The diagnosis of drug-induced liver diseases often is
difficult. Patients may not have symptoms of liver disease or may have only
mild, nonspecific symptoms. Patients may be taking multiple drugs, which makes
it difficult to identify the offending drug. Patients also may have other
potential causes of liver diseases such as non-alcoholic fatty liver disease
(NAFLD) and alcoholism.
- History: History must include dose, route of administration, duration, previous administration, and use of any concomitant drugs, including over-the-counter medications and herbs. Knowing whether the patient was exposed to the same drug before may be helpful. The latency period of idiosyncratic drug reactions is highly variable; hence, obtaining a history of every drug ingested in the past 3 months is essential.
- Onset: The onset is usually within 5-90 days of starting the drug.
- Exclusion of other causes of liver injury/cholestasis: Excluding other causes of liver injury is essential.
- Dechallenge: A positive dechallenge is a 50% fall in serum transaminase levels within 8 days of stopping the drug. A positive dechallenge is very helpful in cases of use of multiple medications.
- Track record of the drug: Previously documented reactions to a drug aid in diagnosis.
- Rechallenge: Deliberate rechallenge in clinical situations is unethical and should not be attempted; however, inadvertent rechallenge in the past has provided valuable evidence that the drug was indeed hepatotoxic.
The diagnosis of liver disease is based
on a patient's symptoms (such as loss of appetite, nausea, fatigue, itching,
and dark urine), findings on the physical examination (such as jaundice,
enlarged liver), and abnormal laboratory tests (such as blood levels of liver
enzymes or bilirubin and blood clotting times). If a patient has symptoms,
signs, and abnormal liver tests, doctors then try to decide whether drug(s) are
causing the liver disease by:
- Taking a careful history of alcohol consumption to exclude alcoholic liver disease.
- Performing blood tests to exclude viral hepatitis B and hepatitis C , and to exclude chronic liver diseases such as autoimmune hepatitis and primary biliary cirrhosis (PBC).
- Performing abdominal ultrasound or computerized tomography (CT) scan of the liver to exclude gallbladder disease and tumors of the liver.
- Taking a careful history of ingestion-particularly recent initiation--of drugs that are commonly associated with liver disease.
5.
Differential diagnoses
6. Acute viral hepatitis
7.
Autoimmune hepatitis
8.
Shock liver
9.
Cholecystitis
10. Cholangitis
11. Budd-Chiari syndrome
12. Alcoholic liver disease
13. Cholestatic liver
disease
14. Pregnancy-related
conditions of liver
15. Malignancy
16. Wilson disease
17. Hemochromatosis
18. Coagulation disorders
Laboratory studies
Performing
laboratory tests to assess and diagnose the effects of the suspected medication
is essential. These include complete blood cell count, basic metabolic profile,
and urinalysis. Patients with a hepatocellular process generally have a
disproportionate elevation in serum aminotransferase levels compared with
alkaline phosphatase levels, while those with cholestasis have the opposite
findings. Hepatitis B serology (hepatitis B surface antigen, anti–hepatitis B
surface antibody, anti–hepatitis B core antibody, hepatitis C serology) and
hepatitis A serology (anti–hepatitis A virus antibody) should be performed to
exclude an infectious etiology.
ANA
testing may help in cases of possible autoimmune hepatitis. Positive ANA and
ASMA findings may add to the diagnostic evaluation but are usually confusing
and hence not used. The presence of antibodies to specific forms of CYP has
been associated with hypersensitivity to some drugs. For example, some
antibodies and the associated drugs involved are as follows: CYP 1A2,
dihydralazine; CYP 3A1, anticonvulsants; and CPY 2E1, halothane. Their role in
pathophysiology is uncertain but may help in diagnosis. Lymphocyte
transformation to test drugs may be observed for drugs acting through
immunologic reactions, but this is not commonly used.
Hepatic function tests and their interpretations
are as follows:
- Bilirubin (total) - To diagnose jaundice and assess severity
- Bilirubin (unconjugated) - To assess for hemolysis
- Alkaline phosphatase - To diagnose cholestasis and infiltrative disease
- AST/serum glutamic oxaloacetic transaminase (SGOT) - To diagnose hepatocellular disease and assess progression of disease
- ALT/serum glutamate pyruvate transaminase (SGPT) - ALT relatively lower than AST in persons with alcoholism
- Albumin - To assess severity of liver injury (HIV infection and malnutrition may confound this.)
- Gamma globulin - Large elevations suggestive of autoimmune hepatitis, other typical increase observed in persons with cirrhosis
- Prothrombin time after vitamin K - To assess severity of liver disease
- Antimitochondrial antibody - To diagnose primary biliary cirrhosis
- ASMA - To diagnose primary sclerosing cholangitis
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