Volume 1, Issue 2, June-2018: 1-4

International Journal of Current Innovations in Advanced Research ISSN: 2636-6282

Plasma Liver Enzymes Status in Sudanese Rheumatic

Arthritis Patients Treated With Methotrexate
Nada Yousif Awad Alla Hassan1, Maissa. K. Albagir2 and Nassr
Eldin M.A. Shrif3*
1
Department of Clinical chemistry- Faculty of Medical Laboratory Sciences-
Alneelain University–Sudan
2
Department OF Clinical chemistry- Faculty of Medical Laboratory Sciences-
Alzaeim Alazhary University–Sudan
3
Department OF Clinical Chemistry- Faculty of Medical Laboratory Sciences-
Alzaeim Alazhary University–Sudan.
Corresponding author E-mail: aboamr124@hotmail.com

Abstract
Background: Methotrexate, a drug used for rheumatic arthritis treatment is suspected to has
hepatotoxicity.
Objectives: This study aimed to assess liver enzymes activity in plasma as indicator of MTX
hepatotoxicity in RA Sudanese patients.
Methodology: It is a Descriptive cross sectional study, conducted in Khartoum state from
January to September 2016 in RA patients treated with MTX, the plasma AST, ALT and
ALP activities were measured in study groups. Then, the Generated data analyzed using the
statistical package (SPSS).
Result: Plasma AST, ALT activities were higher in MTX treated group than healthy group.
Plasma ALP activity was not significantly differ between the study groups.
Conclusion: MTX increases plasma AST and ALT activity in RA patients, but it has no
effect on plasma ALP.
Keywords: Methotrexate (MTX), Rheumatoid arthritis (RA), Aspartate transaminase (AST),
Alanine transaminase (ALT), Alkaline phosphatase (ALP).

Citation: Nada Yousif Awad Alla Hassan, Maissa. K. Albagir and Nassr Eldin M.A. Shrif,
2018. Plasma Liver Enzymes Status in Sudanese Rheumatic arthritis Patients Treated with
Methotrexate. International Journal of Current Innovations in Advanced Research, 1(2): 1-4.
Copyright: This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited. Copyright©2018; Nada
Yousif Awad Alla Hassan, Maissa. K. Albagir and Nassr Eldin M.A. Shrif.

Introduction
Rheumatoid Arthritis is an autoimmune disease that occurs when the immune system starts
attacking the body causing inflammation in joint due to effects on bone and cartilage (Pablos
and Canete, 2013). RA attracts between 0.5 and 1% of adult in the developed world and
about 50 per 100,000 people newly developing the condition each year (Smolen et al.,
2016).There are different drugs used in the treatment of RA (Lopez–Olive ma, 2014;
Cronstein, 2005; Solomon, 2014) methotrexate (MTX) is sometimes a choice therapy for
treatment of RA (Visser et al., 2009). Concerning liver, MTX- has been proposed to induced
hepatotoxicity mechanisms including cellular antioxidant defense deregulation which cause
more oxidative stress-induced damages to the liver cells (Ali et al., 2014). Liver Cirrhosis

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International Journal of Current Innovations in Advanced Research ISSN: 2636-6282
and fibrosis occur more than twice as frequently in patients receiving daily MTX therapy
when compared with those receiving intermittent dosing (Lewis and Schiff, 1988). MTX is
indirectly involved in liver mitochondria damage via depletion of mitochondria enzymatic
and non-enzymatic antioxidants machinery (Kolli et al., 2013). Several histopathology and
serology markers have been previously used to investigate MTX-induced liver toxicity,
including increased relative fatty acid changes in hepatocytes and sinusoidal lining cells,
necrosis, inflammation (Tian and Cronstein, 2007). An experimental Study Showed
prominent pathological changes in the liver tissue of MTX-treated animals including
inflammatory cells infiltration, severe centrilobular/intermediate zone/periportal
degeneration, bile duct hyperplasia, hyperemia and necrosis (Adel Rezaei Moghadam et al.,
2015) and severe histopathological changes that prominent around dilation and congestion of
central vein (cv) and portal vein (Adel Rezaei Moghadam et al., 2015). Liver enzymes are
present in liver cell and are spilled out in to the blood stream when there is an injury to the
liver the most common liver enzymes that are released ALT and AST (Ramaiah, 2007). So
this study measure the plasma levels of these enzymes as indicator of liver deterioration in
patients under MXT treatment.

Materials and Methods

This is a qualitative descriptive cross sectional study done in Khartoum state from January to
September 2016. Fifty rheumatoid patients under treatment with methotrexate were enrolled
in the study and matched with healthy control group. After formal consent, 5ml of blood was
collected in lithium heparin container to measure AST, ALT and ALP activities. Biosystem
Kits were used to measure these enzymes. Generated data was analyzed using the statistical
package (SPSS).

Results
The study includes 50 RA patients treated with MTX and 50 gender and age matched healthy
individuals. The characteristic of RA individuals is presented in Table 1. Plasma ALT and
AST were significantly higher in rheumatoid patients treatment by methotrexate when
compared to the control group. But plasma ALK shows no significant differences between
patients and the control group (Table 2).

Table 1. Base line characteristic of Rheumatoid Arthritis patients

Age -year 15-20y 20-30y 30-50y 50-70y
Male - 1 5 4
Female 2 4 13 21
Total 2 5 18 25

Table 2. Comparison of liver enzymes means

Parameter Case(M±SD) Control(M±SD) P. Value
AST 20.1±14.3 9.36±6.8 0.00
ALT 17.68±11.79 13.6±8.23 0.049
ALP 84.5± 28.3 83.0± 22.0 0.08

Discussion
Methotrexate is indirectly involved in liver mitochondria damage via depletion of
mitochondria enzymatic and non-enzymatic antioxidants machinery (Kolli et al., 2013) and it
is known that in the liver, alt is localized solely in the cellular cytoplasm, whereas AST is
both cytosolic (20% of total activity) and mitochondrial (80% of total activity), AST is a
mitochondrial enzyme (Rej, 1989). In this study there is significant difference in AST and
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International Journal of Current Innovations in Advanced Research ISSN: 2636-6282
ALT between patient treated with MTX and control group (p<0.001) (Table 2), this is agree
with some studies that reported that several changes of ALT and AST lead to liver problem
(Cohen et al., 2001; Zimmerman, 1999). Cholestasis enhances the synthesis and release of
ALP, and accumulating bile salts increase its release from the cell surface (Moss, 1997) and
drug-induced liver injury may present with a cholestatic pattern, preferential increase in ALP
although the degree of ALP alteration is variable (Velayudham and Farrell, 2003). But in this
study there is no significant difference in ALP between patient treated with MTX and control
group (p>0.05) (Table 2) which suggest that MTX hepatotoxicity is not cholestatic pattern
but this disagree with study done by Adel Rezaei Moghadam et al., (2015) and this disagree
may due to difference in the study design and population.

Conclusion
MTX increase plasma AST and ALT activity in RA patients, but it has no effect on plasma
ALP so it is preferred to measure plasma liver enzymes activities as monitor of MXT hepatic
side effects.

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