6 Clinical
Pharmacy Practice News • August 2022
Hepatology
IFALD FORMULA
protection against PNALD (Cochrane Database Syst Rev 2019;6:CD013163). continued from page 4 Even with a better understanding of the limitaIn a 2020 study of neonates diagnosed with IFALD, tions of soybean oil, the choice of lipid emulsion for switching to 100% fish oil (Omegaven, Fresenius Kabi) patients coming into the neonatal ICU isn’t always reversed the liver disease in 11 of 15 infants (J Clin Med straightforward. Drs. Cohran and Gura said they continue to use soybean oil for their patients. Dr. Cohran 2020;9[11]:3393). However, a meta-analysis from 2016 did not find prefers a composite lipid emulsion, one made of mulfish oil containing SMOFlipid to have a strong protec- tiple lipid types such as soybean oil, olive oil, MCT tive effect against IFALD compared with 100% soy- (or medium-chain triglycerides) oil and fish oil. She bean oil, despite a sevenfold reduction in phytosterols uses soybean oil in low amounts and carefully moni(J Pediatr Gastroenterol Nutr 2016;62[5]:776-792). tors total and direct bilirubin. When bilirubin reaches Similarly, a Cochrane Review did not find any lipid 2 mg/dL, an indication of IFALD, she switches patients emulsions with or without fish oil to provide better to Omegaven.
Lifestyle Changes Improve Pediatric NAFLD By Kate O’Rourke
P
harmacists often are relied on by their physician colleagues for their medication management expertise. But their worth on the care team also hinges on the ability to recommend non-pharmacologic therapy when appropriate. A new study of pediatric patients with nonalcoholic fatty liver disease (NAFLD) suggests that may indeed be the best approach. The study—results of which were presented at the 2021 Liver Meeting (abstract 45) and published in Clinical Gastroenterology and Hepatology (2021 Dec 4. doi:10.1016/j.cgh.2021.11.039)—found that an intensive multidisciplinary lifestyle management program resulted in significant weight loss and reduced steatosis and fibrosis in pediatric patients with NAFLD. The results are an encouraging development, given the prevalence of the disease, noted investigator Sander Lefere, MD, PhD, a postdoctoral researcher in the Department of Gastroenterology and Hepatology at Ghent University, in Belgium. Secondary to increasing rates of obesity in children and adolescents, pediatric NAFLD is now the most common pediatric liver disease worldwide (J Pediatr 2016;172:9–13), he noted. The prospective study included children and adolescents with NAFLD admitted for severe obesity at a tertiary center, the Zeepreventorium De Haan, in Belgium, between July 2019 and January 2021, who were placed on an intensive lifestyle regimen composed of caloric restriction, physical activity, education and psychosocial support in a residential multidisciplinary setting. To assess liver steatosis and fibrosis, the researchers performed liver ultrasonography and transient elastography with controlled attenuation parameter (CAP) and liver stiffness measurement at baseline and after six and 12 months. Fibrosis was defined as a liver stiffness measurement of at least 7 kPa for F2 fibrosis, at least 9 kPa for F3 and at least 11 kPa for F4; CAP values of at least 248 dB/m were considered elevated. The median age of the 204 patients was 14.0 years, and the median body mass index z score was 2.8. NAFLD was found on ultrasound in 71.1% of patients, whereas 68.6% had CAP values measuring at least 248 dB/m. In the cohort, 32.8% of patients had at least F2 fibrosis, including 10.3% with transient elastography measurements of at least 9 kPa. After six months, median weight loss was 16% in the 167 patients who were evaluated. Liver steatosis and fibrosis also were markedly improved, with regression and resolution of fibrosis occurring in 73.1% and 61.5%
of patients who had fibrosis at baseline, respectively. Resolution of steatosis occurred in 47.1% of patients with steatosis at baseline, the investigators reported. Fasting serum alanine aminotransferase (ALT) levels and for insulin resistance decreased significantly over the one-year period (P<0.001). “To our knowledge, this is the largest study to date to investigate the efficacy of a structured weight loss program on improving NAFLD in children and adolescents with severe obesity (aged 8-18 years). Our findings are strengthened by the use of transient elastography for the diagnosis and follow-up of liver fibrosis in the study population,” Dr. Lefere said, noting that previous studies that have investigated the efficacy of lifestyle intervention for pediatric NAFLD have relied on serum ALT levels or liver ultrasound, which are suboptimal and do not provide data on liver fibrosis, the key outcome marker in these patients. “Based on our results, prompt careful hepatic examination of children and adolescents with severe obesity is warranted, as well as timely referral to weight loss programs,” Dr. Lefere Median weight loss said. “These data further support the importance of the development and evaluation of alternative and Liver steatosis effective weight loss proresolution grams for NAFLD in the outpatient setting.”
16% 47.1%
61.5% Liver fibrosis
Comprehensive Approach Is Needed
resolution
Ali Mencin, MD, the director of the Pediatric Fatty Liver Clinic and Pediatric Endoscopy at Columbia Doctors Children’s Health, in New York City, said the study demonstrates the importance of healthy lifestyle in improving liver injury in NAFLD. “Previous studies have shown that weight loss through diet and exercise or bariatric surgery result in improvements in ALT and liver histology. However, most patients struggle with adhering to a healthy lifestyle recommendation. “The degree of NAFLD improvement in Dr. Lefere’s study can likely be attributed to the intervention— intensive lifestyle changes in a residential setting with education and psychosocial support,” Dr. Mencin said. “This highlights the need for a more comprehensive approach to lifestyle management beyond standardof-care counseling to achieve improved outcomes in NAFLD. Unfortunately, few patients have access to such programs.” Dr. Mencin said it would be interesting to know “the specifics of the intervention in this study and more details about their success in reducing BMI.” Drs. Lefere and Mencin reported no relevant financial disclosures.
Dr. Gura said each lipid source has its limitations and its place in treating unique patient cases. A soybean oil such as Nutralipid or Intralipid has a long history of use, is efficient in terms of required fatty acids and is well tolerated for a short duration of therapy, she noted. Beyond lipids, experts said prioritizing enteral nutrition in neonates and oral feeding in adults is crucial. In infants, feeding enterally helps the remaining intestine adapt and improves patient safety and the likelihood they can transition from parenteral nutrition (PN) entirely. With “[adult] oral intake, the liver gets first pass at those nutrients,” Ms. Matarese said. In contrast, with PN, the liver typically is last for nutrient delivery. Oral feeding in adults also stimulates enteral hepatic circulation, villus height and crypt depth, she said. “If there is any way I can rehabilitate the remnant bowel, I think it offers the best potential for health and improved quality of life,” Ms. Matarese stressed.
Team Effort Best for Care Transitioning from PN requires a team of experts. In addition to gastroenterologists, surgeons and neonatologists, pharmacists and dietitians are necessary to ensure patients are receiving the appropriate formula based on their intestinal anatomy. The pharmacists and dietitians are also integral for assessing the TPN to ensure patients receive the appropriate vitamins and minerals, especially in the current time of shortages, and that enteral nutrition is formulated for a patient’s unique anatomy and limitations. As an example, if a patient lacks their distal small bowel, they’re likely to have a vitamin B12 deficiency and also absorb fat-soluble vitamins poorly, Dr. Cohran said. If patients are missing their proximal small intestine, they are more susceptible to iron deficiency. Pharmacists and dietitians are also essential as teams work with healthcare companies to access products and reconcile PN recipes, Dr. Cohran said. This collaboration is likely to be one reason that patients who receive treatment at a specialized center have better outcomes. There’s a bigger opportunity for out-of-the-box and holistic thinking with a multidisciplinary team, Dr. Gura said. Dr. Cohran has patients who travel more than five hours to be seen by her team in Chicago. But “everybody can’t jump on a plane to fly to Boston, Cincinnati or Chicago,” Dr. Cohran said. If a provider is trying to support a patient who has IFALD but is not located near a major center, getting in touch with a large center can be critical, Dr. Gura said, as is diving into the rapidly evolving literature on IFALD. It may be useful to ask nearby professionals such as pharmacists, dietitians, social workers or neonatologists to help. At first, a gastroenterologist may need to mentor a pharmacist because most don’t receive formal training in this area, Dr. Gura said. However, it will become a very useful partnership quickly, she said. All three experts said there is a way to see patients return to a more normal life, to see children safe to swim and rough-house with their siblings, Dr. Cohran said. “What drives me is tapering children from PN and allowing them to live their best life.” Dr. Cohran reported financial relationships with Abbott Nutrition, Nutricia and Takeda. Dr. Gura reported financial relationships with Alcresta, Fresenius Kabi, Lexicomp, NorthSea Therapeutics and Otsuka Pharmaceutical Factory. Dr. Matarese reported no relevant financial disclosures.
