Epatopatie croniche attive e diabete: aspetti terapeutici. Como 15 giugno, 2013

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1 Paolo Cavallo Perin University of Turin (Italy) Epatopatie croniche attive e diabete: aspetti terapeutici. Como 15 giugno, 2013

2 Stile di vita: - dieta - attività fisica

3 HCV-associated insulin resistance: therapeutic strategies Kawaguchi T, Sata M. World J Gastroenterol 2010;16:

4 Metabolic treatment for HCV infection Adinolfi LE et al. Expert Opin Pharmacother (2011) 12:

5 Aerobic exercise improves insulin resistance in patients with HCV-related hepatitis - body weight - fat weight - visceral fat - ALT - HOMA-IR significantly decreased (P = ) Konishi I et al. Hepatology Research 2011; 41:

6 Farmaci anti-iperglicemici nelle epatopatie croniche - metformina - sulfoniluree - acarbose - pioglitazone - DPP-4 inibitori - GLP-1 agonisti - inibitori SGLT-2 - pramlintide - colesevelam - attivatori della glucochinasi

7 Rischio nell insufficienza epatica o rischio di acidosi lattica - neutri: DPP4-i, GLP-1 agonisti, acarbosio, insulina - rischio moderato: sulfoniluree, glinidi, glitazoni - rischio lieve: nessuno - rischio grave: metformina AACE Glycemic Control Algorithm, Endocr Pract. 2009;15:

8 Key Benefits and Risks of Medications in type 2 DM AACE Glycemic Consensus Statement. Endocr Pract. 2009;15:

9 Metformina

10 Metformina: effetti indesiderati Effetti gastro-intestinali: frequenti gusto metallico, anoressia, nausea, dolore addominale, diarrea - minimizzati con aumento graduale dose da 500 mg/die - diminuiscono con la durata del trattamento - intolleranza: alcuni devono sospendere o non raggiungono la dose piena Acidosi lattica: molto rara, ma grave/fatale Controindicazioni: insufficienza renale (GFR < 30 ml/min), epatopatie attive, etilismo cronico, sepsi, ipossiemia acuta, mezzi contrasto radiologico. Altri (rari): ipoglicemia, anemia da carenza di vitamina B12 ADA/ESD Consensus Statement. Diabetes Care 2009;32: Canadian Guidelines 2008

11 Metformin on the efficacy of antiviral therapy (degree of steatosis) in HCV-related hepatitis (MET/PL for 48 weeks on PEG-INFalfa-2a+ribav) Control group n = 49 (n.s.) MET group n = 49 (p=0.04) Yu J-W et al. International Journal of Infectious Diseases 16 (2012) e436 e441

12 Metformin on the Prognosis of HCV-Cirrhosis in patients with DM-2 Nkontchou G. et al. J Clin Endocrinol Metab 96: , 2011

13 Sulfoniluree

14 1-year treatment of with pio, met or gliclaz M G P G. Belcher and G. Schernthaner Diabet. Med. 22, (2005)

15 Acarbose

16 Acarbose in insulin-treated DM-2 patients with cirrhosis (n = 100; 28 weeks) no significant variations in liver function tests Gentile S et al. Diabetes, Obesity and Metabolism 3;2001,33-40

17 Pioglitazone

18 PIO decreases the serum HCV RNA titers independently of PEG-Interferon-a2/ribavirin treatment Chojkier M et a. PLoS ONE 7(3): e31516,2012

19 Total body water was not altered significantly either after pioglitazone (from 45.4 ± 2.3 to 45.6 ± 2.7 l, p = NS) or placebo. Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments.

20 Inibitori DPP-4

21 Sitagliptin (48 weeks) for DM-2 and HCVrelated chronic liver disease Arase Y et al. Hepatology Research 2011; 41:

22 The effectiveness of Sitagliptin in NASH patients with DM-2 Ohki T et al. Scientific World Journal 2012;2012:49645

23 GLP-1 agonists

24 Exenatide treatment in a patient with HCV and NASH Ellrichmann M et al. Am J Gastroenterol 2009; 104:

25 The effectiveness of Liraglutide in NASH patients with DM-2 Ohki T et al. Scientific World Journal 2012;2012:49645

26 Chirurgia bariatrica

27 Influence of Sleeve Gastrectomy on NASH and DM-2 Karcz WK et al. J Obes 2011;2011:765473

28 DM-2 prevention in HCV-related hepatitis

29 Hepatitis C and DM: one treatment for two diseases? SVR = sustained virological response to therapy (interferon/ribavirin) Arase Y et al. Hepatology 2009;49:

30 Antidiabetic drugs and risk of HCC in chronic liver disease

31 Antidiabetic drugs and risk of HCC in chronic liver disease OR in patients with DM 2.20 (CI ; p = 0.01) OR insulin or sulphonylureas 2.99 (CI ; p = 0.007) OR metformin 0.33 (CI ; p = 0.006) Donadon V et al. World J Gastroenterol 2009; 15:

32 Metformin on HCC occurrence in patients with DM-2 and HCV-cirrhosis Nkontchou G. et al. J Clin Endocrinol Metab 96: , 2011

33 Statine

34 Statins are associated with a reduced risk of HCC in a large cohort of patients with Diabetes Adjusted OR = 0.74 (0.64, 0.87) El-Serag HB et al. Gastroenterology 2009; 136:

35 Vaccinazioni HAV e HBV nei pazienti con DM

36 In the diabetic cohort, HepA vaccination rates increased from 9.3% ± 1.1% to 15.4% ± 1.7% and HepB rates increased from 15.2% ± 1.5% to 22.4% ± 1.7%. All changes were similar to those observed in the general population. Although vaccination rates in CLD and diabetic cohorts are increasing, they remain low. Younossi ZM and Stepanova M. Hepatology 2011;54:

37 Conclusioni - rilevanza epidemiologica del problema: aumento comorbidità - pochi dati EBM - insoddisfacenti raccomandazioni nelle Linee Guida - l unico farmaco ritenuto «neutro» è l insulina - sulfoniluree: non utili, potenzialmente dannose - metformina: controindicato nelle epatopatie croniche gravi, ma potenzialmente utile e poco rischioso (1500 mg/die) nelle forme non gravi - pioglitazone, DPP-4 inibitori, GLP-1 agonisti: potenziale interesse nelle forme non gravi - altri farmaci: inibitori SGLT-2?

38 Patient-centered care and standardized algorithmic management are conflicting approaches, but they can be made more compatible by recognizing. clinical circumstances that may call for comanagement by (different) specialty clinicians. Diabetes Care 36: , 2013