Management of persistent minor elevations of alt [<3 url]

Management of Persistent
Minor Elevations of ALT
[<3URL] in Adults


Developed by: Dr B Lopez; Dr Peter Astley
Date of Issue: June 05

Ratified at Clinical Effectiveness Committee: September 2005

Review date:

Management of persistent minor elevations of ALT [<3 URL] in adults

Raised ALT <X3 URL
ALT>3XURL on 2 separate
Raised ALT
If ALT remains abnormal, investigations are warranted. Prioritise if risk factors for liver disease are present.

Investigations: 2
2. Clinical suspicion chronic liver disease If appropriate
Probable NAFLD
Recheck LFT’s and prothrombin time at 3 months, 6 Consider diabetic clinic referral if poor glycaemic control.
Explanatory notes:

1. Do not stop statins unless ALT>X3 URL. For patients with minor elevations, consider
investigating for liver disease if ALT remains persistently elevated.2, 3, 4 2. Consider investigations even if suspected alcohol abuse. 3. Current recommended “sensible” limits: 12,13 4. NAFLD is believed to represent the liver component of the metabolic syndrome. At present there is no established therapy for NAFLD based on evidence from large RCT’s. Treatment for all patients should therefore be directed at the associated risk factors taking into consideration possible effects on the liver. Weight loss by a combination of moderate calorie restriction and increased exercise [150 minutes /week] aiming to lose 10% of body weight at a rate of 0.5 -1 kg per week 8, 9,12. More rapid weight loss may exacerbate liver damage. 6, 7 Diet should consist of a low saturated fat, 10 “heart healthy” diet or standard diabetic diet if indicated. 6. In overweight patients with NAFLD and type 2 diabetes, tight glycaemic control with metformin is recommended since this has been shown to reduce the risk of diabetes-related microvascular complications and death and all cause mortality.15 Treatment with metformin may also be beneficial to the liver.16, 17,18 7. Use statins for conventional indications including Type 2 diabetes and cardiovascular risk >20% over 10 years. There is no evidence that patients with NAFLD are at greater risk from statin-induced hepatotoxicity 1, 2 Consider using a fibrate first line if isolated raised triglycerides 5-10 mmol/l.19, 20 Refer Lipid Clinic if triglycerides > 10mmol/l.19 8. Look for and treat hypertension particularly in patients with type 2 DM22, 23 Consider ACE Inhibitors or A2RA’s as first line therapies for hypertensive patients with NAFLD.12, 21,23
References:

1. Chalsani et al. Patients with elevated liver enzymes are not at higher risk for
statin hepatotoxicity. Gastroenterology 2004: 128 1287-1292 2. Chalsani N. Statins and hepatotoxicity: Focus on patients with fatty liver. American Journal of Cardiology Vol 89;1374-1380 4. The physician desk reference 2005. 59th Edition. Montvale, NJ: Thompson 5. Anderson et al . Hepatic effects of dietary weight loss in morbidly obese 6. Luyckx et al. Liver abnormalities in severely obese subjects : effect of drastic weight loss after gastroplasty. Int j Obes 1998;22:222-6 7. Ueno et al. Therapeutic effects of a restricted diet and exercise in obese patients with fatty liver. J Hepatol;1997; 27: 103-7. 8. NHLBI-NIDDK Clinical Guidelines on the identification, evaluation and treatment of overweight and obese adults 9. Musso et al. Dietary habits and their relations to insulin resistance and post-prandial lipaemia in NASH. Gastroenterology 2002;123:1705-25. 10. AGA Technical review on NAFLD. Gastroenterology; 2002; 123: 1705-25 11. Day. C. Non-alcoholic fatty liver disease. Evidence-based Gastroenterology. August 2004; 393-403. 12. Dixon et al. NAFLD: predictors of NASH and liver fibrosis in the severely obese. Gastroenterology 2001; 121: 91-100 13. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. NEJM 2002;346:393-403 15. UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. Lancet 1998;352:854-65 16. Lin et al. Metformin reverses fatty liver disease in obese, leptin deficient 17. Marchesini et al. Metformin in NASH. Lancet 2001;358:893-4 18. Nair et al. Metformin in NASH: efficacy and safety. A preliminary report. 19. NHS Prodigy Guidance. Hyperlipidaemia 20. Ye JM Iglesias et al. PPAR-alpha /gamma ragaglitizar eliminates fatty liver and enhances insulin action in fat fed rats in the absence of hepatomegaly. Am J physiol Endocrinol Metabol 2003; 284: E531-540 21. Yoshiji. Angiotensin II type 1 receptor interaction is a major regulator for liver fibrosis in rats. Heptology 2001; 34: 745-50. 22. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes [UKPDS 38] BMJ 1998; 317:703-13. 23. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of the ACE inhibitor Ramipril, on cardiovascular events on high risk patients. NEJM;342: 145-53.

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