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The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). 1383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (

Background: The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. Methods:This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). Results:1,383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (P< 0.001; low vs high albumin group: HR 22.9, 95% CI 8.21–63.9, P< 0.001). Conclusions: Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin.

Circulating albumin structures, including their oxidized and reduced forms, are involved in hepatic encephalopathy (HE) development. However, the effects of rifaximin, a key drug in HE treatment, on the circulating albumin structure in patients with liver cirrhosis remain unclear. In this multicenter prospective study, eight patients with hyperammonemia (≥80 μg/dL) were enrolled. The circulating albumin structure was evaluated using the ratio of oxidized albumin (human nonmercaptalbumin, HNA). Patients were administered 400 mg rifaximin 3 times/day for 3 months, and laboratory data were assessed at baseline and during observation. Among the eight patients, three were men; the median age and body mass index were 70 years and 26.4 kg/m2, respectively. The median HNA and serum ammonia levels at baseline were 41% and 143 μg/dL, respectively. After rifaximin therapy, HNA showed a decreasing tendency (median; from 41% to 36%, p = 0.321), but serum albumin levels showed no significant change (from 3.5 g/dL to 3.5 g/dL, p = 1.00); serum ammonia levels significantly reduced (median: 143 μg/dL to 76 μg/dL, p = 0.015). Thus, rifaximin reduces serum ammonia levels and may improve circulating albumin structure in patients with cirrhosis. Further large-scale studies are required to confirm these preliminary results.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Video Video 1 After insertion of the cholangioscope into the common bile duct, electrohydraulic lithotripsy was performed. All common bile duct stones were shattered and successfully removed using a basket and balloon catheter.

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

After an abdominal injury, a woman in her 20s presented to our hospital with abdominal pain. Pancreatic trauma was discovered on computed tomography, along with a pancreatic duct injury and pancreatic juice leakage. Endoscopic retrograde pancreatography revealed a 10-mm rupture of the pancreatic body's main pancreatic duct (MPD) and intraperitoneal leakage of contrast enzyme from the MPD. The pancreatic injury was treated with the placement of a 5-Fr endoscopic nasopancreatic drainage tube in the ruptured distal side of the pancreatic duct;however, 3 months later, the MPD stenosis occurred. The MPD stenosis was improved using a 7-Fr pancreatic stent, and finally, placement of the pancreatic stent was not required for MPD drainage.

Eosinophilic esophagitis (EoE), an atopic disease of the esophagus, has become increasingly recognized over the last 15 years. The epidemiology of EoE has now been reported from many countries around the world. While the clinical diagnosis of this disease depends on the patient’s clinical manifestations, the final diagnosis should be made based on the histopathological examination of esophageal mucosal biopsies. In the diagnosis of EoE, to facilitate the appropriate treatment of patients, it is extremely important to precisely recognize the presence of eosinophils in biopsy specimens of the esophageal mucosa. If eosinophils are present, EoE patients should be referred to an allergist for appropriate management with dietary modification, pharmacological agents (including corticosteroids), and/or mechanical dilation of the esophagus. We herein present and recommend the use of direct fast scarlet staining for the easy and precise recognition of eosinophils in biopsy specimens of the esophageal mucosa, a technique that has been routinely used in our laboratory.

Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) following self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS remains unexplored till date. This study aimed to evaluate the efficacy of UDCA following SEMS for malignant distal biliary obstruction (MDBO).A total of 354 patients were included, among which, 60 received UDCA. Additionally, we conducted a propensity-score matched (PSM) cohort analysis on 110 patients with SEMS placement for MDBO to reduce the selection bias. The patients were categorized into two groups (n=55 each), based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) following SEMS. The secondary endpoint was to evaluate the SEMS occlusion rate and early adverse events (AEs).The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P=0.0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs. 154 days, P=0.0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio 2.28 [95% confidence interval 1.06-4.88], P=0.0348). The overall early AEs rate showed insignificant differences between the groups.Administering UDCA after SEMS was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion.

The antiviral agent ritonavir is a substrate for cytochrome P450 3A4 (CYP3A4); therefore, concomitant use of CYP3A4-metabolising drugs might cause adverse reactions to this drug. We investigated the plasma level of calcium channel blockers (CCBs) as CYP3A4 substrates and peripheral edema as a potential adverse drug reaction possibly caused by the anti-hepatitis C virus (HCV) regimen of ombitasvir/paritaprevir/ritonavir (OPR) and CCBs.We enrolled Japanese patients prescribed OPR for HCV infection. Peripheral edema was graded according to the Common Terminology Criteria for Adverse Events ver. 4. Plasma samples were collected on days 0, 7, 14, 28, and 42 after antiviral treatment, at the trough level.Out of 52 patients, 64% experienced grade 1 or grade 2 peripheral edema, but not grade 3. Concomitant use of CCBs significantly increased the emergence of grade 2 edema (62%), compared with patients treated solely with OPR (48%). The use of OPR significantly increased the plasma concentration of amlodipine.Peripheral edema in patients treated with OPR and CCBs, although tolerable, should be closely monitored.

There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.

Background and study aims Preoperative assessment of the superficial ductal spread (SDS) of perihilar cholangiocarcinoma (PCCA) is important for determining its resectability. A virtual endoscopic imaging method, magnetic resonance cholangioscopy (MRCS), wherein a three-dimensional image is created from magnetic resonance imaging (MRI) data, can evaluate all aspects of arbitrary bile ducts. Patients and methods Overall, 15 patients with PCCA who underwent preoperative MRI were enrolled. All patients underwent surgical treatment. Results MRCS could be performed based on preoperative MRI data in all patients. MRCS could not be used in one patient due to debris in the obstructed bile duct. The remaining 14 patients (93 %) were diagnosed with obstructed bile duct or irregular surface of the bile duct, signifying tumor invasion. The accuracy rate of diagnosing the SDS was 93 % (14/15). Seven patients underwent preoperative peroral cholangioscopy; the scope could not pass through the tumor in three patients. In these three patients, MRCS was able to be use dtoevaluate the obstructed side of the bile duct and faciliated accurate diagnosis of SDS. Conclusions MRCS can be used to noninvasively evaluate the bile duct in all directions. This novel method makes it easy to create virtual images and can be useful for diagnosing the preoperative SDS of PCCA.

EarthCARE, the Earth Cloud Aerosol and Radiation Explorer, is the third Earth Explorer Core Mission of the European Space Agency's Earth Observation Envelope Programme. These are defined as major missions led by ESA to cover primary research objectives set out in the Living Planet Program. EarthCARE is being developed in cooperation with the Japan Aerospace Exploration Agency (JAXA), which is providing the Cloud Profiling Radar.

The Earth Clouds, Aerosols and Radiation Explorer (EarthCARE) is a Japanese-European collaborative earth observation satellite mission. The Cloud Profiling Radar (CPR) is one of the EarthCARE instruments and it is the world's first on-board millimeter-wave Doppler radar in space. The Japan Aerospace exploration agency (JAXA) is responsible for development of the CPR in this mission in cooperation with the National Institute of Information and Communications Technology (NICT). This paper mainly describes the development status and performance of EarthCARE CPR Proto Flight Model (PFM).

In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment. Of 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP

Hepatitis E virus subtype 3f (HEV-3f) strains are usually isolated in Europe and Thailand. Recently, HEV-3f strains were detected from six acute hepatitis E patients in Japan, none of whom had a history of travel to endemic areas. We inferred the origin and transmission route of the six HEV-3f strains. A time-scaled phylogenetic tree of the six strains with reference strains was constructed using a Bayesian statistical inference framework. The time-scaled tree indicated that the six strains independently derived from similar European strains between 2008 and 2014. The pattern suggested recent inflow of multiple HEV-3f strains from Europe to Japan. Japan imports a substantial amount of pork from European countries every year. The emergence of acute hepatitis cases caused by HEV-3f strains in Japan, in patients with no history of travel abroad, might be influenced by the increased opportunities to consume pork products imported from European countries.

Background Bilateral self-expandable metallic stent (SEMS) placement is effective for long-term management of unresectable malignant hilar biliary obstruction (UMHBO). However, endoscopic reintervention (ERI) for bilateral SEMSs is not well-studied. This study aimed to evaluate ERI efficacy after stent-in-stent placement. Methods Data of 31 patients who underwent ERI from May 2000 to July 2018 were analyzed. Results The technical success rate was 80.7% (25/31) and no adverse events occurred. The functional success rate was 100% (25/25). In a multivariate logistic regression analysis, the angle between the bilateral SEMSs (ABBS) >104° (odds ratio 50.49, 95% CI 3.370-2131, P = 0.0039) and overgrowth (odds ratio 25.70, 95% CI 1.121-1234, P = 0.0423) were risk factors for ERI failure. Multiple liver metastases, which sometimes cause overgrowth, were also risk factors. After ERI, some patients underwent additional SEMS (n = 4), plastic stent (n = 14) placement, or internal cleaning of the initial SEMS alone (n = 7). There were no significant intergroup differences in the 50% time to recurrent biliary obstruction. Conclusions ABBS >104° and overgrowth were risk factors for ERI failure after stent-in-stent placement. In the decision-making process for initial SEMS placement for UMHBO, patient condition should be considered, including the angle between bilateral bile ducts and multiple liver metastases.

DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies.In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b).SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred.SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.