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Lin SH, Wang CC, Huang KT, Chen KD, Hsu LW, Eng HL, Chiu KW. Liver Graft Pathology and Low Serum 25-Hydroxyvitamin D after Living Donor Liver Transplantation. Metabolites 2022; 12:388. [PMID: 35629892 PMCID: PMC9147938 DOI: 10.3390/metabo12050388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/22/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Most cases of advanced liver diseases are associated with low serum 25-hydroxyvitamin D and vitamin D deficiency. This phenomenon may occur in living donor liver transplantation (LDLT). AIMS We conducted this study to explore the interplay between VDR and CYP2R1 in liver graft and compared our findings with the pathological interpretation of serum 25(OH)D concentration. METHODS In total, 60 patients received liver graft biopsy after LDLT and were separated (1:1) into two groups: graft rejection group and graft non-rejection group. We extracted both of the recipients' and donors' serum DNA to investigate the vitamin D receptor (VDR) rs2228530 and CYP2R1 rs10741657 single nucleotide polymorphisms (SNPs) using real-time polymerase chain reaction. We also extracted DNA from liver graft tissues to explore the genetic alleles of VDR rs2228530 and CYP2R1 rs10741657 after LDLT. Serum biochemistry profile and 25(OH)D concentrations were measured before and after LDLT. RESULTS There were no significant differences in serum VDR rs2228530 and CYP2R1 rs10741657 genetic alleles between recipients and donors. The percentage of genetic modification was 33.4% (10/30) for the rejection and non-rejection groups in VDR rs2228530, and 66.7% (20/30) for both groups in CYP2R1 rs10741657. Serum 25(OH)D concentrations were significantly lower after LDLT D30 than that before LDLT in the rejection (p = 0.0001) and non-rejection graft pathology (p = 0.0017) groups. CONCLUSIONS The presence of low serum 25(OH)D concentrations after LDLT suggested that post-transplant low serum 25(OH)D concentrations may develop with the homogenous phenomenon of VDR rs2228530 and CYP2R1 rs10741657 genetic modifications in recipients regardless of graft pathology.
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Affiliation(s)
- Shu-Hsien Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
| | - Chih-Chi Wang
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;
| | - Kuang-Tzu Huang
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Kuang-Den Chen
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Li-Wen Hsu
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - Hock-Liew Eng
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
| | - King-Wah Chiu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; (K.-T.H.); (K.-D.C.); (L.-W.H.)
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan;
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LIN S, WANG W, SHI L, YANG X, CHEN Y, LIU X, LI J, YE F, AN X, ZHANG X. Severe Vitamin D Deficiency Is Strongly Associated with Liver Dysfunction and Disease Severity in Hepatitis B Virus Related Cirrhosis and Liver Failure Patients. J Nutr Sci Vitaminol (Tokyo) 2022; 68:16-22. [DOI: 10.3177/jnsv.68.16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Shumei LIN
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Wen WANG
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Lei SHI
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Xueliang YANG
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Yunru CHEN
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Xiaojing LIU
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Jianzhou LI
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Feng YE
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Xiaocui AN
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
| | - Xi ZHANG
- Department of Infectious Diseases, First Affiliated Hospital of Xi’an Jiaotong University
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Ali ME, Halby HM, Ali MY, Hassan EA, El-Mokhtar MA, Sayed IM, Thabet MM, Fouad M, El-Ashmawy AM, Mahran ZG. Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents. Viruses 2021; 13:2008. [PMID: 34696438 PMCID: PMC8539757 DOI: 10.3390/v13102008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 09/17/2021] [Accepted: 09/25/2021] [Indexed: 12/12/2022] Open
Abstract
Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.
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Affiliation(s)
- Mohamed E. Ali
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Hamada M. Halby
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Mamdouh Yones Ali
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Elham Ahmed Hassan
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Mohamed A. El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; (M.A.E.-M.); (I.M.S.)
| | - Ibrahim M. Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; (M.A.E.-M.); (I.M.S.)
| | - Marwa M. Thabet
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Magdy Fouad
- Hepato-Gastroenterology Unit, Tropical Medicine Department, Faculty of Medicine, El-Minia University, Minya 61519, Egypt;
| | - Ahmed M. El-Ashmawy
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Zainab Gaber Mahran
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
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Handgrip Strength and Vitamin D as Predictors of Liver Fibrosis and Malnutrition in Chronic Hepatitis C Patients. DISEASE MARKERS 2021; 2021:6665893. [PMID: 33884041 PMCID: PMC8041557 DOI: 10.1155/2021/6665893] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 03/15/2021] [Accepted: 03/22/2021] [Indexed: 02/06/2023]
Abstract
Background In patients with chronic hepatitis C (CHC), a negative impact of associated malnutrition on both morbidity and mortality was reported. We aimed to elucidate the efficacy of serum liver fibrosis markers (fibronectin (FN), hydroxyproline (Hyp), and hyaluronic acid (HA)) and their respective indices (HA index, Hyp index, and FN index) and vitamin D status in predicting malnutrition associated with liver fibrosis in CHC patients and to investigate their association with the value of current clinical malnutrition assessment tools subjective global assessment (SGA), handgrip strength (HGS), and muscle mass scores (SGA, BMI, MAMC, and HGS). Materials and Methods A cross-sectional study was conducted on 80 patients aged 40-60 years with proven viremia, HCV antibodies, HCV-RNA positivity, genotype determinations, and established chronic hepatitis C virus for more than 6 years and 80 control subjects. SGA, HGS, and muscle mass score (MAMC) were estimated in both patients and control subjects. Based on SGA scores, CHC patients were classified into three groups: well nourished (n = 12; SGA-A); mild or moderately malnourished (n = 25; SGA-B); and severely malnourished (n = 43; SGA-C). Liver fibrosis markers, inflammatory indicator α-Fetoprotein (AFP), tumor necrosis factor-alpha (TNF-α), 25-hydroxyvitamin D, and PTH were estimated using immunoassay techniques. Results CHC patients with moderate and severe malnutrition SGA scores showed a significant decline in the levels of vitamin D, increased PTH, and lower values of HGS and muscle mass indices compared to well-nourished patients and control subjects. In addition, malnutrition, vitamin D deficiency, and lower values of HGS, MAC, TSF, and MAMC showed significant correlation with liver severity among CHC patients. Liver fibrosis markers Hyp, HA, FN, APRI, HypI, HAI, and FNI as noninvasive biomarkers showed significant correlation with both severity of liver diseases and associated malnutrition, especially in cirrhotic HCV patients (F4) compared to those with significant fibrosis (F2-F3). Conclusion The results showed that deficiency in vitamin D levels, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) could be used as markers of liver pathogenicity in patients with CHC. In addition, the study concluded that noninvasive biomarkers Hyp, HA, FN, APRI, HypI, HAI, and FNI separately or in association with vitamin D status, HGS, SGA, and muscle mass scores (MAC, MAMC, or TSF) were significantly associated with an incidence of malnutrition between ~70.5% and 89.6% of CHC patients with significant fibrosis and cirrhosis.
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Sriphoosanaphan S, Thanapirom K, Kerr SJ, Suksawatamnuay S, Thaimai P, Sittisomwong S, Sonsiri K, Srisoonthorn N, Teeratorn N, Tanpowpong N, Chaopathomkul B, Treeprasertsuk S, Poovorawan Y, Komolmit P. Effect of vitamin D supplementation in patients with chronic hepatitis C after direct-acting antiviral treatment: a randomized, double-blind, placebo-controlled trial. PeerJ 2021; 9:e10709. [PMID: 33614272 PMCID: PMC7879942 DOI: 10.7717/peerj.10709] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/15/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Replacement of vitamin D (VD) among patients with chronic hepatitis C (CHC) before viral eradication has demonstrated a protective effect on serum markers associated with hepatic fibrogenesis. We therefore hypothesized that VD may facilitate further fibrosis amelioration following curative treatment with direct-acting antivirals (DAA). METHODS This study was a randomized, double-blind, placebo-controlled trial conducted between February 2018 and August 2018. Patients with CHC and VD deficiency were randomized in a 1:1 ratio to either receive ergicalciferol or placebo over 6 weeks. Biochemical analysis indicators, including 25-hydroxyvitamin D (25(OH)D), fibrogenic markers [(transforming growth factor beta 1 (TGF-β1) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1)], and fibrolytic markers [matrix metalloproteinase 9 (MMP-9) and amino terminal type III procollagen peptide (P3NP)], were assessed at baseline and at 6 weeks. Serum 25(OH)D was analyzed by a chemiluminescence immunoassay. Serum hepatic fibrogenesis markers were measured using a quantitative sandwich enzyme-linked immunosorbent assay. RESULTS Seventy-five patients with CHC and VD deficiency were randomly assigned to VD (n = 37) and placebo (n = 38) groups. At the end of the study, the mean serum 25(OH)D level had risen to a normal level in the VD group, but was still deficient in the placebo group (41.8 ± 9.1 vs. 18.1 ± 4.6 ng/mL, p < 0.001). Upon restoration of the VD level, there were no significant mean differences in the change from baseline for TGF-β1 (-0.6 ng/mL (95% confidence interval (95% CI) [-2.8-1.7]), p = 0.63), TIMP-1 (-5.5 ng/mL (95% CI [-26.4 -15.3]), p = 0.60), MMP-9 (122.9 ng/mL (95% CI [-69.0 -314.8]), p = 0.21), and P3NP (-0.1 ng/mL (95% CI [-2.4 -2.2]), p = 0.92) between the VD and placebo groups. CONCLUSION Short-term VD supplementation after DAA treatment in patients with CHC does not improve serum fibrogenesis markers and may not expedite the residual liver fibrosis healing process. Future studies are warranted to evaluate the long-term effect of VD supplementation on hepatic fibrosis regression.
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Affiliation(s)
- Supachaya Sriphoosanaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, Thai Red Cross, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, Thai Red Cross, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Stephen J. Kerr
- Biostatistics Excellence Center, Department of Research Affairs, Chulalongkorn University, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, Thai Red Cross, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sukanya Sittisomwong
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Kanokwan Sonsiri
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nunthiya Srisoonthorn
- Center of Excellence in Liver Diseases, Thai Red Cross, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Nicha Teeratorn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Bundit Chaopathomkul
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence in Liver Diseases, Thai Red Cross, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
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Jeong JY, Jun DW, Park SJ, Sohn JH, Kim SG, Lee SW, Jeong SW, Kim MY, Kim W, Shim JJ, Kim HS, Suk KT, Ahn SB. Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study. Korean J Intern Med 2020; 35:1074-1083. [PMID: 31710801 PMCID: PMC7487303 DOI: 10.3904/kjim.2018.273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 11/05/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.
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Affiliation(s)
- Jae Yoon Jeong
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Seoul, Korea
- Correspondence to Dae Won Jun, M.D. Department of Internal Medicine, Hanyang University College of Medicine, 222-1 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea. Tel: +82-2-2290-8338, Fax: +82-2-972-0068, E-mail:
| | - Sol Ji Park
- Department of Clinical Pharmacology, Sungkyunkwan University, Seoul, Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Se Whan Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jae-Jun Shim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Hyoung Su Kim
- Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Eulji University School of Medicine, Seoul, Korea
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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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Gupta S, Read SA, Shackel NA, Hebbard L, George J, Ahlenstiel G. The Role of Micronutrients in the Infection and Subsequent Response to Hepatitis C Virus. Cells 2019; 8:E603. [PMID: 31212984 PMCID: PMC6627053 DOI: 10.3390/cells8060603] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 06/13/2019] [Indexed: 12/13/2022] Open
Abstract
Micronutrient deficiencies develop for a variety of reasons, whether geographic, socioeconomic, nutritional, or as a result of disease pathologies such as chronic viral infection. As micronutrients are essential for a strong immune response, deficiencies can significantly dampen both the innate and the adaptive arms of antiviral immunity. The innate immune response in particular is crucial to protect against hepatitis C virus (HCV), a hepatotropic virus that maintains chronic infection in up to 80% of individuals if left untreated. While many micronutrients are required for HCV replication, an overlapping group of micronutrients are also necessary to enact a potent immune response. As the liver is responsible for the storage and metabolism of many micronutrients, HCV persistence can influence the micronutrients' steady state to benefit viral persistence both directly and by weakening the antiviral response. This review will focus on common micronutrients such as zinc, iron, copper, selenium, vitamin A, vitamin B12, vitamin D and vitamin E. We will explore their role in the pathogenesis of HCV infection and in the response to antiviral therapy. While chronic hepatitis C virus infection drives deficiencies in micronutrients such as zinc, selenium, vitamin A and B12, it also stimulates copper and iron excess; these micronutrients influence antioxidant, inflammatory and immune responses to HCV.
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Affiliation(s)
- Sunil Gupta
- Blacktown Clinical School, Western Sydney University, Blacktown, NSW 2148, Australia.
| | - Scott A Read
- Blacktown Clinical School, Western Sydney University, Blacktown, NSW 2148, Australia.
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, Australia.
| | - Nicholas A Shackel
- Department of Medicine, University of New South Wales, Kensington, NSW 2052, Australia.
| | - Lionel Hebbard
- Department of Molecular and Cell Biology, Centre for Molecular Therapeutics, James Cook University, Australian Institute of Tropical Health and Medicine, Townsville, QLD 4814, Australia.
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, Australia.
| | - Golo Ahlenstiel
- Blacktown Clinical School, Western Sydney University, Blacktown, NSW 2148, Australia.
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead 2145, Australia.
- Department of Medicine, Blacktown Hospital, Blacktown, NSW 2148, Australia.
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9
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Konstantinides P, Alexopoulou A, Hadziyannis E, Kanellopoulou T, Dourakis SP. Interleukin-17A and B-cell activating factor in chronic hepatitis C patients with or without asymptomatic mixed cryoglobulinemia: effects of antiviral treatment and correlations with vitamin D. Ann Gastroenterol 2018; 31:705-711. [PMID: 30386121 PMCID: PMC6191865 DOI: 10.20524/aog.2018.0310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 08/23/2018] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Several studies have provided conflicting results regarding the immune responses in chronic hepatitis C (CHC) patients with mixed cryoglobulinemia (MC). The importance of B-cell activating factor (BAFF) in MC has been described, but the role of interleukin (IL)-17A is less clear. METHODS Serum concentrations of IL-17A, BAFF and 25-OH vitamin D were measured in CHC patients at baseline, end of treatment, and 6 months post-treatment with pegylated interferon-α and ribavirin, versus 12 healthy controls. RESULTS Thirty-four patients (20 male, mean age 40.7±9.2 years, 12 of genotype 1 or 4, 22 of genotype 2 or 3) were included, of whom 64.7% achieved a sustained virological response (SVR). MC was detected in 52.9% of the patients. Higher levels of both cytokines were found in patients with MC compared to those without. Patients who achieved SVR had higher pretreatment IL-17A and lower BAFF levels compared to those without SVR. IL-17A was downregulated during and following treatment in responders, whereas upregulation was observed in non-responders. CHC patients demonstrated low vitamin D levels compared to HC. Moreover, the changes in IL-17A over the treatment period were significantly associated with vitamin D changes (β=-0.04, SE=0.02, P=0.046). No difference in IL-17A, BAFF and vitamin D values was seen between patients with cirrhosis (n=14) and those without. CONCLUSIONS CHC patients with asymptomatic MC have increased levels of IL-17A and BAFF. IL-17A levels decline significantly while BAFF increases during treatment in responders. An interplay between IL-17A and vitamin D concentrations was revealed during the antiviral treatment.
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Affiliation(s)
- Polydoros Konstantinides
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Theoni Kanellopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Spyridon P. Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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Gayam V, Mandal AK, Khalid M, Mukhtar O, Gill A, Garlapati P, Tiongson B, Sherigar J, Mansour M, Mohanty S. Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study. Gastroenterology Res 2018; 11:309-316. [PMID: 30116431 PMCID: PMC6089592 DOI: 10.14740/gr1072w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 07/23/2018] [Indexed: 12/11/2022] Open
Abstract
Background Low serum vitamin D levels in chronic hepatitis C (CHC) is associated with advanced liver fibrosis; and there remains an imprecise relationship with the treatment response based on the vitamin D levels. Previous studies have shown conflicting results on the vitamin D levels, and association with treatment response in CHC treated with interferon-based regimens. Methods Patients with CHC treated with direct-acting antivirals (DAAs) between January 2016 and December 2017 in the community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in CHC patients with deficient, insufficient, and normal levels of vitamin D measured before the initiation of DAA therapy. Results Two hundred and ninety-one patients were included in the study. Direct-acting antivirals included in the study were ledipasvir/sofosbuvir ± ribavirin, ombitasvir + paritaprevir + ritonavir + dasabuvir ± ribavirin, and sofosbuvir/velpatasvir. An overall sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12 rates among patients with vitamin D deficiency, vitamin D insufficiency and normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not statically significant (P = 0.214). A total of 71 patients were cirrhotic. The prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20 ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this, pretreatment vitamin D levels did not show any impact on the virologic response. The most common adverse effect observed was fatigue. None of the patients had to discontinue the treatment due to adverse events. Conclusions DAAs are safe and effective with a high overall SVR 12 in CHC and treatment response does not depend on the pretreatment vitamin D levels. The prevalence of both vitamin D insufficiency and deficiency was observed to be higher in cirrhotic cohorts compared to non-cirrhotic counterparts.
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Affiliation(s)
- Vijay Gayam
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Amrendra Kumar Mandal
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Mazin Khalid
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Osama Mukhtar
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Arshpal Gill
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Pavani Garlapati
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Benjamin Tiongson
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Jagannath Sherigar
- Department of Medicine and Division of Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, 506, 6th St, Brooklyn, NY 11215, USA
| | - Mohammed Mansour
- Department of Medicine and Gastroenterology, Interfaith Medical Center, 1545 Atlantic Avenue. Brooklyn, NY 11213, USA
| | - Smruti Mohanty
- Department of Medicine and Division of Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, 506, 6th St, Brooklyn, NY 11215, USA
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11
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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: 38] [Impact Index Per Article: 5.4] [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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