Pediatric NAFLD Guidelines 2017

Posted on March 21, 2017 by gutsandgrowth

The concise recommendations (M Vos et al. JPGN 2017; 64: 319-34) from the Expert Committee on NAFLD (ECON)/NASPGHAN provide helpful advice on this increasingly common disorder. Link to full text: NASPGHAN Clinical Practice Guideline for NAFLD

The recommendations are graded on strength of recommendation and quality of the evidence.

Some key points:

Use ALT as a screening tool (despite its imperfections). Persistently elevations (>2xULN) should be evaluated for liver disease, including NAFLD. (Norms: 22 U/L for girls, 26 U/L for boys). Values above 80 U/L “warrants increased clinical concern.”
Screening should be considered between ages 9 and 11 years for all obese children and for overweight children with additional risk factors.
Ultrasound and CT scans are NOT recommended.
Liver biopsy should be considered for the assessment of NAFLD in children who have increased risk of NASH and/or advanced fibrosis. This could include those with splenomegaly, AST/ALT>1, higher ALT (>80 U/L), panhypopituitarism, and type 2 diabetes.
Treatment: Lifestyle modifications recommended. No currently avaiable medications or supplements are recommended.
Look for & avoid comorbidities: dyslipidemias, hypertension, and diabetes. Assure vaccinations against Hep A/Hep B and counsel against binge drinking and against smoking.

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Bariatric Surgery and Reversal of NASH

Posted on February 7, 2017 by gutsandgrowth

A small prospective study (M Manco et al. J Pediatr 2017; 180: 31-7) provides evidence that bariatric surgery/sleeve gastrectomy is effective at reversing nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in adolescents (n=20).

All patients in this study had BMI >35 and weere 13-17 yrs of age.

Key findings at one year following intervention:

Among the 20 patients who underwent sleeve gastrectomy, there was a 21.5% loss in baseline weight, which compared with weight loss of 3.4% among 20 patients who received intragastric balloon device and weight increase of 1.7% among 53 patients who received lifestyle intervention counseling.
Sleeve gastrectomy group had resolution of NASH in all 20 and disappearance of hepatic fibrosis in 18 (90%). In the intragastric balloon group, NASH reverted in 24% and fibrosis in 37% whereas there was no improvement in the lifestyle intervention group.

Full text link: Sleeve Gastrectomy for NASH

Limitations are discussed in the editorial by Inge and Xanthakos (pgs 6-7) and included small sample size, absence of patients with type 2 diabetes, and short followup period. Nevertheless, this is “the largest and most informative series…in select adolescents with severe obesity.”

My take: Given the lack of effective pharmaceutical therapy and the typically impotent effects of lifestyle intervention, this data supports bariatric surgery to facilitate weight loss/NASH reversal in select adolescents.

Related article: JCF Leung et al. Hepatology 2017; 65: 54-64. This study showed that the histologic severity and clinical outcomes are modestly better in nonobese patients (n=72) with NAFLD compared with obese patients (n=307). High triglycerides and higher creatinine were associated with more advanced liver disease in nonobese patients.

Briefly noted: D Houghton et al. Clin Gastroenterol Hepatol 2017; 15: 96-102. This study with 24 subjects with nonalcoholic steatohepatitis showed that exercise reduced hepatic triglyceride content, visceral fat, and plasma triglycerides. However, circulating markers of inflammation and fibrosis was not reduced. The implication is that exercise should be part of NASH treatment but that weight management/diet are needed as well.

Glacier Natl Park

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Fatty Liver Improved with Exercise

Posted on November 10, 2016 by gutsandgrowth

A recent study (LA Orci et al. Clin Gastroenterol Hepatol 2016; 14: 1398-1411) analyzed data from 28 randomized trials (>1600 patients) and performed a meta-analysis regarding the utility of exercise for nonalcoholic fatty liver disease (NAFLD).

Key finding:

Physical activity, independently from diet change, was associated with improvement in intrahepatic lipid content (-0.69) and with reduction in alanine aminotransferase.

The authors note that the effects of lipid reduction due to exercise is considered moderate-to-large. In several trials, another effect of exercise that was measured was a reduction in insulin resistance.

Limitations:

The duration of the effect of exercise is not known and there is not a clear “dose” of exercise.
Lack of histologic data (only 2 studies had histology data)

My take: This study suggests that exercise by improving metabolic status is important in improving NAFLD; thus, a fatty liver is not just about being fat.

Bar Harbor at Sunset

Concise Review: Fatty Liver in Pediatrics

Posted on June 24, 2016 by gutsandgrowth

A recent review (J Schwimmer. Hepatology 2016; 1718-25) provides a succinct up-to-date approach to the common problem of Nonalcoholic Fatty Liver Disease.

As this was a review, much of the material has been covered by this blog and previous publications. The review discusses the upper limit of normal for alanine aminotransferase and its utility. Liver imaging is discussed: “MRI is well suited for use in clinical research” whereas “ultrasound does not meet the standard clinical threshold required to be used to diagnose fatty liver…or used as an outcome measure.”

Dr. Schwimmer reviews a prospective study of 347 overweight or obese children with suspected NAFLD (blog review of this study: Screening for NAFLD). He notes that 24% (n=61) of those who underwent liver biopsy ultimately had other diagnoses, especially autoimmune liver disease (n=11) and celiac disease (n=4). “The clinical challenge is to determine who needs how much of a workup. The greater potential for hepatotoxicity and the more advanced the disease is believed to be, the greater the need to be certain of the diagnosis and to properly grade and stage the disease.” Currently, “no other diagnostic modality has shown sufficient accuracy to be appropriate for clinical use in the place of biopsy.”

He reviews associated health conditions with NAFLD including obesity, dyslipidemia, hypertension, cardiac dysfunction, and obstructive sleep apnea (~60% of NAFLD patients).

What about treatment? “There is not an available, proven, safe, and effective [pharmacologic] treatment for NAFLD in children…Current treatment is …focused on optimizing lifestyle, including nutrition, physical activity, and mental well-being.”

My take: Despite 20 years of clinical practice, the workup for NAFLD remains a vexing problem. It is not practical to offer a liver biopsy to 10% of the pediatric population. So determining who (besides those with more severe presentations) will benefit from an exhaustive workup remains unclear. In the meanwhile, at a minimum, we need to keep looking for treatable liver conditions (eg. autoimmune hepatitis, celiac disease, Wilson’s disease, and viral hepatitis).

An article with a similar focus (Dr. Schwimmer is the corresponding author): J Pediatric 2016; 172: 9-13. This report and Dr. Schwimmer’s review both tout the safety of liver biopsy. Neither report presents much data on costs of either liver biopsies or MRI.

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Zoo Atlanta 2016

Interesting Fatty Liver Articles -Spring 2016

Posted on May 23, 2016 by gutsandgrowth

J Bousier et al. Hepatology 2016; 63: 764-75. This study showed an association between the severity of nonalcoholic fatty liver disease and gut dysbiosis/shift in gut microbiome in 57 patients. Specifically, Bacteroides was independently associated with NASH and Ruminococcus with significant fibrosis.

V WS Wong et al. Hepatology 2016; 63: 754-63. This study showed that NAFLD (identified by ultrasonography screening) was frequent (58.2%) among 612 consecutive patients who were undergoing coronary angiogram. During a followup (3679 patient-years), NAFLD patients had a lower adjusted HR of death (0.36). Older age and diabetes were indepenently associated with cardiovascular events. In addition, during f/u NAFLD patients in their cohort rarely developed liver cancer or cirrhotic complications. Thus, NAFLD is common among patients with coronary artery disease but did not predict a worsened outcome.

F Piscaglia et al. Hepatology 2016; 63: 827-38. This report was a study of 756 patients with liver cancer (HCC) due to either NAFLD (145) or HCV (611). HCC in NAFLD patients had a larger volume, was more infiltrative, and was detected outside surveillance. NAFLD-HCC was associated with a lower survival (25.5 months compared with 33.7 months for HCV-HCC). The authors note that after patient matching for tumor stage, the survival rate was similar. The difference in survival does not account for lead-time bias (What’s More Important: Improving Mortality Rate or Survival …). Overall, the study indicates that without surveillance, HCC is detected later. Due to the frequency of NAFLD, it is unclear which patients would benefit from surveillance and what type of surveillance should be recommended.

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Farjado, Puerto Rico

Should Teenagers with Severe NAFLD Undergo Bariatric Surgery?

Posted on December 28, 2015 by gutsandgrowth

A recent commentary (Stavra A. Xanthakos and Jeffrey B. Schwimmer. Nat Rev Gastroenterol Hepatol. 2015 Jun; 12(6): 316–318.) discusses the role of bariatric surgery for teenagers with severe nonalcoholic fatty liver disease (NAFLD). Full text Link: On a knife-edge—weight-loss surgery for NAFLD in adolescents.

Here’s an excerpt:

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… 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.

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Overlooking Obesity in Hospitalized Children

Posted on November 24, 2015 by gutsandgrowth

A recent study (MA King et al. J Pediatr 2015; 167: 816-20) shows that physicians and physician trainees rarely addressed overweight/obesity in hospitalized children at a Utah pediatric hospital.

Using a chart review and an administrative database, the authors note that overweight/obesity was identified in 8.3% (n=25) and addressed in 4% (n=12) of 300 hospitalized children with overweight/obesity. They conclude that “this represents a missed opportunity for both patient care and physician trainee education.”

My take: In many cases, addressing overweight/obesity at a stressful time like a hospitalization may be unwelcome. In children who are not very sick, offering nutritional counseling would be worthwhile. For others, I think encouraging outpatient followup would be reasonable.

Also noted: “High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery” SA Xanthakos et al. Gastroenterol 2015; 149: 623-34. In this cohort of 242 adolescents, 59% had NAFLD. None had cirrhosis; stage 3 fibrosis was identified in 0.7%. Comment: I’m surprised that only 59% had NAFLD.

NASH Update -September 2015

Posted on September 24, 2015 by gutsandgrowth

Briefly noted:

Obeticholic acid, a Farnesoid X Receptor Ligand, is being studied as a potential agent in nonalcoholic steatohepatitis (NASH). According to a recent study (Lancet 2015; 385: 956-65), patients assigned to receive obeticholic acid were more likely to have improved liver histology compared with placebo (50/110 [45%] compared with 23/109 [21%]). The obeticholic group had increase serum cholesterol and LDL cholesterol. This study looked at a subgroup of patients in the FLINT study who had undergone liver biopsies.

E Vilar-Gomez et al. Gastroenterol 2015; 149: 367-78. This prospective study of 293 patients with histologically-proven NASH were followed after undergoing lifestyle changes for 52 weeks. At week 52, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (steatohepatitis, NAS activity score, and fibrosis.

G Lassailly et al. Gastroenterol 2015; 149: 379-88. Between 1994-2013, 109 morbidly-obese patients with histologically-proven NASH underwent bariatric surgery. One year after surgery, NASH had disappeared from 85% of the patients.

P Angulo et al. Gastroenterol 2015; 149: 389-97. In this retrospective analysis of 619 patients with NAFLD (1979-2005), the authors noted that “fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.”

When Will MRI Obviate the Need for a Liver Biopsy in Pediatric NAFLD?

Posted on July 14, 2015 by gutsandgrowth

A recent study (JB Schwimmer et al. Hepatology 2015; 1887-95, editorial Vos MB, pages 1779-80) examines the accuracy of magnetic resonance imaging (MRI) compared with liver histology in children with nonalcoholic fatty liver disease.

This prospective validation study enrolled 174 children with a mean age of 14 years. The MRI estimated the liver proton density fat fraction (PDFF).

Key findings:

Liver MRI-PDFF correlated with steatosis grade; the correlation was particularly strong at high and low end values. Thus, a very low MRI-PDFF was highly likely to predict a steatosis grade 0 or 1 while a very high value corresponded to high steatosis levels.
Liver MRI-PDFF was weaker in children with stage 2-4 fibrosis than in children with no fibrosis

The editorial notes that this study “is one of hundreds now published in the literature on MRI and NAFLD…The superiority of MR-based methods…over ultrasound is clear. The question is why are we still ordering abdominal ultrasounds to diagnose NAFLD in children?” The barriers for usage of MRI include cost, potential sedation, and nonuniform methods for MRI usage.

The paper conclude that “MRI is not yet sufficient to replace liver biopsy in children.” The editorial also indicates that the MRI era is fast approaching but not viable today.

Take-home point: Due to the huge numbers of patients with pediatric NAFLD, MRI remains a terrific area for research but remains problematic in clinical practice. Given the expense of MRI, until its use can reduce liver biopsies or improve management, its role is likely to remain limited.

Turner Field

Reaching Consensus on Bariatric Intervention in Children and Adolescents

Posted on May 15, 2015 by gutsandgrowth

A recent medical position paper (Nobili V, et al. JPGN 2015; 60: 550-61) provides guidance for bariatric surgery intervention in children and adolescents with and without nonalcoholic fatty liver disease (NAFLD).

While the authors acknowledge that bariatric surgery can “dramatically reduce the risk of adulthood obesity and obesity-related diseases,” they advocate its use in adolescents with the following:

BMI >40 kg/m-squared with severe comorbidities: type 2 diabetes mellitus, moderate-to-severe sleep apnea, pseudotumor cerebri, or NASH with advanced fibrosis (ISHAK score >1)
BMI >50 kg/m-squared with mild comorbidities: hypertension, dyslipidemia, psychological distress, gastroesophageal reflux, anthropathies, NASH, impairment in activities of daily living, mild obstructive sleep apnea, panniculitis, chronic venous insufficiency, urinary incontinence
Additional criteria: have attained 95% of adult stature, failed behavioral/medical treatments, psychological evaluation perioperatively, avoid pregnancy for 1 year after surgery, will adhere to nutritional guidelines after surgery, informed assent from teenager (along with parental consent)

Key points:

“There is a lack of randomized controlled trials examining the effects of bariatric surgery on NAFLD or NASH.” In Table 3, the authors provide a summary of 16 previous studies/outcomes; though none of the studies enrolled more than 60 patients.
In an adult prospective study with 381 patients (Mathurin P et al. Gastroenterol 2009; 137: 532-40), there was a significant decline in the severity/prevalence of steatosis and resolution of NASH at 1 and 5 years.
Bariatric surgery, in adult studies, have improved diabetes, insulin resistance, hypertension, and dyslipidemia.
Patients who have “undergone bariatric surgery show higher suicide rates than the general population.” Psychological evaluation should be integrated with surgical decision.
Type of surgery: Roux-en-Y Gastric Bypass (RYGB) is favored by the authors; they also discuss studies with Laparoscopic Adjustable Gastric Banding (LAGB). “RYGB and LAGB are the 2 main surgical procedures that have been used in pediatric obesity. RYGB is considered a safe and effective option for adolescents with extreme obesity, as long as appropriate long-term follow-up is provided. LAGB has not been approved by Food and Drug Administration for use in adolescents, and there should be considered investigational only.”

It is interesting that the authors are so deferential to the Food and Drug Administration. It is clear from their position paper that LAGB has similar evidence supporting its use in adolescents as RYGB. They even note that it has potential for reversibility and “an excellent safety profile with a lower risk of postoperative vitamin deficiencies when compared with biliopancreatic diversion and RYGB.”

Bottomline: Given the continuation of the obesity epidemic, additional pediatric medical expertise will be needed to help evaluate adolescents for bariatric surgery and to follow them postoperatively.

gutsandgrowth

Pediatric Gastroenterology

Tag Archives: nonalcoholic fatty liver disease