Interpreting Liver Function Tests
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Med/Psych Update pSYCHIATRY Tonya L. Fancher, MD, MPH Interpreting liver function tests Assistant professor Department of internal medicine Amit Kamboj, MD Medicine resident Department of internal medicine Patients’ elevated LFT results can indicate John Onate, MD Assistant professor hepatocyte injury, cholestasis, or both Department of psychiatry and human behavior rs. W, age 53, is referred by her Interpreting psychiatric patients’ liver University of California, Davis Medical primary provider for consultation function tests (LFTs) can be challenging, Center on depressive symptoms, including Sacramento M ® Dowdenespecially in Healththose with polypharmacy,Media worsening depressed mood, anhedonia, co-occurring substance abuse, or risk fac- anxiety, and suicidal thoughts for 2 months. tors for viral hepatitis. You can improve She reports at least 2 similarCopyright episodes Forin the personalcollaboration withuse primary only care providers past 15 years. Mrs. W has a remote history by understanding: of IV drug use and history of alcohol abuse, • what an LFT measures but she attends Alcoholics Anonymous and • how to interpret abnormal results has 10 years of sobriety. She has no history • which conditions to suspect, based on of hospitalizations for medical illness and the results. denies any medical problems. A standard LFT usually measures sev- Mrs. W is taking amitriptyline, 50 mg, eral enzymes and proteins, typically ALT, for insomnia. She has no history of manic AST, alkaline phosphatase (ALP), total or psychotic symptoms, and the mental bilirubin (TBIL), albumin (ALB), and total status examination is consistent with major protein (TP). Measures of gamma-glutamyl depression. Her past depressive episodes transpeptidase (GGT) and prothrombin were treated successfully with a medication time (PT) are often requested with an LFT. that she does not recall. Table 1 (page 62) provides normal ranges The psychiatrist diagnoses recurrent and and ranges that indicate liver damage for severe major depression and prescribes cognitive- several of these parameters.1,2 behavioral therapy and sertraline, 25 mg/d, “Liver function test” is a misnomer be- titrated to 50 mg/d over the next 2 weeks. cause LFTs do not directly measure liver Amitriptyline is discontinued. function. Rather, they refl ect hepatocyte When the psychiatrist receives Mrs. W’s injury or cholestasis (blockage or dam- medical records, electrolytes, complete blood age in the biliary system). ALB and PT count, thyroid stimulating hormone level, and measure liver synthetic function, but are fasting glucose are within normal limits, but nonspecifi c. ALB levels can be altered by alanine aminotransferase (ALT) and aspartate nutritional status, protein-losing enter- aminotransferase (AST) are greatly elevated opathies, or nephropathies, whereas PT at 250 U/L and 150 U/L, respectively. Progress may be modifi ed by warfarin, vitamin K Current Psychiatry notes contain no references to liver disease. defi ciency, or consumptive coagulopathy. Vol. 6, No. 5 61 continued For mass reproduction, content licensing and permissions contact Dowden Health Media. Med/Psych Update Table 1 Test results: what’s normal, what suggests liver damage Normal Range indicating Parameter Description range liver damage Alanine Enzyme highly concentrated in 3 to 30 U/L >3 times upper limit of aminotransferase the liver normal (ALT) Alkaline Enzyme highly concentrated in the 35 to 150 U/L >2 times upper limit of phosphatase (ALP) liver, bile ducts, placenta, and bone normal Aspartate Enzyme highly concentrated in 11 to 32 U/L Used to evaluate aminotransferase heart muscle, liver cells, skeletal elevations in other serum (AST) muscle cells, and (to a lesser enzyme level degree) other tissues Clinical Point Gamma-glutamyl Enzyme highly concentrated in the 5 to 40 U/L Used to evaluate When interpreting transpeptidase liver, bile ducts, and kidneys elevations in other serum (GGT) enzyme levels LFTs, consider the Total bilirubin Yellow bile pigment produced when 0.3 to 1.1 >2 times upper limit of patient’s complete (TBIL) liver processes waste products mg/dL normal if associated with clinical picture, elevation in ALT or ALP including symptoms, Sources: References 1,2 medical history, and medications CASE CONTINUED origin of elevated ALP or support a suspi- Spotting a pattern of injury cion of alcohol use in patients with an AST: Mrs. W’s elevated ALT and AST levels are ALT ratio >2:1. of unknown duration. Her AST:ALT ratio is If an asymptomatic patient has elevated approximately 2:1, suggesting hepatocellular LFT results, fi rst repeat the test. If repeat re- injury. sults are normal, perform the test again in 3-6 months. Keep in mind, however, that normal LFT results do not always indicate Interpreting abnormal LFT results the absence of disease. For example, up to To properly interpret LFTs, consider the pa- 16% of patients with hepatitis C and 13% of tient’s symptoms, physical exam fi ndings, patients with nonalcoholic steatohepatitis medical history, medical illnesses, potential (NASH) have normal LFT results despite substance use, risk factors for HIV and viral histologic abnormalities.4 hepatitis, and medication list. Collaborate If repeat results are abnormal, obtain with the patient’s primary care provider or the patient’s consent to inform the primary facilitate primary care (Figure 1). care provider. Then take a thorough his- ALT and AST are highly concentrated in tory and perform a focused physical exam. the liver, but ALT is a more specifi c indicator In the history, focus on use of prescription of liver injury. For both, levels may vary ac- and nonprescription medications, includ- cording to age, sex, and ethnicity but in gen- ing over-the-counter and herbal thera- eral, levels <30 U/L are considered normal.1,2 pies, alcohol, and drugs of abuse, such as ALP originates predominately from the MDMA (“ecstasy”), phencyclidine (“angel liver and from bone. Persistently elevated dust”), and glues or solvents. Also assess ALP levels in the liver may indicate chron- for risk factors for infectious hepatitis, such ic cholestasis or infi ltrative liver disease. as IV drug use, work-related blood expo- GGT is best used to evaluate the mean- sure, and tattoos. Ask about a family his- 3 ing of elevations in other serum enzymes. tory of liver disease. Focus your physical Current Psychiatry 62 May 2007 Elevated GGT can help confi rm hepatic exam on visible stigmata of chronic liver Med/Psych Update Figure 1 Interpreting liver function test results Receive results Elevated TBIL: Check ALT and ALP ALT or AST Elevated ALP >2 Low ALB >10 times AST >ALT ALT>AST times normal or TP normal Patient Review Screen for Check GGT, Evaluate for Clinical Point requires medications, alcohol repeat LFT, systemic If your patient’s ALT urgent refer patient use, review coordinate illness or medical for medical medications, further malnutrition is disproportionately evaluation evaluation or repeat LFT workup, elevated, estimate collaborate collaborate with PCP with PCP the ratio of AST:ALT Screen for substance abuse, HIV, HBV, HCV ALB: albumin; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transpeptidase; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodefi ciency virus; LFT: liver function test; PCP: primary care provider; TBIL: total bilirubin; TP: total protein disease, such as jaundice, temporal wast- C, and a comprehensive physical exam. The ing, ascites, and palmar erythema. psychiatrist screens for alcohol use, asks the Next, analyze the severity and pattern patient about her use of herbal therapies of the LFT abnormality. Liver injury is de- and substance abuse relapse, and evaluates fi ned as: cognitive mental status for symptoms of • ALT >3 times the upper limit of normal encephalopathy. Results reveal that Mrs. W’s • ALP >2 times the upper limit of normal ALT and AST are elevated because of chronic • or total bilirubin >2 times the upper active hepatitis C. limit of normal if associated with any elevation of ALT or ALP.5 If ALT elevations predominate, consid- Causes of hepatocellular injury er hepatocellular injury. If ALP elevations Further evaluation of your patient’s test predominate, suspect cholestatic injury. results can help narrow down potential Elevations of both ALT and ALP suggest a causes of liver damage. If your patient’s mixed pattern of hepatocellular and chole- ALT is disproportionately elevated, esti- static injury. mate the: • severity of aminotransferase elevation CASE CONTINUED • ratio of AST:ALT Pinpointing a diagnosis • rate of change over multiple LFTs. Mrs. W undergoes repeat LFTs with GGT If AST or ALT is >10 times normal, con- Current Psychiatry testing, screening tests for hepatitis B and sider toxin-induced or ischemic injury.6 Vol. 6, No. 5 63 continued Med/Psych Update Table 2 Medications that aff ect liver function test (LFT) results Medication Hepatocellular Cholestatic injury Mixed injury class injury (ìALT) (ìALP and ìALT) (ìALP and ìTBIL) Psychotropic Bupropion, fl uoxetine, Chlorpromazine, Amitriptyline, paroxetine, risperidone, mirtazapine, tricyclic carbamazepine, sertraline, trazodone, antidepressants phenobarbital, valproic acid phenytoin, trazodone Cardiovascular Amiodarone, lisinopril, Clopidogrel, irbesartan Captopril, enalapril, losartan, statins verapamil Endocrine Acarbose, allopurinol — — Gastrointestinal Omeprazole — — Clinical Point Herbal remedies Germander, kava — — If liver enzymes