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Ravaioli F, Pivetti A, Di Marco L, Chrysanthi C, Frassanito G, Pambianco M, Sicuro C, Gualandi N, Guasconi T, Pecchini M, Colecchia A. Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease. Int J Mol Sci 2022; 23:ijms23169016. [PMID: 36012285 PMCID: PMC9409132 DOI: 10.3390/ijms23169016] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/09/2022] [Accepted: 08/11/2022] [Indexed: 12/12/2022] Open
Abstract
Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease.
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Affiliation(s)
- Federico Ravaioli
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Department of Medical and Surgical Sciences, University of Bologna, 40128 Bologna, Italy
- Correspondence:
| | - Alessandra Pivetti
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Lorenza Di Marco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Christou Chrysanthi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Gabriella Frassanito
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Martina Pambianco
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Chiara Sicuro
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Noemi Gualandi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Tomas Guasconi
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Maddalena Pecchini
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Department of Medical Specialties, University Hospital of Modena, University of Modena & Reggio Emilia, 41121 Modena, Italy
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He Y, Zhang M, Li T, Tan Z, Zhang A, Ou M, Huang D, Wu F, Wang X. Metabolomics Analysis Coupled With UPLC/MS on Therapeutic Effect of Jigucao Capsule Against Dampness-Heat Jaundice Syndrome. Front Pharmacol 2022; 13:822193. [PMID: 35153793 PMCID: PMC8831696 DOI: 10.3389/fphar.2022.822193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
Dampness-heat Jaundice Syndrome (DHJS) is a complex Chinese medicine syndrome, while Jigucao capsule (JGCC) is an effective compound preparation of Chinese medicine for the treatment of DHJS about liver and gallbladder, but its mechanism is not clear yet. The purpose of this study is to clarify the pathogenesis of DHJS and the treatment mechanism of JGCC. We used ultra-high performance liquid chromatography/mass spectrometry (UPLC/MS) combined with pattern recognition, accompanied the advanced software and online database for the urine metabolomics of rats. The potential biomarkers disturbing metabolism were identified and the metabolic pathway was analyzed. We investigated the callback of biomarkers after treatment with JGCC. Finally, A total of 25 potential urine biomarkers were identified, including Arachidonic acid, Phenylpyruvic acid, L-Urobilin and so on, and 14 related metabolic pathways were disturbed. After treatment with JGCC, the clinical biochemical indexes and histopathological were significantly improved, and the disturbed biomarkers were also obviously adjusted. It is proved that JGCC has remarkable effect on the treatment of DHJS.
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Affiliation(s)
- Yanmei He
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Mengli Zhang
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Taiping Li
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zhien Tan
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Aihua Zhang
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Min Ou
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Danna Huang
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Fangfang Wu
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
| | - Xijun Wang
- National Engineering Laboratory for the Development of Southwestern EndangeredMedicinal Materials, Guangxi Botanical Garden of Medicinal Plants, Nanning, China
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Chinmedomics Research Center of State Administration of TCM, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
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Licata A, Zerbo M, Como S, Cammilleri M, Soresi M, Montalto G, Giannitrapani L. The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement? Nutrients 2021; 13:nu13114014. [PMID: 34836267 PMCID: PMC8620546 DOI: 10.3390/nu13114014] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/28/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022] Open
Abstract
Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed.
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Affiliation(s)
- Anna Licata
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
- Correspondence: ; Tel.: +39-091-655-2280; Fax: +39-091-655-2156
| | - Maddalena Zerbo
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Silvia Como
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Marcella Cammilleri
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Maurizio Soresi
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Giuseppe Montalto
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
| | - Lydia Giannitrapani
- Internal Medicine & Hepatology Section, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties—PROMISE, University of Palermo Medical School, 90127 Palermo, Italy; (M.Z.); (S.C.); (M.C.); (M.S.); (G.M.); (L.G.)
- Institute for Biochemical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy
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Vitamin D deficiency in patients with chronic hepatitis D viral infection. Clin Exp Hepatol 2021; 7:141-148. [PMID: 34295980 PMCID: PMC8284160 DOI: 10.5114/ceh.2021.106505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 01/22/2021] [Indexed: 01/10/2023] Open
Abstract
Aim of the study Vitamin D deficiency is known to be associated with disease severity, unresponsiveness to treatment, and morbidity among patients with chronic viral hepatitis B and C, autoimmune hepatitis, and alcoholic hepatitis. This study aims to research vitamin D levels in patients suffering from cirrhotic and non-cirrhotic phases of hepatitis D. Material and methods 170 individuals in total were included in the study in the form of two groups: the first group of 100 patients with chronic hepatitis D (CHD), 30 of whom had cirrhosis, and the second control group of 70 individuals with similar characteristics to those of the first group in terms of age, type, and seasonal sampling. Levels of 25-hydroxy vitamin D [25(OH)D] were measured in the serum collected from patients and the control group. Results The lowest 25(OH)D levels were identified in patients with cirrhotic CHD. When these levels were compared with those of the control group, they were found to be significant (15.30 ±6.92 and 18.90 ±8.30 ng/ml, respectively, p = 0.04). 25(OH)D deficiency (< 10 ng/ml) was detected at significantly higher rates in patients with both cirrhotic and non-cirrhotic CHD compared to the healthy controls (30%, 25%, and 8.5%, respectively, p = 0.01). A significant correlation was established between 25(OH)D levels and bilirubin in patients with CHD (r = 0.252, p = 0.012). Multivariate analysis showed that chronic hepatitis D (odds ratio [OR] = 3.608, 95% confidence interval [CI]: 1.31-9.89, p = 0.013) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.033) were associated with vitamin D deficiency. Conclusions Frequency of 25(OH)D vitamin deficiency is higher in patients with CHD. The identification of vitamin D levels and the replacement of any deficiency may create a positive effect on disease progression, morbidity, and mortality levels.
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Chen HW, Chiu YL, Hsieh TY, Chen PJ, Huang TY, Lin HH, Shih YL, Lin JC. Relationships Between Vitamin D Status and Cytokine: Results from Interferon-Based Therapy in Non-Cirrhotic, Treatment-Naïve Patients with Chronic Hepatitis C Infection. J Inflamm Res 2021; 13:1207-1218. [PMID: 33402842 PMCID: PMC7778440 DOI: 10.2147/jir.s283768] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/11/2020] [Indexed: 12/13/2022] Open
Abstract
Background Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans. Methods A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus. Findings The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders. Conclusion In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.
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Affiliation(s)
- Hsuan-Wei Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Lin Chiu
- Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Peng-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsuan-Hwai Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yu-Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jung-Chun Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Abstract
OBJECTIVE(S) Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients' survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients' mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics' mortality. METHODS One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1β, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array. RESULTS 25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients' survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002). CONCLUSION The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients' mortality, possibly through a proinflammatory immune response.
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The association of vitamin D with hepatitis B virus replication: Bystander rather than offender. J Formos Med Assoc 2020; 119:1634-1641. [PMID: 31932201 DOI: 10.1016/j.jfma.2019.12.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 11/10/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/PURPOSE Low vitamin D is frequent in hepatitis B virus (HBV)-infected patients and several studies show an inverse association of serum vitamin D level with HBV viral load. However, the causal relationship remains unclear. METHODS HBV carriers receiving regular 6-month surveillance without current antiviral treatment or cirrhosis were invited to participate into this trial. The markers of HBV replication included serum HBV DNA and quantitative HBsAg (qHBsAg) levels. Those with undetectable HBV DNA or sufficient vitamin D levels, cancer or electrolyte imbalance were excluded. The eligible subjects were randomized to receive either vitamin D supplement 2000 IU per day for 2 months (vitamin D group) or none (control group). RESULTS A total of 196 HBV carriers (93 males and 103 females; mean age 51.9 ± 10.0 years) were screened. Of them, 28 patients had undetectable serum HBV DNA levels, which is defined as spontaneous viral clearance. The vitamin D levels were not different between patients with detectable HBV DNA and those without (p = 0.18). After exclusion, 149 patients were randomized to two groups: 75 in vitamin D group and 74 in control group. After 2 months vitamin D supplement, the serum vitamin D levels were significantly higher in the vitamin D group than the control group (p < 0.001). However, the serum qHBsAg and HBV DNA levels were comparable between these two groups. CONCLUSION There is no causal relationship between vitamin D and HBV replication. The role of liver reserve on serum vitamin D levels in patients with chronic HBV infection needs further investigation.
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Lin YT, Wang LK, Hung KC, Wu ZF, Chang CY, Chen JY. Patient characteristics and analgesic efficacy of antiviral therapy in postherpetic neuralgia. Med Hypotheses 2019; 131:109323. [PMID: 31443749 DOI: 10.1016/j.mehy.2019.109323] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 07/20/2019] [Indexed: 01/16/2023]
Abstract
Postherpetic neuralgia (PHN) is the most common complication of shingles caused by reactivation of varicella zoster virus (VZV). Management of PHN is often suboptimal while using current conventional treatments. Antiviral therapy was used to reduce PHN-associated pain in two small trials which showed conflicting results. We hypothesize the analgesic efficacy of antiviral therapy on PHN is affected by patient characteristics including pathophysiology of the participants and serum vitamin D levels. Pathophysiology of PHN includes neuronal excitability and chronic VZV ganglionitis (persistent active VZV infection in ganglions). VZV-DNA positivity or a positive IgG coupled with a positive IgM indicates recent or current VZV infection. Positive VZV-DNA or IgG/IgM tests are used to confirm whether the patients experience chronic VZV ganglionitis. Antiviral therapy decreases pain in PHN patients with chronic VZV ganglionitis; whereas, antiviral therapy shows no effects in PHN patients with negative VZV-DNA or IgM. Vitamin D is a natural antiviral mediator. Studies show a high prevalence of vitamin D deficiency in hepatitis B/C virus-infected patients. Serum vitamin D levels and vitamin D supplementation are factors which affect the antiviral efficacy on hepatitis B/C virus infection. Serum 25-OHD levels of hospitalized patients with shingles were significantly lower compared to healthy controls. Accordingly, PHN patient may have a high prevalence of vitamin D deficiency which negatively affects the antiviral efficacy. Vitamin D supplementation may improve the antiviral efficacy on PHN. Future trials regarding antiviral therapy on PHN should consider patient characteristics and should be conducted among different subgroups of PHN patients.
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Affiliation(s)
- Yao-Tsung Lin
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Li-Kai Wang
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Kuo-Chuan Hung
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Zhi-Fu Wu
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chia-Yu Chang
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan; The Center for General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Jen-Yin Chen
- Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of the Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
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Yousif MM, Sadek AMEM, Farrag HA, Selim FO, Hamed EF, Salama RI. Associated vitamin D deficiency is a risk factor for the complication of HCV-related liver cirrhosis including hepatic encephalopathy and spontaneous bacterial peritonitis. Intern Emerg Med 2019; 14:753-761. [PMID: 30706253 DOI: 10.1007/s11739-019-02042-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Accepted: 01/19/2019] [Indexed: 02/07/2023]
Abstract
The influence of vitamin D, 25-hydroxyvitamin D (25(OH)D), deficiency on hepatitis C virus (HCV)-related cirrhosis had been poorly elucidated especially in patients with hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). We aimed to investigate the association between vitamin D deficiency and the risk of SBP or HE, including the mortality rate. Serum 25(OH)D levels were prospectively determined in 135 patients. Of them, 45 patients had complications with HE and 45 patients had complications with SBP; 45 cirrhotic patients without complication served as the control group. Vitamin D deficiency was defined as 25(OH)D levels < 20 ng/ml. Receiver operating characteristic (ROC) and Kaplan-Meier method with log-rank test were used in our statistical analysis. Predictors of survival were determined using Cox regression analysis. Serum 25(OH)D levels were significantly (P < 0.05) lower in the HE and SBP groups than in the control group (6.81 ± 2.75, 7.15 ± 2.10, 16.28 ± 6.60, respectively). Moreover, serum 25(OH)D levels were significantly lower in the high HE grade than in the low grade (P < 0.001). Regarding the SBP group, classic SBP was associated with lower 25(OH)D levels compared to other types (P < 0.001). ROC curve revealed that lower 25(OH)D levels less than 7.1 ng/ml and 6.6 ng/ml could predict the mortality in SBP and HE patients, respectively, with high sensitivity and specificity. Serum 25(OH)D levels < 5 ng/ml were associated with significant higher mortality rate (HR = 2.76, P = 0.001). Lower 25(OH)D levels were associated with HE and SBP in cirrhotic patients. In addition, it may be considered a prognostic parameter for the severity of liver cirrhosis.
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Affiliation(s)
- Monkez Moteih Yousif
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | | | - Hesham Ahmad Farrag
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Fayrouz Othman Selim
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Emad Fawzi Hamed
- Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Sharkia, 44519, Egypt
| | - Rasha Ibrahim Salama
- Tropical Medicine Department, Faculty of Medicine, Zagazig University Hospitals, Zagazig, Egypt
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Teixeira HC, Dias LDS, Bizarro HDDS, Castro JMDA. Efeitos contrastantes da vitamina D sobre a resposta imune inata e adquirida e seu impacto na recuperação da tuberculose. HU REVISTA 2019. [DOI: 10.34019/1982-8047.2018.v44.22232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A vitamina D é um hormônio essencial para o organismo, podendo ser obtida da dieta ou, principalmente, gerada pela pele após exposição à luz solar ultravioleta B. Na sua forma ativa (1,25(OH)2D) ela controla a absorção de cálcio e fósforo do intestino para a corrente sanguínea e participa de diversos processos celulares e fisiológicos. A ligação da 1,25(OH)2D ao receptor da vitamina D (VDR) presente em diversas células, como as células do sistema imunológico, induz a transcrição de genes que podem, por exemplo, modular a resposta imune inata e adquirida. A deficiência de vitamina D ou do VDR é associada a problemas de saúde como desordens esqueléticas, hipertensão, doenças cardiovasculares, diabetes mellitus, dislipidemias, doenças autoimunes e doenças infecciosas. Neste sentido, a suplementação com vitamina D tem sido proposta como uma possível medida preventiva, podendo ser aplicada em muitas patologias, em especial na tuberculose. Principal causa de morte por um único agente infeccioso, a tuberculose é responsável por cerca de 1,3 milhões de óbitos por ano no mundo. Publicações recentes apontam efeitos diversos da vitamina D na resposta imune inata e adquirida. A 1,25(OH)2D3 na presença do interferon (IFN)-γ é capaz de aumentar a atividade bactericida do macrófago contra o M. tuberculosis, aumentando a produção de peptídios antimicrobianos e estimulando a autofagia, favorecendo assim a lise de bacilos localizados em fagossomos. Por outro lado, a vitamina D em linfócitos T mostra efeito tolerogênico que favorece o controle de respostas inflamatórias excessivas. Neste trabalho de revisão são apresentados estudos recentes envolvendo efeitos da vitamina D na resposta imune inata e adquirida. Além disso, considerações sobre deficiência de vitamina D e maior risco de contrair tuberculose, e efeitos contrastantes da suplementação com vitamina D na prevenção e tratamento da TB, são discutidos.
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Behera MK, Shukla SK, Dixit VK, Nath P, Abhilash VB, Asati PK, Jain AK. Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India. Indian J Med Res 2019; 148:200-206. [PMID: 30381543 PMCID: PMC6206764 DOI: 10.4103/ijmr.ijmr_1295_15] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background & objectives: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. Methods: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 μg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). Results: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). Interpretation & conclusions: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.
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Affiliation(s)
- Manas Kumar Behera
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Sunit Kumar Shukla
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Vinod Kumar Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Preetam Nath
- Department of Gastroenterology, SCB Medical College, Cuttack, India
| | - V B Abhilash
- Department of Gastroenterology, ESIC, Model & Super Specialty Hospital, Kollam, India
| | - Pankaj Kumar Asati
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Ashok Kumar Jain
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
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12
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Pacifico L, Osborn JF, Bonci E, Pierimarchi P, Chiesa C. Association between Vitamin D Levels and Nonalcoholic Fatty Liver Disease: Potential Confounding Variables. Mini Rev Med Chem 2019; 19:310-332. [PMID: 30360708 DOI: 10.2174/1389557518666181025153712] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 06/16/2017] [Accepted: 08/25/2017] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), historically considered to be the hepatic component of the metabolic syndrome, is a spectrum of fat-associated liver conditions, in the absence of secondary causes, that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Disease progression is closely associated with body weight or fatness, dyslipidemia, insulin resistance, oxidative stress, and inflammation. Recently, vitamin D deficiency has been linked to the pathogenesis and severity of NAFLD because of vitamin D "pleiotropic" functions, with roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. Indeed, several studies have reported an association between vitamin D and NAFLD/NASH. However, other studies have failed to find an association. Therefore, we sought to critically review the current evidence on the association between vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables that may interfere with this evaluation, such as host-, environment-, and heritability-related factors regulating vitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respect to skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D; and methods of diagnosing NAFLD as well as quantifying adiposity, the cardinal link between vitamin D deficiency and NAFLD.
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Affiliation(s)
- Lucia Pacifico
- Policlinico Umberto I Hospital, Sapienza University of Rome, Viale Regina Elena, 324 00161-Rome, Italy
| | - John F Osborn
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale Regina Elena, 324 00161- Rome, Italy
| | - Enea Bonci
- Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324 00161- Rome, Italy
| | - Pasquale Pierimarchi
- Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere, 100 00133- Rome, Italy
| | - Claudio Chiesa
- Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere, 100 00133- Rome, Italy
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13
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Gürbüz F, Ağın M, Mengen E, Elçi H, Ünal İ, Tümgör G, Yüksel B. Kronik karaciğer hastalığı olan çocukların D vitamini düzeyleri. CUKUROVA MEDICAL JOURNAL 2018. [DOI: 10.17826/cumj.365057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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14
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Wu DB, Wang ML, Chen EQ, Tang H. New insights into the role of vitamin D in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2018; 12:287-294. [PMID: 29140126 DOI: 10.1080/17474124.2018.1406307] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In addition to being crucial for host immune defense, vitamin D is involved in cell proliferation, apoptosis, differentiation, inflammation, invasion and metastasis, angiogenesis and micro-RNA modulation. To date, clinical studies have demonstrated that vitamin D deficiency is common not only in patients with chronic liver diseases but also in those with hepatocellular carcinoma (HCC). Experimental studies have also demonstrated that vitamin D and its receptors are related to the occurrence of HCC and the prognoses of patients with HCC. Areas covered: In this review, we discuss the potential anti-tumor role of vitamin D in HCC based on current findings from epidemiological studies, basic science, and clinical studies and provide new insights into the pathogenesis and treatment of HCC. Expert commentary: Recent studies have revealed the anti-tumor effects of vitamin D to a certain degree. Vitamin D and its analogs may provide new treatment targets and prognostic factors for HCC that might be essential for the primary or secondary prevention of HCC and the monitoring of its progression.
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Affiliation(s)
- Dong-Bo Wu
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - Meng-Lan Wang
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - En-Qiang Chen
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
| | - Hong Tang
- a Center of Infectious Diseases , West China Hospital of Sichuan University , Chengdu , China
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15
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Current therapies in alleviating liver disorders and cancers with a special focus on the potential of vitamin D. Nutr Metab (Lond) 2018; 15:13. [PMID: 29449867 PMCID: PMC5807831 DOI: 10.1186/s12986-018-0251-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023] Open
Abstract
Background Liver dysfunction is a topic of global concern with many advancing therapies being researched. Though vitamin D takes a center place, other therapies especially nutritional are also gaining ground. Vitamin D has gone beyond its role in skeletal disorders by showcasing its associations in other metabolic dysfunctions too. Result Epidemiological evidences show a correlation between the status of vitamin D and different forms of cancer. Vitamin D receptors and alterations in gene expression appear decisive in the development of chronic liver disorders. Nutritional status therefore plays a significant role in avoiding the complications related to liver dysfunctions, making it mandatory in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty acids, antioxidants, amino acids, steroids also render benefits which could be further explored. Recent research on the progression of certain forms of liver cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise. Conclusion The anti-inflammatory and immuno- regulatory properties of vitamin D makes its analogs, suitable candidates of better choice for the prevention and treatment of liver disorders and cancer.
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16
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Yu R, Tan D, Ning Q, Niu J, Bai X, Chen S, Cheng J, Yu Y, Wang H, Xu M, Shi G, Wan M, Chen X, Tang H, Sheng J, Dou X, Shi J, Ren H, Wang M, Zhang H, Gao Z, Chen C, Ma H, Jia J, Hou J, Xie Q, Sun J. Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B. Hepatol Res 2018; 48:E213-E221. [PMID: 28834607 DOI: 10.1111/hepr.12972] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/17/2017] [Accepted: 08/18/2017] [Indexed: 02/05/2023]
Abstract
AIM The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. METHODS Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. RESULTS The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. CONCLUSIONS Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.
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Affiliation(s)
- Rui Yu
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Deming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junqi Niu
- Hepatology Unit, No. 1 Hospital affiliated to Jilin University, Changchun, China
| | - Xuefan Bai
- Department of Infectious Diseases, Tangdu Hospital, Xi'an, China
| | - Shijun Chen
- Ji'nan Infectious Diseases Hospital, Ji'nan, China
| | - Jun Cheng
- Beijing Ditan Hospital, Beijing, China
| | - Yanyan Yu
- Department of Infectious Diseases, First Hospital of Peking University, Beijing, China
| | - Hao Wang
- Hepatology Unit, Peking University People's Hospital, Beijing, China
| | - Min Xu
- 8th People's Hospital, Guangzhou, China
| | - Guangfeng Shi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Mobin Wan
- Department of Infectious Diseases, Changhai Hospital, Shanghai, China
| | | | - Hong Tang
- Department of Infectious Diseases, West China Hospital, Chengdu, China
| | - Jifang Sheng
- Department of Infectious Diseases, Zhejiang University 1st Affiliated Hospital, Hangzhou, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China
| | | | - Hong Ren
- Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Maorong Wang
- Department of Infectious Diseases, 81st PLA Hospital, Nanjing, China
| | | | - Zhiliang Gao
- Department of Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou, China
| | - Chengwei Chen
- Department of Infectious Diseases, 85th PLA Hospital, Shanghai, China
| | - Hong Ma
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jinlin Hou
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jian Sun
- Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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17
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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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18
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Boglione L, Cardellino CS, Cusato J, De Nicolò A, Cariti G, Di Perri G, D'Avolio A. Treatment with PEG-IFN and ribavirin in patients with chronic hepatitis C, low grade of hepatic fibrosis, genotype 1 and 4 and favorable IFNL3 genotype: A pharmacogenetic prospective study. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2017; 51:167-172. [PMID: 28315743 DOI: 10.1016/j.meegid.2017.03.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 03/08/2017] [Accepted: 03/14/2017] [Indexed: 12/12/2022]
Abstract
The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes. 65 patients were included in the study. Overall SVR was observed in 50 patients (76.9%); SVR rates among different genotypes were as follows: 15 with GT1a (71.4%), 27 with GT1b (79.4%) and 8 for GT4 (80%). The RBV cutoff at 2weeks of 1800ng/mL, predictor of RVR, was determined (p=0.003; sensibility=60.4%, specificity=88.2%, positive predictive value=88.9%, negative predictive value=100%). In multivariate analysis, factors significantly associated with treatment failure were living alone condition (OR=4.302; 95%IC=1.254-16.257; p=0.034) and RBV plasma level <1800ng/mL at 2weeks (OR=4.970; 95%IC=1.405-17.565; p=0.009). Considering a pharmacogenetic-guided approach, dual therapy with PEG-IFN and RBV can be considered a reliable option for patients ineligible for IFN-free treatments, who are motivated and well informed about all the aspects related to PEG-IFN administration.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
| | - Chiara Simona Cardellino
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Jessica Cusato
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Amedeo De Nicolò
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
| | - Antonio D'Avolio
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy
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Thanapirom K, Suksawatamnuay S, Sukeepaisarnjaroen W, Tangkijvanich P, Treeprasertsuk S, Thaimai P, Wasitthankasem R, Poovorawan Y, Komolmit P. Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients. BMC Gastroenterol 2017; 17:54. [PMID: 28415985 PMCID: PMC5392932 DOI: 10.1186/s12876-017-0613-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 04/11/2017] [Indexed: 12/16/2022] Open
Abstract
Background Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. Methods The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis. Results SVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0–1 (OR = 5.00; 95% CI, 2.02–12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03–7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13–3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection. Conclusion The DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0613-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kessarin Thanapirom
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Sirinporn Suksawatamnuay
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Wattana Sukeepaisarnjaroen
- Gastroenterology unit, Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, No. 123 Mittraparp Highway, Muang District, Khon Kaen, 40002, Thailand
| | - Pisit Tangkijvanich
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Sombat Treeprasertsuk
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Panarat Thaimai
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Rujipat Wasitthankasem
- Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, No. 1873 Rama IV road, Bangkok, 10330, Thailand
| | - Piyawat Komolmit
- Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand. .,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand.
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20
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Komolmit P, Charoensuk K, Thanapirom K, Suksawatamnuay S, Thaimai P, Chirathaworn C, Poovorawan Y. Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial. PLoS One 2017; 12:e0174608. [PMID: 28376103 PMCID: PMC5380326 DOI: 10.1371/journal.pone.0174608] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 03/12/2017] [Indexed: 12/31/2022] Open
Abstract
Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC. TRIAL REGISTRATION Thai Clinical Trials Registry TCTR20160429001.
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Affiliation(s)
- Piyawat Komolmit
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kriangsak Charoensuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Division of Gastroenterology, Department of Internal medicine, Buddhachinaraj Hospital School of Medicine, Phitsanulok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Chintana Chirathaworn
- Division of Immunology, Department of Microbiology, Chulalongkorn university, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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21
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Yang CC, Tseng TC, Chen JH, Li CH, Wang PC, Lin HH, Wang CC. Serum vitamin D level not correlated with hepatitis B virus replication in patients with chronic hepatitis B virus infection. ADVANCES IN DIGESTIVE MEDICINE 2017. [DOI: 10.1002/aid2.12012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Chun-Chun Yang
- Department of Laboratory Medicine; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Tai-Chung Tseng
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Jiann-Hwa Chen
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Chung-Hsien Li
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Pin-Chao Wang
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Hans Hsienhong Lin
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
| | - Chia-Chi Wang
- Department of Gastroenterology; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Taiwan
- School of Medicine; Tzu Chi University; Hualien Taiwan
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22
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Paternostro R, Wagner D, Reiberger T, Mandorfer M, Schwarzer R, Ferlitsch M, Trauner M, Peck-Radosavljevic M, Ferlitsch A. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr 2016; 129:8-15. [PMID: 27888359 PMCID: PMC5247538 DOI: 10.1007/s00508-016-1127-1] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Accepted: 04/09/2016] [Indexed: 12/14/2022]
Abstract
Background and aims Vitamin D deficiency is frequent in patients with cirrhosis. The aims of this study were to evaluate the relation of vitamin D status to portal hypertension, degree of liver dysfunction and survival. Methods Patients with cirrhosis who have been tested for 25-OH-vitamin D levels were retrospectively included. Vitamin D deficiency was defined as 25-OH-vitamin D levels <10 ng/ml. Child–Pugh score, model for end-stage liver disease (MELD) and available hepatic venous pressure gradient (HVPG) were recorded. Mortality was documented during follow-up. Results A total of 199 patients were included. Prevalence of vitamin D deficiency (<10 ng/ml) was 40% (79/199), with 14% in Child–Pugh stage A, 39% in Child–Pugh stage B and 47% in Child–Pugh stage C (p = 0.001). Vitamin D deficiency was more common in patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mm Hg) than in patients without (43.5% vs. 24.4%, p = 0.025). Significantly more deaths were observed in patients with vitamin D deficiency (32.9%, 26/79 vs. 13.3%, 16/120; p = 0.001). COX regression found presence of hepatocellular carcinoma (p < 0.001; HR: 5.763 95%CI:2.183–15.213), presence of CSPH (p = 0.026; HR: 5.487 95%CI: 1.226–24.55) and Child–Pugh stage C (p = 0.003; HR:5.429 95%CI: 1.771–16.638) as independent risk factors for mortality. Furthermore we could show a tendency towards group vitamin D deficiency being an independent risk factor (p = 0.060; HR: 1.86 95%CI:0.974–3.552). Conclusions Vitamin D levels progressively decrease in more advanced Child stages and in patients with increasing HVPG. Vitamin D deficiency might be a valuable predictor of mortality in cirrhosis.
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Affiliation(s)
- Rafael Paternostro
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Doris Wagner
- Department of Surgery, Medical University of Graz, Graz, Austria
| | - Thomas Reiberger
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Remy Schwarzer
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Monika Ferlitsch
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Vienna Hepatic Hemodynamic Laboratory, Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. .,Divison of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
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23
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Loftfield E, O’Brien TR, Pfeiffer RM, Howell CD, Horst R, Prokunina-Olsson L, Weinstein SJ, Albanes D, Morgan TR, Freedman ND. Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials. PLoS One 2016; 11:e0166036. [PMID: 27832143 PMCID: PMC5104464 DOI: 10.1371/journal.pone.0166036] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/11/2016] [Indexed: 12/17/2022] Open
Abstract
More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFNα) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFNα/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (≤20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH)D ≥30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43–0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20–1.17).
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Affiliation(s)
- Erikka Loftfield
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
- * E-mail:
| | - Thomas R. O’Brien
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Ruth M. Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Charles D. Howell
- Department of Medicine, Howard University College of Medicine, Washington, DC, United States of America
| | - Ron Horst
- Heartland Assays, Ames, IA, United States of America
| | - Ludmila Prokunina-Olsson
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
| | - Timothy R. Morgan
- VA Long Beach Healthcare System, Long Beach, CA, United States of America
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America
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24
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Abdelsalam A, Rashed L, Salman T, Hammad L, Sabry D. Molecular assessment of vitamin D receptor polymorphism as a valid predictor to the response of interferon/ribavirin-based therapy in Egyptian patients with chronic hepatitis C. J Dig Dis 2016; 17:547-553. [PMID: 27128845 DOI: 10.1111/1751-2980.12353] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 03/01/2016] [Accepted: 04/20/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to find an association between serum concentration of vitamin D and vitamin D receptor (VDR) polymorphisms to achieve a sustained virological response (SVR). METHODS We conducted a case-control study in which 250 participants were recruited and divided into three groups (100 chronic hepatitis C [CHC] patients who achieved SVR, 100 CHC patients who did not achieve SVR and 50 apparently healthy individuals as controls). Blood samples were collected to measure serum vitamin D concentration, and four VDR polymorphisms (FokI, ApaI, TaqI, and BsmI) were detected using polymerase chain reaction-restriction fragment length polymorphism. RESULTS Non-responders were found to have significantly low vitamin D concentration compared with responders and control groups. Concerning VDR polymorphisms, both FokI and TaqI polymorphisms were associated with successful treatment. CONCLUSION Vitamin D concentration, FokI, and TaqI may be considered as the predictors for the response of CHC patients to a combination therapy of pegylated interferon and ribavirin.
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Affiliation(s)
- Ahmed Abdelsalam
- Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
| | - Laila Rashed
- Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tarek Salman
- Department of Biochemistry, Faculty of Pharmacy, Al Azhar University, Cairo, Egypt
| | - Lamiaa Hammad
- Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt
| | - Dina Sabry
- Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt
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25
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Belle A, Gizard E, Conroy G, Lopez A, Bouvier-Alias M, Rouanet S, Peyrin-Biroulet L, Pawlotsky JM, Bronowicki JP. 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients. United European Gastroenterol J 2016; 5:69-75. [PMID: 28405324 DOI: 10.1177/2050640616640157] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 02/24/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIM The impact of 25-OH vitamin D on sustained viral response (SVR) to antiviral therapy and on fibrosis progression in hepatitis C is debated. We assessed the impact of 25-OH vitamin D concentration on the efficacy of antiviral therapy in naïve genotype 1 hepatitis C virus (HCV)-infected patients. METHODS The study population consisted of treatment-naïve genotype 1 patients enrolled in a randomised controlled trial. A total of 516 patients received peginterferon α-2a 180 µg/week plus ribavirin 800 mg/day for 24 weeks. There were 349 patients with undetectable HCV RNA (<50 IU/ml) at week 24 (W24) who were randomised to continue dual therapy (n = 173) or to continue peginterferon alone (n = 176) until week 48. 25-OH vitamin D concentration was measured at baseline in frozen serum. RESULTS A total of 461 patients could be analysed for virologic response at W24, and 285 (119 non-responders at W24 + 166 responders who continued dual therapy until W48) for the impact of SVR. There were 487 patients who could be analysed for fibrosis progression. Metavir fibrosis scores (centralised analysis) were: F1 30%, F2 34%, F3 27% and F4 9%. Median 25-OH vitamin D concentrations were similar in virologic responders (13.5 ng/ml) and in non-responders at W24 (12.6 ng/ml), as well as in patients with SVR (12.8 ng/ml) and without SVR (12.8 ng/ml, 3.99) at W72. Median 25-OH vitamin D concentrations were: F1: 14.30 ng/ml, F2: 13.50 ng/ml, F3: 13.30 ng/ml and F4: 12.80 ng/ml. CONCLUSION In this study, 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naïve genotype 1 HCV-infected patients.
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Affiliation(s)
- Arthur Belle
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Emmanuel Gizard
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Guillaume Conroy
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Anthony Lopez
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Magali Bouvier-Alias
- National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France
| | | | - Laurent Peyrin-Biroulet
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
| | - Jean-Michel Pawlotsky
- National Reference Center for Viral Hepatitis B, C and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France
| | - Jean-Pierre Bronowicki
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
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26
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Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol 2016; 29:297-306. [PMID: 27366029 PMCID: PMC4923814 DOI: 10.20524/aog.2016.0037] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 03/26/2016] [Indexed: 02/06/2023] Open
Abstract
There is ongoing evidence that vitamin D is related to the pathophysiology of cirrhosis. Although the incidence of vitamin D deficiency in chronic liver diseases and cirrhosis is strongly documented, its pathogenic association with advanced liver fibrosis remains controversial. There is evidence of a significant relation of 25(OH)D levels with the degree of liver dysfunction, considering that an inverse correlation of 25(OH)D levels with both Child-Pugh score and Model for End-Stage Liver Disease has been reported. In addition, vitamin D deficiency has been shown to increase the risk for overall mortality and infections in patients with cirrhosis. Vitamin D deficiency has been also associated with advanced stages of hepatocellular carcinoma and poor prognosis. Finally, there are studies suggesting that patients with chronic hepatitis C and normal vitamin D levels have higher virological response to treatment. However, there are not enough studies conducted in cirrhotic-only populations. The association between vitamin D and cirrhosis demonstrates a great potential for clinical application. The relation between vitamin D deficiency and the degree of liver function, degree of fibrosis and infectious complications could support its use as a prognostic index and a diagnostic tool.
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Affiliation(s)
| | | | - Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | - Christos Triantos
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
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27
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Arooj M, Malik A, Basit A, Husain Qazi M, Asif M, Sarwar Jamal M, Mostafa Mahmoud M, Choudhry H, Natesan Pushparaj P, Rasool M. Implications of prognostic variables in the assessment of autoimmunity in hepatitis C patients receiving interferon therapy. Bioinformation 2016; 12:131-134. [PMID: 28149047 PMCID: PMC5267956 DOI: 10.6026/97320630012131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 05/26/2016] [Indexed: 02/08/2023] Open
Abstract
Systematic administration of interferon-alpha (INF-alpha) is considered as the backbone of HCV therapy since 1991. Interferon (IFN) therapy can cause vasculitis, glomerulonephritis, cryoglobulinemia and certain other autoimmune diseases such as sialoadentitis, lichen planus and thyroiditis. Related to the factors of interferons, extensively studied gland is thyroid gland. A strong association was observed between thyroid disease and HCV patient when they were exposed to IFN therapy. Vitamin D, malondialdehyde (MDA), thyroid hormones and auto antibodies were biochemically assessed from the venous blood of seventy five HCV patients and fifty healthy controls. The results of all parameters were analyzed by independent sample t-test. The results of the study demonstrated a clear picture that the levels of vitamin D decreased as compared to control but increases in case of MDA. The levels of antibody titer represent that thyroglobulin-antibody (TGAb) thyroid peroxidase-antibody (TPOAb) as well as thyroid stimulating hormone receptor-antibody (TSHRAb) were raised in the patients suffering from HCV with thyroid dysfunction as compared to control. Similarly, the levels of thyroid hormones were also elevated in the HCV patients. Antibodies generated against thyroidal enzymes leads to impaired function of these enzymes thus causing decreased synthesis of thyroid hormones. As exogenous INF triggers the release of cytokines that mediate the recruitment of immune cells with increased production of inflammatory markers lead to production of lytic granules which have direct toxic action on thyroid cells and ultimately increased lipid peroxidation of thyrocytes. The results of the present study clearly demonstrated that the decreased levels of vitamin D in HCV patients receiving IFN therapy were responsible to induce autoimmunity against thyroid gland and adjutant therapy may be helpful to alleviate the possible thyroid disorders.
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Affiliation(s)
- Mahwish Arooj
- University College of Medicine and Dentistry (UCMD), the University of Lahore, Lahore, Pakistan
| | - Arif Malik
- Institute of Molecular Biology and Biotechnology (IMBB), the University of Lahore, Lahore, Pakistan
| | - Abdul Basit
- Institute of Molecular Biology and Biotechnology (IMBB), the University of Lahore, Lahore, Pakistan
| | - Mahmood Husain Qazi
- Center for Research in Molecular Medicine (CRiMM), the University of Lahore, Lahore, Pakistan
| | - Muhammad Asif
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences (BUITEMS), Quetta, Pakistan
| | - Mohammad Sarwar Jamal
- King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, Saudi Arabia
| | - Maged Mostafa Mahmoud
- King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, Saudi Arabia;; Department of Molecular Genetics and Enzymology, Division of Human Genetics and Genome Research, National Research Centre, El-Buhouth St., P.O. 12622, Dokki, Giza, Egypt (Affiliation ID 60014618)
| | - Hani Choudhry
- Department of Molecular Genetics and Enzymology, Division of Human Genetics and Genome Research, National Research Centre, El-Buhouth St., P.O. 12622, Dokki, Giza, Egypt (Affiliation ID 60014618)
| | - Peter Natesan Pushparaj
- Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mahmood Rasool
- Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.; Institute of Molecular Biology and Biotechnology (IMBB), the University of Lahore, Lahore, Pakistan
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28
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Vosoghinia H, Esmaeilzadeh A, Ganji A, Hosseini SMR, Jamehdar SA, Salehi M, Bahari A, Ghanaei O, Sahebari M, Rajabzadeh F, Ghaffarzadehgan K, Goshayeshi L. Vitamin D in Standard HCV Regimen (PEG-Interferon Plus Ribavirin), Its Effect on the Early Virologic Response Rate: A Clinical Trial. RAZAVI INTERNATIONAL JOURNAL OF MEDICINE 2016. [DOI: 10.17795/rijm36632] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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29
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Atsukawa M, Tsubota A, Shimada N, Yoshizawa K, Abe H, Asano T, Ohkubo Y, Araki M, Ikegami T, Okubo T, Kondo C, Osada Y, Nakatsuka K, Chuganji Y, Matsuzaki Y, Iwakiri K, Aizawa Y. Effect of native vitamin D3 supplementation on refractory chronic hepatitis C patients in simeprevir with pegylated interferon/ribavirin. Hepatol Res 2016; 46:450-8. [PMID: 26289410 DOI: 10.1111/hepr.12575] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/11/2015] [Accepted: 08/11/2015] [Indexed: 02/08/2023]
Abstract
AIM Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT. METHODS Patients were randomly assigned to receive simeprevir (100 mg/day) for 12 weeks plus PEG IFN/ribavirin for 24 weeks (control group, n = 58), or vitamin D (2000 IU/day) for 16 weeks including a lead-in phase plus PEG IFN/ribavirin for 24 weeks (vitamin D group, n = 57). The primary end-point was sustainably undetectable viremia 24 weeks after the end of treatment (SVR). RESULTS SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels. CONCLUSION Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors.
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Affiliation(s)
- Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo
| | | | | | - Hiroshi Abe
- Jikei University School of Medicine Katsushika Medical Center
| | - Toru Asano
- Tokyo Metropolitan Bokutoh Hospital, Tokyo
| | | | | | | | - Tomomi Okubo
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai
| | | | | | | | | | | | - Yoshio Aizawa
- Jikei University School of Medicine Katsushika Medical Center
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El-Derany MO, Hamdy NM, Al-Ansari NL, El-Mesallamy HO. Integrative role of vitamin D related and Interleukin-28B genes polymorphism in predicting treatment outcomes of Chronic Hepatitis C. BMC Gastroenterol 2016; 16:19. [PMID: 26911666 PMCID: PMC4765184 DOI: 10.1186/s12876-016-0440-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Accepted: 02/17/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Improving prediction of treatment outcomes in chronic hepatitis C (CHC) genotype 4 (G4) is necessary to increase sustained viral response (SVR) rates. Vitamin D related and interferon stimulated genes are good candidates as they are recently crosstalk altering interferon response. Thus single nucleotide polymorphisms (SNPs) within some of these genes and multiple stepwise regression analysis including other independent predictors (IL28B(rs12979860), serum 25OH-vitamin D, serum alfa-fetoprotein (AFP)) were performed on a cohort of 200 Egyptian CHC patients treated with Pegylated interferon-alpha (Peg-IFN) plus ribavirin. METHODS SNPs in cytochrome P-450 (CYP2R1)(rs10741657AG), vitamin D receptor (VDR)(rs2228570AG, rs1544410CT), oligoadenylate synthetases-like (OASL)(rs1169279CT) and adenosine deaminases acting on RNA (ADAR)(rs1127309TC) genes were analyzed by real-time PCR. RESULTS The carrier state of A allele in VDR rs2228570 and CYP2R1 rs10741657 genes were independently associated with SVR [OR 6.453 & 3.536, p < 0.01 respectively]. Combining carriers of A allele in CYP2R1 and VDR genes with IL28B C/C genotype increased the probability of SVR from 80 % to reach 87.8 %, 93 % and 100 %. No relation was found between VDR rs1544410CT, ADAR rs1127309TC, OASL rs1169279CT polymorphisms and treatment outcome. Combining VDR rs2228570 A/A genotype with IL28B C/C genotype increased the probability of SVR from 82 % to reach 100 % and from 29 % to reach 80 % in C/T+ T/T IL28B genotype in none F4 liver disease patients. CONCLUSION Vitamin D related (VDR rs2228570 and CYP2R1 rs10741657) and IL28B rs12979860 genes polymorphisms accurately assure SVR in naïve CHC G4 patients treated with low cost standard therapy.
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Affiliation(s)
- M O El-Derany
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - N M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - N L Al-Ansari
- Endemic Medicine Department & Hepatology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - H O El-Mesallamy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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Cariani E, Roli L, Missale G, Villa E, Ferrari C, Trenti T. Interleukin 28B polymorphisms as predictors of sustained virological response in chronic hepatitis C: systematic review and meta-analysis. THE PHARMACOGENOMICS JOURNAL 2016; 16:18-29. [PMID: 25918016 DOI: 10.1038/tpj.2015.28] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 02/05/2015] [Accepted: 03/02/2015] [Indexed: 12/11/2022]
Abstract
Polymorphism of interleukin 28B gene represents a powerful outcome predictor for interferon-based regimens in hepatitis C virus infection. However, some studies report conflicting results. The predictive value of interleukin 28B genotype over the outcome interferon-α/ribavirin treatment was thoroughly evaluated and compared with virological predictors of response. Literature revision was performed on PubMed. Pooled odds ratios (ORs) were calculated by fixed- or random-effects models. Heterogeneity and publication bias were also assessed. Sixty-two eligible papers including 20 290 patients were retrieved. Both polymorphisms (rs12979860 and rs8099917) were strongly associated with response (OR=4.09 and 4.00, respectively), however, the association was weaker for subjects infected with viral genotypes 2 and 3 (OR=1.52 and 1.49, respectively). Compared with interleukin 28B genotype, the association with response was lower for baseline viremia (OR=2.15) and higher for rapid virological response (OR=13.86). These results provide a critical evaluation of interleukin 28B genotype as a pharmacogenetic predictor in hepatitis C patients.
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Affiliation(s)
- E Cariani
- Department of Laboratory Medicine, Clinical Pathology-Toxicology, Ospedale S Agostino-Estense, Modena, Italy
| | - L Roli
- Department of Laboratory Medicine, Clinical Pathology-Toxicology, Ospedale S Agostino-Estense, Modena, Italy
| | - G Missale
- UO Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria, Parma, Italy
| | - E Villa
- Department of Gastroenterology, University of Modena and Reggio Emilia, Modena, Italy
| | - C Ferrari
- UO Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria, Parma, Italy
| | - T Trenti
- Department of Laboratory Medicine, Clinical Pathology-Toxicology, Ospedale S Agostino-Estense, Modena, Italy
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32
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Association of vitamin D receptor gene polymorphisms with response to peginterferon plus ribavirin in Asian patients with chronic hepatitis C. J Formos Med Assoc 2015; 115:278-83. [PMID: 26725771 DOI: 10.1016/j.jfma.2015.11.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 11/05/2015] [Accepted: 11/10/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Recent studies have shown that serum vitamin D deficiency is a negative predictor of response to peginterferon plus ribavirin therapy for Caucasian patients with chronic hepatitis C (CHC). Whether vitamin D receptor (VDR) gene polymorphisms associate with antiviral response in Asian CHC patients remains unclear. METHODS We recruited 139 Asian patients with CHC genotype-1 who achieved 80/80/80 adherence of response-guided peginterferon plus ribavirin therapy. BsmI rs1544410, ApaI rs7975232, and TaqI rs731236 were genotyped and related to clinical and virological features and to treatment outcome. RESULTS Patients carrying bAt [CCA] haplotype (p=0.033), ApaI CC genotype (p = 0.033), and TaqI AA genotype (p = 0.037) had a higher HCV load as compared to those with other haplotypes, ApaI CA/AA genotype and TaqI AG genotype, respectively. A sustained virological response (SVR) was achieved in 74 (53%) of the patients. Polymorphisms in VDR gene did not correlate with rapid virological response and SVR achievement. Stepwise logistic regression analysis showed that rs12979860 CC type [odds ratio (OR): 5.56, p=0.007], platelet counts ≥ 15 × 10(10)/L (OR: 4.80, p=0.001), and rapid virological response achievement (OR: 8.36, p<0.001) were independent factors of SVR. CONCLUSION Despite their associations with high hepatitis C virus load, VDR gene polymorphisms are not related to the response to peginterferon plus ribavirin therapy in Asian CHC patients.
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Kitson MT, Sarrazin C, Toniutto P, Roberts SK. Relationship between vitamin D status and response to hepatitis C virus therapy. Hepatology 2015; 62:1642-3. [PMID: 25808060 DOI: 10.1002/hep.27797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Accepted: 02/06/2015] [Indexed: 12/31/2022]
Affiliation(s)
- Matthew T Kitson
- Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia
| | - Christoph Sarrazin
- J. W. Goethe-University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany
| | | | - Stuart K Roberts
- Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia
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Arai T, Atsukawa M, Tsubota A, Kondo C, Shimada N, Abe H, Itokawa N, Nakagawa A, Okubo T, Aizawa Y, Iwakiri K. Vitamin D-related gene polymorphisms do not influence the outcome and serum vitamin D level in pegylated interferon/ribavirin therapy combined with protease inhibitor for patients with genotype 1b chronic hepatitis C. J Med Virol 2015; 87:1904-12. [PMID: 25964133 DOI: 10.1002/jmv.24244] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2015] [Indexed: 12/16/2023]
Abstract
Although several vitamin D-related gene polymorphisms were reported to affect the outcome of pegylated interferon/ribavirin (PR) therapy in chronic hepatitis C patients, there are no reports on the impact of the vitamin D-related gene polymorphisms in PR therapy combined with protease inhibitor (PI). Vitamin D-related gene polymorphisms were determined in 177 genotype 1b-infected chronic hepatitis C patients who received 12 weeks of PR therapy with telaprevir, a first-generation PI, followed by 12 weeks of PR therapy. The sustained virologic response (SVR) rate was 83.1% (147 of 177 patients). The frequencies of vitamin D-related gene polymorphisms were: 83 non-TT and 94 TT genotypes for GC, 97 non-AA and 80 AA genotypes for DHCR7, 151 non-AA and 26 AA genotypes for CYP2R1, 162 non-GG and 15 GG genotypes for CYP27B1, and 105 non-GG and 72 GG genotypes for VDR gene. Multivariate analysis extracted IL28B TT genotype (P = 2.05 × 10(-6)) and serum 25(OH) D3 level (P = 0.024) as independent factors contributing to the achieving of SVR. The SVR rate in IL28B TT genotype patients with serum 25(OH) D3 level of < 25 ng/ml was significantly low compared to other patients. None of the vitamin D-related gene polymorphisms affected the treatment outcome and serum 25(OH) D3 level. In conclusions, the IL28B polymorphism and serum 25(OH) D3 level contributed significantly and independently to SVR in PR combined with PI for genotype 1b-infected chronic hepatitis C patients. However, none of vitamin D-related gene polymorphisms had an impact on the treatment outcome and serum 25(OH) D3 level.
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Affiliation(s)
- Taeang Arai
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Chiba Tokushukai Hospital, Chiba, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Ai Nakagawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Yoshio Aizawa
- Division of Gastroenterology and Hepatology, Jikei University School of Medicine Katsusika Medical Center, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
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Pineda-Tenor D, García-Álvarez M, Jiménez-Sousa MA, Fernández-Rodríguez A, Resino S. Reply: To PMID 24975775. Hepatology 2015; 62:1643. [PMID: 25807876 DOI: 10.1002/hep.27796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Affiliation(s)
- Daniel Pineda-Tenor
- Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Mónica García-Álvarez
- Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - María A Jiménez-Sousa
- Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Viral Infection and Immunity Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
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Coppola N, Pisaturo M, Sagnelli C, Onorato L, Sagnelli E. Role of genetic polymorphisms in hepatitis C virus chronic infection. World J Clin Cases 2015; 3:807-822. [PMID: 26380828 PMCID: PMC4568530 DOI: 10.12998/wjcc.v3.i9.807] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 12/09/2014] [Accepted: 06/08/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC).
METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.
RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation.
CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
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Atsukawa M, Tsubota A, Shimada N, Yoshizawa K, Abe H, Asano T, Ohkubo Y, Araki M, Ikegami T, Kondo C, Itokawa N, Nakagawa A, Arai T, Matsushita Y, Nakatsuka K, Furihata T, Chuganji Y, Matsuzaki Y, Aizawa Y, Iwakiri K. Influencing factors on serum 25-hydroxyvitamin D3 levels in Japanese chronic hepatitis C patients. BMC Infect Dis 2015; 15:344. [PMID: 26286329 PMCID: PMC4543479 DOI: 10.1186/s12879-015-1020-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2015] [Accepted: 07/13/2015] [Indexed: 02/06/2023] Open
Abstract
Background Serum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients. Methods The subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed. Results The cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6–61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7–52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 × 10−8). In multivariate analysis, independent contributors to serum 25-hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 × 10−4, odds ratio = 2.290, 95 % confidence interval = 1.479–3.545), older age (p = 4.30 × 10−4, odds ratio = 1.038, 95 % confidence interval = 1.017–1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095–2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009–1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635–7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117–2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163–4.342). Conclusions Serum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement.
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Affiliation(s)
- Masanori Atsukawa
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, 3-25-8, Minato-ku, Tokyo, Japan.
| | - Noritomo Shimada
- Chiba Tokushukai Hospital, 2-11-1 Takanedai, Funabashi, Chiba, Japan.
| | - Kai Yoshizawa
- Machida Municipal Hospital, 2-15-41 Asahi-cho, Machida, Tokyo, Japan.
| | - Hiroshi Abe
- Jikei University School of Medicine Katsusika Medical Center, 6-41-2 Aoto, Katsushika, Tokyo, Japan.
| | - Toru Asano
- Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Koutoubashi, Sumida, Tokyo, Japan.
| | - Yusuke Ohkubo
- Saiseikai Yokohamashi Tobu Hospital, 3-6-1 shimosueyoshi, Tsurumi, Kanagawa, Japan.
| | - Masahiro Araki
- Ibaraki Central Hospital, Kasama, 6528, Koihuchi, Ibaraki, Japan.
| | - Tadashi Ikegami
- Tokyo Medical University, Ibaraki Medical Center, 3-20-1 amichochuo, Inashiki, Ibaraki, Japan.
| | - Chisa Kondo
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
| | - Norio Itokawa
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
| | - Ai Nakagawa
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
| | - Taeang Arai
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
| | | | | | - Tomomi Furihata
- Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
| | - Yoshimichi Chuganji
- Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Koutoubashi, Sumida, Tokyo, Japan.
| | - Yasushi Matsuzaki
- Tokyo Medical University, Ibaraki Medical Center, 3-20-1 amichochuo, Inashiki, Ibaraki, Japan.
| | - Yoshio Aizawa
- Jikei University School of Medicine Katsusika Medical Center, 6-41-2 Aoto, Katsushika, Tokyo, Japan.
| | - Katsuhiko Iwakiri
- Nippon Medical School Chiba Hokusoh Hospital, 1715, Inzai, Chiba, Japan.
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Fialho A, Fialho A, Kochhar G, Shen B. The presence of primary sclerosing cholangitis in patients with ileal pouch anal- anastomosis is associated with an additional risk for vitamin D deficiency. Gastroenterol Rep (Oxf) 2015; 4:320-324. [PMID: 26290513 PMCID: PMC5193058 DOI: 10.1093/gastro/gov035] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 06/17/2015] [Accepted: 09/15/2015] [Indexed: 12/23/2022] Open
Abstract
Objective: Vitamin D deficiency is common in patients with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Whether vitamin D levels are further lowered in patients with concomitant IPAA and primary sclerosing cholangitis (PSC) is not known. The aim of this study was to evaluate the presence of PSC as a risk factor for vitamin D deficiency in patients with UC and IPAA. Methods: In this case control study, 74 patients with concurrent IPAA and PSC were included in the study group, and 79 patients with IPAA, but without PSC, served as controls. Forty-four variables were analyzed. Univariate analysis and multivariate analysis with stepwise logistic regression were performed. Results: A total 153 eligible patients were included, with 74 (48.4%) in the study group and 79 (51.6%) in the control group. Vitamin D level in the study group was 18.9 ± 1.4 ng/dL compared with 30.3 ± 1.7 ng/d in the control group (P = 0.011). Vitamin D deficiency (≤ 20 ng/dL) was present in 65 (42.5%) patients. PSC occurred in 49 (75.4%) of the 65 patients with vitamin D deficiency. In the multivariate analysis, only the presence of PSC (odds ratio [OR]: 7.56; 95% confidence interval [CI]: 2.39–24.08; P = 0.001) and vitamin D supplementation (OR: 2.58; 95% CI: 1.57–9.19; P = 0.018) remained associated with vitamin D deficiency. Conclusion: The presence of PSC was found to be an independent risk factor for vitamin D deficiency in UC patients with IPAA. These patients should be routinely screened and closely monitored for vitamin D deficiency.
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Affiliation(s)
- Andre Fialho
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA and
| | - Andrea Fialho
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA and
| | - Gursimran Kochhar
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Bo Shen
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH, USA
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40
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Anty R, Canivet CM, Patouraux S, Ferrari-Panaia P, Saint-Paul MC, Huet PM, Lebeaupin C, Iannelli A, Gual P, Tran A. Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis. Alcohol Clin Exp Res 2015; 39:1027-33. [PMID: 25941109 DOI: 10.1111/acer.12728] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 03/10/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Among its pleiotropic effects, vitamin D may protect the liver from fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology in hepatitis C remains unclear, and very few studies including alcoholic patients with liver pathologies have been performed. Here we compared the levels of 25-OH vitamin D in the blood of alcoholic patients with the occurrence of alcoholic steatohepatitis (ASH) or bridging fibrosis. METHODS One hundred and one alcoholic patients were included. All the patients received a liver biopsy, and the levels of 25-OH vitamin D were evaluated with the Liaison 25-OH vitamin D assay. Logistic regression analyses were performed to obtain predictive factors of liver histology. RESULTS Among alcoholic patients, 40.6% presented ASH and 39.6% presented bridging fibrosis. A severe deficiency in 25-OH vitamin D (<10 ng/ml) was seen in 60.4% of patients. This deficiency was frequent in patients with ASH (85.4%) and in those with bridging fibrosis (80%) but was independently associated only with ASH (odds ratio = 8.46 [95% confidence interval 2.05 to 34.89], p = 0.003). CONCLUSIONS In alcoholic patients, a severe deficiency in 25-OH vitamin D was independently associated with the occurrence of ASH.
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Affiliation(s)
- Rodolphe Anty
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France
| | - Clémence M Canivet
- Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France
| | - Stéphanie Patouraux
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France.,Biological Center, Centre Hospitalier Universitaire of Nice, Nice, France
| | | | | | - Pierre-Michel Huet
- Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France
| | - Cynthia Lebeaupin
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France
| | - Antonio Iannelli
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France
| | - Philippe Gual
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France
| | - Albert Tran
- U1065, Team 8, "Hepatic Complications in Obesity", Institut National de la Santé et de la Recherche Médicale (INSERM), Nice, France.,Digestive Center, Centre Hospitalier Universitaire of Nice, Nice, France.,Faculty of Medicine, University of Nice-Sophia-Antipolis, Nice, France
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Yu R, Sun J, Zheng Z, Chen J, Fan R, Liang X, Zhu Y, Liu Y, Shen S, Hou J. Association between vitamin D level and viral load or fibrosis stage in chronic hepatitis B patients from Southern China. J Gastroenterol Hepatol 2015; 30:566-74. [PMID: 25238258 DOI: 10.1111/jgh.12783] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/30/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The role of vitamin D playing in patients with chronic hepatitis C has been intensively studied. However, studies on the potential interaction between vitamin D level and chronic hepatitis B are still limited. This study aimed to explore whether any association existed between serum vitamin D level and liver histology or virological parameters in patients with chronic hepatitis B infection in Southern China. METHODS 25-Hydroxyvitamin D serum levels were determined in a cohort of 242 treatment-naïve chronic hepatitis B patients. Histologic assessment was based on Knodell histologic activity index and Ishak fibrosis staging. Predictors of vitamin D insufficiency were identified using multivariate analysis. RESULTS Mean 25-hydroxyvitamin D value was 33.90 ng/mL. The percentage of patients with different concentration of 25-hydroxyvitamin D (≥ 30 ng/mL, 20-30 ng/mL, < 20 ng/mL) were 59.9%, 31.4%, and 8.7%, respectively. Gender, season, age, and viral genotype were independent predictors of vitamin D insufficiency (< 30 ng/mL). Patients with genotype B virus infection had a lower mean 25-hydroxyvitamin D level (P = 0.023) and higher prevalence of vitamin D insufficiency than those with genotype C (P = 0.021), while no association was found between vitamin D status and viral load. In addition, 25-hydroxyvitamin D level did not significantly vary according to activity grade or fibrosis stage. CONCLUSIONS The prevalence of vitamin D insufficiency is relatively low in our cohort. Patients infected with genotype B had a higher prevalence of vitamin D insufficiency than genotype C. 25-Hydroxyvitamin D serum level is not associated with viral load or fibrosis stage in chronic hepatitis B patients.
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Affiliation(s)
- Rui Yu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response? Int J Hepatol 2015; 2015:617623. [PMID: 26640716 PMCID: PMC4657070 DOI: 10.1155/2015/617623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/23/2015] [Accepted: 10/25/2015] [Indexed: 02/06/2023] Open
Abstract
Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.
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Iruzubieta P, Terán &A, Crespo J, Fábrega E. Vitamin D deficiency in chronic liver disease. World J Hepatol 2014; 6:901-915. [PMID: 25544877 PMCID: PMC4269909 DOI: 10.4254/wjh.v6.i12.901] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/14/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.
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Riva E, Scagnolari C, Turriziani O, Antonelli G. Hepatitis C virus and interferon type III (interferon-λ3/interleukin-28B and interferon-λ4): genetic basis of susceptibility to infection and response to antiviral treatment. Clin Microbiol Infect 2014; 20:1237-45. [PMID: 25273834 DOI: 10.1111/1469-0691.12797] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 08/12/2014] [Accepted: 08/17/2014] [Indexed: 02/06/2023]
Abstract
There has been a significant increase in our understanding of the host genetic determinants of susceptibility to viral infections in recent years. Recently, two single-nucleotide polymorphisms (SNPs), rs12979860 T/C and rs8099917 T/G, upstream of the interleukin (IL)-28B/interferon (IFN)-λ3 gene have been clearly associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Because of their power in predicting the response to IFN/ribavirin therapy, the above SNPs have been used as a diagnostic tool, even though their relevance in the management of HCV infection will be blunt in the era of IFN-free regimens. The recent discovery of a new genetic variant, ss469415590 TT/ΔG, upstream of the IL-28B gene, which generates the novel IFN-λ4 protein, has opened up a new and alternative scenario to understand the functional architecture of type III IFN genomic regions and to improve our knowledge of the pathogenetic mechanism of HCV infection. A role of ss469415590 in predicting responsiveness to antiviral therapy has also been observed in HCV-infected patients receiving direct antiviral agents. The underlying biological mechanism that links the above IL-28B polymorphisms (in both IFN-λ3 and IFN-λ4) to spontaneous and treatment-induced clearance of HCV infection remains to be discovered. Despite this, shedding some light on this issue, which is the main aim of this review, may provide new insights into the general topic of 'host genetics and viral infections'.
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Affiliation(s)
- E Riva
- Department of Integrated Research, Virology Section, University Campus Bio-Medico of Rome, Rome, Italy
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Atsukawa M, Tsubota A, Shimada N, Kondo C, Itokawa N, Nakagawa A, Hashimoto S, Fukuda T, Matsushita Y, Narahara Y, Iwakiri K, Nakatsuka K, Kawamoto C, Sakamoto C. Serum 25-hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load. Hepatol Res 2014; 44:1277-85. [PMID: 24417888 DOI: 10.1111/hepr.12298] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Revised: 12/11/2013] [Accepted: 01/07/2014] [Indexed: 02/08/2023]
Abstract
AIM Much is unknown about the effect of 25-hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus-related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25-hydroxyvitamin D3 , that contribute to a sustained virological response (SVR) in patients with cirrhosis. METHODS We analyzed whether 25-hydroxyvitamin D3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients. RESULTS SVR was achieved in 43 patients. The median 25-hydroxyvitamin D3 level was 20 ng/mL. Univariate analysis showed that the following factors contributed to SVR: low-density lipoprotein cholesterol, albumin, 25-hydroxyvitamin D3 , core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity-determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25-hydroxyvitamin D3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25-hydroxyvitamin D3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and ≥15 ng/mL of 25-hydroxyvitamin D3 , whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15 ng/mL of 25-hydroxyvitamin D3 . The SVR rate was 56.9% in patients with IL28B major genotype and ≥15 ng/mL of 25-hydroxyvitamin D3 . Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15 ng/mL of 25-hydroxyvitamin D3 . CONCLUSION IL28B genotype and 25-hydroxyvitamin D3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25-hydroxyvitamin D3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
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Kitson MT, Sarrazin C, Toniutto P, Eslick GD, Roberts SK. Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: a systematic review and meta-analysis. J Hepatol 2014; 61:1247-52. [PMID: 25135863 DOI: 10.1016/j.jhep.2014.08.004] [Citation(s) in RCA: 32] [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: 06/25/2014] [Revised: 07/30/2014] [Accepted: 08/04/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The baseline 25-hydroxyvitamin D (25[OH]D) level has recently been reported to be an independent predictor of sustained virologic response (SVR) to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. However, studies have yielded inconsistent results. Thus, we conducted a systematic review and meta-analysis to clarify any association between baseline 25(OH)D level and SVR in HCV therapy. METHODS Two reviewers searched four electronic databases (Medline, Embase, PubMed, and Cochrane trials register) and relevant international conference proceedings up to March 2014 for studies treating chronic HCV infection with PEG-IFN plus RBV where baseline 25(OH)D level was tested. Studies involving patients with HIV co-infection, previous liver transplantation or those receiving vitamin D supplementation were excluded. The mean baseline 25(OH)D level was compared between those who achieved and those who failed to achieve SVR. Pooled standard difference in mean 25(OH)D level, odds ratios (OR) and 95% confidence intervals (CI) were calculated with the Comprehensive Meta-Analysis software (version 2.0) using a random effects model. RESULTS 11 studies comprising 2605 patients were included in the meta-analysis. There was no significant association between the baseline mean 25(OH)D level and SVR (OR 1.44, 95% CI 0.92-2.26; p=0.11), either in patients infected with genotypes 1/4/5 (OR 1.48, 95% CI 0.94-2.34; p=0.09) or genotypes 2/3 (OR 1.51, 95% CI 0.26-8.87; p=0.65). CONCLUSIONS The baseline 25(OH)D level is not associated with SVR to PEG-IFN plus RBV therapy in chronic HCV infection, regardless of genotype. Any effect of vitamin D supplementation on SVR is yet to be definitively determined.
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Affiliation(s)
- Matthew T Kitson
- Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; Department of Gastroenterology, Monash University, Melbourne, Australia
| | - Christoph Sarrazin
- Department of Gastroenterology & Hepatology, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany
| | | | - Guy D Eslick
- Department of Surgery, University of Sydney, Sydney, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; Department of Gastroenterology, Monash University, Melbourne, Australia.
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Imawari M. Does vitamin D supplementation improve sustained virological response in cirrhotic patients with hepatitis C virus genotype 1b and high viral load? Hepatol Res 2014; 44:1265-7. [PMID: 25409555 DOI: 10.1111/hepr.12328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Michio Imawari
- Institute for Gastrointestinal and Liver Diseases, Shin-yurigaoka General Hospital, Kawasaki, Kanagawa, Japan
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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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Atsukawa M, Tsubota A, Shimada N, Abe H, Kondo C, Itokawa N, Nakagawa A, Iwakiri K, Kawamoto C, Aizawa Y, Sakamoto C. Serum 25(OH)D3 levels affect treatment outcomes for telaprevir/peg-interferon/ribavirin combination therapy in genotype 1b chronic hepatitis C. Dig Liver Dis 2014; 46:738-43. [PMID: 24880716 DOI: 10.1016/j.dld.2014.05.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/26/2014] [Accepted: 05/01/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Close relationships between chronic hepatitis C and vitamin D levels have been reported. For genotype 1b infection, the current standard of care is pegylated interferon/ribavirin therapy combined with a protease inhibitor. The present study analyzed the relationship between outcomes of triple therapy and serum 25(OH)D3 levels. METHODS Factors contributing to sustained virological response were investigated in 177 patients with chronic hepatitis C who received telaprevir-based triple therapy in this prospective study. RESULTS The sustained virological response rate was 86.9% in patients with 25(OH)D3 levels of >18 ng/ml; this was higher than the 66.7% in patients with 25(OH)D3 levels of ≤ 18 ng/ml (P=0.003). 25(OH)D3 levels and IL28B genotype were identified as significantly independent factors contributing to sustained virological response. The sustained virological response rate did not differ according to 25(OH)D3 levels in patients with the IL28B major genotype. The sustained virological response rate was 64.9% in patients with the IL28B minor genotype and 25(OH)D3 levels of >18 ng/ml, and was 38.5% in those with decreased 25(OH)D3 levels (P=0.045). CONCLUSIONS In triple therapy, 25(OH)D3 levels were an independent factor contributing to sustained virological response. Of particular note, the sustained virological response rate was significantly lower in patients with the IL28B minor genotype.
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Affiliation(s)
- Masanori Atsukawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
| | - Akihito Tsubota
- Institute of Clinical Medicine and Research (ICMR), Jikei University School of Medicine, Kashiwa, Chiba, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo, Chiba, Japan
| | - Hiroshi Abe
- Jikei University School of Medicine Katsusika Medical Center, Division of Gastroenterology and Hepatology, Katsushika-ku, Tokyo, Japan
| | - Chisa Kondo
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Norio Itokawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Ai Nakagawa
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan
| | - Chiaki Kawamoto
- Nippon Medical School, Division of Gastroenterology and Hepatology, Bunkyo-ku, Tokyo, Japan
| | - Yoshio Aizawa
- Jikei University School of Medicine Katsusika Medical Center, Division of Gastroenterology and Hepatology, Katsushika-ku, Tokyo, Japan
| | - Choitsu Sakamoto
- Nippon Medical School, Division of Gastroenterology and Hepatology, Bunkyo-ku, Tokyo, Japan
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Gerova DI, Galunska BT, Ivanova II, Kotzev IA, Tchervenkov TG, Balev SP, Svinarov DA. Prevalence of vitamin D deficiency and insufficiency in Bulgarian patients with chronic hepatitis C viral infection. Scandinavian Journal of Clinical and Laboratory Investigation 2014; 74:665-72. [PMID: 25005344 DOI: 10.3109/00365513.2014.930710] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
AIMS The present pilot study aimed to determine vitamin D status in Bulgarian patients with chronic HCV infection in respect to the severity of liver disease and response to interferon-ribavirin therapy. METHODS The study encompassed 296 patients: 161 males (54.4%) aged 42.08 ± 14.87 years, 135 females (45.6%) aged 45.72 ± 14.34 years, 86.5% of them infected with HCV genotype 1. Total 25-hydroxyvitamin-D (25OHD) was determined by liquid chromatography/tandem-mass spectrometric detection. RESULTS The median 25OHD level of the studied cohort was 50.40 nmol/L (range: 29.6-71.05). 25OHD deficient (< 25 nmol/L) were 16% of patients, 33% showed profound insufficiency (25-50 nmol/L), another 33% were in the range 50-80 nmol/L (mild insufficiency), the rest 18% were 25OHD sufficient. Significantly lower 25OHD levels were registered in cases with advanced fibrosis compared to those with mild or absent fibrosis (37.10 nmol/L vs. 53.00 nmol/L, respectively, p < 0.05). This association remained unchanged by seasonal variations in 25OHD levels. Inverse relationship was found between 25OHD and HCV-RNA (p < 0.01). Patients with sustained virological response to therapy had significantly higher 25OHD levels, compared to patients who failed to achieve viral eradication (56.90 nmol/L vs. 45.00 nmol/L, p = 0.012). CONCLUSION More than 80% of HCV-infected patients were vitamin D-deficient and -insufficient. The inverse relationship between 25OHD levels and viral load, liver fibrosis and treatment outcomes supports the hypothesis that improvement of vitamin D status may have considerable potential to amend the host defense against HCV infection and response to therapy.
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Affiliation(s)
- Daniela Ivanova Gerova
- Department of Clinical Laboratory, Medical University - Varna "Prof. Dr. Paraskev Stoyanov" , Varna , Bulgaria
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