Evaluation of liver function tests to identify hepatotoxicity in patients with acute lymphoblastic leukemia who receive chemotherapy induction


Study area and design

The study was conducted at the Black Lion Hospital in Addis Ababa, Ethiopia. Black Lion Specialty Hospital is affiliated with Addis Ababa University. It is the largest tertiary hospital in the country. From July 1 to September 30, 2019, a cohort study was conducted to assess chemotherapy-induced hepatotoxicity in patients with acute lymphoblastic leukemia.

Patient information

Patients older than 1 year who were diagnosed with acute lymphoblastic leukemia at Black Lion Hospital between July 1 and September 30, 2019 were included. The same study group is divided into three groups based on the dosages of the induction chemotherapy drugs. These were the Baseline Study Group, the Second Week Induction Study Group, and the Fourth Week Induction Study Group.

Eligible criteria

Patients have been hospitalized for at least one month and have not yet started induction therapy.

Variables and operational definition

Dependent variables: Hepatotoxicity.

Independent variables: age, sex, alcohol consumption, weight, blood transfusion and chemotherapy induction drugs.

Induction protocol: all patients were treated according to the modified Berlin-Frankfurt-Munster 95 dosing regimen in phase A of induction chemotherapy27 (Table 1).

Table 1 Modified Berlin-Frankfurt-Munster 95 dosage regimen in phase A of induction chemotherapy.

Children are defined as those under the age of 1828.

Hepatotoxicity is defined as one of the following: ALT levels greater than or equal to a five-fold increase from baseline, or ALT levels greater than or equal to a three-fold increase, with an increase simultaneous bilirubin concentration greater than twice the reference value (Table 2)29.

Table 2 Drug-induced liver injury index29.


Liver function tests of the same groups were performed three times a month at baseline, the second week after induction, and the fourth week after induction.

Sample size and sampling method

Each of the three measures included 40 patients, totaling 120. Purposive sampling was used to select study participants.

Data Collection and Blood Sampling Procedures

Data gathering

During the data collection period, all participants who were willing to receive induction of chemotherapy were included without discrimination. Informed consent was obtained from each study participant after a brief explanation of the purpose of the study. Baseline information was collected through structured interview questionnaires. Then, serum blood samples were taken.

Collection and processing of blood sample data

Blood samples were collected from participants in 5 ml serum separator tubes once before induction and twice after induction of chemotherapy during the 2nd and 4th weeks. After holding the tube for 20 min to clot, the specimen was centrifuged at 1500 rpm for 5 min, and the serum was separated and stored at 40° until testing. Liver function tests were performed on serum at the Ethiopian Institute of Public Health.

Test analysis

The principle of a spectrophotometer was analyzing the liver function test to measure the analyst’s absorption spectrum at each wavelength. A Roche-COBAS Integra® 400 automated chemistry analyzer was used. All tests were performed according to the manufacturer’s protocol.

Data quality assurance

There was a fair procedure for selecting study participants and measuring results.

Data analysis

Data were entered into a database sheet in SPSS version 23. The Shapiro-Wilk test showed that the distributions of all liver function tests were biased. Accordingly, a log 10 transformation was calculated. The mean and standard deviation were calculated using a log 10 transform. The mean and standard deviations (SD) were then back-transformed. A mixed ANOVA model is used to examine the relationship between the independent factors and the times (baseline, second week of induction and fourth week of induction). Greenhouse–Geisser was applied when the sphericity assumption was violated. A Bonferroni post hoc test was performed when the F test was significant. If there is an interaction between the independent variables and the dependent variable, a splitting method was used to determine in which group the association occurred. p a value

Ethical consideration

Ethical clearance was obtained from the Ethics Review Board (ERB), College of Health Sciences, Addis Ababa University. All methods were performed in accordance with current guidelines and regulations. No one was injured as a result of their participation in this study. After a brief explanation of the purpose of the study, informed consent was obtained from adults and the child’s guardian. In addition to the informed consent of the parents, the informed assent of the child was obtained as far as the capacity of the child. The right of participants to withdraw at any time has been respected. By eliminating identifiers from questionnaires, confidentiality was preserved.


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