Manifestations of Liver Disease

Hepatomegaly

Enlargement of the liver can be caused by several mechanisms ( Table 382.1 ). Normal liver size estimations are based on age-related clinical indices, such as the degree of extension of the liver edge below the costal margin, the span of dullness to percussion, or the length of the vertical axis of the liver, as estimated from imaging techniques. In children, the normal liver edge can be felt up to 2 cm below the right costal margin. In a newborn infant, extension of the liver edge more than 3.5 cm below the costal margin in the right midclavicular line suggests hepatic enlargement. Measurement of liver span is carried out by percussing the upper margin of dullness and by palpating the lower edge in the right midclavicular line. This may be more reliable than an extension of the liver edge alone. The 2 measurements may correlate poorly.

The liver span increases linearly with body weight and age in both sexes, ranging from approximately 4.5-5.0 cm at 1 wk of age to approximately 7-8 cm in boys and 6.0-6.5 cm in girls by 12 yr of age. The lower edge of the right lobe of the liver extends downward (Riedel lobe) and can normally be palpated as a broad mass in some people. An enlarged left lobe of the liver is palpable in the epigastrium of some patients with cirrhosis. Downward displacement of the liver by the diaphragm (hyperinflation) or thoracic organs can create an erroneous impression of hepatomegaly.

Examination of the liver should note the consistency, contour, tenderness, and presence of any masses or bruits, as well as assessment of spleen size, along with documentation of the presence of ascites and any stigmata of chronic liver disease.

Ultrasound is useful in assessment of liver size and consistency, as well as gallbladder size. Gallbladder length normally varies from 1.5-5.5 cm (average: 3 cm) in infants to 4-8 cm in adolescents; width ranges from 0.5-2.5 cm for all ages. Gallbladder distention may be seen in infants with sepsis. The gallbladder is often absent in infants with biliary atresia.

Jaundice (Icterus)

Yellow discoloration of the sclera, skin, and mucous membranes is a sign of hyperbilirubinemia (see Chapter 123.3 ). Clinically apparent jaundice in children and adults occurs when the serum concentration of bilirubin reaches 2-3 mg/dL (34-51 µmol/L); the neonate might not appear jaundiced until the bilirubin level is >5 mg/dL (>85 µmol/L). Jaundice may be the earliest and only sign of hepatic dysfunction. Liver disease must be suspected in the infant who appears only mildly jaundiced but has dark urine or acholic (light-colored) stools. Immediate evaluation to establish the cause is required.

Measurement of the total serum bilirubin concentration allows quantitation of jaundice. Bilirubin occurs in plasma in 4 forms: unconjugated bilirubin tightly bound to albumin; free or unbound bilirubin (the form responsible for kernicterus, because it can cross cell membranes); conjugated bilirubin (the only fraction to appear in urine); and δ fraction (bilirubin covalently bound to albumin), which appears in serum when hepatic excretion of conjugated bilirubin is impaired in patients with hepatobiliary disease. The δ fraction permits conjugated bilirubin to persist in the circulation and delays resolution of jaundice. Although the terms direct and indirect bilirubin are used equivalently with conjugated and unconjugated bilirubin, this is not quantitatively correct, because the direct fraction includes both conjugated bilirubin and δ bilirubin.

Investigation of jaundice in an infant or older child must include determination of the accumulation of both unconjugated and conjugated bilirubin. Unconjugated hyperbilirubinemia might indicate increased production, hemolysis, reduced hepatic removal, or altered metabolism of bilirubin ( Table 382.2 ). Conjugated hyperbilirubinemia reflects decreased excretion by damaged hepatic parenchymal cells or disease of the biliary tract, which may be a result of obstruction, sepsis, toxins, inflammation, and genetic or metabolic disease ( Table 382.3 ).

Pruritus

Intense generalized itching can occur in patients with chronic liver disease often in association with cholestasis (conjugated hyperbilirubinemia). Symptoms can be generalized or localized (commonly to palms and soles), are usually worse at night, are exacerbated with stress and heat, and are relieved by cool temperatures. Pruritus is unrelated to the degree of hyperbilirubinemia; deeply jaundiced patients can be asymptomatic.

The pathogenesis of pruritus remains unknown, however, multiple suspected pruritogens have been reported including bile acids, histamine, serotonin, progesterone metabolites, endogenous opioids, the potent neuronal activator lysophosphatidic acid (LPA), and the LPA-forming enzyme, autotaxin (ATX). Ultimately, a multifactorial process is suspected as evidenced by the symptomatic relief of pruritus after administration of various therapeutic agents including bile acid-binding agents (cholestyramine), choleretic agents (ursodeoxycholic acid), opiate antagonists, antihistamines, serotonin reuptake inhibitors (sertraline), and antibiotics. Plasmapheresis, molecular adsorbent recirculating system therapy, and surgical diversion of bile (partial and total biliary diversion) have been used in attempts to provide relief for medically refractory pruritus.

Spider Angiomas

Vascular spiders (telangiectasias) , characterized by central pulsating arterioles from which small, wiry venules radiate, may be seen in patients with chronic liver disease. These are usually most prominent in the superior vena cava distribution area (on the face and chest). Their size varies between 1 and 10 mm and they exhibit central clearing with pressure. They presumably reflect altered estrogen metabolism in the presence of hepatic dysfunction.

Palmar Erythema

Blotchy erythema, most noticeable over the thenar and hypothenar eminences and on the tips of the fingers, is also noted in patients with chronic liver disease. Abnormal serum estradiol levels and regional alterations in peripheral circulation have been identified as possible causes.

Xanthomas

The marked elevation of serum cholesterol levels (to >500 mg/dL) associated with some forms of chronic cholestasis, especially Alagille syndrome, can cause the deposition of lipid in the dermis and subcutaneous tissue. Brown nodules can develop, first over the extensor surfaces of the extremities; rarely, xanthelasma of the eyelids develops.