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Patel S, Bull L, Salimi K, Shui AM, Siao K, Yang B, Maher JJ, Khalili M. Exploring the impact of graded alcohol use on atherogenic lipid profiles among Latinos with underlying chronic liver disease. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2025; 49:792-803. [PMID: 40022301 DOI: 10.1111/acer.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 01/31/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND Alcohol use and hepatitis C virus (HCV) often coexist and are associated with cardiovascular disease. One of the underlying drivers is dyslipidemia. We assessed lipid and lipoprotein levels and the relationship between alcohol use and atherogenic lipid profiles, specifically small dense low-density lipoprotein cholesterol (sdLDL-C), in Latinos with and without HCV. METHODS From June 1, 2002, to January 1, 2016, 150 Latino adults underwent demographic, clinical, metabolic, lipid/lipoprotein, and genetic evaluations. Linear regression (adjusted for age, sex, and recent alcohol use) assessed factors associated with sdLDL-C. RESULTS Participant characteristics were as follows: median age 44 years, 64% male, 39% HCV+, and alcohol use in the last 12 months was 19% heavy and 47% moderate. Ancestries were as follows: 52% European, 40% Native American (NA), and 4.3% African. 29% had non-CC PNPLA3, 89% non-CC TM6SF2, and 73% non-CC IL-28b genotypes. High-density lipoprotein (HDL) cholesterol, HDL-3, apolipoprotein A-1, and lipoprotein-associated phospholipase A2 levels differed by alcohol use groups (p < 0.05). On multivariable analysis, female sex (est. -6.08, p < 0.001), HCV+ status (est. -8.49, p < 0.001), and heavy alcohol use (vs. none) (est. -4.32, p = 0.03) were associated with lower, while NA ancestry (est. 0.92; p = 0.01) and adipose tissue insulin resistance (est. 3.30, p < 0.001) were associated with higher sdLDL-C levels. The positive association between NA ancestry and sdLDL-C was dampened by the presence of a non-CC IL28b genotype (interaction est. -1.95, p = 0.01). CONCLUSIONS In this Latino cohort, ancestry and metabolic dysfunction, independent of alcohol use and HCV, were associated with atherogenic risk. In addition to HCV treatment in this population, cardiometabolic health should be optimized.
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Affiliation(s)
- Shyam Patel
- Department of Medicine, California Pacific Medical Center, San Francisco, California, USA
| | - Laura Bull
- Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
- UCSF Liver Center, University of California, San Francisco, San Francisco, California, USA
| | - Kian Salimi
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Amy M Shui
- UCSF Liver Center, University of California, San Francisco, San Francisco, California, USA
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
| | - Kevin Siao
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
- UCSF Liver Center, University of California, San Francisco, San Francisco, California, USA
| | - Bokun Yang
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Jacquelyn J Maher
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
- UCSF Liver Center, University of California, San Francisco, San Francisco, California, USA
| | - Mandana Khalili
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
- UCSF Liver Center, University of California, San Francisco, San Francisco, California, USA
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Mladenova IL, Tan EF, Ng JY, Sharma P. Non-alcoholic fatty liver disease (NAFLD) and its association to cardiovascular disease: A comprehensive meta-analysis. JRSM Cardiovasc Dis 2025; 14:20480040251325929. [PMID: 40123646 PMCID: PMC11930486 DOI: 10.1177/20480040251325929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 03/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction. Methods We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis. Results We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)]. Conclusion NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.
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Affiliation(s)
| | - Eu Fon Tan
- Queen Mary University of London, London, UK
| | | | - Pankaj Sharma
- Institute of Cardiovascular Research, Royal Holloway University, Egham, Greater London, UK
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Wang HW, Wang YC, Huang YT, Jiang MY. All-cause and cause-specific mortality risk among men and women with hepatitis C virus infection. PLoS One 2024; 19:e0309819. [PMID: 39250481 PMCID: PMC11383219 DOI: 10.1371/journal.pone.0309819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 08/19/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection affects men and women differently, yet few studies have investigated sex differences in long-term mortality risk among the HCV-infected population. We conducted a population-based study to elucidate all-cause and cause-specific mortality among men and women with HCV infection. METHODS The study population consisted of adult participants from the 1999-2018 National Health and Nutrition Examination Survey, including 945 HCV-infected and 44,637 non-HCV-infected individuals. HCV infection was defined as either HCV seropositivity or detectable HCV RNA. Participants were followed until the date of death or December 31, 2019, to determine survival status. RESULTS The HCV-infected population, both male and female, tended to be older, more likely to be Black, single, have lower income, lower BMI, higher prevalence of hypertension, and were more likely to be current smokers. During a median follow-up of 125.0 months, a total of 5,309 participants died, including 1,253 deaths from cardiovascular disease (CVD) and 1,319 deaths from cancer. The crude analysis showed that the risk of death from all causes and from cancer, but not from CVD, was higher in the HCV-infected population. After adjusting for potential confounders, we found that both HCV-infected men (HR 1.41, 95% CI 1.10-1.81) and women (HR 2.03, 95% CI 1.36-3.02) were equally at increased risk of all-cause mortality compared to their non-HCV infected counterparts (p for interaction > 0.05). The risk of cancer-related mortality was significantly increased in HCV-infected women (HR 2.14, 95% CI 1.01-4.53), but not in men, compared to non-HCV-infected counterparts. Among HCV-infected population, there was no difference in the risks of all-cause, CVD-related, or cancer-related death between men and women. CONCLUSION Both men and women with HCV infection had an increased risk of death from all causes compared to their non-HCV infected counterparts, but we did not observe a significant sex difference.
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Affiliation(s)
- Hung-Wei Wang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Hospital Chiali, Tainan, Taiwan
| | - Yen-Chung Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Hospital Liouying, Tainan, Taiwan
| | - Yun-Ting Huang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Yan Jiang
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Pharmacy, Chia Nan University of Pharmacy & Science, Tainan, Taiwan
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Abosheaishaa H, Nassar M, Abdelhalim O, Bahbah AA, Abbas S, Morsi SM, Ghallab M, Alagha Z, Omran A, Elfert K, Bandaru P, Forlemu AN, Reddy M. Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:592-607. [PMID: 38489662 DOI: 10.1097/meg.0000000000002721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND OBJECTIVE Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. METHODOLOGY Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. RESULTS No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. CONCLUSION This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.
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Affiliation(s)
- Hazem Abosheaishaa
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | - Mahmoud Nassar
- University at Buffalo School of Medicine and Biomedical Sciences, New York, USA
| | - Omar Abdelhalim
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | | | - Sharif Abbas
- Koc University School of Medicine, Istanbul, Turkey
| | - Samah M Morsi
- John's Hopkins School of Medicine, Department of Radiology, Duke University, Department of Radiology
| | - Muhammad Ghallab
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | - Zakaria Alagha
- Marshall University, Joan Edward School of Medicine, West Virginia, New York, USA
| | - Ahmed Omran
- Trinitas Regional Medical Center|RWJBH, Lindon
| | | | - Praneeth Bandaru
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, New York, USA
| | | | - Madhavi Reddy
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
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Wu D, Xiong F, Ran Q, Liu J, Wu Q, Wang L, Lv W. Mendelian randomization of chronic hepatitis B and cardiovascular disease. Front Cardiovasc Med 2024; 11:1332557. [PMID: 38559670 PMCID: PMC10978653 DOI: 10.3389/fcvm.2024.1332557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 03/01/2024] [Indexed: 04/04/2024] Open
Abstract
Background Evidence from observational studies suggests that chronic hepatitis B (CHB) is associated with cardiovascular disease (CVD). However, results have been inconsistent and causality remains to be established. We utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between CHB and CVD, including atherosclerosis, coronary heart disease, hypertension, and ischemic stroke. Methods The analysis was conducted through genome-wide association studies (GWAS), considering chronic hepatitis B as the exposure and cardiovascular disease as the endpoint. The primary method for evaluating causality in this analysis was the inverse-variance weighted (IVW) technique. Additionally, we employed the weighted median, MR-Egger regression, weighted mode, and simple mode methods for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multiple effects analyses were conducted. Results In a random-effects IVW analysis, we found that genetic susceptibility to chronic hepatitis B was associated with an increased risk of atherosclerosis [OR = 1.048, 95% CI (1.022-1.075), P = 3.08E-04], as well as an increased risk of coronary heart disease [OR = 1.039, 95% CI (1.006-1.072), P = 0.020]. However, it was found to be inversely correlated with ischemic stroke risk [OR = 0.972, 95% CI (0.957-0.988), P = 4.13E-04]. There was no evidence that chronic hepatitis B was associated with hypertension [OR = 1.021, 95% CI (0.994-1.049), P = 0.121]. Conclusion Our research indicates that chronic hepatitis B has a correlation with an elevated risk of developing atherosclerosis and coronary heart disease, while it is associated with a decreased risk of experiencing an ischemic stroke.
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Affiliation(s)
- Dongjie Wu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Feiyang Xiong
- Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Qingzhi Ran
- Department of Cardiovascular Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Jing Liu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Qingjuan Wu
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Liang Wang
- Beijing Century Forum Hospital, Capital Medical University, Beijing, China
| | - Wenliang Lv
- Department of Infectious Diseases, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
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Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact. Biomedicines 2023; 11:biomedicines11020271. [PMID: 36830808 PMCID: PMC9953247 DOI: 10.3390/biomedicines11020271] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.
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Xiao J, Ng CH, Chin YH, Tan DJH, Lim WH, Lim G, Quek J, Tang ASP, Chan KE, Soong RY, Chew N, Tay B, Huang DQ, Tamaki N, Foo R, Chan MY, Noureddin M, Siddiqui MS, Sanyal AJ, Muthiah MD. A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia. J Clin Transl Hepatol 2022; 10:1042-1049. [PMID: 36381095 PMCID: PMC9634784 DOI: 10.14218/jcth.2022.00095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/13/2022] [Accepted: 05/04/2022] [Indexed: 12/04/2022] Open
Abstract
Background and Aims Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation. Methods Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups: (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA). Results Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: -0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: -0.46, Crl: -0.49 to -0.43), bile acids (MD: -0.22, Crl: -0.35 to -0.09), and inflammation (MD: -0.08, Crl: -0.13 to -0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: -1.27, Crl: -1.76 to -0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: -1.03, Crl: -1.09 to -0.97) and energy (MD: -0.37, Crl: -0.39 to -0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids. Conclusions Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.
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Affiliation(s)
- Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cheng-Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yip-Han Chin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen-Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Grace Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kai-En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Rou-Yi Soong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Center, National University Hospital, Singapore
| | - Benjamin Tay
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Daniel Q. Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore
| | - Nobuharu Tamaki
- NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla, CA, USA
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Roger Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Center, National University Hospital, Singapore
| | - Mark Y. Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Center, National University Hospital, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark D. Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
- National University Center for Organ Transplantation, National University Health System, Singapore
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Zhang GH, Yuan TH, Yue ZS, Wang L, Dou GR. The presence of diabetic retinopathy closely associated with the progression of non-alcoholic fatty liver disease: A meta-analysis of observational studies. Front Mol Biosci 2022; 9:1019899. [PMID: 36458094 PMCID: PMC9706004 DOI: 10.3389/fmolb.2022.1019899] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/01/2022] [Indexed: 07/30/2023] Open
Abstract
Background and Objective: Although growing evidence indicates that non-alcoholic fatty liver disease is related to diabetic retinopathy (DR), research results significantly vary. Therefore, we conducted a meta-analysis to assess the association between the progression of non-alcoholic fatty liver disease and the onset of DR. Methods: PubMed, Embase, and Cochrane databases were searched until 7 November 2021. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Results: We identified 18 studies involving 12,757 patients. The pooled effect assessment showed that liver fibrosis was positively correlated with DR (OR = 1.69, 95%CI 1.30-2.20; p < 0.0001); non-alcoholic fatty liver disease was not associated with the risk of DR (OR = 1.15, 95%CI 0.75-1.76; p = 0.51); non-alcoholic fatty liver disease was positively correlated with DR in patients with type 1 diabetes (OR = 2.96, 95%CI 1.48-5.94; p = 0.002). In patients with type 2 diabetes, there was no association between non-alcoholic fatty liver disease and DR (OR = 0.92, 95%CI 0.59-1.43; p = 0.70). Subgroup analysis showed no correlation in both Asian and Caucasian races. Conclusion: There is a significant correlation between liver fibrosis and DR. This suggests that the ocular examination of DR could be helpful in predicting whether patients with non-alcoholic fatty liver disease would progress to liver fibrosis.
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Affiliation(s)
- Guo-heng Zhang
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of Ophthalmology, 942 Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Yin’chuan, China
| | - Tian-hao Yuan
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of The Cadet Team 6 of School of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Zhen-sheng Yue
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Guo-Rui Dou
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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Chun HS, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Kim SU. Prevalence and Risk Factors of Cardiovascular Disease in Patients with Chronic Hepatitis B. Dig Dis Sci 2022; 67:3412-3425. [PMID: 34476661 DOI: 10.1007/s10620-021-07157-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 07/05/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The association between chronic hepatitis B (CHB) and cardiovascular disease (CVD) remains unclear. We investigated the prevalence and risk factors of CVD in patients with CHB. METHODS Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analyzed. Significant liver fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile, highest Forns index quintile, or fibrosis-4 ≥ 2.67. The CVD risk was calculated using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score from the 2013 ACC/AHA Guidelines. RESULTS Among the 506 subjects with CHB, 15 (3.0%) and 150 (29.6%) patients had a CVD history and significant liver fibrosis, respectively. Patients with CVD history were significantly older; showed a significantly higher prevalence of hypertension, metabolic syndrome, and significant liver fibrosis; and had a significantly higher platelet count, lower aspartate and alanine aminotransferase levels, higher triglyceride level, lower high-density lipoprotein level, and higher ASCVD risk than those without (all p < 0.05). In multivariate analysis, higher ASCVD risk (odds ratio [OR] = 1.090) and significant liver fibrosis (OR = 4.341) independently predicted the risk of CVD history (p < 0.05). The prevalence of CVD risk (6.7% vs. 1.4%; OR = 5.014) and high ASCVD risk (> 15%) (34.0% vs. 7.3%; OR = 6.538) was significantly higher in patients with significant liver fibrosis than in those without (all p < 0.05). CONCLUSIONS Significant liver fibrosis was independently associated with the risk of CVD history in patients with CHB. Prospective studies are needed to validate the longitudinal association between fibrotic burden and CVD development in patients with CHB.
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Affiliation(s)
- Ho Soo Chun
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
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10
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Tang ASP, Chan KE, Quek J, Xiao J, Tay P, Teng M, Lee KS, Lin SY, Myint MZ, Tan B, Sharma VK, Tan DJH, Lim WH, Kaewdech A, Huang D, Chew NWS, Siddiqui MS, Sanyal AJ, Muthiah M, Ng CH. Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals. Clin Mol Hepatol 2022; 28:483-496. [PMID: 35232007 PMCID: PMC9293613 DOI: 10.3350/cmh.2021.0406] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/27/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. METHODS Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. RESULTS From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36-43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37-4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74-9.09%) with an odds ratio of 1.88 (95% CI, 1.23-2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. CONCLUSION This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.
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Affiliation(s)
- Ansel Shao Pin Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jingxuan Quek
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Phoebe Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Margaret Teng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
| | - Keng Siang Lee
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - May Zin Myint
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Benjamin Tan
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Vijay K Sharma
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Nicholas WS Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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11
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Wang Y, Wang W, Wang M, Shi J, Jia X, Dang S. A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2022; 2022:5389044. [PMID: 35356132 PMCID: PMC8958112 DOI: 10.1155/2022/5389044] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/25/2022] [Accepted: 02/26/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The use of statins is a potential protective factor against the development of hepatocellular carcinoma. Therefore, we conducted a meta-analysis to evaluate the contribution of statins to the risk of hepatocellular carcinoma. METHODS We searched for PubMed and EMBASE through January 2021. RESULTS Thirty-two studies (eighteen cohort, eleven case-control, and three randomized controlled trials) reporting 56,838 cases of hepatocellular carcinoma in 4,963,518 persons were included. Statin users were less likely to develop hepatocellular carcinoma than nonusers (adjusted odds ratio, 0.58; 95% CI: 0.51-0.67). Stratified analysis showed that statins reduced the risk of hepatocellular carcinoma in Asian and Western populations (odds ratio, 0.54 vs. 0.60). Besides, statins have protective effects against hepatocellular carcinoma after hepatitis B virus (odds ratio, 0.44; 95% CI: 0.22-0.85) and hepatitis C virus infections (odds ratio, 0.53; 95% CI: 0.49-0.57). Statins have protective effects on people with chronic liver disease (odds ratio, 0.52; 95% CI: 0.40-0.68) and on the general population (odds ratio, 0.60; 95% CI: 0.50-0.72). Lipophilic statins can prevent hepatocellular carcinoma (odds ratio, 0.51, 95% CI: 0.46-0.57), while hydrophilic statins cannot (odds ratio, 0.77, 95% CI: 0.58-1.02). The single-drug analyses showed that simvastatin (odds ratio, 0.53, 95% CI: 0.48-0.59), atorvastatin (odds ratio, 0.54, 95% CI: 0.45-0.64), rosuvastatin (odds ratio, 0.55, 95% CI: 0.37-0.83), lovastatin (odds ratio, 0.30, 95% CI: 0.15-0.62), and pitavastatin (odds ratio, 0.36, 95% CI: 0.17-0.75) had significant benefits. Further studies have shown that those in the high-dose group experienced better effects in preventing hepatocellular carcinoma (adjusted hazard ratio, 0.38 vs. 0.55). Further research found that the combined use of aspirin did not increase the chemoprevention effect of liver cancer (odds ratio, 0.57; 95% CI: 0.40-0.81). In addition, the preventive effect of statins improved with the extension of follow-up time (odds ratio, 0.54 vs. 0.65). CONCLUSION Our meta-analysis shows that the use of statins is associated with a lower risk of liver cancer.
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Affiliation(s)
- Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Muqi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Juanjuan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
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12
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Mansouri A, Reiner Ž, Ruscica M, Tedeschi-Reiner E, Radbakhsh S, Bagheri Ekta M, Sahebkar A. Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases. J Clin Med 2022; 11:1313. [PMID: 35268403 PMCID: PMC8911353 DOI: 10.3390/jcm11051313] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023] Open
Abstract
Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.
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Affiliation(s)
- Atena Mansouri
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran;
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
| | - Željko Reiner
- Department of Internal Medicine, School of Medicine, University Hospital Center Zagreb, University of Zagreb, 10000 Zagreb, Croatia;
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20100 Milan, Italy;
| | - Eugenia Tedeschi-Reiner
- University Hospital Center Sestre Milosrdnice, University of Osijek, Vinogradska Cesta 29, 10000 Zagreb, Croatia;
| | - Shabnam Radbakhsh
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran;
- Department of Medical Biotechnology and Nanotechnology, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
| | - Mariam Bagheri Ekta
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, A.P. Avtsyn Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia;
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
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13
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Riveiro-Barciela M, Marcos-Fosch C, Martinez-Valle F, Bronte F, Orozco O, Sanz-Pérez I, Torres D, Salcedo MT, Petta S, Esteban R, Craxi A, Buti M. Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study. World J Gastroenterol 2021; 27:5112-5125. [PMID: 34497439 PMCID: PMC8384736 DOI: 10.3748/wjg.v27.i30.5112] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/13/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects.
AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.
METHODS Prospective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017: 201 naïve HBeAg-negative hepatitis B virus-infected [49 chronic hepatitis B (CHB) and 152 inactive carriers(ICs)] and 201 healthy controls. Anthropomorphic and metabolic measures, liver stiffness and carotid Doppler ultrasound were performed. Subclinical atherosclerosis was established on an intima-media thickness increase of ≥1.2 mm and/or the presence of carotid plaques. Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test. Categorical variables were compared between groups using the χ2 or Fisher exact test.
RESULTS Carotid plaques were found more often in CHB (32.7%) than ICs (17.1%) or controls (18.4%) (P = 0.048). Subclinical atherosclerosis was also increased in CHB (40.8%) vsICs (19.1%) or controls (19.4%) (P = 0.003). No differences in the risk of atherosclerosis were observed between controls and ICs. The factors independently associated with the presence of carotid plaques were age [odds ratio(OR) 1.43, P < 0.001] and CHB (OR 1.18, P = 0.004) and for subclinical atherosclerosis, age (OR 1.45, P < 0.001), CHB (OR 1.23, P < 0.001) and diabetes (OR 1.13, P = 0.028). In the subset of young subjects (< 50 years), carotid plaques (12.5% vs 1.1%, P = 0.027) and subclinical atherosclerosis (12.5% vs 2.2%, P = 0.058) were more frequent among CHB than ICs.
CONCLUSION Untreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis, while ICs present a similar risk to controls.
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Affiliation(s)
- Mar Riveiro-Barciela
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Cristina Marcos-Fosch
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
| | - Fernando Martinez-Valle
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Fabrizio Bronte
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Olimpia Orozco
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Isidro Sanz-Pérez
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Daniele Torres
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Maria-Teresa Salcedo
- Pathology Department, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Salvatore Petta
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Rafael Esteban
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Antonio Craxi
- Sezione di Gastroenterologia, Di.Bi.M.I.S, University of Palermo, Palermo 90133, Italy
| | - Maria Buti
- Department of Medicine of the UAB, Hospital Universitari Vall d’Hebron, Barcelona 08035, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid 28029, Spain
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14
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Hsu PY, Wei YJ, Liang PC, Lee JJ, Niu SW, Huang JC, Hsu CT, Jang TY, Huang CI, Lin YH, Hsieh MY, Hsieh MH, Chen SC, Dai CY, Lin ZY, Chen SC, Huang JF, Chang JM, Yeh ML, Huang CF, Chiu YW, Hwang SJ, Chuang WL, Yu ML. Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis. J Gastroenterol Hepatol 2021; 36:2261-2269. [PMID: 33651428 DOI: 10.1111/jgh.15480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/02/2021] [Accepted: 02/23/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.
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Affiliation(s)
- Po-Yao Hsu
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Ju Wei
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Jung Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sheng-Wen Niu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jiun-Chi Huang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Ting Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Chia Chen
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jer-Ming Chang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Wen Chiu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shang-Jyh Hwang
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
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15
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Broker M, Frager SZ, Patel NS, Lebovics E, Frishman WH. The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis. Cardiol Rev 2021; 29:178-183. [PMID: 32618587 DOI: 10.1097/crd.0000000000000314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.
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Affiliation(s)
- Michael Broker
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Shalom Z Frager
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - Nayan S Patel
- Department of Medicine, University of Rochester/Strong Memorial Hospital, Rochester, NY
| | - Edward Lebovics
- Department of Medicine, Division of Gastroenterology and Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - William H Frishman
- From the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
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Haykal M, Matsumori A, Saleh A, Fayez M, Negm H, Shalaby M, Bassuony S. Diagnosis and treatment of HCV heart diseases. Expert Rev Cardiovasc Ther 2021; 19:493-499. [PMID: 33861939 DOI: 10.1080/14779072.2021.1917383] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is an important cause of a variety of otherwise unexplained heart diseases and myocardial injury. A high prevalence of HCV infection has been noted in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia/cardiomyopathy and myocarditis. Various arrhythmias, conduction disturbances and QT prolongation were also associated with HCV infection. A possible role of HCV infection in the pathogenesis of diabetes and atherosclerosis, and the role of immunogenetics of HCV cardiomyopathies is discussed. Recent studies suggest that mononuclear cells may be the major target of HCV, and clinical applications to test this new hypothesis are discussed. AREAS COVERED In this review, we will evaluate the evidence that HCV causes various cardiovascular diseases, and discuss on the pathogenesis of these disorders. EXPERT OPINION HCV is the cause of many different forms of heart disease worldwide, but their existence has not been recognized by most of cardiologists. The recognition and diagnosis are indispensable for the early treatment of these diseases. The diverse clinical manifestation of HCV infection and the presence of multiple extrahepatic disease syndromes could be explained by a new hypothesis that the target of HCV is leukocytes.
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Affiliation(s)
- Mohammad Haykal
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Akira Matsumori
- Clinical Research Center, Kyoto Medical Center, Kyoto, Japan
| | - Ahmed Saleh
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Moatez Fayez
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Hany Negm
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Mohammad Shalaby
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
| | - Samar Bassuony
- Cardiovascular and Ultrasonography Research Unit (CURU), Research Institute of Ophthalmology (RIO), Cairo, Egypt
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17
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Pennisi G, Spatola F, DI Marco L, DI Martino V, DI Marco V. Impact of Direct-Acting Antivirals (daas) on cardiovascular diseases in patients with chronic hepatitis C. Minerva Gastroenterol (Torino) 2021; 67:254-263. [PMID: 33971709 DOI: 10.23736/s2724-5985.21.02875-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
In the last years the hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. This review aims to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.
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Affiliation(s)
- Grazia Pennisi
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy -
| | - Federica Spatola
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Lorenza DI Marco
- Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia, Modena, Italy
| | - Vincenzo DI Martino
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
| | - Vito DI Marco
- Section of Gastroenterology and Hepatology, Dipartimento Di Promozione Della Salute, Materno Infantile, Medicina Interna e Specialistica Di Eccellenza (PROMISE), University of Palermo, Palermo, Italy
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18
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Impact of DAA-Based Regimens on HCV-Related Extra-Hepatic Damage: A Narrative Review. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1323:115-147. [PMID: 33326112 DOI: 10.1007/5584_2020_604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Two-third of patients with chronic hepatitis C show extrahepatic manifestations due to HCV infection of B lymphocytes, such as mixed cryoglobulinemia and non-Hodgkin B-cell lymphoma, or develop a chronic inflammatory status that may favor the development of adverse cardiovascular events, kidney diseases or metabolic abnormalities.DAAs treatments induce HCV eradication in 95% of treated patients, which also improves the clinical course of extrahepatic manifestations, but with some limitations. After HCV eradication a good compensation of T2DM has been observed, but doubts persist about the possibility of obtaining a stable reduction in fasting glucose and HbA1c levels.Chronic HCV infection is associated with low total and LDL cholesterol serum levels, which however increase significantly after HCV elimination, possibly due to the disruption of HCV/lipid metabolism interaction. Despite this adverse effect, HCV eradication exerts a favorable action on cardiovascular system, possibly by eliminating numerous other harmful effects exerted by HCV on this system.DAA treatment is also indicated for the treatment of patients with mixed cryoglobulinemia syndrome, since HCV eradication results in symptom reduction and, in particular, is effective in cryoglobulinemic vasculitis. Furthermore, HCV eradication exerts a favorable action on HCV-related lymphoproliferative disorders, with frequent remission or reduction of clinical manifestations.There is also evidence that HCV clearance may improve impaired renal functions, but same conflicting data persist on the effect of some DAAs on eGFR.
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Medhioub M, Bouzaidi K, Bachali A, Khsiba A, Hamzaoui L, Azouz MM. The risk of subclinical carotid atherosclerosis in patients with chronic hepatitis C. LA TUNISIE MEDICALE 2021; 99:449-455. [PMID: 35244930 PMCID: PMC8734473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The role of hepatitis C virus in the pathogenesis of atherosclerotic disease has been suggested by several studies. AIM To assess the association between subclinical carotid atherosclerosis and chronic hepatitis C. METHODS 40 patients infected with chronic hepatitis C and 40 control cases were evaluated by anthropometric and metabolic measurements. The risk of subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness. A high cardiovascular risk atherosclerosis was defined by carotid intima-media thickness > 75th percentile. RESULTS The carotid intima-media thickness and the prevalence of high cardiovascular risk atherosclerosis were significantly higher in the group infected with hepatitis C compared to the control group (0.68 VS 0.60, p=0.02) and (82.5% vs. 40%; 0.001) respectively. In multivariate studies, activity ≥ A2 and age> 40 years were the independent factors associated with the carotid intima-media thickness and hepatitis C was the only independent factor associated with high cardiovascular risk atherosclerosis (OR=4.81 CI at 95%: 1.6-14.42). CONCLUSIONS In our study, chronic hepatitis C was associated with a high risk of carotid atherosclerosis.
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Affiliation(s)
| | | | - Asma Bachali
- 3- Biochemistry laboratory
Mohamed Taher Maamouri Hospital, Nabeul -Tunisia. / Université de Tunis el Manar, faculté de médecine de Tunis,
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20
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Hussein A, Abdel Ghany M, Mahmoud HEM. Short- and long-term outcomes following percutaneous coronary intervention in hepatitis C virus seropositive patients. Egypt Heart J 2020; 72:44. [PMID: 32712829 PMCID: PMC7382666 DOI: 10.1186/s43044-020-00079-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/09/2020] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatitis C virus (HCV) infection is progressively recognized as a potential atherogenic condition that is associated with coronary artery disease (CAD). Factors that affect the cardiovascular system as diabetes mellitus and dyslipidemia also may affect the outcomes following PCI. So, HCV infection may have an impact on the outcomes following PCI. We aimed to investigate the impact of HCV seropositivity on the outcomes following percutaneous coronary intervention (PCI).
Results
We conducted a multi-center prospective cohort study on 400 patients candidate for elective PCI using drug-eluting stents; 200 patients were HCV seropositive and did not received antiviral treatment, and 200 patients were HCV seronegative. The patients were followed up for 1 year for the development of major adverse cardiovascular events (MACEs) and clinical in-stent restenosis. Multivariate Cox hazard regression analyses for MACEs and clinical in-stent restenosis at 12 months after adjustment for confounding factors showed that HCV seropositivity did not present a higher hazard upon MACEs (adjusted hazard ratio (HR) 0.74; 95% CI 0.41–1.32; p value 0.302), the individual cardiovascular outcomes (target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cerebrovascular stroke (CVS), stent thrombosis, major bleeding, coronary artery bypass graft (CABG), cardiac death, and non-cardiac death), or the incidence of clinical in-stent restenosis (adjusted HR was 1.70; 95% CI 0.64–4.51; p value 0.28) compared to seronegative patients.
Conclusion
HCV seropositivity had no impact on MACEs, individual cardiovascular outcomes, or clinical in-stent restenosis following PCI for a 1 year follow-up period.
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21
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Hepatitis C: Does Successful Treatment Alter the Natural History and Quality of Life? Gastroenterol Clin North Am 2020; 49:301-314. [PMID: 32389364 DOI: 10.1016/j.gtc.2020.01.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The cure of chronic hepatitis C infection has a major impact on the morbidity and mortality of infected patients. It is now clear that sustained virologic response improves overall survival and significantly reduces the risk of liver failure, fibrosis progression, need of liver transplantation, and incidence of hepatocellular carcinoma. Moreover, hepatitis C eradication improves a broad range of extrahepatic manifestations, such as dermatologic, neoplastic, cardiovascular, and endocrine, and improves quality of life.
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22
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Abstract
Hepatits C virus (HCV) infection has been largely associated with extrahepatic comorbidities such as diseases related to dysregulation of the immune system, neuropsychiatric disorders, and cardiometabolic alterations. These clinical consequences, together with experimental evidence, suggest a potential (in)direct effect of HCV, contributing to the pathogenesis of these diseases. Various studies have reported a positive effect of viral eradication on occurrence and outcomes of extrahepatic diseases. These observations and the availability of safe and effective direct antiviral agents further underline the need to search for virological eradication in all infected individuals independent of the severity of the liver disease.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, PROMISE, Università di Palermo, Italia.
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, PROMISE, Università di Palermo, Italia
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23
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Samji NS, Heda R, Kovalic AJ, Satapathy SK. Similarities and Differences Between Nonalcoholic Steatohepatitis and Other Causes of Cirrhosis. Gastroenterol Clin North Am 2020; 49:151-164. [PMID: 32033761 DOI: 10.1016/j.gtc.2019.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Nonalcoholic fatty liver disease includes a spectrum of liver disorders that range from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Risk factors such as obesity, hypertension, hyperlipidemia, chronic kidney disease, and smoking status increase risk of progression to cirrhosis among patients with NASH. Cirrhosis derived from non-NASH causes may share similar features with patients with NASH but embody distinct pathogenetic mechanisms, genetic associations, prognosis, and outcomes. This article discusses in detail the comparison of clinical, genetic, and outcome characteristics between patients with NASH cirrhosis as opposed to alternative causes of chronic liver disease.
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Affiliation(s)
- Naga Swetha Samji
- Tenova Cleveland Hospital, 2305 Chambliss Avenue Northwest, Cleveland, TN 37311, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN 38163, USA
| | - Alexander J Kovalic
- Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston Salem, NC, USA
| | - Sanjaya K Satapathy
- Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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24
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Dearborn AD, Marcotrigiano J. Hepatitis C Virus Structure: Defined by What It Is Not. Cold Spring Harb Perspect Med 2020; 10:cshperspect.a036822. [PMID: 31501263 DOI: 10.1101/cshperspect.a036822] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) represents an important and growing public health problem, chronically infecting an estimated 70 million people worldwide. This blood-borne pathogen is generating a new wave of infections in the United States, associated with increasing intravenous drug use over the last decade. In most cases, HCV establishes a chronic infection, sometimes causing cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Although a curative therapy exists, it is extremely expensive and provides no barrier to reinfection; therefore, a vaccine is urgently needed. The virion is asymmetric and heterogeneous with the buoyancy and protein content similar to low-density lipoparticles. Core protein is unstructured, and of the two envelope glycoproteins, E1 and E2, the function of E1 remains enigmatic. E2 is responsible for specifically binding host receptors CD81 and scavenger receptor class B type I (SR-BI). This review will focus on structural progress on HCV virion, core protein, envelope glycoproteins, and specific host receptors.
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Affiliation(s)
- Altaira D Dearborn
- The Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.,Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
| | - Joseph Marcotrigiano
- The Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
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25
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Sevastianos VA, Voulgaris TA, Dourakis SP. Hepatitis C, systemic inflammation and oxidative stress: correlations with metabolic diseases. Expert Rev Gastroenterol Hepatol 2020; 14:27-37. [PMID: 31868062 DOI: 10.1080/17474124.2020.1708191] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Hepatitis C chronic infection has long been correlated with numerous systemic diseases, such as diabetes mellitus and hepatic steatosis. Recent studies have also revealed an association with atherosclerosis.Areas covered: An analysis is presented on the mechanisms through which the hepatitis C viral infection can lead to a systemic increase in pro-inflammatory markers, especially tumor necrosis factor-a and interleukin-6. The immunological imbalance created may, through different mechanisms, act on the metabolic pathways that contribute to the development of insulin resistance, the accumulation of lipids in the liver, and even the formation of atherosclerotic plaques. Moreover, an additional contributing factor to the above-mentioned metabolic derangements is the unopposed oxidative stress observed in chronic hepatitis C viral infection. The virus itself contributes to the formation of oxidative stress, through alterations in the trace metal homeostasis and its effect on pro-inflammatory cytokines, such as tumor necrosis factor-a.Expert opinion: The scope of this review is to emphasize the importance of the metabolic manifestations of hepatitis C viral infection and to elucidate the pathophysiological mechanisms behind their emergence.
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Affiliation(s)
- Vassilios A Sevastianos
- Department of Internal Medicine and Liver Outpatient Clinic, "Evangelismos" General Hospital, Athens, Greece
| | - Theodoros A Voulgaris
- Department of Internal Medicine and Liver Outpatient Clinic, "Evangelismos" General Hospital, Athens, Greece
| | - Spyros P Dourakis
- Department of Internal Μedicine, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens Ippokrateio, Athens, Greece
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26
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Wang CC, Cheng PN, Kao JH. Systematic review: chronic viral hepatitis and metabolic derangement. Aliment Pharmacol Ther 2020; 51:216-230. [PMID: 31746482 DOI: 10.1111/apt.15575] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/08/2019] [Accepted: 10/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. AIM To summarise the interplay among hepatitis viruses, MetS and its components. METHODS We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. RESULTS With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. CONCLUSIONS In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Department of Medical Research and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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27
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Ichikawa T, Miyaaki H, Miuma S, Motoyoshi Y, Narita S, Toda S, Takahashi Y, Honda T, Yajima H, Uehara R, Hino N, Hori T, Hirata R, Taura N, Nakao K. Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection. Intern Med 2019; 58:1209-1215. [PMID: 30626818 PMCID: PMC6543209 DOI: 10.2169/internalmedicine.1514-18] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.
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Affiliation(s)
- Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | | | - Syouhei Narita
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Satomi Toda
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Youichi Takahashi
- Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Japan
| | - Tetsurou Honda
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Hiroyuki Yajima
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Ryouhei Uehara
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Naoyuki Hino
- Department of Comprehensive Community Care Systems, Graduate School of Biomedical Sciences, Nagasaki University, Japan
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Tomoko Hori
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Ryousuke Hirata
- Department of Gastroenterology, Nagasaki Harbor Medical Center, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Japan
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28
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Wen D, Du X, Dong JZ, Ma CS. Hepatitis C virus infection and risk of coronary artery disease: A meta-analysis. Eur J Intern Med 2019; 63:69-73. [PMID: 31006509 DOI: 10.1016/j.ejim.2019.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 01/08/2019] [Accepted: 03/05/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND A few recent studies have demonstrated that hepatitis C virus (HCV) infection was associated with coronary artery diseases (CAD). However, there still existed studies did not confirm this correlation. OBJECTIVE The objective of this study was to evaluate the association between HCV infection and CAD using a meta-analysis. METHODS Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) and relative risk (RR) with 95% confidence interval (CI) were calculated using the fixed and random effects models. RESULTS Eight cohort studies and six case-control and cross-sectional studies were enrolled in this meta-analysis. In the cohort studies, the overall RR and 95% CIs of HCV infection for CAD was 1.25, 1.12-1.40 in random effects model. For the case-control and cross-sectional studies, the overall OR and 95% CIs of HCV infection for CAD were 1.94, 1.58-2.38 in fixed effects model. No publication bias was found in this meta-analysis. CONCLUSIONS This meta-analysis showed that HCV infection was a risk factor for CAD.
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Affiliation(s)
- Dan Wen
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Xin Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Jian-Zeng Dong
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China
| | - Chang-Sheng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
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29
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC University of Paris and Inflammation-Immunopathology-Biotherapy Department and INSERM, UMR_S 959 and CNRS FRE3632 and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
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30
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Osama A, Ashour Y, Abd El-Razek R, Monir D. Assessment of carotid intima-media thickness and carotid plaque formation among patients with ischemic stroke and hepatitis C virus infection. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2019. [DOI: 10.1186/s41983-019-0054-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
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31
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Hemmat N, Ebadi A, Badalzadeh R, Memar MY, Baghi HB. Viral infection and atherosclerosis. Eur J Clin Microbiol Infect Dis 2018; 37:2225-2233. [PMID: 30187247 DOI: 10.1007/s10096-018-3370-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 08/28/2018] [Indexed: 12/22/2022]
Abstract
Several risk factors have been described for the pathogenesis of atherosclerosis. Infectious diseases are suggested to be a causative factor, and some viruses have been studied for their relation with atherosclerotic diseases. Studies report two hypotheses, direct and indirect effects, for the role of viral infections in atherogenesis. Viruses are able to initiate atherosclerosis by two different pathways. They can exert their direct effects on atherogenesis by infecting vascular cells and then inducing inflammation in the endothelium and smooth muscle cells. Alternatively, they can also apply indirect effects by infecting non-vascular cells and inducing systemic inflammation. In this review, we consider the available data about the effects and correlations of DNA and RNA viruses on atherosclerosis.
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Affiliation(s)
- Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran
| | - Amin Ebadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran
| | - Reza Badalzadeh
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Yousef Memar
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran.,Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran. .,Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Petta S, Adinolfi LE, Fracanzani AL, Rini F, Caldarella R, Calvaruso V, Cammà C, Ciaccio M, Di Marco V, Grimaudo S, Licata A, Marrone A, Nevola R, Pipitone RM, Pinto A, Rinaldi L, Torres D, Tuttolomondo A, Valenti L, Fargion S, Craxì A. Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis. J Hepatol 2018; 69:18-24. [PMID: 29505844 DOI: 10.1016/j.jhep.2018.02.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 02/14/2018] [Accepted: 02/19/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIMS Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ± 10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ± 0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. RESULTS All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ± 0.29 mm vs. 0.81 ± 0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. CONCLUSION HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. LAY SUMMARY Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy.
| | - Luigi Elio Adinolfi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Francesca Rini
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Rosalia Caldarella
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vincenza Calvaruso
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Calogero Cammà
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Marcello Ciaccio
- Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy
| | - Vito Di Marco
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Stefania Grimaudo
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Anna Licata
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
| | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Riccardo Nevola
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | | | - Antonio Pinto
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Rinaldi
- Department of Medical, Surgical, Neurological, Geriatric, and Metabolic Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy
| | - Daniele Torres
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Antonino Tuttolomondo
- Sezione di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), Università di Palermo, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Italy
| | - Antonio Craxì
- Sezione di Gastroenterologia e Epatologia, Di.Bi.M.I.S, Università di Palermo, Italy
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Wang Y, Xiong J, Niu M, Xu W, Xu K, Zhong H. Hepatitis B virus and the risk of coronary heart disease: A comprehensive systematic review and meta-analyses of observational studies. Int J Cardiol 2018; 265:204-209. [PMID: 29706430 DOI: 10.1016/j.ijcard.2018.04.059] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 02/27/2018] [Accepted: 04/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several studies have reported that hepatitis B virus (HBV) infection affects the risk of coronary heart disease. However, its association is controversial. Thus, we conducted a systematic review and meta-analysis to better understand it. METHODS Relevant studies published before October 2017 were identified by searching PubMed, EMBASE, and ISI Web of Science. The relationships between HBV and the risk of coronary heart disease were assessed using Relative risk (RR) values and the corresponding 95% confidence intervals (CIs). We used the random effects model proposed by DerSimonian and Laird to quantify the relationship. RESULTS Nine articles, including 65,058 HBV-infected patients and 534,998 uninfected controls, were included in the meta-analysis. The present study does not support that HBV infection is associated with the risk of coronary heart disease (RR = 0.99, CI = 0.76-1.22; I2 = 68.9%). Sensitivity analysis and 'trim and fill' method yielded similar results. No evidence of publication bias was observed. CONCLUSIONS HBV infection does not increase the risk of coronary heart disease. The associations were not significant both in cohort studies and in case-control studies.
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Affiliation(s)
- Yaqin Wang
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China
| | - Meng Niu
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Weiyu Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100730, China
| | - Ke Xu
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China..
| | - Hongshan Zhong
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China..
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Moctezuma-Velázquez C, Abraldes JG, Montano-Loza AJ. The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. ACTA ACUST UNITED AC 2018; 16:226-240. [PMID: 29572618 DOI: 10.1007/s11938-018-0180-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Statins are drugs developed to treat hypercholesterolemia. Its use in patients with liver disease has been limited because one of its potential and most feared side effects is hepatotoxicity. However, there is robust evidence that supports the safety of statins in this population in the absence of severe liver dysfunction. In this review, we will summarize the efficacy and safety of statins in cirrhosis. RECENT FINDINGS Statins are effective in the treatment of dyslipidemia in patients with liver disease, because of their pleiotropic properties. These properties are independent of their effect on cholesterol levels, such as improving endothelial dysfunction or having antioxidant, antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic, or immunomodulation properties. Statins have been studied in other areas such as in treatment of portal hypertension, prevention of hepatocellular carcinoma, and/or protection against ischemia/reperfusion injury. Approved indications for statins in patients with cirrhosis are those of the general population, including dyslipidemia and increased cardiovascular risk. Compensated cirrhosis is not a contraindication. In patients with decompensated cirrhosis, statins should be prescribed with extreme caution at low doses, and with frequent monitoring of creatinine phosphokinase levels in order to detect adverse events in a timely fashion.
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Affiliation(s)
- Carlos Moctezuma-Velázquez
- Division of Gastroenterology and Liver Unit, University of Alberta, 8540 112 Street NW, Zeidler Ledcor Centre, Room 1-20B, Edmonton, Alberta, T6G 2X8, Canada
| | - Juan G Abraldes
- Division of Gastroenterology and Liver Unit, University of Alberta, 8540 112 Street NW, Zeidler Ledcor Centre, Room 1-20B, Edmonton, Alberta, T6G 2X8, Canada
| | - Aldo J Montano-Loza
- Division of Gastroenterology and Liver Unit, University of Alberta, 8540 112 Street NW, Zeidler Ledcor Centre, Room 1-20B, Edmonton, Alberta, T6G 2X8, Canada.
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Kuo SH, Hung WT, Tang PL, Huang WC, Yang JS, Lin HC, Mar GY, Chang HT, Liu CP. Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan. BMJ Open 2018; 8:e017412. [PMID: 29374659 PMCID: PMC5829782 DOI: 10.1136/bmjopen-2017-017412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD). METHODS NHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis. RESULTS The 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14). CONCLUSIONS HCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.
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Affiliation(s)
- Shu-Hung Kuo
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wang-Ting Hung
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pei-Ling Tang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chun Huang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiou Yang
- Department of Physical Therapy, Fooyin University, Kaohsiung, Taiwan
| | - Hsiao-Chin Lin
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Guang-Yuan Mar
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Hong-Tai Chang
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chun-Peng Liu
- Critical Care Center and Cardiovascular Medical Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Vassalle C, Petta S, Pepe A, Craxi A, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with cardiovascular disease. Antivir Ther 2018; 23:35-46. [PMID: 30451152 DOI: 10.3851/imp3248] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.
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Affiliation(s)
- Cristina Vassalle
- Laboratory Medicine Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | - Alessia Pepe
- MRI Unit, Fondazione CNR-Regione Toscana G Monasterio, Pisa, Italy
| | - Antonio Craxi
- Section of Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy
| | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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Babiker A, Jeudy J, Kligerman S, Khambaty M, Shah A, Bagchi S. Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review. J Clin Transl Hepatol 2017; 5:343-362. [PMID: 29226101 PMCID: PMC5719192 DOI: 10.14218/jcth.2017.00021] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 07/15/2017] [Accepted: 07/27/2017] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.
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Affiliation(s)
| | - Jean Jeudy
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Seth Kligerman
- Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Miriam Khambaty
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Anoop Shah
- Division of Cardiology, University of Edinburgh, Little France, Edinburgh
| | - Shashwatee Bagchi
- Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, MD, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
- *Correspondence to: Shashwatee Bagchi, Division of Infectious Diseases, University of Maryland School of Medicine, 725 West Lombard Street, N359, Baltimore, MD 21201, USA. Tel: +1-410-706-4606, Fax: +1-410-706-3243, E-mail:
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Pang N, Kow W, Law J, Pan L, Lim B, Wong C, Chang K, Ganpathi I, Madhavan K. Role of Coronary Angiography in Pre–Liver Transplantation Cardiac Evaluation: Experience From an Asian Transplant Institution. Transplant Proc 2017; 49:1797-1805. [DOI: 10.1016/j.transproceed.2017.04.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 04/02/2017] [Accepted: 04/27/2017] [Indexed: 02/09/2023]
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Lonardo A, Targher G. NAFLD: Is There Anything New under the Sun? Int J Mol Sci 2017; 18:1955. [PMID: 28895919 PMCID: PMC5618604 DOI: 10.3390/ijms18091955] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 09/10/2017] [Accepted: 09/10/2017] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is an "umbrella" definition that encompasses a spectrum of histological liver changes ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, "cryptogenic" cirrhosis, and hepatocellular carcinoma (HCC), occurring in a dysmetabolic milieu, though in the absence of excessive alcohol consumption and other competing etiologies of chronic liver disease [1].[...].
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Affiliation(s)
- Amedeo Lonardo
- Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, Azienda Ospedaliero-Universitaria, Ospedale Civile di Baggiovara, 41125 Modena, Italy.
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy.
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40
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Association between volume and glucose metabolism of abdominal adipose tissue in healthy population. Obes Res Clin Pract 2017; 11:133-143. [DOI: 10.1016/j.orcp.2016.12.007] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 12/18/2016] [Accepted: 12/21/2016] [Indexed: 12/30/2022]
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Chou CH, Ho CS, Tsai WC, Wang MC, Tsai YS, Chen JY. Effects of chronic hepatitis C infection on arterial stiffness. ACTA ACUST UNITED AC 2017; 11:716-723. [PMID: 28923555 DOI: 10.1016/j.jash.2017.08.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 08/06/2017] [Accepted: 08/18/2017] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with increased arterial stiffness. Although chronic hepatitis C virus (HCV) infection was shown to be associated with metabolic disorder and chronic inflammation, the effects of chronic HCV infection on arterial stiffness remain unclear. This study recruited 221 patients including 32 normal controls, 72 NAFLD patients, and 117 subjects with HCV infection. Arterial stiffness was assessed by peripheral arterial stiffness index, Compliance Index (CI), and central arterial stiffness index, Stiffness Index derived from digital volume pulse by photoplethysmography. Levels of oxidative stress marker and inflammatory markers were also measured. The HCV group had significantly lower CI (4.8 ± 3.1 units vs. 3.9 ± 2.1 units vs. 3.0 ± 1.7 units; P for trend <.001) and higher Stiffness Index (7.0 ± 1.6 m/s vs. 8.3 ± 2.3 m/s vs. 8.4 ± 2.3 m/s; P for trend = .001) compared with the normal controls and NAFLD groups. Multivariate linear regression analysis showed that CI was independently correlated with systolic blood pressure (beta = -0.202, P = .013) and HCV infection (beta = -0.216, P = .036). Chronic HCV infection was independently associated with peripheral arterial stiffness. Peripheral arterial stiffness in chronic HCV infection was not associated with a marker of general inflammation (high-sensitivity C-reactive protein); however, a role for more specific markers of inflammation cannot be ruled out.
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Affiliation(s)
- Chang-Hua Chou
- Division of Gastroenterology, Department of Internal Medicine, Tainan Sinlau Hospital, Tainan, Taiwan
| | - Chin-Shan Ho
- Department of Adapted Physical Education, National Taiwan Sport University, Taoyuan, Taiwan
| | - Wei-Chuan Tsai
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Cheng Wang
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yau-Sheng Tsai
- Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan
| | - Ju-Yi Chen
- Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Abstract
Hepatitis C virus (HCV) infection is a prevalent condition associated with numerous extrahepatic manifestations. Epidemiologic studies have found that HCV is associated with increased cardiovascular morbidity and mortality, in particular with carotid atherosclerosis, cerebrovascular events, and coronary heart disease. The mechanisms involved encompass a chronic systemic inflammatory state, insulin resistance, and a potential, direct infection of the vascular endothelium. Sustained virologic response with interferon-based regimens is associated with reduced cardiovascular events, although this must be validated with newer direct-acting antivirals. This clear association between HCV and cardiovascular events may have significant economical and public health implications.
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Affiliation(s)
- Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland
| | - Francesco Negro
- Division of Gastroenterology and Hepatology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland; Division of Clinical Pathology, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, Geneva 4 1211, Switzerland.
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Moon SH, Hong SP, Cho YS, Noh TS, Choi JY, Kim BT, Lee KH. Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease. J Nucl Cardiol 2017; 24:892-899. [PMID: 26510948 DOI: 10.1007/s12350-015-0297-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 08/27/2015] [Accepted: 09/19/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatic F-18 fluoro-2-deoxyglucose (FDG) uptake is associated with non-alcoholic fatty liver disease (NAFLD) which is an independent risk factor for cardiovascular disease. However, the value of hepatic FDG uptake for predicting future cardiovascular events has not been explored. METHODS AND RESULTS Study participants were 815 consecutive asymptomatic participants who underwent a health screening program that included FDG positron emission tomography/computed tomography (PET/CT), abdominal ultrasonography, and carotid intima-media thickness (CIMT) measurements (age 51.8 ± 6.0 year; males 93.9%). We measured hepatic FDG uptake and assessed the prognostic significance of this parameter with other cardiovascular risk factors including Framingham risk score and CIMT. Multivariate Cox proportional hazards analyses including all study participants revealed that NAFLD with high-hepatic FDG uptake was the only independent predictor for future cardiovascular events [hazard ratio (HR) 4.23; 95% CI 1.05-17.04; P = .043). Subgroup analysis conducted in the NAFLD group showed that high-hepatic FDG uptake was a significant independent predictor of cardiovascular events (HR 9.29; 95% CI 1.05-81.04; P = .045). CONCLUSIONS This exploratory study suggests that high-hepatic FDG uptake may be a useful prognostic factor for cardiovascular events in individuals with NAFLD.
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Affiliation(s)
- Seung Hwan Moon
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Sun-Pyo Hong
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Young Seok Cho
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Tae Soo Noh
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Joon Young Choi
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Byung-Tae Kim
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea
| | - Kyung-Han Lee
- Department of Nuclear Medicine and Molecular Imaging, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
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Serum HBV surface antigen positivity is associated with low prevalence of metabolic syndrome: A meta-analysis. PLoS One 2017; 12:e0177713. [PMID: 28505202 PMCID: PMC5432182 DOI: 10.1371/journal.pone.0177713] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 05/02/2017] [Indexed: 02/06/2023] Open
Abstract
Background and aim As there is conflicting evidence for the relationship between hepatitis B virus surface antigen (HBsAg) positivity and the prevalence of metabolic syndrome (MetS), we performed a meta-analysis to investigate whether HBsAg positivity affects the incidence of MetS. Methods Observational studies on the relationship between HBsAg positivity and MetS were obtained from PubMed, Web of Science, and the Cochrane Library in April 2016. The pooled odds ratios (ORs) of MetS and its components (central obesity, increased fasting glucose, increased blood pressure, dyslipidemia) for subjects with or without HBsAg positivity were synthesized. The standardized mean difference of MetS components between HBsAg-positive participants and healthy controls was calculated. Heterogeneity was explored with subgroup analysis and sensitivity analysis. Publication bias was detected using Egger’s test and Begg’s test. Results Thirty studies were eligible for meta-analysis. The MetS OR for HBsAg-positive participants was significantly decreased compared with the controls [OR = 0.80, 95% confidence interval (CI), 0.70–0.90]. The negative effect of HBsAg positivity on elevated triglycerides (OR = 0.62, 95% CI, 0.59–0.64) was strong, while that for increased fasting blood glucose was weak (OR = 0.94, 95% CI, 0.90–0.98). The pooled ORs of central obesity (OR = 0.97, 95% CI, 0.91–1.04), reduced high-density lipoprotein cholesterol (OR = 0.98, 95% CI, 0.83–1.14), and elevated blood pressure (OR = 1.00, 95% CI, 0.80–1.25) for HBsAg-positive participants were all not significantly different compared with the controls. No publication bias was detected. Conclusions Serum HBsAg positivity is inversely associated with the prevalence of MetS. Among the five components of MetS, elevated triglycerides had the strongest inverse relationship with HBsAg positivity.
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Dhar-Mascareno M, Rozenberg I, Iqbal J, Hussain MM, Beckles D, Mascareno E. Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreased steatosis in ApoE null mice fed atherogenic diet. Int J Biochem Cell Biol 2017; 83:56-64. [PMID: 28013147 DOI: 10.1016/j.biocel.2016.12.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Revised: 12/14/2016] [Accepted: 12/19/2016] [Indexed: 01/13/2023]
Abstract
Hexim-1 is an inhibitor of RNA polymerase II transcription elongation. Decreased Hexim-1 expression in animal models of chronic diseases such as left ventricular hypertrophy, obesity and cancer triggered significant changes in adaptation and remodeling. The main aim of this study was to evaluate the role of Hexim1 in lipid metabolism focused in the progression of atherosclerosis and steatosis. We used the C57BL6 apolipoprotein E (ApoE null) crossed bred to C57BL6Hexim1 heterozygous mice to obtain ApoE null - Hexim1 heterozygous mice (ApoE-HT). Both ApoE null backgrounds were fed high fat diet for twelve weeks. Then, we evaluated lipid metabolism, atherosclerotic plaque formation and liver steatosis. In order to understand changes in the transcriptome of both backgrounds during the progression of steatosis, we performed Affymetrix mouse 430 2.0 microarray. After 12 weeks of HFD, ApoE null and ApoE-HT showed similar increase of cholesterol and triglycerides in plasma. Plaque composition was altered in ApoE-HT. Additionally, liver triglycerides and steatosis were decreased in ApoE-HT mice. Affymetrix analysis revealed that decreased steatosis might be due to impaired inducible SOCS3 expression in ApoE-HT mice. In conclusion, decreased Hexim-1 expression does not alter cholesterol metabolism in ApoE null background after HFD. However, it promotes stable atherosclerotic plaque and decreased steatosis by promoting the anti-inflammatory TGFβ pathway and blocking the expression of the inducible and pro-inflammatory expression of SOCS3 respectively.
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Affiliation(s)
- Manya Dhar-Mascareno
- Department of Biological Sciences, State University of New York, College at Old Westbury, Old Westbury, New York 11568, USA
| | - Inna Rozenberg
- Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA
| | - Jahangir Iqbal
- Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA
| | - M Mahmood Hussain
- Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA
| | - Daniel Beckles
- Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA; Departments of Surgery, Medicine and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA
| | - Eduardo Mascareno
- Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, 11203 USA.
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Shiffman ML, Gunn NT. Impact of hepatitis C virus therapy on metabolism and public health. Liver Int 2017; 37 Suppl 1:13-18. [PMID: 28052632 DOI: 10.1111/liv.13282] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 10/20/2016] [Indexed: 12/22/2022]
Abstract
Chronic hepatitis C virus (HCV) is associated with insulin resistance (IR) and leads to type 2 diabetes mellitus (T2DM) and hepatic steatosis in many patients. These metabolic complications of HCV have been shown to accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma. The metabolic syndrome is a common disorder that also includes IR, T2DM and hepatic steatosis. Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome. The cause of steatosis in patients with the features of both the metabolic syndrome and chronic HCV is sometime difficult to determine. Patients with metabolic syndrome and chronic HCV are also at risk of developing renal, cardiovascular and cerebrovascular disease. Recent data suggest that HCV is an independent risk factor for renal, coronary and cerebral vascular disease, and may increase mortality associated with these disorders. The treatment of HCV can now result in a sustained virological response and cure nearly all patients with chronic HCV. The eradication of HCV reduces the risk of developing IR and T2DM, improves IR and 2TDM, reduces the risk of developing chronic kidney disease, end-stage renal disease, acute cardiac syndrome and stroke in patients with 2TDM. Thus, treatment of chronic HCV can provide a significant public health benefit, but only if all patients with chronic HCV are identified and universally treated.
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Affiliation(s)
- Mitchell L Shiffman
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
| | - Nadege T Gunn
- Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA, USA
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Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, Targher G. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - Evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol 2016; 22:9674-9693. [PMID: 27956792 PMCID: PMC5124973 DOI: 10.3748/wjg.v22.i44.9674] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/29/2016] [Accepted: 10/30/2016] [Indexed: 02/06/2023] Open
Abstract
Fatty liver, which frequently coexists with necro-inflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.
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Kim G, Jang SY, Han E, Lee YH, Park SY, Nam CM, Kang ES. Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case-control study. Int J Cancer 2016; 140:798-806. [PMID: 27861855 DOI: 10.1002/ijc.30506] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 11/02/2016] [Indexed: 12/23/2022]
Abstract
Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5-year HCC-free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22-0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14-0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32-1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose-dependent manner, especially in individuals with liver disease.
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Affiliation(s)
- Gyuri Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suk-Yong Jang
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eugene Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong-Ho Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Se-Young Park
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chung Mo Nam
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Health Services Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Seok Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.,Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea.,Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea
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Prevalence of Hepatitis C Virus Seropositivity and Its Impact on Coronary Artery Disease among Egyptian Patients Referred for Coronary Angiography. Cardiol Res Pract 2016; 2016:1623197. [PMID: 27882261 PMCID: PMC5110946 DOI: 10.1155/2016/1623197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/18/2016] [Accepted: 10/13/2016] [Indexed: 12/19/2022] Open
Abstract
Background. We tested the prevalence and impact of HCV seropositivity among Egyptian patients referred for coronary angiography. Subjects and Methods. This cross-sectional study was conducted in Zagazig University hospitals including 509 patients scheduled for elective coronary angiography between June 2013 and June 2014. By taking full history on admission, laboratory workup including HCV Ab, echocardiography study, and coronary angiography, we calculated the mean number of coronary artery lesions and the mean number of affected coronary artery vessels for all patients. The severity of the coronary lesions was estimated using the Gensini score. Results. HCV seropositive patients referred for coronary angiography were about 30.3% (which is greater than the prevalence of HCV seropositivity among general population in Egypt), patients proved to have CAD who are HCV antibody positive had more severe coronary lesions than in seronegative one (p < 0.05), and patients proved to have CAD who are HCV antibody positive had comparable prevalence of cardiovascular risk factors as seronegative patients except for diabetes and hypertension which are more prevalent in seronegative patients (p < 0.05). Conclusion. Prevalence of HCV antibody positive patients referred for coronary angiography was about 30.3%, and CAD patients who are HCV antibody positive had more severe coronary lesions and less prevalence of diabetes and hypertension than HCV antibody negative.
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Petta S. Hepatitis C virus and cardiovascular: A review. J Adv Res 2016; 8:161-168. [PMID: 28149651 PMCID: PMC5272956 DOI: 10.1016/j.jare.2016.06.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 06/05/2016] [Accepted: 06/11/2016] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is a systemic disease that leads to increased risks of cirrhosis and its complications, as well as extrahepatic disturbances, including immune-related disorders and metabolic alterations such as insulin resistance and steatosis. Recent accumulating evidence suggests that HCV infection can increase cardiovascular risk, and that viral eradication can improve cardiovascular outcomes in the clinical setting. These data are strengthened by evidence identifying potential mechanisms (in)directly linking HCV infection to vascular damage. However, the high prevalence of both HCV infection and cardiovascular alterations, as well as the presence of contrasting results not identifying any association between HCV infection and cardiovascular dysfunction, provides uncertainty about a direct association of HCV infection with cardiovascular risk. Further studies are needed to clarify definitively the role of HCV infection in cardiovascular alterations, as well as the impact of viral eradication on cardiovascular outcomes. These features are now more attractive, considering the availability of new, safe, and very effective interferon-free antiviral agents for the treatment of HCV infection. This review aims to discuss carefully available data on the relationship between HCV infection and cardiovascular risk.
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Affiliation(s)
- Salvatore Petta
- Sezione di Gastroenterologia, Dipartimento Biomedico di Medicina Interna e Specialistica, Piazza delle Cliniche, 2, 90127 Palermo, Italy
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