Sarcopenia in nonalcoholic fatty liver disease: new challenges for clinical practice

ABSTRACT

Introduction: Sarcopenia is increasingly recognized in patients with nonalcoholic liver disease (NAFLD). Initially recognized as a consequence of advanced liver disease, there is now emerging evidence that sarcopenia may be a novel risk factor for the development of NAFLD, with a role in fibrosis and disease progression.

Areas covered: This review examines the epidemiology, pathogenesis, and complex interplay between NAFLD and sarcopenia. Furthermore, the authors discuss the challenges with diagnosis of sarcopenia in the clinic and the evidence-based management of sarcopenia in patients with NAFLD. A MEDLINE and PubMed search was undertaken using the terms; ‘sarcopenia,’ ‘frailty,’ ‘muscle,’ ‘obesity,’ ‘non-alcoholic fatty liver disease,’ ‘non-alcoholic steatohepatitis’, and ‘cirrhosis’ up to 31 September 2019.

Expert opinion: Sarcopenia may be masked by the co-existence of morbid obesity, which is most notable in patients with NAFLD. Sarcopenia is a key indicator of adverse outcomes in patients with cirrhosis, such as hepatic decompensation, poor quality of life and premature mortality. Patients with NAFLD and advanced fibrosis/cirrhosis should undergo anthropometric measures (handgrip strength), dry body mass index, and measures of physical frailty (including muscle function, not just mass) to enable targeted early interventions of nutrition (low fat, 1.5 g/kg/day protein intake, 2–3 hourly food intake) and exercise (combined resistance and aerobic).

KEYWORDS:

• Frailty
• cirrhosis
• steatohepatitis
• muscle
• fatty liver

Article Highlights

• Reduced muscle mass and strength is common in patients with NAFLD, especially in those with advanced liver disease.

• Sarcopenia predicts clinical outcomes in patients with NAFLD cirrhosis independent of the underlying liver disease severity, as assessed by model for end stage liver disease (MELD).

• Sarcopenic obesity, which refers to the combination of reduced muscle strength and function with obesity (BMI >30 kg/m²), can mask muscle wasting in patients with NAFLD and thereby go unrecognized.

• Although there are some arguments for a causal link between sarcopenia and NAFLD without advanced liver disease, there remains a lack of strong experimental data to clarify the mechanistic pathways by which muscle loss could promote NAFLD progression, or vice-versa how NAFLD could induce sarcopenia and frailty.

• Muscle strength and function can be easily assessed using simple clinical tools such as handgrip strength (HGS), the short physical performance battery (SPPB), and the liver frailty index (LFI).

• Evidence-based nutritional interventions for sarcopenia in patients with NAFLD cirrhosis include targeting protein intake (aim 1.5-2.0g/Kg/day) with dietary modifications and protein supplements, as well as a late evening snack to shorten overnight fasting.

Declarations

MJ Armstrong has received unrelated speaker fees from Novo Nordisk and Norgine. The authors have no other relevant affiliations, financial involvement with any organization, entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart-from those disclosed. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research (NIHR) or the Department of Health.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This paper was not funded.