The main difference in management approaches is between people found to have simple steatosis, remaining under primary care, and those referred to specialists due to high risk of advanced fibrosis. Lifestyle intervention is recommended as the first-line treatment option for all people with NAFLD, however, those with advanced disease may require surgical intervention.

As discussed in the referral and diagnosis section, in cases of steatosis, where advanced fibrosis cannot be ruled out, referral to a liver specialist for further investigation is vital. If a diagnosis of advanced fibrosis due to NASH is confirmed, a shared management and follow-up programme should be agreed between primary and secondary care providers.

Follow-up

The optimal follow-up period for people with NAFLD is still undetermined. People with advanced fibrosis due to NASH should be referred to a liver specialist and monitored, while those at risk or with early stage disease may be monitored by their primary care provider (PCP).

NAFLD status may change over time, warranting transfer of care between PCPs and liver specialists and individuals may require more or less frequent follow-up as their NAFLD status changes.

EASL recommendations on follow-up1

NAFL, nonalcoholic fatty liver; NASH, nonalcoholic steatohepatitis.

 

Follow-up period

Advanced fibrosis due to NASH

6 months – 1 year

NAFL without worsening of metabolic risk factors

2 – 3 years

Patients with metabolic risk factors

3 – 5 years

 

Lifestyle interventions

Lifestyle interventions are recommended for everyone with NAFLD regardless of severity. The focus should be on weight loss and regaining glycaemic control through diet and exercise, similar to interventions in people with obesity and/or type 2 diabetes mellitus (T2DM).2–4

Adherence to diet and exercise regimens in people with NAFLD can lead to improvements in overall liver histology, fibrosis severity and in some instances, complete reversal of steatosis, regardless of overall weight loss.3,4

Weight loss

Weight loss

Achieving a healthy weight should be the primary lifestyle goal for people with NAFLD who are overweight or obese. Even modest reductions in body weight have been shown to improve steatosis, with the effect on liver health linked to the percentage of weight lost.

In a study of 293 people with T2DM, weight loss due to lifestyle intervention was shown to correlate with a reduction in NAFLD and NASH. Of the participants that who achieved >5% weight loss, 58% experienced NASH resolution, and 82% experienced a 2-point reduction in NAFLD activity score (NAS). In those that achieved >10% weight loss, 90% had NASH resolution, 100% saw a 2-point reduction in NAD, and 45% had fibrosis regression.5 In another study, eight people with obesity, T2DM and NAFLD were placed on a moderately hypocaloric, very-low-fat diet (3% fat by weight). In some cases, hepatic steatosis was almost entirely reversed by moderate weight loss. A reduction in body weight of ~8% normalised fasting plasma glucose and led to an ~80% improvement in steatosis.2

Even modest reductions in body weight have been shown to improve steatosis, with the effect on liver health linked to the percentage of weight lost.

Diet

The most effective route to weight loss is through a calorie-restricted diet. While no particular type of diet is recommended for people with NAFLD, some dietary factors have been associated with positive outcomes.

The Mediterranean diet (high in monounsaturated fat) has been associated with additional steatosis reduction. This diet was investigated in a study of 12 people without diabetes, compared with a standard low-fat, high-carbohydrate diet.6 All participants undertook both diets in random order for 6 weeks each, with a 6-week wash-out period in between. The Mediterranean diet resulted in a greater reduction in steatosis vs the low-fat, high-carbohydrate diet over the same time period, despite the total weight loss remaining the same for each diet.

Restricting carbohydrate intake via a ketogenic diet, defined as <20 g carbohydrate/day, may provide an additional benefit to people with NAFLD. A pilot study in five people with NASH placed on a low-carbohydrate, ketogenic diet resulted in histological improvements by biopsy in four participants.7

Other studies evaluating low-calorie, low-carbohydrate and low-fructose diets have found similar benefits in reversing steatosis and NASH.8,9 Ultimately, the ability to adhere may be the most important factor when choosing a diet, as long as calorie restriction is incorporated

Alcohol consumption at moderate levels (20g, men; 30g, women), does not significantly impact steatosis and may even be protective against NAFLD. However, in people with NASH, total abstinence should be considered to reduce the risk of hepatocellular carcinoma (HCC).1,10 Drinking coffee has also been shown to be protective in NAFLD.1

Referral to a specialist dietician or other multi-disciplinary weight management service may be considered for those who have difficulty managing their diet.11

Exercise

Exercise should supplement dietary changes where possible to assist weight loss and development of a healthy lifestyle. Regular exercise combined with dietary changes has been shown to significantly improve weight loss and reduce hepatic fat deposits.3

In a study of 50 people with NAFLD, attainment of high fitness levels was associated with significantly reduced (−31%) hepatic fat deposits. Baseline fitness was the strongest factor predicting change in liver steatosis, followed by exercise intensity.

Although new exercise regimens are usually coupled with dietary alterations, multiple studies have found that exercise in isolation has a positive effect on hepatic steatosis, independent of weight loss.3,4 In terms of exercise type, both aerobic and resistance training have been shown to benefit people with NAFLD. In a randomised, controlled trial comparing both exercise types in 40 participants, hepatic fat content decreased by 32.8% and 25.9% in aerobic and resistance exercise groups, respectively. Hepatic steatosis also disappeared in approximately one quarter of both groups.12

Referral to an exercise physiologist, or a physiotherapist if injuries are preventing exercise, may help people achieve these goals.

Regular exercise combined with dietary changes has been shown to significantly improve weight loss and reduce hepatic fat deposits.3

Surgical interventions

Surgical interventions may be considered for people with more severe weight issues. Bariatric surgery can help some people lose weight, with potential knock-on or independent effects on reducing NAFLD severity.13–15 Liver transplantation is generally considered to be a last resort for people with NASH who are experiencing liver failure with no chance of disease reversal and restoration of healthy liver functioning.

Bariatric surgery

Randomised trials exploring the efficacy of bariatric surgery for the treatment of NAFLD or NASH have not been conducted,16,13 however, several retrospective and prospective studies have compared liver histology before and after surgery.13–15 In a prospective study of 381 adults followed over 5 years, there was a significant improvement in the prevalence and severity of steatosis and ballooning following either gastric band, biliointestinal bypass or gastric bypass procedures. In addition, people with probable or definite NASH experienced significant improvements in steatosis, ballooning, and resolution of NASH itself.14 Further meta-analyses appear to corroborate these findings,15 but the lack of randomised trials prevents endorsement of bariatric surgery to treat NASH or NAFLD in clinical guidelines.1

Liver transplantation

People with NASH who have progressed to liver failure, or have developed HCC, are candidates for liver transplantation. NASH is currently the second leading risk factor for liver disease and is on a trajectory to become the leading indication for liver transplantation following a four-fold increase in just 10 years.17,18

People with NASH-HCC have the most urgent requirement for liver transplantation. Among all causes of HCC, including alcoholic liver disease and hepatitis C virus (HCV), people with NASH-HCC have the largest 90-day waitlist mortality.17–19

Pharmacological interventions

Currently no pharmacological therapies are approved for the treatment of NAFL or NASH.

A number of insulin-sensitising agents have been investigated in people with NASH, however, results have been largely inconclusive. Studies into these compounds have shown either limited efficacy or concerning long-term safety profiles.20–25 As such, none of the compounds are endorsed by EASL for the treatment of NAFLD.1

The antioxidant properties of vitamin E have been shown to have beneficial effects on NASH histology in people without diabetes; a greater number of people showed improvement in steatohepatitis following 800 IU/day for 96 weeks compared with placebo.22 Despite this potential benefit, concerns also remain over long-term safety.For this reason, vitamin E supplementation is also not recommended by EASL guidelines for use in NAFLD patients.

Multidisciplinary management

Given the links between NASH and common morbidities, such as obesity, people with NAFLD may benefit from a multi-disciplinary team (MDT) approach.26 While the composition of MDTs will vary between units, a typical MDT will likely include hepatologists, diabetes consultants, dieticians and specialist nurses.27,28

In one study, the MDT approach led to new diagnoses of severe asymptomatic NAFLD in people with T2DM, and the involvement of dieticians resulted in weight loss and associated reductions in biomarkers of liver stress, indicating significant improvement of hepatic steatosis.26

Although potentially effective, the MDT approach to NAFLD investigation and management has not been extensively studied and use of such an approach is rare in clinical practice.29

NAFLD and NASH

A brief introduction to NAFLD and NASH and related content on site.

The Burden of NAFLD and NASH

Exploring the epidemiology, comorbidities and societal impact of NAFLD and NASH.

Identifying people with NAFLD

Information on primary care tests such as the NAFLD fibrosis score, ELF™ score and Fibrosis-4 index.

Referral and diagnosis

An overview of diagnostic testing which can help detect advanced fibrosis due to NASH.

Obesity and NASH

Exploring the links between obesity and advanced fibrosis due to NASH and obesity and NAFLD.

Diabetes and NASH

An overview of NAFLD and advanced fibrosis due to NASH in the context of type 2 diabetes mellitus.

References

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  2. Petersen KF, et al. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005;54:603–8.
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LID/IHQ/18-12//1048d(1) Date of preparation August 2019