Publications by authors named "Yukihisa Fujinaga"

Background: Complete abstinence is the cornerstone of alcohol-related liver disease (ALD) management. However, many patients struggle to achieve or sustain abstinence, prompting growing interest in harm reduction strategies, particularly pharmacological interventions to reduce alcohol intake. Nalmefene, an opioid receptor modulator, has shown efficacy in reducing alcohol consumption among individuals with alcohol dependence.

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Covert hepatic encephalopathy (CHE) can worsen the quality of life and prognosis of patients with cirrhosis. We analyzed the risk factors of CHE and identified patients at high risk for overt hepatic encephalopathy (HE) who would benefit from therapeutic interventions. We included 145 patients without a history of or treatment for overt HE.

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Aim: This study aimed to assess the prognostic significance of hand grip strength (HGS) and skeletal muscle mass index (SMI) in patients with alcohol-related cirrhosis.

Methods: 535 patients with liver cirrhosis (LC) were assessed for HGS and computed tomography (CT)-based SMI. They were categorized into alcohol-related liver disease (ARLD; n = 226), metabolic dysfunction-associated steatohepatitis (MASH; n = 119), and virus-related cirrhosis (VC, n = 190) groups.

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Aim: This study aimed to determine the predictive ability of the histological stage (HS) compared with biochemical response to ursodeoxycholic acid (UDCA) (BR) on developing complications in patients with primary biliary cholangitis (PBC).

Methods: Overall, 226 patients with asymptomatic PBC treated with UDCA were enrolled. Pathological staging was conducted based on the Scheuer and Nakanuma classifications, which were graded for liver fibrosis (fibrosis) and bile duct loss (BDL).

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As endoscopy is increasingly being used to diagnose superficial nonampullary duodenal epithelial tumors (SNADETs), there is a growing need for their early detection and minimally invasive treatment. This study investigated the diagnostic accuracy of biopsy specimens for SNADETs. We conducted a retrospective analysis of clinicopathologic data from 98 patients with SNADETs who had undergone endoscopic resection.

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Aim: The incidence of intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC) still remains high after radiofrequency ablation (RFA). However, serum alpha-fetoprotein (AFP) has insufficient screening power. This study aimed to identify risk factors for IDR in patients with post-RFA HCC.

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Article Synopsis
  • Gastrointestinal subepithelial lesions (SELs) can be benign or malignant, and diagnosing them accurately using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is challenging, especially for smaller lesions (≤ 2 cm).
  • A retrospective study indicated that over 50% of patients with SELs of this size were diagnosed as gastrointestinal stromal tumors (GISTs), highlighting the necessity of using effective EUS-FNB techniques.
  • This multicenter study aims to compare the effectiveness of two types of EUS-FNB needles (22G Fork-tip vs. 22G Franseen) in obtaining adequate tissue samples from SELs ≤ 2 cm, with different endpoints focusing on sample quality and procedural outcomes.
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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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  • 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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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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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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  • * An initial attempt to treat his condition using endoscopic techniques was unsuccessful due to adhesions, leading to a successful placement of a plastic stent that improved his symptoms.
  • * After replacing the plastic stent with a metal one due to frequent occlusions, the patient experienced cholangitis again and the metal stent had migrated; however, he was able to undergo a successful retreatment through the existing fistula.
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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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  • 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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  • - The study investigated a potential marker for sarcopenia in patients with liver cirrhosis, analyzing data from 424 patients divided into sarcopenia (Group S) and nonsarcopenia (Group NS) groups.
  • - Results indicated that Group S had significantly lower handgrip strength, skeletal muscle index, and hemoglobin levels, while showing higher levels of certain collagen biomarkers compared to Group NS.
  • - The study concluded that hemoglobin levels could serve as a predictive biomarker for sarcopenia in liver cirrhosis patients, suggesting the need for further research in this area.
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Acute-on-chronic liver failure (ACLF) has a high risk of short-term mortality. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a metalloproteinase that specifically cleaves multimeric von Willebrand factor (VWF). Imbalance between ADAMTS13 and VWF is associated with portal hypertension, which induces ACLF development.

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