Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

AIM: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. METHODS: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. RESULTS: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. CONCLUSIONS: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

Association between bowel movement frequency and erectile dysfunction in patients with ulcerative colitis: a cross-sectional study.

The association between ulcerative colitis (UC) and erectile dysfunction (ED) has been previously reported. Numerous previous studies have also reported an association between gastrointestinal symptoms and ED. Constipation and diarrhea are common in patients with UC. However, the specific association between bowel movement frequency and ED remains unclear. The aim of this study is to investigate the association between bowel movement frequency and ED in 164 patients with UC. The definition of ED, moderate to severe ED, and severe ED was the Sexual Health Inventory for Men score <22, <12, and <8, respectively. Bowel movement frequency was divided into three categories: (1) high (More than once a day), (2) normal (once a day, reference), and low (less than one time/day). The definition of constipation was based on the Rome I criteria and/or medication for constipation. The prevalence of constipation and ED was 10.4% and 86.0%, respectively. The rate of high, normal, and low bowel movement frequency was 56.1%, 25.0%, and 18.9%, respectively. High bowel movement frequency was independently and positively associated with ED and moderate to severe ED (ED: adjusted odds ratio [OR] 4.42, 95% confidence interval [CI] 1.35-15.98; moderate to severe: adjusted OR 2.98, 95% CI 1.22-7.61). Low bowel movement frequency was independently and positively associated with moderate to severe ED and severe ED (moderate to severe: adjusted OR 3.96, 95% CI 1.27-13.08; severe: adjusted OR 3.20, 95% CI 1.08-9.86). No association between constipation and ED was found. In conclusion, in Japanese patients with UC, both high and low bowel movement frequency were independently and positively associated with ED.

Multimorbidity of Allergic Diseases Is Associated With Functional Gastrointestinal Disorders in a Young Japanese Population.

Background/Aims: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people. Methods: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. Results: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). Conclusion: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease.

Background: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. Conclusion: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Serum albumin levels as a useful complementary marker for erectile dysfunction in ulcerative colitis: A cross-sectional study.

OBJECTIVE: Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC. METHODS: One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression. RESULTS: The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found. CONCLUSION: Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients.

Aging is Associated With Constipation in Japanese Patients With Ulcerative Colitis: A Post Hoc Analysis.

Aim: Age is a risk factor for constipation. Constipation is common in patients with ulcerative colitis (UC) and has been positively associated with disease activity, but evidence is limited. This study aimed to assess the association between disease activity and constipation in patients with UC. Methods: The study subjects consisted of 290 Japanese UC patients. The definition of constipation was based on Rome I criteria and/or medication for constipation. Information on and lifestyle habits was obtained from a self-administered questionnaire. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0. Clinical remission (CR) was defined as both the absence of rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The prevalence of constipation is not associated with MH, CR, duration of UC and disease extent of UC. The prevalence of constipation among age groups, <40, 40-49 years, 50-59 years, 60-69 years, and >70 years was 10.0%, 5.8%, 15.7%, 11.8%, and 25.6%, respectively. >70 years was independently and positively associated with the prevalence of constipation (adjusted odds ratio 3.64 [95% confidence interval 1.26, 10.95], p for trend: .001). Conclusions: Aging was independently and positively associated with the prevalence of constipation in UC.

Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders.

Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5-10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.

Menstrual Status Is Associated with the Prevalence of Irritable Bowel Syndrome in a Japanese Young Population: A Cross-Sectional Study.

INTRODUCTION: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. METHODS: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. RESULTS: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. CONCLUSION: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.

Severity of Nocturia and Constipation in Patients With Ulcerative Colitis.

OBJECTIVE: To investigate the association between nocturia and constipation in patients with ulcerative colitis (UC). Constipation has recently been recognized as an important symptom in patients with UC. Although nocturia has been associated with constipation in the general population, the association between nocturia and constipation in UC patients is uncertain. METHODS: Consecutive series of 290 Japanese patients with UC, Information on constipation, nocturia, and lifestyle habits was obtained using self-administered questionnaires. The definition of constipation was based on Rome I criteria and/or current medication for constipation. Patients were divided into three groups based on nighttime urination: (1) no nocturia, (2) mild nocturia (nocturnal urination - one), and (3) serious nocturia (nocturnal urination - two or more). Multivariate logistic regression was used to evaluate the association between nocturia and constipation. RESULTS: Among all of the UC patients, the prevalence of mild nocturia, serious nocturia, and constipation was 35.2%, 26.9%, and 12.4%, respectively. The prevalence of constipation in the none, mild, and serious nocturia groups was 8.2%, 10.8%, and 20.5%, respectively. After adjustment for confounders such as age, sex, current drinking, current smoking, body mass index, and steroid use, nocturia severity was independently and positively associated with constipation (adjusted odds ratio for mild nocturia: 1.55 [95% confidence interval: 0.57-4.28], serious nocturia: 3.19 [95% confidence interval: 1.09-9.81], P for trend=.035). CONCLUSION: The severity of nocturia is positively associated with constipation, and physicians should consider the interrelationships between nocturia and constipation in managing UC patients.

Clinicopathological features and endoscopic findings of spindle cell oncocytoma: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Spindle cell oncocytoma (SCO) of the pituitary gland is very difficult to differentiate from other pituitary neoplasms and is often misdiagnosed based on imaging procedure features. We report a rare case of SCO arising from the neurohypophysis and suggest a useful diagnostic criterion for accurate diagnosis and surgical pitfalls. CASE PRESENTATION: A 53-year-old man was admitted to our hospital with slight headache and diplopia. Neuroimaging revealed pituitary tumour in the suprasellar and sellar regions with speckled gadolinium enhancement on T1-weighted magnetic resonance imaging, as a so-called blooming artefact. The enhanced anterior pituitary gland was located anteriorly. Computed tomography (CT)-scan demonstrated an isodense mass without calcification showing strong contrast enhancement with iodine contrast medium. Laboratory findings showed no abnormalities. Subtotal resection of the tumour was achieved by an endoscopic endonasal transsphenoidal approach. Histological examinations showed spindle-shaped to epithelioid tumour cells featuring eosinophilic and granular cytoplasm staining strongly for anti-mitochondrial antibody and thyroid transcription factor 1. The tumour was therefore diagnosed as SCO, belonging to tumours of the posterior pituitary. Headache and diplopia were disappeared immediately postoperatively, and follow-up at 12 months demonstrated no signs of recurrence. CLINICAL DISCUSSION: SCO of the pituitary gland is a rare tumour that originates from the neurohypophysis and is difficult to diagnose on routine neuroimaging procedure. CONCLUSION: Accurate diagnosis requires careful identification of clinical signs, neuroimaging features including contrast-enhanced CT, and analysis of combined results from morphological and immunohistochemical evaluation of tumour tissue.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Disease activity and erectile dysfunction in Japanese patients with ulcerative colitis.

Background: The association between disease activity and erectile dysfunction (ED) in patients with inflammatory bowel disease (IBD) is inconsistent, although IBD, including ulcerative colitis (UC), is reported as a risk factor for ED. Aim: The purpose of this study was to explore this association in Japanese patients with UC. Methods: In this study, we enrolled 165 Japanese male patients with UC. Information regarding the Sexual Health Inventory for Men (SHIM) score, medication, and severity of UC was obtained from medical records, self-administered questionnaires, and reports from physicians. The definition of ED and severe ED is a SHIM score <17 and <8, respectively. Outcomes: No association between severity of UC and ED was found in Japanese patients. Aging is independently positively associated with ED in patients with UC. Results: The prevalence of severe ED and ED was 47.9% and 64.9%, respectively. In this study, mucosal healing, clinical remission, duration of UC, disease extent, and medication were not associated with the prevalence of ED. Older age (≥63 years of age) was independently positively associated with ED (adjusted odds ratio, 12.93; 95% CI: 4.51-43.00) and severe ED (adjusted odds ratio, 9.02; 95% CI: 3.66-23.91). Clinical Implications: Disease severity of UC might not be associated with the prevalence of ED in patients with UC. Strengths and Limitations: This is the first study to investigate the association between several factors regarding UC activity and ED. The limitation of this study is the definition of ED based on SHIM scores. Conclusion: No association between severity of UC and ED was found in Japanese patients. As expected, aging may be independently positively associated with ED in patients with UC.

Exercise habits that include exercise partners and irritable bowel syndrome in a young Japanese population: a cross-sectional study.

OBJECTIVE: Evidence regarding the association between exercise habits and irritable bowel syndrome (IBS) remains scarce in a young population. It is also unknown whether the existence of an exercise partner affects this issue. The purpose of this study was to explore the association between exercise habits that include an exercise partner and IBS in a young Japanese population. METHODS: This study enrolled 8923 Japanese university students and examined exercise frequency and intensity, and exercise partners using self-administered questionnaires. IBS and functional dyspepsia were defined according to the Rome III criteria. RESULTS: The prevalence of IBS in this survey was 6.5%. Moderate frequency exercise was inversely related with IBS [adjusted odds ratio (aOR): 0.65 (95% confidence interval, CI: 0.51-0.83), P for trend = 0.005]. Moderate and high exercise intensities were independently and inversely related with IBS, respectively [aORs were moderate: 0.76 (95% CI: 0.61-0.95) and high: 0.62 (95% CI: 0.48-0.78), P for trend = 0.001]. Exercising with a group or with friends instead of alone was independently inversely related with IBS [aOR with groups: 0.53 (95% CI: 0.40-0.70) and with friends: aOR 0.71 (95% CI: 0.54-0.93)]. After excluding subjects with overlapping IBS and functional dyspepsia, an inverse association between high intensity of exercise or exercise in a group and IBS remained significant. CONCLUSION: The frequency and intensity of exercise may be independently inversely related with IBS in a young Japanese population. Also, exercise with others may be important for preventing IBS.

Clinical utility of spoiled-gradient echo 3D-T1 sequence in deciding appropriate treatment strategy for ACTH-producing pituitary adenoma; a case report and review of the literature.

INTRODUCTION AND IMPORTANCE: When treating adrenocorticotropic hormone (ACTH)-producing adenoma, accurate tumor localization is critical. We report a case of Cushing's disease in which MRI with a spoiled-gradient echo 3D T1-weighted sequence was useful in precise localization of an ACTH-producing adenoma and deciding appropriate treatment strategy. CASE PRESENTATION: A 47-year-old woman was admitted to our hospital with signs and symptoms of Cushing's disease. Laboratory findings showed hypercortisolemia and suggested Cushing's disease. However, neuroimaging on conventional pituitary MRI using a spin-echo (SE) protocol did not confirm pituitary adenoma in the sella turcica. Inferior petrosal sinus sampling suggested a higher central/peripheral ratio of ACTH after corticotropin-releasing hormone (CRH) administration on the right side. Reviewing the dynamic MRI using an SE protocol from that perspective, we vaguely identified a 5.0 mm area of gradual contrast on the right side of the pituitary gland. In addition, pituitary MRI with a spoiled-gradient echo 3D T1-weighted sequence, a 2.0 mm hypo-enhancing region was identified on the right side within the anterior pituitary gland. The tumor was resected completely removing the right pituitary gland including the tumor. The histological diagnosis was ACTH-producing pituitary adenoma. Symptoms of Cushing's disease gradually improved and endocrinological function normalized. Follow-up neuroimaging after 1 year showed no signs of recurrence. CLINICAL DISCUSSION: In the treatment of Cushing's disease, accurate detection of ACTH-producing pituitary adenoma is crucial to maximizing curative rates. However, exact confirmation of the tumor location is very difficult. CONCLUSION: MRI with a spoiled-gradient echo 3D T1-weighted sequence may facilitate accurate tumor localization and appropriate treatment strategy.

Patients with Chronic Liver Disease under Surveillance for Hepatocellular Carcinoma Have a Favorable Long-Term Outcome for Pancreatic Cancer Due to Early Diagnosis and High Resection Rate.

Patients with viral hepatitis-related chronic liver disease (CLD) under surveillance for hepatocellular carcinoma (HCC) are often diagnosed with pancreatic cancer (PC) at an early stage. However, the long-term outcomes of these patients are unclear. We aimed to clarify the long-term outcomes of patients with PC with viral hepatitis-related CLD using a chart review. Data collection included the Union for International Cancer Control (UICC) stage at PC diagnosis, hepatitis B virus and hepatitis C virus status, and long-term outcomes. The distribution of the entire cohort (N = 552) was as follows: early stage (UICC 0-IB; n = 52, 9.5%) and non-early stages (UICC IIA-IV; n = 500, 90.5%). At diagnosis, the HCC surveillance group (n = 18) had more patients in the early stages than the non-surveillance group (n = 534) (50% vs. 8.0%), leading to a higher indication rate for surgical resection (72.2% vs. 29.8%) and a longer median survival time (19.0 months vs. 9.9 months). We confirmed that patients with viral hepatitis-related CLD under HCC surveillance were diagnosed with PC at an early stage. Because of the higher indication rate for surgical resection in these patients, they had favorable long-term outcomes for PC.

Role of B Cell-Activating Factor in Fibrosis Progression in a Murine Model of Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor α, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH.

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.

AIMS: HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. METHODS: A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. RESULTS: Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10  IU/ml (p < 0.05) and -0.2677 log10  IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. CONCLUSIONS: Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.

Association between Mucosal Healing and Lipid Profiles in Patients with Ulcerative Colitis: A Cross-Sectional Study.

INTRODUCTION: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC. METHODS: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0-1, respectively. RESULTS: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04-6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22-11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia. CONCLUSIONS: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C.

The albumin to globulin ratio is associated with clinical outcome in Japanese patients with ulcerative colitis.

PURPOSE: The albumin to globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC. METHODS: The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day). RESULTS: The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52-14.18 and adjusted OR, 4.97; 95% CI, 2.14-12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56-11.51 and adjusted OR, 5.22; 95% CI, 1.97-14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06-21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found. CONCLUSION: Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.