Mrs. W, age 53, is referred by her primary provider for consultation on depressive symptoms, including worsening depressed mood, anhedonia, anxiety, and suicidal thoughts for 2 months. She reports at least 2 similar episodes in the past 15 years. Mrs. W has a remote history of IV drug use and history of alcohol abuse, but she attends Alcoholics Anonymous and has 10 years of sobriety. She has no history of hospitalizations for medical illness and denies any medical problems.
Mrs. W is taking amitriptyline, 50 mg, for insomnia. She has no history of manic or psychotic symptoms, and the mental status examination is consistent with major depression. Her past depressive episodes were treated successfully with a medication that she does not recall.
The psychiatrist diagnoses recurrent and severe major depression and prescribes cognitive-behavioral therapy and sertraline, 25 mg/d, titrated to 50 mg/d over the next 2 weeks. Amitriptyline is discontinued.
When the psychiatrist receives Mrs. W’s medical records, electrolytes, complete blood count, thyroid stimulating hormone level, and fasting glucose are within normal limits, but alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are greatly elevated at 250 U/L and 150 U/L, respectively. Progress notes contain no references to liver disease.
Interpreting psychiatric patients’ liver function tests (LFTs) can be challenging, especially in those with polypharmacy, co-occurring substance abuse, or risk factors for viral hepatitis. You can improve collaboration with primary care providers by understanding:
- what an LFT measures
- how to interpret abnormal results
- which conditions to suspect, based on the results.
A standard LFT usually measures several enzymes and proteins, typically ALT, AST, alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Measures of gamma-glutamyl transpeptidase (GGT) and prothrombin time (PT) are often requested with an LFT. Table 1 provides normal ranges and ranges that indicate liver damage for several of these parameters.1,2
“Liver function test” is a misnomer because LFTs do not directly measure liver function. Rather, they reflect hepatocyte injury or cholestasis (blockage or damage in the biliary system). ALB and PT measure liver synthetic function, but are nonspecific. ALB levels can be altered by nutritional status, protein-losing enteropathies, or nephropathies, whereas PT may be modified by warfarin, vitamin K deficiency, or consumptive coagulopathy.
Table 1
Test results: what’s normal, what suggests liver damage
| Parameter | Description | Normal range | Range indicating liver damage |
|---|---|---|---|
| Alanine aminotransferase (ALT) | Enzyme highly concentrated in the liver | 3 to 30 U/L | >3 times upper limit of normal |
| Alkaline phosphatase (ALP) | Enzyme highly concentrated in the liver, bile ducts, placenta, and bone | 35 to 150 U/L | >2 times upper limit of normal |
| Aspartate aminotransferase (AST) | Enzyme highly concentrated in heart muscle, liver cells, skeletal muscle cells, and (to a lesser degree) other tissues | 11 to 32 U/L | Used to evaluate elevations in other serum enzyme level |
| Gamma-glutamyl transpeptidase (GGT) | Enzyme highly concentrated in the liver, bile ducts, and kidneys | 5 to 40 U/L | Used to evaluate elevations in other serum enzyme levels |
| Total bilirubin (TBIL) | Yellow bile pigment produced when liver processes waste products | 0.3 to 1.1 mg/dL | >2 times upper limit of normal if associated with elevation in ALT or ALP |
| Sources: References 1,2 | |||
CASE CONTINUED: Spotting a pattern of injury
Mrs. W’s elevated ALT and AST levels are of unknown duration. Her AST:ALT ratio is approximately 2:1, suggesting hepatocellular injury.
Interpreting abnormal LFT results
To properly interpret LFTs, consider the patient’s symptoms, physical exam findings, medical history, medical illnesses, potential substance use, risk factors for HIV and viral hepatitis, and medication list. Collaborate with the patient’s primary care provider or facilitate primary care (Figure 1).
ALT and AST are highly concentrated in the liver, but ALT is a more specific indicator of liver injury. For both, levels may vary according to age, sex, and ethnicity but in general, levels <30 U/L are considered normal.1,2
ALP originates predominately from the liver and from bone. Persistently elevated ALP levels in the liver may indicate chronic cholestasis or infiltrative liver disease.
GGT is best used to evaluate the meaning of elevations in other serum enzymes.3 Elevated GGT can help confirm hepatic origin of elevated ALP or support a suspicion of alcohol use in patients with an AST: ALT ratio >2:1.
If an asymptomatic patient has elevated LFT results, first repeat the test. If repeat results are normal, perform the test again in 3-6 months. Keep in mind, however, that normal LFT results do not always indicate the absence of disease. For example, up to 16% of patients with hepatitis C and 13% of patients with nonalcoholic steatohepatitis (NASH) have normal LFT results despite histologic abnormalities.4