fibrosis, and splenomegaly gradually progress with the duration of TPN treatment. In infants receiving TPN, the reported incidences of IFALD varies widely from 15% to 85%.3, 4, 5 The incidence correlates inversely with the gestational age and birth weight and is also related to the underlying disease and duration of treatment. The incidence of cholestasis is 50% in infants with birth weight <1,000 g but falls to 7% if birth weight is >1,500 g.6 The highest incidence of IFALD occurs in infants <34 weeks of gestation and <2,000 g body weight.7 A prolonged length of TPN increases the overall incidence of liver injury, with cholestasis occurring in 85% of infants who are on TPN >100 days.
found in older children and adults, typically seen as mild periportal macrovesicular steatosis (Fig. 19.3). Steatohepatitis can develop after long-term TPN and progress to cirrhosis in a small number of patients.13 Ductopenia is frequently seen but is not accompanied by a bile ductular reaction. This ductopenic pattern of injury may have a different mechanism from that of bile sludge or bile duct obstruction, which can also lead to biliary obstructive changes and eventually to biliary cirrhosis with ductopenia (Fig. 19.4).3,12
Figure 19.1 Intestinal failure-associated liver disease (IFALD). A liver explant because of IFALD. The liver appears atrophic with cirrhosis and green discoloration.
Figure 19.2 Neonatal intestinal failure-associated liver disease. Chronic cholestasis with hepatocyte feathery degeneration, cholestatic rosettes, bile plugs, rare acidophil bodies, mild steatosis, and extramedullary hematopoiesis.
failure and TPN therapy is essential to establish the diagnosis of IFALD in the first place.
Figure 19.6 Glycogenic hepatopathy. Diffuse hepatocyte swelling by pale-staining cytoplasm and accentuation of the cell membrane, mimicking plant cells. Megamitochondria in some hepatocytes (arrows).
diagnosis is made by careful attention to the hepatocytes, which show abundant pale or clear cytoplasm and often show prominent cell membranes. PAS stains are strongly positive in both GH and the normal liver, and there is no quantitative method to distinguish normal glycogen content from excessive glycogen accumulation. The clinical and laboratory findings provide important clues to the diagnosis, because essentially all cases of GH occur in the setting of poorly controlled blood sugars with hepatomegaly and elevated liver enzymes.
microangiopathy in the liver has been associated with hepatosclerosis in a recent study.34
Figure 19.9 Liver in congenital hypopituitarism showing neonatal giant cell hepatitis with cholestasis.
hepatitis in some cases can be secondary to treatment with sulfasalazine.48 If the patient is under active immunomodulatory therapy, the biopsy should be carefully examined for cytomegalovirus (CMV) and other opportunistic infections. Finally, approximately 2% to 5% of inflammatory bowel disease patients with hepatobiliary involvement will develop cirrhosis, primarily because of primary sclerosing cholangitis.49
Table 19.1 Liver and Biliary Disorders in Inflammatory Bowel Disease
the hepatic dysfunction is attributed to lupus itself, recent studies have shown that autoantibodies to ribosomal P proteins (anti-ribosomal P), a highly specific marker for systemic lupus erythematosus, are associated with hepatic enzyme abnormalities in patients with systemic lupus erythematosus.72 The prevalence of lupus hepatitis is about 10%.73 However, lupus hepatitis is essentially a diagnosis of exclusion. On biopsy, lupus hepatitis shows a very mild nonspecific reactive hepatitis. The inflammation is mainly in the lobules, with lymphocytic inflammation and occasional acidophil bodies. Portal inflammation is absent or very mild. Lupus hepatitis is not associated with either severe or progressive liver injury (Fig. 19.13).