Background: Esophageal dysmotility and gastroesophageal reflux disease are common in patients with advanced lung disease and can potentially affect outcomes of lung transplant; however, the effects of lung transplant on foregut function remain unknown. We assessed foregut function before and after bilateral lung transplant.Methods: We attempted complete foregut function testing before and after lung transplant. We compared patients with obstructive lung disease and patients with restrictive lung disease who underwent lung transplant between 2015 and 2016.Results: In total, 112 patients met inclusion criteria. The mean age of patients was 62.2 years, and 62 patients were men. A total of 51 patients (45.5%) were diagnosed with obstructive lung disease, and 56 patients (50.0%) were diagnosed with restrictive lung disease. Approximately half of these patients had a change in manometric diagnosis before and after lung transplant, with most achieving increased peristaltic vigor. Pre-lung transplant gastroesophageal reflux disease was more prevalent in the restrictive lung disease cohort than in the obstructive lung disease cohort (42.9% vs 19.6%, P ¼ .010). Thoracoabdominal pressure gradient before lung transplantation was greater in the restrictive lung disease group than in the obstructive lung disease group (23.4 vs 14.7 mm Hg, P < .001), which may explain the mechanism of increased reflux in patients with restrictive lung disease. No differences were seen in the post-lung transplant prevalence of pathological reflux and thoracoabdominal pressure gradient between groups.Conclusions: Esophageal motility and reflux parameters vary significantly between patients with obstructive lung disease and patients with restrictive lung disease, and can be explained by differences in underlying pulmonary dynamics. Restoring pulmonary physiology after lung transplant ameliorates the effects of esophageal dysmotility and reflux. Improved peristaltic vigor after lung transplant in patients with hypomotility is important, which may make them eligible for antireflux surgery if gastroesophageal reflux disease persists after lung transplant.

Advanced lung disease is associated with gastroesophageal reflux disease (GERD). The thoracoabdominal pressure gradient (TAPG) facilitates gastroesophageal reflux, but the effects of TAPG on gastroesophageal reflux in patients with pulmonary disease have not been well defined. Patients diagnosed with end-stage lung disease are expected to have the most extreme derangement in respiratory mechanics. The aim of this study is to explore the relationship between TAPG and reflux in lung transplant (LTx) candidates. We reviewed LTx recipients who underwent pretransplant esophageal high-resolution manometry and a 24-hour pH study. Patients were excluded if they were undergoing redo LTx, had manometric hiatal hernia, or had previously undergone foregut surgery. TAPG was defined as the intra-abdominal pressure minus the intrathoracic pressure during inspiration. Adjusted TAPG was calculated by the TAPG minus the resting lower esophageal sphincter (LES) pressure (LESP). Twenty-two patients with normal esophageal function tests (i.e., normal esophageal motility with neither manometric hiatal hernia nor pathological reflux on 24-hour pH monitoring) were selected as the pulmonary disease-free control group. In total, 204 patients underwent LTx between January 2015 and December 2016. Of these, 77 patients met inclusion criteria. We compared patients with obstructive lung disease (OLD, n = 33; 42.9%) and those with restrictive lung disease (RLD, n = 42; 54.5%). 2/77 patients (2.6%) had pulmonary arterial hypertension. GERD was more common in the RLD group than in the OLD group (24.2% vs. 47.6%, P = 0.038). TAPG was similar between the OLD group and the controls (14.2 vs. 15.3 mmHg, P = 0.850); however, patients in the RLD group had significantly higher TAPG than the controls (24.4 vs. 15.3 mmHg, P = 0.002). Although TAPG was not correlated with GERD, the adjusted TAPG correlated with reflux in all 77 patients with end-stage lung disease (DeMeester score, rs = 0.256, P = 0.024; total reflux time, rs = 0.259, P = 0.023; total number of reflux episodes, rs = 0.268, P = 0.018). Additionally, pathological reflux was seen in 59.1% of lung transplant candidates with adjusted TAPG greater than 0 mmHg (i.e., TAPG exceeding LESP); GERD was seen in 30.9% of patients who had an adjusted TAPG ≤ 0 mmHg. In summary, TAPG varies based on the underlying cause of lung disease. Higher adjusted TAPG increases pathological reflux, even if patients have normal antireflux anatomy and physiology (i.e., no hiatal hernia and manometrically normal LES function). Adjusted TAPG may provide further insights into the pathophysiology of GERD.

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Background Primary absent contractility is an uncommon finding on high-resolution manometry (HRM). The goal of this study was to describe the clinical spectrum and presentation of patients with primary absent contractility. Methods We queried a prospectively maintained esophageal testing registry to identify patients with absent contractility who presented between August 2016 and September 2018. Patients with poor quality studies and patients with insufficient clinical records as well as those with a history of previous foregut surgery or esophagram consistent with achalasia were excluded. Results A total of 2068 patients underwent HRM during the study period. Of these, 66 patients (3.2%) met the inclusion criteria and formed the study cohort; 52 patients in the cohort had an upper gastrointestinal contrast study, 50 had endoscopy, and 51 completed a foregut symptom questionnaire. Thirty-eight patients (57.6%) were women. The mean age was 56.6±13.86 years, and the mean body mass index was 26.37±5.7 kg/m 2 . Almost half of the patients (29/66, 43.9%) were undergoing lung transplant evaluation, and 22 patients (37.3%) had a history of autoimmune immune-mediated or myopathic diseases. On the symptom questionnaire, 42 of 51 patients (82.3%) reported heartburn, 24 of 51 (47.1%) reported dysphagia, and 23 of 51 patients (45.1%) reported both. On ambulatory pH monitoring, 23 of 37 patients (62.2%) had pathological esophageal acid exposure (acid exposure time >6%). Conclusions Absent contractility on HRM is uncommon and is frequently associated with connective tissue, myopathic or autoimmune disorders. The usual clinical presentation is reflux, dysphagia or both.

Hepatitis C virus (HCV) infection affects 2-3% of the population, approximately 170 million people worldwide, causing chronic HCV-related hepatitis with subsequent liver cirrhosis, hepatic failure, hepatocellular cancer, and liver-related mortality in a large number of patients. The gold standard therapy, pegylated interferon alpha in combination with ribavirin can eradicate hepatitis C virus infection in approx. 40% of treatment-naïve patients infected with HCV genotype G1, and only 15-20% of patients with previous treatment. Success rate is substantially improved with the development and registration of two direct acting anti-hepatitis C virus protease inhibitors (boceprevir and telaprevir) in the second decade of 21st century: combined with the standard therapy, almost three quarter of previously untreated, and more than half of previously unsuccessfully treated patients can achieve sustained viral response with protease inhibitor based triple therapies. A major barrier to successful treatment is the association of peginterferon/ribavirin therapy with frequent and sometimes serious adverse effects. In clinical trials, approximately 10-15% of treated patients discontinue peginterferon and ribavirin due to adverse events; however, in routine clinical practice, the rate of treatment discontinuation has been reported to be substantially higher. The side effects of peginterferon/ribavirin therapy affect virtually all organ systems, and addition of protease inhibitor can amplify these side effects (particularly anemia), and/or may lead to new ones (i.e., dysgeusia with boceprevir or skin rush with telaprevir). There is considerable regional and global variability in the nature and prevalence of these adverse effects as well as in the best strategies to ameliorate their impact on hepatitis C virus treatment. This article summarizes the side effects of dual and triple therapies and their management based on the labels of the drugs, on a comprehensive literature review, as well as on the recently published opinion of an international panel of experts - with the provision of providing help for the physicians treating hepatitis C virus infection to achieve the best possible success with the highest possible safety for the patients.