Chapter 40: Congenital Liver Failure and Neonatal Hepatitis

EPIDEMIOLOGY

Neonatal hepatitis is a vague term that describes a heterogeneous group of disorders occurring in infants up to 3 months of age due to a variety of insults. It includes all forms of neonatal cholestasis not attributed to extrahepatic biliary tract obstruction. In many instances, a specific inciting event, infectious agent, or metabolic cause cannot be found. Approximately 40% of cases of neonatal cholestasis are due to neonatal hepatitis.¹

Neonatal acute liver failure (ALF) is rare but often fatal. It is defined as the development of hepatic necrosis associated with hepatic encephalopathy and coagulopathy within 8 weeks of the onset of liver disease without evidence of chronic liver disease. This definition is challenging given prenatal liver disease is challenging to identify, and encephalopathy in neonates is difficult to distinguish. The Pediatric Acute Liver Failure study group defined ALF as hepatic-based coagulopathy defined as prothrombin time (PT) of 15 seconds or longer or international normalized ratio (INR) of 1.5 or more, not corrected by vitamin K, in the presence of clinical hepatic encephalopathy, or a PT of 20 or more or INR of 2 or more regardless of the presence or absence of clinical hepatic encephalopathy, along with biochemical evidence of acute liver injury and no known evidence of chronic liver disease.²

This chapter review focuses on known causes of neonatal hepatitis, concentrating on those that can progress to ALF. Please refer to the chapters on conjugated hyperbilirubinemia, congenital infections, and metabolic diseases for additional discussion.

PATHOPHYSIOLOGY

Sporadic neonatal hepatitis is often ascribed to a specific injury from infectious, ischemic, or environmental factors, whereas familial neonatal hepatitis is assumed to be caused by genetic defects in hepatic metabolic or excretory function. Idiopathic neonatal hepatitis is a generic name for indeterminate causes of ALF. Biopsies classically show formation of syncytial hepatic giant cells, variable inflammation, and lobular cholestasis. A review of 62 cases showed lobular extramedullary hematopoiesis was present in 74%, lobular cholestasis in 84%, and mild patchy chronic inflammation in 54%. Fibrosis was present in 30% of cases. Most cases (49%) remained idiopathic, but 16% of cases were diagnosed with hypopituitarism and 14% as having biliary atresia or Allagille syndrome. The biopsy findings did not readily distinguish between the specific etiologies.³

Neonatal Hepatitis

The classic pathology of neonatal hepatitis is characterized by predominantly parenchymal lobular inflammation with preservation of the zonal distribution of portal tracts and central veins. There is ballooning degeneration of hepatocytes. There can be intense giant cell transformation. Cholestatic features can also be seen, such as cytoplasmic feathery degeneration, formation of cholestatic rosettes, cholestatic plugs, and Kupffer cell activation. No obstructive pathology should be evident, and there are a normal number of bile ducts. Extramedullary hematopoiesis can be seen.³

Neonatal Acute Liver Failure

The most ...