Publications by authors named "Takemi Akahane"

Background And Aims: The clinical characteristics and risk factors involved in the development of liver fibrosis in the subtypes of steatotic liver disease (SLD) remain unknown. We examined the clinical characteristics of SLD subtypes using a large Japanese cohort.

Methods: We performed a cross-sectional analysis (total n = 108,446).

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  • * In rats fed a special high-fat diet, cabozantinib treatment significantly decreased liver inflammation and fibrosis but did not change fat accumulation in liver cells, indicating its targeted impact on fibrosis rather than overall liver health.
  • * The study found that cabozantinib reduced certain harmful liver cell activations and inflammatory responses without hindering liver cell regeneration, suggesting its potential for aiding liver health in cancer treatment.
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  • Alcohol-associated liver disease (ALD) leads to significant liver damage and currently lacks effective treatments; this study investigates the potential of elafibranor (EFN), a dual PPARα and PPARδ agonist, as a therapeutic option.
  • Using a mouse model, the researchers induced ALD and evaluated the effects of EFN on liver fibrosis and gut health by administering EFN and conducting various molecular analyses.
  • Results showed that EFN treatment significantly reduced liver damage and fibrosis, improved lipid metabolism, and strengthened the intestinal barrier, suggesting its potential as a treatment for ALD.
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  • - The study evaluated the effectiveness of inside stent therapy for patients with unresectable malignant hilar biliary obstruction, showing a high clinical success rate of 95.5% in resolving jaundice.
  • - Analysis identified factors influencing stent patency duration; unilateral drainage and chemotherapy were linked to significantly longer stent patency compared to bilateral drainage and no chemotherapy.
  • - The procedure was considered safe, with only a small percentage of patients experiencing early adverse events such as cholangitis and pancreatitis.
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  • The study aimed to determine if the levels of von Willebrand factor (VWF) and a protein called ADAMTS13 can predict the progression of esophagogastric varices (EGV) in patients with liver cirrhosis caused by hepatitis C after successful antiviral treatment.
  • Researchers analyzed 47 patients who achieved a sustained virologic response (SVR) after direct-acting antiviral (DAA) therapy; 18 of these patients showed signs of EGV progression post-treatment.
  • Results indicated that a higher VWF-to-ADAMTS13 ratio (greater than 2.3) was a significant risk factor for EGV progression, suggesting that this ratio can help identify patients at risk for complications
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  • - The study evaluated how the COVID-19 pandemic affected the treatment of acute cholangitis due to choledocholithiasis by analyzing medical records from April 2017 to December 2022 during a declared state of emergency in Japan.
  • - Results showed an increase in the number of endoscopic retrograde cholangiopancreatography (ERCP) cases and successful stone removals after the state of emergency. Additionally, patients treated during this time tended to be in better health, while those on certain medications and with previous health issues were fewer.
  • - The findings indicated that the pandemic led to more efficient single-stage endoscopic treatments and shorter hospital stays without increasing safety risks for patients undergoing ERCP.
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  • Lipopolysaccharides (LPSs) are linked to the progression of hepatocellular carcinoma (HCC), but the exact mechanisms are still unclear.
  • The study hypothesizes that epiregulin (EREG), produced in the presence of LPS by liver cells, is a key factor in HCC growth by affecting the epidermal growth factor receptor (EGFR) in tumors.
  • Experiments in a mouse model show that LPS treatment not only increases tumor size and EREG levels but also enhances blood vessel formation and expression of IL-8, indicating EREG's role in tumor growth and invasion.
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  • * Of the 15,517 cases studied, ALD accounted for 35.4%, while the prevalence of hepatitis C and B virus-associated LC decreased significantly, indicating changing trends in liver disease causation.
  • * The study concluded that the emerging trends suggest a transition in Japan’s liver health landscape, with an increasing number of cases linked to nonviral conditions like ALD and nonalcoholic steatohepatitis (NASH).
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Background: Liver cirrhosis leads to portal hypertension (PH) with capillarization of liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model.

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  • Portal vein thrombosis (PVT) is a serious condition often found in patients with liver cirrhosis, linked to high mortality rates, and is influenced by enzyme and factor imbalances causing increased blood clotting.
  • A study involving 345 liver cirrhosis patients identified two groups: 40 with PVT and 305 without, noticing that 81% were excluded due to various health issues.
  • The findings showed that lower plasma levels of ADAMTS-13 activity indicate a higher risk for developing PVT, making it a potential diagnostic and prognostic biomarker, especially in Japanese patients.
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  • The study aimed to examine the von Willebrand factor to ADAMTS13 ratio (VWF:Ag/ADAMTS13:AC) as a biomarker for predicting outcomes in patients with acute kidney injury (AKI) related to liver cirrhosis (LC).
  • Researchers compared 91 patients with AKI against 91 control patients without AKI, measuring plasma levels of VWF and ADAMTS13 to identify risk factors.
  • Results showed that higher VWF:Ag/ADAMTS13:AC ratios were linked to increased risk of AKI onset, higher 90-day mortality rates, and poorer treatment responses, suggesting this ratio could be a significant predictor for patients with LC.
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Sarcopenia is associated with mortality in patients with nonalcoholic steatohepatitis (NASH). Angiotensin II receptor blocker (ARB) has been suggested to prevent sarcopenia, but reports on its effect on NASH-derived skeletal muscle atrophy in conjunction with insulin-like growth factor 1 (IGF-1)-mediated muscle homeostasis are few. Our aim was to examine the combined effect of the ARB losartan and IGF-1 replacement on skeletal muscle atrophy in a methionine-choline deficient (MCD) diet-fed murine steatohepatitis model.

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Background: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms.

Methods: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs.

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Aim: Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are considered safe nucleoside/nucleotide analogs (NA) for the kidney. This study aimed to investigate the long-term effects of ETV or TAF on renal function in elderly patients with chronic hepatitis B (CHB) in Japan.

Methods: The study included 246 CHB patients treated with ETV (184 patients) or TAF (62 patients) for at least 2 years.

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  • In Japan, food safety concerns have risen due to issues like falsified expiration dates on cookies and health risks from frozen dumplings, prompting food companies to enhance food defense practices.
  • A study aimed to evaluate consumers' willingness to pay for food safety measures and how personality traits affect their shopping decisions.
  • Results showed that about one-third of respondents were not willing to pay extra for food safety, and many would still eat delivery food even if it included incorrect items, highlighting a divide in attitudes towards food safety expenses.
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Endogenous lipopolysaccharide (LPS) that translocates via the disrupted intestinal barrier plays an essential role in the progression of alcohol-related liver disease (ALD). Vitamin D deficiency is observed in ALD, and it participates in regulating gut barrier function. The current study aimed to examine the association between vitamin D deficiency and endotoxemia in patients with ALD-related cirrhosis.

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Background: Various stages of the food chain, from production to processing to distribution, can impact food safety. The concept of "food defense" has emerged as a countermeasure against intentional contamination of food with foreign substances. Although knowledge of food hygiene is common among consumers, there are currently no reports of consumer surveys on food defense.

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Aim: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan.

Methods: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no.

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Aim: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have greater coronavirus disease 2019 (COVID-19) severity compared with patients without NAFLD. Previous studies have reported that noninvasive liver fibrosis scores, including the Fibrosis-4 index, NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio index (APRI), have utility in predicting COVID-19 mortality and disease severity in patients without NAFLD. However, the utility of liver fibrosis scores in predicting COVID-19 mortality and disease severity among patients with NAFLD infected with SARS-CoV-2 has yet to be evaluated.

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  • Alcohol significantly contributes to liver cirrhosis (LC), and this study focused on identifying a surrogate marker for sarcopenia in LC patients with different causes, particularly comparing alcoholic cirrhosis (AC) and nonalcoholic cirrhosis (NAC).
  • The analysis involved 451 patients out of 775, measuring handgrip strength, skeletal muscle mass, and endotoxin activity (EA), revealing that AC patients had higher platelet counts and lower blood urea nitrogen levels compared to NAC patients.
  • Key risk factors for sarcopenia included age, sex, liver function, and hemoglobin levels, with hemoglobin being a strong predictor of sarcopenia; combining hemoglobin with endotoxin
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  • A glucagon-like peptide-1 receptor agonist (GLP-1RA), specifically semaglutide, shows promise for treating skeletal muscle atrophy associated with chronic liver disease (CLD) in diabetic conditions.
  • In mouse models, semaglutide reduced muscle atrophy, enhanced grip strength, and promoted muscle growth by inhibiting protein breakdown pathways and protecting against liver injury.
  • The therapeutic effects of semaglutide were linked to its ability to stimulate GLP-1 receptors in muscle cells, activating several beneficial molecular pathways, leading to improved muscle health in the context of CLD.
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The renin-angiotensin-aldosterone system has gained attention due to its role as a mediator of liver fibrosis and hepatic stellate cell (HSC) activation. Meanwhile, the natriuretic peptide (NP) system, including atrial NP (ANP) and C-type NP (CNP), is a counter-regulatory hormone regulated by neprilysin. Although the combination of an angiotensin receptor and a neprilysin inhibitor (sacubitril/valsartan: SAC/VAL) has shown clinical efficacy in patients with heart failure, its potential effects on hepatic fibrosis have not been clarified.

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  • - Patients with autoimmune hepatitis (AIH) often experience poor quality of life (QOL) due to depression and low zinc levels, especially while on corticosteroid treatment.
  • - A study involving 26 AIH patients found that zinc supplementation significantly increased serum zinc levels and improved the worry aspect of quality of life, although other mental health measures did not show improvement.
  • - The research suggests a connection between the dosage of corticosteroids and mental health scores, indicating that zinc could help alleviate mental issues related to corticosteroid treatment in AIH patients without serious side effects.
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  • The study examined the safety and feasibility of cell-free and concentrated ascites reinfusion therapy (CART) for patients with cirrhosis and refractory ascites, focusing on changes in coagulation factors in the ascitic fluid.
  • Out of 23 patients, CART led to significant decreases in body weight and waist circumference, along with increases in important proteins and coagulation factors in the reinfused fluid.
  • The results indicate that CART is both effective and safe, resulting in improved patient symptoms as measured by the Ascites Symptom Inventory-7 scale.
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