Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 467

Drug‐induced liver injury (DILI) is more common in the elderly due to increased polypharmacy, decreased liver perfusion, and decreased cytochrome p450 function.¹⁸ DILI incidence is 15 cases per 100,000 people, with jaundice occurring in 30% of cases. The diagnosis is challenging as other reasons have to be ruled out, and there are no specific markers or tests for DILI. The https://www.ncbi.nlm.nih.gov website sponsored by the National Institute of Health has descriptions of over 1200 agents that may cause liver injury.

DILI can be subdivided into three categories: direct, idiosyncratic, or indirect. Direct agents such as acetaminophen result in liver injury in a predictable dose‐dependent manner, and the onset of injury is one to five days after administration. Idiosyncratic hepatotoxicity is the result of substances that cause injury only in rare cases in susceptible individuals. This liver injury is further characterized as hepatocellular (increases in transaminases: AST/AST), cholestatic (increase in bilirubin and alkaline phosphatase), and mixed. The differences between these types are made by dividing the alanine aminotransferase level by the alkaline phosphatase level at initial presentation, with both levels expressed as multiples of the upper limit of the normal range. The hepatocellular ratio is >5, mixed level 3–5, and cholestatic level <2. Indirect injury is caused by a medication that exacerbates a pre‐existing liver condition.

When a patient presents with abnormal liver tests or jaundice and other diseases have been ruled out via blood tests, history, and imaging, DILI must be suspected. One needs to know all the medications the patient has taken in the last three months. Then those medications should be looked up in the https://www.ncbi.nlm.nih.gov database online, and the usual reaction of the medication should be compared to the clinical situation. For example, amoxicillin‐clavulanate is a frequent cause of cholestatic or mixed hepatitis and is the most often‐occurring idiosyncratic prescription drug‐induced liver injury. Isoniazid is the second most common idiosyncratic prescription cause of DILI and is hepatocellular hepatitis. INH‐induced hepatitis prevalence increases markedly with age. Herbal and dietary supplements can also cause drug‐induced hepatitis, and in 20% of cases, two or more of these substances are involved.

Once a substance is implicated as resulting in an idiosyncratic liver injury, it should not be reused; substances like acetaminophen, which result in liver injury due to overdosage, can be reused, but the dose of acetaminophen should not exceed 2 g daily in alcoholics or 4 g daily in others.¹⁹