Association between reactive oxygen species production in neutrophils and liver fibrosis in the general population.

Fibrosis, induced by reactive oxygen species (ROS) production in neutrophils, has harmful effects on the liver and various other organs. However, little is known about the association between liver fibrosis and ROS levels in neutrophils in the general population. This large-scale epidemiological study aimed to determine the association between liver fibrosis and neutrophil-generated ROS levels according to age and sex in the general population. This cross-sectional study included 1,000 participants from a district health promotion project. Participants were grouped based on sex (male; female) and age (young, <65 years; old, ≥65 years). The four groups were as follows: male, young (n = 289); male, old (n = 100); female, young (n = 425); and female, old (n = 186). Liver fibrosis was assessed using the fibrosis 4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Basal and stimulated ROS were considered in the analysis. Multiple linear analyses showed (1) significant positive correlations between all liver fibrosis scores and basal ROS in the young groups, and (2) significant negative correlations between NFS and stimulated ROS in females. Preventing liver fibrosis through neutrophil-related immune system enhancement may avert the development of lifestyle-related diseases and infections.

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

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

Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan-Aspartate Aminotransferase Score.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

A case of hepaticojejunal anastomotic obstruction after a living-donor liver transplantation and recanalization using a high-frequency knife under the rendezvous technique.

A 65-year-old woman underwent living-donor liver transplantation (left-lobe graft: GWRW ratio, 0.54) for cirrhosis caused by autoimmune hepatitis. At 68 years, she was diagnosed with obstructive cholangitis due to stricture during a hepaticojejunostomy following impaired liver function. Endoscopic balloon dilation of anastomosis and placement of a plastic stent resulted in improved liver function. However, at 72 years, the patient experienced a flare-up of liver damage. The plastic stent had fallen out, and although endoscopic stenotic dilation was attempted, the anastomotic site was obstructed completely. Therefore, recanalization of the hepaticojejunostomy was attempted using a rendezvous technique. A percutaneous transhepatic biliary drainage tube was inserted through the B3 bile duct, and the complete obstructed anastomosis was confirmed by percutaneous transhepatic and transjejunal approaches. The anastomosis was reopened by excising the scarred tissues from the jejunal side using a 1.5-mm high-frequency knife. A 14-Fr. catheter for the internal fistula tube was percutaneously placed at the opened anastomosis to achieve anastomotic site recanalization. The patient's liver damage improved after the re-internalization, and no symptom recurrence such as obstructive cholangitis developed for 1 year. There are few reports of recanalization of the hepaticojejunostomy with a high-frequency knife. Herein, we report the case with a literature review.

Evaluation of metabolic dysfunction-associated fatty liver disease using FibroScan, diet, and microbiota: A large cross-sectional study.

OBJECTIVE: We evaluated the clinical characteristics of metabolic dysfunction-associated fatty liver disease (MAFLD) to evaluate the usefulness of the MAFLD diagnostic criteria in a resident health survey. METHODS: In 1056 participants of a health survey, we compared obesity, diabetes, metabolic dysregulation, FibroScan-aspartate aminotransferase (FAST) score, dietary habits, and gut microbiota between healthy individuals and participants with MAFLD and Nonalcoholic fatty liver disease (NAFLD). RESULTS: The proportion of participants with MAFLD in the fatty liver was higher than that with NAFLD (88.1% vs. 75.5%, respectively). Of 36 participants with a FAST score > 0.35, 29 (80.6%) participants had MAFLD and 23 (63.9%) participants had NAFLD. Of 29 patients with liver fibrosis, 26 (89.7%) participants had obesity and metabolic dysregulation. In the evaluation of diet, the total energy, protein, dietary fiber, and salt intake were significantly higher in participants with MAFLD than those in participants without fatty liver. In the microbiota analysis, the results of the linear discriminant analysis effect size analysis revealed nine bacterial genera that were significantly different in participants with MAFLD in comparison with participants without fatty liver. Of these genera, the relative abundance of Blautia was especially low in participants with MAFLD. CONCLUSION: In a resident health survey, participants with MAFLD had a higher proportion of fatty liver than those with NAFLD. MAFLD criteria could help in improved screening of participants with liver fibrosis. Therefore, the MAFLD criteria could be a useful diagnostic tool for aggressively identifying participants with a high risk of fatty liver. Additionally, Blautia might be involved in the development of MAFLD.

Objective Response by mRECIST to Initial Lenvatinib Therapy Is an Independent Factor Contributing to Deep Response in Hepatocellular Carcinoma Treated with Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy.

Objective: There is limited information regarding the benefits of Lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for unresectable hepatocellular carcinoma (u-HCC). We compared the efficacy and safety of LEN-TACE sequential therapy to LEN monotherapy and investigated the factors contributing to the LEN-TACE sequential therapy deep response. Methods: We enrolled a multicenter cohort of 247 patients with u-HCC treated with LEN between 2018 and 2020. Propensity score matching identified 63 matching pairs of patients with well-balanced characteristics. We retrospectively compared the clinical outcomes, including overall survival (OS), progression-free survival (PFS), and incidence of adverse events (AEs), between the LEN-TACE and LEN monotherapy groups. Additionally, we evaluated the tumor response, change in albumin-bilirubin (ALBI) score, factors affecting PFS and OS, and independent predictors contributing to the LEN-TACE sequential therapy deep response. In this study, at eight weeks after resumption of LEN after initial TACE, "deep response" was defined as achieving complete response or partial response (PR) on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and at least a 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters as the reference. Results: The OS and PFS in the LEN-TACE group were significantly higher than those in the LEN monotherapy group (p = 0.002 and p = 0.037, respectively). The incidence of AEs related to LEN was not significantly different between the two groups. In LEN-TACE sequential therapy, the objective response rate was 61.9%, and the disease control rate was 74.6%, according to the mRECIST criteria. No significant change in the ALBI score was observed during sequential LEN-TACE therapy. Multivariable analyses revealed that deep response was independently associated with the outcome of the initial response to LEN by mRECIST: PR (odds ratio: 5.176, 95% confidence interval: 1.528-17.537, p < 0.001). Conclusions: LEN-TACE sequential therapy may provide more clinical benefits than LEN monotherapy in u-HCC patients who responded to initial LEN treatment. Objective response according to mRECIST to initial LEN is an independent factor contributing to LEN-TACE sequential therapy deep response.

Reduced Equol Production and Gut Microbiota Features in Men With Lean Nonalcoholic Fatty Liver Disease.

Patients with lean nonalcoholic fatty liver disease (NAFLD) may have different metabolic profiles than those with NAFLD. Estrogenic activity is associated with NAFLD pathogenesis. We evaluated the production ability of equol, which has estrogenic activity, in lean NAFLD and assessed their gut microbiota in relation to their equol-producing ability. Among 684 adult participants, 276 (40%) had NAFLD and 293 (43%) were equol producers. The rates of equol producers in the normal and NAFLD groups were 43% and 42%, respectively. Among the patients with NAFLD, 55 (20%) had lean NAFLD of which 18 (33%) were equol producers. The rate of equol production in men with lean NAFLD was 8%, which was the lowest, while the corresponding rate in the other participants was approximately 40%. The gut microbiota composition of equol producers and nonproducers showed many significant differences. The gut microbiota of men with lean NAFLD showed increased abundance of Caulobacter and decreased abundances of Slackia and Terrisporobacter. Thus, almost all men with lean NAFLD lacked equol-producing ability, and their gut microbiota showed a reduced abundance of Slackia, which is related to equol production. The pathology of lean NAFLD in men may be strongly associated with equol-producing ability and gut microbiota.

Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project.

We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77-0.91] in men and 0.72 in women (95% CI, 0.65-0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93-0.99) in men and 0.79 (95% CI, 0.66-0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.

Pre-stimulus alpha oscillation and post-stimulus cortical activity differ in localization between consciously perceived and missed near-threshold somatosensory stimuli.

Conscious perception of a near-threshold (NT) stimulus is characterized by the pre- and post-stimulus brain state. However, the power of pre-stimulus neural oscillations and strength of post-stimulus cortical activity that lead to conscious perception have rarely been examined in individual cortical areas. This is because most previous electro- and magnetoencephalography (EEG and MEG, respectively) studies involved scalp- and sensor-level analyses. Therefore, we recorded MEG during a continuous NT somatosensory stimulus detection task and applied the reconstructed source data in order to identify cortical areas where the post-stimulus cortical activity and pre-stimulus alpha oscillation predict the conscious perception of NT somatosensory stimuli. We found that the somatosensory hierarchical processing areas, prefrontal areas and cortical areas belonging to the default mode network showed stronger cortical activity for consciously perceived trials in the post-stimulus period, but the cortical activity in primary somatosensory area (SI) is independent of conscious perception during the early stage of NT stimulus processing. In addition, we revealed that the pre-stimulus alpha oscillation only in SI is predictive of conscious perception. These findings suggest that the bottom-up stream of somatosensory information flow following SI and pre-stimulus alpha activity fluctuation in SI as a top-down modulation are crucial constituents of conscious perception.

Association between serum ß-carotene-to-retinol ratio and severity of hepatic steatosis in non-alcoholic fatty liver disease in Japan: A cross-sectional study.

OBJECTIVES: Retinol and ß-carotene have been reported to be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, clinical studies are limited. The aim of this study was to investigate the relationship between serum the ratio of ß-carotene to retinol (SC/SR) and hepatic steatosis in NAFLD diagnosed by ultrasonography. METHODS: The participants were 606 Japanese adults who were enrolled in a health survey. Clinical profile, dietary nutrition intake, blood biochemistry, serum retinol, and carotenoids were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. RESULTS: Women had higher daily intake of α- and ß-carotene, although there were no differences in daily retinol and carotenoid intake between participants with or without NAFLD in both men and women. Women had a higher SC/SR ratio than men regardless of the presence or absence of NAFLD, and the SC/SR ratio in women decreased with exacerbation of hepatic steatosis, whereas the SC/SR ratio in men did not change despite exacerbation of hepatic steatosis. After adjusting for confounding factors, the likelihood of NAFLD among participants in the highest quartile of SC/SR ratio decreased by two-thirds compared with participants in the lowest quartile (adjusted odds ratio, 0.64; 95% confidence interval, 0.21-1.92; P = 0.041). The SC/SR ratio was positively correlated with serum high-density lipoprotein cholesterol level, and negatively correlated with serum triacylglycerol level. CONCLUSIONS: The SC/SR ratio was lower in NAFLD with sex differences, and was associated with the severity of hepatic steatosis and lipid profile. Future studies are needed to expand on these findings.

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study.

Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.

Items Selection for the Japanese Version of the Preschool Activity Card Sort.

Preschool Activity Card Sort (PACS) is a valid measure of preschoolers' participation and is a useful and unique tool for focusing on the extent and frequency of their participation. However, given the cultural differences between Japan and other countries, researchers should consider these differences when adapting the PACS for use with children in Japan. The purpose of this study was to select culturally suitable activity items to develop the Japanese version of PACS (PACS-JPN). A two-round survey of parents (who had typically developing children aged between 3 and 6 years) was conducted. The final version of the PACS-JPN included 98 activity items. The PACS-JPN reflects Japanese sociocultural background and allows occupational therapists to assess preschoolers' actual participation by assessing multiple aspects of children's community life. The psychometric properties, including the validity and reliability of the PACS-JPN should be examined in future research.

Leptin/adiponectin ratio correlates with hepatic steatosis but not arterial stiffness in nonalcoholic fatty liver disease in Japanese population.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship of leptin-to-adiponectin (L/A) ratio with hepatic steatosis and arterial stiffness in NAFLD. METHODS: The subjects were 871 Japanese adults who participated in a health survey. Dietary intake, body composition, lipid profile, serum interleukin-6 (IL-6), leptin, and adiponectin were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. Arterial stiffness was evaluated by the brachial-ankle pulse wave velocity (baPWV). RESULTS: The subjects with NAFLD had a greater body mass index (BMI) and body fat percentage (BFP); a higher intake of daily energy (kcal) and carbohydrates; and a higher prevalence of hypertension, diabetes, and hyperlipidemia. The subjects with NAFLD had higher serum leptin and lower serum adiponectin concentrations and a higher L/A ratio than subjects without NAFLD. The L/A ratio increased with increasing severity of steatosis. The L/A ratio showed positive correlations with BMI and BFP, and a negative correlation with age. Women had higher L/A ratio and BFP levels than men regardless of the presence or absence of NAFLD. There was a weak positive correlation between baPWV and severity of steatosis. BaPWV was strongly correlated with age, while no relation was found between baPWV and L/A ratio. IL-6 level was correlated with baPVW and age, while the correlation between Il and 6 level and L/A ratio was very weak. The L/A ratio was correlated with triglycerides and the ratio of total cholesterol to high-density lipoprotein-cholesterol. CONCLUSION: L/A ratio and arterial stiffness were associated with the severity of steatosis, whereas there was no correlation between L/A ratio and arterial stiffness in NAFLD. These findings suggest that not only leptin and adiponectin but also other factors might be involved in the pathogenesis for atherosclerosis in NAFLD.

Tailoring Confining Jacket for Concrete Column Using Ultra High Performance-Fiber Reinforced Cementitious Composites (UHP-FRCC) with High Volume Fly Ash (HVFA).

Ultra-High Performance Fibre-Reinforced Cementitious Composites (UHP-FRCC) show excellent mechanical performances in terms of strength, ductility, and durability. Therefore, these cementitious materials have been successfully used for repairing, strengthening, and seismic retrofitting of old structures. However, UHP-FRCCs are not always environmental friendly products, especially in terms of the initial cost, due to the large quantity of cement that is contained in the mixture. Different rates of fly ash substitute herein part of the cement, and the new UHP-FRCCs are used to retrofit concrete columns to overcome this problem. To simulate the mechanical response of these columns, cylindrical specimens, which are made of normal concrete and reinforced with different UHP-FRCC jackets, are tested in uniaxial compression. Relationships between the size of the jacket, the percentage of cement replaced by fly ash, and the strength of the columns are measured and analyzed by means of the eco-mechanical approach. As a result, a replacement of approximately 50% of cement with fly ash, and a suitable thickness of the UHP-FRCC jacket, might ensure the lowest environmental impact without compromising the mechanical performances.

Selection of Activity Items for Development of the Activity Card Sort-Japan Version.

The Activity Card Sort (ACS) can both record the clients' participation and any changes, which is a useful tool for practitioners to establish tailored occupation-focused goals. However, there is a limitation to apply the ACS to Japanese older adults as it consists of culturally relevant activities in the United States. The aim of this study was to select activity items reflecting Japanese older adults' lifestyles and opinions to develop the Activity Card Sort-Japan Version (ACS-JPN). In the item selection process, a two-round questionnaire survey was conducted for community-dwelling Japanese older adults (Round 1: n = 177, M age = 69.9 years; Round 2: n = 178, M age = 74.9 years). Seventy-two activity items were finally included in the ACS-JPN and were classified into four domains. The ACS-JPN has some unique features compared with other ACS versions. This study only selected activity items. Further work on psychometric properties is needed.

Interventional Treatment for Giant Hepatic Hemangioma Accompanied by Arterio-portal Shunt with Ascites.

A 73-year-old woman with massive ascites associated with a giant hepatic mass accompanied by arterio-portal (AP) shunt was admitted to our hospital. Based on contrast-enhanced computed tomography (CT) and angiography findings, hepatic hemangioma with AP shunt and ascites due to portal hypertension was diagnosed. Transcatheter arterial embolization (TAE) by N-butyl-2-cyanoacrylate (NBCA) was performed without complications. The patient's ascites disappeared, and her liver function test results improved after the treatment. The patient has maintained a steady state for two years. This case indicates that TAE with NBCA is a safe and effective treatment for hepatic hemangioma accompanied by AP shunt.

Kidney Injury due to Ureteral Obstruction Caused by Compression from Infected Simple Hepatic Cyst.

Simple hepatic cysts are common and most often asymptomatic. In symptomatic cases, hemorrhage, rupture, and infection are major complications. However, urinary tract obstruction caused by a simple hepatic cyst is rare. We treated an 82-year-old Japanese man with an infected giant hepatic cyst causing right hydronephrosis who had a past history of left nephrectomy for renal cell carcinoma. The patient underwent ultrasound-guided percutaneous drainage and sclerotherapy with minocycline hydrochloride for the infected hepatic cyst. Right hydronephrosis was relieved, and renal dysfunction improved with regression of the hepatic cyst after treatment. This is the first report of hydronephrosis due to ureteral obstruction caused by compression from a hepatic cyst.

Two Cases of Primary Sclerosing Cholangitis Overlapping with Autoimmune Hepatitis in Adults.

Overlap syndrome between primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) is extremely rare in Japan. We herein report two adult patients with PSC-AIH overlap syndrome. They were diagnosed with PSC-AIH overlap syndrome based on the findings of endoscopic retrograde cholangiography and liver biopsy, and using the International Autoimmune Hepatitis Group scoring system. In both cases, PSC preceded AIH, and combination therapy with steroid and ursodeoxycholic acid was effective. Because there are few reported cases in Japan, it is important to study more cases to shed light on the clinical and pathological features of PSC-AIH overlap syndrome.

Effect of Cognitive Load on Seating Posture in Children.

Although children are frequently required to sit upright, it is often difficult to maintain this posture when performing cognitive tasks. Information about the relationship between a cognitive tasks and postural seating control is important for children to complete tasks more effectively. To determine the muscle activity and body sway of children in a seated posture while performing a cognitive task, changes in muscle activity and center of pressure (COP) were recorded while 4(th) grade children performed arithmetic tasks. Electromyography was recorded from the internal oblique and lumbar multifidus muscles, and the COP was recorded using a baropodometer placed on the stool. These variables were measured during easy (EA) and difficult (DA) arithmetic tasks. EMG activity decreased during the EA and DA tasks, while the COP was displaced in the DA task. The results of the arithmetic tasks were not related to the EMG or COP changes. Attention to maintain a seated posture may be reduced when children perform cognitive tasks. Therefore, it may be better to allow children to alter their posture especially when they are performing difficult tasks. In this research, we only used arithmetic tasks as the cognitive exercise, and therefore, other types of tasks should be examined.

A successful case of transcatheter arterial embolization with n-butyl-2-cyanoacrylate for pancreatic arteriovenous malformation.

A 57-year-old man was referred and admitted to our hospital for treatment of a symptomatic pancreatic mass. Pancreatic arteriovenous malformation (AVM) was diagnosed based on the findings of contrast-enhanced computed tomography (CT) and angiography, and transcatheter arterial embolization (TAE) with N-butyl-2-cyanoacrylate (NBCA) was performed without complications. The patient's symptoms subsequently improved after TAE, and resolution of the pancreatic AVM was detected on contrast-enhanced CT performed six months after the embolization procedure. This case indicates that TAE with NBCA is a safe and effective treatment for pancreatic AVM.