Total bilirubin ranges 1.0 to 1.5 mg/dL normally, and decreases to the level 0.2 to 0.9 mg/dL in 95% of the population. The normal value of indirect bilirubin is 0.8 to 1.2 mg/dL. The normal upper limit of direct bilirubin is 0.3 mg/dL. Even a small increase of direct bilirubin means the possibility of liver injury. In patients with jaundice, the ratio of direct bilirubin to total bilirubin does not differentiate obstructive jaundice from liver parenchymal jaundice. A ratio over 20% traditionally means cholestasis in children. The degree and duration of hyperbilirubinemia is not a prognostic factor for liver disease. But, the higher the serum bilirubin is, the deeper the severity of liver injury is.

Serum aminotransferases was called transaminases in the past. It is the most sensitive marker for acute liver injury. AST and ALT catalyze the α-amino group of L-aspartic acid and alanine, respectively, to move to the α-keto group. AST, which was previously called serum glutamic oxaloacetic transaminase, are in the cytosol and mitochondria of cells. It most commonly distributes to cardiac muscle, followed by the skeletal muscle, kidney, brain, pancreas, lung, leukocyte and erythrocytes. ALT, which was previously called serum glutamic pyruvic transaminase, is cytoplasmic enzyme, and exists most commonly in hepatocyte. So, it is a more specific marker for the evaluation of liver injury, than AST. The normal value of ALT is generally less than 30 U/L in men, and less than 19 U/L in women. But, the value is dependent on the laboratories.

Most serum ALP is made in liver and bones. The normal value of ALP depends on the age. Adolescents have two times higher level than adults. The difference between adolescents and adults seems to be due to bone growth. A high level of ALP, when the increase of GGTP and 5'NT is identified, must originate from liver, rather than the bone.

GGTP is on the cell membrane of the liver (hepatocyte and bile duct cell), kidney, pancreas, spleen, heart and brain, etc. A high concentration of serum GGTP has a limitation for clinical use; because although the sensitivity is high, the specificity is low for hepatobiliary diseases. The increase of GGTP can be detected in patients taking phenytoin and barbiturates.

5'-NT is associated with canalicular among hepatocytes, and sinusoidal plasma membrane neighboring hepatocytes. The function of 5'NT is not well known. 5'NT exists in the small bowel, brain, heart, blood vessel and pancreas. The normal value of serum 5'NT increases with aging. 5'NT, as well as GGTP, is used for differential diagnosis of high serum ALP level alone.

Albumin is the most important plasma protein, in terms of quantity. It is responsible for 75% of plasma colloid osmotic pressure, and is synthesized only in hepatocytes. When albumin loss occurs rapidly, the liver can make 2 times the usual production. The half life of albumin is 14 to 20 days. The final site of break down is not known. Albumin synthesis is regulated by nutritional status, osmotic pressure, systemic inflammation, and hormone concentration in the blood. Therefore, when hypoalbuminemia is detected, differential diagnosis should include live cell dysfunction, protein-losing enteropathy, nephrotic syndrome, chronic systemic inflammation, and imbalance of hormone.

A long half-life of albumin is the cause of low usability for liver synthetic function, when acute liver injury has developed. In chronic liver disease or liver cirrhosis; however, albumin is an excellent marker for the synthetic function of the liver.

All coagulation factors, except factor VIII, are synthesized in the liver. Prothrombin time measures the extrinsic pathway of hemosatasis. Factors II, V, VII and X are clotting factors involved in prothrombin production. Prolongation of prothrombin time may occur from other liver diseases, beside of liver synthetic dysfunction. Vitamin K deficiency and disseminated intravascular coagulation are representative causes of prolonged prothrombin time. The measuring of prothrombin time is most useful in patients with acute liver disease. In contrast to serum albumin, prothrombin time can evaluate the actual liver synthetic function. Prothrombin time is also a valuable prognostic factor of liver failure.

In the domestic area, the prevalence of hepatitis A virus (HAV) infection has shown several outbreaks since the second half of the 1990s, and tremendous increase since year 2000 [9-11]. The possibility of meeting the patients is rising in outpatient clinics. The earlier child may be a little bit sick, without jaundice. In contrast, the older child and adults prominently complain of hepatobiliary symptoms [9,11]. Symptoms include fever, anorexia, nausea, vomiting, fatigue and jaundice. The typical symptoms may continue for 1 to 2 weeks. AST, ALT, bilirubin, ALP, 5'NT and GTTP become over the normal limits. The disease can be easily confirmed by positive anti-HAV antibody (immunogrobulin M [IgM]). ALT rapidly increases to the top, before symptom development. From this point, symptoms such as jaundice begin. After this, ALT gradually decreases, and normalizes, when jaundice disappears.

The hepatitis B surface antigen (HBsAg) positive rate of school ages, born before the induction of HBV vaccine, was 3.2% in 1988. But, the rate decreased to 0.9% in a survey (Seoul area, 1995) of infant and toddlers born after the vaccine induction [12,13]. At present, domestic children of preschool ages have 70% to 80% of positive hepatitis B surface antibody (HBsAb). The positive rates of HBsAg are 0.4% in 20s, and 0.2% in adolescents [14]. But, we can occasionally meet children with HBV infection in outpatient clinics.

The most common pathway of HBV transmission in childhood is vertical infection from an HBsAg pospositive mother [15]. Over 90% of vertically infected children develop chronic HBV infection. In their natural history, the change from the immune tolerance phase to the immune clearance phase occurs in 15% of patients before 20 years of age [16]. The immune tolerance phase is a period of normal AST, ALT, positive HBeAg and high concentration of HBV DNA in the serum. The immune clearance phase means the period of elevated AST, ALT, positive HBeAg, and decreasing concentration of HBV DNA. In the immune clearance phase, the mean of AST and ALT can increase 3 to 4 times over that of the immune tolerance phase [15,17].

We can often see the disease in children with viral respiratory infection and viral gastroenteritis [1]. The disease is usually accompanied by fever. Most patients don't have other liver dysfunction, except for elevated AST and ALT. Rarely, AST and ALT of 10 to 20 times higher than normal value can be seen. In that case, it may take 6 to 12 months, until the enzymes normalize. Viruses can be identified, using polymerase chain reaction for respiratory infection or gastroenteritis. Hepatitis caused by cytomegalovirus or Epstein bar virus etc. may occur, and the tests to identify these viruses are necessary [1].

Wilson disease is an autosomal recessive genetic disorder, which is caused by difficulty of copper excretion to bile duct from the liver cell, and is accompanied by liver and neurologic disease [18]. The domestic prevalence of children is approximately 1 per 37,000 persons. In East Asia, including Korea, the most common mutation is R778L (Arg778Leu) of the ATP7B gene [19]. The disease usually does not show abnormal liver function until 5 years old. So, most patients visit outpatient clinics with abnormal liver function in the health check-up of elementary or middle school. In particular, when siblings with abnormal liver function visit the clinic together, we can easily suspect Wilson disease. In most patients, other liver dysfunctions, other than elevated AST and ALT, are not detected. The screening test is the measure of serum ceruloplasmin. If the value is under 20 mg/dL, the confirmative test should be done. The patients should take drugs for Wilson disease throughout life. Fortunately, if the disease is diagnosed before it is accompanied by neurologic complication, most patients can maintain health through life. Earlier diagnosis for Wilson disease can prevent severe neurologic complication. Therefore, suspicion and diagnosis is crucial for Wilson disease.

Most NAFLDs are discovered in obese children. Yang et al. [20] reported that 33 of 111 children with NAFLD had elevated hepatic enzymes and nonalcoholic steatohepatitis. In this way, obese children visiting clinics tend to have the possibility of abnormal liver function. Other abnormal liver functions are rare, except for elevated hepatic enzymes. If habits of diet, exercise, life and mind are appropriately managed, the obesity will be improved, and followed by normalization of the liver function.

Diseases that have only jaundice, without elevated hepatic enzymes, are divided into two groups [8]. One is the disease with increased indirect bilirubin. These include Gilbert syndrome, and Crigller Najjar type I and II. Another is the disease with increased direct bilirubin. That includes Rotor syndrome and Dubin-Johnson syndrome.

In the earlier child with Duchenne muscular dystrophy, elevated levels of AST and ALT can always be seen [7]. Muscular dystrophy can be easily discovered in the child with marked delay of motor development, and musculoskeletal symptoms. With only elevated AST and ALT levels, and without perception of sign of motor dysfunction; however, some children can be referred to the gastroenterologist. The elevation of AST and ALT level in these children originates in excessive excretion from the musculoskeletal muscle. Serum creatine kinase (CK) excreted from muscle usually ranges 15,000 to 35,000 IU/L (normal<160 IU/L) [21]. For this reason, serum CK should be included in the screening test for the earlier child with abnormal AST and ALT levels.