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Background: Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis., Methods: Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography., Results: After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P < 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P < 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC., Conclusions: Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

Background: Fatty liver is an important clinical feature not only in alcoholic and non-alcoholic fatty liver diseases, but in other chronic liver diseases as well. Our aim was to elucidate the effect and relationship between habitual alcohol intake and obesity in the development of fatty liver disease., Methods: We enrolled 8,029 subjects undergoing abdominal ultrasonography with general medical examinations, and analyzed the factors associated with fatty liver based on daily alcohol intake, body mass index (BMI), and waist circumference., Results: For fatty liver, BMI, waist circumference, total cholesterol, triglycerides, and fasting plasma glucose were significant and independent risk factors. Heavy alcohol intake (50 g/day) was a significant risk factor for fatty liver in women (odds ratio [OR], 3.35). Analysis based on the presence or absence of obesity revealed that moderate alcohol intake was a significant negative risk factor for fatty liver in both male and female obese (BMI ≥25 kg/m(2)) subjects (OR, 0.74 for non-obese and 0.39 for obese patients, respectively). Heavy alcohol intake was also a significant negative risk factor in obese males (0.62). In contrast, heavy alcohol intake was a risk factor in non-obese males (OR, 1.29) and in all females (OR, 2.22 for non-obese and 6.6 for obese patients, respectively)., Conclusions: The influence of alcohol intake on fatty liver differed depending on the level of alcohol consumption, gender, and the presence of obesity, and showed biphasic effects.

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. This study aimed to assess the recent prevalence of NAFLD and to predict the prevalence of nonalcoholic steatohepatitis (NASH) with liver fibrosis using established scoring systems in the general population., Methods: A cross-sectional study was conducted among 8352 subjects who received health checkups from 2009 to 2010 in three health centers in Japan. Subjects with an intake over 20 g of alcohol/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. The probability of NASH with advanced fibrosis was calculated according to the body mass index, age, ALT, and triglyceride (BAAT) and FIB-4 (based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet counts) indices., Results: A total of 5075 subjects were enrolled. The overall prevalence of NAFLD was 29.7%. There was a significant threefold difference in the mean prevalence between males (41.0%) and females (17.7%). This prevalence showed a linear increase with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even without obesity. The estimated prevalence of NASH according to the BAAT index ≥3 was 2.7%, and according to the FIB-4 index it was 1.9%., Conclusions: The prevalence of NAFLD has increased in the general population, especially in males. There is a linear relationship between the prevalence of NAFLD and various metabolic parameters, even in nonobese subjects. The prevalence of NASH with advanced fibrosis is estimated to be considerably high in subjects with NAFLD.

Background: Our previous studies have indicated a close association between visceral fat accumulation and hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). This study investigated whether visceral fat accumulation was related to the pathogenesis and disease progression of nonalcoholic steatohepatitis (NASH)/NAFLD., Methods: First, a total of 550 subjects who underwent a health checkup and measurement of visceral fat accumulation, done with a bioelectrical impedance analyzer (X-SCAN; Owa Medical, Fukuoka, Japan), were included. The relationship between visceral fat accumulation and biochemical parameters was examined. Second, a total of 74 patients with NASH/NAFLD who underwent liver biopsy were reviewed. Visceral fat accumulation was determined by abdominal computed tomography. The association between visceral fat accumulation and the histopathological grade/stage determined by the NAFLD activity score and Brunt's classification was evaluated., Results: There was a significant relationship between visceral fat accumulation and glucose, triglyceride, and alanine aminotransferase (ALT; r = 0.423, P < 0.01). In stepwise regression analysis, visceral fat area (VFA), serum triglyceride level, and serum low-density lipoprotein (LDL)-cholesterol level were selected as predictor variables for serum ALT level, in a continuous manner (serum ALT level = -1.359 + 0.143 × VFA + 0.046 × triglyceride + 0.059 × LDL, R(2) = 0.217, P < 0.001). In patients with NASH, there was no correlation between histological grade and the visceral fat volume. Visceral fat accumulation in patients with stage 3/4 advanced NASH was greater than that in patients with stage 1/2 early NASH (P < 0.05)., Conclusions: These results suggest that visceral fat accumulation plays a role in steatosis and fibrosis in the pathogenesis and prognosis of NAFLD.

Objectives: We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V(2) receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis., Methods: Tolvaptan was orally administrated at titrated doses of 15, 30, and 60 mg once daily after breakfast for 3 days at each dose to 18 liver cirrhosis patients with persistent ascites and/or lower limb edema despite receiving oral furosemide at 40 mg/day or higher., Results: Decreased body weight and abdominal circumference and improvement of ascites and edema were observed following tolvaptan administration beginning from 15 mg. Composite ascites/edema improvement rate was 88.2% at individual maximum doses and 64.7, 80.0, and 90.9%, respectively, after 3-day administration at 15, 30, and 60 mg. Changes in body weight after 3-day administration at 15, 30, and 60 mg were -1.6 ± 0.9, -2.6 ± 1.2, and -3.4 ± 2.1 kg (mean ± SD), respectively, and decreases of 1 kg or more were seen from day 2 (24 h after first dosing). Changes in abdominal circumference ranged from -2.8 to -6.0 cm. Cumulative 24-h urine volumes after 3-day administration at 15, 30, and 60 mg were, respectively, 3240.3 ± 1014.5, 3943.3 ± 1060.6, and 4537.4 ± 1621.3 mL/day (mean ± SD). Urine osmolarity was markedly decreased and remained decreased until the end of treatment., Conclusion: Tolvaptan dose-dependently decreased body weight and abdominal circumference and improved ascites and edema beginning from 15 mg, demonstrating a potent aquaretic effect.

Background: Although nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity, the relationship between visceral fat accumulation and skeletal muscle steatosis in patients with NAFLD has not been established. We evaluated: (1) the relationship between multifidus muscular tissue steatosis, visceral fat accumulation, and biochemical data in a cross-sectional study, and (2) the influence of weight reduction on multifidus muscular tissue steatosis in a longitudinal study., Methods: Three hundred thirty-three NAFLD patients were enrolled. Hepatic steatosis, visceral fat area, and the multifidus muscle/subcutaneous fat attenuation ratio (MM/F ratio) were evaluated by computed tomography. To evaluate how weight reduction produced by diet and exercise affected the MM/F ratio, changes in the MM/F ratio were compared between weight reduction and non-weight reduction groups., Results: There was a gender difference in MM/F ratios. The MM/F ratio was significantly correlated with age (male r = 0.613, P < 0.01; female r = 0.440, P < 0.01). The MM/F ratio was positively correlated with visceral fat area (male: r = 0.262, P < 0.01; female: r = 0.214, P < 0.01). A decrease in the MM/F ratio, concomitant with reduced visceral fat accumulation, led to alleviation of hepatic steatosis in 20 patients with weight reduction, but not in 22 patients without weight reduction., Conclusions: The MM/F ratio was closely related to aging and visceral fat accumulation. The MM/F ratio was improved by weight reduction, indicating that fat accumulation in the multifidus muscle evaluated by computed tomography might be a therapeutic indicator of NAFLD.

Background: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome. The aim of this study was to evaluate a 6-month home-based lifestyle modification intervention delivered in collaboration with physicians, hygienists, registered dietitians, and nurses., Methods: Outpatients with NAFLD diagnosed by abdominal ultrasonography were eligible for this study. Abdominal computed tomography (CT) scan evaluated liver fat deposition by the liver-spleen ratio (L/S ratio) and visceral fat accumulation as the visceral fat area (VFA; cm(2)). During the 6-month home-based lifestyle modification intervention, each patient was examined by physicians, nurses, hygienists, and registered dietitians, who provided individualized advice to the patients. Patients recorded their daily weight for self-control of weight with recommended diet and exercise regimens., Results: Sixty-seven NAFLD patients were enrolled in this study and 22 patients (32.8%) completed the 6-month intervention. Nineteen of the 22 patients achieved significant improvements in body weight, body mass index (BMI), waist circumference, VFA, L/S ratio, and systolic blood pressure, with improved laboratory data. Overall, 39 patients withdrew from the intervention. The mean age of the patients who withdrew was 50.0 +/- 11.0 years, which was significantly younger than that of the patients who were followed up (60.1 +/- 10.1 years; P < 0.01)., Conclusions: The reduction in body weight achieved by NAFLD patients during the 6-month intervention was associated with improved fat deposition and liver function. This intervention offers a practical approach for treating a large number of NAFLD patients with lifestyle modification therapy.

Purpose: The purpose of this study was to compare the efficacy of proton pump inhibitor (PPI) with H(2) receptor antagonist (H(2)RA) in treatment of upper abdominal symptoms., Methods: This was a multi-center, open study conducted at 102 hospitals in Japan. Patients with reflux esophagitis received famotidine 10 mg twice daily for 2 weeks, then omeprazole 10 mg once daily for 2 weeks. Thereafter, patients were switched to famotidine 10 mg twice daily for a third 2-weekperiod, provided those with a medical condition agreed to continue the study. Patients evaluated the treatment response to each gastrointestinal symptom using a predefined patient questionnaire and gastrointestinal symptom rating scale (GSRS)., Results: 161 patients entered the study, of whom 8 were excluded from all analyses due to lack of participation following entry. Overall symptom improvement rate (n = 130) at week 4, after the 2-week omeprazole treatment, was 75.4% and this was significantly higher than that after the first 2-week famotidine treatment (41.5%) at week 2. In patients (n = 36) who completed 6 weeks of treatment, 2-week omeprazole treatment at week 4 showed a significantly higher overall symptom improvement rate compared with both the first 2-week and third 2-week famotidine treatments., Conclusions: Omeprazole was superior to famotidine for treatment of upper abdominal symptoms in patients with reflux esophagitis, which suggested that gastric acid might be a cause not only of reflux symptoms, but also of ulcer symptoms and dysmotility symptoms such as epigastric pain and feeling of fullness in reflux esophagitis.

Background: Nonalcoholic fatty liver diseases are often associated with obesity, insulin resistance, and excessive visceral fat accumulation. The aims of this study were (1) to evaluate the relationship between the severity of fatty liver and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to investigate the relationships of fatty liver with biochemical data and insulin resistance., Methods: One hundred twenty-nine subjects (63 women) with fatty liver diagnosed by ultrasonography were enrolled. Subjects positive for hepatitis B virus, hepatitis C virus, or autoimmune antibodies and those whose alcohol intake was over 20 g/day were excluded. The visceral fat area at the umbilical level and the liver-spleen ratio were evaluated by computed tomography., Results: The severity of fatty liver evaluated by ultrasonography showed a significant positive relationship with the visceral fat area and waist circumstance (fatty liver severity: mild, 92.0 +/- 30.9 cm(2); moderate, 122.1 +/- 32.6 cm(2); severe, 161.0 +/- 48.4 cm(2); P < 0.0001). The visceral fat area and liver-spleen ratio were negatively correlated (r = -0.605, P < 0.0001). The severity of fatty liver showed strong positive relationships with serum aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, fasting plasma insulin, and insulin resistance. The severity of fatty liver was positively related to the visceral fat area in 49 nonobese subjects (body mass index <25)., Conclusions: The severity of fatty liver was positively correlated with visceral fat accumulation and insulin resistance in both obese and nonobese subjects, suggesting that hepatic fat infiltration in nonalcoholic fatty liver disease may be influenced by visceral fat accumulation regardless of body mass index.

A 66-year-old man with ascites and marked edema in the lower extremities was suspected of having secondary Budd-Chiari syndrome due to primary liver cancer, based on imaging diagnosis, i.e., ultrasonography, computed tomography, and inferior venacavogram. At autopsy, an encapsulated small liver cancer was found to have extended into the inferior vena cava and right atrium. There have been few reports of small hepatocellular carcinoma with intravascular tumor growth into the right atrium.