WHAT CAN YOU USE IN YOUR CLINIC TODAY FOR THE TREATMENT OF NASH?

Transcription

1 WHAT CAN YOU USE IN YOUR CLINIC TODAY FOR THE TREATMENT OF NASH? Helena Cortez-Pinto Laboratório de Nutrição, FML, Serviço de Gastrenterologia, Hospital St Maria, Lisboa, Portugal EASL Governing Board: EU Policy Councillor 20 de maio 2017 Workshop on Nonalcoholic Fatty Liver Disease

2 NAFLD Management AIMS Decrease NASH-related mortality, and reduce progression to cirrhosis or HCC EASL guidelines, 2016

3 MANAGEMENT OF NAFLD Diet and lifestyle changes Drug treatment Bariatric (metabolic) surgery Liver transplantation

4 Diet and lifestyle changes If possible refer to a team, including a dietician Start a period of 6 months of lifestyle intervention including weight-loss and implementation of physical activity

5 Weight-loss Any weight loss has a significant effect on steatosis and insulin resistance A cognitive-behaviour therapy, lifestyle intervention resulted in more weight loss, more frequent resolution of NASH and higher reduction in the NAS score A loss > 7% was associated with histological improvement Promrat et al, Hepatol, 2010

6 Modest lifestyle-induced weight loss associated with NASH regression (25%) without worsening of fibrosis 12-month study with 261 paired biopsies Improvement significantly depends on weight loss percentage Vilar-Gomez et al, Gastroenterology, 2015

7 Scores can be used to predict resolution of NASH Score: using: WL degree, presence of diabetes, a NAS 5, ALT normalization, and age Two cut-offs: and may predict low or high probability of NASH resolution Vilar-Gomez et al, Hepatology, 2016

8 Advise on lifestyle changes Patients without NASH or fibrosis Only counselling for healthy diet and physical activity and no pharmacotherapy for their liver condition In overweight/obese NAFLD 7 10% weight loss Dietary recommendations Energy restriction and exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose). Macronutrient composition should be adjusted according to the Mediterranean diet EASL guidelines, 2016

9 Soft drinks and sugar-sweetened beverages FRUCTOSE!! Mucci L, et al. Intern Emerg Med 2012

10 The Good and the Bad guys Zelber-Sagi et al, Liver Int, 2017

11 Advantages of the Mediterranean diet Zelber-Sagi et al, Liver Int, 2017

12 Alcohol Strictly keep alcohol below the risk threshold (30 g, men; 20 g, women) If cirrhosis is present, complete abstinence Increased risk of HCC n Ascha et al, Hepatology, 2010

13 Diet Obese patient Normo-ponderal 5 to 10% weight loss (slow but consistent) Weight maintenance Diet composition Increase n-3 / n-6 Reduce added sugars to minimum Avoid soft drinks: Fructose!! Increase fibre Reduce meat Minimize fast food

14 Exercise Moderate intensity aerobic physical activities in 3-5 sessions: min/week Resistance training is also effective and promotes musculoskeletal fitness, with effects on metabolic risk factors Association of aerobic and resistance may have advantages It has to be very much adapted to the patient EASL guidelines, 2016

15 Drug treatment - indications Progressive NASH (bridging fibrosis and cirrhosis) Early-stage NASH with increased risk of fibrosis progression (age >50 years; diabetes, MetS, increased ALT or active NASH with high necroinflammatory activity No specific therapy can be firmly recommended EASL guidelines, 2016

16 Drug treatment Insulin sensitizers Antioxidants, cytoprotective and lipid lowering agents EASL guidelines, 2016

17 Insulin sensitizers Scarce evidence for a histological efficacy of metformin in NASH Anti-tumorigenic activity of metformin on liver cancer - Bhalla K, Cancer Prev Res, 2012 Thiazolidinediones - PPAR γ agonists - pioglitazone EASL guidelines, 2016

18 Pioglitazone PIVENS study Improved more frequently all histological aspects of NASH (except fibrosis), as well as resolution of steatohepatitis, than placebo in non-diabetics - Sanyal, NEJM, 2010 Problems: Weight gain Risk of heart failure Risk of bone fractures It is a good option, mostly in diabetics

19 Vitamin E 2 major studies PIVENS study (Sanyal) and TONIC (Lavine) demonstrated benefit 800 IU /day alfatocoferol n Lavine, JAMA, 2012; Sanyal, NEJM; 2010 Increased mortality from all causes small but significant Increased risk of prostate cancer in males over 50, and of haemorrhagic stroke

20 Ursodesoxicolic acid 12mg/kg/d to 35mg/kg, during periods up to 2 years Contradictory results Only showed some biochemical but no histological improvements n Lindor, Hepatology, 2004

21 Liraglutide - GLP-1 Analogue Incretin mimetic Led to resolution of non-alcoholic steatohepatitis in 39% patients Vs 9%) in placebo Subcutaneous injections of 1 8 mg liraglutide Armstrong et al, Lancet, 2016

22 Omega - 3 PUFA as treatment In a phase 2 trial, EPA-E (1800 or 2700 mg) had no significant effect on the histologic features of NASH n Sanyal et al, Gastro, 2014 Omega-3 PUFAs at 3000 mg/day for one year did not lead to significant changes in the overall histological activity in NASH patients n Argo, J Hepatol, 2015

23 Statins and Omega-3 PUFA in dyslipidemia EASL guidelines, 2016

24 Bariatric surgery In patients unresponsive to lifestyle changes and pharmacotherapy, Bariatric (metabolic) surgery reduces liver fat and is likely to reduce NASH progression No solid data on the comparative effects of different bariatric procedures on liver fat are available.

25 All studies showed an improvement in steatosis; the majority also improvement in fibrosis Lassailly, J Hepatol, 2013 Lassailly et al, J Hepatol, 2013

26 Bariatric Surgery what is the best technique on NAFLD? The technique of Roux-en-Y gastric bypass seems to be more effective than the adjustable gastric band. Partially explained by greater weight loss n Caiazzo, Mathurin, Ann Surg, 2014

27 Lassailly, J Hepatol, 2013

28 > Lassailly, J Hepatol, 2013

29 Liver Transplantation NAFLD carries a higher risk of death from cardiovascular complications and sepsis It is among the three top indications Liver transplantation is an accepted procedure in NASH patients with end-stage liver disease, with comparable overall survival to other indications, despite a higher cardiovascular mortality. NASH patients with liver failure and/or HCC are candidates for liver transplantation

30 Summary Attempt to reduce excess weight and implement lifestyle changes Control metabolic risk factors Insulin resistance/diabetes; Dyslipidemia; Hypertension If evidence of NASH / progressive fibrosis, consider pioglitazone or Vitamin E, if no contraindication If morbid obesity, consider bariatric surgery If decompensated cirrhosis, consider liver transplantation Consider including the patient in a clinical trial