INTRODUCTION:

Gaucher disease (GD) is an autosomal recessive hereditary illness. The Ashkenazi Jewish community is the most affected¹. The absence of the enzyme glucocerebrosidase (also known as acid β -glucosidase) causes the most prevalent lysosomal storage disorder.

This enzyme cleaves the β-glucosidic bond of glucosylceramide to generate ceramide and glucose, with the latter being degraded to sphingosine and fatty acid by lysosomal acid ceramidase².

The mononuclear phagocyte system, particularly histiocytes in the lymph nodes, spleen, and bone marrow; osteoclasts; Kupffer cells; gastrointestinal tract; genitourinary tract; microglia; alveolar macrophages are the most affected cells in which the glucocerebrosides are accumulated as a result of impaired β-glucocerebrosidase function³. As consequences, Gaucher cells (lipid-loaded macrophages) were found in almost every organ, but particularly in liver, spleen, and bone marrow. Glucosylceramide levels were found to be higher in the plasma of GD patients, indicating that it is transported as a component of the lipoprotein complexes⁴.

Gaucher disease has a wide range of clinical symptoms. Three distinct phenotypic variations of GD are typically differentiated based on the incidence and age of onset of neurological symptoms:

Depending on the clinical signs/symptoms, the phenotype has been classified into three major types. The most prevalent type of GD, type 1, is characterized by abdominal discomfort and/or enlargement owing to hepatosplenomegaly, as well as a combination of anemia, leukocytopenia, and thrombocytopenia as clinical symptoms. Liver is the most important organ, which plays a pivotal role in regulating various physiological processes in the body. It is involved in several vital functions, such as metabolism, secretion and storage. It has great capacity to detoxicate toxic substances and synthesize useful principles⁵. Liver damage is always associated with cellular necrosis with an increase in the serum levels of many biochemical markers like SGOT, SGPT, triglycerides, cholesterol, bilirubin, alkaline phosphatase^6-8. Prothrombin time and partial thromboplastin time may be prolonged due to decreased hepatic function with an increase in the activity of liver enzyme that may be accompanied by an impaired other liver functions such as protein synthesis and bilirubin excretion⁹.

The mainstay of treatment for Gaucher disease, which was the first effectively treated lipid storage illness, is enzyme replacement therapy with recombinant glucocerebrosidase. Oral enzyme replacement and/or gene therapy therapies may be used in the future¹⁰. In the current study, the levels of AST, ALT, total protein and total bilirubin were determined in an attempt to assess their role in monitoring the liver function improvement in children receiving ERT for the treatment of Gaucher disease.

MATERIALS AND METHODS:

A case-control study was performed on 67 children (girls and boys) with GD who were recruited from the Children Welfare Hospital Consultation Clinic, the Gastroenterology and Hepatology Teaching Hospital, and the Central Child's Teaching Hospital.

The levels of ALT, AST, total bilirubin and total protein were measured calorimetrically in the samples of 67 Gaucher patients who were categorized as:

· Group I: newly diagnosed un treated children (n=9)

· Group II: children receiving ERT for 3-6 months (n=18)

· Group III: children receiving ERT for 6-12 months (n=20)

· Group IV: children receiving ERT for more than one year (n=20)

These groups were compared with twenty comparable age-matched control subjects (Group V). A Control group with exclusion criteria that include patients with chronic infections, those suspected to have tuberculosis (TB) and patients with chronic inflammatory conditions as chronic arthritis in addition to other factors that affect enzyme activity such as:

1- Fungal infection e.g. Candida albicans

2- Parasitic infection e.g. Malaria

3- Blood disorder e.g. β-thalassemia

4- Asthma

5- Other inherited disease e.g. Niemann-Pick Disease

The study's practical requirement was performed at research laboratories in the College of Pharmacy, Al-Maaql University and the Department of Pharmacy, Al-Turath University College during the period from December 2020 to March 2021.

RESULTS:

Some anthropometric characteristics of the studied groups were summarized in table 1 which showed that the incidence of Gaucher disease in male children was non-significantly (p>0.05) lower than that of female children in all studied groups. The age and sex in male children were non-significantly differ from that of female in all studied groups showed. ANOVA test revealed that there were non-significant differences in age (p=0.51) and weight (p=0.66) among the studied groups.

As demonstrated in table (2):

1. Children with Gaucher disease showed a significantly (p<0.05) lower levels of Total protein (6.29±0.73) in comparison with control (6.81±0.32).

2. Non-significant differences were obtained in the levels of ALT, AST, and total bilirubin.

Table (1): Anthropometric characteristics of the Gaucher children and controls.

	Group V	Whole Gaucher patients	Group I	Group II	Group III	Group IV
N	20	67	9	18	20	20
Male (n, %)	9 (45%)	31(46.3%)	4 (44.4%)	8 (44.4%)	9 (45%)	10 (50%)
Female (n, %)	11(55%)	36(53.7%)	5 (55.6%)	10 (55.6%)	11(55%)	10 (50%)
OR		1.05	0.98	0.98	1	1.22
95% CI		0.39 -2.87	0.20- 4.76	0.27- 3.52	0.29- 3.48	0.35- 4.24
P-value		0.92	0.98	0.98	1	0.75
Age	5.3±2.34	5.3±2.94	4.11±2.76	4.97± 3.62	5.3± 2.72	6.13± 2.49
P-value with control		0.74	0.24	0.6	0.79	0.52
Weight	19.93± 8.61	18.61± 7.55	15.49± 6.12	18.46± 10.34	18.86± 7.37	19.91± 5.06
P-value with control		0.51	0.18	0.64	0.68	0.99

OR: Odd Ratio, CI: confidence interval.

Table (2) Levels ALT, AST, Total Bilirubin (TB) and Total Protein (TP) in Gaucher children against controls using independent t-test

P value	Patients N=67 Mean ±SD	Control N=20 Mean ±SD	Parameter
0.144	49.16 ± 7.54	24.2 ± 4.56	ALT (IU/L)
0.131	49.08 ± 5.32	30.85 ± 4.39	AST (IU/L)
0.146	0.39 ± 0.20	0.31 ± 0.14	TB (mg/dl)
0.003*	6.29 ± 0.73	6.81 ± 0.32	TP (g/dl)

ALT levels were significantly (p< 0.05) higher in newly diagnosed patients and children received ERT for 3-6 and 6-12 months (186.14±14.97, 27.22±4.54 and 29.6±4.99, respectively) in comparison with control (24.2±4.56), while children received ERT for more than one year (26.84±3.97) showed non-significant differences from that of control as described in table (3.7) and figure 3.10. Moreover, significant decrease in ALT levels were shown in newly diagnosed children in comparison with children received ERT for 3-6, 6-12 months and more than one year. On the other hand, table (3.7) revealed that there were non-significant differences in ALT levels in children received ERT for 6-12 months in comparison with children received ERT for 3-6 months and also in children received ERT for more than one year in comparison with children received ERT for 3-6 and 6-12 months.

In a manner differing from that of ALT, table (3) and figure (1) reveled that AST levels were significantly (p< 0.05) higher in newly diagnosed patients (186.14± 14.97) in comparison with control (24.2±4.56), while children received ERT for 3-6, 6-12 months and for more than one year showed a non-significant differences (p>0.05) from that of control. Non-significant differences were also obtained between children received ERT for 3-6 and 6-12 months and also between children received ERT for 6-12 months treatment and patient receiving treatment for more than one year.

Figure (1): Histogram showing the ALT (GPT) and AST (GOT) levels of control and Gaucher patient subgroups.

Levels of total Bilirubin in newly diagnosed untreated patients (0.53±0.036) and children received ERT for 3-6 months (0.45±0.156) were significantly higher than that of controls (0.31±0.14) as illustrated in table (3.8) and figure 3.12, while children received ERT for 6-12 months (0.32±0.15) and for more than one year (0.34±0.11) showed a non-significant differences from that of control. Additionally, non-significant differences were obtained between newly diagnosed patients and children received ERT for 6-12 months and for more than one year while a significant decrease in total bilirubin levels in children received ERT for more than one year was obtained in comparison with newly diagnosed untreated patients.

As demonstrated in table (4), Total Protein showed significantly lower levels (p< 0.05) in newly diagnosed untreated patients and children received ERT for 3-6 and 6-12 months (5.65±0.64, 6.06±0.77 and 6.54±0.44, respectively) in comparison with control (6.81±0.32), while children received ERT for more than one year (6.52±0.78) showed non-significant differences (p>0.05) from that of control. Moreover, non-significant differences also obtained

Table (3): Comparison of ALT and AST levels among all studied groups using independent t-test

Parameter

Group

Mean ±SD

P-values

P^a

P^b

P^c

P^f

P^g

P^h

Pⁱ

P^j

ALT (IU/l)

Group V n = 20

24.2 ± 4.56

<0.001

0.048

0.001

0.059

<0.001

0.14

0.78

0.06

Group I n = 9

186.14±14.97

Group II n = 18

27.22 ± 4.54

Group III n = 20

29.6±4.99

Group IV n = 20

26.84± 3.97

AST (IU/l)

Group V n = 20

30.85 ± 4.39

<0.001

0.73

0.071

0.082

<0.001

0.21

0.25

0.85

Group I n = 9

154.89±29.99

Group II n = 18

31.39± 5.32

Group III n = 20

33.35± 4.12

Group IV n = 20

33.11± 3.57

Group V n = 20

192.11±57.13

P^a: Newly diagnosed children vs control.

P^b: Children receiving treatment for 3-5 months vs control

P^c: Children receiving treatment for 6-12 months vs control

P^d: Children receiving treatment for >1 year vs control.

P^e: Newly diagnosed children vs children receiving treatment for 3-5 months

P^f: Newly diagnosed children vs children receiving treatment for 6-12 months

P^g: Newly diagnosed children vs children receiving treatment for >1 year

P^h : Children receiving treatment for 3-5 months vs those receiving treatment for 6-12 months

Pⁱ Children receiving treatment for 3-5 months vs those receiving treatment for >1 year

P^j Children receiving treatment for 6-12 months vs those receiving treatment for >1 year

Interestingly, significant increase in total protein levels was shown in children received ERT for 6-12 months treatment in comparison with newly diagnosed patents. In addition to all previous data, table (4) also demonstrated a non-significant difference in the level of total protein between patients receiving the treatment for 6-12 months and those who receive the treatment for more than one year.

Table (4): Comparison of Total protein (TP) and Total bilirubin (TB) levels among all studied groups using independent t-test

Parameter

Group

Mean ±SD

P^b

P^c

P^d

P^e

P^f

P^g

P^h

Pⁱ

P^j

TB (mg/dl)

Group Vn = 20

0.31 ± 0.14

0.03

0.007

0.97

0.67

0.45

0.032

0.035

0.01

0.65

Group In = 9

0.53 ±0.036

Group IIn = 18

0.45±0.156

Group IIIn = 20

0.32±0.15

Group IVn = 20

0.34±0.11

TP (g/dl)

Group Vn = 20

6.81 ± 0.32

<0.001

0.04

0.136

0.18

<0.001

0.007

0.022

0.08

0.89

Group In = 9

5.65±0.64

Group IIn = 18

6.06 ±0.77

Group IIIn = 20

6.54± 0.44

Group IVn = 20

6.52±0.78

P^a: Newly diagnosed children vs control.

P^b: Children receiving treatment for 3-5 months vs control

P^c: Children receiving treatment for 6-12 months vs control

P^d: Children receiving treatment for >1 year vs control.

P^e: Newly diagnosed children vs children receiving treatment for 3-5 months

P^f: Newly diagnosed children vs children receiving treatment for 6-12 months

P^g: Newly diagnosed children vs children receiving treatment for >1 year

P^h : Children receiving treatment for 3-5 months vs those receiving treatment for 6-12 months

Pⁱ Children receiving treatment for 3-5 months vs those receiving treatment for >1 year

P^j Children receiving treatment for 6-12 months vs those receiving treatment for >1 year

Table (5): Comparison of ALT, AST, Total protein (TP) and Total bilirubin (TB) levels among all studied groups using Analysis of variance (ANOVA) test

	Group IV n = 20 Mean ±SD	Group III n = 20 Mean ±SD	Group II n = 18 Mean ±SD	Group I n = 9 Mean ±SD	Group V N=20 Mean ±SD	Parameters
<0.001	26.84± 3.97	29.6±4.99	27.22 ± 4.54	186.14± 14.97	24.2 ± 4.56	ALT (IU/L)
<0.001	33.11± 3.57	33.35±4.12	31.39 ± 5.32	154.89 ± 29.99	30.85 ± 4.39	AST (IU/L)
0.01	0.34±0.11	0.32±0.15	0.45±0.156	0.53 ±0.036	0.31 ± 0.14	TB (mg/dl)
0.003	6.52±0.78	6.54± 0.44	6.06 ±0.77	5.65±0.64	6.81 ± 0.32	TP (g/dl)

As revealed in table (5), the levels of ALT, AST and total bilirubin showed significant decrease with the treatment which is obviously obtained from the significant P value (p<0.05) obtained by ANOVA test for all patient subgroups. In contrary, a significant increase in the levels of total protein with treatment as shown in table (5) which revealed their levels was increased in parallel with the duration of receiving treatment.

According to the results demonstrated in table (6), In whole Gaucher patients there were many positive and negative significant correlations but the most important correlations were the correlations of the studied parameters with the duration of ERT administration as reveled by the negative significant correlations between ALT, AST and total bilirubin with the duration of ERT administration while total protein showed a significant positive correlation with the duration of ERT administration.

Table (6): The association of ALT, AST, Total protein (TP) and Total bilirubin (TB) levels with the duration of receiving ERT by Pearson's correlation coefficient

Parameter		Duration of treatment with ERT
ALT (IU/L)	R	- 0.490
ALT (IU/L)	P	< 0.001
AST (IU/L)	R	- 0.526
AST (IU/L)	P	< 0.001
TB (mg/dl)	R	- 0.359
TB (mg/dl)	P	0.003
TP (g/dl)	R	0.402
TP (g/dl)	P	0.001

As demonstrated in table (7), levels of ALT, AST and total protein, exhibited high AUC values (1, 1 and 0.961 respectively) with high values of accuracy presented as specificity (100%, 100% and 89% respectively) and sensitivity (100%, 100%, and 90% respectively) in newly diagnosed untreated Gaucher patients comparing with healthy control children.

Table (7): ROC curve results of ALT, AST, Total protein (TP) and Total bilirubin (TB) in newly diagnosed patients in comparison with controls.

Parameters	AUC	Sensitivity (%)	Specificity (%)	Cut-off value
ALT	1.00	100	100	38.5
AST	1.00	100	100	40
TB	0.669	88.9	45	0.275
TP	0.961	90	89	6.41

As shown in table (8), levels of ALT and AST exhibited high AUC values (1 and 0.994 respectively) with high values of accuracy presented as specificity (100% and 94.4% respectively) and sensitivity (100%) in newly diagnosed untreated Gaucher patients comparing with children received ERT for 3-6 months.

Table (8) ROC curve results of ALT, AST, Total protein (TP) and Total bilirubin (TB) in newly diagnosed patients in comparison with children received ERT for 3-6 months.

Parameters	AUC	Sensitivity (%)	Specificity	Cut-off value
ALT	1	100	100	41
AST	0.994	100	94.4	40.5
Total Bilirubin	0.537	61.1	66.6	0.415
Total Protein	0.676	77.8	55.6	5.65

DISCUSSION:

The liver has an enormous task of maintaining the body’s metabolic homeostasis. This includes, the processing of dietary amino acids, carbohydrates, lipids, and vitamins; synthesis of serum proteins; and detoxification and excretion into bile of endogenous waste products and pollutant xenobiotics¹¹. Modifications in SGOT and SGPT values are conveyed in hepatic disease or impairment. SGOT, SGPT and bilirubin are the bio-markers for liver functions^12,13. In the current study, the liver involvements were monitored by assessing the liver enzymes such as Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) and in addition to total bilirubin and total protein. All these tests used as monitoring tests for the assessment of liver synthetic function, execratory functions and the integrity of hepatocytes^14-17.

Table (2) showed that the level of total protein was significantly lower than that of control. On the other hand, the levels of other tests were non-significantly differing from that of control. The comparison was between the whole GD patients including the newly diagnosed patients and children received ERT with different durations ranging from 3 months to more than one year and healthy control children.

Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) enzymes can be considered as the most important liver enzymes that can be used to diagnose and monitor the liver cell damage¹⁴.

In this study the level of these two enzymes in whole patients showed to be non-significantly differ from that of control as demonstrated in table (2) while in table (3) the level of these enzymes showed to be significantly higher in newly diagnosis untreated patents when compared with the healthy control subjects. In addition, significant reduction in AST and ALT levels were observed after receiving treatment and the level of their activity were returned to nearly normal levels that indicate the improvement in the liver cell integrity and decrease in the hepatic damage within the first six months of treatment in consistent with other previous study that reported a rapid liver function improvement within six months of receiving ERT^9,18,19.

Other studies revealed that there was rarely cytolysis and the levels of these enzymes were non-significantly differ from that of healthy children^20,21 which is disagree with the results of this study. The possible explanation of this disagreement with the previous literature is the differences in the classification of patients. Other study conducted by Hassan and his coworkers was agree with the current study in that untreated Gaucher patients showed a significantly higher level of AST in comparison to that of control and the level of this enzyme then significantly reduced to nearly normal level while the level of ALT showed a non-significant differences among their studied groups²².

The wide range of differences between all the previous studies and the current study may be due to differences in the age of untreated newly diagnosed patients and also the treated children which affect the normal level of liver enzymes in children.

Additionally, ANOVA test results shown in table (5) revealed that there was a significant difference among the patient subgroups that also indicate the restoring of the normal levels of these enzymes within 3 to 6 months of treatment with ERT.

According to Receiver Operating Characteristic (ROC) curve results showed in table (7), ALT and AST showed high AUC, sensitivity and specificity and can be considered as a very good parameter for the diagnosis of newly diagnosed untreated patients but on the other hand, ALT and AST activity levels showed a low specificity, sensitivity and AUC in whole patients with Gaucher.

Additionally, the level of ALT and AST showed to be good markers that indicate the improvement of liver functions within the first 6 months of treatment which is cleared by ROC curve results of patients received treatment for 3-6 months in comparison with newly diagnosed untreated patients as in table (8). Table (6) also revealed that the ALT and AST activities showed significant negative correlation with the duration of treatment that also confirms that the ERT received cause a significant decrease in their levels and also showed a direct correlation with the level of Chitotriosidase activity which is considered as the most powerful biomarkers for Gaucher disease.

As demonstrated in table (2), a significant reduction in total protein level was observed with a non-significant increase in the bilirubin level in Gaucher patients in comparison with control. The possible explanation of this controversially results may be due to that the comparison done between the whole patient and control and that may indicate that the patients received treatment showed a comparable levels of bilirubin with a control group that in turn indicate that the level of bilirubin rapidly respond to the ERT while total protein level showed a significant decrease even after receiving the treatment. These results may indicate that the excretory function of liver restored before the synthetic function.

These results also consistent with the results obtained by Hassan and his co-workers who found that bilirubin level was elevated non-significantly in Gaucher children in comparison with controls while the levels of serum total protein collectively were non- significantly differ from that of control which disagree with the results obtained in the current study²². As mentioned above, more recent study reviewed that sometimes Gaucher patients may suffer from cholestasis with an increase in alkaline phosphatase and bilirubin levels²⁰ which is in agreement with the present study.

Table (4) demonstrated that newly diagnosed children and children who received ERT for 3-6 months showed a significant higher level of bilirubin and a significant lower level of total protein in comparison with control that indicate the liver excretory and synthetic functions were significantly affected by Gaucher’s disease. Total bilirubin level returns to the level comparable to that of control within 6-12 months while total protein level return to nearly control subjects’ level after more than one year of treatment. It is also demonstrated that a significant increase in total protein level and a significant decrease in bilirubin levels were observed in patients received ERT in a comparison with newly diagnosed non treated patients that confirm the previous findings.

ANOVA test results also indicate the significant change in the levels of total protein and bilirubin among the patient subgroups as reveled in table (5) which is consistent with results demonstrated in table (6) that revealed a negative correlation that was statistically significant between bilirubin level and the duration of receiving ERT whereas a significant positive correlation were obtained between total protein level and the ERT receiving duration.

As tabulated in table (7), results of ROC curve showed that the test for bilirubin level in whole Gaucher patients and newly diagnosed untreated patients in addition to other patient subgroups has a low significant values due to low AUC, sensitivity and specificity and cannot be considered as a good parameter which can be involved in diagnosis, prognosis and monitoring for Gaucher patient’s treatment while total protein can be regarded as highly significant tool for the diagnosis of children early who did not received treatment yet but on the other hand, total protein levels showed a low AUC, specificity and sensitivity values in whole children with Gaucher and patients receiving ERT, so it may be used as a good marker to diagnose or confirm the diagnosis in a suspected cases but according to these results it is considered as poor parameter for monitoring of Gaucher treatment with ERT.

Collectively, total protein, bilirubin and other liver function test showed to be improved within 3-12 months of receiving treatment which are in agreement with previous studies^9,18,19.

As a conclusion, liver function tests revealed that the liver enzymes (ALT and AST) returned rapidly to normal levels within 3-6 months of treatment with ERT while total bilirubin levels were normal in all studied groups including control subjects with a significant reduction in their levels with treatment. On the other hand, total protein levels showed a significant reduction in patients comparing with controls and showed a response to treatment within 6-12 months that indicating by the restoration of normal levels.

REFERENCES:

1. Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C, Fahn S, Dorovski T, Chung WK, Pauciulo M, Nichols W, Rana HQ, Balwani M, Bier L, Elstein D, Zimran A. Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes. JAMA Neurol. 2014;71(6):752-7.

2. Kanneganti M, Kamba A, Mizoguchi E. Role of chitotriosidase (chitinase 1) under normal and disease conditions. J Epithel Biol Pharmacol. 2012;5:1-9.

3. Chen Y, Sam R, Sharma P, Chen L, Do J, Sidransky E. Glucocerebrosidase as a therapeutic target for Parkinson's disease. Expert Opin Ther Targets. 2020;24(4):287-294.

4. Nagral A. Gaucher Disease. J Clin Exp Hepatol. 2014; 4(1): 37–50.

5. J. Krishnaveni, T. Ananthi. Hepatoprotective Effect of Moringa oleifera in Isoniazid Induced Rats. Research J. Pharm. and Tech. 4(12): Dec. 2011; Page 1901-1903.

6. Vrunda V. Shah, Vipul K. Shah, N. R. Sheth, M. M. Patel. Hepatoprotective and Anti-inflammatory activities of Hydroalcoholic extract of Bark of Erythrina indica. Res. J. Pharmacology and Pharmacodynamics. 2017; 9(4): 189-194. doi: 10.5958/2321-5836.2017.00033.7

7. Fadheelah S Azeez, Ali M Saadi. Evaluation of Liver Function in Type 2 Diabetic Patients during Clinical Trials in Kirkuk City. Research J. Pharm. and Tech. 2019; 12(4):1659-1663. doi: 10.5958/0974-360X.2019.00278.6

8. Amera Kamal Mohammed, Thanaa Abdulmahdi Mokif, Mahmoud Hussein Hadwan. The effect of Morbid Obesity on the Liver Function Enzymes. Research J. Pharm. and Tech. 2019; 12(5): 2241-2244. doi: 10.5958/0974-360X.2019.00373.1

9. Linari S, Castaman G. Clinical manifestations and management of Gaucher disease. Clin Cases Miner Bone Metab. 2015;12(2):157-64.

10. Peters H, Ellaway C, Nicholls K, Reardon K, Szer J. Treatable lysosomal storage diseases in the advent of disease-specific therapy. Intern Med J. 2020;50 Suppl 4:5-27.

11. Vaibhav Tripathi, Adeep Kujur, Manmeet Singh Saluja. Hepatoprotective Activity of Stem Bark of Nyctanthes arbor-tristis linn. Research Journal of Pharmacology and Pharmacodynamics. 2015; 7(3): 124-128. doi: 10.5958/2321-5836.2015.00023.3

12. Dr. P. Muthukumaran, Dr. V. Hazeena Begum. Effect of Poorna Chandrodayam Chendooram (PCM - Metallic Drug) on Lipid Profile, Liver Function and Kidney Function Parameters of Rats. Asian J. Pharm. Ana. 2020; 10(1):27-31. doi: 10.5958/2231-5675.2020.00006.X

13. Edokwe Chinelo, Obidoa Onyechi, Joshua Parker Elijah. Biochemical Effects of Persea americana (Avocado) and Dacryodes edulis (African Pear) Extracts on Liver Function Test of Albino Wistar Rats. Research J. Science and Tech. 2010; 2(2): 34-37 .

14. Limdi JK, Hyde GM. Evaluation of abnormal liver function tests. Postgrad Med J. 2003; 79(932):307-12.

15. B Suneetha, K V S R G Prasad, P. Deepthi Nishanthi, B R Soumya, B Sampath Kumar. Hepatoprotective and Antioxidant Activity of Methanolic Extract of Actinodaphne madraspatana against Carbon tetrachloride Induced Hepatotoxicity. Res. J. Pharmacognosy & Phytochem. 2014; 6(4): 176-180.

16. P Natarajan, A Thanga Thirupathi, T Raja Sekharan, AS William Arputha Sundar, R Arivukkarasu, M Ganesan. Hepatoprotective effect of Glinus oppositifolius Linn. Research J. Pharmacology and Pharmacodynamics. 2010; 2(4): 289-292.

17. Jinan Hussein Murtadha, Iman Hashim, Abdul Razzaq. Study of Liver Function and Lipid Profile Changes in Iraqi Cirrhotic patients. Research J. Pharm. and Tech. 2020; 13(4):1837-1840. doi: 10.5958/0974-360X.2020.00331.5

18. Shawky RM, Elsayed SM. Treatment options for patients with Gaucher Disease. The Egyptian Journal of Medical Human Genetics 2016;17: 281–285

19. Smid BE, Ferraz MJ, Verhoek M, Mirzaian M, Wisse P, Overkleeft HS, Hollak CE, Aerts JM. Biochemical response to substrate reduction therapy versus enzyme replacement therapy in Gaucher disease type 1 patients. Orphanet J Rare Dis. 2016;11:28.

20. Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017;18(2). pii: E441.

21. Rizk TM, Ariganjoye RO, Alsaeed GI. Gaucher disease. Unusual presentation and mini-review. Neurosciences (Riyadh). 2015;20(3):271-6.

22. Hassan MH, Sayed AA, Ahmed AE, Saleem TH, Elsayh KI and Mohammed NBB. Effect of Enzyme Replacement Therapy on Disease Burden Biomarkers in Gaucher's Disease. International Journal of Biochemistry Research & Review 2016; 15(2): 1-6.

Received on 02.12.2021 Modified on 13.01.2022

Research J. Pharm. and Tech. 2022; 15(8):3490-3496.

DOI: 10.52711/0974-360X.2022.00585