Liver Function Tests - Interpretation

8/17/01

Question: How are liver function tests interpreted in the diagnosis of liver disease or injury?

<1>

Unique Identifier: 20228763 / PubMed Identifier: 10781624

Authors: Pratt DS. Kaplan MM.

Institution: New England Medical Center, Boston, MA 02111, USA.

<2>

Unique Identifier: 20154001 / PubMed Identifier: 10689411

Authors: Gopal DV. Rosen HR.

Institution: Division of Gastroenterology and Hepatology, Oregon Health Sciences University School of Medicine, Portland, USA.

Abstract: Evaluating abnormal liver test results requires careful attention to the corresponding clinical data obtained during history taking and physical examination. Generally, it is helpful to separate liver tests into three categories: tests that assess synthetic function, tests that assess hepatocellular necrosis (hepatocellular enzymes), and tests that assess cholestasis. The clinical setting together with the specific pattern of liver function abnormalities can narrow differential diagnosis and provide a cost-effective approach to assessing patients and identifying those who need liver biopsy. [References: 17]

<3>

Unique Identifier: 99236496 / PubMed Identifier: 10221307

Authors: Johnston DE.

Institution: Division of Gastroenterology, University of New Mexico School of Medicine, Albuquerque 87131-5271, USA.

Abstract: A number of pitfalls can be encountered in the interpretation of common blood liver function tests. These tests can be normal in patients with chronic hepatitis or cirrhosis. The normal range for aminotransferase levels is slightly higher in males, nonwhites and obese persons. Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis. Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase and gamma-glutamyltransferase levels do not become elevated for several days. Asymptomatic patients with isolated, mild elevation of either the unconjugated bilirubin or the gamma-glutamyltransferase value usually do not have liver disease and generally do not require extensive evaluation. Overall hepatic function can be assessed by applying the values for albumin, bilirubin and prothrombin time in the modified Child-Turcotte grading system. [References: 32]

<4>

Unique Identifier: 99001076 / PubMed Identifier: 9784897

Authors: Minuk GY.

Institution: University of Manitoba, Liver Diseases Unit, Winnipeg. gminuk@cc.umanitoba.ca

<5>

Unique Identifier: 98201071 / PubMed Identifier: 9540248

Authors: Younossi ZM.

Institution: Department of Gastroenterology, Cleveland Clinic, USA.

Abstract: Because elevated liver enzymes are found in 1% to 4% of asymptomatic persons, extensive evaluation of all abnormal tests would expose many patients to undue risks and medical costs. On the other hand, not evaluating minor elevations of liver enzymes could result in missing the early diagnosis of potentially treatable disorders. This review discusses likely causes of elevated aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase levels and provides algorithms for evaluating abnormal liver enzyme values in apparently healthy patients in the primary care setting. [References: 21]

<6>

Unique Identifier: 97335396 / PubMed Identifier: 9192062

Authors: Noack KB. Speer T.

Institution: Hepatobiliary Unit, Royal Melbourne Hospital, Victoria, Australia.

Abstract: About one-half of patients with ulcerative colitis develop abnormal liver function tests at some time during the course of the illness. This should prompt an investigation for primary sclerosing cholangitis and other common hepatobiliary diseases. Primary sclerosing cholangitis occurs in 2-10% of patients with ulcerative colitis. The diagnosis of primary sclerosing cholangitis is most often made by endoscopic retrograde cholangiography. Liver histopathology is often inconclusive but magnetic resonance cholangiography shows promise as a useful non-invasive diagnostic tool. Cholangiocarcinoma complicates 20-40% of patients with end-stage primary sclerosing cholangitis and is now one of the most common causes of death in patients with ulcerative colitis. Distinction between benign and malignant strictures can be difficult and is best done with a combination of clinical suspicion, repeated imaging for mass lesions, cholangiography, and endoscopic brushings and/or biopsies. Dominant lesions of the common bile duct or common hepatic duct produce progressive jaundice and liver damage. Early treatment may improve prognosis. Single strictures can be dilated endoscopically. If the stricture is more complicated and extends into the intrahepatic ducts or there is suspicion of cholangiocarcinoma, surgical resection may be more appropriate. Liver transplantation should be considered in end-stage disease. [References: 49]

<7>

Unique Identifier: 97059478 / PubMed Identifier: 8903799

Authors: Renner EL.

Abstract: For optimal timing of liver transplantation and for the evaluation of new pharmacotherapeutic options, objective modalities for estimating the liver's functional reserve and prognosis in an individual patient are highly desirable. In the past a number of tests and several scoring systems have been proposed and validated to varying degrees for this purpose. The issues still to be clarified include: (1) any observed prognostic value of individual quantitative function tests and of scoring systems must be validated in independent, large enough and well defined patient populations; (2) it must be prospectively defined which (serially performed) quantitative test(s) add(s) prognostic information for the individual patient to the survival estimates defined by the more universally available scores and in which disease state(s); and (3) existing scoring systems must be validated, or new ones developed, that allow follow-up data to be used in order to adapt the original prognosis estimate to the evolution of the disease, e.g. during therapy. [References: 145]

<8>

Unique Identifier: 96397473 / PubMed Identifier: 8804367

Authors: Moseley RH.

Institution: Gastroenterology Section, Ann Arbor Department of Veterans Affairs Medical Center, Michigan 48105, USA.

Abstract: Although the liver can be affected in a wide range of disorders, the differential diagnosis of abnormal liver function tests can be substantially narrowed by a comprehensive history and physical examination and by the recognition of relatively distinct biochemical patterns of liver injury. Although referral to a specialist may be required for the performance of, for example, percutaneous liver biopsy and long-term management of chronic liver disease, a presumptive diagnosis can usually be made in the vast majority of patients who present to primary care physicians with abnormal liver function tests. [References: 96]

<9>

Unique Identifier: 96210180 / PubMed Identifier: 8623723

Authors: Theal RM. Scott K.

Institution: Department of Family Medicine, Kaiser Permanente Medical Center, Fontana, CA 92335-6720, USA.

Abstract: Asymptomatic patients with abnormal results on liver function test pose a diagnostic challenge. In general, determinations of routinely ordered tests of liver function are neither sensitive nor specific for liver disease. Fatty liver, alcohol-related liver damage and chronic viral hepatitis are the most common causes of abnormal liver function test results in asymptomatic patients. Causes of asymptomatic liver disease include hemochromatosis, Wilson's disease, drug toxicity, chronic autoimmune hepatitis, biliary cirrhosis, sclerosing cholangitis, alpha1-antitrypsin deficiency and sarcoidosis. The most efficient screening tests for liver damage are alanine transaminase, alkaline phosphatase and bilirubin. Repeat testing when results are abnormal, and use of ancillary tests, such as creatine phosphokinase or gamma-glutamyl-transferase, may confirm liver damage. Imaging studies help exclude biliary obstruction or neoplasm. Treatable illnesses should be ruled out. Three to six months of observation for progressive symptoms and liver dysfunction may follow. After the period of observation, further laboratory tests, a diagnostic liver biopsy and/or referral to gastroenterologist may be needed. [References: 21]

<10>

Unique Identifier: 95383518 / PubMed Identifier: 7654888

Authors: Jalan R. Hayes PC.

Institution: Department of Medicine, Royal Infirmary of Edinburgh, UK.

Abstract: The search continues for a single reliable test of liver function that provides accurate prognostic information in chronic liver disease, in acute liver failure, and about graft function following orthotopic liver transplantation. Although transaminases, the commonly used markers of hepatocellular injury, have a high sensitivity in screening for liver disease, they do not provide any information about prognosis. Rational assessment of liver function using bilirubin, serum albumin and prothrombin-time is limited by the relative lack of sensitivity of these measurements and their inability to identify the functional reserve of the liver. Dynamic liver function tests are an improvement on the static tests but are generally cumbersome. The ideal liver function test would be cheap, easy to perform and analyse, safe, have a simple pharmacokinetic profile with minimal drug interactions, have a high predictive value and provide quick results. Numerous quantitative liver function tests have been developed and have shown promise in some studies. The aim of this review is to assess the place of these tests in the practical management of liver disease. [References: 76]

<11>

Unique Identifier: 94906104 / PubMed Identifier: 10146457

Authors: Roe PG.

Institution: Addenbrooke's Hospital, Cambridge, UK.

Abstract: The liver has a wide range of functions that may be disturbed in different ways by the many diseases which affect it and, in consequence, there are a large number of tests which look at different aspects of its function. Specific diagnoses are made using a range of clinical, biochemical, histological and radiological methods. Measurement of the plasma concentration of alanine aminotransferase (ALT, SGPT), gamma-glutamyl transpeptidase (gammaGT) and albumin are particularly valuable as these substances are specifically affected by liver disease. Their elevation can reveal increases in the membrane permeability of hepatocytes (ALT), cholestasis and toxic damage (gammaGT), or an impairment of liver protein synthesis and secretion (albumin), respectively. If their activities remain within the normal range the likelihood of significant liver disease is less than 2%. A series of quantitative liver function tests are described which each examine one aspect of hepatic function. Table 1 lists several situations where the assessment of hepatic function is necessary. Liver function tests are classified in Table 2. [References: 70]

<12>

Unique Identifier: 94906104 / PubMed Identifier: 10146457

Authors: Roe PG.

Institution: Addenbrooke's Hospital, Cambridge, UK.

Abstract: The liver has a wide range of functions that may be disturbed in different ways by the many diseases which affect it and, in consequence, there are a large number of tests which look at different aspects of its function. Specific diagnoses are made using a range of clinical, biochemical, histological and radiological methods. Measurement of the plasma concentration of alanine aminotransferase (ALT, SGPT), gamma-glutamyl transpeptidase (gammaGT) and albumin are particularly valuable as these substances are specifically affected by liver disease. Their elevation can reveal increases in the membrane permeability of hepatocytes (ALT), cholestasis and toxic damage (gammaGT), or an impairment of liver protein synthesis and secretion (albumin), respectively. If their activities remain within the normal range the likelihood of significant liver disease is less than 2%. A series of quantitative liver function tests are described which each examine one aspect of hepatic function. Table 1 lists several situations where the assessment of hepatic function is necessary. Liver function tests are classified in Table 2. [References: 70]

<13>

Unique Identifier: 93165547 / PubMed Identifier: 8094554

Authors: Herrera JL.

Institution: Division of Gastroenterology, University of South Alabama College of Medicine, Mobile 36617.

Abstract: Chronic elevation of liver enzyme levels requires attention, because it may indicate serious liver disease. The pattern of elevation, whether hepatocellular or cholestatic, is used to guide the evaluation. The goal is to diagnose treatable forms of liver disease. Occasionally, a diagnosis cannot be established with noninvasive screening tests, and regular follow-up is then recommended. The role of liver biopsy in such cases is controversial. [References: 21]

<14>

Unique Identifier: 91306379 / PubMed Identifier: 1853522

Authors: Herlong HF.

Institution: Johns Hopkins University School of Medicine.

<15>

Unique Identifier: 91156563 / PubMed Identifier: 2000347

Authors: King PD.

Institution: Department of Medicine, University of Missouri-Columbia School of Medicine 65212.

Abstract: Chronic elevation of serum aminotransferase levels, even in the absence of symptoms, often reflects chronic hepatitis or other significant underlying liver disease. Patients with persistently abnormal alkaline phosphatase levels may have extrahepatic biliary tract disease or a chronic cholestatic disorder. Physicians can discover unsuspected liver disease without undue risk, expense, or inconvenience to the patient by means of the following: a carefully taken history and thorough physical examination, appropriate timing of follow-up blood tests, and timely referral for percutaneous liver biopsy or endoscopic retrograde cholangiopancreatography. [References: 17]

<16>

Unique Identifier: 90360037 / PubMed Identifier: 2202455

Authors: Laker MF.

Institution: University of Newcastle upon Tyne Medical School.

<17>

Unique Identifier: 90146093 / PubMed Identifier: 2694908

Authors: Johnson PJ.

Institution: Liver Unit, King's College Hospital School of Medicine and Dentistry, London, UK.

Abstract: A prerequisite of current therapy in liver disease is precise diagnosis. The rapid increase in the number of tests available--immunological, virological, histological and radiological--testifies to this, and reflects the inadequacy of the 'standard' liver function tests (LFTs). The LFTs are, however, in contrast to these more sophisticated tests, observer independent and despite their lack of specificity, several characteristic patterns of abnormality can be recognised which direct the physician to the most appropriate definitive investigation. The cheapness and non-invasive nature of the LFTs makes them particularly appropriate for monitoring the course of liver diseases once the diagnosis has been established and this, together with screening for hepatotoxicity of newly developed drugs, is now their main role. A second generation of liver function tests based on the capacity of the liver to eliminate various test compounds may come closer to offering a true estimate of liver function. More accurate methods of measuring the various bilirubin fractions, particularly bilirubin conjugates may also become available in the near future and provide more sensitive tests of liver dysfunction. [References: 24]

<18>

Unique Identifier: 89372470 / PubMed Identifier: 2774372

Authors: Van Ness MM. Diehl AM.

Institution: Bethesda Naval Hospital, Maryland.

Abstract: STUDY OBJECTIVE: To determine the diagnostic usefulness of percutaneous liver biopsy in evaluating patients with chronically elevated liver-associated enzymes. DESIGN: Comparison of diagnosis made before biopsy by one physician on the basis of a noninvasive work-up (history, physical examination, laboratory values, and imaging studies) and final diagnosis made after biopsy by a second physician formulated after review of all available noninvasive information and study of the biopsy specimen. SETTING: Referral-based gastroenterology clinic at a U.S. Navy medical center. PATIENTS: Sequential sample of 107 patients with elevated liver-associated enzymes for a minimum of 3 months. Ninety patients were eligible for study. INTERVENTIONS: The final diagnosis made by the second physician blinded to the first clinician's diagnosis served as the criterion standard. MEASUREMENTS AND MAIN RESULTS: Four diagnostic groups were selected for analysis: Alcoholic liver disease, fatty liver, chronic necroinflammatory diseases, and miscellaneous. The positive predictive value of the prebiopsy diagnosis ranged from 88% (CI, 75% to 100%) for alcoholic liver disease to 56% (CI, 37% to 75%) for fatty liver. Higher elevations of transaminase values (greater than three times the upper limit of normal) correlated positively with increased prebiopsy diagnostic accuracy. Fatty liver was present in 19% of the cohort. Liver diseases requiring specific therapy other than alcohol abstinence were overlooked and diagnosed only after review of the biopsy in five cases. Conversely, four cases of liver disease, thought to require specific therapy on the basis of noninvasive work-up, were ruled out by biopsy. CONCLUSION: The cause of chronic liver disease is best elucidated when the noninvasive work-up is complemented by review of a biopsy specimen.