Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Impact of the COVID-19 pandemic on the treatment of acute cholangitis caused by choledocholithiasis: A single-center retrospective study in Japan.

Objectives: This study aimed to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the treatment of acute cholangitis caused by choledocholithiasis. Methods: The Japanese government declared a state of emergency in April 2020 due to the COVID-19 pandemic. We retrospectively reviewed the medical records of 309 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis caused by choledocholithiasis between April 2017 and December 2022. Results: Patients were categorized into a pregroup (n = 134) and a postgroup (n = 175), depending on whether they were diagnosed before or after the state of emergency declaration. The total number of ERCP cases and the number of ERCP cases with endoscopic stone removals increased after the state of emergency declaration. Compared with the pregroup, the numbers of patients with performance status of 0-1 and surgically altered anatomy increased, whereas the numbers of patients taking oral antiplatelets or anticoagulants and those with cerebrovascular disease decreased in the postgroup. The number of single-stage endoscopic stone removals increased and hospital stays were significantly shorter in the postgroup. No differences in adverse event rates were detected between the two groups. Conclusions: Although our hospital provides tertiary care, the number of patients with cholangitis in good general condition and no underlying disease increased after the state of emergency declaration. The COVID-19 pandemic resulted in an increase in the number of single-stage endoscopic treatments and shortened hospital stays for patients with acute cholangitis caused by choledocholithiasis. No safety issues with ERCP were detected, even during the pandemic.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown. AIM: To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model. METHODS: ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays. RESULTS: The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and ß-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation. CONCLUSION: EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Ratio of von Willebrand factor to ADAMTS13 is a useful predictor of esophagogastric varices progression after sustained virologic response in patients with hepatitis C virus-related liver cirrhosis.

AIM: Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)-related liver cirrhosis (HCV-LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct-acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin-like metalloproteinase with thrombospondin type-1 motif 13 (ADAMTS13) can predict EGV progression with HCV-LC after SVR achievement. METHODS: This retrospective study enrolled 47 patients with HCV-LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty-nine patients did not experience EGV progression after the SVR was achieved (non-EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment. RESULTS: The EGV progression group had significantly higher plasma VWF antigen levels (p = 0.00331) and VWF-to-ADAMTS13 ratios (p = 0.000249) than the non-EGV progression group. Multivariate logistic regression models found that a VWF-to-ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08-109; p = 0.00138). During the observation period, patients with a VWF-to-ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF-to-ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78-22.96; p = 0.0044). CONCLUSIONS: The VWF-to-ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement.

Tofogliflozin Delays Portal Hypertension and Hepatic Fibrosis by Inhibiting Sinusoidal Capillarization in Cirrhotic Rats.

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. METHODS: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. RESULTS: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. CONCLUSIONS: Our study provides strong support for tofogliflozin in the prevention of liver cirrhosis-related PH.

Methotrexate-associated lymphoproliferative disorder: A rare pancreatic tumor diagnosed via endoscopic ultrasound-guided fine-needle biopsy.

A 73-year-old woman with a history of rheumatoid arthritis treated with methotrexate (MTX) for the last 10 years was referred to our hospital for a pancreatic tumor examination. Contrast-enhanced abdominal computed tomography revealed a 20-mm-diameter hypovascular tumor in the pancreatic tail. A hypoechoic mass with heterogeneous internal echo was found on an endoscopic ultrasound (EUS). An EUS-guided fine-needle biopsy (EUS-FNB) was performed with a 22-gauge Franseen-tip needle. Histologic examination of EUS-FNB specimens from the pancreatic tumor revealed the proliferation of atypical spindle cells. Immunohistochemical staining for CD20 and Ki-67 was positive in the atypical cells. Immunohistochemical staining for CD3 was partially positive in the atypical cells. Epstein-Barr virus-encoded RNA in situ hybridization showed positive staining. MTX-related lymphoproliferative disorder (MTX-LPD) with Epstein-Barr virus infection was diagnosed. MTX treatment was immediately discontinued, and treatment was initiated by a hematologist. However, her condition rapidly deteriorated, and she died of multiple organ failure 4 weeks after diagnosis. MTX-LPD can complicate gastrointestinal lesions. However, most lesions are localized in the stomach and rarely complicate pancreatic lesions. MTX-LPD is classified as an "iatrogenic" LPD. Therefore, immediate action, such as MTX discontinuation, is necessary. In conclusion, endoscopists should be aware that MTX-LPD lesions can occur in the pancreas and gastrointestinal tract. Moreover, EUS-FNB can be useful in the diagnosis of this rare pancreatic tumor.

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis.

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21-3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.

Improvement of liver histology in hepatic sarcoidosis due to treatment with corticosteroids and ursodeoxycholic acid: a case report.

We report the case of a 48-year-old male with a history of pulmonary and ocular sarcoidosis. Non-caseating granulomas, identified histologically, are the most characteristic manifestation of sarcoidosis. Hepatic sarcoidosis is difficult to diagnose using radiological imaging. In the patient reported in this study, ultrasound and contrast-enhanced computed tomography scans identified multiple intra-abdominal lymphadenopathies, with evidence of liver and splenic infiltrations. The first liver biopsy revealed non-caseating granulomatous hepatitis consistent with hepatic sarcoidosis. The patient was treated with ursodeoxycholic acid (UDCA), but his laboratory parameters did not improve. Prednisone was initiated at a dose of 30 mg daily and slowly tapered. At a dose of 12.5 mg daily, marked improvements in the fibrotic and sarcoid-like lesions were noted at the second biopsy. A third biopsy was performed, with the patient on a prednisone taper of 5 mg/day showed mild fibrous expansion in the portal tracts and mild parenchymal necro-inflammatory lesions. However, overall, fibrosis marker levels remained stable over the course of treatment. A fourth biopsy was performed after a 5-year course of 5 mg/day prednisone. This revealed minimal lobular inflammation without fibrosis. Thus, treatment of this patient with corticosteroids and UDCA resulted in marked improvements in his biochemical and histological parameters.

VWF/ADAMTS13 Ratio as a Potential Predictive Biomarker for Acute Kidney Injury Onset in Cirrhosis.

AIM: We investigated the von Willebrand factor to ADAMTS13 ratio (von Willebrand factor [VWF]:Ag/ADAMTS13:AC) as a potential biomarker for the outcomes of acute kidney injury (AKI) in liver cirrhosis (LC). METHODS: This retrospective cross-sectional study included patients with LC who developed AKI (AKI group: n = 91) and patients with LC who did not develop AKI [non-AKI (NAKI) group, n = 91] as a control group. Plasma levels of the von Willebrand factor antigen (Ag) and ADAMTS13 activity (AC) were measured in patients with AKI or NAKI. Moreover, risk factors for onset of AKI, AKI-associated 90-day mortality, and poor AKI treatment response were identified. RESULTS: The AKI group had a significantly higher VWF:Ag/ADAMTS13:AC than the NAKI group. Values of VWF:Ag/ADAMTS13:AC ≥ 5.7 were identified as risk factors for AKI onset in patients with LC (odds ratio [OR] 2.56; 95% CI 1.26-4.99; p < 0.001). Among patients with AKI, values of VWF:Ag/ADAMTS13:AC ≥ 9.0 were identified as risk factors for 90-day mortality (OR 6.83; 95% CI 2.32-20.10; p < 0.001). Cumulative survival was significantly lower in those with high (≥ 9.0) than in those with low (< 9.0) VWF:Ag/ADAMTS13:AC. Furthermore, values of VWF:Ag/ADAMTS13:AC ≥ 7.4 were identified as risk factors for poor treatment response (OR 4.2; 95% CI 1.39-12.70; p < 0.001). The treatment response rates were significantly higher in those with low (< 7.4) VWF:Ag/ADAMTS13:AC than in those with high (≥ 7.4) VWF:Ag/ADAMTS13:AC. CONCLUSION: VWF:Ag/ADAMTS13:AC potentially predicts the onset, prognosis, and treatment response of AKI in patients with LC.

Effects of entecavir and tenofovir alafenamide fumarate treatment on renal function in Japanese elderly patients with chronic hepatitis B.

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. These patients were divided into two groups: those <65 years of age (130 patients) and those ≥65 years of age (116 patients). The effects of the NAs on renal functions were examined by comparing the estimated glomerular filtration rates (eGFR) from baseline to 2 years between the two groups. RESULTS: The change in eGFR from baseline to 1 or 2 years after treatment was significantly decreased in both groups. However, the amount of change at 1 and 2 years was significantly greater in the group aged ≥65 years than in the group aged <65 years. The amount of change in eGFR from baseline to 1 and 2 years after treatment was significantly greater in the group aged ≥65 years than in the group aged <65 years, regardless of the type of NA, the prior treatment history, cirrhosis/chronic hepatitis, hypertension, dyslipidemia, and diabetes. Additionally, logistic regression analysis showed that age ≥65 years was independently associated with a decreased eGFR after 2 years of NA treatment. CONCLUSIONS: Long-term administration of NA to CHB patients over 65 years of age should be carefully monitored for renal impairment.

Complete migration of a fully covered self-expandable metallic stent after endoscopic ultrasound-guided hepaticogastrostomy: A case report.

A male patient underwent gastrojejunal bypass surgery in 2017. In 2020, he was referred to our hospital for suspected obstructive jaundice. Subsequently, he was diagnosed with cholangiocarcinoma, and endoscopic retrograde cholangiopancreatography was attempted via balloon-assisted enteroscopy. However, the endoscope did not reach the duodenal papilla owing to the abdomen-small intestine adhesion. Therefore, endoscopic ultrasound-guided hepaticogastrostomy was performed using a dedicated plastic stent. After stent placement, obstructive jaundice and cholangitis promptly improved. However, we replaced the plastic stent with a fully covered self-expandable metal stent because stent occlusions occurred frequently. Two months after fully covered self-expandable metal stent placement, the patient developed cholangitis again. Notably, during the endoscopic procedure, the stent was found to be completely migrated. Nevertheless, the fistula was still open, and the patient was successfully retreated with the maintained fistula of endoscopic ultrasound-guided hepaticogastrostomy.

Hemoglobin and Endotoxin Levels Predict Sarcopenia Occurrence in Patients with Alcoholic Cirrhosis.

Alcohol is a major risk factor of liver cirrhosis (LC). This study aimed to elucidate a surrogate marker of sarcopenia in patients with LC of different etiology. Out of 775 patients with LC, 451 were assessed for handgrip strength and skeletal muscle mass (by computed tomography). They were then divided into two groups: alcoholic cirrhosis (AC; n = 149) and nonalcoholic cirrhosis (NAC; n = 302). Endotoxin activity (EA) levels were measured with an EA assay. Group AC showed significantly higher platelet counts (p = 0.027) and lower blood urea nitrogen levels and fibrosis-4 index than group NAC (p = 0.0020 and p = 0.038, respectively). The risk factors of sarcopenia were age ≥ 65 years, female sex, CP-C LC, Hb levels < 12 g/dL, and EA level > 0.4 in all patients with LC; hemoglobin (Hb) levels < 12 g/dL and EA level > 0.4 in group AC; and age ≥ 65 years, CP-C LC, and Hb levels < 12 g/dL in group NAC. The prediction accuracy of Hb for sarcopenia in group AC, group NAC, and all patients was 83.6%, 75.9%, and 78.1% (sensitivity: 92.0%, 69.0%, and 80.2%; specificity: 66.4%, 71.0%, and 64.0%), respectively. Although not significant, the predictive performance was better when using the combination of Hb and EA measurements than when using Hb alone in group AC but was comparable in all patients. Hb levels can predict sarcopenia in patients with LC, but in those with AC, the combination of Hb and EA improves the prediction performance.

Glucagon-like peptide-1 receptor agonist, semaglutide attenuates chronic liver disease-induced skeletal muscle atrophy in diabetic mice.

A glucagon-like peptide-1 receptor agonist (GLP-1RA) has recently been established as a pharmacological option for the treatment of type 2 diabetes. Recent studies have demonstrated the molecular role of GLP-1R in skeletal muscle homeostasis; however, the therapeutic efficacy of semaglutide, a GLP-1RA, on skeletal muscle atrophy in chronic liver disease (CLD) under diabetic conditions remains unclear. In the present study, semaglutide effectively inhibited psoas muscle atrophy and suppressed declines in grip strength in a diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-fed diabetic KK-Ay mouse model. Moreover, semaglutide inhibited ubiquitin-proteosome-mediated skeletal muscle proteolysis and promoted myogenesis in palmitic acid (PA)-stimulated C2C12 murine myocytes. Mechanistically, this effect of semaglutide on skeletal muscle atrophy was mediated by multiple functional pathways. First, semaglutide protected against hepatic injury in mice accompanied by increased production of insulin-like growth factor 1 and reduced accumulation of reactive oxygen species (ROS). These effects were associated with decreased proinflammatory cytokines and ROS accumulation, leading to the suppression of ubiquitin-proteosome muscle degradation. Moreover, semaglutide inhibited the amino acid starvation-related stress signaling that was activated under chronic liver injury, resulting in the recovery of the mammalian target of rapamycin activity in the skeletal muscle of DDC-diet fed KK-Ay mice. Second, semaglutide improved skeletal muscle atrophy by directly stimulating GLP-1R in myocytes. Semaglutide induced cAMP-mediated activation of PKA and AKT, enhanced mitochondrial biogenesis, and reduced ROS accumulation, thereby resulting in inhibition of NF-κB/myostatin-mediated ubiquitin-proteosome degradation and the augmentation of heat-shock factor-1-mediated myogenesis. Collectively, semaglutide may have potential as a new therapeutic strategy for CLD-related skeletal muscle wasting.

A Combination of an Angiotensin II Receptor and a Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation.

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. This study assessed the effects of SAC/VAL in carbon tetrachloride (CCl4)-induced murine liver fibrosis as well as the in vitro phenotypes of HSCs. Treatment with SAC and VAL markedly attenuated CCl4-induced liver fibrosis while reducing α-SMA+-HSC expansion and decreasing hepatic hydroxyproline and mRNA levels of pro-fibrogenic markers. Treatment with SAC increased plasma ANP and CNP levels in CCl4-treated mice, and ANP effectively suppressed cell proliferation and TGF-ß-stimulated MMP2 and TIMP2 expression in LX-2 cells by activating guanylate cyclase-A/cGMP/protein kinase G signaling. Meanwhile, CNP did not affect the pro-fibrogenic activity of LX-2 cells. Moreover, VAL directly inhibited angiotensin II (AT-II)-stimulated cell proliferation and the expression of TIMP1 and CTGF through the blockade of the AT-II type 1 receptor/protein kinase C pathway. Collectively, SAC/VAL may be a novel therapeutic treatment for liver fibrosis.

Hemoglobin levels as a surrogate marker of sarcopenia in patients with liver cirrhosis.

AIM: This study aimed to elucidate a surrogate marker of sarcopenia in patients with liver cirrhosis (LC). METHODS: A total of 424 patients were assessed for handgrip strength (HGS) and skeletal muscle index (SMI). They were divided into two groups: sarcopenia (Group S; n = 80) and nonsarcopenia (Group NS; n = 344). RESULTS: Group S showed significantly lower HGS, SMI, and hemoglobin (Hb) levels in males and female patients, and lower serum levels of albumin, cholinesterase, and zinc (all p < 0.001), along with significantly higher serum levels of procollagen type III-N-peptide and type IV collagen 7S-domain (p < 0.001 and p < 0.0017) than Group NS. The risk factors for sarcopenia were age 65 years or older, female gender, Child-Pugh class C, and Hb levels <10.9 g/dL in women and <12.4 g/dL in men (p = 0.012, p < 0.001, p = 0.031, and p < 0.001, respectively). Significant positive correlations were found between the Hb level and the SMI and HGS (r = 0.4, p < 0.001 and r = 0.4, p < 0.001, respectively). Sarcopenia, low HGS, and low SMI were significantly associated with overall survival in patients with LC (all p < 0.001). The predictive accuracy of Hb levels for predicting sarcopenia was significantly higher than for predicting SMI and tended to be higher than for predicting HGS (p = 0.014 and p = 0.059, respectively). CONCLUSION: Hemoglobin levels are predictive of sarcopenia in patients with LC and warrants further investigation as a biomarker for sarcopenia in LC.

Changes in Coagulation and Fibrinolytic Factors in Patients With Cirrhotic Refractory Ascites Undergoing Cell-free and Concentrated Ascites Reinfusion Therapy: A Retrospective Observational Study in Japan.

BACKGROUND/AIM: The management of refractory ascites is critical for the treatment of patients with decompensated cirrhosis. This study aimed to evaluate the feasibility and safety of cell-free and concentrated ascites reinfusion therapy (CART) in patients with cirrhosis and refractory ascites, with a focus on changes in coagulation and fibrinolytic factors in ascitic fluid following CART. PATIENTS AND METHODS: This was a retrospective cohort study including 23 patients with refractory ascites undergoing CART. Serum endotoxin activity (EA) before and after CART and the levels of coagulation and fibrinolytic factors and proinflammatory cytokines in original and processed ascitic fluid were measured. The Ascites Symptom Inventory-7 (ASI-7) scale was used for subjective symptom assessment before and after CART. RESULTS: Body weight and waist circumference significantly decreased after CART, whereas serum EA did not significantly change after CART. Similar to the previous reports, ascitic fluid concentrations of total protein, albumin, high-density lipoprotein cholesterol, γ-globulin, and immunoglobulin G levels were significantly increased after CART; mild elevations in body temperature and interleukin 6 and tumor necrosis factor-alpha levels in ascitic fluid were also observed. Importantly, the levels of antithrombin-III, factor VII, and X, which are useful for patients with decompensated cirrhosis, were markedly increased in the reinfused fluid during CART. Finally, the total ASI-7 score was significantly lower following CART, compared with the pre-CART score. CONCLUSION: CART is an effective and safe approach for the treatment of refractory ascites that allows the intravenous reinfusion of coagulation and fibrinolytic factors in the filtered and concentrated ascites.