Utility of pemafibrate in nonalcoholic steatohepatitis model mice induced by a choline-deficient, high-fat diet and dextran sulfate sodium.

Aim: The purpose of this study was to examine the effect of pemafibrate in a murine model of non-alcoholic steatohepatitis (NASH). Methods: Forty-two, 19-week-old, male, C57BL/6J mice were divided into three groups: a Control group (n = 14), a dextran sulfate sodium (DSS) group (n = 14), and a DSS + PEM group (n = 14). All mice were given a standard rodent diet for the first week, followed by a choline-deficient, high-fat diet (CDHF) for the next 12 weeks. The 22nd day after the animals arrived was taken as Day 1 of the experiment. The Control group continued the CDHF diet and MilliQ water. The DSS group continued the CDHF diet, but starting on Day 1, the group received 0.8 % DSS to drink for 7 consecutive days, followed by MilliQ water for 10 days; this was taken as one course, and it was repeated on the same schedule until autopsy. The DSS + PEM group received the CDHF diet with PEM 0.1 mg/kg/day. Their drinking water was the same as that of the DSS group. On Seven animals from each group were autopsied on each of Day 50 and Day 120, and histopathological and immunohistochemical examinations, as well as quantitative RNA and cytokine measurements, of autopsied mice were performed. Results: Pemafibrate improved hepatic steatosis (decreased steatosis area), improved liver inflammation enhanced by DSS (decreased aspartate transaminase and alanine aminotransferase), improved hepatic fibrosis promoted by DSS (decreased fibrotic areas and a marker of fibrosis), inhibited tumorigenesis, and decreased intestinal inflammation in the NASH model mice. Conclusions: In a murine model of NASH, mixing PEM 0.1 mg/kg/day into the diet inhibited disease progression and tumor formation.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely related to the development of gastric cancer (GC). However, GC can develop even after H. pylori eradication. Therefore, it would be extremely useful if GC could be predicted after eradication. The Kyoto classification score for gastritis (GA) is closely related to cancer risk. However, how the score for GC changes after eradication before onset is not well understood. AIM: To investigate the characteristics of the progression of Kyoto classification scores for GC after H. pylori eradication. METHODS: Eradication of H. pylori was confirmed in all patients using either the urea breath test or the stool antigen test. The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier. In addition, the modified atrophy score was evaluated and compared between the GC group and the control GA group. RESULTS: In total, 30 cases of early GC and 30 cases of chronic GA were evaluated. The pathology of the cancer cases was differentiated adenocarcinoma, except for one case of undifferentiated adenocarcinoma. The total score of the Kyoto classification was significantly higher in the GC group both at the time of cancer onset and three years earlier (4.97 vs 3.73, P = 0.0034; 4.2 vs 3.1, P = 0.0035, respectively). The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group (5.3 vs 5.3, P = 0.5; 3.73 vs 3.1, P = 0.0475, respectively). CONCLUSION: The course of the modified atrophy score is useful for predicting the onset of GC after eradication. Patients with severe atrophy after H. pylori eradication require careful monitoring.

Post-embolization syndrome-like symptoms due to shedding of necrotic material of hepatocellular carcinoma into the bile duct following transcatheter arterial chemoembolization: an instructive case.

Fever, abdominal pain, and liver dysfunction are almost inevitable complications of transcatheter arterial chemo embolization (TACE) for hepatocellular carcinoma, but these symptoms may also be due to bile duct obstruction caused by shedding of necrotic tumor material into the bile duct. A 68-year-old man presented with persistent fever, liver dysfunction, and abdominal pain after TACE. Computed tomography revealed stone-like hyperdensities in the bile duct. Endoscopic retrograde cholangiopancreatography revealed these structures to be necrotic material from hepatocellular carcinoma. We believe this is an instructive case of an often overlooked situation.

Utility of ultrasonography in a mouse model of non-alcoholic steatohepatitis induced by a choline-deficient, high-fat diet and dextran sulfate sodium.

Background: Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that can progress to cirrhosis and hepatocellular carcinoma. The prevalence of NASH is increasing year by year. However, the etiology and progression of NASH, along with the processes leading to carcinogenesis, remain poorly understood. A range of animal models are used in research, but investigators have been unable to establish a model that results in tumorigenesis from a stable disease state. The present study aimed to create a stable, low-mortality model of NASH using abdominal ultrasonography (US) to assess NASH stage and diagnose liver tumors. Methods: Thirty-four 19-week-old male C57BL/6J mice were fed a choline-deficient, high-fat (CDHF) diet. Twenty animals were given seven courses of 0.8 % dextran sulfate sodium (DSS) for 7 days followed by 10 days of MilliQ water (CDHF+DSS group). The remaining 14 animals drank only MilliQ water (CDHF group). All animals were weighed weekly and US was performed on Days 35 and 120. After necropsy, samples were taken for biochemical analysis and histopathological evaluation. Results: The CDHF+DSS group had significantly lower body weight on Days 35 and 120, and significantly higher liver/body weight (%) on Day 35 compared to the CDHF group. US on Days 35 and 120 revealed significantly shorter long intestine and higher colonic histological score in the CDHF+DSS group compared to the CDHF group. IL-1ß and IL-6 levels in the large intestinal tissue were significantly higher in the CDHF+DSS group. Conclusions: A stable, low-mortality model of NASH was created with a CDHF diet and intermittent 0.8 % DSS. Abdominal US can assess the degree of fatty degeneration and evaluate liver tumorigenesis without necropsy. This assessment procedure will reduce the number of mice killed unnecessarily during experiments, thereby contributing to animal welfare.

Hepatic invasion of a gastric ulcer confirmed by endoscopy and surgery.

A 66-year-old woman who had been suffering from chronic anorexia for two years was transported to the hospital after being unable to consume food for three days. She had no hematemesis or abdominal pain and had no history of taking nonsteroidal anti-inflammatory drugs. Blood tests showed marked anemia with hemoglobin of 3.3 g/dL, and esophagogastroduodenoscopy revealed a large ulcer lesion in the lesser curvature of the gastric body and a liver-like mass protruding from the ulcer base. Biopsy of the mass showed proliferation of cells showing irregular cord-like structures, suggestive of normal liver tissue or hepatocellular carcinoma. Computed tomography scan showed no obvious free air in the abdomen. Despite conservative treatment, the patient developed hematemesis and progressive anemia, and surgery was performed (total gastrectomy with partial hepatectomy). Surgical specimen showed an ulcer lesion with fibrosis and loss of wall structure in all layers of the stomach, and liver adhesion with fibrosis deep in the ulcer, but no malignant findings. With the advent of powerful gastric acid secretion inhibitors, gastric ulcer invasion into the liver is now very rare, and this case is thus a valuable example showing very clear images.

Progress of ulcerative colitis patients during the COVID-19 pandemic.

BACKGROUND: We have previously demonstrated that the first wave of the coronavirus disease 2019 (COVID-19) pandemic caused exacerbations in ulcerative colitis (UC) patients, probably through psychological and physical stress. However, successive waves of the COVID-19 pandemic continuously followed the first. The effects of this chronic stress on the disease condition in UC patients are of interest. AIM: To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave. METHODS: Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020, the period of the first wave of the COVID-19 pandemic. In this study, an identical group of 289 UC patients was evaluated using UC-disease activity index (UC-DAI), endoscopic mucosal appearance score, and Matts pathological grade scoring. RESULTS: Of the 289 UC patients included in the study in 2020, 10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022, making three groups for 2020, 2021 and 2022. No significant differences in characteristics were found among the three groups. UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic, but significantly recovered in 2021 and remained stable in 2022. Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022. CONCLUSION: Disease activity of UC patients recovered in 2021 and remained stable in 2022, aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.

Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance.

BACKGROUND: The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM: To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS: This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS: A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION: In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.

Novel multi-parametric diagnosis of non-alcoholic fatty liver disease using ultrasonography, body mass index, and Fib-4 index.

BACKGROUND: Shear wave speed (SWS), shear wave dispersion (SWD), and attenuation imaging (ATI) are new diagnostic parameters for non-alcoholic fatty liver disease. To differentiate between non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL), we developed a clinical index we refer to as the "NASH pentagon" consisting of the 3 abovementioned parameters, body mass index (BMI), and Fib-4 index. AIM: To investigate whether the area of the NASH pentagon we propose is useful in discriminating between NASH and NAFL. METHODS: This non-invasive, prospective, observational study included patients diagnosed with fatty liver by abdominal ultrasound between September 2021 and August 2022 in whom shear wave elastography, SWD, and ATI were measured. Histological diagnosis based on liver biopsy was performed in 31 patients. The large pentagon group (LP group) and the small pentagon group (SP group), using an area of 100 as the cutoff, were compared; the NASH diagnosis rate was also investigated. In patients with a histologically confirmed diagnosis, receiver-operating characteristic (ROC) curve analyses were performed. RESULTS: One hundred-seven patients (61 men, 46 women; mean age 55.1 years; mean BMI 26.8 kg/m2) were assessed. The LP group was significantly older (mean age: 60.8 ± 15.2 years vs 46.4 ± 13.2 years; P < 0.0001). Twenty-five patients who underwent liver biopsies were diagnosed with NASH, and 6 were diagnosed with NAFL. On ROC curve analyses, the areas under the ROC curves for SWS, dispersion slope, ATI value, BMI, Fib-4 index, and the area of the NASH pentagon were 0.88000, 0.82000, 0.58730, 0.63000, 0.59333, and 0.93651, respectively; the largest was that for the area of the NASH pentagon. CONCLUSION: The NASH pentagon area appears useful for discriminating between patients with NASH and those with NAFL.

A case of eosinophilic pancreatitis in a patient with ulcerative colitis.

Eosinophilic pancreatitis (EP) is very rare and characterised by infiltration of eosinophils into the pancreatic parenchyma. A 40-year-old man was diagnosed with total-colitis-type ulcerative colitis at the age of 15 years. He was then diagnosed with steroid-dependent ulcerative colitis. He was given golimumab, which resulted in remission. Ten months after beginning golimumab, he was urgently hospitalised with a diagnosis of acute pancreatitis. Hence, endoscopic ultrasound-guided fine needle biopsy was performed to obtain a definitive diagnosis. Pathologically, abundant infiltration of eosinophils was observed in the edematous intralobular stroma of the pancreas. He was diagnosed with EP, and treated with corticosteroids.

Endoscopic Treatment for Submucosal Heterotopic Gastric Gland in a Case Observed over Nine Years from Development to Enlargement.

A 70-year-old Japanese man with a submucosal gastric mass that continued to increase in size underwent endoscopic submucosal dissection using the pocket creation method. Histologically, some epithelial cell nuclei were enlarged, but there was little atypia overall and no sign of malignancy, suggesting a diagnosis of submucosal heterotopic gastric gland (SHGG). SHGG that enlarges over time has been associated with gastric cancer, but a preoperative diagnosis is difficult. This case was very valuable, as it enabled us to follow the course of SHGG over a period of about nine years, from the onset to enlargement.

Safe Performance of Track Dilation and Bile Aspiration with ERCP Catheter in EUS-Guided Hepaticogastrostomy with Plastic Stents: A Retrospective Multicenter Study.

OBJECTIVES: Endoscopic-ultrasound-guided hepaticogastrostomy (EUS-HGS) with plastic stent placement is associated with a high incidence of adverse events that may be reduced using an endoscopic retrograde cholangiopancreatography (ERCP) contrast catheter in the track dilation step. In this study, we evaluated the usefulness of track dilation and bile aspiration performed with an ERCP contrast catheter in EUS-HGS with plastic stent placement. METHODS: In a multicenter setting, 22 EUS-HGS cases dilated with an ERCP contrast catheter were analyzed retrospectively and compared between a bile aspiration group and no bile aspiration group. RESULTS: Overall, adverse events occurred in three (13.6%) cases of bile leakage, three (13.6%) cases of peritonitis, and one (4.5%) case of bleeding. Comparing patients with and without bile aspiration, 6 of the 11 patients (54.5%) with no bile aspiration had adverse events, whereas only 1 of the 11 patients (9.1%) who had bile aspiration, as much bile as possible, had an adverse event (bleeding). In univariate analysis, the only factor affecting the occurrence of adverse events was bile aspiration whenever possible (odds ratio, 12.0; 95%CI 1.12-128.84). CONCLUSIONS: In EUS-HGS with plastic stent placement, track dilation and bile aspiration with an ERCP contrast catheter may be useful in reducing adverse events.

Usefulness of duckbill-type anti-reflux self-expandable metal stents for distal malignant biliary obstruction with duodenal invasion: A pilot study.

Objectives: Early obstruction of a self-expandable metal stent placed for distal malignant biliary obstruction is more likely to occur in the presence of duodenal invasion. An anti-reflux self-expandable metal stent (ARMS) has been developed for the purpose of preventing duodenal fluid reflux into the bile duct. In this study, we evaluated the usefulness and safety of a duckbill-type ARMS (D-ARMS) in the situation of duodenal invasion. Methods: We retrospectively analyzed 10 consecutive patients who received D-ARMS for distal malignant biliary obstruction with duodenal invasion. We evaluated non-occlusion cholangitis, recurrent biliary obstruction (RBO), and adverse events after D-ARMS placement. Results: There were no cases of non-occlusion cholangitis. RBO was observed in 2 patients (20%), and time to RBO was 236 days and 117 days, respectively. The causes of RBO were overgrowth and sludge formation. The median time to RBO was 382 days (range, 117-382 days). Only one adverse event was observed (cholecystitis). Conclusions: D-ARMS shows potential as an optimal ARMS.

Use of a twin-channel endoscope for removal of a lumen-apposing metal stent that migrated spontaneously after cystogastrostomy.

Kobori and colleagues report a case of late-onset spontaneous internal migration of a lumen-apposing metal stent in a patient hospitalized with obstructive jaundice caused by a pancreatic fluid collection. Although difficult, it was possible to remove the migrated stent by grasping it with two forceps using a twin-channel endoscope.

Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus.

PURPOSE: To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS: Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS: The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION: In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.