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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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Shahpar A, Sofiani VH, Nezhad NZ, Charostad M, Ghaderi R, Farsiu N, Kiskani AK, Pezeshki S, Nakhaie M. A narrative review: exploring viral-induced malignancies through the lens of dysregulated cellular metabolism and glucose transporters. BMC Cancer 2024; 24:1329. [PMID: 39472817 PMCID: PMC11520837 DOI: 10.1186/s12885-024-13013-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 10/01/2024] [Indexed: 11/02/2024] Open
Abstract
INTRODUCTION In this narrative review, we unravel the complex interplay between oncogenic viruses, cellular metabolism, and glucose transporter (GLUT) dysregulation in viral-induced malignancies. METHODS By explaining the diverse mechanisms through which seven major oncoviruses manipulate metabolic pathways and GLUT expression, particularly GLUT1, we provide novel insights into the critical role of metabolic reprogramming in viral replication and oncogenesis. RESULTS Our exploration of the molecular pathways targeted by viral oncoproteins reveals a similarity between the metabolic alterations induced by viral infections and those observed in neoplastic transformation. A key finding of our review is the overexpression of GLUTs, particularly GLUT1, as a hallmark of both viral infections and many cancers. CONCLUSIONS By elucidating the complex interplay between viral oncoproteins, oncogene activation, tumor suppressor gene loss, and GLUT overexpression, we highlight the potential of GLUTs as novel targets for diagnosis, prognosis, and therapy of viral-induced malignancies.
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Affiliation(s)
- Amirhossein Shahpar
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Nazanin Zeinali Nezhad
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Marzieh Charostad
- Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
| | - Reza Ghaderi
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Niloofar Farsiu
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Amin Karimzadeh Kiskani
- Clinical Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran
| | - Sara Pezeshki
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohsen Nakhaie
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
- Clinical Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran.
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Chen B, Iqbal U, Desai SK, Gries J, Verheyen E, Xie M, El Halabi M, Gaines S, Weisberg I. The role of treatment of hepatitis C with direct-acting antiviral agents on glycaemic control in diabetic patients: An updated systematic review and meta-analysis. J Viral Hepat 2024; 31:633-642. [PMID: 39046172 DOI: 10.1111/jvh.13984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 05/25/2024] [Accepted: 07/16/2024] [Indexed: 07/25/2024]
Abstract
Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A1c (HbA1c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA1c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I2 = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA1C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication.
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Affiliation(s)
- Bing Chen
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, Pennsylvania, USA
| | | | - Shivani K Desai
- Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Jacob Gries
- Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA
| | | | - Mengdan Xie
- MetroHealth/Case Western Reserve University, Cleveland, Ohio, USA
| | | | - Sara Gaines
- Department of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, Pennsylvania, USA
| | - Ilan Weisberg
- Division of Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, USA
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Cheng PN, Sun HY, Feng IC, Chiu YC, Wang ST, Tan DC, Chiu HC, Chien SC, Young KC. Interdependence of glycemic and lipid modulation in cured chronic hepatitis C patients by direct-acting antiviral agents. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:20-30. [PMID: 35842406 DOI: 10.1016/j.jmii.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 05/01/2022] [Accepted: 06/16/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection causes various liver diseases and metabolic disorders. With direct-acting antiviral agents (DAAs), which effectively eradicate pan-genotypic HCV, hepatic and concomitant metabolic restorations are achieved. The study aims to evaluate the posttherapeutic benefits of lipid and glycemic homeostasis. METHODS Nighty-five chronic hepatitis C patients who achieved sustained virological response (SVR) by using DAAs were enrolled to collect plasma samples and fractionated lipoproteins at baseline, SVR, and during the post-SVR follow-ups for 6 months (pS6m) and 1 year (pS1yr). The lipid and glycemic parameters were analyzed to establish muturally modulatory relationships. RESULTS Plasma cholesterol (Chol) and glucose were elevated at SVR from baseline, whereas plasma Chol remained increased until pS1yr; however, glucose returned to the basal level. The post-SVR responses included a peak elevation of glycated hemoglobin at pS6m, a sustained elevation of triglyceride (Tg), and sustained declines in insulin, homeostasis model assessment (HOMA)-insulin resistance, and HOMA-beta levels until pS1yr. The changes in plasma Chol and high-density-lipoprotein Chol showed positive correlations, as did the plasma Tg with low-density-lipoprotein Tg and very-low-density-lipoprotein Tg per particle load. Very-low-density-lipoprotein was found to be loaded with increased Tg and Chol and underwent efficient Tg catabolism in the form of conversion into low-density-lipoprotein. Additionally, the posttherapeutic dynamics exhibited correlations of high-density-lipoprotein Chol with plasma glucose and HOMA-beta. CONCLUSION Irrespective of the baseline metabolic status, the posttherapeutic interdependent modulation of blood glycemic and lipid metabolic parameters were revealed in chronic hepatitis C patients following clearance of HCV viremia by DAA treatment.
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Yu Sun
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha, China; Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha, China; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Che Feng
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Sin-Tian Wang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Dyoness Charmaine Tan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chih Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kung-Chia Young
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection. BIOLOGY 2022; 12:biology12010023. [PMID: 36671716 PMCID: PMC9855523 DOI: 10.3390/biology12010023] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 12/06/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022]
Abstract
Hepatitis C virus (HCV) is a significant cause of chronic liver diseases worldwide and is associated with negative consequences, including cirrhosis, hepatic decompensation, hepatocellular carcinoma, and increased risk of mortality. In addition to liver-related morbidities, HCV is also associated with several extrahepatic manifestations, including mixed cryoglobulinemia, diabetes mellitus, cardiocerebrovascular disease, lymphoma, and autoimmune diseases. These non-liver-related complications of HCV increase the complexity of this disease and can contribute to the economic burden, morbidity, quality of life, and mortality throughout the world. Therefore, understanding how this virus can contribute to each extrahepatic manifestation is worth investigating. Currently, the advancement of HCV treatment with the advent of direct-acting anti-viral agents (DAAs) has led to a high cure rate as a result of sustained virologic response and tremendously reduced the burden of extrahepatic complications. However, HCV-associated extrahepatic manifestations remain a relevant concern, and this review aims to give an updated highlight of the prevalence, risk factors, associated burdens, and treatment options for these conditions.
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Angel M, Petrosyan Y, Doyle MA, Cooper C. HCV infection characteristics, treatment uptake and outcomes in patient with diabetes mellitus. BMC Endocr Disord 2022; 22:277. [PMID: 36371200 PMCID: PMC9652941 DOI: 10.1186/s12902-022-01198-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/03/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The interplay between HCV, DM, and DAA therapy is poorly understood. We compared HCV infection characteristics, treatment uptake, and treatment outcomes in patients with and without DM. METHODS: A retrospective cohort study was conducted using data from The Ottawa Hospital Viral Hepatitis Program. Statistical comparisons between diabetes and non-diabetes were made using χ2 and t-tests. Logistic regression analyses were performed to assess predictors of DM and SVR. RESULTS One thousand five hundred eighty-eight HCV patients were included in this analysis; 9.6% had DM. Patients with DM were older and more likely to have cirrhosis. HCC and chronic renal disease were more prevalent in the DM group. Treatment uptake and SVR were comparable between groups. Regression analysis revealed that age and employment were associated with achieving SVR. Post-SVR HCC was higher in DM group. CONCLUSION The high prevalence of DM in our HCV cohort supports screening. Further assessment is required to determine if targeted, early DAA treatment reduces DM onset, progression to cirrhosis and HCC risk. Further studies are needed to determine if optimization of glycemic control in this population can lead to improved liver outcomes.
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Affiliation(s)
- Marina Angel
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Yelena Petrosyan
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Mary-Anne Doyle
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada
| | - Curtis Cooper
- Ottawa Hospital Research Institute, G12-501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
- Department of Medicine, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, K1G 5Z3, Canada.
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Abdel-Hamid NM, Sherif MH, Al Samahy AE, Abdelhamid MS. Plasma Insulin/Erythrocytic Aldose Reductase Ratio as a Predictor for Hepatocellular Carcinoma among Type II Diabetics and Hepatitis C Virus-infected Patients. Asian Pac J Cancer Prev 2022; 23:3815-3823. [PMID: 36444594 PMCID: PMC9930971 DOI: 10.31557/apjcp.2022.23.11.3815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 11/17/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a possible oncogenic progression during persistent hepatitis C-infection +/- type II diabetes mellitus (DM). We aim to investigate the plasma insulin, erythrocytic aldose reductase (AR) and sorbitol dehydrogenase (SDH) as possible predictive tools for HCC in hepatitis C-infected patients (HCV) +/- DM. Erythrocytes (RBCs) were adopted as a possible vehicle for pre-malignant variations being of short life span. Methods: The study included 20 healthy control and 100 patients of 48-64 years old, divided into 5 equal groups as; type II DM, HCC, HCC with DM, DM- HCV infected and non-DM HCV infected. Plasma levels of AFP and insulin were measured. RESULTS It showed an elevated AR, significant reduction of SDH in RBCs and plasma of DM patients. These values were greatly elevated among HCV, HCC, diabetic HCV, and diabetic HCC patients. All DM patients showed elevated insulin levels than normoglycemic controls. CONCLUSION The study substantiated the use of RBCs as a vehicle for early diagnostic markers better than plasma. We recommend the use of insulin/ erythrocytic AR ratio as a new laboratory marker for predicting HCC among type II diabetics or non-treated HCV-infected patients with control insulin/ erythrocytic AR ratio by each laboratory.
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Affiliation(s)
| | - Mohamad H Sherif
- Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt.
| | - Asmaa E Al Samahy
- Biochemistry Division, Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, Egypt.
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Alzahrani N. Hepatitis C Virus, Insulin Resistance, and Diabetes: A Review. Microbiol Immunol 2022; 66:453-459. [PMID: 35941761 DOI: 10.1111/1348-0421.13023] [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: 01/25/2022] [Revised: 07/19/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are two chronic diseases that are a cause of significant health and economic burdens worldwide. HCV is associated with the development of insulin resistance (IR) and diabetes mellitus (DM). The mechanisms through which HCV induces IR and DM include direct viral effects, pro-inflammatory cytokines and other immune-mediated processes. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are both chronic diseases that involve impaired glucose homeostasis, albeit through different mechanisms. T1DM is an autoimmune disease that leads to the destruction of pancreatic beta cells resulting in insulin deficiency. In T2DM, a combination of peripheral insulin resistance and irregular production of insulin eventually lead to beta cell destruction and insulin insufficiency. Both type 1 and type 2 DM etiologies involve a combination of genetic and environmental factors. The data on HCV and T1DM association is limited, unlike T2DM, where a large body of evidence linking HCV to T2DM is available. Here, we intend to outline the current state of knowledge on HCV, IR, and DM. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Nabeel Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, 14611, Saudi Arabia
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Kumar R, García-Compeán D, Maji T. Hepatogenous diabetes: Knowledge, evidence, and skepticism. World J Hepatol 2022; 14:1291-1306. [PMID: 36158904 PMCID: PMC9376767 DOI: 10.4254/wjh.v14.i7.1291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 04/27/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India.
| | - Diego García-Compeán
- Department of Gastroenterology, University Hospital, Universidad Autónoma de Nuevo León, México, Monterrey 64700, México
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Gundling F. Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2022; 15:42-52. [DOI: 10.1007/s41969-022-00158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 01/04/2025]
Abstract
Zusammenfassung
Hintergrund
Patienten mit Leberzirrhose entwickeln häufig Störungen des Glukosemetabolismus wie Glukoseintoleranz oder einen hepatogenen Diabetes, welche neben der hepatozellulären Funktionseinschränkung durch die ausgeprägte Insulinresistenz als Folge der chronischen Lebererkrankung verursacht sind.
Diskussion
Empfehlungen mit Leitliniencharakter zur Diagnostik und Therapie des hepatogenen Diabetes fehlen bislang. Im Hinblick auf basistherapeutische Maßnahmen sollte eine ausreichende Deckung des Energie- und Proteinstoffwechsels gewährleistet sein, da ein Großteil der Zirrhosepatienten mangelernährt ist. Bei der medikamentösen Behandlung des hepatogenen Diabetes muss auf die erhöhte Hypoglykämiegefährdung geachtet werden. Aufgrund der Nebenwirkungen sind Biguanide sowie PPAR-gamma-Liganden bei Leberzirrhose kontraindiziert. Geeignete orale Antidiabetika sind insbesondere Sulfonylharnstoffanaloga und kurz wirksame Sulfonylharnstoffe. Wenn eine suffiziente Diabeteseinstellung mit oralen Antidiabetika nicht gelingt, sollte eine prandiale Insulintherapie mit Insulinen von kurzer Wirkdauer oder kurz wirksamen Insulinanaloga eingesetzt werden.
Schlussfolgerung
Die Optimierung einer diabetischen Stoffwechsellage hat neben der Vermeidung typischer diabetischer Spätkomplikationen eine wichtige Bedeutung für die Vermeidung und Reduzierung von Zirrhose-assoziierten Komplikationen wie z. B. gastrointestinalen Blutungsereignissen, hepatischer Enzephalopathie oder dem Auftreten eines hepatozellulären Karzinoms.
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Increased Insulin Resistance in Hepatitis-C Infection-Association with Altered Hepatic Function Testing. PATHOPHYSIOLOGY 2022; 29:326-332. [PMID: 35893594 PMCID: PMC9326586 DOI: 10.3390/pathophysiology29030024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/14/2022] [Accepted: 06/17/2022] [Indexed: 12/15/2022] Open
Abstract
Introduction: Hepatitis C virus (HCV) infection is a serious global public health problem. It is estimated that 2% to 3% of the world’s population is infected with the virus. It was found that chronic hepatitis C is an independent predictor of the development of type 2 diabetes mellitus. Infection with HCV or the inflammatory response to HCV infection likely contributes to the development of insulin resistance (IR), which increases the risk of developing type 2 diabetes in the long term. This study aimed to assess the insulin resistance in hepatitis C and its correlation with various metabolic parameters. Materials and Methods: This cross-sectional observational study was conducted at a tertiary care hospital in North India in the Department of Internal Medicine with hepatitis C-positive patients attending an out-patient or in-patient department. We took a total of 100 patients aged > 18 years and divided them into two groups: Group A with hepatitis C (cases) and Group B without hepatitis C (controls). There were a total of 50 hepatitis C patients and 50 patients without hepatitis C. Results: A total of 100 patients were included in the present study after obtaining informed consent. There was a significantly higher level of serum ferritin and insulin in group A patients than group B patients. There was a positive correlation of insulin resistance with the serum insulin, ferritin levels, cholesterol, LDL and triglyceride level and a negative correlation with the serum HDL level. The incidence of insulin resistance was positively correlated with changes in fibrosis in the liver due to the hepatitis C infection. Conclusions: From our study, we found that there is an increased incidence of insulin resistance in the patients with hepatitis-C infection, and insulin resistance is associated with the presence of altered hepatic function test results.
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Treatment-Resistant Hepatitis C Viral Infection: A Case Report and Literature Review. Case Reports Hepatol 2022; 2022:3556780. [PMID: 35309181 PMCID: PMC8933098 DOI: 10.1155/2022/3556780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/12/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C virus (HCV) is an ongoing global public health threat affecting millions worldwide. Increasing recognition of its impact and recent advances towards HCV prevention and cure have provided incentive for the World Health Organization to call for global elimination by 2030. The goal of therapy is to achieve a sustained virologic response (SVR-12), defined as undetectable HCV-RNA within 12 weeks after treatment completion. In 2011, approval was given for the first direct-acting antiviral agents (DAAs). More recently, in 2013, more effective DAAs, with pan-genomic properties, have been introduced, and these regimens boast increasing rates of SVR. The ultimate goal is that the history of HCV ends with the pan-genotypic efficacy of multiple, easy-to-use and tolerate, combination regimens. These regimens have already demonstrated the ability to cure previously challenging patient groups. However, limitations exist in the current portfolio of agents, with suboptimal outcomes for patients with HCV genotype 3. In addition to this, access to DAAs remains an obstacle for many patients. We present this case of a 61-year-old male with HCV genotype 3 who has had several treatment failures with standard HCV therapy who was eventually approved for compassionate use of a 16-week course of glecaprevir (GLE)/pibrentasvir (PIB), sofosbuvir (SOF), and ribavirin (RBV) which ultimately led to SVR-12.
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Association between SNPs of Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1)and the susceptibility to chronic Hepatitis C infection in virus C-infected patients. Virus Res 2022; 310:198684. [DOI: 10.1016/j.virusres.2022.198684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/10/2022] [Accepted: 01/12/2022] [Indexed: 12/15/2022]
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García-Compeán D, Orsi E, Kumar R, Gundling F, Nishida T, Villarreal-Pérez JZ, Del Cueto-Aguilera ÁN, González-González JA, Pugliese G. Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives. World J Gastroenterol 2022; 28:775-793. [PMID: 35317103 PMCID: PMC8900578 DOI: 10.3748/wjg.v28.i8.775] [Citation(s) in RCA: 6] [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: 10/10/2021] [Revised: 11/19/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, Fdn IRCCS Ca Granda, Endocrine Unit, Padigl Granelli, Milan 20121, Italy
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Felix Gundling
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Diabetics, Metabolism and Infectious Diseases, Sozialstiftung Bamberg, Bamberg 96049, Germany
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka 560-8565, Japan
| | | | - Ángel N Del Cueto-Aguilera
- Department of Gastroenterology and Internal Medicine, Faculty of Medicine, University Hospital, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. José E González and Medical School, Monterrey 64460, Nuevo León, Mexico
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, La Sapienza University, Roma 00161, Italy
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Fader Kaiser CM, Romano PS, Vanrell MC, Pocognoni CA, Jacob J, Caruso B, Delgui LR. Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions. Front Cell Dev Biol 2022; 9:826248. [PMID: 35198567 PMCID: PMC8860030 DOI: 10.3389/fcell.2021.826248] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 12/22/2021] [Indexed: 12/17/2022] Open
Abstract
Lipid droplets (LD) have long been considered as mere fat drops; however, LD have lately been revealed to be ubiquitous, dynamic and to be present in diverse organelles in which they have a wide range of key functions. Although incompletely understood, the biogenesis of eukaryotic LD initiates with the synthesis of neutral lipids (NL) by enzymes located in the endoplasmic reticulum (ER). The accumulation of NL leads to their segregation into nanometric nuclei which then grow into lenses between the ER leaflets as they are further filled with NL. The lipid composition and interfacial tensions of both ER and the lenses modulate their shape which, together with specific ER proteins, determine the proneness of LD to bud from the ER toward the cytoplasm. The most important function of LD is the buffering of energy. But far beyond this, LD are actively integrated into physiological processes, such as lipid metabolism, control of protein homeostasis, sequestration of toxic lipid metabolic intermediates, protection from stress, and proliferation of tumours. Besides, LD may serve as platforms for pathogen replication and defense. To accomplish these functions, from biogenesis to breakdown, eukaryotic LD have developed mechanisms to travel within the cytoplasm and to establish contact with other organelles. When nutrient deprivation occurs, LD undergo breakdown (lipolysis), which begins with the LD-associated members of the perilipins family PLIN2 and PLIN3 chaperone-mediated autophagy degradation (CMA), a specific type of autophagy that selectively degrades a subset of cytosolic proteins in lysosomes. Indeed, PLINs CMA degradation is a prerequisite for further true lipolysis, which occurs via cytosolic lipases or by lysosome luminal lipases when autophagosomes engulf portions of LD and target them to lysosomes. LD play a crucial role in several pathophysiological processes. Increased accumulation of LD in non-adipose cells is commonly observed in numerous infectious diseases caused by intracellular pathogens including viral, bacterial, and parasite infections, and is gradually recognized as a prominent characteristic in a variety of cancers. This review discusses current evidence related to the modulation of LD biogenesis and breakdown caused by intracellular pathogens and cancer.
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Affiliation(s)
- Claudio M Fader Kaiser
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
| | - Patricia S Romano
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
| | - M Cristina Vanrell
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
| | - Cristian A Pocognoni
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
| | - Julieta Jacob
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
| | - Benjamín Caruso
- Instituto de Investigaciones Biologicas y Tecnologicas, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Cordoba, Cordoba, Argentina
| | - Laura R Delgui
- CONICET Dr. Mario H. Burgos Institute of Histology and Embryology (IHEM), Mendoza, Argentina
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Hegazy WAH, Rajab AAH, Abu Lila AS, Abbas HA. Anti-diabetics and antimicrobials: Harmony of mutual interplay. World J Diabetes 2021; 12:1832-1855. [PMID: 34888011 PMCID: PMC8613656 DOI: 10.4239/wjd.v12.i11.1832] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/26/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.
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Affiliation(s)
- Wael A H Hegazy
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Azza A H Rajab
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
| | - Amr S Abu Lila
- Department of Pharmaceutics, Zagazig University, Faculty of Pharmacy, Zagzig 44519, Egypt
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi Arabia
| | - Hisham A Abbas
- Department of Microbiology and Immunology, Zagazig University, Zagzig 44519, Egypt
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Kumada T, Toyoda H, Yasuda S, Tada T, Ito T, Tanaka J. Long-term outcomes of viral eradication in patients with hepatitis C virus infection and mild hepatic fibrosis. J Viral Hepat 2021; 28:1293-1303. [PMID: 34185932 DOI: 10.1111/jvh.13562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 05/11/2021] [Accepted: 06/03/2021] [Indexed: 12/09/2022]
Abstract
The impact of antiviral therapy on clinical outcomes in patients with hepatitis C virus (HCV) infection and mild liver fibrosis (FIB-4 score <1.45) is not well understood. We aimed to clarify the impact of viral eradication on hepatocarcinogenesis and mortality in patients with mild fibrosis.The subjects were 657 patients who achieved sustained virologic response (SVR) (Clearance group) and 586 patients who did not receive antiviral therapy or did not achieve SVR (No clearance group). We applied inverse probability weighting because the groups had different baseline characteristics. Multivariate proportional hazards models were used to analyse factors associated with hepatocarcinogenesis and mortality using a time-dependent covariate. In addition, we compared the mortality rate of the Clearance group stratified by age to the mortality rate of the general population.Clearance of HCV RNA was significantly associated with hepatocarcinogenesis and all-cause, liver-related and non-liver-related mortality (adjusted hazard ratios [95% confidence interval], 0.2653 [0.1147-0.6136, p = 0.0019], 0.3416 [0.2157-0.5409, p < 0.0001], 0.2474 [0.0802-0.8917, p = 0.0381] and 0.4118 [0.2449-0.6925, p = 0.0008], respectively). The Clearance group had significantly higher mortality than the general population matched by age, sex and follow-up duration (p < 0.0001). However, there were no significant differences between patients who achieved SVR before age 50 and the general population matched by age, sex and follow-up duration (p = 0.1570). HCV eradication in patients with mild fibrosis reduces liver-related and non-liver-related mortality. If HCV is eradicated before age 50, prognosis is likely be similar to that of the age-matched and sex-matched general population. (249 words).
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Affiliation(s)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Toshifumi Tada
- Department of Internal medicine, Himeji Red Cross Hospital, Himeji, Hyogo, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Reed J, Bain S, Kanamarlapudi V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes Metab Syndr Obes 2021; 14:3567-3602. [PMID: 34413662 PMCID: PMC8369920 DOI: 10.2147/dmso.s319895] [Citation(s) in RCA: 164] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/09/2021] [Indexed: 12/13/2022] Open
Abstract
Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.
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Affiliation(s)
- Josh Reed
- Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UK
| | - Stephen Bain
- Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UK
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Gantumur G, Batsaikhan B, Huang CI, Yeh ML, Huang CF, Lin YH, Lin TC, Liang PC, Liu TW, Lee JJ, Lin YC, Lin IL, Huang JF, Chuang WL, Yu ML, Tu HP, Dai CY. The association between hepatitis C virus infection and renal function. J Chin Med Assoc 2021; 84:757-765. [PMID: 34074934 DOI: 10.1097/jcma.0000000000000561] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) still remains controversial. We aimed to investigate whether HCV really affects renal function, and to analyze the association between clinical effects of CHC and decreased kidney function (assessed by glomerular filtration rate (eGFR) level). METHODS An estimated 3360 patients with HCV infection and 3360 age- and sex-matched community-based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016. We used the modification of diet in renal diseases to calculate eGFR. Demographic and laboratory parameters were assessed, and appropriate statistical methods were performed for the analysis. RESULTS Multivariate logistic regression analysis revealed that serum alanine aminotransferase level (odds ratio [OR] 0.998; 95% confidence interval [CI] 0.997-0.999; P = 0.001), platelet count (OR 0.997; 95% CI 0.995-0.999; p = 0.002), and hypertension (OR 1.31; 95% CI 1.03-1.66; P = 0.027) were significantly associated with HCV infection and serum triglyceride levels (OR 1.001; 95% CI 1.00-1.002; p = 0.005), platelet count (OR 0.996; 95% CI 0.995-0.997; p < 0.001), body mass index (BMI) >25 (OR 1.43; 95% CI 1.23-1.67; p < 0.001), hypertension (OR 1.69; 95% CI 1.42-1.99; p < 0.001), hyperlipidemia (OR 1.32; 95% CI 1.02-1.71; p = 0.035), and diabetes (OR 1.33; 95% CI 1.03-1.71; p = 0.032) were significantly associated with a low eGFR (<90 mL/min/m3) in control subjects. The BMI >25 kg/m2, hypertension, and diabetes were found to be associated with low eGFR interaction with the HCV infection, via a multivariate analysis. CONCLUSION Our study found that the patients with HCV infection are associated with a low eGFR compared with non-HCV-infected patients. This association is consistent in obese, diabetic, and hypertensive patients.
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Affiliation(s)
- Gantsetseg Gantumur
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Medical Research and Development, PubMend Medical Research Center, Ulaanbaatar, Mongolia
| | - Batbold Batsaikhan
- Department of Internal Medicine, Institute of Medical Sciences, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Ching-I Huang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yi-Hung Lin
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Tzu-Chun Lin
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Po-Cheng Liang
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ta-Wei Liu
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Jia-Jung Lee
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Yi-Ching Lin
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - I-Ling Lin
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Wan-Long Chuang
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Hung-Pin Tu
- Department of Public Health and Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine & Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC
- Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, ROC
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Yousef AS, Sallam AM, kotb NS, El-Mesallamy HO. The association of Fat Mass and Obesity-Associated (FTO) gene polymorphism (rs9939609) with metabolic disturbances and response to sofosbuvir, ribavirin and interferon triple therapy in patients with viral hepatitis C. Meta Gene 2021. [DOI: 10.1016/j.mgene.2021.100888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Wu K, Fan S, Zou L, Zhao F, Ma S, Fan J, Li X, Zhao M, Yan H, Chen J. Molecular Events Occurring in Lipophagy and Its Regulation in Flaviviridae Infection. Front Microbiol 2021; 12:651952. [PMID: 34093468 PMCID: PMC8175637 DOI: 10.3389/fmicb.2021.651952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/21/2021] [Indexed: 12/17/2022] Open
Abstract
Diseases caused by Flaviviridae have a wide global and economic impact due to high morbidity and mortality. Flaviviridae infection usually leads to severe, acute or chronic diseases, such as liver injury and liver cancer resulting from hepatitis C virus (HCV) infection, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) caused by dengue virus (DENV). Given the highly complex pathogenesis of Flaviviridae infections, they are still not fully understood at present. Accumulating evidence suggests that host autophagy is disrupted to regulate the life cycle of Flaviviridae. Organelle-specific autophagy is able to selectively target different organelles for quality control, which is essential for regulating cellular homeostasis. As an important sub process of autophagy, lipophagy regulates lipid metabolism by targeting lipid droplets (LDs) and is also closely related to the infection of a variety of pathogenic microorganisms. In this review, we briefly understand the LDs interaction relationship with Flaviviridae infection, outline the molecular events of how lipophagy occurs and the related research progress on the regulatory mechanisms of lipophagy in Flaviviridae infection. Exploring the crosstalk between viral infection and lipophagy induced molecular events may provide new avenues for antiviral therapy.
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Affiliation(s)
- Keke Wu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Shuangqi Fan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Linke Zou
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Feifan Zhao
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Shengming Ma
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Jindai Fan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Xiaowen Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Mingqiu Zhao
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Huichao Yan
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
| | - Jinding Chen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China
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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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Qasim SF, Jami A, Imran P, Mushtaque R, Khan RN. Frequency of Metabolic Syndrome in Chronic Hepatitis C Patients: Findings From a Lower Middle Income Country. Cureus 2020; 12:e11975. [PMID: 33425547 PMCID: PMC7790323 DOI: 10.7759/cureus.11975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Introduction The world over, hepatitis C virus (HCV) engenders the risk of developing chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). It has many extrahepatic manifestations, among which diabetes and metabolic syndrome (MetS) has been increasingly recognized and has become an active research field. The current study aimed to ascertain the frequency of MetS in chronic hepatitis C patients and to curb its long-term adverse outcomes. Methods In our cross-sectional analysis, a total of 331 subjects diagnosed with chronic HCV were registered from June 2017 to November 2018 in two tertiary care hospitals of Karachi, Pakistan. Metabolic syndrome (MetS) was delineated following the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Categorical variables were compared by using the Chi-square test, and a significant P value was at the value of < 0.05. Results We found that adults of 40 - 49 years of age were the worst sufferers of hepatitis C. Out of the total 331 patients of hepatitis C, 97 (29.3%) cases were suffering from metabolic syndrome. Conclusion Prevalence of MetS is substantial among HCV-infected individuals Therefore estimation of MetS in individuals with HCV infection is imperative and patients should be educated for lifestyle modification, diet, and weight control. However, we cannot generalized the results of our study as it was done in some tertiary care centres, so additional surveys are warranted to know the actual prevalence of MetS in our entire population.
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Affiliation(s)
- Saeeda Fouzia Qasim
- Internal Medicine, Liaquat College of Medicine and Dentistry, Karachi, PAK.,Endocrinology, Diabetes and Metabolism, Jinnah Postgraduate Medical Centre, Karachi, PAK
| | - Ajmaal Jami
- Medicine, Hamdard College of Medicine and Dentistry, Hamdard University, Karachi, PAK
| | - Paras Imran
- Endocrinology, Diabetes and Metabolism, Jinnah Postgraduate Medical Centre, Karachi, PAK.,Medicine, Civil Hospital Karachi, Karachi, PAK
| | - Romana Mushtaque
- Internal Medicine, Kulsoom Bai Valika Social Security Site Hospital, Karachi, PAK
| | - Rashid Naseem Khan
- Internal Medicine, Liaquat College of Medicine and Dentistry, Karachi, PAK
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Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma. Clin Exp Hepatol 2020; 6:235-242. [PMID: 33145430 PMCID: PMC7592085 DOI: 10.5114/ceh.2020.99517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 05/28/2020] [Indexed: 12/16/2022] Open
Abstract
Aim of the study Hepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC. Material and methods We included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin. Results Compared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage. Conclusions Metabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.
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Diniz KGD, Vieira DA, Colosimo EA, Coelho MPP, Bering T, Teixeira R, Correia MITD, Rocha GA, Silva LD. Derivation and validation of a simple anthropometric equation to predict fat-free mass in patients with chronic hepatitis C. Clin Nutr 2020; 40:1281-1288. [PMID: 32861484 DOI: 10.1016/j.clnu.2020.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 07/11/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Loss of skeletal muscle mass is very common in chronic liver diseases and affects 30.0-70.0% of the patients with cirrhosis. Given the relevance of muscle wasting in hepatic diseases, a practical screening tool for earlier detection of skeletal muscle mass loss is of utmost significance. AIMS To develop and validate a simple anthropometric prediction equation for fat-free mass estimation by using Bioelectrical Impedance Analysis (BIA) as a reference method in patients with chronic hepatitis C (CHC). METHODS We prospectively, included 209 CHC patients, randomly allocated into two groups, 158 patients in a development model (derivation sample) and 51 patients in a validation group (validation sample). Predictive equations were developed using backward stepwise multiple regression and the most adequate and simplest derived predictive equation was further explored for agreement and bias in the validation sample. The accuracy of the predictive equation was evaluated using the coefficient of determination (R2). RESULTS The predictive equation with an optimal R2 was Fat-Free Mass (Kg) = Sex × 0.17 + Height (m) × 16.83 + Weight (Kg) × 0.62 + Waist Circumference (cm) × (-0.15) + Weight (Kg) × Sex × (-0.30) + Sex × Waist Circumference (cm) × 0.14-6.23; where sex = 1 for female and 0 for male. R2 = 0.93, standard error of the estimate = 2.6 Kg and coefficient of variation = 20.0%, p < 0.001. CONCLUSIONS Our developed and cross-validated anthropometric prediction equation for fat-free mass estimation by using BIA attained a high coefficient of determination, a low standard error of the estimate, and lowermost coefficient of variation. This study indicates that predictive equations may be reliable and useful alternative methods for clinical evaluation of fat-free mass in patients with CHC.
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Affiliation(s)
- Kiara Gonçalves Dias Diniz
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Diego Alves Vieira
- Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Enrico Antonio Colosimo
- Department of Statistics, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Marta Paula Pereira Coelho
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Tatiana Bering
- Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Food and Nutrition, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Mato Grosso, Brazil
| | - Rosangela Teixeira
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | | | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Luciana Diniz Silva
- Sciences Applied to Adult Health Care Post-Graduate Programme, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil; Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
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Frisardi V. Commentary: Coronavirus and Obesity: Could Insulin Resistance Mediate the Severity of Covid-19 Infection? Front Public Health 2020; 8:351. [PMID: 32733840 PMCID: PMC7358339 DOI: 10.3389/fpubh.2020.00351] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 06/22/2020] [Indexed: 01/04/2023] Open
Affiliation(s)
- Vincenza Frisardi
- Geriatric and NeuroRehabilitation Department, Clinical and Nutritional Lab, AUSL-IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
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Surlin P, Gheorghe DN, Popescu DM, Martu AM, Solomon S, Roman A, Lazar L, Stratul SI, Rusu D, Foia L, Boldeanu MV, Boldeanu L, Danilescu M, Rogoveanu I. Interleukin-1α and -1β assessment in the gingival crevicular fluid of periodontal patients with chronic hepatitis C. Exp Ther Med 2020; 20:2381-2386. [PMID: 32765719 PMCID: PMC7401928 DOI: 10.3892/etm.2020.8906] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 05/26/2020] [Indexed: 12/12/2022] Open
Abstract
The study assessed whether the increased production of interleukin-1α (IL-1α) and interleukin-1β (IL-1β), as a result of chronic hepatic inflammation, could be the expression of the negative impact on periodontal disease. The study included chronic periodontitis patients who were systemically healthy, chronic periodontitis patients suffering from chronic hepatitis C, as well as control patients, being systemically and periodontally healthy. After periodontal examination and the assessment of certain periodontal parameters, gingival crevicular fluid was collected from all participating patients. By using the enzyme-linked immunosorbent assay method, a quantitative assessment of IL-1α and IL-1β levels was possible. The immunologic results were correlated to the clinical periodontal data. The gingival fluid levels of cytokines were higher for periodontitis patients with chronic hepatitis C than for the systemically healthy periodontitis patients (1.8-fold higher for IL-1α and 2.1-fold higher for IL-1β). In addition, the gingival fluid cytokine levels were significantly higher for the periodontal patients (with/without chronic hepatitis C) than for the control group. Positive correlations were found between gingival fluid IL-1α and IL-1β levels and certain clinical periodontal parameters or the age of the viral hepatitis C diagnosis, in periodontitis patients with chronic hepatitis C. The chronic hepatic inflammation may have an important additional negative impact on the periodontal status, as both inflammatory reactions seem to be promoted by common pro-inflammatory cytokines.
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Affiliation(s)
- Petra Surlin
- Department of Periodontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dorin Nicolae Gheorghe
- Department of Periodontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dora Maria Popescu
- Department of Periodontology, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Alexandra Maria Martu
- Department of Periodontology, Faculty of Dental Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Sorina Solomon
- Department of Periodontology, Faculty of Dental Medicine, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Alexandra Roman
- Department of Periodontology, Faculty of Dental Medicine, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania
| | - Luminita Lazar
- Department of Periodontology, Faculty of Dental Medicine, 'George Emil Palade' University of Medicine, Pharmacy, Science and Technology, 540139 Targu-Mures, Romania
| | - Stefan Ioan Stratul
- Department of Periodontology, Faculty of Dental Medicine, 'Victor Babes' University of Medicine and Pharmacy, 300230 Timisoara, Romania
| | - Darian Rusu
- Department of Periodontology, Faculty of Dental Medicine, 'Victor Babes' University of Medicine and Pharmacy, 300230 Timisoara, Romania
| | - Liliana Foia
- Department of Biochemistry, 'Grigore T. Popa' University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Mihail Virgil Boldeanu
- Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lidia Boldeanu
- Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Monica Danilescu
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ion Rogoveanu
- Department of Gastroenterology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Shawky M, Mohammed A, Hassan A, Ali B, Moustafa H. Insulin resistance in nondiabetic Egyptian patients with chronic hepatitis C virus. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2019.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Shawky MA, Mohammed AQ, Hassan AM, Ali BH, Moustafa HM. Insulin resistance in nondiabetic Egyptian patients with chronic hepatitis C virus. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:173-179. [PMID: 31784195 DOI: 10.1016/j.rgmx.2019.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 05/27/2019] [Accepted: 05/31/2019] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVE Insulin resistance and diabetes mellitus are frequently associated with chronic hepatitis C virus (HCV) infection, and it is thought that the presence of insulin resistance aggravates liver disease. We aimed to evaluate insulin resistance in nondiabetic Egyptian patients with chronic HCV infection. MATERIALS AND METHODS Sixty nondiabetic patients with chronic HCV infection and 30 healthy nondiabetic non-HCV-infected volunteers were enrolled in our study. They were divided into 3 groups: group 1 included 30 patients with chronic HCV infection with no cirrhosis, group 2 included 30 patients with chronic HCV infection and cirrhosis of the liver, and group 3 included 30 healthy volunteers as controls. The entire study population underwent a detailed clinical history and physical examination, weight and height measurement, routine laboratory tests, and viral marker determination that included hepatitis B surface antigen and HCV antibodies. PCR analysis was carried out on the patients with positive HCV antibodies. Fasting blood sugar and fasting insulin levels were measured in all the patients, and insulin resistance was calculated according to the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS Patients with cirrhosis of the liver (2 patients with Child class A, 12 patients with Child class B, and 16 patients with Child class C) showed higher insulin resistance levels (2.76±0.97) than the patients with chronic HCV infection and no cirrhosis (2.03±0.743) and the control group (1.22±0.38). The p value was significantly different between the 3 groups. There were direct and significant correlations between insulin resistance, fasting blood sugar, and fasting insulin levels. Patients with chronic HCV infection showed significantly higher fasting insulin and glucose levels than the control group. CONCLUSION Chronic HCV-infected patients showed significantly higher insulin resistance levels than the normal population, even in the absence of hepatic dysfunction and cirrhosis.
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Affiliation(s)
- M A Shawky
- Departamento de Medicina Tropical y Gastroenterología, Universidad de Al-Azhar, Assiut, Egipto.
| | - A Q Mohammed
- Departamento de Medicina Tropical y Gastroenterología, Universidad de Al-Azhar, Assiut, Egipto
| | - A M Hassan
- Departamento de Medicina Tropical y Gastroenterología, Universidad de Al-Azhar, Assiut, Egipto
| | - B H Ali
- Medicina Interna, Centro Sohag de Hepatología y Cardiología, Sohag, Egipto
| | - H M Moustafa
- Departamento de Medicina Tropical y Gastroenterología, Universidad de Al-Azhar, Assiut, Egipto
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Iliescu EL, Mercan-Stanciu A, Toma L. Safety and efficacy of direct-acting antivirals for chronic hepatitis C in patients with chronic kidney disease. BMC Nephrol 2020; 21:21. [PMID: 31948406 PMCID: PMC6966843 DOI: 10.1186/s12882-020-1687-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment. METHODS We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion. RESULTS All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients. CONCLUSIONS HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.
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Affiliation(s)
- Elena Laura Iliescu
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania.
| | - Adriana Mercan-Stanciu
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania
| | - Letitia Toma
- Department of Internal Medicine II, Fundeni Clinical Institute, 022328, Bucharest, Romania
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Niccum BA, Stine JG, Wynter JA, Kelly V, Caldwell SH, Shah NL. Success of Direct-Acting, Antiviral-Based Therapy for Chronic Hepatitis C Is Not Affected by Type 2 Diabetes. Clin Diabetes 2020; 38:40-46. [PMID: 31975750 PMCID: PMC6969670 DOI: 10.2337/cd18-0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Chronic hepatitis C virus (HCV) is a risk factor for type 2 diabetes. In the era of interferon-based HCV therapy, type 2 diabetes was associated with decreased likelihood of sustained virologic response (SVR). Preliminary studies suggest that type 2 diabetes may not reduce the efficacy of regimens involving direct-acting antiviral (DAA) medications. We aimed to determine whether preexisting type 2 diabetes is associated with a reduced rate of SVR achieved 12 weeks after treatment of HCV with DAA-based regimens.
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Affiliation(s)
- Blake A. Niccum
- Department of Internal Medicine, Massachusetts General Hospital, Boston, MA
| | - Jonathan G. Stine
- Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Javelle A. Wynter
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Virginia Kelly
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Stephen H. Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
| | - Neeral L. Shah
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA
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Altered Metabolic Profile and Adipocyte Insulin Resistance Mark Severe Liver Fibrosis in Patients with Chronic Liver Disease. Int J Mol Sci 2019; 20:ijms20246333. [PMID: 31888144 PMCID: PMC6940758 DOI: 10.3390/ijms20246333] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/06/2019] [Accepted: 12/09/2019] [Indexed: 02/07/2023] Open
Abstract
Metabolomics/lipidomics are important tools to identify novel biomarkers associated with liver damage. Patients with chronic liver disease (CLD) and hepatitis C virus (HCV) infection often have alterations in glucose, lipid and protein metabolism. The aim of this study was to evaluate if dysfunctional lipid and amino acid metabolism was associated with fibrosis severity and insulin resistance in CLD/HCV patients. We analyzed the baseline sera of 75 subjects with CLD/HCV infection HCV genotype-1, with proven liver biopsy prior to antiviral treatment. We measured amino acid (AA) and lipid concentration by gas and liquid chromatography-mass spectrometry respectively. Alterations in peripheral glucose metabolism due to insulin resistance (IR) were assesed by HOMA-IR (Glucose x Insulin/22.5), while adipose tissue IR was estimated as (Adipo-IR = Free Fatty Acids x Insulin). Baseline HOMA-IR and Adipo-IR were related to the degree of liver fibrosis. Reduction in ceramides 18:1/22:0, 18:1/24:0, diacylglycerol 42:6 and increased phosphocholine 40:6 were associated with higher fibrosis. Adipo-IR was related to lower levels of lysophosphatidylcholine 14:0 and 18:2 and with higher levels of sphingomyelin 18:2/24:0 and 18:2/24:1. Almost all AA were positively associated with Adipo-IR but not with HOMA-IR. We further confirmed the potential use of metabolomics and lipidomics in CLD/HCV subjects finding novel biomarkers of hepatic fibrosis and show that the adipose tissue IR is associated with more severe liver disease and is an important marker not only of altered lipid but also AA metabolism.
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Hepatitis C Virus Downregulates Core Subunits of Oxidative Phosphorylation, Reminiscent of the Warburg Effect in Cancer Cells. Cells 2019; 8:cells8111410. [PMID: 31717433 PMCID: PMC6912740 DOI: 10.3390/cells8111410] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/05/2019] [Accepted: 11/06/2019] [Indexed: 02/08/2023] Open
Abstract
Hepatitis C Virus (HCV) mainly infects liver hepatocytes and replicates its single-stranded plus strand RNA genome exclusively in the cytoplasm. Viral proteins and RNA interfere with the host cell immune response, allowing the virus to continue replication. Therefore, in about 70% of cases, the viral infection cannot be cleared by the immune system, but a chronic infection is established, often resulting in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Induction of cancer in the host cells can be regarded to provide further advantages for ongoing virus replication. One adaptation in cancer cells is the enhancement of cellular carbohydrate flux in glycolysis with a reduction of the activity of the citric acid cycle and aerobic oxidative phosphorylation. To this end, HCV downregulates the expression of mitochondrial oxidative phosphorylation complex core subunits quite early after infection. This so-called aerobic glycolysis is known as the “Warburg Effect” and serves to provide more anabolic metabolites upstream of the citric acid cycle, such as amino acids, pentoses and NADPH for cancer cell growth. In addition, HCV deregulates signaling pathways like those of TNF-β and MAPK by direct and indirect mechanisms, which can lead to fibrosis and HCC.
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Kalmykova ZA, Kononenko IV, Mayorov AY. [Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis]. TERAPEVT ARKH 2019; 91:106-111. [PMID: 32598639 DOI: 10.26442/00403660.2019.10.000165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 12/12/2022]
Abstract
In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.
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Alsebaey A, Elhelbawy M. Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C. Trop Doct 2019. [DOI: https:/doi.org/10.1177/0049475519863231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Chronic hepatitis C (HCV) patients commonly have insulin resistance which is a risk factor for disease progression. Oesophageal varices may bleed with high mortality. We aimed to assess the relationship between insulin resistance and oesophageal varices. HCV-related compensated liver cirrhosis patients (n = 146) underwent gastroscopy and homeostasis model assessment (HOMA)-IR, HOMA-β and HOMA-S calculations. Their average age was 54.98 years; most (84.9%) patients were men and non-diabetic (60.3%). Patients with oesophageal varices had higher median Model for End-Stage Liver Disease (MELD) scores and comparable Child-Pugh class. Patients with and without oesophageal varices had comparable ( P > 0.05) HOMA scores and insulin resistance percentage of 82.9% versus 85.5%. We therefore conclude that insulin resistance is unrelated to the presence of oesophageal varices.
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Affiliation(s)
- Ayman Alsebaey
- Associate Professor, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
| | - Mostafa Elhelbawy
- Lecturer, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
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Alsebaey A, Elhelbawy M. Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C. Trop Doct 2019; 49:281-285. [PMID: 31296148 DOI: 10.1177/0049475519863231] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Chronic hepatitis C (HCV) patients commonly have insulin resistance which is a risk factor for disease progression. Oesophageal varices may bleed with high mortality. We aimed to assess the relationship between insulin resistance and oesophageal varices. HCV-related compensated liver cirrhosis patients (n = 146) underwent gastroscopy and homeostasis model assessment (HOMA)-IR, HOMA-β and HOMA-S calculations. Their average age was 54.98 years; most (84.9%) patients were men and non-diabetic (60.3%). Patients with oesophageal varices had higher median Model for End-Stage Liver Disease (MELD) scores and comparable Child-Pugh class. Patients with and without oesophageal varices had comparable (P > 0.05) HOMA scores and insulin resistance percentage of 82.9% versus 85.5%. We therefore conclude that insulin resistance is unrelated to the presence of oesophageal varices.
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Affiliation(s)
- Ayman Alsebaey
- Associate Professor, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
| | - Mostafa Elhelbawy
- Lecturer, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
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Alsebaey A, Elhelbawy M. Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C. Trop Doct 2019. [DOI: https://doi.org/10.1177/0049475519863231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Chronic hepatitis C (HCV) patients commonly have insulin resistance which is a risk factor for disease progression. Oesophageal varices may bleed with high mortality. We aimed to assess the relationship between insulin resistance and oesophageal varices. HCV-related compensated liver cirrhosis patients (n = 146) underwent gastroscopy and homeostasis model assessment (HOMA)-IR, HOMA-β and HOMA-S calculations. Their average age was 54.98 years; most (84.9%) patients were men and non-diabetic (60.3%). Patients with oesophageal varices had higher median Model for End-Stage Liver Disease (MELD) scores and comparable Child-Pugh class. Patients with and without oesophageal varices had comparable ( P > 0.05) HOMA scores and insulin resistance percentage of 82.9% versus 85.5%. We therefore conclude that insulin resistance is unrelated to the presence of oesophageal varices.
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Affiliation(s)
- Ayman Alsebaey
- Associate Professor, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
| | - Mostafa Elhelbawy
- Lecturer, Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
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Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism. Int J Mol Sci 2019; 20:ijms20184569. [PMID: 31540136 PMCID: PMC6769880 DOI: 10.3390/ijms20184569] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 08/29/2019] [Accepted: 09/09/2019] [Indexed: 12/13/2022] Open
Abstract
Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
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Liu Y, Ye S, Xiao X, Zhou T, Yang S, Wang G, Sun C, Zhang B, Wang G. Association of diabetes mellitus with hepatitis B and hepatitis C virus infection: evidence from an epidemiological study. Infect Drug Resist 2019; 12:2875-2883. [PMID: 31686868 PMCID: PMC6751765 DOI: 10.2147/idr.s218536] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 09/02/2019] [Indexed: 12/17/2022] Open
Abstract
Objective To study the association between glucose metabolism disorders and hepatotropic virus infection. Methods A cross-sectional analysis was performed using data from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Outcomes of the analysis were test results of kidney function, liver function, lipid metabolism, and the prevalence of hepatitis B virus (HBV) infection and potential hepatitis C virus (HCV) infection (positive hepatitis C virus antibody) among individuals with and without diabetes mellitus (DM) or pre-diabetes mellitus (pre-DM). Results Of the 10,080 patients who participated in the study, 7665 eligible subjects were included in the analysis. There was no significant difference in the prevalence of HBV infection between DM and normal subjects, pre-DM and normal subjects, and DM or pre-DM and normal subjects (p-values of 0.9180, 0.8154, and 0.6448, respectively). There was also no significant difference in the prevalence of potential HCV infection between DM and normal subjects, pre-DM and normal subjects, and DM or pre-DM and normal subjects (p-values of 0.1190, 0.0591, and 0.5591, respectively). Lipid metabolism showed a significant difference between DM or pre-DM subjects and normal subjects (p-values were less than 0.0221 in all cases). Multiple logistic regression analysis revealed hypertension as the leading significant variable associated with DM, pre-DM, and both. Other significant factors included gender, body mass index, age, and alanine aminotransferase. Conclusion No significant association was detected between DM or pre-DM and HBV or potential HCV infection. Significant association was detected between lipid metabolism disorders and DM, but this association was absent in pre-DM patients when adjusting for other factors.
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Affiliation(s)
- Yujia Liu
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Shangyuan Ye
- Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Xianchao Xiao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Tong Zhou
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Shuo Yang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Gang Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Chenglin Sun
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Bo Zhang
- Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
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Alsebaey A, Elhelbawy M, Abdel-Razek W, Hashim M, Elshenawy H, Waked I. HCV treatment with direct acting antivirals improves the insulin sensitivity. Expert Rev Anti Infect Ther 2019. [DOI: https://doi.org/10.1080/14787210.2019.1653184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Affiliation(s)
- Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Wael Abdel-Razek
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Mohammed Hashim
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Hassan Elshenawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
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Alsebaey A, Elhelbawy M, Abdel-Razek W, Hashim M, Elshenawy H, Waked I. HCV treatment with direct acting antivirals improves the insulin sensitivity. Expert Rev Anti Infect Ther 2019. [DOI: https:/doi.org/10.1080/14787210.2019.1653184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Affiliation(s)
- Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Wael Abdel-Razek
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Mohammed Hashim
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Hassan Elshenawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen Elkoom, Egypt
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Alsebaey A, Elhelbawy M, Abdel-Razek W, Hashim M, Elshenawy H, Waked I. HCV treatment with direct acting antivirals improves the insulin sensitivity. Expert Rev Anti Infect Ther 2019; 17:749-754. [PMID: 31393188 DOI: 10.1080/14787210.2019.1653184] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 08/05/2019] [Indexed: 02/08/2023]
Abstract
Background: There is strong link between hepatitis C virus (HCV) infection and the insulin resistance panel. Homeostatic model assessment (HOMA) β is an indirect measurement of insulin secretion from pancreatic β cells, while HOMA-S accounts for insulin sensitivity. Aim: We examined the impact of HCV treatment with direct acting antivirals (DAAs) on HOMA-β and HOMA-S results. Methods: HOMA-IR, HOMA-β, and HOMA-S were calculated before and 12 weeks after treatment in 511 treatment eligible patients with HCV. Five DAA treatment protocols were used. Values before and after treatment were compared. Results: The mean age of patients was 50.63 years with a 3.2:1 male: female ratio. A total of 29.7% of patients were treatment experienced and 24.7% had diabetes. HCV sustained virological response (SVR) was achieved in 91% of patients. Unlike non-responders, SVR patients showed significantly decreased post-treatment HOMA-Β. Delta HOMA-Β was comparable between groups. HOMA-S increased significantly in patients with SVR compared to in non-responders, as did delta HOMA-S. HOMA-S and HOMA-β improved significantly under 5 and 2 DAA protocols, respectively. The treatment status did not affect the HOMA-β and S dynamics during treatment. Conclusions: Insulin sensitivity improved markedly in patients who achieved HCV SVR.
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Affiliation(s)
- Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
| | - Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
| | - Wael Abdel-Razek
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
| | - Mohammed Hashim
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
| | - Hassan Elshenawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University , Shebeen Elkoom , Egypt
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Coronel-Castillo CE, Qi X, Contreras-Carmona J, Ramírez-Pérez OL, Méndez-Sánchez N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in HIV infection: a metabolic approach of an infectious disease. Expert Rev Gastroenterol Hepatol 2019; 13:531-540. [PMID: 30905208 DOI: 10.1080/17474124.2019.1599284] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 03/21/2019] [Indexed: 02/07/2023]
Abstract
With the successes of antiretroviral therapy, patients infected with human immunodeficiency virus (HIV) living longer. Regarding this, the common diseases of HIV population (i.e., opportunistic infections) are now losing ground in front of metabolic alterations. This phenomenon is related to the delay in progression to acquired immune deficiency syndrome (AIDS), making it so that patients live in a chronic inflammatory state which, combined with other mechanisms such infectious ones, cause metabolic diseases. Areas covered: Considering a high prevalence of metabolic alterations, the relationship between metabolic syndrome (MetS) with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and liver diseases as a major cause of death in the HIV-infected population, this paper aims to overview the mechanisms and prevalence of NAFLD and NASH as they relate to the developed metabolic diseases of HIV patients. Expert opinion: The pathways underlying MetS include the effects of HIV and ART on the liver, adipose tissue, and muscle. These mechanisms result in liver damage, consequently leading to NAFLD and its more severe form NASH. These conditions have increased in HIV-infected population in recent years and since their life expectancy is improving it is important to be ready to attend their new emerging diseases.
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Affiliation(s)
| | - Xingshun Qi
- b Department of Gastroenterology , General Hospital of Shenyang Military Area , Shenyang , China
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Bai J, Liu F. The cGAS-cGAMP-STING Pathway: A Molecular Link Between Immunity and Metabolism. Diabetes 2019; 68:1099-1108. [PMID: 31109939 PMCID: PMC6610018 DOI: 10.2337/dbi18-0052] [Citation(s) in RCA: 158] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 03/04/2019] [Indexed: 02/06/2023]
Abstract
It has been appreciated for many years that there is a strong association between metabolism and immunity in advanced metazoan organisms. Distinct immune signatures and signaling pathways have been found not only in immune but also in metabolic cells. The newly discovered DNA-sensing cGAS-cGAMP-STING pathway mediates type I interferon inflammatory responses in immune cells to defend against viral and bacterial infections. Recent studies show that this pathway is also activated by host DNA aberrantly localized in the cytosol, contributing to increased sterile inflammation, insulin resistance, and the development of nonalcoholic fatty liver disease (NAFLD). Potential interactions of the cGAS-cGAMP-STING pathway with mTORC1 signaling, autophagy, and apoptosis have been reported, suggesting an important role of the cGAS-cGAMP-STING pathway in the networking and coordination of these important biological processes. However, the regulation, mechanism of action, and tissue-specific role of the cGAS-cGAMP-STING signaling pathway in metabolic disorders remain largely elusive. It is also unclear whether targeting this signaling pathway is effective for the prevention and treatment of obesity-induced metabolic diseases. Answers to these questions would provide new insights for developing effective therapeutic interventions for metabolic diseases such as insulin resistance, NAFLD, and type 2 diabetes.
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Affiliation(s)
- Juli Bai
- Department of Pharmacology, UT Health San Antonio, San Antonio, TX
| | - Feng Liu
- Department of Pharmacology, UT Health San Antonio, San Antonio, TX
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Liang J, Lv C, Chen M, Xu M, Zhao C, Yang Y, Wang J, Zhu D, Gao J, Rong R, Zhu T, Yu M. Effects of preoperative hepatitis B virus infection, hepatitis C virus infection, and coinfection on the development of new-onset diabetes after kidney transplantation. J Diabetes 2019; 11:370-378. [PMID: 30203544 DOI: 10.1111/1753-0407.12853] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Revised: 09/03/2018] [Accepted: 09/05/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The effects of preoperative hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and HBV plus HCV coinfection on the development of new-onset diabetes after transplantation (NODAT) remain unexplored in kidney transplant recipients (KTRs). This study examined the association between preoperative viral status (i.e., HBV, HCV, and HBC + HCV infection) and incident NODAT in a large population of Chinese KTRs. METHODS This population-based retrospective cohort study enrolled 557 subjects who underwent kidney transplantation between 1993 and 2014 at Zhongshan Hospital. Pre-, peri-, and postoperative data were extracted and analyzed. Viral status was defined by serological results for hepatitis B surface antigen and anti-HCV antibody. The cumulative incidence of NODAT was compared across four groups of KTRs with different viral status. Multivariate Cox regression models were used to estimate the effects of HBV, HCV, and HBC + HCV infection on incident NODAT after adjusting for important confounders. RESULTS Patients seropositive for HCV (both HCV monoinfection and HBC + HCV coinfection) had a significantly higher cumulative incidence of NODAT than KTRs who were not infected with HCV (P < 0.05 for both). However, only HCV infection alone was found to be a risk factor for NODAT, increasing the NODAT risk 3.03-fold (95% confidence interval 1.77-5.18; P < 0.001). There was no independent correlation between HBV infection (alone or combined with HCV) and incident NODAT in KTRs. CONCLUSIONS Preoperative HCV infection significantly increased the risk of NODAT in Chinese KTRs, whereas HBV infection and HBC + HCV coinfection were not correlated with NODAT development.
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Affiliation(s)
- Jing Liang
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Geriatric Endocrinology, Zhengzhou Seventh People's Hospital, Zhengzhou, China
| | - Minling Chen
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Endocrinology and Metabolism, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (The People's Hospital of Fujian Province), Fuzhou, China
| | - Ming Xu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Chenhe Zhao
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinqiu Yang
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jina Wang
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Dong Zhu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Ruiming Rong
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
- Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tongyu Zhu
- Department of Urology, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Mingxiang Yu
- Departments of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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Huang CH, Wu LS, Jeng WJ, Cheng YF, Ko YS, Sheen IS, Lin CY. In HCV-related liver cirrhosis, local pulse wave velocity increases and in decompensated patients correlates with poorer survival. PLoS One 2019; 14:e0212770. [PMID: 30889181 PMCID: PMC6424395 DOI: 10.1371/journal.pone.0212770] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 02/08/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease. METHODS Control group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status. RESULTS There were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817). CONCLUSIONS In patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Lung-Sheng Wu
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Wen-Juei Jeng
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Yu-Fu Cheng
- Department of Internal medicine, Chang-Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan
| | - Yu-Shien Ko
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - I-Shyan Sheen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
- College of Medicine, Chang-Gung University, Taoyuan, Taiwan
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Ray RB, Ray R. Hepatitis C Virus Manipulates Humans as its Favorite Host for a Long-Term Relationship. Hepatology 2019; 69:889-900. [PMID: 30102776 PMCID: PMC6351149 DOI: 10.1002/hep.30214] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis C virus (HCV) infection-associated liver disease is a global health problem. HCV often causes silent disease, and eventually progresses to end-stage liver disease. HCV infects hepatocytes; however, initial manifestation of liver disease is mostly displayed in hepatic stellate cells (HSCs), causing fibrosis/cirrhosis, and is believed to occur from inflammation in the liver. It remains unclear why HCV is not spontaneously cleared from infected liver in the majority of individuals and develops chronic infection with progressive liver disease. Direct-acting antivirals (DAAs) show excellent results in controlling viremia, although beneficial consequence in advanced liver disease remains to be understood. In this review, we highlight the current knowledge that has contributed to our understanding of the role of HCV in inflammation, immune evasion, metabolic disorders, liver pathogeneses, and efforts in vaccine development.
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Affiliation(s)
- Ratna B. Ray
- Department of Pathology, Saint Louis University, Saint Louis, Missouri 63104, USA,Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri 63104, USA
| | - Ranjit Ray
- Department of Internal Medicine, Saint Louis University, Saint Louis, Missouri 63104, USA
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Elhelbawy M, Abdel-Razek W, Alsebaey A, Hashim M, Elshenawy H, Waked I. Insulin resistance does not impair response of chronic hepatitis C virus to direct-acting antivirals, and improves with the treatment. Eur J Gastroenterol Hepatol 2019; 31:16-23. [PMID: 30024489 DOI: 10.1097/meg.0000000000001215] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Insulin resistance (IR) is a common complication in chronic hepatitis C virus (HCV) patients. The impact of IR on outcome of therapy with direct antivirals has not been studied. AIM The aim was to assess the impact of direct-acting antiviral (DAA) therapy on IR status in chronic HCV patients. PATIENTS AND METHODS A total of 511 patients [mean age: 50.7±10.4 years, 29.7% pegylated interferon and ribavirin (RBV) experienced] were enrolled. Patients with uncontrolled diabetes, decompensated liver disease, or previous nonresponse to DAAs were excluded. Homeostatic model assessment (HOMA) was calculated before and 12 weeks after treatment, and IR was defined as HOMA greater than 1.9. Patients were treated according to the treating physician's choice, and received 12 weeks of either ombitasvir/ritonavir/paritaprevir/RBV (n=28); sofosbuvir (SOF)/simeprevir (n=36); SOF/ravidasvir (n=101); SOF/pegylated interferon/RBV (n=192); or 24 weeks of SOF/RBV (n=154). RESULTS Most patients received IR pretreatment (80.6%); 51.3% had fibrosis stage F4 and 24.7% had diabetes. A sustained virological response (SVR) at 12 weeks after treatment (SVR12) was achieved in 465 (91%) patients. SVR12 was achieved in 90.5% of patients with IR and in 92.9% of patients without IR (P=0.560), and pretreatment HOMA was not different in responders and nonresponders (P=0.098). The number of patients with IR decreased significantly in patients who achieved an SVR much more than in nonresponders (P<0.0001) and HOMA improved significantly more in patients with SVR than in nonresponders (P=0.001). All treatment protocols were associated with a comparable improvement in HOMA (P=0.101). Predictors of SVR12 included age, platelets, and liver stiffness, but not pretreatment IR. CONCLUSION IR does not impair the response of patients with HCV treated with DAAs, and improves significantly in patients who achieve an SVR.
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Affiliation(s)
- Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Koom, Egypt
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Pan-Genotypic Hepatitis C Treatment with Glecaprevir and Pibrentasvir for 8 Weeks Resulted in Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function: A Post-Hoc Analysis of Phase 3 Clinical Trials. Infect Dis Ther 2018; 7:473-484. [PMID: 30368684 PMCID: PMC6249176 DOI: 10.1007/s40121-018-0218-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Indexed: 02/06/2023] Open
Abstract
Introduction Chronic hepatitis C (CHC) infection is associated with extrahepatic manifestations (EHMs) which can affect renal, cardiovascular and other comorbidities. The effect of CHC treatment with short-duration regimens on these EHMs is not well defined. Hence, we examined longitudinal estimated glomerular filtration rate (eGFR), triglycerides and glucose values to assess the impact of short-duration CHC therapy on renal, cardiovascular and metabolic diseases, respectively. Methods We conducted analyses of all patients without cirrhosis treated with glecaprevir and pibrentasvir (G/P) for 8 weeks in two phase 3 clinical trials. In addition, one phase 3 trial was carried out to explore the effects of treatment on renal EHMs in patients with advanced renal impairment at baseline. As a sensitivity analysis, we included all CHC patients treated with G/P for 8 or 12 weeks enrolled across five phase 3 trials. Adjusting for baseline demographics and clinical properties via mixed regression models enabled evaluation of changes in EHMs through end of treatment. Results G/P treatment for 8 weeks resulted in statistically significant declines in triglycerides (− 28.6 mg/dl) and glucose (− 11.2 mg/dl), while there was no statistically significant decline in eGFR. Biomarker improvements were greatest among patients with elevated triglycerides and elevated glucose at baseline. Similar effects were observed across all patients treated with G/P for 8 or 12 weeks. Conclusion Short-duration treatment with G/P resulted in stable renal function and improvements in cardiovascular and metabolic EHM markers, especially in patients with severe EHMs at baseline. Funding AbbVie Inc. Electronic supplementary material The online version of this article (10.1007/s40121-018-0218-x) contains supplementary material, which is available to authorized users.
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Iliescu L, Mercan-Stanciu A, Toma L, Ioanitescu E. A SEVERE CASE OF HYPERGLYCEMIA IN A KIDNEY TRANSPLANT RECIPIENT UNDERGOING INTERFERON-FREE THERAPY FOR CHRONIC HEPATITIS C. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2018; 14:533-538. [PMID: 31149309 PMCID: PMC6516407 DOI: 10.4183/aeb.2018.533] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
CONTEXT Hepatitis C and diabetes represent important health problems globally. The new-onset diabetes after transplantation is a particular entity that appears due to the use of immunosuppression among transplanted patients. OBJECTIVE We aim to describe the clinical and biological aspects of severe hyperglycemia in a kidney transplant recipient undergoing Interferon-free therapy for chronic hepatitis C, discussing the interference of different factors with the glucose metabolism. DESIGN The occurrence of diabetes in a patient with history of renal transplantation and Interferon-free treated hepatitis C was studied from both clinical and paraclinical points of view. SUBJECTS AND METHODS When presenting to the hospital, extensive blood tests were performed on the patient, revealing significant hyperglycemia and an elevated level of blood tacrolimus. Creatinine clearance was calculated. ECG presented T-wave alterations. Intensive insulin protocol was applied, the case being managed in a multidisciplinary approach. RESULTS Blood glucose and tacrolimus were slowly normalized, under therapy. The antiviral treatment was continued, with the achievement of sustained virologic response. CONCLUSIONS Diabetes mellitus can have many causes, hepatitis C and transplantation both having an impact on glucose metabolism. The association of the three entities should be carefully managed, due to its enhancing effect on morbidity and mortality.
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Affiliation(s)
- L. Iliescu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - A. Mercan-Stanciu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - L. Toma
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - E.S. Ioanitescu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
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