Nonalcoholic Fatty Liver Disease as a Systemic Disease and the Need for Multidisciplinary Care

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease, and there has been a rapid increase in cases worldwide. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma and is also associated with an increased risk of cardiovascular disease or exacerbation of other organ diseases, thus posing a significant health problem from both a medical and a socioeconomic perspective. NAFLD is a systemic disease and requires the involvement of numerous medical professionals. Multidisciplinary collaboration, in which different professionals within different specialties come together and work together toward a common goal, supports better patient care by integrating perspectives of multiple experts and facilitating the exchange of opinions. Due to the large number of potential patients, gastroenterologists and hepatologists cannot manage the patients alone, and collaboration between specialists in various fields, including family doctors, dentists, nutritionists, and pharmacists is required for treatment of NAFLD. This review will discuss NAFLD from the perspective of various specialties and introduce multidisciplinary collaboration.

Clinical outcomes of permanent stenting with endoscopic ultrasound gallbladder drainage

Background/Aims@#Endoscopic ultrasound gallbladder drainage (EUS-GBD) is gaining attention as a treatment method for cholecystitis. However, only a few studies have assessed the outcomes of permanent stenting with EUS-GBD. Therefore, we evaluated the clinical outcomes of permanent stenting using EUS-GBD. @*Methods@#This was a retrospective, single-center cohort study. The criteria for EUS-GBD at our institution are a high risk for surgery, inability to perform surgery owing to poor performance status, and inability to obtain consent for emergency surgery. EUS-GBD was performed using a 7-Fr double-pigtail plastic stent with a dilating device. The primary outcomes were the recurrence-free rate of cholecystitis and the late-stage complication-avoidance rate. Secondary outcomes were technical success, clinical success, and procedural adverse events. @*Results@#A total of 41 patients were included in the analysis. The median follow-up period was 168 (range, 10–1,238) days. The recurrence-free and late-stage complication-avoidance rates during the follow-up period were 95% (38 cases) and 90% (36 cases), respectively. There were only two cases of cholecystitis recurrence during the study period. @*Conclusions@#EUS-GBD using double-pigtail plastic stent was safe and effective with few complications, even in the long term, in patients with acute cholecystitis.

Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future

Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

Natural History of Chronic Intestinal Pseudo-obstruction and Need for Palliative Care

Background/Aims@#Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients. @*Methods@#From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course. @*Results@#Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m2 , 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care. @*Conclusion@#CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.

Safety and Efficacy of Elobixibat, an Ileal Bile Acid Transporter Inhibitor, in Elderly Patients With Chronic Idiopathic Constipation According to Administration Time: Interim Analysis of Post-marketing Surveillance

Background/Aims@#Elobixibat, an ileal bile acid transporter (apical sodium-dependent bile acid transporter) inhibitor, was recently launched in Japan for the treatment of chronic idiopathic constipation. We conducted an interim analysis of post-marketing surveillance to evaluate the safety and efficacy of elobixibat in elderly patients with chronic constipation and compared the efficacy according to administration time. @*Methods@#Safety and efficacy outcomes were evaluated through patient interviews for 4 weeks. @*Results@#Adverse drug reactions (ADRs) were observed in 5.24% of the 1049 patients analyzed; diarrhea (2.19%) and abdominal pain (1.81%) were the most common. A serious ADR of death was reported in one patient (0.10%). The incidence of ADRs in the ≥ 65-year old or ≥ 75-year-old subpopulation was similar to that in the total patient population. Mean bowel movements per week significantly increased from 2.9 ± 2.5 at baseline to 5.0 ± 3.1 (P< 0.001) at Week 2 and 5.3 ± 2.6 (P < 0.001) at Week 4. The mean Bristol Stool Form Scale score significantly increased from 2.3 ± 1.4 at baseline to 3.8 ± 1.3 (P < 0.001) at Week 2 and 3.9 ± 1.1 at Week 4 (P < 0.001). Bowel movements significantly increased in the elderly population and subpopulations receiving elobixibat before breakfast, lunch, or dinner. The median time to bowel movement was 5 hours. @*Conclusion@#The results suggested that elobixibat was well-tolerated and efficacious in elderly patients with chronic constipation and can be administered before any meals.

Endoscopic Interventions for the Early and Remission Phases of Acute Biliary Pancreatitis: What are the More Concrete and Practical Situations for Performing Them?

Background/Aims@#The use of endoscopic intervention (EI) for acute biliary pancreatitis (ABP) remains controversial because the severity of biliary obstruction/cholangitis/pancreatitis is not reflected in the indications for early EI (EEI). @*Methods@#A total of 148 patients with ABP were included to investigate 1) the differences in the rate of worsening cholangitis/pancreatitis between the EEI group and the early conservative management (ECM) group, especially for each severity of cholangitis/pancreatitis, and 2) the diagnostic ability of imaging studies, including endoscopic ultrasound (EUS), to detect common bile duct stones (CBDSs) in the ECM group. @*Results@#No differences were observed in the rate of worsening cholangitis between the EEI and ECM groups, regardless of the severity of cholangitis and/or the existence of impacted CBDSs. Among patients without impacted CBDSs and moderate/severe cholangitis, worsening pancreatitis was significantly more frequent in the EEI group (18% vs. 4%, p=0.048). In patients in the ECM group, the sensitivity and specificity for detecting CBDSs were 73% and 98%, respectively, for EUS, whereas the values were 13% and 92%, respectively, for magnetic resonance cholangiopancreatography. @*Conclusions@#EEI should be avoided in the absence of moderate/severe cholangitis and/or impacted CBDSs because of the high rate of worsening pancreatitis. EUS can contribute to the accurate detection of residual CBDSs, for the determination of the need for elective EI.

Feasibility of Endoscopic Papillary Large Balloon Dilation in Patients with Difficult Bile Duct Stones without Dilatation of the Lower Part of the Extrahepatic Bile Duct

BACKGROUND/AIMS: There is no consensus for using endoscopic papillary large balloon dilation (EPLBD) in patients without dilatation of the lower part of the bile duct (DLBD). We evaluated the feasibility and safety of EPLBD for the removal of difficult bile duct stones (diameter ≥10 mm) in patients without DLBD. METHODS: We retrospectively reviewed the records of 209 patients who underwent EPLBD for the removal of bile duct stones from October 2009 to July 2014. Primary outcomes were the clearance rate and additional mechanical lithotripsy. Secondary outcomes were the incidence of complications and recurrence rate. RESULTS: Fifty-seven patients had DLBD (27.3%), and 152 did not have DLBD (72.7%). There were no significant differences in the overall success rate or the use of mechanical lithotripsy. Success rate during the first session and procedure time were better in the DLBD than the without-DLBD group (75.7% vs 66.7%, 48.1±23.0 minutes vs 58.4±31.7 minutes, respectively). As for complications, there were no significant differences in the incidence of pancreatitis, perforation or bleeding after endoscopic retrograde cholangiopancreatography. The recurrence rate did not differ significantly between the two groups. CONCLUSIONS: EPLBD is a useful and safe method for common bile duct stone removal in patients without DLBD.

Early Effect of Single-dose Sitagliptin Administration on Gastric Emptying: Crossover Study Using the 13C Breath Test

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.

Visceral Obesity as a Risk Factor for Left-Sided Diverticulitis in Japan: A Multicenter Retrospective Study

BACKGROUND/AIMS: Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan. METHODS: Right-sided diverticulitis and left-sided diverticulitis patients (total of 215) were compared with respect to background, particularly obesity-related factors to identify risk factors for diverticulitis. RESULTS: There were 166 (77.2%) right-sided diverticulitis patients and 49 (22.8%) left-sided diverticulitis patients. The proportions of obese patients (body mass index > or =25 kg/m2, p=0.0349), viscerally obese patients (visceral fat area > or =100 cm2, p=0.0019), patients of mean age (p=0.0003), and elderly patients (age > or =65 years, p=0.0177) were significantly higher in the left-sided-diverticulitis group than in the right-sided-diverticulitis group. The proportion of viscerally obese patients was significantly higher in the left-sided-diverticulitis group than in the left-sided-diverticulosis group (p=0.0390). CONCLUSIONS: This study showed that obesity, particularly visceral obesity, was a risk factor for left-sided diverticulitis in Japan.

Comparative Study of 2 Different Questionnaires in Japanese Patients: The Quality of Life and Utility Evaluation Survey Technology Questionnaire (QUEST) Versus the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease Questionnaire (FSSG)

BACKGROUND/AIMS: The aim of this study was to examine the convenience of the quality of life and utility evaluation survey technology (QUEST) questionnaire and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire as self-assessment diagnostic instrument. METHODS: This was a two-way crossover study conducted over 6 weeks from September 2010 to November 2010. The subjects were 60 consecutive patients admitted to the Hiratsuka city hospital with a gastrointestinal condition, regardless of the coexistence of heartburn. They were assigned to fill in both the QUEST and FSSG questionnaires in random order. We analyzed the time taken to complete the questionnaires, whether subjects asked any questions as they filled in the questionnaire, and the questionnaire scores. RESULTS: Comparison of the QUEST and the FSSG revealed significant differences in the completion time (196.5 vs. 97.5 seconds, respectively; P or = 4 was lower than < 4 (170.5 vs. 214.0 seconds, respectively; P = 0.022), and the QUEST score was significantly higher without questions than with question (3 vs. 1 points, respectively; P = 0.025). CONCLUSIONS: This study revealed that the FSSG questionnaire may be easier for Japanese subjects to complete than the QUEST questionnaire.

Change of Gastric Emptying With Chewing Gum: Evaluation Using a Continuous Real-Time 13C Breath Test (BreathID System)

BACKGROUND/AIMS: There are few reports on the correlation between chewing gum and the gastrointestinal functions. But previous report showed use of chewing gum to be an effective method for controlling gastrointestinal symptoms. The aim of this study was to determine the correlation between chewing gum and gastric emptying using the continuous real time 13C breath test (BreathID system). METHODS: Ten healthy male volunteers participated in this randomized, 2-way crossover study. The subjects fasted overnight and were randomly assigned to chewing gum (Xylish, 2-3/1 tablet) for an hour following intake of a test meal (200 kcal/200 mL) or intake of the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, T1/2 (median, 111.82 vs 109.26 minutes; P = 0.575), Tlag (median, 53.28 vs 56.53 minutes; P = 0.333), gastric emptying coefficient (median, 3.58 vs 3.65; P = 0.285), regression-estimated constant beta (median, 1.85 vs 1.80; P = 0.575) and regression-estimated constant kappa (median, 0.61 vs 0.62; P = 0.959) were observed between the test meal alone group and the test meal and chewing gum group. CONCLUSIONS: This study showed that chewing gum had no effect on the rate of gastric emptying. Therefore, since chewing gum did not enhance the speed of gastric emptying, it may ameliorate gastrointestinal symptoms through other mechanisms, such as saliva and autonomic nervous system.

Effects of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors on the Rate of Gastric Emptying: A Crossover Study Using a Continuous Real-Time 13C Breath Test (BreathID System)

BACKGROUND/AIMS: The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous 13C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). METHODS: Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of 13C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the 13C-acetic acid breath test performed using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, the T1/2, Tlag, GEC, beta and kappa, were observed among the 3 test conditions. CONCLUSIONS: The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.

Mosapride Accelerates the Delayed Gastric Emptying of High-Viscosity Liquids: A Crossover Study Using Continuous Real-Time 13C Breath Test (BreathID System)

BACKGROUND/AIMS: The administration of liquid nutrients to patients is often accompanied by complications such as gastroesophageal reflux. To prevent gastroesophageal reflux, high-viscosity liquid meals are used widely, however, it still remains controversial whether high-viscosity liquid meals have any effect on the rate of gastric emptying. The present study was conducted with the aim of determining whether high-viscosity liquid meals had any effect on the rate of gastric emptying and mosapride might accelerate the rate of gastric emptying of high-viscosity liquid meals. METHODS: Six healthy male volunteers underwent 3 tests at intervals of > 1 week. After fasting for > 8 hours, each subject received one of three test meals (liquid meal only, high-viscosity liquid meal [liquid meal plus pectin] only, or high-viscosity liquid meal 30 minutes after intake of mosapride). A 13C-acetic acid breath test was performed, which monitored the rate of gastric emptying for 4 hours. Using the Oridion Research Software (beta version), breath test parameters were calculated. The study parameters were examined for all the 3 test conditions and compared using the Freidman test. RESULTS: Gastric emptying was significantly delayed following intake of a high-viscosity liquid meal alone as compared with a liquid meal alone; however, intake of mosapride prior to a high-viscosity liquid meal was associated with a significantly accelerated rate of gastric emptying as compared with a high-viscosity liquid meal alone. CONCLUSIONS: This study showed that high-viscosity liquid meals delayed gastric emptying: however, mosapride recovered the delayed rate of gastric emptying by high-viscosity liquid meals.