Development of a novel multipoint traction device for gastric and colorectal endoscopic submucosal dissection and evaluation of its efficacy and safety.

BACKGROUND: Proper traction allows safer and easier endoscopic submucosal dissection; however, single-point traction may not be sufficient. In this study we assessed the safety, efficacy, and feasibility of our newly developed multipoint traction device. METHODS: During an ex vivo study using a Konjac training model, two experts and two trainees resected 80 mock lesions of 20-mm diameter by performing endoscopic submucosal dissection with and without multipoint traction. The primary outcome was the success rate of the procedure involving traction. The secondary outcomes were the submucosal dissection time, dissection speed, and perforation during endoscopic submucosal dissection. During the in vivo study, to clarify the initial clinical outcomes, we used data from the electronic medical record of patients at our institution who underwent gastric and colorectal endoscopic submucosal dissection, which was performed by experts with our newly developed multipoint traction device, from March to December 2022. RESULTS: The ex vivo study indicated that all traction procedures were successful. Higher resection speeds were observed with endoscopic submucosal dissection with traction than without traction (P < 0.001). Perforations were not observed. During the first in vivo clinical study, traction was feasible during 20 gastric and colorectal endoscopic submucosal dissection procedures. No adverse events occurred. CONCLUSIONS: Our multitraction device can increase the submucosal dissection speed and simplify endoscopic submucosal dissection techniques, thus safely reducing technical challenges. The application of this device for endoscopic submucosal dissection could lead to safer and more efficient procedures. Clinical registration UMIN Clinical Trials Registry, Japan (registration number UMIN000053384).

Operational effectiveness of three-dimensional flexible endoscopy: an ex vivo study using a new model.

BACKGROUND AND OBJECTIVES: Two-dimensional (2D) images lack depth information and thus provide probabilistic recognition that do not completely match the actual three-dimensional (3D) information. Here, we investigated the operability of 3D endoscopes. METHODS: A 3D operation model was developed by passing 20 silk threads through upper and lower plates at 2-mm intervals in front and back rows separated by 1 mm. We evaluated accuracy and time of operating an electrosurgical knife. A successful operation was defined as pulling only a front-row thread; an unsuccessful operation was defined as pulling no thread (miss) or simultaneously pulling front- and back-row threads. Endoscopists (four experts, six trainees) repeated the operation under 2D and 3D conditions until individually accumulating 10 successful attempts under each condition. RESULTS: Operation accuracy was significantly higher for 3D compared with 2D in all endoscopists (88.5% vs. 61.3%; p < 0.01) and in both experience groups (trainees: 84.5% vs. 61.2%; experts: 95.2% vs. 61.5%; both p < 0.01). Operation time was significantly shorter for 3D compared with 2D in all endoscopists (12.5 ± 4.1 s vs. 14.8 ± 4.7 s; p < 0.01) and in both experience groups (trainees: 12.8 ± 4.2 s vs. 15.2 ± 4.9 s; experts: 12.1 ± 4.0 s vs. 14.3 ± 4.3 s; both p < 0.01). DISCUSSION: Compared with 2D endoscopy, 3D endoscopy significantly improved operation accuracy and shortened operation time, suggesting that 3D endoscopy enables accurate operation by depth information, aiding spatial recognition.

Esophageal Motility after Extensive Circumferential Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is sometimes extensive, and in our experience, patients not infrequently present with dysphagia after ESD even in the absence of esophageal stricture. The aim of this study was to evaluate esophageal motility using high-resolution manometry (HRM) in patients with and without dysphagia after extensive circumferential ESD. METHODS: HRM was performed in a total of 52 patients who had undergone ESD for superficial esophageal cancer and a mucosal defect after ESD exceeded more than two-thirds of the esophageal circumference. The frequency and type of esophageal dysmotility and the relationship between esophageal motility and dysphagia were evaluated. RESULTS: Esophageal dysmotility was observed in 13 patients (25%): jackhammer esophagus in 4, esophagogastric junction outflow obstruction in 4, absent contractility in 2, and distal esophageal spasm, ineffective esophageal motility, and fragmented peristalsis in 1 patient each. Of the 22 patients with dysphagia after ESD, 9 (41%) had esophageal dysmotility. Of the 30 patients without dysphagia after ESD, 4 (13%) had esophageal dysmotility. The relationship between dysmotility and dysphagia was significant (p = 0.025). CONCLUSIONS: Esophageal dysmotility exists in approximately one-quarter of patients after extensive circumferential ESD, which is associated with dysphagia in the absence of esophageal stricture.

Characterization of Helicobacter pylori-Naïve Early Gastric Cancers.

AIM: Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. SUBJECTS AND METHODS: Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. RESULTS: It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. CONCLUSIONS: H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.

Postoperative bleeding after gastric endoscopic submucosal dissection in patients receiving antithrombotic therapy.

BACKGROUND AND AIMS: It is controversial whether antithrombotic therapy increases the risk of bleeding after endoscopic submucosal dissection (ESD). The aim of this study was to evaluate the effects of antithrombotic therapy on gastric ESD. METHODS: Patients who underwent gastric ESD at Toranomon Hospital between April 2005 and July 2014 were enrolled. The risk of post-ESD bleeding was evaluated by multivariate logistic regression analysis. RESULTS: Of 1781 patients enrolled, 253 were taking an antithrombotic; 186 discontinued taking a single antithrombotic (n = 150) or multiple antithrombotics (n = 36) before ESD, whereas 15 continued taking a single antiplatelet agent and another 52 switched to heparin alternative therapy during the peri-ESD period. Post-ESD bleeding occurred in 101 patients (5.7 %): 68 patients (3.8 %) who did not take an antithrombotic, 11 patients (7.3 %) who discontinued taking a single antithrombotic, six patients (16.7 %) who discontinued taking multiple antithrombotics, one patient (6.7 %) who continued taking a single antiplatelet agent, and 15 patients (28.8 %) who switched to heparin therapy. In multivariate analysis, heparin alternative therapy [odds ratio (OR) 10.04, 95 % confidence interval (CI) 4.35-23.16], discontinuation of the use of multiple antithrombotics before ESD (OR 5.44, 95 % CI 2.00-14.79), tumor location in the lower third of the stomach (OR 2.17, 95 % CI: 1.32-3.58), and a long procedure time (100 min or greater; OR 2.00, 95 % CI 1.25-3.20) were independent risk factors for post-ESD bleeding. Among 52 subjects who switched to heparin therapy, one developed acute renal infarction and one developed cerebral bleeding. CONCLUSIONS: Because heparin alternative therapy significantly increases the risk of post-ESD bleeding and may not decrease the risk of thromboembolic events, other options should be considered for patients receiving anticoagulation therapy.

Feasibility Study of the Three-Dimensional Flexible Endoscope in Endoscopic Submucosal Dissection: An ex vivo Animal Study.

BACKGROUND/AIM: Clinical application of 3-dimensional (3D) technology for flexible endoscopes has not been reported. We developed a 3D flexible endoscope and conducted a feasibility study of endoscopic submucosal dissection (ESD) in porcine stomach. METHODS: Four endoscopists used a 3D flexible endoscope to perform a total of 8 ESD procedures on resected porcine stomachs. We assessed the en bloc resection rate, perforation rate, and mechanical issues that arise during ESD. A visual analog scale (0, 2D superior; 100, 3D superior) was used to evaluate the depth perception, sense of security of the procedure, and eyestrain of 3D visualization. RESULTS: En bloc resection was achieved in all cases and there were no cases of perforation or mechanical issues. Depth perception and sense of security were rated 85.5 ± 12.4 and 70.7 ± 9.7 respectively (mean ± SDs). Eyestrain was rated high for 3D visualization (mean ± SDs, 12.6 ± 8.6). CONCLUSIONS: ESD using a 3D flexible endoscope was technically feasible. The endoscopists reported good depth perception and a high sense of security when using 3D visualization but also noted strong eyestrain.

Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection for Non-Ampullary Superficial Duodenal Tumor.

BACKGROUND: Endoscopic submucosal resection (ESD) and endoscopic mucosal resection (EMR) are well established as curable and safety procedures for treating superficial tumors of the stomach, esophagus and colon. However, a majority of endoscopic resection strategies for non-ampullary superficial duodenal tumors (NASDTs) remains undefined. The aim of this study was to clarify which was the right method for NASDT treatment - EMR or ESD. SUMMARY: We analyzed 129 consecutive endoscopic resection (74 ESD and 55 EMR) procedures performed with NADSTs and divided the ESD group into 49 large ESD groups (more than 20 mm in diameter) and 25 small ESD groups (less than 20 mm in diameter). With respect to the technical outcomes of EMR/ESD for small size NASDTs, EMR was safer than ESD, but its nature of curability was inferior to that of ESD. The rates of complication such as perforation or delayed bleeding were significantly higher in both ESD groups than in the EMR group. However, the prophylactic endoscopic closure of large mucosal defects after ESD was useful for resolving those complications. The limitations of our study were involvement of a single-center, limited sample size, short follow-up duration and the retrospective design, which may have introduced selection bias. However, the present findings suggest that adequate endoscopic treatment strategy for NASDTs can lead to favorable outcomes and an excellent prognosis. Key Message: It is necessary to select EMR or ESD adequately for R0 resection of small NASDTs, according to their size and location. For large NASDTs, duodenal ESD with essential management is feasible and useful as a therapeutic procedure.

Feasibility of a Newly Developed Thumb Control Device for Simultaneous Manipulation of the Endoscope and Treatment Devices in Endoscopic Submucosal Dissection: A Clinical Feasibility Study.

BACKGROUND/AIM: We developed a new device for the simultaneous manipulation of an endoscope and treatment devices, which we named the Smart Shooter®. The aim of this study was to validate the feasibility of using the Smart Shooter® in endoscopic submucosal dissection (ESD). METHODS: This pilot feasibility study conducted between March and June 2014 involved 20 consecutive patients who underwent ESD for superficial gastrointestinal neoplasia. The primary endpoint was a serious adverse event during the ESD procedure. The secondary endpoints were completion rate of ESD using the Smart Shooter® and a mechanical problem with the Smart Shooter® during ESD. RESULTS: A total of 20 patients underwent ESD for 23 lesions: 5 pharyngeal, 8 esophageal, 7 gastric, and 3 colonic lesions. There were no serious adverse events or mechanical problems during ESD. The completion rate of ESD using the Smart Shooter® was 82.6% (19/23). CONCLUSION: ESD using the Smart Shooter® appears to be technically feasible. CLINICAL TRIAL REGISTRATION: UMIN 000013710.

Conventional White Light Endoscopic Features of Small Superficial Barrett's Esophageal Adenocarcinoma.

BACKGROUND: Superficial Barrett's esophageal adenocarcinoma (BEA) arising from short-segment Barrett's esophagus (SSBE) is visualized as a reddish lesion located on the right or anterior side wall of the esophagogastric mucosal junction (EGJ) and showing an elevated macroscopic appearance under conventional white light endoscopy (WLE). However, because the form and color are variable, misdiagnosis as reflux esophagitis or SSBE is frequent under WLE. The aim of this study is to clarify conventional WLE features of small superficial BEA. SUMMARY: We retrospectively analyzed 30 lesions ≤20 mm in diameter in 30 patients who underwent endoscopic mucosal resection or endoscopic submucosal dissection at Toranomon Hospital between 2002 and 2014. Mean age of patients with small superficial BEA arising from SSBE was 64.3 ± 11.2 years, and mean tumor size was 12.0 ± 4.8 mm. Small superficial BEA fell into the following 4 categories based on WLE features: EGJ polyp type, 43.3% (13 of 30 lesions); triangular SSBE type, 43.3% (13 of 30 lesions); cardiac erosion type, 10.0% (3 of 30 lesions); and unclassified or mixed type, 3.4% (1 of 30 lesions). EGJ polyp-type tumors were located on the right or anterior side wall of the EGJ, and no tumors showed invasion to the submucosal layer. On the other hand, triangular SSBE-type tumors were located anywhere in the EGJ, and 38.5% showed submucosal invasion (5 of 13 lesions). KEY MESSAGES: We consider this classification significantly contributes to the detection of small superficial BEA arising from SSBE under WLE.

Endocytoscopy is a promising modality with high diagnostic accuracy for gastric cancer.

BACKGROUND AND STUDY AIM: Endocytoscopy (ECS) enables in vivo microscopic imaging, which allows analysis of mucosal structures at the cellular level; however, limited data are available on the validity of ECS in the stomach. The aim of this study was to evaluate the feasibility of ECS in the diagnosis of early gastric cancer. PATIENTS AND METHODS: Gastric lesions that were the targets of histopathological diagnosis by endoscopic submucosal dissection or biopsy specimen were prospectively enrolled and evaluated using a single charge-coupled device-integrated endocytoscope, following double staining with crystal violet and methylene blue. High grade ECS atypia was defined according to specific irregularities in gland structure and cell nuclei. The primary end point was the accuracy of ECS diagnosis for gastric cancer, using histopathological diagnosis as the gold standard. RESULTS: A total of 82 lesions were investigated, including 23 early gastric cancers, 10 gastric adenomas, and 49 non-neoplastic lesions. Ten lesions could not be clearly observed by ECS because of poor staining due to viscous mucus or plaque; thus, assessability rates with ECS were 88 % in total and 91 % for gastric cancer. High grade ECS atypia was observed in 86 % of assessable gastric cancers, but not in any cases of gastric adenomas or non-neoplastic lesions. The sensitivity, specificity, positive and negative predictive values of high grade ECS atypia as the criterion for the diagnosis of gastric cancer were 86 %, 100 %, 100 %, and 94 %, respectively. No serious complications occurred during or after the examinations. CONCLUSION: ECS is a clinically feasible modality to obtain in vivo histology, with high diagnostic accuracy in gastric cancer.

Ex vivo comparison study of smart Shooter®, a new endoscopic device for safe and speedy treatment.

BACKGROUND: In many endoscopic procedures, the operative view can be compromised when manipulating the treatment device because the endoscopists must release their hand from the endoscope. We have developed a new device called the Smart Shooter® (SS) for simultaneous manipulation of the endoscope and treatment device, and evaluated the utility of the SS compared with the conventional method. METHODS: The SS is a semirigid, loop-shaped channel extender that enables endoscopists to manipulate the treatment device with the thumb of the right hand while holding the endoscope with the same hand. We conducted a comparative study of gastric endoscopic submucosal dissection (ESD) and esophageal injection sclerotherapy (EIS) in a porcine model to compare the utility of the SS method with the conventional method. RESULTS: In gastric ESD, all lesions were resected en bloc with no perforation. The mean operative time was significantly shorter with the SS method than with the conventional method (287.5 ± 155.4 vs. 403.5 ± 215.6 s, p = 0.04). In esophageal EIS, 4 paravenous injections were given with the SS method and 5 were given using the conventional method. Similarly, the mean operative time was significantly shorter with the SS method than with the conventional method (19.0 ± 7.8 vs. 23.8 ± 10.0 s, p = 0.04). CONCLUSION: Use of the SS enabled a shorter operative time for gastric ESD and esophageal EIS with no adverse events. The present results suggest that the SS can contribute to safe and speedy endoscopic treatment.

Delayed bleeding after endoscopic submucosal dissection for non-ampullary superficial duodenal neoplasias might be prevented by prophylactic endoscopic closure: analysis of risk factors.

BACKGROUND AND AIM: Duodenal endoscopic submucosal dissection (ESD) is technically challenging because of anatomical specificities and, to date, has not been validated concerning the high rate of complications such as perforation and delayed bleeding. In the present study, the risk factors for delayed bleeding after duodenal ESD are presented with the goal of establishing preventive measures. METHODS: We analyzed 63 patients with non-ampullary superficial duodenal neoplasias treated by ESD from April 2005 to March 2014. To analyze the risk factors of delayed bleeding after duodenal ESD, we divided the patients into a delayed bleeding group and a non-bleeding group. To verify the risk factors of delayed bleeding after duodenal ESD, we analyzed various patient-, lesion-, and treatment-related factors. RESULTS: Delayed bleeding was experienced in 11 patients (17.5%) Univariate analysis of patient-related risk factors of delayed bleeding indicated no significant risk factor. Univariate analysis of lesion-related and treatment-related risk factors indicated only endoscopic closure as a significant risk factor. Multivariate analysis also identified endoscopic closure (not done > done: P = 0.049) as an independent factor significantly associated with delayed bleeding after duodenal ESD. Hypertension (present > absent: P = 0.055) showed a non-significant tendency of association by multivariate analysis. CONCLUSIONS: This retrospective evaluation found that endoscopic closure was associated with a reduced risk of delayed bleeding after duodenal ESD. Delayed bleeding after duodenal ESD might be prevented by prophylactic endoscopic closure.

Accuracy and concordance of endocytoscopic atypia for the diagnosis of gastric cancer.

BACKGROUND AND AIM: High-grade atypia demonstrated by endocytoscopy may be a key criterion for the diagnosis of gastric cancer. We therefore sought to verify whether endocytoscopic atypia can provide satisfactory levels of diagnostic accuracy and concordance among trainee and expert endoscopists. METHOD: A total of 100 lesions evaluated by endocytoscopy and histopathology were enrolled to create an endocytoscopic image catalog (44 early cancers, 10 low-grade adenomas, 46 non-neoplastic lesions). Four endoscopists (two trainees and two experts) independently reviewed the catalog images and evaluated each of them for the presence or absence of endocytoscopic atypia. High-grade endocytoscopic atypia, as a criterion for cancer diagnosis, was defined as the consistent observation of any of the following features: lumen absence, lumen fusion, and irregular nuclei showing the three typical features (heterogeneous shape, swelling, and disarrangement). RESULTS: High-grade endocytoscopic atypia was observed in 78 %, 18 %, and 4 % of cancers, adenomas, and non-neoplastic lesions, respectively. The sensitivity, specificity, accuracy, and positive and negative predictive values for cancer diagnosis by endocytoscopy were 78.4 %, 93.3 %, 87.3 %, 85.4 %, and 87.3 %, respectively. The concordance rate for the results of high-grade endocytoscopic atypia was good among the four endoscopists (κ value 0.682). No significant difference in diagnostic accuracy or concordance was observed between trainee and expert endoscopists. CONCLUSION: Using the defined high-grade atypia as a diagnostic criterion of cancer, endocytoscopy provided a satisfactory level of accuracy and concordance for the diagnosis of early gastric cancer, regardless of endoscopic expertise.

A new device for simultaneous manipulation of an endoscope and a treatment device during procedures: an ex vivo animal study.

BACKGROUND AND STUDY AIMS: Endoscopists must maneuver both endoscope and treatment device during procedures, requiring them to release their hand from the scope to manipulate the treatment device. Aiming to improve this situation, we developed a new device called the Thumb Drive. PATIENTS AND METHODS: The Thumb Drive comprises a controller and catheter. After attaching the controller to the endoscope's grip, the catheter is inserted into the forceps channel. The treatment device is then inserted into the Thumb Drive and fixed with its tip protruding from the endoscope tip. A single endoscopist resected 10 lesions in a porcine stomach by endoscopic submucosal dissection (ESD) using the Thumb Drive. RESULTS: All lesions were resected en bloc using this new device without any perforations. The mean incision, dissection, and operative times were 97.2 ± 48.7 seconds, 121.6 ± 53.6 seconds, and 218.8 ± 67.8 seconds, respectively. CONCLUSIONS: The Thumb Drive enables the endoscopist to manipulate the treatment device with the thumb while handling the endoscope with the right hand during ESD. Its utility should be examined in in vivo studies as a next step.

Clinicopathological features of patients with acute graft-versus-host disease of the upper digestive tract.

BACKGROUND AND AIMS: Acute graft-versus-host disease (GVHD) occurring within 100 days post-transplant is one of critical factors influencing prognosis in transplant recipients. Among cases of GVHD of the gastrointestinal (GI) tract, GVHD rarely affects the upper GI. In this study, we retrospectively examined the frequency of upper GI GVHD and diagnostic accuracy. PATIENTS AND METHODS: From among 868 patients who underwent allogeneic hematopoietic stem cell transplantation at our hospital between January 2005 and June 2012, 115 of whom underwent biopsy for upper GI symptoms. The endoscopic findings and histologic diagnosis from these 115 patients were retrospectively analyzed. RESULTS: GVHD was histologically diagnosed in 85 patients overall (9.8% of all 868 transplant recipients). Although gastric mucosal exfoliation was not commonly observed, this endoscopic finding when used as a diagnostic predictor had both a specificity and positive predictive value (PPV) of 100%. When using redness, luster, and mucosal change as predictors, specificity and PPV were relatively high, suggesting that these gastric endoscopic findings are useful in the diagnosis of upper GI GVHD. Among the duodenal endoscopic findings, erosion as a diagnostic predictor had both a high specificity and PPV. The biopsy results often lead to a diagnosis of GVHD even in cases judged to be endoscopically normal. CONCLUSIONS: Among the gastric endoscopic findings, mucosal exfoliation, although rare, and redness, luster, and mucosal change are likely to be useful diagnostic predictors of upper GI GVHD. GVHD was frequently diagnosed in patients with endoscopically normal duodenum, suggesting that biopsies are important for definitive diagnosis.

PIVKA­II is associated with liver function, bone metabolism, and muscle function in patients with liver disease.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Direct­acting antiviral treatment decreases serum undercarboxylated osteocalcin in male patients with chronic hepatitis C.

Hepatic osteodystrophy (HOD) is a common complication of chronic liver disease, including viral hepatitis. Hepatitis C virus (HCV) infection is associated with an increased risk of osteoporosis and bone mineral density (BMD) loss. Direct-acting antiviral (DAA) treatment is used to treat HCV infections; however, its effects on bone metabolism have not been reported. We compared the clinical data and bone metabolic markers at the start of DAA treatment and 1 year later in 78 patients. There were 41 female and 37 male patients. HCV was successfully treated with DAA in all patients. Bone metabolic markers included undercarboxylated osteocalcin (ucOC), 25(OH) vitamin D (VD), total type I procollagen N-propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and BMD. BMD was measured in the lumbar spine (mean, L2-L4) and femoral neck using dual-energy X-ray absorptiometry. ucOC in males decreased at 1 year after treatment initiation but not in females. In males, ucOC changes were related to alterations in proteins induced by vitamin K absence-II (PIVKA-II), hemoglobin A1c, and TRACP-5b, which contributed to P1NP and lumbar BMD at the start of DAA. Changes in ucOC among women contributed to the changes in grip strength and TRACP-5b levels. DAA treatment improved ucOC, a useful bone metabolic marker, in HCV-infected male patients. Changes in ucOC contributed to changes in PIVKA-II that likely ameliorated the vitamin K deficiency. DAA treatment has been reported to improve various extrahepatic disorders and abnormal bone metabolism, especially in HOD.

Change in tartrate-resistant acid phosphatase isoform 5b levels, a marker of bone metabolism, in patients with chronic hepatitis B treated with tenofovir alafenamide.

Hepatitis B virus (HBV) infection is associated with the risk of osteoporosis and bone mineral density (BMD) loss. Tenofovir alafenamide (TAF) is associated with a slightly lower degree of BMD loss compared with tenofovir disoproxil, without loss of the excellent anti-HBV effects. The aim of the present study was to verify the effect of bone metabolism in patients with HBV treated with TAF. A total of 87 patients were treated with TAF. Of these, 32 patients were treatment naïve, and 55 patients were treated with entecavir (ETV) for at least 1 year, after which ETV was switched to TAF. At the start of TAF and after 1 year, BMD in the lumbar and neck of the femur, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) levels as a marker of bone metabolism and serum inorganic phosphorus (P) were compared to estimate bone metabolism. Serum creatinine (Cr), cystatin C, urine protein and ß2 microglobulin levels were evaluated to estimate kidney function. Treatment with TAF for 1 year decreased TRACP-5b levels, particularly in patients with bone disease, except for a minimal significant change (MSC; decrease of 12.4%) in TRACP-5b levels. The change in rate of TRACP-5b levels were positively associated with changes in P, Cr-estimated glomerular filtration rate and TRACP-5b levels at the start of TAF. Logistic regression analysis showed that increased BMD in the lumbar region contributed to the switch from ETV to TAF. TAF induced a decrease in TRACP-5b levels in patients with HBV. Bone disease was a contributing factor for MSC. Since TRACP-5b can be used as a marker of bone metabolism and fractures, TAF may exhibit potential in preventing fractures in patients with HBV.

Comparison of calculated body muscle mass and SARC-F as methods of screening for sarcopenia in patients with chronic liver disease.

A simple method is required to screen for sarcopenia in patients with chronic liver disease. In the present study, the value of the existing SARC-F questionnaire as well as calculated body muscle mass (CBMM) approaches were assessed for screening of sarcopenia. A total of 482 patients with chronic liver disease underwent CBMM, grip strength (GS) and SARC-F score assessments. Cross-sectional computed tomography images of the third lumbar vertebrae were analyzed to determine the skeletal muscle (SM) mass in 303 patients. Cutoff CBMM values for sarcopenia were <27.903 in females and <39.731 in males. The cutoff SARC-F score for sarcopenia was ≥4 points. Sarcopenia was diagnosed using the criteria described in the Japan Society of Hepatology. GS was moderately correlated with SARC-F score (females, R=-0.578; males, -0.453) and CBMM (females, R=0.497; males, 0.548). The SM index was moderately correlated with CBMM for both sexes (females, R=0.546; males, 0.612), but not with SARC-F score in females (females, R=-0.132; males, -0.246). The area under the curve (AUC) for CBMM against sarcopenia (0.85964) was significantly larger than that for SARC-F score (0.72013) amongst males (P=0.03577) but not females. The AUCs for a modified SARC-F questionnaire (encompassing the SARC-F questionnaire, CBMM, sex and age; mSARC-F) against sarcopenia were 0.864 in males and 0.78185 in females. As a screening method, SARC-F is less useful than CBMM. However, the AUC for mSARC-F is greater than SARC-F and CBMM.

Direct-acting Antivirals Improved the Quality of Life, Ameliorated Disease-related Symptoms, and Augmented Muscle Volume Three Years Later in Patients with Hepatitis C Virus.

Objective Patient-reported outcomes (PROs) are important measures of the quality of life (QOL) and symptoms in patients with hepatitis C virus (HCV). We evaluated the PROs at the beginning of direct-acting antiviral (DAA) treatment and three years later. A low QOL in patients with chronic liver disease suggested a low muscle mass. We compared the relationship between the QOL and muscle mass. Methods DAAs were administered to 100 patients with HCV infection. The PROs included the cirrhosis-related symptom score (CSS), presence of restless legs syndrome, Pittsburg sleep quality index (PSQI) to evaluate sleep disturbance, SF-36 to measure the QOL, and calculated body muscle mass (CBMM) measured at the beginning of treatment and three years later. Computed tomography (CT) was used to screen 82 patients for hepatocellular carcinoma at the beginning of treatment and three years later. Cross-sectional CT images of the third lumbar vertebrae were analyzed to evaluate the body composition. Results The general health perception (GHN) of SF-36 was better at three years after DAA administration than at the beginning. Changes in the GHN (dGHN) were related to an improved sleep quality on the PSQI and CSS and increased CBMM. The dGHN was positively related to changes in the skeletal muscle. The sleep quality, sleep latency, fatigue, and abdominal fullness were related to dGHN. Conclusion The QOL is related to sleep disturbance and several other symptoms. Furthermore, in patients with an increased muscle volume after DAA treatment, increased muscle mass is associated with an improvement in the QOL.