EVALUATION OF HEPATOTOXICITY IN ELDERLY WITH HIV/AIDS USING ISONIAZID

Laboratory


INTRODUCTION
The aging of the population becomes notorious from the 20th century, reaching several countries of the world, so epidemiological data show that individuals easily exceeded 60 years of age in the 21st century (WHO, 2015) Physiological changes due to aging increase the incidence and prevalence of noninfectious diseases in this population such as hypertension, diabetes, arthritis, osteoporosis. There is also the occurrence of infectious diseases such as AIDS and Tuberculosis. (RIBAS, 2014) The comorbidities mentioned have a negative impact on the elderly because pharmacological interventions are needed as the main treatment. (RIBAS, 2014) Acquired immunodeficiency syndrome (AIDS) emerged as one of the main epidemics of infectious diseases of the 20th century (BIGGAR, 1984;COOK, 2011). AIDS, caused by HIV infection, is the result of damage mainly to cell-mediated immunity, although there is also impairment of humoral immunity. (BARASA, 2011;MOIR, 2011) Data from the 2019 Epidemiological Bulletin of the Ministry of Health report an increase in the incidence of AIDS among elderly males in the period 2008 to 2018 of 9.7% and a 5% reduction among women in the same period. (BRASIL, 2019)  The impairment of the immune system favors the emergence of diseases considered opportunistic caused by viruses, fungi and bacteria in patients living with HIV/AIDS and Tuberculosis is the leading cause of death among individuals with AIDS (El-SADR, 2008;STERLING, 2010;JONG, 2004) In relation to Tuberculosis (TB), this is an important clinically important pathology, being a chronic, infectious and contagious disease, caused by Mycobacterium tuberculosis (Mtb), which can reach all age groups, but 85% of TB cases occur in adults. (SILVA, 2004).
One of the measures to prevent TB/HIV co-infection in young and elderly adults, according to the World Health Organization, is preventive treatment with isoniazid medication that aims to reduce the risk of illness by Mtb and consequently the manifestation of TB. (CONDE, 2009;HORSBURGH, 2011;DUARTE, 2007).
In Brazil, in order to reduce the risk of TB in patients living with HIV/AIDS, the Ministry of Health recommends Preventive Therapy with Isoniazid (PTI) at a dose of 5 to 10 mg / kg / day of weight up to 300mg for 6 consecutive months for treatment (CONDE, 2009) Adverse Reaction to the Medicine is defined as "any harmful or unwanted effect that occurs after the administration of the drug, in doses normally used in men for prophylaxis, diagnosis or treatment of a disease. (WHO, 2002) Regarding the use of isoniazid, hepatotoxicity, is a potentially serious adverse reaction that can result even in death if the drug is not withdrawn soon after the development of hepatitis symptoms. (COUNT, 2009;COHN, 2000;LOBUE, 2003) Hepatotoxicity can be evaluated with asymptomatic elevation of liver enzymes such as AST (aspartate aminotransferase), ALT (alanine aminotransferase) and GGT (gammaglutamyltransferase). (CHURCHYARD, 2007;LOBUE, 2003) With the increased incidence of HIV/AIDS in the elderly population and the risk of tuberculosis, the need for an effective assessment of the risk of hepatotoxicity in the elderly in preventive treatment with isoniazid to elderly patients living with HIV/AIDS is justified. (SILVA, 2004;LEUNG, 2011) The pharmaceutical professional can collaborate through his technical knowledge in the assessment of the risk of hepatotoxicity as the main adverse reaction present in  Since a study was conducted based on secondary data, there was no need to apply a Free and Informed Consent Form to patients.
HIV/AIDS patients aged 60 years or older using PTI at a dose of 5 to 10 mg/kg/day of weight up to 300mg for up to 6 months were considered eligible for the study.
The statistical analyses were performed in the statistical program SPSS -Statistics, version 20, presented the descriptive analyses of the variables of interest in the form of measures of central tendency (mean, median, standard deviation, minimum and maximum) and proportions. The analysis of the association between the laboratory values of liver markers before and concomitant with the use of isoniazid was performed using the paired t-test with 95% CI, being considered with statistical significance p ≤ 0.05%.

RESULTS
We analyzed 12 patients with a minimum age of 60 years and a maximum of 74 years, of whom 75% (9) were men (mean age of 63 years) and 25% (3)   There was an increase in laboratory results concomitant with the use of PTI in 20.9% of AST enzymes and 11.5% of GGT in relation to pre-treatment values.
On average, the AST result concomitant with the ICC (M =31.0 U/L) was higher than the pre-PTI result (24.5 U/L) with p = 0.02.

DISCUSSION
The elderly population increases in the world. (WHO, 2015). In the present study, only 2 female patients were 70 years of age or older. It is important to highlight that when aging there is also an increase in chronic diseases with greater use of medications to control these conditions (RIBAS, 2014

FINAL CONSIDERATIONS
Hepatotoxicity related to the use of isoniazid was present in elderly patients on preventive therapy confirming the theory related to this drug. However, there was no suspension of treatment, however, in view of the use of polypharmacy, it is necessary to follow the patient by the multidisciplinary team including the clinical pharmacist in the prevention of liver complications.