Liver steatosis is a risk factor for hepatotoxicity in patients with inflammatory bowel disease under immunosuppressive treatment.
OBJECTIVE
In inflammatory bowel disease (IBD), hepatic disorders are frequently due to nonalcoholic fatty liver disease and drug-induced hepatotoxicity. Immunosuppressive treatment is known to exert hepatotoxic side effects by a still unknown mode. The relevance of liver steatosis for the development of drug-related hepatotoxicity in IBD is unknown.


METHODS
The charts of 259 patients with IBD under immunosuppression with either azathioprine, 6-mercaptopurine, or methotrexate were reviewed. The prevalence of liver steatosis was assessed by means of ultrasound reports. Aspartate transaminase and alanine transaminase above the normal range were used to indicate liver abnormalities.


RESULTS
Liver steatosis on the basis of ultrasound criteria was observed in 73 patients (28.2%). In patients with liver steatosis, the presence of elevated liver enzymes (ELE) was found to be significantly more prevalent (28.8 vs. 14.5%, P=0.0095). The finding of liver steatosis was associated with higher age (44.1 vs. 34.5 years, P<0.0001) and body weight (BMI 26.7 vs. 23.4 kg/m, P<0.0001). Development of ELE under immunosuppression was seen in 50 patients (19.3%). Of the patients who developed ELE, 44.0% (vs. 24.4%, P=0.0095) showed liver steatosis. Logistic regression analysis revealed that male individuals showed an increased likelihood of developing ELE associated with steatosis (P=0.0118, odds ratio=3.93) and that patients who received steroids less often developed ELE in association with liver steatosis (P=0.0414, odds ratio=0.31).


CONCLUSIONS
This study suggests that fatty liver represents a risk factor for hepatotoxicity in patients with IBD under immunosuppressive treatment and should be routinely considered in treatment strategies.
Departments of aMedicine I bDermatology, University Hospital Schleswig-Holstein, Campus Lübeck cGastroenterology Practice, Lübeck, Germany.
Torsten
T
Schröder
Klaus J
KJ
Schmidt
Vera
V
Olsen
Steffen
S
Möller
Tilo
T
Mackenroth
Christian
C
Sina
Hendrik
H
Lehnert
Klaus
K
Fellermann
Jürgen
J
Büning
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001379:Azathioprine / Q000009:adverse effects; D015992:Body Mass Index; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D005234:Fatty Liver / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D014463:Ultrasonography; D055815:Young Adult
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001379:Azathioprine; D008727:Methotrexate