Update in Pediatrics by Shalea Piteau

Author:Shalea Piteau
Language: eng
Format: epub, pdf
Publisher: Springer International Publishing, Cham

Pathogenesis

Acute liver failure (ALF) results from rapid death or injury to a large proportion of hepatocytes, leaving insufficient hepatic parenchymal mass to sustain liver function. The pathophysiological mechanisms that lead to ALF are yet to be fully elucidated. However, acute hepatic necrosis is the most common mechanistic pathway of a variety of insults to the liver (Taylor and Whitington 2016). In 1999, the PALF Study Group was formed to develop a database that would facilitate an improved understanding of the etiopathogenesis, treatment and outcome of ALF in children. A report of the first 348 patients enrolled in the PALF registry found that the etiologic categories of non-acetaminophen-induced ALF in children were similar to adults and included metabolic, infectious, and immune-mediated conditions as well as drug injury (Squires et al. 2006).

Acute acetaminophen (APAP) toxicity was the most common identifiable cause of ALF in children ≥3 years (21%) (McGill et al. 2012). Non-APAP drug-related ALF was recognized primarily in older children. In most of these cases, the mechanism of injury leading to ALF is thought to be an idiosyncratic drug reaction. An infectious etiology was identified in 6% of patients, with herpes simplex virus (HSV) and Epstein-Barr virus (EBV) the most common identifiable infections in children <3 years and ≥3 years, respectively (Squires et al. 2006). Autoimmune hepatitis (AIH) also accounted for 6% of patients and occurred in all age groups. A metabolic cause for ALF was established in 18% of children <3 years of age. This group of diseases can lead to structural liver damage as a result of acute or progressive accumulation of toxic metabolites within the liver (Hansen and Horslen 2008). Unfortunately, an indeterminate cause of ALF was assigned to 54% of children <3 years of age and 49% overall (Taylor and Whitington 2016). Replacement of hepatic parenchyma with nonfunctioning tissue is an occasional cause of PALF with hepatic hemangioma, leukemia, and various other liver tumors representing the most prominent etiologies. Hypoxic-ischemic liver injury is an uncommon cause of ALF, but never in the absence of other major organ dysfunction. Gestational alloimmune liver disease (GALD) , the most common cause of neonatal ALF, is caused by transplacental passage of maternal alloantibody that activates fetal complement and leads to the formation of a membrane attack complex, resulting in hepatocyte injury (Whitington 2012).

It is unclear why some individuals recover from ALF spontaneously while others die or require LT. The final outcome is likely dependent on the underlying etiology, modifying effects of host factors, and whether or not the massive parenchymal loss can be compensated by liver progenitor cell (LPC) -mediated regeneration. Due to the rapid and severe course of the disease, several factors may determine whether LPC-dependent liver regeneration can save the failing liver, including the number of activated cells, speed of cell proliferation, and direction of cell differentiation (Weng et al. 2015). These critical issues are awaiting further investigation.

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