La sindrome metabolica e il suo impatto dopo la guarigione nel paziente HIV/HCV

Transcription

1 WORKSHOP HCV: la guarigione e il parallelismo tra risposta virologica sostenuta e outcome clinico Milano, 25 Ottobre 2018 Ospedale San Raffaele IRCCS - Sede Turro La sindrome metabolica e il suo impatto dopo la guarigione nel paziente HIV/HCV Fracanzani AL Dipartimento di Fisiopatologia e dei Trapianti Centro Malattie Metaboliche del Fegato Fondazione Ca Granda IRCCS, Ospedale Maggiore Policlinico, Università di Milano

2 High triglycerides Visceral obesity Metabolic syndrome Insulin resistance/dia betes Low HDL Cholesterol Hypertension NAFLD Criteria for diagnosis of Metabolic Syndrome (MetS)

3 Prevalence of NAFLD Rinella, Hepatology 2016

4 Vanni, Hepatology 2009 Milner, Gastroenterology 2010 HCV, MetS and its complications HCV, hepatic and extrahepatic IR and atherosclerosis: possible mechanisms

5 HCV, MetS and its complications Relationship between HCV, the metabolic syndrome and its complications Shiffman and Gunn, Liv Int 2016

6 HCV, MetS and its complications Prevalence of extrahepatic manifestations in patients with HCV infection 2TDM (15%) Chronic kidney or end stage renal disease (16%) Lymphoma (0.4% ) Mixed cryoglobulinemia (5% ) Sjogren s syndrome (12%) Depression (25% ) Cardiovascular disease (12%) Stroke (1.9%) Younossi, Gastroenterology 2016

7 HCV, MetS and its complications Characteristics of patients with HCV chronic hepatitis with or without steatosis Adinolfi, Atherosclerosis 2012

8 HCV, MetS and its complications HCV infection and cardiovascular disease Carotid plaques Stroke Petta, Gastroenterology 2016

9 HCV, MetS and its complications Cardiovascular parameters in HCV patients with or without steatosis, in NAFLD/NASH and controls

10 HCV, MetS and therapy Independent factors associated with major cardiovascular events in patients with compensated HCV-related cirrhosis Cacoub, Am Heart J 2018

11 HCV, MetS and therapy Metabolic and cardiovascular risk according to response to anti viral therapy in HCV positive patients Mahale, Gut 2018

12 Cumulative development rate of T2D (%) HCV, MetS and therapy Cumulative incidence of type 2 diabetes in chronic hepatitis C: SVR vs non-svr 2842 Japanese non-diabetic patients with chronic hepatitis C followed for an average of 6.4 years after antiviral therapy Non-SVR Non-SVR 40 (n=139) (n=975) 40 p<0.001 p= p= Non-SVR (n=151) SVR (n=535) SVR (n=54) SVR (n=90) years 0 10 years 0 10 Age >50 years Cirrhosis Pre-diabetes years HCV eradication reduces the risk of developing T2D by more than two-thirds Arase, Hepatology 2009

13 HCV, MetS and therapy Diabetes free survival according to PegINF + Ribavirin response Pandya, J Investing Med 2017

14 HCV, MetS and therapy Metabolic syndrome and DAA sustained virological response HCV clearance with DAAs is associated with a clinically significant decrease in HbA1c This change was consistent across all genotypes and treatment regimens Successful treatment with DAA is associated with a decreased likelihood of requiring higher insulin doses for DM management. Metabolic syndrome or its individual components (Hypertension, T2DM, Obesity, HLD) does not negatively affect SVR12 rates Dong, WJG 2018

15 HCV, MetS and therapy Effect of DDA on carotid atherosclerosis in patients with HCV and severe fibrosis Petta, J Hepatol 2018

16 HCV, MetS and therapy Risk of stroke in HCV infected veterans according to time to initiation of anti viral therapy Mahale, Gut 2018

17 HCV, MetS and its complications Conclusion: HCV, metabolic syndrome and its complications HCV alters glucose metabolism and can lead to insulin resistance (IR) or type 2 diabetes mellitus (T2DM) Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome The metabolic complications of HCV accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma

18 HIV and MetS HIV and metabolic syndrome : open questions Global prevalence of metabolic syndrome (MetS) in HIV-infected populations and variation by the different diagnostic criteria Prevalence of complications of Met S (cardiometabolic alterations) Impact of HIV therapy in patients with MetS and its complications development

19 HIV and MetS HIV and Metabolic Syndrome: common features Both present: Hypertriglyceridemia Low high-density lipoprotein cholesterol (HDL-C) Insulin resistance Increased waist circumference

20 HIV and MetS A new entity: Virus-associated fatty liver disease (VAFLD) Systemic chronic inflammation associated to HIV infection and diabetes promote increased CVD risk HIV-lipodystrophy syndrome (in 18-80%) lipohypertrophy : expansion of ectopic fat depots (abdomen, liver, dorso-cervical region, trunk, heart) determined by both virus and HAART regimens

21 HIV and MetS Prevalence of MetS in HIV Prevalence of MetS in HIV ranges between 11-26% and 33-45% according to different studies

22 HIV and MetS Global prevalence of MetS in HIV Nguyen, Plos One 2016

23 HIV and MetS Risk factors for NAFLD in HIVmonoinfected patients BMI waist circumference type 2 diabetes hypertension high triglycerides high total cholesterol low HDL cholesterol high fasting glucose high ALT High AST high CD4 + T-cell count No association with HIV viral load, duration of HIV infection, duration of antiretroviral therapy Maurice, AIDS 2017

24 HIV and MetS Clinical, anthropometric and biochemical differences between HIV-NAFLD and primary NAFLD Chraracteristics HIV-NAFLD Primary NAFLD p Vodkin et al, Aliment Pharmacol Ther 2015

25 HIV and MetS Prevalence of NASH in primary NAFLD and HIV-NAFLD In HIV: More lobular inflammation More acidophil bodies Vodkin et al, Aliment Pharmacol Ther 2015

26 HIV and MetS MetS and liver fibrosis, evaluated by Fibroscan, in HIV-monoinfected patients Estimated prevalence of significant fibrosis 15-27% Lemoine, AIDS 2017

27 HIV and MetS Serum adipokines and macrophage activation markers according to the severity of liver fibrosis Lemoine, AIDS 2017

28 HIV and MetS Prevalence of clinical manifestation of MetS in HIV New-onset T2D in about 5-10% Dyslipidemia 20-30% Hypertension 25% Obesity difficult to define for large variability according to different populations

29 HIV and MetS Prevalence of risk factors for CV across age categories in HIV Ekrikpo, BMJ Open 2018

30 HIV and MetS Cardiovascular disease risk in women with HIV Womack, J Am Heart Assoc 2014

31 HIV, MetS and therapy MetS in naïve and HAART treated HIV Similar 3 years incidence (2.65 and 2.75 cases/100 person years) in HAART treated higher triglycerides blood glucose HDL cholesterol Bonfanti, Biomedicine & Pharmacotherapy 2012

32 HIV, MetS and therapy Risk of MetS and of diabetes development with use of protease inhibitors MetS Diabetes Echecopar-Sabogal, International Journal of STD & AIDS 2018

33 Conclusion: HIV, MetS and its complications Although the prevalence of MetS is similar to that of the general population HIV and anti retroviral therapy remain independently associated with mitochondrial dysfunction, altered glucose and fatty acid metabolism, and insulin resistance These metabolic alterations contribute to the elevated incidence of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. Moreover the presence MetS worsens the liver disease Pharmaceutical and lifestyle modification interventions are necessary to prevent MetS complications