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.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

Serum Globulin Is Associated with Endoscopic Findings and Mucosal Healing in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Serum globulin is an inflammation marker. To date, no evidence regarding the association between serum globulin and disease activity in patients with ulcerative colitis has been reported. AIMS: We evaluated the association between serum globulin and endoscopic activity in patients with ulcerative colitis. METHODS: Serum globulin was divided into tertiles based on the distribution of study subjects (low globulin, ≤ 2.7 g/dl (reference); moderate globulin, 2.7-3.1 g/dl; and high globulin, > 3.1 g/dl). A single endoscopic specialist evaluated the endoscopic findings, and mucosal healing was based on Mayo endoscopic subscore. RESULTS: A total of 277 patients with ulcerative colitis were included in the study. Serum globulin was independently positively associated with diminished or absent vascular markings [moderate: adjusted odds ratio (OR) 3.70 (95% confidence interval, CI: 1.82-7.88) and high: adjusted OR 2.40 (95%CI: 1.20-4.94), p for trend = 0.005]. A similar positive association between globulin and erosion was found [high: adjusted OR 2.00 (95%CI: 1.05-3.86)]. Serum globulin was independently inversely associated with mucosal healing [moderate: adjusted OR 0.37 (95%CI: 0.18-0.73) and high: adjusted OR 0.31 (95%CI: 0.14-0.64), p for trend = 0.001] and adjusted partial mucosal healing [moderate: OR 0.51 (95%CI: 0.26-0.98), p for trend = 0.048]. The inverse association between globulin and mucosal healing was significant in the low but not the high C-reactive protein group. CONCLUSIONS: In patients with ulcerative colitis, serum globulin was significantly positively associated with endoscopic activity, and was significantly inversely associated with mucosal healing, especially in the low C-reactive protein group.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Dietary intake of vegetables, fruit, and antioxidants and risk of ulcerative colitis: A case-control study in Japan.

OBJECTIVES: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk. METHODS: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively). CONCLUSIONS: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.

Association between platelet count and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study.

BACKGROUND: Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC. METHODS: The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0-1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors. RESULTS: The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI 0.19-0.810], very high: OR 0.37 [95%CI 0.17-0.77], p for trend = 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI 0.18-0.73], high: OR 0.41 [95% CI 0.19-0.83], and very high: OR 0.45 [95% CI 0.21-0.94], p for trend = 0.033) after adjustment for confounding factors. CONCLUSIONS: Among patients with UC, platelet count was independently inversely associated with MH.

Depletion of B cell-activating factor attenuates hepatic fat accumulation in a murine model of nonalcoholic fatty liver disease.

Obesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF-/- mice fed a high-fat diet (HFD). HFD-fed BAFF-/- mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice. Moreover, inflammation, especially the accumulation of CD11c+ adipose-tissue macrophages, and fibrosis of epididymal adipose tissue were reduced, contributing to healthy adipose-tissue expansion in obese BAFF-/- mice. In line with metabolically healthy obesity, hepatic steatosis also decreased, and we observed attenuated de novo lipogenesis in both the livers and hepatocytes of BAFF-/- mice. Our data revealed that BAFF serves as a potential stimulator of unhealthy adipose-tissue expansion by triggering inflammation and fibrosis and ultimately leading to enhanced insulin resistance and NAFLD. Therefore, these results suggest that BAFF is a promising target for diabetes and NAFLD treatment.

Surveillance of Hepatitis Viruses in Several Small Islands of Japan by Ship: A Public Health Approach for Elimination of Hepatitis Viruses by 2030.

AIM: In 1990, an epidemiological survey by ship in some Japanese islands revealed high prevalence of hepatitis viruses and human T cell leukemia virus (HTLV). A second prevalence study of these viruses were accomplished in 2018, 28 years after initial survey. Analysis of these studies provide insights about strategies of elimination of hepatitis viruses at remote areas. MATERIALS AND METHODS: In 2018, prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and HTLV was checked in 305 subjects in the islands those covered in 1990's survey. Hepatitis A virus was checked by the presence of anti-HAV IgG in sera; HBV was affirmed when hepatitis B surface antigen (HBsAg) in sera. Hepatitis C virus infection was evaluated by the presence of antibody to HCV (anti-HCV) and infection with HTLV was estimated by immunoassay. The methodology of assessment of different hepatitis viruses were optimized on the basis of present scientific knowhow. RESULTS: In 1990, the prevalence of HAV (presence of anti-HAV), HBV (presence of HBsAg), HCV (positivity for anti-HCV), and HTLV was found in 79.3%, 11.1%, 2.2%, and 3.3% of apparently health subjects of the islands, respectively. The prevalence of HAV, HBV, HCV, and HTLV was 47.9%, 4.6%, 1.0%, and 3.0%, respectively, in 2018. A shift of age of infected persons tilted towards right as the days progressed. CONCLUSION: The study indicates a scenario of elimination of hepatitis viruses in Japan as lower trends of prevalence of HAV, HBV, and HCV have been recorded in 2018 compared with 1990, mainly by preventive measures. The most notable finding is that there are almost no new case below the age of 40 years, indicating an effective containment measure against these viruses. HOW TO CITE THIS ARTICLE: Akao T, Onji M, Kawasaki K, et al. Surveillance of Hepatitis Viruses in Several Small Islands of Japan by Ship: A Public Health Approach for Elimination of Hepatitis Viruses by 2030. Euroasian J Hepato-Gastroenterol 2019;9(2):57-62.

Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases.

AIM: The aim of the study was to assess the implication of Zonulin, a mediator protein synthesized by intestine and the liver,in patients with chronic liver diseases. MATERIALS AND METHODS: Twenty-six patients with chronic liver diseases due to hepatitis C virus (HCV) and hepatitis B virus (HBV) were enrolled in this study. Out of total 26 patients, 17 were diagnosed as chronic hepatitis (CH) and 9 were patients with liver cirrhosis (LC). Twenty-four of these patients were infected with hepatitis C virus (HCV) and the rest two by hepatitis B virus (HBV). The study was conducted at Saiseikai-Imabari Hospital, Imabari, Ehime, Japan. Serum levels of Zonulin along with different parameters of liver function test were measured in all patients and comparative analyses were accomplished. RESULTS: The serum levels of Zonulin were significantly lower in CH patients compared to controls (p<0.001). Also, the levels of Zonulin were significantly lower in patients with LC compared to CH and normal controls (p<0.001). Further analysis revealed that serum Zonulin was significantly lower in patients with LC having ascites than those without ascites (p <0.05). There was a significant correlation of serum levels of Zonulin with platelet count, cholinesterase, and albumin in patients with chronic liver diseases. DISCUSSION: Decreased levels of Zonulin may be related to impaired production of this mediator in the diseased liver. It will be tempting to assess the regulation of Zonulin in the liver, a production site of the mediator. ABBREVIATIONS: LC: Liver cirrhosis, CH: Chronic hepatitis, HCV: Hepatitis C virus, HBV: Hepatitis B virus, LGS: Leaky gut syndromeHow to cite this article: Akao T, Morita A, Onji M, Miyake T, Watanabe R, Uehara T, Kawasaki K, Miyaike J, Oomoto M. Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases. Euroasian J Hepatogastroenterol, 2018;8(2):112-115.

Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease.

Myeloid-derived suppressor cells (MDSCs) are potent suppressors of T cell immunity in tumors and inflammatory diseases. They are identified by surface expression of CD11b+Gr1+ in mice, and CD11b+Gr1+ cells accumulate in the livers of obese mice. However, many myeloid cells share these CD11b+Gr1+ markers. Accordingly, the aim of this study was to identify the authentic phenotype of MDSCs and investigate their functions in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were divided into 2 diet groups: a normal control group and high-fat group to induce NAFLD. We demonstrated that monocytic CD11b+Gr1dim cells could be further divided into 2 populations based on side scatter (SSC) during flow cytometry. We found that SSClowCD11b+Gr1dim cells accumulated in the livers of NAFLD mice over time, and that these cells were recruited by the chemokine CCL2 and its receptor CCR2 and might expand in the liver via macrophage colony-stimulating factor stimulation. Furthermore, SSClowCD11b+Gr1dim cells had a strong suppressive ability on T cells; this effect was not observed for SSChighCD11b+Gr1dim cells, and was dependent on nitric oxide production by inducible nitric oxide synthase. Our findings demonstrate that SSClowCD11b+Gr1dim cells represent authentic MDSCs in NAFLD livers, and might serve an important negative feedback function in liver inflammation.

Submucosal tumor-like lesion originating from colon tuberculosis: a case report and review of the literature.

A 76-year-old male had a solitary submucosal tumor-like lesion in the sigmoid colon originating from tuberculosis. The lesion, up to 1 cm in diameter, was found incidentally during a routine colonoscopy, which revealed a protuberant submucosal growth with a shallow depression of the overlying mucosa in the center of the tumor. Histologically, the endoscopic biopsy revealed caseating granulomas and infiltration of Langhans giant cells and epithelioid cells, consistent with tuberculosis, were also observed. Five reports of similar lesions from colon tuberculosis were found in a literature review, including the present case. In all cases, the submucosal tumor-like lesions which originated from tuberculosis were small and in an active stage of tuberculosis. Five cases of submucosal tumor-like lesions from gastric tuberculosis were also reported, with characteristics very similar to those of the lesions from colon tuberculosis. Therefore, we propose that lesions originating from tuberculosis should be included in the differential diagnosis of submucosal tumor-like lesions in the colon and stomach.

Short sleep duration reduces the risk of nonalcoholic fatty liver disease onset in men: a community-based longitudinal cohort study.

BACKGROUND: Epidemiologic studies show an association between short sleep duration and the presence of nonalcoholic fatty liver disease (NAFLD). This study examined the association between short sleep duration and the onset of NAFLD. METHODS: This community-based, retrospective, longitudinal cohort study included 6,370 Japanese subjects who had undergone annual health check-ups more than twice at a single center between April 2003 and March 2010. After excluding 3,941 subjects, the records of 2,429 Japanese subjects were reviewed. RESULTS: Two groups comprised the study cohort: those with short (≤ 6 h) sleep durations (n = 1,543) and those with moderate (7-8 h) sleep durations (n = 886). During the observation period, 296 subjects developed NAFLD. Multivariate analysis identified an association between short sleep duration and the reduced onset of NAFLD in men (odds ratio: 0.551, 95% confidence interval 0.365-0.832, p = 0.005). There was no association between short sleep duration and NAFLD onset in women. The prevalence of NAFLD onset in men increased significantly as sleep duration increased, as follows: 12.5, 18.4, and 27.4% among subjects who had sleep durations of ≤ 4, 5-6, and 7-8 h, respectively (p = 0.02). CONCLUSIONS: This study demonstrates an association between sleep duration and NAFLD onset. Short sleep duration reduced the risk of NAFLD onset in men. Correct recognition is important to prevent disease progression and further complications.

Significance of exercise in nonalcoholic fatty liver disease in men: a community-based large cross-sectional study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis, cirrhosis, and liver failure. We aimed to assess the relationship between NAFLD and lifestyle habits. METHODS: Using a community-based, cross-sectional design, the records of 11,094 Japanese subjects who had undergone at least 1 annual health checkup were reviewed. RESULTS: Of the 6,370 subjects who qualified for enrolment, 1,346 met the diagnostic criteria for NAFLD. The prevalence rate (PR) of NAFLD increased significantly to 36.6, 41.5, and 41.1 % with no snacking, snacking less than once/day, and snacking ≥2 times/day, respectively, in men (P = 0.0495) and to 10.8, 11.7, and 15.3 %, respectively, in women (P = 0.002). In men, the NAFLD PR decreased significantly to 48.8, 36.9, and 29.9 % with no exercise, exercise consciousness, and periodical exercise, respectively (P < 0.001). In women, the NAFLD PR decreased significantly to 19.3, 13.5, 11, and 8 % with sleep durations of ≤4, 5-6, 7-8, and ≥9 h, respectively (P = 0.003). Periodical exercise was identified as an independent factor associated with NAFLD in men (odds ratio 0.707, 95 % confidence interval 0.546-0.914; P = 0.008). CONCLUSIONS: Performing regular exercise was associated with a reduced risk for NAFLD in men. Men with a high risk for NAFLD can be identified using questionnaires on exercise in an outpatient setting. Disease progression and further complications may be prevented by educating high-risk NAFLD patients about the importance of exercise.

Hyperuricemia is a risk factor for the onset of impaired fasting glucose in men with a high plasma glucose level: a community-based study.

BACKGROUND: It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. METHODS: We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18-80 years old and had > 2 annual check-ups during 2003-2010. After excluding persons who had fasting plasma glucose levels ≥ 6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥ 6.11 mM during the observation period. RESULTS: In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001-1.005, P = 0.041). CONCLUSIONS: Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose.

B cell activating factor in obesity is regulated by oxidative stress in adipocytes.

Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, and plays a key role in the integration of systemic metabolism. We have previously shown that B cell activating factor is produced mainly in visceral adipose tissue and affects insulin sensitivity in obese individuals. In this study, we identified the signals that lead to production of B cell activating factor in adipocytes. 3T3-L1 and C3H/10T 1/2-clone 8 cells showed increased B cell activating factor expression upon exposure to hydrogen peroxide, and these changes were inhibited by treatment with the antioxidant N-acetyl-cysteine. B cell activating factor levels in both serum and visceral adipose tissue were increased in high fat diet-fed mice, and these increases were correlated with oxidative stress. In addition, serum BAFF levels in high fat diet-fed mice were reduced by N-acetyl-cysteine treatment. We also found that oxidative stress-induced B cell activating factor expression in adipocytes was regulated by NF-κB activation. These data indicate that control of the redox state in visceral adipose tissue is a potentially useful target for treating metabolic syndromes through regulation of adipokine production.

Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity.

Chronic inflammation is an important contributor to the development and progression of metabolic syndrome. Recent evidence indicates that, in addition to innate immune cells, adaptive immune cells have an important role in this process. We previously showed that the serum level of B-cell-activating factor (BAFF) was increased in patients with nonalcoholic steatohepatitis. However, it is currently unknown whether BAFF and BAFF-R (BAFF-R) have a role in lipid metabolism in the liver. To address this issue, the role played by BAFF and BAFF-R signaling in the development of insulin resistance and hepatic steatosis was examined in BAFF-R(-/-) mice fed a high-fat diet (HFD). Furthermore, the effect of BAFF on lipid metabolism in hepatocytes was analyzed in vitro. BAFF-R(-/-) mice showed improvements in HFD-induced obesity and insulin resistance. In addition, the number of B cells, levels of serum IgG, and inflammation of visceral fat were reduced in these mice. However, the expression of steatogenic genes and fatty acid deposition in the liver was higher in these mice than in control mice. BAFF was also found to downregulate the expression of steatogenesis genes and enhance steatosis in hepatocytes through BAFF-R. Collectively, these data indicated that, in addition to its known functions in inflammation and glucose metabolism, BAFF has a protective role in hepatic steatosis by regulating lipid metabolism in the liver.

B cell-activating factor is associated with the histological severity of nonalcoholic fatty liver disease.

PURPOSE: B cell-activating factor (BAFF) is expressed in adipocytes and affects lipogenesis and insulin sensitivity. In addition, the BAFF receptor is expressed in visceral adipose tissue and liver. The aim of this study was to analyze serum BAFF levels in patients with nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) and to compare their respective clinical and histological findings. METHODS: A total of 96 patients with nonalcoholic fatty liver disease (20 with SS and 76 with NASH) were enrolled and their serum BAFF levels were analyzed. Comprehensive blood chemistry analysis and histological examination of liver samples were also conducted. RESULTS: Serum BAFF levels were higher in patients with NASH than in those with SS (p = 0.016). NASH patients with ballooning hepatocytes and advanced fibrosis had higher levels of BAFF in sera (p = 0.016 and p = 0.006, respectively). In addition, the prevalence of NASH increased significantly as the serum BAFF level increased (p = 0.004). Higher serum BAFF levels were found to be an independent risk factor for development of NASH (OR 1.003, 95% CI 1.0003-1.006; p = 0.047). CONCLUSIONS: Nonalcoholic steatohepatitis patients had higher levels of serum BAFF than patients with SS, and higher levels were associated with the presence of hepatocyte ballooning and advanced fibrosis. The serum BAFF level may be a useful tool for distinguishing NASH from SS.

B cell-activating factor controls the production of adipokines and induces insulin resistance.

Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell-activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate-1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF-receptor (BAFF-R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.