Mexican researchers Alfredo Larrosa-Haro and Erika A. Caro-Sabido recently authored a literature review on the pathophysiology, diagnosis, and needed nutritional intervention in infants with malnutrition secondary to chronic cholestatic liver disease (CCLD), such as Alagille syndrome. Infant malnutrition can lead to death if not managed well; hence, it is an issue that is at once important and urgent. We will be looking at some of their findings in this article.

“The relationship between liver physiology and human nutrition is very close, such that malnutrition is the main factor involved in the long-term clinical outcomes of CCLD in infants,” Larrosa-Haro and Caro-Sabido wrote. This should be apparent from the anatomical proximity of the liver to the gastrointestinal tract, and the role that bile plays in intestinal digestion and absorption. 

CCLD is an umbrella term for a number of liver diseases that are usually diagnosed within the first 2 years of age, one of them being Alagille syndrome. CCLDs are a heterogeneous group that differ in etiology, diagnosis, disease course, and prognosis, but they all share the risk of causing early malnutrition. Infants, being as vulnerable as they are, are particularly sensitive to any pathology that disrupts health and homeostasis, especially during their first growth spurt. 


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Read more about Alagille syndrome etiology 

Larrosa-Haro and Caro-Sabido provided a summary of the pathophysiological mechanisms of secondary malnutrition in infants with CCLD: 

  • Decreased bone calcium accretion 
  • Impaired intermediate metabolism 
  • Decreased synthesis of nutrients and complex molecules 
  • Fat malabsorption and malabsorption of fat-soluble vitamins 
  • Hormonal dysregulation 
  • Decreased intake of energy and nutrients. 

Combined, these pathophysiological features manifest most commonly as growth retardation, loss of muscle mass, osteopenia, decreased fat stores, and fat-soluble vitamin deficiency. 

Screening and Diagnosis 

Pediatricians are used to looking out for signs of malnutrition; it would do well for physicians of other disciplines to follow suit. A team of Canadian researchers, Hulst et al, wrote a study on pediatric screening tools for malnutrition. There are a number of different screening tools that are used for different conditions and in different countries. 

The screening tool that is recommended for biliary atresia is STRONGkids. The STRONGkids questionnaire features 4 “yes-or-no” questions that can be completed within a few minutes. A study demonstrated that the STRONGkids questionnaire was able to identify children with malnutrition upon hospital admission. It did so by allowing physicians to compare the original and adjusted nutrition-risk cut-offs with the Subjective Global Nutritional Assessment (SGNA). 

Read more about Alagille syndrome diagnosis 

Malnutrition in infants can result in obvious impairment in their physical growth. Larrosa-Haro and Caro-Sabido wrote about a few parameters for physicians to measure. First, length. “Length is probably the best indicator of growth impairment in infants with CCLD and is directly correlated with the extent of liver damage assessed using tests, including conjugated bilirubin, albumin, or alkaline phosphatase levels,” they wrote. 

Second, body composition. “The body composition evaluation of infants with CCLD focuses on fat stores, muscle mass, and bone mineral density,” Larrosa-Haro and Caro-Sabido wrote. However, studies have shown that indicators based on weight and length tend to underestimate the nutritional status impairment of patients with conditions such as hepatomegaly, splenomegaly, and ascites. An alternative for estimating body composition is anthropometry of the arm. 

Third, bone mineral density. “The bone mineral density in infants with CCLD is often severely affected, with z-scores well below -2 [standard deviation], especially when the serum direct bilirubin level is >2 mg/dL,” the Mexican researchers wrote. 

In addition to these established parameters of nutritional status, medical researchers are currently identifying new biomarkers that can be used to assess growth and body composition in a manner that is more comprehensive and accurate. 

Nutritional Intervention 

If malnutrition secondary to CCLD is diagnosed, nutritional intervention is warranted. Secondary malnutrition differs from primary malnutrition in that there is an established cause of the malnourished status.

“From this point of view, its therapeutic approach would be conditioned to the resolution of pathophysiological circumstances associated with primary liver disease: insufficient dietary ingestion to maintain normal growth, impaired intestinal absorption, increased metabolic rate, and impaired micro- and macronutrient metabolic pathways,” Larrosa-Haro and Caro-Sabido wrote. 

Needless to say, a nutritionist should be part of the multidisciplinary team. However, the gold standard of treatment requires the involvement of a hepatobiliary surgeon: “Currently, the best therapeutic alternative for preventing and treating malnutrition in infants with CCLD is liver transplantation,” they wrote. Studies have shown that liver transplantation results in improvement in anthropometric indicators, such as body mass index, arm fat, and muscles. Improvements are usually noticeable around 12 to 24 months post-transplantation. 

There are other therapeutic options, such as early and effective portoenteroanatomosis (once again a surgical procedure), but the best available evidence indicates that they are limited at best. 

In conclusion, it is important that we as physicians use the screening and diagnostic tools available when seeing infants with CCLD. If secondary malnutrition is established, intervention should be determined in a multidisciplinary setting, involving nutritionists and hepatobiliary surgeons. 

References

Larrosa-Haro A, Caro-Sabido EA. Secondary malnutrition and nutritional intervention in cholestatic liver diseases in infantsFront Nutr. Published online November 15, 2021. doi:10.3389/fnut.2021.716613

Hulst JM, Huysentruyt K, Joosten KF. Pediatric screening tools for malnutrition: an updateCurr Opin Clin Nutr Metab Care. 2020;23(3):203-209. doi:10.1097/MCO.0000000000000644