Table 2
Medications that affect liver function test (LFT) results
| Medication class | Hepatocellular injury (↑ALT) | Cholestatic injury (↑ALP and ↑ALT) | Mixed injury (↑ALP and ↑TBIL) |
|---|---|---|---|
| Psychotropic | Bupropion, fluoxetine, paroxetine, risperidone, sertraline, trazodone, valproic acid | Chlorpromazine, mirtazapine, tricyclic antidepressants | Amitriptyline, Amitriptyline, phenobarbital, phenytoin, trazodone |
| Cardiovascular | Amiodarone, lisinopril, losartan, statins | Clopidogrel, irbesartan | Captopril, enalapril, verapamil |
| Endocrine | Acarbose, allopurinol | – | – |
| Gastrointestinal | Omeprazole | – | – |
| Herbal remedies | Germander, kava | – | – |
| Anti-infectives | HAART drugs, isoniazid, ketoconazole, pyrazinamide, rifampin, tetracycline, trovafloxacin | Amoxicillin/clavulanic acid, erythromycins, terbinafine | Clindamycin, nitrofurantoin, trimethoprim-sulfamethoxazole |
| Rheumatologic | Acetaminophen, baclofen, methotrexate, NSAIDs | Anabolic steroids | Azathioprine, sulfonamides |
| Others | – | Oral contraceptives, estrogens, phenothiazines | Cyproheptadine, flutamide |
| ALP: alkaline phosphatase; ALT: alanine aminotransferase; HAART: highly active antiretroviral therapy; NSAID: nonsteroidal anti-inflammatory drug; TBIL: total bilirubin | |||
| Source: Reference 5 | |||
Less common causes
Hemochromatosis is an autosomal recessive disease that causes pathologic deposition of iron in the liver, pancreas, and heart and leads to cirrhosis, diabetes, and heart disease. Suspect it in patients with a clinical syndrome and transferrin saturation index >45%.12 A hemochromatosis gene mutation analysis confirms the diagnosis.
Autoimmune hepatitis occurs primarily in women ages 20 to 50 years.13 Because >80% of patients with autoimmune hepatitis have hypergammaglobulinemia, serum protein electrophores is a useful screening test.5
Wilson’s disease is a genetic disorder of biliary copper excretion classically diagnosed in young people with concomitant neurologic or psychiatric conditions. Those affected have low serum ceruloplasmin. Neuropsychiatric symptoms include parkinsonian-like tremor, rigidity, clumsiness of gait, slurred speech, drooling, and inappropriate and uncontrollable grinning (risus sardonicus).8 Psychosis and suicidality also are common in patients with Wilson’s disease.
Alpha-1 antitrypsin deficiency. Alpha-1 antitrypsin is a protein produced primarily in the liver that protects the lungs from neutrophil elastase. Suspect alpha-1 antitrypsin deficiency in patients with abnormal LFTs and emphysema. Low serum alpha-1 antitrypsin confirms the diagnosis.
Celiac disease. Consider celiac disease in patients with chronic diarrhea or abdominal distension and abnormal LFTs. Small bowel biopsy and elevated tissue transglutaminase antibodies and anti-endomysial antibodies confirm the diagnosis.
Causes of cholestatic injury
If your patient has a disproportionate ALP elevation, identify the source of the ALP by testing GGT. GGT levels are elevated in liver disease but not in bone disease. Partial bile duct obstruction is a common cause of ALP elevation. For initial testing, include ultrasonography of the right upper quadrant.
Medications. Many medications can cause biliary stasis and cholestatic LFTs, including mirtazapine, tricyclic antidepressants, anabolic steroids, phenytoin, and estrogens.
Primary sclerosing cholangitis is inflammatory disease of the bile ducts that can lead to cholestasis (blockage of bile transport blockage). Consider it in patients with inflammatory bowel disease. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography aid diagnosis.
Primary biliary cirrhosis generally presents in middle-aged women with other autoimmune processes, cholestasis, and pruritus. Consider testing serum antimitochondrial antibodies.
Infiltrative liver diseases such as sarcoidosis, metastatic disease, or lymphoma can also present with cholestasis. Liver imaging is required for these diagnoses.
Causes of mixed injury
If LFT results suggest a mixed injury pattern, focus on the predominant pattern and evaluate the causes listed above. Certain medications typically result in a mixed injury pattern.
Related resources
- American Gastroenterological Association medical position statement: evaluation of liver chemistry tests. www.guideline.gov/summary/summary.aspx?ss=15&doc_id=3492&nbr=002718.
- Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician 1999;59(8):2223-30.
Drug brand names
- Amitriptyline • Elavil
- Bupropion • Wellbutrin
- Carbamazepine • Carbatrol, Equetro, Tegretol
- Chlorpromazine • Thorazine
- Fluoxetine • Prozac
- Mirtazapine • Remeron
- Paroxetine • Paxil
- Phenobarbital • Luminal
- Phenytoin • Dilantin
- Risperidone • Risperdal
- Sertraline • Zoloft
- Trazodone • Desyrel
- Valproic acid • Depakene
- Warfarin • Coumadin
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.