HEPATOTOXICITY INDUCED BY XENOBIOTICS AND TYPING OF THE HUMAN LEUKOCYTE ANTIGEN-HLA
Abstract
INTRODUCTION: Increased reporting of cases of drug-induced liver injuries reflects growing number of new agents introduced into clinical practice in the last decades. Besides, due to technological progress, many new chemicals are coming into contact with humans. Drug-induced liver injuries make persisting and challenging problem for physicians, health agencies and pharmaceutical companies.
RESEARCH OBJECTIVES: The aim of the study was determination of the most common causes of drug-induced liver injury in our surrounding. Relative importance of hepatotoxic action of drugs was compared with that of other noxa in human environment. The link between sensitivity to certain chemicals and hepatotoxicity was investigated. We also examined relative importance of different drugs in the development of hepatotoxicity, regardless the dose.
MATERIALS AND METHODS: We analyzed 52 patients with a diagnosis of hepatotoxic liver injury (medical history, detailed clinical evaluation of patients, histopathological analysis of the liver, abdominal ultra sound, and laboratory determination of standard liver function tests) and followed them up for 12 months. During the period from 01.04.2005 to 01.04.2009, when the patients attended the Institute of Gastroenterology and Hepatology, Clinical Center of Serbia in Belgrade, we monitored liver function tests and morphological findings. We also used biological markers relevant for making differential diagnosis, monitoring the disease progression and response to therapy.
The results of the patients with hepatotoxic liver injury were compared with the values of the findings from 52 patients in the control group, diagnosed with chronic viral hepatitis and hospitalized in the same institution during the same period of time.
RESULTS: The causes of toxic liver damage in our study were the following agents, classified into groups: industrial toxins (8 patients), food and beverages (9 pts), antirrheumatics and analgesics (6 pts), antiarrhythmic drugs (4 pts), antilipemics (4 pts), antibiotics (4 pts), vitamins (3 pts), antihypertensive drugs (3 pts), antiplatelet drugs (2 pts), anticonvulsants (2 pts), drugs for osteoporosis (2 pts), antithyroid drugs (1 pt), oral antidiabetic agents (1 pt), oral contraceptives (1 pt), glucocorticoids (1 pt) and antidepressants (1 pt). We got the results of HLA typing for 29 patients of the 52 patients with hepatotoxic liver injury and for 22 patients of 52 patients with chronic viral hepatitis.
CONCLUSION: This study puts some light on hepatotoxicity, which is not rare in our population. Types of xenobiotics causing liver toxicity in our environment are mainly industrial toxins, as well as foods and beverages, more than drugs. It would be worthwhile examining what ingredients of food are causing hepatotoxicity. It would be very useful to cover wider population with HLA typing in our population, in order to identify the patients at risk for developing hepatotoxicity.