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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 25  |  Issue : 1  |  Page : 37-41

The effect of chronic khat chewing on liver enzyme levels ( a Yemenian study)


1 Department of Tropical Medicine and Liver, Cairo University, Cairo, Egypt
2 Department of Hepato-gastroenterology, Sana'a University, Sana'a, Yemen

Date of Submission18-Oct-2012
Date of Acceptance13-Nov-2012
Date of Web Publication5-Jul-2014

Correspondence Address:
Mohammad Abdelbary
MD, Department of Tropical Medicine and Liver, Cairo University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJIM.0000425957.34390.61

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  Abstract 

Background

Khat is a natural stimulant from the Catha edulis plant, which grows mainly in Yemen. The liver has been suspected to be vulnerable to the harmful effects of khat use.

Aim

The aim of the study was to investigate the effect of khat chewing on the liver function in healthy Yemeni individuals.

Methods

Liver function tests were performed on 30 chronic khat chewers (group I) and 20 individuals who did not chew khat (group II).

Results

Twenty percent of group I and only 5% of group II reported abnormally elevated alanine transaminase (ALT) levels, with no statistically significant difference between the mean ALT values (P=0.208); 13.3% of group I showed elevated aspartate aminotransferase levels (P=0.058). With regard to other liver function tests there was no statistically significant difference between the two groups. ALT levels increased with increasing duration of khat chewing.

Conclusion

Chronic khat chewing causes subclinical hepatocellular damage, whereas transient khat chewing has no effect on the liver function.

Keywords: alanine transaminase, aspartate aminotransferase, chewing duration, khat, subclinical


How to cite this article:
Ramzy I, Abdelbary M, Abdelhafez H, Omran D, Al-Amrany M, Al-Shami AM. The effect of chronic khat chewing on liver enzyme levels ( a Yemenian study). Egypt J Intern Med 2013;25:37-41

How to cite this URL:
Ramzy I, Abdelbary M, Abdelhafez H, Omran D, Al-Amrany M, Al-Shami AM. The effect of chronic khat chewing on liver enzyme levels ( a Yemenian study). Egypt J Intern Med [serial online] 2013 [cited 2019 Sep 21];25:37-41. Available from: http://www.esim.eg.net/text.asp?2013/25/1/37/135998


  Introduction Top


Khat (Catha edulis) is a natural stimulant from the C. edulis plant [Figure 1] found in the flowering evergreen tree or large shrub of the Celastracea family, which grows mainly in Yemen, Ethiopia, Somalia, Kenya, Saudi Arabia, and at high altitude areas in South Africa and Madagascar 1.
Figure 1: Morphology of the

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Early clinical observations suggested that khat had amphetamine-like properties 2. Subsequent chemical analyses confirmed that the fresh leaves contain a number of compounds, including phenylalkylamine compounds (alkaloids) such as norpseudoephedrine (cathine) and α aminopropiophenone (cathinone), the latter being structurally related 3 and pharmacologically similar to amphetamine 4.

The liver has been suspected to be particularly vulnerable to the harmful effects of khat use 2, 5, and a disturbance in liver function and architecture has been described in experimental animals both on short-term 6 and long-term 7 feeding with C. edulis leaves.

Khat administered chronically to animals causes an increase in liver transaminases, leading to signs of chronic hepatic inflammation. Recent studies in UK have revealed many cases of acute idiopathic severe liver damage in Somalian khat chewers who live there. Another study has shown a high prevalence of cryptogenic liver disease among Somalian khat chewers. Moreover, some of them who had autoimmune antibodies like SMA failed to respond to therapy with immunosuppressants and those who quit khat chewing recovered markedly and needed no more immunosuppressants 8.

This study was carried out to detect the effect of khat chewing on liver function in healthy Yemeni individuals.


  Patients and methods Top


Study objectives

The aim of this study was to assess the liver function in healthy Yemeni chronic khat chewers and detect any significant difference in the liver function test results from those of healthy Yemeni individuals.

Method and study design

Fifty healthy Yemeni individuals of both sexes with a BMI less than 25 kg/m2 were enrolled in our study from among the relatives of patients who were admitted to Al-Thawra University Hospital, Sana’a, Yemen. The 50 healthy individuals were categorized into two groups according to khat consumption: group I comprised 30 healthy khat chewers and group II comprised 20 healthy non-khat chewers. The mean duration of khat chewing in patients of group I was 10.32±6.5 years; accordingly, patients in group I were further categorized into two groups: the first group comprised those who had been chewing khat for less than 10 years and the second group comprising those who had been chewing khat for at least 10 years. Patients with any chronic medical disease, diabetes mellitus, or with metabolic disorders, as well as those on regular medication, alcoholics, or those with positive HBV or HCV markers, were excluded from the study.

After signing a written informed consent, blood samples were collected and liver function tests were conducted. Also, HBsAg, HBc total Ab, and HCV Ab were tested using ELISA. Those who had abnormal liver enzyme levels were investigated for serum anti-smooth muscle antibody (ASMA), antinuclear antibody (ANA), and anti mitochondrial antibody (AMA) titers and were subjected to a conventional abdominal ultrasonographic examination.

Statistical methods

Patients’ data were analyzed using SPSS 17.0 (SPSS Inc., Chicago, Illinois, USA) for Windows 7. Quantitative variables were compared using the Student t-test and the Mann–Whitney test. Qualitative variables were comparedusing the χ2 and Fisher exact tests when appropriate. P-value was considered significant if less than 0.05.


  Results Top


The data of individuals included in the khat-chewer group and non-khat-chewer group are given in [Table 1]. Our study reported that the average quantity of khat chewed by each candidate in the khat-chewer group was 250 g/day. With regard to the liver function test, the values of total and direct bilirubin, prothrombin time (PT), prothrombin concentration (PC), and international normalized ratio (INR) of both groups were within the normal reference range. On analyzing the alanine transaminase (ALT) values in both groups it was reported that only one person (5%) among the non-khat chewers had a high ALT value, whereas six (20%) khat chewers had abnormally high ALT values; however, there was no statistically significant difference between the groups in terms of the mean ALT values (P=0.208) [Table 2]. With regard to the aspartate aminotransferase (AST) values in both groups it was reported that all non-khat chewers had values within the normal reference range, whereas four (13.4%) of the khat chewers had abnormally elevated AST values. On comparing the mean AST values between both groups it was reported that the mean AST values in the khat-chewer group was greater than that in the non-khat-chewer group with a P-value approaching significance (0.058) [Figure 2]. With regard to gamma glutamyl transferase (GGT) values there was one person (5%) among non-khat chewers and two (6.6%) among khat chewers with elevated GGT levels; however, on comparing the mean GGT values between the two groups, no statistically significant difference was detected (P=0.77). The same results were obtained for phosphatase; no statistically significant difference was observed between the non-khat-chewer and khat-chewer groups.
Table 1: Data and liver biochemical profile of both khat chewers (group I) and non-khat chewers (group II)

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Table 2: Comparison between the liver enzymes of khat chewers and non-khat chewers

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Figure 2: Graph representing the aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in both khat and non-khat chewers; there is no statistically significant difference between the two groups (P=0.058 and 0.208, respectively).

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With regard to total protein and albumin levels, only one person had a low level for both in each group; there was no statistically significant difference in their levels between the groups.

The khat chewers were divided into two groups according to the duration of khat chewing: the first group comprised those who had been chewing khat for less than 10 years and the second group comprised those who had been chewing khat for at least 10 years [Table 3]. The results of our study showed that the duration of khat chewing had no effect on liver enzymes; in the khat-chewing group there was no association between the duration of khat chewing and level of ALT (P=0.426). The same result was observed for the levels of AST (P=0.815) and GGT (P=0.232).
Table 3: Comparison of the liver enzyme levels according to the short-term and long-term effect of khat chewing, and the effect of cigarette smoking on the level of liver enzymes

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Age did not have a significant effect on the level of liver enzymes in khat chewers; in group I there was no statistically significant difference in the mean age between individuals with normal ALT levels and those with elevated ALT levels (P=0.934); the same result was observed for AST (P=0.714) and GGT levels (P=0.687) [Table 4].
Table 4: The mean age in the khat-chewer group according to the liver enzyme level

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Blood samples were collected from eight individuals during khat chewing and from the remaining 22 after khat chewing. The results show that liver enzyme levels during khat chewing did not vary significantly from those collected after khat chewing. There was no association between ALT levels and sampling time (P=0.536); the same result was observed for AST (P=0.195) and GGT levels (P=0.271) [Table 3].

There was no association between smoking and abnormally elevated liver enzymes levels in the khat-chewing group, nor was there an association between smoking status and ALT (P=0.819) and AST levels (P=0.107) [Figure 3].
Figure 3: The percentage of cigarette smokers among khat chewers and non-khat chewers.

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Only one individual with abnormally elevated ALT levels in the khat-chewer group (n=6) showed positive ASMA and ANA, whereas the remaining were negative for ASMA, ANA, and AMA.

Only khat chewers (n=8) and non-khat chewers (n=2) with abnormally elevated serum liver enzymes were subjected to a conventional abdominal ultrasonographic examination. No abnormality was detected in any of them except for the case of two khat chewers: one of them with elevated serum ALT levels showed a bright liver with normal size and texture, and the second one with elevated serum ALT, AST, and GGT and decreased total protein and albumin levels, with an autoimmune profile showing positive ANA and ASMA titers (1/80 and 1/40, respectively), had a coarse liver texture with normal size and an enlarged spleen (14 cm), but with normal portal vein diameter.


  Discussion Top


Our cross-sectional study reported that chronic khat chewing causes subclinical hepatocellular damage, which may be related to the duration of khat chewing or to the use of pesticides, whereas transient khat chewing has no effect on the liver function. Although there is no statistically significant difference in the abnormal increase observed in both ALT and AST levels among the khat chewers compared with the non-khat chewers, the increased ratios in the khat-chewer group may indicate possible khat-induced liver damage, which is commensurate with the results reported in other studies 9. Human and animal studies demonstrate that regular intake of khat for long periods causes hepatocellular damage. Animal studies 7 demonstrated a significant increase in ALT and AST serum levels of rats fed khat for 6 months, whereas in other studies there was a nonsignificant increase 10. A case report published in 2011 11 supported the concept of khat chewing impairing the liver function.

With regard to the effect of khat chewing duration on the liver function, our study showed that ALT serum level was higher in those who had been chewing khat for 10 years or more, although the results were nonsignificantly different from those who had been chewing khat for less than 10 years (23.81 vs. 11.2%); however, this difference may indicate that the longer the duration of khat chewing, the more the hepatocellular damage. With regard to the AST and GGT levels, there was no statistically significant difference in their levels with the increase in chewing duration.

With regard to PT, PC, and INR, the values in both khat chewers and non-khat chewers were nearly equal and within the normal range, which was expected as the coagulation profile in liver disease is not affected during the early stages whatever the cause and our participants were normal healthy asymptomatic individuals. Moreover, it is well known that the synthetic function of the liver changes in manifested or late-stage chronic liver disease. Similar results were also reported with regard to total bilirubin, direct bilirubin, alkaline phosphatase, and GGT; no statistically significant difference was observed in their levels between khat chewers and non-khat chewers, which is in agreement with that reported in animal studies conducted by Al-Zubairi et al. 10 and by Al-Meshal et al. 12; however, these results are not in agreement with those reported by Al-Habori et al. 7 and Al-Mamary et al. 6, nor do they agree with the results of Tash et al. 13 in their studies on rats.

Total protein and serum albumin results showed no statistical difference between khat chewers and non-khat chewers. This may be explained by the fact that serum albumin reflects the synthetic function of the liver, which will decrease only in manifested or late-stage liver disease.

Age had no effect on liver function in the khat-chewing group, indicating that the difference in liver enzyme levels is mainly due to khat chewing and no other factor such as age, khat chewing duration, and sex has a role.

Khat chewing may be a risk factor for autoimmune hepatitis that responds well to treatment 14,15; the results of our study showed that only one case of chronic khat chewing had a positive titer for ASMA and ANA. Whether these results are due to autoimmune hepatitis or are a hypersensitivity reaction to khat chewing can be determined only from larger randomized controlled studies including autoimmune profile and liver biopsies.

Moreover, we reported that cigarette smokers were more prevalent in the chronic khat-chewer group, similar to the results of Elmi 16, which may add a synergistic adverse effect in that group.

We should point out some limitations of the study. First, an antimicrosomal antibody was not tested in our studied groups, which could be attributed to the limited financial resources of our study, as Al-Thawra University Hospital is a nonprofit organization. Second, there exists a discrepancy between our study and other studies with regard to the results of both the abdominal ultrasonographic examination and the ALT levels, as the ultrasonographic examination is an operator-dependent imaging method (more than one person operated it in the current study); moreover, the relatively small sample size of our study may contribute to this discrepancy in the results.


  Conclusion Top


We showed that chronic khat chewing causes subclinical hepatocellular damage, which may be related to the duration of khat chewing, and further randomized controlled studies with larger sample sizes are recommended.[16]

 
  References Top

1.Weir S Qat in Yemen: consumption and social change. 1985 London British Museum Publications  Back to cited text no. 1
    
2.Halbach H. Medical aspects of the chewing of khat leaves. Bull World Health Organ. 1972;47:21–29  Back to cited text no. 2
    
3.Szendri K. The chemistry of khat. Bull Narc. 1980;32:5–35  Back to cited text no. 3
    
4.Kalix P. Cathinone, alkaloid from khat leaves with an amphetamine-like releasing effect. Psychopharmacology (Berl). 1981;74:269–270  Back to cited text no. 4
    
5.Luqman W, Danowski TS. The use of khat (Catha edulis) in Yemen: social and medical observations. Ann Inter Med. 1976;85:246–249  Back to cited text no. 5
    
6.Al-Mamary M, Al-Habori M, Al-Aghbari AM. Investigation into the toxicological effects of Catha edulis leaves: a short term study in animals. Phytother Res. 2002;16:127–132  Back to cited text no. 6
    
7.Al-Habori M, Al-Aghbari A, Al-Mamary M. Toxicological evaluation of Catha edulis leaves: a long term feeding experiment in animals. J Ethnopharmacol. 2002;83:209–217  Back to cited text no. 7
    
8.Peevers CG, Moorghen M, Collins PL. Liver disease and cirrhosis because of Khat chewing in UK Somali men: a case series. Liver Int. 2010;30:1242–1243  Back to cited text no. 8
    
9.Bajubair MA Effect of khat on the function of the liver, kidney and on the blood glucose level [MSc Thesis]. Sudan: Faculty of Pharmacy, University of Khartoum; 1997  Back to cited text no. 9
    
10.Al-Zubairi A, Ismail P, Pei CP. Genotoxic effect of Catha edulis (Khat) crude extract after sub-chronic administration in rats. Environ Toxicol Pharmacol. 2008;25:298–303  Back to cited text no. 10
    
11.Roelandt P, George C, d’Heygere F, Aerts R, Monbaliu D, Laleman W, et al. Acute liver failure secondary to khat (Catha edulis)-induced necrotic hepatitis requiring liver transplantation: case report. Transplant Proc. 2011;43:3493–3495  Back to cited text no. 11
    
12.Al-Meshal IA, Qureshi S, Ageel AM. The toxicity of Catha edulis in mice. J Subst Abuse. 1991;3:107–115  Back to cited text no. 12
    
13.Tash FM, Farag RM, El-Deep T. The effect of khat and its active principle cathinone on the liver. Ain Shams Med Congress. 1983;8:3–7  Back to cited text no. 13
    
14.Fallatah HI, Akbar HO. Qat chewing and autoimmune hepatitis – true association or coincidence. Middle East J Fam Med. 2010;8:6–9  Back to cited text no. 14
    
15.Al-Subee O. Khat and autoimmune hepatitis in men. Am J Gastroenterol. 2010;104:492–495  Back to cited text no. 15
    
16.Elmi AS. The chewing of khat in Somalia. J Ethnopharmacol. 1983;8:163–176  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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