 2014; 29:1706-14. [PMID: 24730732 DOI: 10.1111/jgh.12613] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/14/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. METHODS Fibrosis stage was defined as mild (< 7.1 kPa); moderate (7.2-9.4 kPa); severe (9.5-14 kPa), and cirrhosis (> 14 kPa). Hypovitaminosis D was defined as 25(OH)D < 30 ng/mL. Logistic regression analyses were used to assess predictors for significant fibrosis. Serum 25(OH) D levels, HCV genotypes (GT), interleukin-28B (IL28B) and HCV-RNA were assessed. RESULTS A total of 331 HCV and 130 HIV/HCV patients were enrolled (70% male, 35% people who inject drugs [PWIDs]). HCV GT distribution was as follows: GT3 47%, GT1 34%, GT6 17%. IL-28B CC genotype (rs12979860) were found in 88% of HIV/HCV and 85% of HCV. In HCV, liver fibrosis was mild in 56.5%; moderate in 18.4%; severe in 12.4%; and cirrhosis in 12.7%. In HIV/HCV, these figures were 30.6%, 27.8%, 17.6%, and 24.1%, respectively. Patients with significant fibrosis were more often male, older, with HIV infection, hypovitaminosis D, and less likely to be infected with GT6. Factors associated with significant fibrosis by multivariate analysis were HIV infection (adjusted odd ratio [95% confidential interval]: 2.67, 1.20-5.93), P = 0.016, Fib-4 score > 1.45 (6.30, 2.70-14.74), P < 0.001, and hypovitaminosis D (2.48, 1.09-5.67), P = 0.031. GT 6 was less likely to have advanced liver fibrosis (0.17, 0.05-0.65), P = 0.01. CONCLUSIONS HIV infection, Fib-4 score > 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited settings.
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Affiliation(s)
- Anchalee Avihingsanon
- HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand; Division of Allergy and Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Martel-Laferrière V, Dieterich DT. Hepatitis C Direct-Acting Antiviral Agents in HIV/HCV Co-infected Patients. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2014. [DOI: 10.1007/s40506-014-0010-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Havers F, Smeaton L, Gupte N, Detrick B, Bollinger RC, Hakim J, Kumarasamy N, Andrade A, Christian P, Lama JR, Campbell TB, Gupta A. 25-Hydroxyvitamin D insufficiency and deficiency is associated with HIV disease progression and virological failure post-antiretroviral therapy initiation in diverse multinational settings. J Infect Dis 2014; 210:244-53. [PMID: 24799602 DOI: 10.1093/infdis/jiu259] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Low 25-hydroxyvitamin D (25(OH)D) has been associated with increased HIV mortality, but prospective studies assessing treatment outcomes after combination antiretroviral therapy (cART) initiation in resource-limited settings are lacking. METHODS A case-cohort study (N = 411) was nested within a randomized cART trial of 1571 cART-naive adults in 8 resource-limited settings and the United States. The primary outcome (WHO stage 3/4 disease or death within 96 weeks of cART initiation) was met by 192 cases, and 152 and 29 cases met secondary outcomes of virologic and immunologic failure. We studied prevalence and risk factors for baseline low 25(OH)D (<32 ng/mL) and examined associated outcomes using proportional hazard models. RESULTS Low 25(OH)D prevalence was 49% and ranged from 27% in Brazil to 78% in Thailand. Low 25(OH)D was associated with high body mass index (BMI), winter/spring season, country-race group, and lower viral load. Baseline low 25(OH)D was associated with increased risk of human immunodeficiency virus (HIV) progression and death (adjusted hazard ratio (aHR) 2.13; 95% confidence interval [CI], 1.09-4.18) and virologic failure (aHR 2.42; 95% CI, 1.33-4.41). CONCLUSIONS Low 25(OH)D is common in diverse HIV-infected populations and is an independent risk factor for clinical and virologic failure. Studies examining the potential benefit of vitamin D supplementation among HIV patients initiating cART are warranted.
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Affiliation(s)
- Fiona Havers
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Laura Smeaton
- Bloomberg School of Public Health, Johns Hopkins University
| | - Nikhil Gupte
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland HIV Clinical Trials Unit, B.J. Medical College, Pune, India
| | - Barbara Detrick
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert C Bollinger
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland Bloomberg School of Public Health, Johns Hopkins University HIV Clinical Trials Unit, B.J. Medical College, Pune, India
| | - James Hakim
- Department of Medicine, University of Zimbabwe, Harare, Zimbabwe
| | | | - Adriana Andrade
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Javier R Lama
- IMPACTA PERU Clinical Trials Unit, Asociacion Civil Impacta Salud y Educacion, Lima, Peru
| | - Thomas B Campbell
- Division of Infectious Diseases, University of Colorado Denver, Aurora
| | - Amita Gupta
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland Bloomberg School of Public Health, Johns Hopkins University HIV Clinical Trials Unit, B.J. Medical College, Pune, India
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Borella E, Nesher G, Israeli E, Shoenfeld Y. Vitamin D: a new anti-infective agent? Ann N Y Acad Sci 2014; 1317:76-83. [PMID: 24593793 DOI: 10.1111/nyas.12321] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Before the antibiotic era, treatment of tuberculosis patients was restricted to sun exposure in sanatoria. Years later, it was found that 1,25-dihydroxyvitamin D3 stimulates production of cathelicidins, a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes. Cathelicidins serve a critical role in innate immune defense, which plays an important role in the suppression of Mycobacterium infections and other pathogens. It is believed that the increased incidence of the common cold and pneumonia during winter is related, in part, to decreased exposure to sunlight, resulting in a decreased synthesis of 1,25-dihydroxyvitamin D3. An association has been established between low levels of vitamin D and upper respiratory and enteric infections, pneumonia, otitis media, Clostridium infections, vaginosis, urinary tract infections, sepsis, influenza, dengue, hepatitis B, hepatitis C, and HIV infections. Accumulating evidence suggests that 1,25-dihydroxyvitamin D3 exerts protective effects during infections by upregulating the expression of cathelicidin and β-defensin 2 in phagocytes and epithelial cells. Vitamin D may be acting as a panaceal antibiotic agent and thus may be useful as an adjuvant therapy in diverse infections.
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Affiliation(s)
- Elisabetta Borella
- Division of Rheumatology, Department of Medicine, University of Padua, Padua, Italy; Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center at Tel Hashomer, Tel Aviv, Israel
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Piekuse L, Kreile M, Zarina A, Steinberga Z, Sondore V, Keiss J, Lace B, Krumina A. Association between inherited monogenic liver disorders and chronic hepatitis C. World J Hepatol 2014; 6:92-97. [PMID: 24575168 PMCID: PMC3935058 DOI: 10.4254/wjh.v6.i2.92] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 12/16/2013] [Accepted: 01/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C.
METHODS: This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing.
RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Case-control analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087).
CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.
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Branch AD, Barin B, Rahman A, Stock P, Schiano TD. Vitamin D status of human immunodeficiency virus-positive patients with advanced liver disease enrolled in the solid organ transplantation in HIV: multi-site study. Liver Transpl 2014; 20:156-64. [PMID: 24338934 PMCID: PMC3946843 DOI: 10.1002/lt.23784] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Accepted: 10/04/2013] [Indexed: 01/12/2023]
Abstract
An optimal vitamin D status may benefit liver transplantation (LT) patients. Higher levels of 25-hydroxyvitamin D [25(OH)D] mitigate steroid-induced bone loss after LT, correlate with better hepatitis C virus treatment responses, and increase graft survival. This study investigated 25(OH)D levels and assessed strategies for vitamin D deficiency prevention in human immunodeficiency virus (HIV)-positive patients with advanced liver disease who were enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study. 25(OH)D was measured in banked specimens from 154 LT candidates/recipients with the DiaSorin assay; deficiency was defined as a 25(OH)D level < 20 ng/mL. Information about vitamin D supplement use after LT was obtained from medication logs and via surveys. Logistic regression, Cox regression, and linear repeated measures analyses were performed with SAS software. We found that none of the 17 academic medical centers in the United States routinely recommended vitamin D supplements before LT, and only a minority (4/17) recommended vitamin D supplements to all patients after LT. Seventy-one percent of the 139 patients with pre-LT values had vitamin D deficiency, which was significantly associated with cirrhosis (P = 0.01) but no other variable. The vitamin D status improved modestly after LT; however, the status was deficient for 40% of the patients 1 year after LT. In a multivariate linear repeated measures model, a higher pre-LT 25(OH)D level (P < 0.001), specimen collection in the summer (P < 0.001), a routine vitamin D supplementation strategy after LT (P < 0.001), and the time elapsing since LT (P = 0.01) were significantly associated with increases in the post-LT 25(OH)D level; black race was associated with a decreased level (P = 0.02). In conclusion, the majority of patients awaiting LT were vitamin D deficient, and approximately half were vitamin D deficient after LT. More extensive use of vitamin D supplements, more sun exposure, or both are needed to prevent this deficiency in HIV-positive LT candidates and recipients.
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Affiliation(s)
- Andrea D Branch
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
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Lee TH, Tillmann HL, Patel K. Individualized therapy for hepatitis C infection: focus on the interleukin-28B polymorphism in directing therapy. Mol Diagn Ther 2014; 18:25-38. [PMID: 24022240 DOI: 10.1007/s40291-013-0053-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus—a major global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma—affects millions of people worldwide. Pegylated interferon (Peg-IFN) and ribavirin (RBV) had been the standard treatment for a decade until availability of the protease inhibitors in 2011. However, current antiviral therapy is still IFN-based and is associated with significant side effects and variable treatment response. Thus, various host and viral factors have been evaluated before and during treatment for the prediction of sustained virologic response to antiviral therapy. In 2009, genome-wide association studies found the single-nucleotide polymorphisms, located near the host interleukin-28B (IL28B) gene that encodes IFN-λ3, to be the best pretreatment predictor of virologic response to Peg-IFN and RBV therapy in chronic hepatitis C genotype 1 patients. Additionally, inosine triphosphatase (ITPA) gene variants were found to be associated with RBV-induced hemolytic anemia, which could affect treatment dose for selected patients. IL28B, ITPA, and other treatment predictors allowed for a potential individualized approach to treat hepatitis C. In the era of increased overall virologic response rates and good tolerability of the rapidly developing non-IFN oral direct-acting antiviral therapy regimens, the need for individualized treatment is likely to diminish. Various predictors of response, including IL28B will likely be of reduced importance in the near future.
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Mandorfer M, Reiberger T, Payer BA, Breitenecker F, Aichelburg MC, Obermayer-Pietsch B, Rieger A, Puoti M, Zangerle R, Trauner M, Peck-Radosavljevic M. Revisiting predictors of virologic response to PEGIFN + RBV therapy in HIV-/HCV-coinfected patients: the role of metabolic factors and elevated GGT levels. J Viral Hepat 2014; 21:33-41. [PMID: 24329855 DOI: 10.1111/jvh.12118] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 03/26/2013] [Indexed: 12/26/2022]
Abstract
Evaluation of metabolic factors and elevated γ-glutamyltransferase (GGT) levels as independent predictors of treatment failure in a thoroughly documented cohort of HIV-/HCV-coinfected patients (HIV/HCV). Sixty-four HIV/HCV patients treated with pegylated interferon-α-2a plus ribavirin (PEGIFN + RBV) at the Medical University of Vienna within a prospective trial were included in this study. In addition, 124 patients with HIV/HCV from the AIFA-HIV and AHIVCOS cohorts were included as a validation cohort. Advanced liver fibrosis, GGT elevation, insulin resistance (IR) and low CD4+ nadir were defined as METAVIR F3/F4, GGT levels >1.5× sex-specific upper limit of normal, homoeostasis model assessment of insulin resistance >2 and CD4+ nadir <350 cells/μL, respectively. HCV-genotype 1/4 (OR26.3; P = 0.006), advanced liver fibrosis (OR20.2; P = 0.009), interleukin 28B rs12979860 non-C/C SNP (OR8.27; P = 0.02) and GGT elevation (OR7.97; P = 0.012) were independent predictors of treatment failure, while both IR (OR3.51; P = 0.106) and low CD4 + nadir (OR2.64; P = 0.263) were not independently associated with treatment failure. A statistically significant correlation between GGT elevation and prior alcohol abuse (r = 0.259; P = 0.039), liver steatosis (r = 0.301; P = 0.034) and low-density lipoprotein-cholesterol (r = -0.256; P = 0.041) was observed. The importance of GGT elevation as an independent predictor of treatment failure was confirmed in a validation cohort (OR2.76; P = 0.026). While GGT elevation emerged as an independent predictor of treatment failure in both the derivation and the validation cohort, no independent associations between metabolic factors and treatment failure were observed. Thus, our findings suggest that GGT elevation is an independent predictor of treatment failure in HIV/HCV that can easily be incorporated into predictive algorithms.
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Affiliation(s)
- M Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria
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Mandorfer M, Neukam K, Rivero A, Puoti M, Boesecke C, Baumgarten A, Grzeszczuk A, Zangerle R, Ernst D, Rockstroh JK, Trauner M, Pineda JA, Peck-Radosavljevic M, Reiberger T. Strategies for assignment of HIV-HCV genotype-1-coinfected patients to either dual-therapy or direct-acting antiviral agent-based triple-therapy. Antivir Ther 2013; 19:407-14. [PMID: 24342953 DOI: 10.3851/imp2717] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2013] [Indexed: 10/25/2022]
Abstract
BACKGROUND The aim of this study was to evaluate strategies for assignment of HIV-HCV genotype-1-coinfected patients (HIV-HCV-GT1) to either dual-therapy or direct-acting antiviral agent (DAA)-based triple-therapy. METHODS A total of 148 treatment-naive HIV-HCV-GT1 who received antiviral therapy with pegylated interferon/ribavirin were included in this multinational, retrospective analysis. Patients with rapid virological response (RVR) were treated for 48 weeks, while patients without RVR received either 48 or 72 weeks of treatment. IL28B rs12979860 (IL28B) non-C/C, advanced liver fibrosis and high HCV RNA were considered as established risk factors for treatment failure. RESULTS A trend toward higher sustained virological response (SVR) rates in patients with IL28B C/C (65% [37/57] versus 51% [40/79]; P=0.097) was observed. Higher SVR rates were observed in patients without advanced liver fibrosis (61% [47/77] versus 42% [22/52]); P=0.036) and without high HCV RNA (73% [35/48] versus 49% [49/100]; P=0.006), as well as in patients with RVR (90% [35/39] versus 45% [49/109]; P<0.001). SVR rates varied statistically significantly between the risk factors for treatment failure subgroups (86% [6/7] versus 69% [34/49] versus 48% [21/44] versus 20% [4/20] for zero, one, two and three risk factors, respectively; P<0.001). In patients without RVR, higher rates of SVR were observed in those treated for 72 weeks (62% [23/37]), when compared to patients treated for 48 weeks (36% [26/72]; P=0.01). CONCLUSIONS RVR had an excellent positive predictive value for the response to dual-therapy in HIV-HCV-GT1, emphasizing the utility of a lead-in phase for assigning these patients to dual-therapy or DAA-based triple-therapy. The use of an IL28B-guided approach was suboptimal, while a combination of established baseline predictors may provide guidance for individual treatment decisions prior to the initiation of antiviral therapy. However, the extension of treatment duration to 72 weeks in HIV-HCV-GT1 without RVR should be strongly considered if triple-therapy is not available.
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Affiliation(s)
- Mattias Mandorfer
- Vienna HIV & Liver Study Group, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Mandorfer M, Neukam K, Reiberger T, Payer BA, Rivero A, Puoti M, Boesecke C, Baumgarten A, Grzeszczuk A, Zangerle R, Meyer-Olson D, Rockstroh JK, Trauner M, Pineda JA, Peck-Radosavljevic M. The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients. AIDS 2013; 27:2707-14. [PMID: 23835502 DOI: 10.1097/01.aids.0000432460.44593.ef] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVE According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients. DESIGN Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis. METHODS Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa. RESULTS In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage. CONCLUSION Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.
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Affiliation(s)
- Mattias Mandorfer
- aDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria bUnit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville cDepartment of Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain dDepartment of Infectious Diseases, AO Ospedale Niguarda Ca' Granda, Milano, Italy eDepartment of Internal Medicine I, University of Bonn, Bonn fPraxis Driesener Strasze, Berlin, Germany gDepartment of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland hDepartment of Dermatology, Medical University of Innsbruck, Innsbruck, Austria iDepartment of Clinical Immunology and Rheumatology, Medical University Hannover, Hannover, Germany
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Guzmán-Fulgencio M, García-Álvarez M, Berenguer J, Jiménez-Sousa MÁ, Cosín J, Pineda-Tenor D, Carrero A, Aldámiz T, Alvarez E, López JC, Resino S. Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients. J Infect 2013; 68:176-84. [PMID: 24184809 DOI: 10.1016/j.jinf.2013.10.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 09/27/2013] [Accepted: 10/25/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To study the association of plasma 25-hydroxy vitamin D (25(OH)D) levels in HIV/HCV coinfected patients with severity of liver disease and virological response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV). METHODS A cross-sectional study in 174 HIV/HCV coinfected patients that underwent a liver biopsy previously to start HCV therapy and a retrospective study of 125 of them. Plasma 25(OH)D levels were quantified by enzyme immunoassay. Liver biopsies were evaluated by METAVIR score. A sustained virological response (SVR) was defined as an undetectable serum HCV viral load (<10 IU/mL) up through 24 weeks after the end of HCV treatment. RESULTS The median of plasma 25(OH)D level was 48 nmol/L (p25th: 32.5; p75th: 56.1) and 27 (15.5%) had 25(OH)D deficiency (<25 nmol/L). The percentage of 25(OH)D deficiency was higher in patients with significant fibrosis (F ≥ 2) (92.6% vs. 57.1%; p = 0.010) and moderate necroinflammatory activity grade (A ≥ 2) (85.2% vs. 60%; p = 0.043). However, adjusted logistic regression analyses showed that 25(OH)D deficiency was only associated with severity of liver disease [F ≥ 2 (OR = 8.47 (95% of confidence interval (CI) = 1.88; 38.3); p = 0.005) and A ≥ 2 (OR = 3.25 (95%CI = 1.06; 10.1); p = 0.040)]. Moreover, any significant relationship was found between 25(OH)D deficiency and SVR after HCV therapy. CONCLUSION Plasma 25(OH)D deficiency was associated with liver disease severity in HIV/HCV coinfected patients, but it was not associated with HCV treatment failure.
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Affiliation(s)
- María Guzmán-Fulgencio
- Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Mónica García-Álvarez
- Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Juan Berenguer
- Infectious Diseases - HIV Unit, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Health Research Institute "Gregorio Marañón", Madrid, Spain
| | - M Ángeles Jiménez-Sousa
- Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Jaime Cosín
- Infectious Diseases - HIV Unit, Hospital General Universitario "Gregorio Marañón", Madrid, Spain
| | - Daniel Pineda-Tenor
- Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Ana Carrero
- Infectious Diseases - HIV Unit, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Health Research Institute "Gregorio Marañón", Madrid, Spain
| | - Teresa Aldámiz
- Infectious Diseases - HIV Unit, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Health Research Institute "Gregorio Marañón", Madrid, Spain
| | - Emilio Alvarez
- Pathology Department, Hospital General Universitario "Gregorio Marañón", Madrid, Spain
| | - Juan Carlos López
- Infectious Diseases - HIV Unit, Hospital General Universitario "Gregorio Marañón", Madrid, Spain
| | - Salvador Resino
- Unit of Viral Infection and Immunity, National Centre of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
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Abstract
Vitamin D plays a role in the synthesis of antibacterial peptids and in autophagy. Several studies have shown that low levels of vitamin D are associated with the susceptibility and the severity of acute infections on one hand, and with an unfavorable outcome of some chronic infections (such as HIV infection). Vitamin D supplementation improves response to treatment of some viral (such as chronic hepatitis C infection) or bacterial infections (such as pulmonar tuberculosis). Vitamin D supplementation demonstrated no benefit in reducing the incidence of pulmonary infections. The target level of vitamin D to be reached after supplementation is not known yet.
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Branch AD, Kang M, Hollabaugh K, Wyatt CM, Chung RT, Glesby MJ. In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use. Am J Clin Nutr 2013; 98:423-9. [PMID: 23739141 PMCID: PMC3712551 DOI: 10.3945/ajcn.112.048785] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Among patients with hepatitis C virus (HCV) monoinfection, 25-hydroxyvitamin D [25(OH)D] concentrations are positively associated with a response to peg-interferon/ribavirin. Data on the relation between 25(OH)D concentrations and HCV treatment response in HIV-infected patients are limited. OBJECTIVE The objective was to determine whether baseline 25(OH)D concentrations predict virologic response in HIV/HCV co-infected patients and to examine variables associated with 25(OH)D concentrations ≥30 ng/mL. DESIGN Data and samples from 144 HCV genotype 1, treatment-naive patients from a completed HCV treatment trial were examined in this retrospective study. Early virologic response (EVR) was defined as ≥2 log10 reduction in HCV RNA and/or HCV RNA <600 IU/mL at week 12 of peg-interferon/ribavirin treatment. Baseline 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. RESULTS Compared with the non-EVR control group (n = 68), the EVR group (n = 76) was younger, had fewer cirrhotic subjects, had a higher proportion with the IL28B CC genotype, had a higher albumin concentration, and had a lower HCV viral load at baseline (P ≤ 0.05). The difference in baseline 25(OH)D concentrations between EVR and non-EVR patients was not statistically significant (median: 25 ng/mL compared with 20 ng/mL; P = 0.23). Similar results were found for sustained virologic response (SVR). In multivariable analysis, white and Hispanic race-ethnicity (OR: 6.26; 95% CI: 2.47, 15.88; P = 0.0001) and ritonavir use (OR: 2.68; 95% CI: 1.08, 6.65; P = 0.033) were associated with higher 25(OH)D concentrations (≥30 ng/mL). CONCLUSION Baseline 25(OH)D concentrations did not predict EVR or SVR. Because ritonavir impairs the conversion of 25(OH)D to the active metabolite, utilization of 25(OH)D may have been impaired in subjects taking ritonavir. This trial was registered at www.clinicaltrials.gov as NCT00078403.
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Affiliation(s)
- Andrea D Branch
- Divisions of Liver Diseases and Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA.
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40
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Zhu M, Xu LM. Relationship between vitamin D and chronic liver diseases. Shijie Huaren Xiaohua Zazhi 2013; 21:1714-1719. [DOI: 10.11569/wcjd.v21.i18.1714] [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] [Indexed: 02/06/2023] Open
Abstract
Vitamin D is a fat-soluble vitamin with multiple biological effects that is predominantly synthetized in the liver. Various kinds of chronic liver diseases are associated with vitamin D deficiency, and vitamin D supplementation may influence treatment outcome. This article summarizes the role of vitamin D in the pathogenesis and treatment of chronic liver diseases to provide new insight into the treatment of these diseases.
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