Losing weight decreases cardiovascular and diabetes risk and also regresses liver disease.
ReviewTreatment of NAFLD with diet, physical activity and exercise
Introduction
Non-alcoholic fatty liver disease (NAFLD) is a major health problem because of its high prevalence and the associated risk of progression to liver cirrhosis, liver cancer and also, increased cardiovascular and solid neoplasm risk. NAFLD comprises a wide pathological spectrum ranging from simple steatosis to steatohepatitis (NASH) with variable degrees of fibrosis and cirrhosis.1 The strongest predictor of fibrosis progression in NAFLD is the presence of steatohepatitis.2 The risk of detrimental outcomes is increased in patients with significant fibrosis, or steatohepatitis, whilst it is lower in patients with simple steatosis. Liver biopsy remains the gold standard for histological evaluation of the disease. Non-invasive methods combining imaging and biochemical tests are warranted to pre-empt the need for liver biopsies.
The prevalence of NAFLD varies largely from 20% to 30% and increases with age,3 with an annual incidence of around two new cases/100 patients/year. Since NASH is becoming one of the most frequent causes of cirrhosis and liver transplantation worldwide,[4], [5] it is crucial to identify patients at risk of NAFLD progression in order to implement therapeutic interventions that can lead to prevention or reversal of the deleterious consequences of advanced NASH.
Patients with NAFLD are frequently obese and/or have diabetes, and insulin resistance is a key pathogenic trigger. Four phenotypes of patients with NAFLD have been defined: i) obese, ii) type 2 diabetes, iii) metabolic syndrome and iv) lean patients. PNPLA3 is the genetic hallmark of NAFLD. Patients bearing genotype GG were at three times greater risk of NAFLD. This increased risk is more evident in patients without metabolic syndrome.6 Indeed, TM6SF2 mutation has an additive effect on NAFLD risk.7
Section snippets
Role of energy restriction
Excess caloric consumption leading to obesity and related comorbidities is a leading risk factor for NAFLD.8 Furthermore, weight gain by itself, even only a modest 3–5 kg, predicts the development of NAFLD, regardless of baseline body mass index (BMI).9 Interestingly, not only excess caloric consumption, but also the way food consumption is distributed throughout the day, affects liver fat accumulation. In a 6-week randomised controlled trial (RCT), high fat high sugar, or high sugar
Weight loss as the first endpoint treating NASH
The primary approach to treat NAFLD focuses on the control of the underlying risk factors like diabetes, hyperlipidaemia, obesity and other comorbidities. Lifestyle changes through diet and physical activity modifications are well-established therapeutic strategies for conditions such as diabetes and cardiovascular disease.[138], [139] To date, only a few studies have evaluated the impact of lifestyle
Behavioural aspects of lifestyle modification
There is no doubt that lifestyle modification and weight loss pose a great challenge to both the patients and caregivers. NAFLD patients may have a low level of readiness for change and motivation to adopt a healthier lifestyle.159 Furthermore, NAFLD diagnosis is not necessarily associated with lower general health perception nor is it associated with higher health care utilisation.160 It has been repeatedly demonstrated that weight loss achieved by diet is highest at 6-months follow-up and
Summary & conclusions
Lifestyle change, including dietary habits and physical activity, are and should be the first line of treatment in NAFLD and NASH. Weight reduction is the most established treatment for both NAFLD and NASH, with a clear dose-response association. Generally, any form of healthy diet (low fat or low carbohydrates or Mediterranean diet), which will lead to caloric reduction and is acceptable by the patient, should be encouraged. For those who find caloric restriction difficult, changing dietary
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Authors’ contribution
All three authors contributed equally in the elaboration of the manuscript.
Acknowledgement
PI 16/ 01842 Instituto de Salud Carlos III, MINECO, Spain.
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