(1)
Departments of Internal Medicine & Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Hepatitis is inflammation of the liver and detected usually by abnormal labs. Though liver function tests (LFTs) are a commonly used term for all tests related to the liver, some tests measure liver function and some measure biochemical health. Abnormalities in liver biochemistry do not necessarily reflect a defect in function.
Pathology
Liver disease can be broadly classified into hepatocellular injury and cholestatic disease that results from biliary disease or obstruction. The following tests are typically performed in labs as a test of liver health.
Lab tests to measure liver health
Test | Significance/cause of abnormality |
---|---|
Alanine aminotransferase (ALT) | Hepatic cell inflammation |
Aspartate aminotransferase (AST) | Hepatic cell inflammation |
Alkaline phosphatase (AP) | Mainly cholestasis from biliary obstruction; hepatic injury |
Gamma glutamyl transpeptidase (GGT) | Cholestasis from biliary obstruction |
Serum bilirubin | Both liver and biliary disease; hemolysis |
Serum albumin | Liver synthetic function abnormality; kidney disease; malnutrition |
Prothrombin test | Liver synthetic function; other bleeding and clotting disorders |
Etiology
The most common causes for elevation in liver enzymes are listed as follows. Medications can cause both hepatocellular and cholestatic injury. Many medications can cause mild to modest hepatitis but only a few cause frank liver failure. A notable example is acetaminophen at high doses.
Most common causes of hepatic disease
Viral hepatitis |
Alcoholic liver disease |
Nonalcoholic fatty liver disease |
Medication reaction |
Other less common disease processes causing liver dysfunction include hemochromatosis (disorder of iron storage), Wilson disease (impaired cellular copper transport), autoimmune disease, alpha-1-antitrypsin deficiency (extra-pulmonary manifestation), and thyroid disorders. Some causes of biliary disease are Gilbert syndrome, hemolytic anemias , primary biliary cirrhosis, primary sclerosing chlolangitis, and other causes of bile duct obstruction.
Psychotropic Medications and Hepatitis
Psychotropic medications usually act by injury to hepatic cells though a cholestatic mechanism is implicated with some medications. The mechanism is metabolic or immune mediated. Some medications cause liver abnormalities by causing weight gain and subsequent fatty liver disease . Two psychotropic medications commonly known to cause liver injury are valproate (microvesicular steatosis is seen in liver cells) and carbamazepine (the liver toxicity appears to be part of a systemic hypersensitivity syndrome).
Psychotropic medications usually cause hepatic cell injury via a metabolic process or immune-mediated reaction; a cholestatic injury is less commonly implicated.
Generally, the liver enzymes (usually transaminases ) rise in the first 3–6 months of treatment. Mild hepatitis is seen in up to 30% patients on antipsychotics [1, 2]. Clinically significant elevations that require the medication to be discontinued occur in less than 5% cases. The prevalence of transaminase elevation with antidepressants, including clinically significant elevations, is less than 3% [3].
Naltrexone is generally safe to use in patients with preexisting liver disease. Though some studies suggest rise in transaminases up to 50%, clinically significant elevation occurs only in 1% patients [4].
Clinically significant elevation is considered rise of transaminases to at least more than two times normal or presence of clinical symptoms. Liver enzymes generally return to normal when the medication is stopped. Even when medication is continued, the enzyme abnormality has been reported to resolve in approximately 50% cases of antipsychotics [1]. Age and polypharmacy are risk factors to develop hepatic injury. Preexisting liver disease may predispose to developing hepatitis though evidence is unclear on this. Liver injury is generally considered to be independent of medication dose .
Rise in transaminases usually occurs in first 3–6 months of treatment and can occur even at low doses; elevation that is more than two times normal is considered clinically significant.