On a knife-edge—weight-loss surgery for NAFLD in adolescents (original) (raw)

. Author manuscript; available in PMC: 2015 Dec 1.

Published in final edited form as: Nat Rev Gastroenterol Hepatol. 2015 Apr 14;12(6):316–318. doi: 10.1038/nrgastro.2015.59

Abstract

A new position statement from Europe endorses expert-based recommendations to consider bariatric surgery as a treatment for severe NAFLD in severely obese adolescents. This article discusses the problem of severe paediatric obesity, its relationship with NAFLD, and the knowledge and needs regarding bariatric surgery in adolescents.

A new position statement from the Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) provides an overview of adolescent bariatric surgery indications and outcomes, with a particular emphasis on adolescents with NAFLD.1 In many countries, NAFLD is the most common form of chronic liver disease in children. NAFLD ranges from bland steatosis to NASH, which includes inflammation, hepatocellular injury and can progress to cirrhosis. The high prevalence of NAFLD among children raises concern that childhood-onset NASH will lead to high future rates of liver transplantation, given that no proven, safe and effective pharmacotherapy options exist for children with NAFLD or NASH.2Because many children with NAFLD are overweight or obese, lifestyle interventions, including weight loss, are often recommended as the first-line intervention.2

In the USA, one in three children are overweight or obese, while severe obesity prevalence has quadrupled to 5% of adolescents.3 However, obesity and NAFLD should not be considered interchangeable. Not every overweight or obese child has NAFLD, and children with NAFLD have higher rates of dyslipidaemia, impaired glucose metabolism, and hypertension than their age, sex, and weight-matched peers.4 We also routinely see children who are normal weight with NAFLD. Thus, although some children with NAFLD are severely obese, most children with NAFLD are younger and less obese than adolescents undergoing surgical treatment of obesity.

In children, improvement in health via weight loss typically requires participation in intensive comprehensive lifestyle interventions, which include frequent visits to work with multidisciplinary specialists.5 Although these programs can reduce BMI by 1.9 to 3.3 units compared with conventional counselling, they are not widely available.5 Further, sustained clinically significant weight loss is even more challenging for children with severe obesity. Only one comprehensive lifestyle study included a large proportion of severely obese adolescents and yielded only a ‐1.7 unit BMI decrease with a very high attrition rate of 53%.6 Moreover, the presence of NAFLD might also make weight loss more difficult.

There is great interest in bariatric surgery as a potential treatment for severe NAFLD in adolescents because of a high prevalence of severe paediatric obesity, a dearth of effective pharmacotherapy options, and the reliance on weight loss as a primary therapy. Bariatric surgery can substantially reduce BMI in severely obese adolescents (Supplementary Box 1). Furthermore, bariatric surgery can yield favorable changes in glucose tolerance, dyslipidaemia and systemic inflammation, all of which might theoretically benefit NASH.1

As summarized in Table 1, clinical guidelines regarding adolescent bariatric surgery have evolved. The earliest guideline in 2004 was the most conservative, reflecting limited outcome and safety data in adolescents.7 Subsequently, studies have shown that adolescent bariatric surgery can produce meaningful weight loss, improvements in cardiometabolic risk factors, and quality of life (Supplementary Box 1). Accordingly, the BMI threshold proposed for adolescent bariatric surgery was lowered to a BMI of ≥35 kg/m2 with type 2 diabetes, obstructive sleep apnoea, pseudotumor cerebri or severe NAFLD.8,9 The rationale for including these comorbidities as surgical criteria at a lower BMI is their potential to increase short-term morbidity. However, as the ESPGHAN statement notes, the data supporting improvements in diabetes and sleep apnoea are more robust in adults, with only a few small case series showing improvements in teenagers with these conditions.1

Table 1.

Overview of published recommendations for adolescent bariatric surgery criteria

Reference Lower BMI criteria: Higher BMI criteria:
Inge et al. (2004)7 BMI ≥ 40 kg/m2with:Type 2 diabetesObstructive sleep apnoeaPseudotumor cerebri BMI ≥ 50 kg/m2with:HypertensionDyslipidaemiasNASHVenous stasis diseaseQuality of life impairment
Pratt et al. (2009)9 BMI ≥ 35 kg/m2 with comorbidities associated with greater short-term morbidity:Type 2 diabetesSevere steatohepatitisPseudotumor cerebriModerate-to-severe obstructive sleep apnoea BMI ≥ 40 kg/m2 with comorbidities associated with long-term morbidity (not specified)
Michalsky et al.(2012)8 BMI ≥ 35 kg/m2 with major comorbidities:Type 2 diabetesSevere steatohepatitisPseudotumor cerebriModerate-to-severe obstructive sleep apnoea (apnoea-hypopnea index ≥ 15) BMI ≥ 40 kg/m2 and other comorbidities:HypertensionInsulin resistanceGlucose intoleranceImpaired quality of lifeDyslipidaemia
Nobili et al.(2015)1* BMI >97% percentile (or >40 kg/m2) with major comorbidities:Type 2 diabetes mellitusModerate to severe sleep apnoeaPseudotumor cerebriNASH with significant fibrosis (Ishak score ≥1) BMI >97% percentile (or >50 kg/m2) with other mild comorbidities:HypertensionInsulin resistanceGlucose intoleranceSubstantially impaired quality of lifeDyslipidaemiaMilder sleep apnoea

Notably, no comprehensive lifestyle or bariatric surgery studies have focused specifically on severely obese adolescents with NAFLD (Supplementary Box 1). Therefore, the safest and most effective approach to weight loss for the treatment of NASH in adolescents remains unknown and controversial, with divergent recommendations on whether NASH should be an indication for bariatric surgery. Although some adolescent bariatric surgery guidelines include NASH as an indication8,9—on the basis of preliminary data in adults—a practice guideline on NAFLD management from three major gastroenterology and hepatology professional societies did not recommend bariatric surgery as a specific treatment for NASH owing to a lack of controlled studies.2 Similarly, a 2010 Cochrane meta-analysis of bariatric surgery for NASH concluded that, “the lack of scientifically sound evidence precludes any recommendation to support or reject bariatric surgery to treat patients with NAFLD”.10 In addition, it is important to remember that bariatric surgery is not always appropriate for every adolescent even if they meet accepted criteria for surgery. It requires a high degree of commitment and psychosocial readiness on the part of the adolescent and their family to be maximally successful.

Critical knowledge gaps remain, including the following: one, does bariatric surgery result in significant improvement in more histologically severe NASH, in particular advanced fibrosis; two, is bariatric surgery safe in patients with compensated NASH-related cirrhosis; three, does the hepatic outcome in response to bariatric surgery depend upon the response of specific comorbid conditions, such as type 2 diabetes and obstructive sleep apnoea; four, can NASH recur long-term, particularly if substantial weight regain occurs; five, does the type of surgery affect NASH outcome; and six, are there beneficial effects from surgery independent from weight loss? For example, bariatric surgical procedures have been shown to have varying actions on gastrointestinal hormone and bile acid pathways that might have a role in the pathogenesis of NAFLD and might also alter the gastrointestinal microbiome, which has been linked to NAFLD.

To address these questions, it is critical that adolescents with NAFLD undergoing bariatric surgery be evaluated and managed in bariatric surgery centres with appropriate paediatric multidisciplinary expertise and a commitment to rigorously phenotype NAFLD histology at baseline and to follow outcomes prospectively as long as possible. These procedures can be particularly challenging in adolescents, who are prone to relocate in adulthood and thus might not return for follow-up. High quality prospective multicentre studies with low attrition rates, such as the Teen Longitudinal Assessment of Bariatric Surgery (USA) and the Adolescent Morbid Obesity Study (Sweden) have begun to provide short to intermediate term (1–2 year) outcomes after adolescent bariatric surgery, but do not include prospectively collected data on histological liver outcomes to support evidence-based recommendations regarding NASH as a specific indication for bariatric surgery. However, given the benefits that are emerging for type 2 diabetes and sleep apnoea, (which are comorbid conditions often associated with NASH), we concur with previously published expert guidelines that conclude that bariatric surgery is not contraindicated in a non-cirrhotic patient with NAFLD who otherwise meets appropriate medical and psychosocial criteria for bariatric surgery.2 The adolescent and family should, however, be counselled that a positive outcome with respect to NAFLD is, as yet, not a foregone conclusion.

Supplementary Material

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Acknowledgments

The work of the authors is supported in part by DK088925, DK090350, DK088831, and DK100429. The funders did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Footnotes

Competing interests

The authors declare no competing interests.

Supplementary information is linked to the online version of the paper atwww.nature.com/nrgastro

References

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Supplementary Materials

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