消化内科文献.doc

Novel Diagnostic Strategies for the Evaluation of Helicobacter pylori and Functional Dyspepsia using Multiplex PCR Testing
Rudra Rai, MD, FACG,1 Metul Shah, BS2
1. Johns Hopkins Medical Institutions, Baltimore, MD; 2. Gastro Center of Maryland, Columbia, MD. 
Purpose: Helicobacter pylori (HP) represents an extremely common infection worldwide. Functional dyspepsia (FD) is a remarkably common syndrome characterized by chronic and recurrent symptoms in the absence of known organic disease likely to explain the symptoms. Previous trials have shown a higher prevalence of HP in FD patients, and a meta-analysis showed HP infection was greater than controls with an odd ratio of 2.3 (95% CI, 1.9-2.7). However, availability of PCR diagnostic techniques were lacking.

Methods: We performed a prospective study of 325 adult patients with chronic gastro-duodenal symptoms who underwent upper endoscopic (EGD) examination. Biopsies were obtained by the same endoscopist from the gastric antrum and fundus and duplicate samples were sent simultaneously for immunohistochemistry (IHC) and commercially available multiplex PCR testing (TZAM diagnostics). Primers specific for H. pylori urease A gene, 26-kd protein antigen, hpaA gene, 0.86-kb DNA fragment, and DNA sequences of 16S ribosomal RNA were used as amplification targets. The IHC was evaluated by a single experienced pathologist.

Results: Prevalence studies in the 325 patients showed 26 patients (8%) were positive for HP on IHC, while 64 patients (19.7%) were positive on PCR testing (p<0.0001, Fisher’s test). Although the IHC testing showed 100% specificity, its sensitivity was a mere 40.63%. PCR testing captured all 26 patients (100% sensitivity) of patients positive on IHC, with no false negatives (100% specificity).

Conclusion: Advances in PCR diagnostics allows a much greater proportion of patients with HP to be diagnosed at the time of EGD. Indeed, IHC only had a sensitivity of 40.6% in diagnosing low-level HP infection, possibly due to changes in HP morphology associated with widespread PPI use. The majority of HP patients, i.e., 38 patients of 64 (59.4%) would have been missed on IHC, and likely labeled FD. Indeed, 38 of the 325 patient cohort (11.7%) would have been misdiagnosed, and be at risk of HP associated complications. Nearly all of these patients experienced significant improvement after standard HP treatment.