Dr Hind I Fallatah MBCh B,
Arab Board and Saudi Board of Internal Medicine, MACP.
Consultant Hepatologist Assistant professor
King Abdul Aziz University Hospital Jeddah
Saudi Arabia

Dr Hisham O Akbar MBCh B, FRCP
Associate professor Consultant Hepatologist
King Abdul Aziz University Hospital Jeddah
Saudi Arabia

Correspondence:
Dr Hind I Fallatah
Po box 9714 Jeddah 21423
Saudi Arabia
Fax +96626751149
Phone +966501267336
Email: hindfallatah@hotmail.com

Qat is a medium size tree known in Yemen as Gat or Khat. It is named scientifically as Cathaedlius (cathinone). Cathinone is a psycho stimulant substance which causes euophoria.(1) Qat chewing is a socio-cultural habit widely practiced in East Africa and Yemen,(2) but its practice in Yemen is more than other countries.(2,3) It has been estimated that up to 80% of Yemenis between 16-80 years have chewed qat on at least one occasion.(1) Qat chewing has been reported by both men and women of different age groups.(2) Recently because of increased immigration from Yemen and Africa to North America and Europe, qat chewing is increasingly recognized especially in the United Kingdom (UK).(3,4) The qat chewing habit in Yemen has great potential social and economic burdens. 40% of the country's water is used for its irrigation and money spent on Qat has doubled 280% from 1990-1995.(1,3)

In addition to its socio-economic burden Cathinone can cause multiple health problems.(1) It is similar in structure and pharmacological activity to amphetamine.(5,6) . It can cause CNS, gastrointestinal, renal, genitourinary, cardiovascular , and hepatic toxicity. It also causes oral ulceration and increased risk of oral cancers.(1,2,3,7)

D- amphetamine is known to exert different forms of hepatotoxicity in-vivo and in-vitro when tested on hepatocytes.(8,9) Because of structural similarity qat is expected to cause similar toxic effects on the liver but the available data on this issue are few and sporadic. In this article we reported three patients from Yemen with autoimmune hepatitis possibly related to qat chewing habits.

First patient
A 21 year old Yemeni male patient high school student. He had jaundice for two years, abdominal distension for 2 weeks and disturbed sleep pattern for 2 days. There was no family history of liver disease. He started Qat chewing almost daily from the age of 15 years. He had no history of alcohol intake. See Table 1 for clinical findings and Tables 2 and 3 for lab results. Abdominal ultrasound showed coarse cirrhotic liver and a moderate amount of ascitic fluid. Upper gastrointestinal endoscopy (EGD) was normal. Ascitic fluid cell count and culture were negative for spontaneous bacterial peritonitis (SBP). Because of coagulopathy and advanced disease, liver biopsy was not performed. The diagnosis of AIH was based on the clinical and the immunological data. He was treated for hepatic encephalopathy with lactulose and started on oral prednisolone 30 mg daily. After 3 months of treatment his serum Alanine transferrase (ALT), aspartate amine transferrase (AST) and bilirubin came down but not to normal reference range. Azathioprine (AZA) 50mg daily was added. He had complete biochemical response after 12 month of treatment - the liver enzymes and bilirubin were completely normal. Prednisolone was gradually reduced to 5mg and AZA was continued. He sustained remission on treatment for 2 years then he went to back Yemen, resumed qat chewing and came back to our hepatology clinic after 6 months with elevated serum ALT 144U/L, AST197U/L and bilirubin 207umol/L. Prednisolone was increased to 30mg until he had remission. On his latest follow up his ALT, AST and bilirubin were normal and he was maintained on prednisolone 5mg and AZA 50mg daily.

Second patient
A 21 year old Yemeni male patient was diagnosed in April 2006 to have AIH. He had jaundice for 36 months, abdominal distension for 2 months and hepatic encephalopathy for one week. He was brought to the emergency department by his brother comatose ( in stage IV hepatic encephalopathy). He chewed qat for more than 6 years. He denied alcohol intake. He had no family history of liver disease, (Table 1) for clinical findings and Tables 2 and 3 for laboratory results. Abdominal ultrasound showed evidence of liver cirrhosis, small shrunken liver and moderate ascites. EGD showed grade III esophageal varices and portal hypertensive gastropathy. Similar to the first patient, because of advanced disease and coagulopathy liver biopsy was not obtained. He was diagnosed to have AIH based on clinical and immunological data. Ascitic fluid cell count and culture did not reveal evidence of bacterial peritonitis. He received treatment for HE with lactulose and metronidazole, and treatment for AIH prednisolone 40 mg daily. Over 2 weeks he had gradual improvement and was discharged on prednisolone 40mg to be followed in the clinic. Four weeks after starting treatment his ALT, AST, and bilirubin significantly improved but he developed severe proximal myopathy. AZA was started and prednisolone was reduced to 15 mg (the dose that he was able to tolerate without having proximal myopathy). He had complete biochemical response after 20 months of treatment. Early in 2008 he went to Yemen, stopped treatment and resumed Qat chewing. He had a flare of AIH ( jaundice, ALT 728u/L, AST 949u/L TBil 372umol/L Alp357u/L). We resumed him on AZA 75mg and predisolone 15 mg daily. The liver functions improved over 3 months but did not go back to normal. On his last visit his liver functions were ALT 135u/L, AST 87u/L, TBil42umol/L, ALP 282u/L. He is still on active follow up with our clinic.

Third patient
A 37 year old recently came from Yemen for assessment of 6 month history of jaundice. He denied alcohol intake and there was no family history of liver disease. He chewed qat for more than 20 years. The rest of the history was unremarkable.

See Table 1 for clinical findings and Tables 2 and 3 for laboratory results. Abdominal ultrasound examination showed coarse cirrhotic liver, mild splenomegaly and there was no ascites. He had liver biopsy that showed chronic hepatitis with features consistent with AIH ( interface hepatitis and chronic inflammatory cells infiltration mainly plasma cells and lymphocytes). He was started on prednisolone 30 mg daily and AZA was added after 2 months. He completed 10 months of treatment; his liver enzymes and bilirubin are normal (ALT 51u/L, TBil 22umol/L)

Testing for Wilson's disease by 24 hour urine copper and Serum copper were negative for all the patients.

Table 1: Clinical assessment of the three patients at the time of diagnosis

Table 2: Laboratory results at the time of diagnosis

Complete blood count (CBC) at the time of diagnosis [white blood cells (WBC), hemoglobin (Hg), platelets count (plat)]

Liver function tests LFT [serum alanine aminotransferase (ALT), Aspartate Amino Transferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total protein (TP), albumin (Alb), and total and direct bilirubin.]

Table 3: Immunological results for the three patients

Anti nuclear antibody ANA) done by indirect immunofluorescence( IIF) weakly positive 1/40 and strongly positive 1/1280, smooth muscle antibody (SMA) detected by ELISA, liver kidney microsomal-1(LKM-1) detected by ELISA, antimitochondrial (AMA) detected by ELISA, method normal range 5.4-16.1, and antinetrophil cytoplasmic antibody (ANCA) detected by IIF, immunoglobulin-G (IgG) level by the nephelometer. Hepatitis serology hepatitis B virus (HBSAg, HBeAg, HBeAb, HBcAb), hepatitis C virus (HCVAb) and in patients with acute presentation the result of Hepatitis A virus (HAVAb-IgM)