Safety and Effectiveness of Ustekinumab for Crohn's Disease With Perianal Manifestations: Ad hoc Analysis Data From 1-Year Post-Marketing Surveillance Study in Japan.

Background: Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with perianal disease being one of the challenging possible manifestations. Here, we report, an ad hoc analysis of the safety and effectiveness of 1-year use of ustekinumab (UST) for CD in patients with perianal manifestations using post-marketing surveillance (PMS) data in Japan. Methods: Among 341 patients enrolled in the PMS, 229 and 224 patients who had baseline Crohn's Disease Activity Index (CDAI) data used for evaluating perianal manifestations were included in the safety and efficacy analysis sets, respectively. Incidence of adverse drug reactions, clinical remission, the mean or its change in CDAI scores, and CDAI items were evaluated through week 52 in the presence or absence of perianal manifestations at baseline. The prevalence of perianal manifestations was also described. Results: Comparing patients with and without baseline perianal manifestations at week 52, there was no difference in ADR incidence (9.1% [n = 66] vs. 15.3% [n = 163]), no difference in clinical remission (68.3% vs. 59.9%; P = 0.269), and decreased mean change of CDAI score (-82.9 [n = 60] vs. -68.8 [n = 137]). The proportion of patients with perianal manifestations decreased after UST treatment in both biologics-naïve patients (23.5% [n = 4/17]) and patients who had received biologics (35.0% [n = 14/40]) at week 52. Conclusions: In Japanese clinical practice, UST is safe and effective in CD patients with and without perianal manifestations. The therapy might be also beneficial in those with manifestations regardless of prior use of other biologics.

Grip strength complements performance status in assessing general condition in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

AIM: An accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) on the clinical outcomes of patients with unresectable HCC (u-HCC) treated with atezolizumab plus bevacizumab. METHODS: This observational cohort study analyzed 89 patients with u-HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan-Meier curve were used to identify the prognostic factors associated with survival outcomes. RESULTS: There were 33 patients who had low GS and 16 had an ECOG-PS ≥1. The frequency of patients with low GS increased as the ECOG-PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression-free survival between the normal GS group and low-GS group (p = 0.28). Among the patients in the ECOG-PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin-bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06-4.73), α-fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20-4.58), and low GS (HR 2.87; 95% CI 1.31-6.27) were independently associated with a poor overall survival. CONCLUSIONS: The present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u-HCC patients treated with atezolizumab plus bevacizumab.

Risk factors and pattern of metastatic recurrence after endoscopic resection with additional treatment for esophageal cancer.

Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence.

Low liver reserve is a risk factor for acute pancreatitis in patients with acute liver failure.

AIM: Acute pancreatitis is a complication of acute liver failure (ALF). This study aimed to investigate the prevalence of and clinical features associated with acute pancreatitis in patients with ALF. METHODS: We retrospectively analyzed a cohort of ALF patients without hepatic encephalopathy diagnosed during a period 2011-2018, and compared clinical features between patients with acute pancreatitis and those without. Acute pancreatitis was diagnosed according to the Acute Pancreatitis Clinical Practice Guidelines 2021. A multivariate analysis was carried out to identify factors associated with acute pancreatitis. RESULTS: There were 83 ALF patients without hepatic encephalopathy (34 men; 11 deaths; 6 liver transplants; median age, 63 years). Acute pancreatitis occurred in nine patients (10.8%). The median time duration from ALF to the onset of acute pancreatitis was 8 days. The survival rate was lower in patients with than those without acute pancreatitis (22% vs. 86%). The model for end-stage liver disease score (hazard ratio 1.10, 95% confidence interval 1.03-1.18) was found to be a significant factor associated with acute pancreatitis, whereas triglyceride, age, and sex were not. CONCLUSIONS: A high model for end-stage liver disease score may be a marker to stratify patients with ALF at a risk of acute pancreatitis.

Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection.

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

Positive impact of obesity on the prognosis of liver cirrhosis.

BACKGROUND AND AIM: The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease. METHODS: This retrospective observational study enrolled patients with chronic hepatitis (n = 746) and liver cirrhosis (n = 434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥ 25 kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively. RESULTS: The mean observation period was 2.5 years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥ 65 years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients. CONCLUSIONS: Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

A genome-wide study of gastric intramucosal neoplasia based on somatic copy number alterations, gene mutations, and mRNA expression patterns.

We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array-based methods in 97 intestinal-type IMNs, including 39 low-grade dysplasias (LGDs), 37 high-grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.

Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan.

BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.

Outcomes of Metastatic and Unresectable Small Bowel Adenocarcinoma in Japan According to the Treatment Strategy: A Nationwide Observational Study.

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Immune checkpoint inhibitor-associated colitis in unresectable hepatocellular carcinoma: two cases of early onset after treatment with durvalumab plus tremelimumab.

The HIMALAYA trial is the first chemotherapeutic trial to demonstrate the efficacy of combined immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (u-HCC). The STRIDE regimen used in this trial consists of a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor and programmed cell death ligand 1 (PD-L1) inhibitor. Herein, we report two cases of ICI-colitis that occurred immediately after the initiation of the STRIDE regimen for u-HCC. A 73-year-old man and 75-year-old man with u-HCC were treated with the STRIDE regimen. Both patients developed grade 3 diarrhea (Common Terminology Criteria for Adverse Events, ver. 5.0) within 10 days of treatment initiation. Colonoscopy revealed aphthous erosions and erythema extending from the terminal ileum to the rectum in one case, while the other showed aphthous ulcers in the terminal ileum and shallow ulcers in the colorectum. Histopathological examination of a biopsy specimen revealed epithelial cell apoptosis and neutrophil infiltration bodies, consistent with ICI-colitis. Prednisolone (0.5 mg/kg) was effective in both patients. Our experience suggests the need for both careful monitoring and early endoscopic examination of ICI colitis in patients with unresectable HCC treated with the STRIDE regimen.

Seroprevalence and incidence of hepatitis E virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study.

AIM: Hepatitis E virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low. METHODS: Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2 years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction. RESULTS: Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20-89 years. A total of 90 participants were found to be positive for anti-HEV immunoglobulin G on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%-8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p < 0.001), and in those aged in their 50s-80s than in those aged in their 20s-40s (p = 0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%-1.0%), indicating the incidence of HEV infection to be 272 per 100 000 person-years (95% CI 109-561). CONCLUSIONS: Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

Clinical outcomes of endoscopic submucosal dissection for esophageal squamous cell carcinoma with esophageal varices: Multicenter retrospective study.

OBJECTIVES: Clinical outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) are obscure. We aimed to elucidate the clinical outcomes of ESD for ESCC with EVs in a multicenter, retrospective study. METHODS: We established a retrospective cohort of 30 patients with ESCC complicating EVs, who underwent ESD at 11 Japanese institutions. Rates of en bloc resection and R0 resection, procedure time, and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence, and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD. RESULTS: Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 min. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC. CONCLUSION: This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

Appropriate leucine-rich α-2 glycoprotein cut-off value for Japanese patients with ulcerative colitis.

BACKGROUND: It has been suggested that serum leucine-rich α-2 glycoprotein (LRG) could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease. In particular, the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis (UC) has become a matter of interest. AIM: To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC. METHODS: This was a cross-sectional, single-center, observational study of Japanese patients with UC. Among 213 patients with UC, in whom LRG was measured from September 2020 to February 2022, we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein (CRP) were performed on the same day. We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices, including the Mayo endoscopic subscore and UC endoscopic index of severity. RESULTS: Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant (r = 0.754, P < 0.0001; r = 0.778, P < 0.0001, respectively). There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity (r = 0.599, P = 0.0005; r = 0.563, P = 0.0012, respectively), although the correlation coefficients were higher for LRG. The LRG cut-off value for predicting endoscopic remission was 13.4 µg/mL for a Mayo endoscopic subscore of 0 [area under the curve (AUC): 0.871; 95% confidence interval (CI): 0.744-0.998], and 13.4 µg/mL for an UC endoscopic index of severity of 0 or 1 (AUC: 0.904; 95%CI: 0.792-1.000). CONCLUSION: LRG may be a surrogate marker for endoscopic activity in UC, with a cut-off value of around 13.4 µg/mL for endoscopically inactive disease.

A new model to estimate duration of survival in patients with hepatocellular carcinoma with BCLC intermediate stage.

It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (- 0.0086253) × age + (- 0.34667) × (naïve/recurrence) + (- 0.034962) × (number of nodules) + (- 0.079447) × (the size of the largest nodule) + (- 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (- 0.00014741) × (α-fetoprotein)) × (- natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.

Questionnaire Survey for Inflammatory Bowel Disease Patients in Japan; A Web-Based Japan, Crohn's Disease, Ulcerative Colitis, Patients Survey.

Background/Aims: The prevalence of inflammatory bowel disease (IBD) in Japan has been increasing. We aimed to clarify the symptoms of patients with IBD in Japan using an internet-based questionnaire survey. Methods: Overall, 805 patients with IBD were asked to complete an internet-based questionnaire addressing their history of disturbances in daily activities, prevalence of fecal urgency, incontinence, and treatment preferences. Results: Responses were obtained from 447 patients with IBD (mean age: 54 years; 70% were men), comprising 363 patients with ulcerative colitis (UC), and 84 with Crohn's disease (CD). Notably, 16% of patients with UC and 35% with CD took over 1 year until the diagnosis of IBD, and 5% of patients with CD visited more than 5 medical institutions. Patients with CD were more likely to experience disturbances in their diet, work, travel, and outings than those with UC. Fecal urgency and incontinence were significantly more frequent in patients with CD than in those with UC (72% vs. 44%, and 50% vs. 26%, respectively). In contrast, 26% of the men and 37% of women with IBD had constipation. Acid reflux, sleep disorders, and depressive symptoms were present in approximately 30% of the patients. Oral administration was preferred. Conclusions: Patients with IBD in Japan experience more severe disturbances in their daily activities, and these are more severe in those with CD than those with UC. In addition to fecal urgency and incontinence, care is required for constipation, acid reflux, sleep disorders, and depressive symptoms.

A Case of Autoimmune Hepatitis Complicated by Undiagnosed Factor VII Deficiency: A Pitfall of Coagulopathy.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

Multivariable Quantitative US Parameters for Assessing Hepatic Steatosis.

Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.

Role of TRPV4 on vascular tone regulation in pathophysiological states.

Vascular tone regulation is a key event in controlling blood flow in the body. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) help regulate the vascular tone. Abnormal vascular responsiveness to various stimuli, including constrictors and dilators, has been observed in pathophysiological states although EC and VSMC coordinate to maintain the exquisite balance between contraction and relaxation in vasculatures. Thus, investigating the mechanisms underlying vascular tone abnormality is very important in maintaining vascular health and treating vasculopathy. Increased intracellular free Ca2+ concentration ([Ca2+]i) is one of the major triggers initiating each EC and VSMC response. Transient receptor potential vanilloid family member 4 (TRPV4) is a Ca2+-permeable non-selective ion channel, which is activated by several stimuli, and is presented in both ECs and VSMCs. Therefore, TRPV4 plays an important role in vascular responses. Emerging evidence indicates the role of TRPV4 on the functions of ECs and VSMCs in various pathophysiological states, including hypertension, diabetes, and obesity. This review focused on the link between TRPV4 and the functions of ECs/VSMCs, particularly its role in vascular tone and responsiveness to vasoactive substances.

Endothelial Dysfunction in Superior Mesenteric Arteries Isolated from Adenine-Induced Renal Failure in Model Rats.

Endothelial dysfunction-a hallmark of chronic kidney disease (CKD)-is one of the major risk factors for cardiovascular diseases (CVD). Imbalances in endothelium-derived relaxing factors (EDRFs) and contracting factors (EDCFs) specific to endothelial dysfunction in CKD are yet to be studied. Therefore, using adenine-treated rats-a CKD rat model-we investigated the responsiveness of superior mesenteric artery (SMA) endothelium to acetylcholine (ACh) stimulation under different experimental conditions. Nine-week-old male Wistar rats were treated daily with adenine (200 and 600 mg/kg body weight) by oral gavage, for 10 d; the two groups were named adenine-200 (200 mg/kg body weight) and adenine-600 (600 mg/kg body weight). The systolic blood pressure (measured 1-, 8-, and 15 d post-treatment) was significantly increased in the adenine-600 group compared with that in the control group; whereas that in the adenine-200 group showed only a slight increase. Moreover, in the adenine-600 group the serum creatinine and blood urea nitrogen (BUN) levels (measured at 18 d post-treatment) were significantly elevated when compared with those in control or adenine-200 groups. The ACh-mediated relaxation was slightly reduced in the adenine-200 group. The ACh- and sodium nitroprusside (SNP)-mediated relaxations were impaired in the adenine-600 group. Although no ACh-mediated contraction was observed in the presence of a nitric oxide (NO) synthase inhibitor, ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation was largely impaired in the adenine-600 mg/kg group. This study revealed that in the SMA of adenine-induced CKD model rats, EDCF signaling remained unaltered while the NO and EDHF signaling were impaired.