Perbtani Yaseen B, Westerveld Donevan R, Yang Dennis J, Draganov Peter V
Department of Internal Medicine, University of Florida, Gainesville, Florida, United States.
Division of Gastroenterology and Hepatology, University of Florida, Gainesville, Florida, United States.
Endosc Int Open. 2021 Jun;9(6):E843-E847. doi: 10.1055/a-1401-9853. Epub 2021 May 27.
Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013-2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8-11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.
症状性胃食管反流是经口内镜下肌切开术（POEM）后公认的潜在不良事件。质子泵抑制剂（PPI）是一种有效的一线治疗方法；尽管其疗效可能会受到细胞色素P450 2C19（CYP2C19）基因变异的影响，导致PPI清除率增加。我们研究的目的是评估难治性胃食管反流症状的POEM患者中CYP2C19基因变异的发生率。这是一项单中心、前瞻性队列研究，对7年研究期间（2013 - 2020年）连续的POEM病例进行研究。POEM术后，采用经过验证的胃食管反流病问卷（GerdQ）和客观pH检测来评估反流症状。对所有难治性胃食管反流病（GERD）症状患者进行CYP2C19基因检测，难治性GERD症状定义为pH检测异常且每天服用两次PPI时GerdQ评分≥8。在研究期间，对325例连续患者（48.3%为女性；平均年龄57岁）进行了POEM。根据GerdQ评分（中位数9，范围8 - 11）和pH检测异常，20例患者（6.8%）出现了PPI难治性的POEM术后胃食管反流。CYP2C19基因检测确定这些患者中有55%（11/20）为快速代谢者。其中，9例（82%）在换用受CYP2C19药物遗传学影响较小的PPI后，临床GERD症状有所改善。POEM术后，PPI难治性GERD很少见。如本研究所示，快速代谢者通常通过换用受CYP2C19药物遗传学影响较小的PPI来缓解症状，从而降低GERD长期后果和不必要的抗反流手术的风险。
