This section does not consider fatty liver of pregnancy which requires referral to, and management by, a hospital specialist.
It has been suggested that initial management of patients with suspected or confirmed non alcoholic fatty liver disease (NAFLD) can be carried out according to the LFT results (1):
- if AST:ALT ratio >0.8 – consider specialist referral
- if AST:ALT ratio <0.8
- ALT<50 U/L (within normal range)
- life style modification to achieve weight loss and control
- advice on alcohol reduction if appropriate
- repeat liver function tests in 3-6 months
- if LFT results have improved and satisfying weight control, reinforce and continue
- if LFTs and weight static, reinforce lifestyle advice and continue
- if LFT results increasing move to management step 2 or 3
- ALT 50-150 U/L (1 to 3 times the upper limit of normal)
- life style modification to achieve weight loss and control
- preferably stop any alcohol intake or potentially heaptotoxic drugs
- reassess in 2-3 months
- if LFT results have improved and satisfying weight control, reinforce and continue
- if LFTs and weight static, reinforce lifestyle advice and reassess in 6-12 months
- if LFT results increasing move to next step in management
- ALT >150 U/L (>3 times the upper limit of normal)
- life style modification to achieve weight loss and control
- stop any alcohol intake or potentially heaptotoxic drugs
- reassess in 1-2 weeks
- if LFT results have improved, reinforce and continue to step 1 or 2
- if LFT results static or increasing, reconsider potential causes and refer to specialist (1)
Weight loss and lifestyle improvements are the cornerstone of managing all patients with NAFLD irrespective of their underlying liver histology.
- diet
- although optimum diet to treat NAFLD is not known, a calorie restricted diet (600 Kcal less than a person needs to remain at the same weight) should be recommended aiming to lose 0.5–1 kg per week until the target weight is achieved
- patients should avoid saturated fats, simple carbohydrates and sweetened drinks.
- exercise
- increase physical activity and exercise have been shown to reduce steatosis and improve liver enzyme levels independent of weight loss
- orlistat as an aid to weight loss
- is an enteric lipase inhibitor which causes malabsorption of dietary fat and can aid weight loss in subjects with obesity in conjunction with lifestyle modification (1,2,3)
- explain to people with NAFLD who drink alcohol the importance of staying within the national recommended limits for alcohol consumption (4)
Pharmacological management
Seek expert advice.
Pharmacotherapy options include:
- pioglitazone remains the drug of choice to reduce progression of fibrosis in people with diabetes, although it is often used off-label in the absence of diabetes (6)
- vitamin E is mainly used in children and may be considered in adults without diabetes (6)
- omega-3 fatty acids – may be considered to treat hypertriglyceridemia in patients with NAFLD
- although NICE state should not be used to treat NAFLD per se (7)
- statins
- useful in treating dyslipidemia in patints with NASH and NAFLD
- a large cohort study from the United States demonstrated that patients with elevated liver enzymes were not at higher risk of hepatotoxicity from statin use (5)
- NICE state (7):
- be aware that people with NAFLD who are taking statins should keep taking them
- only consider stopping statins if liver enzyme levels double within 3 months of starting statins, including in people with abnormal baseline liver blood results
- ursodeoxycholic acid (UDCA) – not recommended (3,4)
- SGLT2 inhibitors in NAFLD
- there is evidence of benefit for the use of SGLT2 inhibitors
- in patients with Type2 diabetes and NAFLD (8);
- and patients with NAFLD without type 2 diabetes (9)
Bariatric surgery (6):
- bariatric surgery very effectively promotes weight loss and its maintenance; the effects on body weight largely exceed the 10% weight loss target associated with clearance of liver fat, resolution of NASH, and reversal of fibrosis
- surgery is a possible treatment to reduce the burden of NASH in patients who meet the agreed criteria for the management of obesity (BMI >=40 or BMI >=35 with comorbidities)
In addition components of metabolic syndrome associated with NAFLD should also be managed:
- diabetes mellitus
- around 40%–50% of patients attending secondary care clinics with NAFLD have type 2 diabetes and the majority have evidence of insulin resistance
- initially, management should focus on dietary intervention
- metformin is the recommended first-line pharmacological treatment
- pioglitazone - second-line treatment of type 2 diabetes in NASH
- hypertension
- around 70% of patients with NAFLD have hypertension
- patients with blood pressure >140/90 mm Hg should be managed according to NICE hypertension guidelines
- dyslipidemia
- commonly seen in patients with NAFLD and metabolic syndrome
- primary prevention with statin if ≥20% 10-year risk of developing cardiovascular disease (4)
In obese patients with NAFLD, screen for obstructive sleep apnoea using the STOP BANG questionnaire (4).
Referral indications:
- there are no agreed referral indications but referral should be considered if there are ultrasound or clinical signs of more significant liver disease with AST greater than ALT, and when 'fatty liver' is observed outside the context of the classic insulin-resistant patient phenotype (1)
- NICE state (7):
- with respect to phharmacological treatment
- vitamine E or pioglitazone should be considered in secondary or tertiary care settings only, for adults with advanced liver fibrosis, whether they have diabetes or not
- before prescribing pioglitazone or vitamin E to adults, take into account any comorbidities that they have and the risk of adverse events associated with these conditions
- in tertiary care settings only, consider vitamin E for children with advanced liver fibrosis, whether they have diabetes or not
- in secondary or tertiary care settings only, consider vitamin E for young people with advanced liver fibrosis, whether they have diabetes or not
- offer to retest people with advanced liver fibrosis 2 years after they start a new pharmacological therapy to assess whether treatment is effective
- consider using the ELF test to assess whether pharmacological therapy is effective
- if an adult's ELF test score has risen, stop either vitamin E or pioglitazone and consider switching to the other pharmacological therapy
- if a child or young person's ELF test score has risen, stop vitamin E
Reference:
- (1) Sattar N, Forrest E, Preiss D. Non-alcoholic fatty liver disease. BMJ. 2014;349:g4596
- (2) Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ. 2005;172(7):899-905.
- (3) Chalasani N et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005-23
- (4) Dyson JK, Anstee QM, McPherson S. Republished: Non-alcoholic fatty liver disease: a practical approach to treatment. Postgrad Med J. 2015;91(1072):92-101.
- (5) Chalasani N et al. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004;126:1287-92.
- (6)Petroni ML et al. Management of non-alcoholic fatty liver disease. BMJ 2021;372:m4747http://dx.doi.org/10.1136/bmj.m4747
- (7) NICE (July 2016). Non-alcoholic fatty liver disease (NAFLD): assessment and management
- (8) Scheen AJ. Beneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: A common comorbidity associated with severe complications. Diabetes Metab. 2019 Jun;45(3):213-223. doi: 10.1016/j.diabet.2019.01.008.
- (9)Taheri H et al. Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Adv Ther 37, 4697-4708 (2020). https://doi.org/10.1007/s12325-020-01498-5