RESUMO
Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations. Patients with HCV may develop mixed cryoglobulinemia and its sequelae, ranging from cutaneous and visceral vasculitis to glomerulonephritis and B-cell non-Hodgkin lymphoma. HCV-infected patients have increased rates of insulin resistance, diabetes, and atherosclerosis, which may lead to increased cardiovascular morbidity and mortality. Neurological manifestations of HCV infection include fatigue and cognitive impairment. The mechanisms causing the extrahepatic effects of HCV infection are likely multifactorial and may include endocrine effects, HCV replication in extrahepatic cells, or a heightened immune reaction with systemic effects. Successful eradication of HCV with interferon alfa and ribavirin was shown to improve some of these extrahepatic effects; sustained virological response is associated with resolution of complications of cryoglobulinemia, reduced levels of insulin resistance, reduced incidence of diabetes and stroke, and improved fatigue and cognitive functioning. The availability of new interferon-free, well-tolerated anti-HCV treatment regimens is broadening the spectrum of patients available for therapy, including those in whom interferon was contraindicated, and will likely result in greater improvements in the extrahepatic manifestations of HCV. If these regimens are shown to confer significant benefit in the metabolic, cardiovascular, or neuropsychiatric conditions associated with HCV infection, extrahepatic manifestations of HCV may become a major indication for treatment even in the absence of liver disease.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/mortalidade , Antivirais/administração & dosagem , Crioglobulinemia/epidemiologia , Crioglobulinemia/virologia , Glomerulonefrite/epidemiologia , Glomerulonefrite/virologia , Transtornos do Metabolismo de Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/virologia , Hepacivirus/patogenicidade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Linfoma/epidemiologia , Linfoma/virologia , Morbidade , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Vasculite/epidemiologia , Vasculite/virologiaRESUMO
OBJECTIVE: We investigated prevalence and predictors of glucose metabolism disorders (GMDs) among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART). METHODS: This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to determine predictors. RESULTS: The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0-32.6%] s, with 31.1% (75/240) [95% CI 25.4-37.5%] for efavirenz-based and 19.8% (22/111) [95% CI 12.9-28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240); 95%CI (11.1-20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2-13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age ≥46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in both groups. Whereas the male gender and BMI category were predictors of GMDs among EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were predictors in the ATV/r-based group. CONCLUSIONS: GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age ≥46 years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for early diagnosis of type-2 diabetes and management.
Assuntos
Quimioterapia Combinada/efeitos adversos , Transtornos do Metabolismo de Glucose/epidemiologia , Infecções por HIV/metabolismo , Adulto , Alcinos/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Sulfato de Atazanavir/uso terapêutico , Benzoxazinas/uso terapêutico , Glicemia/análise , Estudos Transversais , Ciclopropanos/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Etiópia/epidemiologia , Feminino , Glucose/metabolismo , Transtornos do Metabolismo de Glucose/virologia , HIV/patogenicidade , Humanos , Insulina/metabolismo , Masculino , Prevalência , Ritonavir/uso terapêuticoRESUMO
BACKGROUND: COVID-19 has become a global epidemic, causing huge loss of life and property. Diabetes will affect the prognosis of COVID-19 patients in many ways. Both hyperglycemia and hypoglycemia can affect oxidative stress and lead to the release of inflammatory mediators, leading to multiple organ damage and chronic inflammation. Here, we want to know whether hyperglycemia or hypoglycemia will adversely affect patients with diabetes and COVID-19 comorbidities. This has very important practical significance for the control of blood glucose in the treatment of diabetes combined with SARS-COV-2 infection. METHODS: We will search electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database using keywords related to COVID-19, diabetes mellitus, hyperglycemia and hypoglycemia. We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies, extract data, and evaluate risk of bias. Data analysis will be conducted using the Review Manager software version 5.3.5 and STATA4.0 software for Mac. The main outcome was the mortality of COVID-19 which was included in meta-analysis and subgroup analysis. The bias of the study was evaluated independently by NOS scale, and published by funnel chart. The sensitivity was analyzed row by row. RESULTS: This study will provide a high-quality synthesis of hyperglycemia and hypoglycemia in patients with COVID-19 combined with diabetes mellitus. To provide evidence for clinical treatment of diabetes mellitus combined with COVID-19. And the results will be published at a peer-reviewed journal.INPLASY registration number INPLASY 202080096.
Assuntos
Infecções por Coronavirus/complicações , Transtornos do Metabolismo de Glucose/complicações , Pneumonia Viral/complicações , Betacoronavirus , Glicemia , COVID-19 , Infecções por Coronavirus/sangue , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/virologia , Humanos , Metanálise como Assunto , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2 , Revisões Sistemáticas como AssuntoRESUMO
Hepatitis C and type 2 diabetes mellitus (DM) are two rising epidemics with significant impact on each other. Hepatitis C-infected patients have a higher incidence of type 2 diabetes, and diabetic patients have a high prevalence of hepatitis C. There is mounting evidence that glucose abnormalities have a negative impact on the disease progression as well as antiviral therapy outcomes. Utilization of oral glucose tolerance testing has the potential to uncover previously undetected DM as well as impaired glucose tolerance or prediabetes in patients with chronic hepatitis C (CHC). Early detection of diabetes and prediabetes with oral glucose tolerance testing in CHC patients can lead to interventions, with significant positive impact on disease progression and antiviral therapy outcomes.
Assuntos
Glicemia/metabolismo , Transtornos do Metabolismo de Glucose/diagnóstico , Transtornos do Metabolismo de Glucose/epidemiologia , Teste de Tolerância a Glucose , Hepatite C Crônica/sangue , Transtornos do Metabolismo de Glucose/virologia , Hepatite C Crônica/complicações , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Insulin resistance is highly prevalent in patients with chronic hepatitis C (CHC) and to some extent accounts for fibrosis and reducing viral eradication. Activated cannabinoid 1 receptor (CB1R) signaling has been implicated in the development of phenotypes associated with insulin resistance and steatosis. We investigated the role of the endocannabinoid system in glucose metabolism disorders induced by hepatitis C virus (HCV) replication. METHODS: Human hepatic stellate cells (HSC; LX-2 cells) were co-cultured with Huh-7.5 cells or Huh-7.5 cells harboring HCV replicon (replicon cells). Endocannabinoid levels were then measured by liquid chromatography/mass spectrometry. The expression of CB1R and its downstream glucose metabolism genes in hepatocytes were determined by real-time PCR and Western blot. Glucose uptake by hepatocytes and glucose production were measured. Glucose metabolism tests and measurements of HCV RNA levels and nonstructural protein 5A (NS5A) levels were taken after treatment with CB1R agonist arachidonyl-2-chloroethanolamide (ACEA) or antagonist AM251. RESULTS: Compared to the co-culture with Huh-7.5 cells, the level of 2-arachidonoylglycerol (2-AG) and the CB1R mRNA and protein levels increased in the co-culture of LX-2 cells with replicon cells. The activation of CB1R decreased AMP-activated protein kinase (AMPK) phosphorylation, inhibited cell surface expression of glucose transporter 2 (GLUT2), and suppressed cellular glucose uptake; furthermore, it increased cyclic AMP response element-binding protein H (CREBH), then up-regulated phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes and down-regulated the glucokinase (GK) gene, thus promoting glucose production. Interferon treatment restored the aforementioned changes. CB1R antagonist improved glucose metabolism disorders by an increase in glucose uptake and a decrease in glucose production, and inhibited HCV replication. CONCLUSIONS: HCV replication may not only increase the 2-AG content, but may also up-regulate the expression of CB1R of hepatocytes, then change the expression profile of glucose metabolism-related genes, thereby causing glucose metabolism disorders of hepatocytes and promoting HCV replication. Treatment with CB1R antagonist improved glucose metabolism disorders and inhibited viral genome replication.
Assuntos
Endocanabinoides/metabolismo , Transtornos do Metabolismo de Glucose/virologia , Hepacivirus/isolamento & purificação , Hepatócitos/virologia , Receptor CB1 de Canabinoide/metabolismo , Replicação Viral , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Araquidônicos/metabolismo , Ácidos Araquidônicos/farmacologia , Linhagem Celular , Sobrevivência Celular , Técnicas de Cocultura , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Genoma Viral , Transtornos do Metabolismo de Glucose/patologia , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Glicerídeos/metabolismo , Hepacivirus/fisiologia , Células Estreladas do Fígado/patologia , Células Estreladas do Fígado/virologia , Hepatite C Crônica/patologia , Hepatócitos/metabolismo , Humanos , Fosforilação , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/metabolismo , Pirazóis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/genética , Transdução de Sinais , Regulação para CimaRESUMO
OBJECTIVES: To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities. PATIENTS AND METHODS: This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months. RESULTS: None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases. CONCLUSION: SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Transtornos do Metabolismo de Glucose/prevenção & controle , Transtornos do Metabolismo de Glucose/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Humanos , Interferon-alfa/efeitos adversos , Estimativa de Kaplan-Meier , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Polietilenoglicóis/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Recidiva , Ribavirina/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVE: To investigate relationship between glucose metabolic disorders and expression of insulin receptor (IR) and tyrosine protein kinase (TPK) in posthepatitic cirrhosis hepatocyte and HBV DNA expression in pancreatic cells. METHODS: To detect HBV DNA in paraffin-embedded pancreatic and hepatic tissues from 12 posthepatitic cirrhosis patients with positive serum HBV markers by using in situ hybridization (ISH) with a digoxigenin labelled probe. The amount of IR and TPK have been evaluated by immunohistochemical quantitative analysis using image analyzer in hepatocyte of 12 patients positive for HBV markers with posthepatitic cirrhosis in serum. Immunofluorescent histochemical double staining technique was used. HBsAg and IR were observed under confocal laser scanning microscope. RESULTS: Eleven of 12 cirrhosis patients? hepatocytes were HBV DNA positive, including 7 patients (7/7) with impaired glucose tolerance (IGT) and 4 patients (4/5) with normal glucose tolerance (NGT). Eight of 12 pancreatic cells were HBV DNA positive, including 7 patients (7/7) with IGT, but only one patient (1/5) with NGT-HBV DNA was found positive in pancreatic cells in significantly more subjects in IGT group than in NGT group (P less than 0.01).IR and TPK amount in hepatocyte of IGT was significantly less than that of NGT patients with posthepatitic cirrhosis (P less than 0.01). IR amount was closely related to the TPK in cirrhosis hepatocyte r=0.82597(P less than 0.01). HBV DNA was mainly localized in the nuclei of hepatocyte and pancreatic acinar and islet cells. Immunofluorescent histochemical double-staining showed that HBsAg was partly localized in the IR positive areas of hepatocytes and pancreatic islet cells. CONCLUSION: HBV can invade acinar cells of pancreas and islet cells, which might be a direct cause of insulin-dependent diabetes mellitus-like the disorder and insulin absence after HBV infection. Decrease of IR and TPK might be main cause of noninsulin-dependent diabetes mellitus-like disorder after having hepatitis or posthepatitic cirrhosis.