Among females older than 50 years, saliva secretion is significantly lower in non-erosive reflux disease patients than in healthy controls.

BACKGROUND: Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD. METHODS: Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: In males, no significant differences were observed in the amount of stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC. CONCLUSION: Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females.

Differences in salivary secretion and epidermal growth factor concentrations in mild reflux esophagitis and non-erosive reflux disease.

BACKGROUND: Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio. METHODS: Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA. RESULTS: No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups. CONCLUSION: After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.

Saliva secretion is reduced in mild reflux esophagitis patients.

BACKGROUND: Salivary secretion in patients with mild reflux esophagitis has not been examined. In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with mild reflux esophagitis were investigated. METHODS: Thirty-eight mild reflux esophagitis patients and 38 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS: The volume of saliva secreted was significantly (p = 0.0412) lower in the mild reflux esophagitis group than in the control group, with medians (25th-75th percentile) of 4.2 mL/3 min [2.6-6.2] and 6.0 [3.9-8.0], respectively. No significant differences were observed in salivary pH (the mild reflux esophagitis group: 7.1 [6.9-7.2], the control group 7.2 [7.1-7.3]). Salivary pH after acid loading was significantly (p = 0.0009) lower in the mild reflux esophagitis group (5.9 [5.5-6.3]) than in the control group (6.3 [6.2-6.5]). No significant differences were noted in salivary EGF concentrations (the mild reflux esophagitis group: 1739.0 pg/mL [1142.3-3329.0], the control group: 1678.0 [1091.8-2122.5]. CONCLUSION: The secretion volume and acid-buffering capacity of stimulated saliva were reduced in patients with mild reflux esophagitis.

Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients.

BACKGROUND: There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with NERD were examined. METHODS: Thirty-one PPI-responsive NERD patients and 31 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS: The amount of saliva secreted was significantly lower in the NERD group than in the control group, with medians (25th-75th percentile) of 4.0 mL/3 min (2.0-6.0) and 6.0 (3.9-8.0), respectively (p = 0.0131). Salivary pH was significantly lower in the NERD group (7.0 [6.8-7.2]) than in the control group (7.2 [7.0-7.3], p = 0.0100). Salivary pH after acid loading was significantly lower in the NERD group (5.8 [5.4-6.2]) than in the control group (6.3 [6.1-6.5], p = 0.0002). The difference in pH of stimulated saliva after acid loading (1.2 [0.9-1.5], p = 0.0021) was significantly higher in the NERD group than in the control group (0.8 [0.7-1.1]). The salivary EGF concentration was significantly higher in the NERD group (2513.0 pg/mL [1497.5-5005.0] than in the PPI-responsive group (1641.0 [1139.8-2092.0], p = 0.0032). CONCLUSION: Stimulated saliva secretion was reduced in PPI-responsive NERD patients.

Differences in clinical characteristics between conservative-treatment-response group and refractory (surgical-treatment) group in patients with jackhammer esophagus.

BACKGROUND: Jackhammer esophagus (JE) is a rare disease with unclear clinical features. The objective of this study was to retrospectively compare the clinical characteristics of patients with JE whose symptoms were controlled with conservative treatment, such as observation or medication, versus those who were required surgical treatment, such as surgical myotomy or per oral endoscopic myotomy. METHODS: Eighteen patients with JE were included in this study. The patients were divided into two groups: patients who responded to conservative treatment (C group) and patients who were refractory to conservative treatment and underwent surgery (S group). Patient age, sex, disease duration before treatment, symptoms, esophagogastroduodenoscopic (EGD) findings, esophagographic findings, esophageal wall thickness on computed tomography, number of swallows with hypercontractile peristalsis in 10 water swallows, and maximum distal contractile integral (DCI) were compared between the groups. RESULTS: Thirteen of 18 patients (72%) were in the C group and five of 18 (28%) were in the S group. There were no significant differences in age, sex, disease duration before treatment, symptoms, EGD findings, esophagographic findings, esophageal wall thickness, or number of swallows with hypercontractile peristalsis between the groups. On Starlet high-resolution manometry, the median maximum DCI value was significantly higher in the S group (32,651 mmHg-s-cm) than in the C group (17,926 mmHg-s-cm) (P = 0.0136). CONCLUSIONS: JE treatment should be carefully considered because some patients require surgery, whereas others are controlled with conservative treatment alone. A higher DCI value in patients with JE may predict resistance to conservative treatment.

Factors influencing subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease.

Although the presence of nonalcoholic fatty liver disease (NAFLD) is known to be related to subclinical atherosclerosis, the relationship between the severity of NAFLD and subclinical atherosclerosis is not clear. This study aimed to clarify the factors related to subclinical arteriosclerosis, including the histopathological severity of the disease and PNPLA3 gene polymorphisms, in NAFLD patients. We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness in 153 biopsy-proven NAFLD patients. The baPWV values were significantly higher in the advanced fibrosis group than in the less advanced group (median, 1679 cm/s vs 1489 cm/s; p = 5.49×10-4). Multiple logistic regression analysis revealed that older age (≥55 years) (p = 8.57×10-3; OR = 3.03), hypertension (p = 1.05×10-3; OR = 3.46), and advanced fibrosis (p = 9.22×10-3; OR = 2.94) were independently linked to baPWV ≥1600 cm/s. NAFLD patients were categorized into low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2) based on their risk factors, including older age, hypertension, and biopsy-confirmed advanced fibrosis. The prevalence of baPWV ≥1600 cm/s was 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high-risk group. Non-invasive liver fibrosis markers and scores, including the FIB-4 index, NAFLD fibrosis score, hyaluronic acid, Wisteria floribunda agglutinin positive Mac-2-binding protein, and type IV collagen 7s, were feasible substitutes for invasive liver biopsy. Older age, hypertension, and advanced fibrosis are independently related to arterial stiffness, and a combination of these three factors may predict risk of arteriosclerosis in NAFLD patients.

Efficacy of long-term maintenance therapy with 10-mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis.

BACKGROUND: To investigate the efficacy of long-term (52 weeks) maintenance therapy by 10-mg vonoprazan administration for proton pump inhibitor-resistant reflux esophagitis continued from the preceding study. METHODS: Sixteen patients with proton pump inhibitor-resistant reflux esophagitis (mean age 70.9 years, eight males) in whom endoscopic healing was achieved by 20-mg vonoprazan administration for 4 weeks and maintenance of remission was maintained by 10-mg vonoprazan administration for 8 weeks were enrolled. Endoscopy was performed at 52 weeks after the initiation of maintenance therapy with 10-mg vonoprazan to evaluate whether there was any recurrence of reflux esophagitis. Changes in the gastric mucosa were investigated at 52 weeks. Symptoms were assessed using the frequency scale for the symptoms of gastroesophageal reflux disease and the fast gastrin level at 8 and 52 weeks following the maintenance therapy. RESULTS: Endoscopic remission was maintained at 52 weeks in 15 (93.8%) of the 16 patients with proton pump inhibitor-resistant reflux esophagitis. One patient relapsed with grade C of reflux esophagitis. There were no significant differences in the symptom score at 8 and 52 weeks, nor the gastrin level at 8 and 52 weeks. There was no change in the stomach on endoscopy at 52 weeks. CONCLUSION: Long-term maintenance therapy by 10-mg vonoprazan administration is very effective for proton pump inhibitor-resistant reflux esophagitis patients in whom endoscopic healing was maintained by 8 weeks maintenance therapy with 10-mg vonoprazan administration.