Research express@ncku - articles digest

Research Express@NCKU Volume 13 Issue 4 - April 2, 2010
Body Mass Index Can Determine the Healing of Reflux
Esophagitis with Los-Angles Grades C and D by
Esomeprazole
, Wei-Lun Chang1,3, Hsui-Chi Cheng1,3, Ai-Wen Kao1 and Cheng-Chan Lu21Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan 2Department of Pathology, Medical College, National Cheng Kung University, Tainan, Taiwan 3Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan Reflux esophagitis is a chronic recurrent disease, and can be assessed in severity by Los-Angles classification. Reflux esophagitis patients with Los-Angles grades C and D (RE-CD) were elucidated as having poor healing rates compared with those having grades A and B. Accordingly, use of a long-term proton pump inhibitor (PPI) was recommended by the Geneva consensus for those patients with RE-CD to achieve sound esophageal ulcer healing and to prevent frequent relapses. The currently available PPIs are mostly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) of the p450 enzyme system in the liver. Hence, a more rapid PPI clearance in the extensive metabolizer (EM) of CYP2C19 genotype is presumed to have potentially poorer acid control than the poor metabolizer (PM). Esomeprazole, the S-isomer of omeprazole, is a promising potent acid suppressor as compared with other currently available PPIs. However, during long-term treatment for RE-CD, the exact impact of the genotypes of CYP2C19 on the healing of RE-CD remains to be validated. Therefore, this study was established to determine whether the cumulative healing rates of RE-CD by esomeprazole for the patients could be related with Moreover, a higher body mass index (BMI) as overweight or obesity was disclosed to be related with the more severe symptoms of reflux esophagitis, and the treatment response of PPI to achieve sustained symptomatic response for the reflux esophagitis in grades A and B. Accordingly, this study also analyzed whether there were any demographic factors, including BMI of the study patients, which could be related to the cumulative ulcer healings of the 6-month 40 mg esomeprazole treatment for RE-CD. One-hundred and thirteen patients with RE-CD received esomeprazole 40 mg daily for six months and completed serial follow-ups regarding healing by endoscopies on the 1st month and the 6th month, respectively. In each patient, demographic factors, including body mass index (BMI), and the CYP2C19 genotypes were checked. The CYP2C19 genotype of each enrolled patient was defined as poor metabolizer (PM), or extensive metabolizer (EM), including both homogenous (HomoEM) and heterogeneous (HeteroEM) patterns. A net-change of BMI was calculated as the post-treatment BMI minus the initial BMI on enrollment. Based on the net change, patients who completed the six-month study period were further divided into subgroups as labeled stationary (net change ranges within -1.5~1.5 kg/m2), increased (net change as > 1.5 kg/m2), and decreased (net change as < -1.5 kg/m2) BMI. Demographic features and CYP2C19 genotypes of the enrolled patients In this prospective study, 125 patients (46 female and 79 male) with RE-CD were consecutively enrolled and 113 of them completed the study. Their mean age was 53.8 years. The CYP2C19 genotypes of these RE-CD patients were disclosed as HomoEM in 58 (46.4%), HeteroEM in 40 (32%), and PM in 27 (21.6%) patients, respectively. There were no differences in the age, gender, smoking, alcohol, coffee, tea drinking habits, symptomatic severity score, the endoscopic severity of reflux esophagitis, and the proportions of hiatus hernia among the patients with The healing rates of GE-CD on the 1st and the 6th month
There were 12 patients excluded from the analysis regarding the healing rate of RE-CD, including 4 patients with poor drug compliance, 3 patients with unscheduled visits to receive additional esomeprazole, and 5 patients lost to follow-up. A total of 113 patients completed the study design. The rate of SSR on the 1st month, but not on the 6th month, was found to be significantly increased as a trend for patients with CYP2C19 genotypes ranking as HomoEM, HeteroEM, and PM (1st month: 50%, 72.2%, and 74.3%, P=0.026; 6th month: 90.7%, 94.4%, and 95.7%, P>0.05). At the end of the 1st month, 53 (46.9%) patients had complete healing. Moreover, on the 6th month, 84 (74.3%) patients were defined as complete healing. However, the complete healing rates of RE-CD on both the 1st and the 6th months were not significantly different among patients with CYP2C19 genotype defined as PM, HeteroEM, and HomoEM (1st month: 44.4%, 40%, 43.1%, P> 0.05; 6th month: 70.4%, 67.5%, 72.4%, P Univariate analysis to factors related to the healing rate of RE-CD
On the 1st month, patients with complete healing had significantly lower rates regarding the presence of hiatus hernia, and the habits of alcohol and coffee drinking than patients without complete healing (P<0.05). Either on the 1st or the 6th month follow-up, the mean BMI were lower in those with complete healing of RE-CD than in those without (P<0.05). Patients with BMI > 25 kg/m2 had a lower complete healing rate of RE-CD than those with BMI < or = 25 kg/m2 on the 1st month and on the 6th month, respectively (1st month: 30% vs. 66%, relative risk [95%CI] = 0.22 [0.11~0.49], P<0.001; 6th month: 60% vs. 98%, relative risk [95%CI] = 0.03 [0.01~0.22], Independent risk factors to have a complete healing of RE-CD
Multivariate logistic regression confirmed BMI > 25 kg/m2, the presence of hiatus hernia, and that the habit of coffee drinking were independent risk factors to having a lower rate of complete healing of RE-CD after one- month of taking esomeprazole (P<0.05). On the 6th-month follow-up, A higher BMI > 25 kg/m2 independently had a 2.32-fold decrease of the healing of RE-CD (P<0.001), but a net decrease of BMI > 1.5 kg/m2 independently had a 3.65-fold increase of the healing of RE-CD (P=0.014). Conclusions: Esomeprazole 40mg daily can be effective for RE-CD patients with different CYP2C19 genotypes.
BMI > 25 kg/m2 is an independent risk factor to determine the healing of RE-CD by esomeprazole. Reducing BMI > 1.5 kg/m2, especially for those with an initial BMI > 25 kg/m2, could be promising to improve the healing

Source: http://proj.ncku.edu.tw/research/articles/e/20100402/3.pdf