Primary Care Guidance Program: Non-Alcohol related Fatty Liver Disease (NAFLD) Guidance on Management in Primary Care

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1 Primary Care Guidance Program: Non-Alcohol related Fatty Liver Disease (NAFLD) Guidance on Management in Primary Care This advice has been developed to help GPs with shared care of patients with Non- Alcohol related Fatty Liver Disease. What is Non-Alcohol related Fatty Liver Disease (NAFLD)? Fatty liver disease is the accumulation of fat within the liver which can progress to inflammation and scarring in 10-15% of cases. The majority of patients (85-90%) have simple fat deposition in their liver, which might come to light as an abnormally raised ALT or on an ultrasound scan where it appears as a bright liver. Other causes of liver disease must be ruled out, such as alcohol excess, viral hepatitis, haemochromatosis, autoimmune liver disease and rare metabolic disorders. Twenty-four per cent of the adult population of England is obese, as defined by a Body Mass Index of 30 or more. Three quarters of these obese individuals will have Fatty Liver Disease, whereas nearly all morbidly obese (BMI greater than 40) individuals will have fatty liver disease. Fatty liver disease can also occur in those with BMI of 26-29kg/m 2 ( overweight ). The accumulation of hepatic fat is often associated with accumulation of visceral, myocardial and muscle fat, which explains why fatty liver disease is associated with greater overall mortality and independently predicts the risk of future cardiovascular events. Indeed, cardiovascular disease remains the leading cause of death in individuals with fatty liver disease, and diseases like diabetes appear in a significant percentage of patients with fatty liver disease, sooner or later. What can be done to treat NAFLD? As cardiovascular disease is the leading cause of death in patients with Fatty Liver Disease treatment must primarily focus on the individual elements of the metabolic syndrome: The key elements of the METABOLIC SYNDROME are obesity, hypertension, glucose intolerance and high circulating levels of fats (high triglycerides and low HDL-cholesterol). 1. Diet Patients with fatty liver disease tend to have diets rich in saturated fats and cholesterol and poor in polyunsaturated fat and fibre. Lifestyle interventions have been shown to be effective in preventing diabetes in patients with impaired Glucose tolerance (Finnish Diabetes Prevention Study). Studies in NAFLD patients have shown improvements in liver histology in patients with modest weight loss (4-7%) achieved by dietary counselling, but most patients have difficulty achieving and maintaining weight loss. Whilst drugs such as Orlistat have been shown to induce weight loss, they have side-effects and are no better than low calorie diets alone in terms of reducing fatty liver. If being considered, it is advisable to discuss with the local liver specialist.

2 Ideally, weight reduction should aim at a BMI of under 26 kg/m 2, but even 10% weight loss will be sufficient to improve metabolic and histopathological abnormalities in most patients with fatty liver disease. Recommendations include a diet low in saturated fats and processed foods (25kcal/kg/day - 60%carbohydrate, 20%fat, 20% protein and 200mg cholesterol), high in fibre and omega-3. The Eatwell plate can help to educate about portion size and proportions of food groups in diet. Organisations such as Weight Watchers and Slimming World seem to offer sensible dietary approaches to weight loss, with overall reduced saturated fat intake. Crash diet programmes are not advised. Dieticians within the network have written advice for GPs in nutritional aspects of liver disease for the Yorkshire and Humber Liver Network (www.yhln.org.uk ). 2. Exercise Lack of physical exercise is associated with central obesity, increased risk of metabolic syndrome and severity of fatty liver disease. The benefits of regular exercise have been investigated in several settings. Obese, non-diabetic patients can reduce their risk of developing diabetes by nearly half, whilst diabetics can reduce their fasting plasma glucose. Recommendations include 150 minutes per week for general health (Brisk walking/jogging/cycling to achieve 60-70% maximum heart rate during 5 days a week) and >200 minutes per week for weight loss. Physical activity improves liver tests. Overall, changes in physical activity are more sustainable than changes in weight achieved by diet manipulation alone. The combination of weight-reducing diet and exercise appears to have a synergistic effect on metabolic profiles. The Diabetes Prevention Study (USA) showed a low-calorie, low-fat diet with 150mins per week of physical activity reduced the incidence of diabetes by 58%. Studies on diet and exercise whilst generally involving small numbers all show improved biochemical parameters, and those that repeated biopsies also showed improved steatosis and one showed improved fibrosis. 3. Hypertension: The BNF clearly outlines recommendations for treating hypertension. In patients with sustained systolic BP 160 mm Hg or sustained diastolic BP 100 mm Hg antihypertensive agents are recommended. They are also recommended in patients with sustained systolic BP in the range mm/hg, and/or diastolic BP in the range mm/hg with known cardiovascular disease, diabetes, target organ damage (i.e. renal impairment); or an estimated CVD risk of 20% over the next 10 years using risk charts or calculator. 4. Diabetes: Patients with established diabetes should aim to control their blood sugars. Target HbA1c levels vary from patient to patient although levels around 6.5% (or 48mmol/ml) are often used. Use of dietetic services, diabetes clinics and specialist nurse services should be considered, as per usual primary care practice. 5. Hypercholesterolaemia The UK guidelines are based on cardiovascular risk, which consider smoking status, blood pressure, weight and medical history (See Cardiovascular Risk Prediction Charts or British National Formulary). If the risk is sufficiently high, a statin should be recommended.

3 Statins are the most effective means of lowering cholesterol, reducing LDL-cholesterol by up to 50%. Rarely, they cause side-effects such as muscle aches etc, sometimes they can cause a rise in liver enzymes, but these can be ignored if the rise is less than twice baseline. See the Yorkshire and Humber Liver Network guidance on prescribing statins in liver disease (www.yhln.org.uk). Ezetimibe can be tried if statins are contraindicated or poorly tolerated for whatever reason. If prescribing fibrates and statins, reduce the dose of statin, give the statin in the evening and the fibrate in the morning, and warn the patient of an increased risk of myositis. 6. Other Treatments There have been number of trials using Ursodeoxycholic acid, Vitamin E, Metformin etc. that have attempted to improve fatty liver disease. PPAR- agonists may have a role, but the data is less than conclusive, and at present no firm recommendations can be made. 7. Alcohol By definition patients with NAFLD are not drinking excessively, although a careful alcohol history is important. Alcohol and obesity can act as co-factors for fibrosis and there is no safe recognised alcohol limit in this condition. It seems prudent to advise that alcohol intake should be limited to under 10 units/week for men, and under 7 units/week for women. Advise against all alcohol intake for patients with advanced fibrosis and cirrhosis. How frequently should I measure LFTs and when should I refer the patient back? Your local liver services will be developing pathways with the CCGs to advise on the appropriate ways of staging how significant the liver disease is in patients with NAFLD. Some are offering a graded review recommendation based on stage of disease. Finding the balance between over monitoring and investigating patients with NAFLD without advanced disease is difficult. There will be progression in some, and for these the liver disease may be the significant aspect of their health, but progression prediction is not clearly understood. In considering the question of LFT monitoring in primary care it is worth remembering: Probably only worth monitoring the liver if the cardiovascular risk factors have been properly addressed, as the liver disease will only significantly impact on survival if the patients is likely to survive from the cardiac point of view, unless the liver disease is severe. LFTs seem to have little predictive value for severity of liver disease or future mortality risk until very late disease manifests and the bilirubin rises or the albumin falls. A low platelet count is also a feature of advanced disease, and if any of these develop in patients not known to have advanced disease, the GP should ask for a review in liver services. Currently there are no effective pharmacological treatments Hence, there seems little or no value in monitoring LFT s on a regular basis. In general terms, it would be better to focus efforts on the lifestyle measures, and monitoring and treating the individual components of the metabolic syndrome. CONCLUSIONS Fatty liver disease is closely associated with obesity and other elements of the metabolic syndrome. As cardiovascular disease is the most likely cause of death in this group, every attempt should be made to optimise weight, blood pressure, cholesterol, glucose where appropriate. Specific therapies are not yet of proven value.

4 References: 1. Vuppalanchi R and Chalasani N. Non Alcoholic Fatty Liver Disease and Non Alcoholic Steatohepatitis: Selected Practical Issues in their Evaluation and Management. Hepatology 2009;49: Statistics on obesity, physical activity and diet: England, January Yu AS, Keefe EB. Non Alcoholic Fatty Liver Disease. Rev Gastroenterol Disorders 2002;2: Adams LA, Lympt JF et al The Natural History of Non Alcoholic Fatty Liver Disease: a population-based cohort study. Gastroeneterology 2005;129: Ekstedt M, Franzen LE et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology : Harrison HA, Day CP. Benefits of lifestyle modification in NAFLD. Gut2007;56: Lindstrom J et al. The Finnish Diabetes Prevention Study: Lifestyle Intervention and 3-Year results on diet and physical activity. Diabetes Care 2003;26: Pan XR et al. Prevalence of diabetes and its risk factors in China, Diabetes Care 1997;20: Saris WH, Blair SN et al. How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO!st Stock Conference and consensus statement. Obesity Review 2003;4: Zivkovic A, German JB Sanyal AJ. Comparative reviews of diets for the metabolic syndrome: implications for non alcoholic fatty liver disease. Am J Clin Nutr 2007: 86; Knowler WC, Barrett-Connor E et al. Reduction in the Incidence of type 2 diabeteswith life-style intervention or metformin. NEng J Med 2002;346: Joint British Societies guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005;91(Suppl V)v1-v Harrison SA, Oliver D et al. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut 2008:57:

5 Fatty Liver Primary Care Guidance Working Group Dr C Millson (Consultant Hepatologist, York) Dr G Abouda(Consultant Hepatologist, Hull) Dr L Claridge (Consultant Hepatologist, Leeds) Dr R Jones (Consultant Hepatologist, Leeds) Dr C McClure (GP, York) Guidance Provenance Written for the Yorkshire and Humber Liver Network Dr C Millson (lead author) Dr G Abouda GP Focus Group meeting held 27/02/2013: GPs from York, Leeds, Wakefield in attendance. Presented at YHLN meeting Dec 2013 Review date November 2016

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