Path modeling suggests a causal sequence over time for the main disease parameters in patients with gastroesophageal reflux disease (GERD), thereby allowing for a prediction of the disease course, according to a study published in Diseases of the Esophagus.

Data on the progression of GERD is controversial. Some reports of increased esophageal acid exposure (EAE) and mucosal damage are considered evidence for a stable disease course, while others interpret these findings as disease progression. Consequently, researchers analyzed a large patient cohort with persisting symptoms indicative of GERD, who were on long-term proton pump inhibitor therapy. This analysis was performed to identify components of disease severity and progression

The researchers evaluated 972 patients with a mean age of 50.5 years, a mean body mass index of 27.2, and a mean time between symptom onset and diagnostic investigations of 8.2 years.

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They found that a longer disease history of GERD was significantly associated with a higher risk for lower esophageal sphincter (LES) incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES incompetence (n=563), compared to 6 years for those with a mechanically intact LES (n=95). A longer period between symptom onset and diagnosis was significantly associated with higher acid exposure.

To elucidate possible causal relationships over time, a path analysis was calculated.  The following model was significant:

‘History’ (P <.001➔LES-Incompetence & Hiatal Hernia➔(P <.001)➔pH-score (P <.001).

The authors concluded, “LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD.”

They added, “Path modeling supports a causal sequence of developing these disease-parameters over time.”


Fuchs KH, DeMeester TR, Otte F, et al. Severity of GERD and disease progression. Dis Esophagus. Published online February 11, 2021. doi:10.1093/dote/doab006