Monday 3 November 2014

Laboratory diagnosis of Liver diseases in children


Laboratory tests play a central role in the diagnosis and management of liver disease in children. In this article the usefulness Liver function tests in the diagnosis of liver disease has been dealt with. Though imaging, histology and endoscopy are also important in the diagnosis of liver diseases covering these tests are beyond the scope of this article
Sometimes abnormal laboratory tests may be the only indication of liver dysfunction.  Although the term liver function tests is in common usage, most of the lab test used routinely do not measure the function of the liver except serum albumin and prothrombin time and the rest are indirect tests and not specific to liver diseases alone.

Tests to evaluate liver disease: 

Tests of biochemical activity

       Alanine aminoTransferase (ALT)
·         Aspartate aminoTransferase (AST)
       Lactic Dehydrogenase (LDH)

Tests of cholestasis

·         Gamma Glutamyltranspeptidase (GGT)
·         Alkaline phoshatase (AP)
·         5’nucleotidase
·         Bilirubin (total and fractionation)
·         Urinary urobilinogen
·         Serum and urine bile acids

Tests for synthetic function

·         Albumin and other serum proteins
·         Prothrombin time
·         Ammonia
·         Serum lipids and lipoproteins, cholesterol and triglycerides
 Miscellaneous specific serum tests (a1-antitrypsin, ceruloplasmin, a-fetoprotein, auto antibodies)
 Tests for quantitative function – difficult to perform and not practically useful

LIVER ENZYMES


A liver enzyme is a protein that helps to speed up a chemical reaction in the liver. Liver enzymes have been useful as a screening test for liver diseases, to determine the pattern of liver disease,assess severity and also in the follow up of the patients with liver disease
Enzymes that detect hepatocellular necrosis Aminotransferases Aspartate aminotransferase (AST, formerly SGOT) and Alanine aminotransferase (ALT, formerly SGPT) are the most frequently utilized and specific indicators of hepatocellular necrosis and usually catalyze the transfer of a-amino group to a-keto group.
Aspartate aminotransferase (AST)is a mitochondrial enzyme present in liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs leukocytes and erythrocytes whereas Alanine aminotransferase (ALT) is a cytosolic enzyme which is more specific for liver damage and present in higher concentration in liver than in heart/skeletal muscle and normal values of these enzymes range from 5-35 IU/l.
The rise in liver enzymes may be severe ( > 20 times, 1000 U/L) in viral hepatitis, drug or toxin induced hepatic necrosis and circulatory shock, moderate (3-20 times) in acute & chronic hepatitis, neonatal hepatitis, and acute biliary tract obstructions or mild (1-3 times) in  sepsis, Extra Hepatic Biliary Atresia (EHBA), Myositis, Duchenne muscular dystrophy and even after vigorous exercise.
Level of enzyme elevation shows poor correlation regards the extent of necrosis and is of little value in predicting the outcome. Similarly decreasing enzyme level though may indicate recovery can also be due to massive destruction when it indicates poor prognosis.
The ratio of AST and ALT (AST/ALT) may be useful to differentiate certain conditions. The normal ratio is less than or equal to 1 and a ratio of more than 2 is seen commonly in alcoholic hepatitis probably due to pyridoxine deficiency and in acute Wilsons the ratio is usually more than 4 and one should remember that a higher ratio may also be seen incirrhosis due to any cause because of reduced plasma clearance of AST.
Low levels of amino transferases have been seen in patients on long term haemodialysis and also in uremia and the cause probably secondary to either dialysate or pyridoxine deficiency.
Other enzymes like glutamate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and sorbitol dehydrogenase have also been found to be raised in hepatocellular necrosis but have not found to be clinically significant.

Enzymes that detect cholestasis

Alkaline phosphatase is found histochemically in the microvilli of bile canaliculi and on the sinusoidal surface of hepatocytes and normally serum values range between 45-115 U/L and the increase in serum levels is usually due to overproduction and leakage in blood secondary to bile ductular damage the increase in serum levels may be due to disorders of bone, kidney, intestine, placenta and tumours in addition to cholestatic liver disease and most circulating alkaline phosphatase usually originates from either liver or bone. Physiologically high values are seen in childhood and puberty due to bone growth. Though highest levels of alkaline phosphatase occur in cholestatic disorders, other causes for increase may be infiltrative liver diseases, abscesses, granulomatose liver disease and amyloidosis. Low levels of alkaline phosphatase can occur in hypothyroidism, pernicious anaemia, zinc deficiency and congenital hypophosphatasia.

GGlutamyltranspeptidase (GGT) is a membrane bound glycoprotein and normal value ranges between 0-30 U/L and increasing serum level is due to overproduction and leakage in blood. In addition to liver, the enzyme is also expressed in the kidney, spleen, pancreas, heart, lung and brain except bones and therefore useful in the exclusion of bone diseases. The new borns may have high levels of GGT 5 to 8 times the upper limit of normal. One should also remember that this enzyme is inducible by certain drugs like anticonvulsants and depressed by female sex hormones
Serum GGT is high in all cholestatic disorders and cannot differentiate between intahepatic and extra hepatic causes. Low levels of GGT is found in certain cholestatic disorders like Proressive familial intrahepatic cholestasis (PFIC) types I and II and Inborn errors of bile acid metabolism where GGT has been useful to differentiate these conditions from other causes of cholestasis.
Other enzymes to detect cholestasis are 5’Nucleotidase and Leucineaminopeptidase but not put used commonly.

Bilirubuin

Bilirubin is a yellow tetrapyrrole pigment formed from the degradation of the heme found in hemoglobin in the red cells of the blood which is also found in myoglobin and certain enzymes including catalase, peroxidase and the cytochromes. About 75% of daily production of bilirubin is from the breakdown of red cells and 22% is produced from heme containing enzymes and a small amount 3% from ineffective erythropoeisis and normally less than 1mg/dl beyond neonatal period. Hyperbilirubinemia or increased serum bilirubin may result from overproduction, impaired uptake, conjugation or excretion or regurgitation.

Increased unconjugated bilirubin: This results from overproduction/impaired uptake, conjugation

Increased conjugated bilirubin: Impaired intrahepatic excretion / regurgitation of unconjugated or conjugated bilirubin from hepatocytes into bile ducts.
Serum bilirubin could be lowered by drugs like salicylates, sulphonamides, free fatty acids which displace bilirubin from its attachment to plasma albumin. On the contrary it could be elevated if the serum albumin increases and the bilirubin may shift from tissue sites to circulation.
Level of bilirubin rise may be mild in liver diseases, physiological jaundice and inherited hyperbilirubinemias. Moderate elevations of serum bilirubin is seen with biliary atresia, drugs, viral hepatitis, inherited hyperbilirubinemias
Other causes of hyperbilirubinemia may be due to extra hepatic sources either hemolysis, ineffective erythropoiesis, hematoma or myoglobinemia
But you should remember that bilirubin fractionation is very important to recognize conjugated bilirubinemia/cholestasis which is always pathological.

Urine Bilirubin & UBG

Conjugated bilirubin is water soluble and excreted in the urine and therefore the presence of urine bilirubin indicates hepatobiliary disease. Laboratory methods can detect low levels of bilirubin in urine. Tests strips impregnated with diazo reagent are easy to use to detect bilirubin in urine
Urobilinogen is formed from the degradation of conjugated bilirubin by bacteria in the intestinal lumen and upto 20% undergoes enterohepatic circulation. A small amount is excreted in urine. Increase in the urobilinogen in urine is a sensitive indicator of hepatocellular dysfunction. In cholestatic jaundice with complete biliary obstruction urobilinogen disappears from urine.

Tests of liver synthetic function:

Albumin and other serum proteins
Albumin is the principal serum protein and increases from a mean of 3.41g/dl in the first month of life to a mean of 4.25g/dl by adolescence. It is synthesized only in the rough endoplasmic reticulum of hepatocytes at a rate of 150mg/kg/day and has a half life of approximately 20 days. The major functions of albumin are to maintain intravascular colloid osmotic pressure and to bind and serve as a carrier protein. Decreases in serum levels may result from decreased production by the liver due to significant parenchymal liver disease. Because of the long half-life low serum albumin is taken as a sign of chronic liver disease. Hypoalbuminemia is not specific for liver disease and can occur in other non hepatic causes like poor nutrition, nephritic syndrome, and protein-losing enteropathies.
Serum globulins are often elevated in chronic liver disease including cirrhosis due to any cause and particularly in autoimmune hepatitis and this is due to increase in gamma globulins usually in the setting of low albumin

Abnormalities of coagulation – Prothrombin time (PT)
The liver plays three roles in the control of coagulation (a) the production partly or exclusively of all coagulation factors with the exception of von Willebrand factor, (b) the production and breakdown of factors integral to fibrinolysis such as plasminogen and plasminogen activator, and (c) the clearance of activated clotting factors from the circulation. Synthesis of factors II, VII, IX and X is dependent on adequate supply of vitamin K.
Prothrombin time (PT) is a measure of the time it takes for prothrombin to be converted into thrombin in the presence of other factors. The result is expressed in seconds or as a ratio of the plasma PT to a control PT. Normal range - 9-11 seconds. A prolongation of more than 2 seconds is considered abnormal.The prolonged PT is not specific for liver diseases. In acute and chronic hepatocellular disease the PT may serve as a prognostic indicator. Prothrombin time corrected by inj. Vitamin K indicates cholestasis causing vitamin k deficiency
Other tests for biosynthetic function of the liver are Serum prealbumin, Serum Ceruloplasmin, Procollagen III peptide, A 1 antitrypsin and Alpha feto protein

Prealbumin: The serum prealbumin level is 0.2- 0.3 g/L. these levels fall in liver disease presumably due to reduced synthesis. Determination of prealbumin has been considered particularly useful indrug-induced hepatotoxicity.

Serum Ceruloplasmin: Normal plasma levels are 0.2-0.4g/L. It is synthesized in the liver and is an acute phase protein. The plasma concentration rise in infections, rheumatoid arthritis, pregnancy, non Wilson liver disease and obstructive jaundice. This is an important diagnostic marker in Wilson disease, in which the plasma level is usually low. Low levels may also be seen in neonates, Menke’s disease, kwashiorkor, marasmus, protein losing enteropathy, copper deficiency and aceruloplasminemia.

Procollagen III Peptide: The serum concentration of this peptide appears to increase not only with hepatic fibrosis but also with inflammation and necrosis. Serial measurement of procollagen III may be helpful in the follow up of chronic liver disease.

a1 Antitrypsin: a1 antitrypsin is a glycoprotein synthesized by the liver and is an inhibitor of serine proteinases, especially elastase. Its normal concentration is 1- 1.6g/L. it is an acute phase protein, serum levels increase with inflammatory disorders, pregnancy and after oral contraceptive pills (OCP). Liver disease is usually seen with deficiency of a 1 antitrypsin, an inherited disorder. Deficiency should be confirmed by quantitative measurement.

Afeto Protein: This protein, the principal one in fetal plasma in early gestation is subsequently present at very low levels (<25mg/L) It is increased in Hepato Cellular Carcinoma (HCC) and more than 90% of such patients have raised levels. Raised values are also found in other liver diseases like chronic hepatitis, in regeneration phase of acute hepatitis and in hepatic metastasis. This is also raised in adenomas associated with tyrosinemia.

Dr. D. Nirmala
Professor and Head
Department of Paediatric Gastroenterology
Institute of Child Health and Hospital for children

Friday 24 January 2014

Success story
Yuvaraj




Name
Yuvaraj
Age
2 years
Sex
Male
Medical Problem
Respiratory Distress
Status
Discharged


Case Background

Yuvaraj was born to Mrs. Nathiya and Mr. Murugan on the 22nd of December, 2011, at the Chengalpet Government Hospital. Right after birth, he was facing difficulties in breathing and was immediately shifted to the hospital’s Neonatal Intensive Care Unit for oxygen support. The baby’s health showed no improvement even after 6 days of ventilator support and so the doctors suggested shifting the child to a private hospital. Mr. Murugan, who works as a coolie and earns about INR 100/day, could not afford a treatment in a private hospital.
Ekam’s Involvement

Dr.Sathya, the Nodal Officer at Chengalpet GH, referred this child to Ekam. Without any delay, we shifted the child to Kanchi Kamakoti Child Trust Hospital’s Neonatal Intensive Care Unit with issues of intrauterine hypoxia, meconium stained amniotic fluid, pneumonia, upper airway obstruction and sepsis.  The child was under ventilator care for about 21 days and his health improved tremendously. The total hospitalization and medication cost came to INR 116754. Meanwhile, the child’s parents also reached out to Women’s Welfare Syndicate for financial support. The below mentioned donors were very helpful in helping Ekam support this child’s case.
1.    Women’s Welfare Syndicate – Rs.33,154/-
2.    Shirdi Sai Trust – Rs.20,000/-
3.    Mr.Ravi –Rs.500/-
4.    Mr.Vinoo Karthick – Rs.1,000/-
           
Current Status

Yuvaraj is now 2 years old and is growing happily with his family. We sincerely thank all the donors who helped us in treating this child.


Ekam Contact

Name                          : Dr.Sathya Jaganathan
Designation                 : Pediatrician
Telephone Number       : 9443701730




Success story
Veeramanikandan
April 2011






Name
Veera Manikandan
Age
7 years
Sex
Male
Medical Problem
Intra abdominal Cysts
Status
Discharged
Date
13/4/2011


Case Background

Veera Manikandan is the third child of Mr. Velmurugan, a laborer in the match industry at Sivakasi. Velmurugan earns around INR 3000 a month and is the sole bread winner of his family. When he was 5 years old, Veera Manigandan was affected with viral fever and received treatment at a local clinic. However, there was no improvement in his health and the ailment went to a critical stage. His parents approached Mr.K.Pandiarajan, the MLA of Virudhunagar and one of the Trustees of Ekam. Mr. Pandiarajan referred the case to Mr. Krishnamurthy, one of the staff members in our foundation.

Ekam’s Involvement

Mr.Krishnamurthy spoke to the family members of Veera Manikandan and asked them to come over to Chennai for further treatment.  The child was admitted into Kanchi Kamakoti Child Trust Hospital’s Pediatric Intensive Care Unit and diagnosed with intra-abdominal cysts and lymphangiomas. Mesenteric cysts are estimated to occur in one out of every 20,000 pediatric admissions while retroperitoneal cysts are less common and more troublesome. The child received 20 days of hospitalization and medication in the hospital’s intensive care unit. Ekam sponsored the treatement for the child.

Current Status

Veeramanikandan has recovered completely and is currently living happily with his family.


Ekam Contact

Name                          : Mr.Charles Robin
Designation                 : Patient Welfare Officer.
Telephone Number       : 7299002848
Success story
Udhayakumar
Jun 2011



Name
Udhayakumar
Age
2 years
Sex
Male
Medical Problem
Congenital Diaphragmatic Hernia
Status
Discharged
Date
27/6/2011


Case Background

Udhyakumar was born prematurely, to Mr. Dhandapani and Mrs. Saridha, on the 24th of June, 2011 at the Chengalpet Government Hospital.  At birth, he was diagnosed with a pathological condition called Congenital Diaphragmatic Hernia(CDH). Congenital Diaphragmatic Hernia is a life-threatening condition and can cause death due to two complications: pulmonary hypoplasia and pulmonary hypertension. Newborns with CDH often have severe respiratory distress unless treated appropriately. The Government Hospital at Chengalpet does not have the necessary facilities to treat this condition.

Dhandapani works as casual laborer and earns about INR 5,000/- as monthly income. Saridha is a house wife. 

Ekam’s Involvement:

Dr.Sathya Jaganathan, who is Nodal officer at the Chengalpet GH, was also the consultant doctor of Udhyakumar. She referred the case to Mr. Krishnamurthy, who was working as Project Coordinator.  Soon after, the baby got shifted from Chengalpet GH to Kanchi Kamakoti Child Trust Hospital’s Neonatal Intensive Care Unit.  He received medical treatment for 45 days and was discharged as a healthy child. The cost of hospitalization totaled to Rs.3, 06,320/- and Ekam paid for the expenses from its funds.

Current Status

Udhayakumar is now a healthy 2 years old and is living happy with his family.

Ekam Contact:

Name                          : Mr.Charles
Designation                 : Patient Welfare Officer
Telephone Number       : 7299002848





Success story
Sudharani
Aug 2013



Name
Sudharani
Age
17 years
Sex
Female
Medical Problem
Aortic Valve Pathology
Status
Discharged
Date
29/8/2013


Case Background

Sudharani is the 17 years old girl child of Mr. Krishna and Mrs. Vijaya.  Her parents work as pushcart vendors and earn around INR 400 a day.  Last year, Sudharani was diagnosed with a critical condition in her aortic valve at a medical camp organized by Ekam in partnership with the Hindu Mission Hospital(HMH). She was immediately admitted to HMH where she underwent an Aortic Valve Replacement Surgery on the 28th of August 2013.  As her family is from Andharpradesh she could not claim relief under the Tamil Nadu Chief Minister’s Insurance scheme.

Ekam’s Involvement

Understanding her family’s financial condition, Ekam volunteered to take up her case. We paid for the total hospitalization cost which came to around INR 1, 78,815, inclusive of surgery and medications. We still needed funds to settle the hospitalization expenses and so we approached the Women’s Welfare Syndicate that helped us raise funds for Sudharani through an advertisement.  

Current Status

She is not completely fine and is attending her school regularly.

Ekam Contact

Name                          : Mr.Charles
Designation                 : Patient Welfare Office
Telephone Number       : 7299002848