What Do Abnormal Liver Enzymes Mean in a Tween William Balistreri
Below I’ve included a few slides and some notes; my notes may have errors of omission or transcription.
- Provided updated normal reference data for ALT/AST along with patterns of abnormalities
- Reviewed step-wise workup for teenagers with elevated ALT/AST, particularly fatty liver disease and drug-induced liver disease
- Increasingly frequent cause of fatty liver disease: psychotropic medications
- Discussed role/indications of liver biopsy. Liver biopsy is NOT practical option for all children with fatty liver disease and elevated liver enzymes
- However, ALT values tend to underestimate severity of liver disease
S Xanthakos et al. Clin Gastroenterol Hepatol 2020; 18: 1070-81. Full Text: Nutritional Risks in Adolescents After Bariatric Surgery
This was a multicenter prospective cohort study with 226 adolescents (mean age 16.5 years, mean BMI of 52.7) who had either Roux-en-Y bypass (RYGB, n=161) or vertical sleeve gastrectomy (VSG, n=67).
- At 5 years, 59% of RYGB and 27% of VSG had ≥2 nutritional deficiencies
- The most prevalent abnormality we observed was hypoferritinemia, which affected nearly twice as many RYGB recipients by Year 5 compared with VSG.
- Vitamin B12 status likewise worsened disproportionately after RYGB, despite similar trajectories of weight loss after VSG
- Image below shows the prevalence of abnormal values for vitamins over time
My take: This study shows that adolescents undergoing VSG had fewer nutritional deficiencies than RYGB and provides data supporting nutritional monitoring after bariatric surgery.
B Koletzko et al. JPGN 2020 70: 702-10. Full Text: Prevention of Childhood Obesity: A Position Paper of the Global Federation of International Societies of Paediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN)
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A recent policy statement (SC Armstrong et al. Pediatrics 2019; 144 (6): e20193223) outlines current evidence regarding adolescent bariatric surgery and makes recommendations for practitioners & policymakers. There is also an accompanying technical report which provides more detail and supporting evidence. Thanks to Ben Gold for this reference.
Full PDF Link: Pediatric Metabolic and Bariatric Surgery: Evidence, Barriers, and Best Practices
This policy statement uses “adolescent” to refer to a person from age 13 years to age 18 years.
Background: “Although nearly 4.5 million US adolescents have severe obesity, current estimates suggest that only a small faction undergo metabolic and bariatric surgery…Many providers prefer a “watchful waiting” approach, or long-term lifestyle management.50 However, current evidence suggests that pediatric patients with severe obesity are unlikely to achieve a clinically significant and sustained weight reduction in lifestyle-based weight management programs53 and that watchful waiting may lead to higher BMI and more comorbid conditions…In addition, comparative data examining
postoperative outcomes along the severely obese BMI spectrum (low, middle, and high) suggest that adolescents within a lower BMI range (BMI <55) at the time of bariatric
surgery have a higher probability of achieving nonobese status when compared with individuals with a higher starting BMI (BMI ≥55).”
From Table 2 -Indications for Bariatric Surgery:
- Class 2 obesity, BMI ≥35, or 120% of the 95th percentile for age and sex, whichever is lower along with clinically significant disease, including obstructive sleep apnea (AHI .5), T2DM, IIH, NASH, Blount disease, SCFE, GERD, and hypertension
- Class 3 obesity, BMI ≥40, or 140% of the 95th percentile for age and sex, whichever is lower. Clinically significant disease is not required but commonly present
Recommendations for practitioners:
- Seek high-quality multidisciplinary centers that are experienced in assessing risks and benefits of various treatments for youth with severe obesity, including bariatric surgery, and provide referrals to where such programs are available.
- Identify pediatric patients with severe obesity who meet criteria for surgery and provide
timely referrals to comprehensive, multidisciplinary, pediatric-focused metabolic and bariatric surgery programs.
- Monitor patients postoperatively for micronutrient deficiencies and consider providing iron, folate, and vitamin B12 supplementation as needed.
- Monitor patients postoperatively for risk-taking behavior and mental health problems.
- Advocate for increased access for pediatric patients of all racial, ethnic, and socioeconomic backgrounds to multidisciplinary programs
- Consider best practice guidelines, including avoidance of unsubstantiated lower age limits, in the context of potential health care benefits and individualized patient-centered care.
- For insurers: Provide payment for care (pre-operative, operative & post-operative). Reduce barriers to pediatric metabolic and bariatric surgery (including inadequate payment, limited access, unsubstantiated exclusion criteria, and bureaucratic
delays in approval requiring unnecessary and often numerous appeals) for patients who meet careful selection criteria.
My take: These recommendations are in general agreement with previous guidelines. I think having the stamp of approval from the AAP is likely to help in getting coverage and may shift attitudes.
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A recent population-based cohort study (JH Kauppila et al. Gastroenterol 2019; 157: 19-27) examined the effects of bariatric surgery on survival from Nordic countries between 1980-2012.
Link: Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study
Among 505,258 obese individuals, 49,977 had bariatric surgery.
- Overall mortality rates were lower in the surgery group during the first 14 years but higher after 15 years (HR 1.20 with CI 1.02-1.42). Thus, overall, obese patients who underwent bariatric surgery had longer survival times than obese patients who did not have surgery. Both groups had higher mortality than the general population
- The improved survival compared to those without surgery was related to decreased mortality from cardiovascular mortality, diabetes and cancer. However mortality due to suicide was increased.
- Limitations: lack of detailed data including BMI, smoking and alcohol consumption
Graphical abstract (available online)
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Studies have shown that adults with obesity who were obese as adolescents have worse medical outcomes than persons who became obese in adulthood (Nat Rev Endocrinol 2018; 14: 183-8; NEJM 2011; 365; 1876-85). Thus, the question is whether earlier intervention would improve outcomes.
A recent study (TH Inge et al. NEJM 2019; 380: 2136-45, editorial TD Adams, pgs 2175-7) compares the 5-year outcomes of adolescents (n=161) and adults (n=396) who underwent Roux-en-Y gastric bypass (RYGB). The two prospectively enrolled cohorts were participants in two related but independent studies.
- There was similar weight loss in both groups at the 5-year mark: -26% in adolescents and -29% in adults
- Adolescents had greater remission in both type 2 diabetes (86% vs 53%) and in hypertension (68% and 41%).
- Three adolescents (1.9%) and seven adults (1.8%) died in the 5-years after surgery. Two of the adolescents deaths were consistent with overdose.
- Reoperations were significantly higher in adolescents than adults (19 vs 10 reoperations per 500 person years). The authors comment that the reason for this finding is unclear, possibly related to recall bias or closer monitoring of the adolescents.
- Nutrient deficiencies were common in adolescents at followup. After 2 years, 48% of adolescents had low ferritin compared with 29% of adults (98% of participants had normal ferritin prior to RYGB. The authors note that this is likely related to adherence to vitamin/mineral supplementation (which is needed lifelong).
Limitations: observational study design
The associated commentary::
- “Almost 6% of adolescents in the U.S. are severely obese and bariatric surgery is now the only successful long-term management…Negative health outcomes of bariatric surgery reported in adolescents mirror those reported in adults — including, for example, potential for self-harm (including suicide) and increased risk of alcohol or drug abuse.”
- “Adolescent patients may not have fully developed the capacity for decision making, especially about a procedure that will have lifetime consequences.”
My take: This study and commentary point out some clear health benefits for adolescents who undergo RYGB. Given the lifelong need for monitoring and adherence with medical treatment as well as some of the negative health outcomes, it is also clear how challenging it is to proceed with RYGB in teenage years.
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Square in Toledo, Spain
A recent systematic review and meta-analysis (Y Lee, et al. Clin Gastroenterol Hepatol 2019; 17: 1040-60) included 32 cohort studies with 3093 liver biopsy specimens from patients with nonalcoholic fatty liver disease (NAFLD).
- Bariatric surgery resulted in a biopsy-confirmed resolution of steatosis in 66%, inflammation in 50%, ballooning degeneration in 76%, and fibrosis in 40%.
- Bariatric surgery resulted in worsening features of NAFLD in 12%.
- The authors note that Roux-en-Y Gastric Bypass (RYGB) “showed greater reduction of liver side effects and higher: resolution of NAFLD.”
- Jejejnoileal bypass (JIB) and biliopancreatic diversion (BPD) “both have been associated with higher liver function morbidity.”
- The overall GRADE quality of evidence was considered very low.
My take: Though better studies are needed, the majority of patients’ livers appear to benefit from bariatric surgery.
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According to a recent study (EL Yu et al. J Pediatr 2019; 207: 64-70), about one-third of boys and one-fourth of girls with obesity have nonalcoholic fatty liver disease (NAFLD).
This study from San Diego with 408 children aged 9-17 years (mean 13.2 years) with obesity evaluated for NAFLD with laboratories (to exclude other etiologies) and with liver MRI proton density fat fraction (PDFF), with ≥5% considered the threshold for NAFLD.
- Prevalence of NAFLD was 26% in this population, with 29.4% in males and 22.6% in females
- The optimal cut offs of ALT for detecting NAFLD in this study were ≥30 U/L for females and ≥42 U/L for males. These are much lower than NASPGHAN guidelines which proposed ≥80 U/L or twice the ULN as thresholds for further investigation. (The NASPGHAN recommendations are likely to have higher specificity in identifying children at greater risk for nonalcoholic steatohepatitis (NASH).)
- 77% of this cohort were hispanic, thus prevalence may vary significantly in other populations.
- MRI-PDFF -the exact cut off is unclear. The authors note that if 3.5% were chosen, the NAFLD prevalence jumped to 49.3% (according to Table II –though the discussion stated 53.2%)
My take: Understanding the likelihood of NAFLD in children at risk is a helpful first step. This study points to the growing use of non-invasive diagnosis with MRI.
On a related topic, briefly noted: “Obesity in Adolescents and Youth: The Case for and against Bariatric Surgery” (A Khattab, MA Sperling. J Pediatr 2019; 207: 18-22). In this review, the authors refer frequently to endocrine society guidelines (J Clin Endocrinol Metab 2017; 102: 709-57). These guidelines generally recommend bariatric surgery only under specific conditions (eg. completion of Tanner 4 or 5 along with a BMI of 40 kg/m-squared or BMI of 35 with significant extreme comorbidities after failure of lifestyle modifications & without untreated psychiatric illness). This review predicts increasing use of bariatric surgery in adolescents “as more data on long-term outcomes in larger cohorts become known.”
Related blog posts on fatty liver disease:
Related blog posts on bariatric surgery:
I did not make it to this year’s meeting but did get a chance to catch up on a lot information via the PG 2018 Syllabus and based on information posted online.
Here are a couple of highlights for me:
My favorite slide from postgraduate course -Dr. Robert Kramer
Slides regarding the topic of Treat-toTarget Dr. Eric Benchimol:
Slides regarding GI symptoms and autism from Dr. Kara Margolis:
Slide regarding the frequency of bariatric surgery: Dr. Rohit Kohli:
Slides regarding intestinal failure population from Dr. Conrad Cole:
From Dr. Miranda van Tilburg regarding psychological therapies for functional GI disorders:
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
A recent prospective study (V Nobili et al. J Pediatr 2018; 194: 100-8) consecutively enrolled 20 severely obese adolescents with biopsy-proven nonalcoholic fatty liver disease (NAFLD). The authors used liver histology, immunohistochemistry and cytokine analysis to assess the changes (after 12 months) induced by bariatric surgery with laparoscopic sleeve gastrectomy (LSG).
- NAFLD Activity Score and fibrosis improved after LSG. Steatosis, hepatocyte ballooning, and NAS score showed a significant improvement (Z=-2.7; P=.007) at 12 months following surgery. Fibrosis improvement (Z=-2.449) was noted as well.
- The histologic improvement “is associated with activation of local cellular compartments (hepatic progenitor cells, hepatic stellate cells, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.”
This study has a large number of figures illustrating the changes in liver architecture and immunohistochemistry changes.
My take: This study shows specific improvements following LSG and shows correlation with cytokines and immunohistochemistry providing a mechanistic explanation for these improvements.
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A recent ‘clinical quality forum’ sponsored by The Children’s Care Network (TCCN) and Nutrition4Kids featured several good lectures. The symposium was titled “It’s Alimentary.” What follows are my notes –the full lectures from these talks will be available in the coming weeks on the Nutrition4Kids website. My notes may include some errors in transcription and errors of omission.
“The Importance of Intestinal Microbiota in Pediatric Health and Disease” by W Allan Walker (Harvard Medical School, Director of Division of Nutrition) reviewed data showing how changes in the microbiome, likely related to a ‘Western lifestyle’ has resulted in numerous health consequences.
- The hygiene hypothesis has correlated a greatly reduced risk of infections inversely to an increase in immune-mediated diseases including Crohn’s disease, multiple sclerosis, type 1 diabetes mellitus, and metabolic syndrome/obesity.
- The consequences of improved hygiene are likely mediated by alterations in gut microbiome
- To counter alterations in a ‘healthy’ microbiome, perhaps most important is normal neonatal colonization. This, in turn, is related to healthy pregnancy/full term gestation, vaginal delivery, absence of antibiotics in the first year of life (if feasible), and exclusive breastfeeding.
- A healthy first-year-of-life microbiome leads to improved tolerance (less allergies) and absence of chronic diseases.
- In those at risk for altered microbiome, probiotics may be beneficial.
- By 12-18 months, the microbiome has an ‘adult’ pattern of colonization with a bacterial signature that is present for the rest of someone’s life
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A subsequent segment addressed “Weight Bias in Healthcare Professionals and What We Can Do About It” by Sheethal Reddy (Strong4Life Clinical Psychologist).
- Physicians have been shown to exhibit decreased empathy with obese patients (KA Gudzune et al. Obesity 2013; 21: 2146-52)
- Bias can not be eliminated but can be better understood. The Implicit Attitude Test can help ascertain one’s level of bias. https://implicit.harvard.edu/implicit
- Ways to address obesity as a topic: “Is it OK to talk about…”, use of health report cards to review BMI
- “The most important thing you can be is kind”
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In another talk was related to obesity: “ERAS Nutrition in Bariatric Surgery” by Mark Wulkan (Emory University Professor of Surgery). ERAS is an acronym for Enhanced Recovery After Surgery –pioneered in colorectal surgery (Previous post on ERAS: ERAS-Enhanced Recovery after surgery)
- Using ERAS protocol, hospital length of stay has been shortened from 2 days to 1 day
- ERAS protocol has been associated with minimal use of narcotics –occasionally for breakthrough pain.
- Current bariatric surgery favored by Strong4Life team –Laparoscopic Sleeve Gastrectomy
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Bariatric Surgery Candidates