4. Probability and causality assessment of drug-induced hepatotoxicity: scales and proposals

patient habits), it is possible for pharmacist to carry out prevention activities and promote the proper use of medications, decreasing deleterious effects on health of patient. Besides, feedback

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Identification of liver toxicity is difficult, because it has no specific manifestations; however, having in mind, this health problem may contribute to a fast clinical response. The next actions

• In the blood samples, analyze if an alteration of liver tests is present: increase in alanine aminotransferase more than three times and/or increase in alkaline phosphatase more

• Ask treating physician or nurse about pathological antecedents like acute coronary syndrome, autoimmune diseases, previous or underlying liver disease or liver tumors, viral hepatitis, alcohol or substances abuse and blood transfusion, to rule out other causes of

• Interview the patient or companion and ask about symptoms like abdominal pain, fever, nausea, vomiting, jaundice, dark urine, pale stools, asthenia, loss of weight or appetite; risk factors such as concomitant administration of drugs or herbal remedies, alcohol consumption, pregnancy or tattoos, use of medications at home and self-medication. Besides, it is important to know about the suspected drug, the beginning or cessation

• To know about the drugs used by the patient; it is recommended to search about adverse

• Use a causality assessment of drug-induced liver injury scale like RUCAM, to define the

To prevent death or harmful effects, it is necessary to suspend the hepatotoxic drug, monitoring liver test and use other medications such as N-acetylcysteine or corticosteroids (prednisone, prednisolone and betamethasone) to improve the status of patient health [36]. Also, it is important to educate patient in proper use of drugs to prevent the occurrence of hepatotoxicity.

Many drugs are hepatotoxic agents, most of these drugs generate idiosyncratic reactions and cause hepatocellular damage in a wide range of patients in different age groups; and moreover, concomitant medications may deteriorate the clinical features of patients. Elevation of liver enzymes, fever and jaundice are common signs and symptoms, with identification and

On the other hand, it is important to have in mind that some patients are asymptomatic and the liver injury identification is based only on the elevation of liver enzymes; therefore, monitoring of liver tests is important to prevent serious effects. In addition, knowing the risk factors

in the interdisciplinary group may optimize the reaction time in a liver injury case.

may help to identify drug-induced liver toxicity:

than two times the upper limit of normal.

reactions in published information.

7. Comments and conclusions

causing agent, as propose in Diagram 1.

time, dose, frequency of use and route of administration.

suspension of offending drug, patients present an adequate evolution.

and habits of patient can improve the response time in a possible case.

liver test alterations.

To solve the difficulty of identification of hepatotoxicity and to try to estimate the probability that a therapeutic agent is associated with a hepatic injury, clinical scales have been developed; these assess aspects such as absence or presence of confounding factors, temporal relation of hepatotoxicity with drug consumption, coexistence of risk factors, previous description in the literature, exclusion of other causes and effects of readministration of the drug. According to the score obtained, a range of causal probability is established.

In this sense, there are scales, such as the Roussel Uclaf Causality Assessment Method scale (RUCAM) and the Clinical Diagnostic Scale (M&V CDS), considering that the RUCAM scale is more appropriate than M&V CDS [12], besides, facilitates to distinguish when patient is using concomitants drugs. However, despite their theoretical utility and being validated, these scales are hardly used in clinical practice [22]. To promote its use, it is advisable to have knowledge of the possible agents associated with hepatotoxicity and to reduce subjectivity bias at the time of its application.
