Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease

Highlights

• In this RCT, lifestyle intervention effectively led to remission of NAFLD in most non-obese and obese patients.

• Weight reduction correlated with NAFLD remission in a dose-dependent manner.

• The amount of weight reduction needed to achieve remission was less in non-obese patients.

• By 6 years, non-obese patients remained more likely to maintain weight reduction and have ALT normalization.

Background & Aims

Around 10–20% of patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The benefit of weight reduction in such patients is unclear. We aim to study the efficacy of lifestyle intervention in non-obese patients with NAFLD and to identify factors that predict treatment response.

Methods

A total of 154 community NAFLD patients were randomised to a 12-month lifestyle intervention programme involving regular exercise, or to standard care. The primary outcome was remission of NAFLD at Month 12 by proton-magnetic resonance spectroscopy. After the programme, the patients were prospectively followed until Year 6. The Asian body mass index (BMI) cut-off of 25 kg/m² was used to define non-obese NAFLD.

Results

Patients were assigned to the intervention (n = 77) and control (n = 77) groups (39 and 38 in each group had baseline BMI <25 and ≥25 kg/m², respectively). More patients in the intervention group achieved the primary outcome than the control group regardless of baseline BMI (non-obese: 67% vs. 18%, p <0.001; obese: 61% vs. 21%, p <0.001). Lifestyle intervention, lower baseline intrahepatic triglyceride, and reduction in body weight and waist circumference were independent factors associated with remission of NAFLD in non-obese patients. Half of non-obese patients achieved remission of NAFLD with 3–5% weight reduction; the same could only be achieved in obese patients with 7–10% weight reduction. By Year 6, non-obese patients in the intervention group remained more likely to maintain weight reduction and alanine aminotransferase normalisation than the control group.

Conclusions

Lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. Weight reduction predicts remission of NAFLD in non-obese patients, but a modest weight reduction may be sufficient in this population.

Lay summary

Some patients with non-alcoholic fatty liver disease (NAFLD) are non-obese. The optimal management of such patients is unclear. In this long-term follow-up study of a clinical trial, we show that remission of NAFLD can be achieved in 67% of non-obese patients after lifestyle intervention. The majority of patients can achieve NAFLD remission with modest weight loss of 3–10%. Non-obese patients are also more likely than obese patients to maintain weight reduction and normal liver enzymes in the long run.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease and is one of the leading causes of end-stage liver disease and hepatocellular carcinoma worldwide.[1], [2] Although NAFLD is strongly associated with metabolic syndrome and obesity,³ around 10–20% of patients with NAFLD have a relatively normal body mass index (BMI), a condition often described as non-obese or lean NAFLD.⁴ Studies based on liver histology or non-invasive tests of fibrosis suggest that these non-obese patients may also harbour non-alcoholic steatohepatitis (NASH) and advanced fibrosis.[5], [6], [7], [8]

Similar to the management of other metabolic disorders, lifestyle modification is the cornerstone for the management of NAFLD. A number of diets including low-carbohydrate diet, low-fat diet, low-glycaemic index diet and the Mediterranean diet have been shown to improve liver enzyme levels, liver fat, and histology in patients with NAFLD.[9], [10], [11], [12], [13], [14], [15], [16], [17] Likewise, beneficial effects have been observed for both aerobic exercise and resistance training.[18], [19] In particular, a reduction of 10% or more in body weight results in the remission of NAFLD and NASH in the majority and improvement in liver fibrosis in almost half of patients.[20], [21]

Nonetheless, while weight reduction makes sense for obese individuals, there have been no data on the efficacy of lifestyle intervention in non-obese patients with NAFLD.⁴ It is also unclear if clinicians should recommend such patients to lose weight. With this background, we report the one- and six-year outcomes of non-obese and obese patients with NAFLD in a clinical trial on lifestyle intervention. We hypothesise that lifestyle intervention is effective in treating NAFLD in both non-obese and obese patients. We also hypothesise that weight reduction is predictive of remission of NAFLD in the non-obese population.