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A liver panel is often referred to as liver function tests or lfts. It is really an indirect measurement of liver function since the enzymes and proteins that are measured are largely produced by the liver cells (hepatocytes).  The typical liver panel includes:

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Novel assay for measuring serum conjugated bilirubin and its clinical relevance.

Morimoto Y, Ishihara T, Takayama M, Kaito M, Adachi Y.

Diagnostic Research & Development Department, R&D Division, Nesco Company, Azwell Inc., Osaka, Japan.


J Clin Lab Anal 2000;14(1):27-31 Abstract quote

We have developed a new enzymatic assay for the determination of conjugated bilirubin (Bc) using stable liquid reagents. In this assay, only Bc is selectively oxidized by bilirubin oxidase at pH 5. 0 in the presence of nitrilotris (methylenephosphonic acid) trisodium salt, ethylenediaminetetraacetic acid disodium manganese (II) salt, and 4-hydroxy-2,2,6,6,-tetramethylpiperidine 1-oxyl. Bc is quantitatively determined from a decrease in the absorbance at 450 nm caused by Bc oxidization.

The reagent solutions of the assay were developed so that they could be stably stored for one year together with bilirubin oxidase, in order to eliminate the need to prepare working solutions every time they are required. The assay has good reactivity, differentiability, measurability, and precision. Neither ascorbic acid nor hemoglobin interfered with the measurement. Bc values determined by the assay reflected more clearly the pathophysiological condition of hepatobiliary disease patients with jaundice than the values of total bilirubin or direct bilirubin determined by conventional methods.

From these observations, we concluded that this Bc assay is valuable for the evaluation of jaundice.

Bilirubin proficiency testing using specimens containing unconjugated bilirubin and human serum: results of a College of American Pathologists study.

Lo SF, Doumas BT, Ashwood ER; College of American Pathologists.

Reference Standards Laboratory, Department of Pathology and Laboratory Medicine, Children's Hospital of Wisconsin, Milwaukee 53226, USA.
Arch Pathol Lab Med. 2004 Nov;128(11):1219-23. Abstract quote  

CONTEXT: Specimens of the College of American Pathologists Neonatal Bilirubin and Chemistry surveys are inadequate for evaluating the performance of clinical laboratories in measuring serum bilirubin because they exhibit strong matrix interference. Recently published data indicate that at least 1 major clinical analyzer provided inaccurate bilirubin values for Neonatal Bilirubin Survey specimens. The composition of the specimens, bovine serum enriched with ditaurobilirubin, was responsible for the erroneous results.

OBJECTIVE: This article evaluates the performance of major clinical analyzers using a survey specimen free of matrix interference.

DESIGN: A human serum-based specimen enriched solely with unconjugated bilirubin was included in the 2003 Neonatal Bilirubin and Chemistry surveys. Its bilirubin concentration (19.4 mg/dL [332 micromol/L]) was determined by the reference method for total bilirubin.

RESULTS: The coefficients of variation for the 4 major clinical analyzers (Dimension, Hitachi, Synchron, and Vitros) ranged from 1.9% to 3.7%. When compared to the bilirubin value measured by the reference method, mean bilirubin values of the 4 major clinical analyzers and College of American Pathologists (CAP) All Data (which refers to the grand mean and overall coefficient of variation of all method principles, all instruments according to CAP terminology) ranged from -3.5% to 5.1%. Direct bilirubin results from most field methods showed good specificity overall.

CONCLUSION: Human serum-based survey specimens, having their bilirubin concentrations determined by the reference method, should be included as frequently as feasible in the Neonatal Bilirubin Survey. Such specimens may be used by instrument manufacturers as standards for calibrating bilirubin methods and for assigning values to calibrators provided to instrument users. A substantial improvement in bilirubin measurements due to the reduction of systematic error is expected.

Measurement of plasma unbound unconjugated bilirubin.

Ahlfors CE.

Department of Pediatrics, Division of Neonatology, California Pacific Medical Center, 3850 California Street, San Francisco, California, 94118, USA.

Anal Biochem 2000 Mar 15;279(2):130-5 Abstract quote

A method is described for measuring the unconjugated fraction of the unbound bilirubin concentration in plasma by combining the peroxidase method for determining unbound bilirubin with a diazo method for measuring conjugated and unconjugated bilirubin.

The accuracy of the unbound bilirubin determination is improved by decreasing sample dilution, eliminating interference by conjugated bilirubin, monitoring changes in bilirubin concentration using diazo derivatives, and correcting for rate-limiting dissociation of bilirubin from albumin. The unbound unconjugated bilirubin concentration by the combined method in plasma from 20 jaundiced newborns was significantly greater than and poorly correlated with the unbound bilirubin determined by the existing peroxidase method (r = 0.7), possibly due to differences in sample dilution between the methods.

The unbound unconjugated bilirubin was an unpredictable fraction of the unbound bilirubin in plasma samples from patients with similar total bilirubin concentrations but varying levels of conjugated bilirubin. A bilirubin-binding competitor was readily detected at a sample dilution typically used for the combined test but not at the dilution used for the existing peroxidase method.

The combined method is ideally suited to measuring unbound unconjugated bilirubin in jaundiced human newborns or animal models of kernicterus.



Hyperbilirubinemia in the term newborn.

Porter ML, Dennis BL.

Dewitt Army Community Hospital, Fort Belvoir, Virginia, USA.

Am Fam Physician 2002 Feb 15;65(4):599-606 Abstract quote

Hyperbilirubinemia is one of the most common problems encountered in term newborns. Historically, management guidelines were derived from studies on bilirubin toxicity in infants with hemolytic disease.

More recent recommendations support the use of less intensive therapy in healthy term newborns with jaundice. Phototherapy should be instituted when the total serum bilirubin level is at or above 15 mg per dL (257 micromol per L) in infants 25 to 48 hours old, 18 mg per dL (308 micromol per L) in infants 49 to 72 hours old, and 20 mg per dL (342 micromol per L) in infants older than 72 hours. Few term newborns with hyperbilirubinemia have serious underlying pathology. Jaundice is considered pathologic if it presents within the first 24 hours after birth, the total serum bilirubin level rises by more than 5 mg per dL (86 micromol per L) per day or is higher than 17 mg per dL (290 micromol per L), or an infant has signs and symptoms suggestive of serious illness.

The management goals are to exclude pathologic causes of hyperbilirubinemia and initiate treatment to prevent bilirubin neurotoxicity.

The value of first-day bilirubin measurement in predicting the development of significant hyperbilirubinemia in healthy term newborns.

Alpay F, Sarici SU, Tosuncuk HD, Serdar MA, Inanc N, Gokcay E.

Department of Pediatrics, Gulhane Military Medical Academy, Ankara, Turkey.

Pediatrics 2000 Aug;106(2):E16 Abstract quote

OBJECTIVE: The recognition, follow-up, and early treatment of neonatal jaundice has become more difficult, since the earlier discharge of newborns from hospitals has become common practice. This prospective study was undertaken to identify the newborns at risk for developing significant hyperbilirubinemia later during the first days of life by measuring the serum bilirubin levels of the first 5 days of life to determine the critical predictive serum bilirubin value on the first day of life.

METHODOLOGY: A total of 498 healthy term newborns were followed with daily serum total bilirubin measurements for the first 5 days of life, and cases with serum bilirubin levels of >/=17 mg/dL after 24 hours of life were defined to have significant hyperbilirubinemia.

RESULTS: No newborns had a serum total bilirubin level of >/=17 mg/dL in the first 72 hours of life. Sixty of 498 cases (12.05%) had significant hyperbilirubinemia after 72 hours of life, and these cases had significantly higher bilirubin levels than those who did not develop significant hyperbilirubinemia on each of the first 5 days' measurements. Of the 206 newborns who had a serum bilirubin level of >/=6 mg/dL in the first 24 hours, 54 (26.21%) developed significant hyperbilirubinemia, whereas only 6 of the 292 newborns (2.05%) who had a serum bilirubin level of <6 mg/dL on the first day developed significant hyperbilirubinemia. A mean serum bilirubin level of >/=6 mg/dL on the first day had the highest sensitivity (90%). At this critical serum bilirubin value, the negative predictive value was very high (97.9%) and the positive predictive value was fairly low (26.2%). Furthermore, because no cases with a serum bilirubin level of <6 mg/dL in the first 24 hours of life required a subsequent phototherapy treatment and because all of those infants requiring a phototherapy treatment with serum bilirubin levels of >/=20 mg/dL were just among the cases whose first-day bilirubin levels were >/=6 mg/dL, the critical bilirubin level of 6 mg/dL on the first day made it possible, with the highest (100%) sensitivity and negative predictive value, to definitely predict all of the infants who would have a bilirubin level of >20 mg/dL, requiring a phototherapy treatment later during the first days of life.

CONCLUSIONS: A serum bilirubin measurement and the use of the critical bilirubin level of 6 mg/dL in the first 24 hours of life will predict nearly all of the term newborns who will have significant hyperbilirubinemia and will determine all those who will require a phototherapy treatment later during the first days of life.



Artifactual Hyperbilirubinemia Due to Paraprotein Interference.

Pantanowitz L, Horowitz GL, Upalakalin JN, Beckwith BA.

Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.


Arch Pathol Lab Med 2003 Jan;127(1):55-59 Abstract quote

Context.-Paraprotein interference in automated chemistry is uncommon. We describe 2 patients with paraproteinemia and elevated total bilirubin levels measured erroneously using the Roche total bilirubin assay.

Objectives.-To explain the mechanism of this artifactual hyperbilirubinemia and to determine its frequency in patients with monoclonal or increased immunoglobulins.

Materials and Methods.-The assay was performed manually using serum from 2 index patients and from control patients (without M proteins). Total bilirubin was also determined using another manufacturer's assay. A prospective study was then undertaken using serum from 100 consecutive patients with various monoclonal gammopathies and from 13 patients with polyclonal hypergammaglobulinemia and cryoglobulins. For all patients, serum immunoglobulin (Ig) G, IgA, IgM, total and direct bilirubin, creatinine, and a direct spectrophotometric assessment of icterus were measured.

Results.-After the addition of assay reagents, a white precipitate formed in the reaction mixtures containing serum from the index patients, but not in other samples. This turbidity, rather than the expected color change to pink, increased the absorbance and falsely elevated the total bilirubin value. Serum from both index patients was anicteric, their direct bilirubin measurements were unaffected, and total bilirubin measured using an alternate assay was normal. Among the 113 patients studied, no additional spurious total bilirubin values were detected.

Conclusion.-Paraprotein interference with the Roche automated total bilirubin assay is caused by precipitate formation. This interference is rare and probably idiosyncratic. Spurious hyperbilirubinemia from paraprotein interference may cause clinical confusion. If artifactual elevation of total bilirubin is suspected, the laboratory should examine the specimen for icterus (manually or by spectrophotometry) or measure total bilirubin using a different method.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.

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Last Updated November 11, 2004

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