Why liver enzymes would be elevated

Although alterations of liver enzymes could be a normal physiological phenomenon in certain cases, it may also reflect potential liver injury in others, necessitating its further assessment and management. In this article, we provide a guide to primary care clinicians to interpret abnormal elevation of liver enzymes in asymptomatic patients using a step-wise algorithm.

Adopting a schematic approach that classifies enzyme alterations on the basis of pattern hepatocellular, cholestatic and isolated hyperbilirubinemia , we review an approach to abnormal alteration of liver enzymes within each section, the most common causes of enzyme alteration, and suggest initial investigations.

Evaluation of abnormal liver enzyme levels in an otherwise healthy patient can pose a challenge to even an experienced clinician. It may not be necessary to pursue extensive evaluation for all abnormal test results, however, as it would expose many patients to unnecessary procedural risks and expenses. Conversely, failure to investigate mild or moderate liver enzyme elevations could mean missing the early diagnosis of potential life-threatening yet treatable conditions.

It has become easier and faster to obtain serum liver enzyme levels with automated laboratory testing, which in turn has led to an increase in the number of incidental abnormal findings.

Since no consensus has yet been established, the aim of this review is to provide primary care providers with a systematic approach to interpreting abnormal liver enzymes.

A comprehensive investigation combining thorough history-taking and physical examination, along with diagnostic tests, liver histology and imaging, can often establish a precise diagnosis. The initial approach to an isolated liver enzyme alteration in an apparently healthy person should begin with repeating the test to confirm the result, unless the clinical context points towards an apparent etiology, like a new medication exposure, etc.

If the abnormality persists, the evaluation should be based on the magnitude of enzyme elevation. This classification is rather subjective, as there is no current consensus of these definitions and various sources use different cut-off points. Once stratification, based on the severity, is completed, the next step is to define the pattern of enzyme elevation, which can be divided into three categories, further assisting in clinical evaluation.

Very few prospective studies have addressed a standardized approach to evaluation of the mild hepatocellular pattern of liver enzyme elevation.

Some of the landmark studies, conducted by Hultcrantz et al. These studies also show that the cause of elevated enzyme levels varies greatly, depending on the population studied. The first step in the evaluation is to obtain a complete history and perform a thorough physical examination in an effort to identify the most common causes of mildly elevated aminotransferase levels.

Some of the important initial questions that will guide further management are: Presence of signs and symptoms of chronic liver disease development of jaundice, edema, pruritus, encephalopathy, gastrointestinal bleeding ;.

History of alcohol consumption including history from family , medication use especially new, careful review of available medical and pharmacy records and laboratory data and toxin exposure;.

Family history of genetic conditions pertaining to liver disease, such as hemochromatosis and WD;. History of chronic diarrhea or inflammatory bowel disease, indicating extrahepatic causes like celiac sprue, thyroid disorders, inflammatory bowel disease, hereditary and acquired muscle disorders, etc.

Physical examination should be thorough and detailed to look for stigmata of acute and chronic liver diseases which may be subtle or absent, like jaundice with close attention to the conjunctiva and soft palate , ascites, peripheral edema, hepatosplenomegaly, gynecomastia, testicular hypotrophy, muscle wasting, telangiectasias, palmar erythema, pubic hair changes, etc.

If a history of exposure is evident, repeat testing should be undertaken after abstinence from alcohol use, medications and toxins before ordering an extensive work-up. Persistently elevated results on liver function tests, after removal of obvious sources, should be followed by targeted testing based on specific clues from the history and physical exam findings.

If the initial assessment from a detailed interview with the patient fails to provide any clues, evaluation should begin with the most common causes of mildly elevated aminotransferase enzymes levels Table 1.

Non-invasive serological tests and imaging procedures may often reveal the most common causes of mild elevations of liver enzymes. If the more common causes have been ruled out and the etiology still remains uncertain, attention should be paid to non-hepatic diseases, such as thyroid disorders, occult celiac disease, etc. If despite investigation, following a systematic approach Fig. It is acceptable to observe patients, if the levels are less than twice the normal value and no chronic liver condition has been identified through non-invasive tests.

This is based on two recent studies which concluded that liver biopsy did not lead to a change in diagnosis or treatment in many such patients and that observation alone proved to be the most cost-effective strategy. Consideration may be given to the effects of decrease in body weight, diabetes control, cessation of alcohol use and other lifestyle modifications. A liver biopsy, though unlikely to change management, may be an acceptable approach for providing reassurance to the patient and the physician that no serious disease is present if the levels are persistently more than twice the normal value.

An indicator that should make the clinician highly suspicious of alcohol-related liver injury is AST:ALT ratio of or more. Gamma-glutamyl transferase GGT is another sensitive but non-specific marker for hepatic injury which cannot be used solely to diagnose alcohol-related hepatic insult. Generally, the enzymes in alcoholic hepatitis are only moderately elevated. ALT levels may even be normal in alcoholic liver disease, and thus a normal serum ALT concentration does not exclude an alcoholic liver disorder.

This pattern is thought to be the result of two mechanisms. Although alcohol is a very frequent cause of liver disease, one should not forget to look at comorbid medical conditions like chronic hepatitis B and C, obesity and diabetes mellitus than can also cause liver damage in a patient with alcoholic liver disease. A large, national, population-based study found increased risk of alcohol-related transaminitis with overweight and obesity.

Since these two viruses have such a high prevalence, some clinicians recommend early and empiric testing for HBV and HCV, even in the absence of risk factors for patients presenting with mildly elevated hepatocellular enzymes. Central America and Asia. Interpretations of these serological markers are discussed in Table 2. Distantly immune: test not sensitive enough to detect a very low level of anti-HBs in serum. The initial screening test for HCV infection begins with serologic test for HCV antibody which is very sensitive, but false positive tests are frequent even with third generation enzyme-linked immunosorbent assays ELISAs as seen in hypergammaglobulinemia of AIH.

As previously mentioned it is the most common cause of mild aminotransferase alteration in the general population of the United States. It rarely causes severe or fulminant rise in enzymes that lead to liver failure. NAFLD is a diagnosis of exclusion. The synthetic function of liver as measured by total bilirubin and albumin is usually preserved in early NAFLD without cirrhosis. Additionally, leucopenia and thrombocytopenia should make the clinician suspicious for the presence of cirrhosis and occult portal hypertension.

Imaging modalities like ultrasonography or computed tomography can help identify fatty infiltration of the liver, but the gold standard for confirming NAFLD remains liver biopsy. In addition, hyaline cytoplasmic inclusions may be found in hepatocytes that appear identical to Mallory bodies, which are characteristic of alcoholic liver disease.

However, it is still being studied and is not used widely; in two pilot studies 40 it was shown to decrease transaminase levels and reverse histologic abnormalities. Hereditary hemochromatosis should be considered early in the evaluation of men with elevated liver enzymes, especially those of northern European descent as the prevalence of this entity is 0. Clinically, patients remain asymptomatic until iron overload causes significant end-organ damage.

Screening for hereditary hemochromatosis can be done by measuring serum iron levels and total iron-binding capacity. Individuals with a positive screening test should undergo liver biopsy to measure hepatic iron levels and assess the severity of liver damage. Genetic testing, which has decreased the need for liver biopsy, has now become available to identify the mutation in the hemochromatosis HFE gene that causes the majority of cases.

Being non-invasive, it seems like an attractive option; yet, genetic testing has failed to replace liver biopsy as the gold standard for confirmatory diagnosis due to its lack of sensitivity. Individuals who are homozygous for the CY mutation seem to carry the greatest risk of iron overload. Liver biopsy in hereditary hemochromatosis patients who are younger than 40 years of age and who have normal liver tests is usually not necessary. In patients with hemochromatosis, due to the increased risk of hepatocellular carcinoma, it is important to exclude cirrhosis.

Similar information is not available for non-CY homozygotes. WD may present only with elevation of liver enzymes and no other clinical symptoms.

It has a homozygote frequency of — As there are numerous genotypic patterns associated with this disease, it is not useful to make the diagnosis of WD with molecular or genetic testing. The disease incidence in Europe and the United States is — It is an uncommon cause of chronic liver disease in adults and it is usually identified in early childhood, with a very small percentage progressing to cirrhosis in adulthood.

AIH primarily occurs in young to middle-aged women with concomitant autoimmune disorders e. Liver biopsy can be performed to confirm the diagnosis, if all other tests are inconclusive. Type 1 AIH is the most common form of autoimmune disease worldwide. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.

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C 10 Repeat liver enzyme testing is not necessary in the initial workup for elevated transaminase levels. B 43 Lifestyle modifications with follow-up are appropriate if history, physical examination, and workup suggest nonalcoholic fatty liver disease. B 4 — 6 , 10 , 11 , 43 If the history and physical examination are unrevealing, clinicians should initiate a stepwise epidemiologic approach to diagnosing the cause of elevated transaminase levels.

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Sign up for the free AFP email table of contents. Navigate this Article. Alcoholic liver disease. Excessive alcohol intake. Polypharmacy, certain herbal supplements. Hepatitis B surface antigen testing. Hepatitis C virus antibody testing. Serum iron, total iron-binding capacity, ferritin measurements. Early-onset emphysema, family history. Serum alpha 1 -antitrypsin measurement. Young women with autoimmune disorders.

Serum ceruloplasmin measurement. For patients who are overweight or obese. Fructose intake: avoid fructose-containing beverages and foods. Coffee drinking: no liver-related limitations. Assess risk of hepatic fibrosis.

Nonsteroidal anti-inflammatory drugs. Bupropion Wellbutrin. Risperidone Risperdal. Selective serotonin reuptake inhibitors. Valproic acid Depakene. Herbal and dietary supplements. Highly active antiretroviral therapy. Omeprazole Prilosec. Log in Best Value! Sign up for free, and stay up-to-date on research advancements, health tips and current health topics, like COVID, plus expert advice on managing your health. Error Email field is required.

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Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. They may test anyone with symptoms of one of the conditions that they know to raise liver enzyme levels. Once they make a diagnosis, the doctor will recommend suitable treatments. Fatty liver disease is the most common cause of elevated liver damage. People with fatty liver disease can manage their condition by losing weight, if necessary, or reducing their alcohol consumption.

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Elevated liver enzymes: Everything you need to know. Medically reviewed by Saurabh Sethi, M.