COMMENTARY

Liver Diseases in Children: Challenges and Opportunities

Digestive Disease Week (DDW) 2015

William F. Balistreri, MD

Disclosures

September 28, 2015

In This Article

Author's Note: At Digestive Disease Week 2015, an American Gastroenterological Association Translational Symposium focused on several advances in pediatric hepatology. This symposium provided an overview of the progress and future opportunities for innovative, therapeutic, and preventive interventions for some of the most frequent liver diseases in children.

An organized focus on disorders of the liver in early life has led to the emergence of pediatric hepatology.[1,2] The development of this clinical subspecialty along with accelerated patient- and laboratory-based research have allowed for a greater understanding of the nature and consequences of genetic or metabolic aberrations on immature liver structure and function.

The unique nature of inherited and acquired liver diseases in infants and children are now recognized, thanks in part to greater insight into hepatobiliary physiology and the development of more precise approaches to the diagnosis and management of liver disease in infants and children, including both liver transplantation and nontransplant treatment options.

Pediatric Nonalcoholic Fatty Liver Disease: An Increasing Public Health Issue

In this presentation, Ronald J. Sokol, MD, emphasized the magnitude of an emerging public health problem in the United States and around the world. The prevalence of obesity has increased not only in the United States but also in low- and middle-income countries.[3,4] He also discussed the long-term consequences. Obesity affects every organ; it is associated with a host of cardiovascular, endocrine, pulmonary, and gastrointestinal disorders. Sokol discussed several of these comorbidities, with a focus on nonalcoholic fatty liver disease (NAFLD), which he defined as >5% of hepatocytes displaying steatosis in the absence of significant ethanol intake and metabolic disease or toxic injury. The major concern was the documented progression of NAFLD to nonalcoholic steatohepatitis (NASH) with the likelihood of cirrhosis and liver failure. NASH was defined as steatosis plus inflammation, ballooning, and fibrosis.

The Consequences of NAFLD and NASH

NAFLD is associated with metabolic syndrome, insulin resistance, and type 2 diabetes. There are well-documented associations with obstructive sleep apnea (OSA) or hypoxia, polycystic ovary syndrome, and psoriasis, among others.

A recent report assessed baseline prevalence of risk factors for cardiovascular disease in severely obese adolescents with NAFLD who were candidates for bariatric surgery.[5] At baseline, 74% of patients had fasting hyperinsulinemia, 75% had elevated C-reactive protein levels, 50% had dyslipidemia, and 49% had elevated blood pressure. Recent studies have shown a high incidence of functional cardiac abnormalities in obese adolescents with NAFLD.[6,7]

Another interesting observation is the relationship between fatty liver and OSA. Elevated aspartate transaminase (AST)/alanine transaminase (ALT) levels have been noted in adults with OSA. Hypoxia associated with OSA leads to hypoxia-reoxygenation with ischemia-reperfusion injury. Sokol discussed his study that tested the hypothesis that OSA with nocturnal hypoxemia was associated with the progression of NAFLD to NASH, presumably related to the generation of reactive oxygen species.[8] In adolescents with NAFLD, a direct relationship between the degree of hypoxemia and severity of hepatic fibrosis was noted.

Estimated Frequency of NAFLD and NASH

NAFLD is now the most common liver disease in adults in the United States, affecting 20%-40% of the population. This increase parallels the obesity epidemic. NAFLD is most commonly noted in males, especially those of Hispanic and Native American descent. Incidence is lower in African Americans.

NAFLD/NASH is responsible for many cases of cryptogenic cirrhosis and hepatocellular carcinoma in adults and is rapidly becoming the leading indication for liver transplantation in the United States.[9] Since 2004, the number of adults with NASH awaiting liver transplantation has almost tripled. Between 2004 and 2013, new US transplant waitlist registrations for adults with NASH increased by 170%. In contrast, hepatitis C virus registrations increased by 14%.

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