A multicenter randomized trial comparing rabeprazole and itopride in patients with functional dyspepsia in Japan: the NAGOYA study.

The aims of this study were to compare the therapeutic effects of a proton pump inhibitor (PPI), rabeprazole (RPZ), and a prokinetic agent, itopride (ITO), and to investigate the role of PPI in the treatment strategy for Japanese functional dyspepsia (FD) patients. We randomly assigned 134 patients diagnosed by Rome III criteria to 4 weeks treatment with RPZ 10 mg/day (n = 69) or ITO 150 mg/day (n = 65). Dyspeptic symptoms were evaluated using FD scores at baseline and after 1, 2 and 4 weeks of treatment. We also divided subjects into predominantly epigastric pain syndrome (EPS) or postprandial distress syndrome (PDS), and evaluated the efficacy of RPZ and ITO respectively. RPZ showed a significant decrease in the Rate of Change (RC) in FD score within 1 week, which was maintained until after 4 weeks, with RPZ a significant effect compared with ITO at all evaluation points. In addition, RPZ showed a significant decrease in FD score in subjects with both EPS and PDS, whereas a significant decrease in the RC with ITO was only shown in those with predominant PDS. Acid-suppressive therapy with RPZ is useful for PDS as well EPS in Japanese FD patients (UMIN Clinical Trials Registry number: UMIN 000013962).

Histology of symptomatic gastroesophageal reflux disease: is it predictive of response to proton pump inhibitors?

BACKGROUND AND AIM: To examine the differences in esophageal histopathology between non-erosive reflux disease (NERD) and reflux esophagitis (RE), and to investigate whether baseline esophageal histopathology can predict the therapeutic response to proton pump inhibitors (PPIs). METHOD: The subjects comprised 94 patients with NERD (n = 71) or mild RE (n = 23). Tissue was biopsied from 5 cm above the squamo-columnar junction (SCJ), and the degree or presence of nine histopathological markers was assessed. The patients were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. If complete heartburn relief was not achieved, RPZ was increased to 10 mg twice daily for another 2 weeks, and then to 20 mg twice daily for another 2 weeks if heartburn remained. RESULTS: Features of esophageal histopathology 5 cm above the SCJ differed between NERD and RE patients. The esophageal histopathology in patients unresponsive to RPZ was characterized by Protein Gene Product (PGP) 9.5 negativity in those with NERD, and intraepithelial bleeding in those with RE. In addition, the combination of dilated intercellular spaces (DIS) (+)/PGP 9.5 (-) was indicative of strong resistance to PPI therapy in NERD patients. CONCLUSION: The therapeutic efficacy of PPI can be predicted from the features of biopsied esophageal tissue. Factors predictive of resistance to treatment with PPI are negativity for PGP 9.5 in NERD patients and intraepithelial bleeding in RE patients.

Predictive Factors for Future Onset of Reflux Esophagitis: A Longitudinal Case-control Study Using Health Checkup Records.

BACKGROUND/AIMS: Although risk factors of reflux esophagitis (RE) have been investigated in numerous cross-sectional studies, little is known about predictive factors associated with future onset of RE. We investigated time courses of clinical parameters before RE onset by a longitudinal case-control study using health checkup records. METHODS: We used health checkup records between April 2004 and March 2014 at 9 institutions in Japan. A multivariate logistic regression analysis was performed to evaluate associations of baseline clinical parameters with RE. The time courses of the clinical parameters of RE subjects were compared with those of non-RE subjects by the mixed-effects models for repeated measures analysis or longitudinal multivariate logistic analysis. RESULTS: Initial data were obtained from 230 056 individuals, and 2066 RE subjects and 4132 non-RE subjects were finally included in the analysis. Body mass index, alanine aminotransferase, smoking, acid reflux symptoms, hiatal hernia, and absence of atrophic gastritis at baseline were independently associated with RE. The time courses of body mass index, fasting blood sugar, triglyceride, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, percentages of acid reflux symptoms, feeling of fullness, and hiatal hernia in the RE group were significantly worse than in the non-RE group. CONCLUSIONS: The RE group displayed a greater worsening of the clinical parameters associated with lifestyle diseases, including obesity, diabetes, hyperlipidemia, and fatty liver for 5 years before RE onset compared with the non-RE group. These results suggest that RE is a lifestyle disease and thus lifestyle guidance to at-risk person may help to prevent RE onset.

Blockage of angiotensin II type 1 receptor regulates TNF-alpha-induced MAdCAM-1 expression via inhibition of NF-kappaB translocation to the nucleus and ameliorates colitis.

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to alpha4beta7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R-/-) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-alpha, but did not inhibit phosphorylation of p38 MAPK or of IkappaB that modulate MAdCAM-1 expression. However, NF-kappaB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R-/- than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R-/- than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-kappaB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup.

BACKGROUND AND AIM: The question of whether fatty liver might predict impaired fasting glucose or type 2 diabetes mellitus in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. METHODS: A total of 12 375 individuals (6799 men and 5576 women) without hyperglycemia or type 2 diabetes mellitus in 2000 and participating in 2005 were included. Multiple logistic regression analyses were performed for both sexes, adjusted for age, body mass index, elevated blood pressure or hypertension, family history of diabetes mellitus, alcohol drinking and smoking. RESULTS: Impaired fasting glucose and type 2 diabetes mellitus were newly diagnosed in 7.6% and 1.0% of men and 3.8% and 0.5% of women, respectively, within the 5-year period. The prevalence of newly diagnosed impaired fasting glucose and type 2 diabetes mellitus was significantly higher in the participants with fatty liver than without fatty liver in both sexes. Fatty liver adjusted for the other factors was thus a risk factor for impaired fasting glucose and/or type 2 diabetes mellitus in both sexes (men odds ratio [OR] 1.91, 95% confidence interval [CI] 1.56-2.34 and women OR 2.15, 95% CI 1.53-3.01). The impact of fatty liver was stronger among the participants with a lower body mass index (men OR 0.92, 95% CI 0.86-0.99 and women OR 0.90, 95% CI 0.81-0.99, for one increment of body mass index). CONCLUSION: Fatty liver is an independent risk factor for impaired fasting glucose and type 2 diabetes mellitus, having a stronger impact in those Japanese with a lower body mass index undergoing a health checkup.

Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease.

BACKGROUND: More than half of patients with refluxrelated symptoms have no endoscopic evidence of mucosal breaks. These patients are considered to have nonerosive gastroesophageal reflux disease (NERD). The pathogenesis of NERD may be multifactorial, but the role played by gastric motility in symptom generation in patients with NERD has not been examined. In this study, we elucidate gastric motility in patients with NERD and the efficacy of a prokinetic agent in the treatment of NERD. METHODS: Gastric motility was evaluated with electrogastrography (EGG) and by measurement of gastric emptying using the acetaminophen method in 26 patients with NERD and in 11 matched healthy controls. NERD patients were treated with a prokinetic agent (mosapride 15 mg, orally three times daily) for a period of 4 weeks, after which gastric motility was measured again. RESULTS: Compared with the healthy controls, the NERD patients showed a significantly lower percentage of normogastria, a lower power ratio in EGG, and delayed gastric emptying. Ten patients had normal gastric motor function (group A), and 16 showed abnormalities of either gastric myoelectrical activity or gastric emptying (group B). After treatment with mosapride, gastric motility improved significantly in both groups of patients compared with pretreatment values. The subjective assessment by the patient after the treatment was improved in 20.0% of group A versus 62.5% of group B patients (P < 0.05). CONCLUSIONS: Gastric hypomotility appears to be an important factor in reflux symptom generation in some NERD patients.

Gastroesophageal and laryngopharyngeal reflux symptoms correlate with histopathologic inflammation of the upper and lower esophagus.

BACKGROUND: The presence of laryngopharyngeal reflux disease is controversial when abnormal sensation of the laryngopharynx is felt without heartburn. GOALS: The aims of this study were to investigate the relationship between abnormal sensation of the laryngopharynx and gastroesophageal reflux, and to elucidate the pathology of laryngopharyngeal reflux disease by investigating histopathologic findings of the upper and lower esophagus. STUDY: Upper and lower esophageal tissues were biopsied by endoscopy in 300 consenting patients, excluding those with serious diseases. RESULTS: Fifty-seven patients (19.0%) reported reflux symptoms alone (reflux symptom group), 48 patients (16.0%) reported abnormal sensation of the laryngopharynx alone (abnormal laryngopharyngeal sensation group), and 74 patients (24.7%) reported both reflux symptoms and abnormal sensation of the laryngopharynx (complication group), whereas 121 patients (40.3%) did not report subjective reflux symptoms and abnormal sensation of the laryngopharynx (control group). Histopathologic inflammation of the upper esophagus was significantly greater in the complication and abnormal laryngopharyngeal sensation groups compared with the control group. Histologic inflammation of the lower esophagus was significantly higher in the complication and reflux symptom groups compared with the control group. CONCLUSIONS: The histopathologic findings of the upper and lower esophagus elucidated an association between gastroesophageal reflux and abnormal sensation of the laryngopharynx.

Gastric-and-intestinal mixed endocrine cell phenotypic expression of carcinoid tumors in the rectum.

We have previously demonstrated that gastric and intestinal endocrine cell (End-cell) marker expression is important for assessment of the histogenesis of endocrine cell tumors. However, the End-cell phenotypes of carcinoid tumors in the rectum remain largely unclear. We therefore examined marker expression of rectal carcinoid tumors. We evaluated 20 rectal carcinoid tumors (as well as 8 from the stomach for comparison) phenotypically, using gastrin, gastric inhibitory polypeptide (GIP) and glucagons-like peptide-1 (GLP-1) as End-cell markers. Rectal carcinoid tumors were divided into 3 endocrine-gastric (e-G), 16 endocrine-gastric-and-intestinal mixed (e-GI), 1 endocrine-intestinal (e-I), and 0 endocrine-null (e-N) types, thus 19 (e-G+ e-GI types, 95%) had gastric phenotypic expression, while 17 (e-GI+ e-I types, 85%) harbored intestinal elements. Stomach carcinoid tumors were classified as 6 e-G and 2 e-N types, respectively. In conclusion, most rectal carcinoid tumors exhibited the e-GI type, suggesting the importance of gastric End-cell marker expression for histogenesis of the rectal carcinoid tumors. Further studies of pathological and biological analyses are needed to clarify the histogenesis of the carcinoid tumors.

Advanced stomach and pancreas cancer successfully treated with combination chemotherapy with S-1/paclitaxel/lentinan.

We report a case of stomach and pancreas cancers that showed marked responses to combination chemotherapy consisting of S-1, paclitaxel (PTX), and lentinan (LNT). A 67-year-old Japanese man was referred to our hospital in July 2005, diagnosed with advanced gastric cancer. Subsequent examination revealed the existence of cancers in the stomach and pancreas, with lymph nodes and peritoneal metastasis and ascites. The patient received combined chemotherapy (one course comprised 3 weeks) with S-1 (100 mg/body, day 1-14 followed by withdrawal for 1 week), PTX (50 mg/m2, day 1 and day 8), and LNT (2 mg/m2, day 1, day 8 and day 15). After completion of 4 courses, the patient achieved partial response (PR), with complete disappearance of the primary gastric tumor and ascites. He maintained in PR for 17 months. We analyzed Th1/ Th2 ratio and LNT binding rate to monocytes by flow cytometry. Combination chemotherapy with S-1/PTX/LNT can be an effective treatment for unresectable advanced gastric carcinoma.

Gastric phenotypic expression and histogenesis of metachronous gastric cancers endoscopically resected.

BACKGROUND/AIMS: Endoscopic Resection (ER) has been performed for early gastric cancers, and metachronous gastric cancers (MGCs) were occasionally observed. Most MGCs were classified histologically as the differentiated type. However, there have been no data on the gastric and intestinal phenotypic classification of MGCs. In our previous study, Hp-infection in MG may trigger intestinalization of gastric cancers. We therefore speculate the phenotype shift in MGC lesions under Hp-chronic-infection. METHODOLOGY: We examined the 17 MGC lesions phenotypically and histologically by using several gastric and intestinal epithelial cell markers, MUC5AC, MUC6, MUC2 and villin. RESULTS: Most lesions (16/17) exhibited the differentiated type. In 8 first cancers, the lesions were divided phenotypically into 2 G, 4 GI, 1 I, and 1 N types. In 9 second/third cancers, the lesions were divided phenotypically into 3 G, 1 GI, 4 I, and 1 N types. The first lesions (6/8) had more gastric phenotypic expression compared with the second/third ones (4/9) in the MGCs, although there was no significant difference between two groups (P = 0.28). CONCLUSION: Our present data suggest the possibility that the cancer retaining G type is detected endoscopically earlier than that obtaining the intestinal phenotypic expression by the phenotypic shift, which may partially explain the MGC occurrence.

Lentinan with S-1 and paclitaxel for gastric cancer chemotherapy improve patient quality of life.

BACKGROUND/AIMS: Lentinan (LNT), a purified beta-glucan, is a biological and immunological modifier and has been used as an anticancer drug in combination with 5-fluorouracil for gastric cancer in Japan. In this prospective randomized study, we evaluated the effects of LNT combination with regard to quality of life (QOL) and LNT binding ratio in monocytes. METHODOLOGY: Twenty patients were evaluated for 12 weeks. One cycle was 3 weeks and S-1 (day1-14) and Paclitaxel (days1 and 8) were administered. LNT was used once a week (days 1, 8 and 15) and it was used for all 12 weeks in the LNT 12-wk group and only for the last 6 weeks in the LNT 6-wk group. QOL was evaluated weekly by QOL-ACD, and binding of LNT to monocytes was measured by flow cytometry. RESULTS: There were individual variations in the binding ratio of LNT to monocytes from 0.16% to 11.95%. Toxicity with chemotherapy was not improved in the LNT 12-wk group, however, the total QOL score was significantly elevated in the LNT 12-wk group (p = 0.018) but not in the LNT 6-wk group. CONCLUSION: LNT combination from the beginning of the chemotherapy may be an important factor for the improvement of patient QOL.

Gastric schwannoma with adjacent external progression harbored aberrant NF2 gene.

Gastric schwannomas are rare benign mesenchymal tumors. We describe a schwannoma of gastric origin with adjacent external progression. Sections showed a spindle cell tumor arranged in interlaced bundles and fascicles that was S-100 and CD34 positive but c-KIT protein negative. Histology and immunohistochemistry revealed the typical appearance of a gastric schwannoma. Genetic evaluation revealed that the tumor harbored a point mutation in exon 6 of the tumor suppressor neurofibromatosis 2 (NF2) gene, which resulted in an amino acid substitution of NF2 protein, and no mutation in exon 4b of the NF1 gene. In conclusion, we identified a rare mutation of the NF2 gene in gastric schwannoma. A diagnosis can only be definitive when based on histological and immunohistochemical findings. Digestive tract schwannomas are rare mesenchymal tumors that are differentiated from gastrointestinal stromal tumors by the absence of KIT protein. Follow up suggested that complete resection is an effective long-term treatment strategy.

An endocrine cell carcinoma with gastric-and-intestinal mixed phenotype adenocarcinoma component in the stomach.

A 77-year-old man complained of bodyweight loss, and a Borrmann 3 type lesion was observed endoscopically in the anterior wall of angular region of the stomach. The endocrine cell carcinoma (ECC) having the cytoplasmic staining of chromogranin A (CgA) was detected pathologically in the biopsy samples. The patient underwent distal gastrectomy plus systemic lymph node (LN) dissection (D2 LN dissection), and pathological examination revealed ECC invading the subserosa, and no LN metastasis (pT2N0M0). None of the gastric and intestinal endocrine cell marker expression was apparent in the ECC cells. The lesion also contained a moderately differentiated type tubular adenocarcinoma component, which was judged to be gastric-and-intestinal mixed (GI type) phenotype, using gastric and intestinal exocrine cell markers. After the surgery, he left the hospital and started oral doxifluridine (600 mg/day). The patient now (March 2008, about 19 months since the surgery) continues this chemotherapy with no recurrence. In conclusion, we experienced ECC with a GI type adenocarcinoma component. The ECC cases with the GI type adenocarcinoma component may have a relatively good prognosis, being similar to the results of advanced gastric cancers from the viewpoint of gastric and intestinal phenotypic expression.

[Case of duodenal stenosis due to hematoma after rupture of the inferior pancreaticoduodenal artery aneurysm treated by coil embolization].

A 59-year-old woman was admitted because of vomiting, CT examinations it was determined that the cause of vomiting was duodenal stenosis due to hematoma after rupture of the inferior pancreaticoduodenal artery aneurysm. In addition, it was believed that the aneurysm had been caused by obstruction of the celiac artery. The aneurysm of the inferior pancreaticoduodenal artery was detected by angiography, and embolization was performed using coils. The embolization was successful. Since then the duodenal stenosis improved and the vomiting symptoms disappeared. We reviewed 28 cases of duodenal stenosis due to rupture of the pancreaticoduodenal artery aneurysm in the Japanese literature.

[The efficacy of probiotics in gastrointestinal disease].

Probiotics are live microbial feed supplement which beneficially affects the host animals by improving its microbial balance. Probiotics have been used in the treatment of bacterial or viral induced acute intestinal infection. In recent years, some clinical studies have shown the therapeutic effects of probiotics in the treatment of chronic inflammatory bowel disease (IBD) or prevention of allergic disease. Evidence exists for therapeutic use of probiotics in acute infectious diarrhea, Clostridium difficile colitis and antibiotic-associated diarrhea. Their exact role in IBD, irritable bowel syndrome and prevention of cancer has not to be determined. This review summarized the data about probiotics in gastrointestinal diseases and examine the mechanisms of action related to their therapeutic effects.

Validity of endoscopic classification of nonerosive reflux disease.

BACKGROUND: Minimal changes, such as erythema without sharp demarcation or whitish turbidity of the lower esophageal mucosa, have recently been used for endoscopic classification of nonerosive reflux disease (NERD) in Japan. This study examined the usefulness of such changes in characterizing the pathophysiology of NERD. METHODS: Physicians specializing in esophageal endoscopy performed endoscopy on 115 patients with NERD. Based on the presence or absence of minimal changes, patients were categorized as displaying NERD with minimal changes (grade M, n = 49) or with no minimal changes or mucosal breaks (grade N, n = 66). Clinical features, quality of life (QOL) scores, and ambulatory 24-h esophageal pH values were compared between groups. Ambulatory 24-h esophageal pH values were monitored in 31 patients (14 grade M and 17 grade N patients) who gave consent out of 115 patients. RESULTS: In ambulatory 24-h esophageal pH monitoring, 57.1% (8/14) of grade M patients had pH < 4 more than 4% of the time (abnormal acid reflux) compared with 11.8% (2/17) in the grade N group, a significant difference (P = 0.018). QOL scores did not differ significantly between grades and were significantly lower in both groups compared with the general Japanese population. No significant differences were observed in patient background between the grade M and grade N groups. CONCLUSIONS: Frequency of abnormal acid reflux with NERD is higher in patients with minimal changes than in patients without such changes. Minimal changes are most likely attributable to gastric acid reflux.

[Histopathological diagnosis in gastroesophageal reflux disease].

We reviewed the histopathological features for the diagnosis of gastroesophageal reflux disease (GERD). The presence of infiltration inflammatory cells, thickened basal cell layer, increased papillary height was histopathologically evaluated in GERD patients. It is often difficult to diagnose GERD symptoms when there were few endoscopic findings, such as lack of hiatal hernia and erosive esophagitis. At that time, we might be able to diagnose GERD by the histopathological examination except the pH monitor was performed. We showed that the histopathological esophagitis correlated with reflux symptoms and laryngopharyngeal symptoms. These indicated that the histopathological esophagitis may be diagnosed as not only typical GERD but also atypical GERD.

Adenosquamous carcinoma of the jejunum.

Primary adenosquamous carcinomas of the intestine are rare, particularly in the small intestine. One case, in the jejunum of an adult female, is described here. The patient was a 70-year-old Japanese woman presenting with upper abdominal pain. Computed tomography of the abdomen showed a mass in the small intestine, measuring 86 x 44 mm, and a double-contrast barium study revealed a filling defect in the upper jejunum. The patient was diagnosed as suffering from upper small-intestinal cancer, and surgical excision was performed. Histological examination, including immunohistochemistry and electron microscopy, revealed the tumor to have both malignant glandular and squamous components. A review of the literature regarding this type of lesion is presented.

Elevated serum uric acid predicts chronic kidney disease.

INTRODUCTION: The question of whether elevated serum uric acid is an independent risk factor for chronic kidney disease in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. METHODS: A total of 14,399 participants (8,161 men and 6,238 women) without medication for hyperuremia in both 2000 and 2005 were included. After exclusion of participants taking treatments influencing serum uric acid and having chronic kidney disease defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2), in 2000, multiple logistic regression analyses were performed for 6,887 men (48.4 ± 9.9 years) and 5,340 women (49.9 ± 9.0 years) to identify independent factors for newly diagnosed chronic kidney disease in 2005. Adjustment was made for age, body mass index, elevated blood pressure or hypertension, hypertriglyceridemia, impaired fasting glucose, either urinary protein or occult blood, alcohol drinking and smoking. RESULTS: The prevalence of chronic kidney disease and the values of body mass index, systolic and diastolic blood pressure and triglyceride were significantly higher in the participants with elevated serum uric acid quartiles. Chronic kidney disease was newly diagnosed in 4.1% of men and 3.7% of women, within the 5-year period. In multivariate models, the higher quartiles of serum uric acid were associated with increased risk of chronic kidney disease in both sexes. The odds ratio and 95% confidence interval for 1 increment of serum uric acid were 1.42 and 1.28 to 1.58 in men and 1.32 and 1.12 to 1.56 in women, respectively. CONCLUSIONS: Elevated serum uric acid predicts chronic kidney disease in subjects undergoing a health checkup.

Elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease in Japanese undergoing a health checkup.

BACKGROUND AND STUDY AIMS: The question of whether elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease evident on ultrasonography was investigated by longitudinal approach in Japanese undergoing a health checkup. PATIENTS AND METHODS: A total of 1,386 male and 3,453 female nondrinkers participating in health checkups in both 2000 and 2005 were included. Multiple logistic regression analyses were performed for 1,042 men (51.4 +/- 11.2 years old) and 3,076 women (51.8 +/- 9.2 years old) to identify independent factors for newly developed nonalcoholic fatty liver disease in 2005. Adjustment was made for age, body mass index, body mass index increase for 5 years, systolic blood pressure, triglyceridemia, fasting blood glucose, and smoking. RESULTS: The prevalence of nonalcoholic fatty liver disease and body mass index, systolic blood pressure, and triglyceride were significantly higher in the participants with elevated serum uric acid, with a significant increasing trend in relation to serum uric acid quartiles. Nonalcoholic fatty liver disease was newly diagnosed in 17.4% of males and 8.2% of females, respectively, in 2005. Serum uric acid adjusted for other factors was a risk factor for nonalcoholic fatty liver disease in both sexes and quartiles 3 and 4 had significantly elevated risks. The odds ratio and 95% confidence interval for one increment of serum uric acid were 1.31 and 1.11-1.56 in men and 1.30 and 1.10-1.53 in women, respectively. CONCLUSIONS: Elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease in Japanese undergoing a health checkup.