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Intestinal microbiota-derived microbial metabolites characterize the metabolic pathways and build the phenotypic expression in alcoholic fatty liver disease (AFLD) and non-AFLD (NAFLD). Microbial metabolites play significant roles in host-microbiota crosstalk. In this review, short-chain fatty acids (SCFAs: acetate (C 2), propionate (C 3) and butyrate (C 4)) and bile acids (BA: primary BAs, deconjugation, and secondary BAs) signify the fatty liver inflammation and liver carcinogenesis in both AFLD and NAFLD. Clinical investigations on autoimmune, inflammation, and malignancy have demonstrated the immunoregulatory capacity of SCFAs and BAs generated from the gut microbiota, which are reliant on dietary components. Variations in signaling, metabolic, and epigenetic states are among the multiple regulatory processes of SCFAs and BAs that support both the beneficial and detrimental effects of bacterial metabolites. In this review, we discuss SCFAs and BAs signaling and their interplay with the gut microbiome in FLD and NFLD. This review aims to define the key metabolites that are altered in AFLD and NAFLD and their roles in pathogenesis. They represent potential biomarkers for metabolic disorders. Furthermore, the clinical therapeutic applications of SCFAs and BAs profiles and metabolisms are selectively highlighted. • The metabolic variations of short-chain fatty acids (SCFAs) were studied in liver diseases. • SCFAs influenced metabolic alterations in liver metabolisms. • SCFAs has inhibited metabolic activity in gut microbiome. • Bile acids induced changes an quantitate variability of metabolites and metabolic pathways. [ABSTRACT FROM AUTHOR]

Chronic liver disease including non‐alcoholic fatty liver disease and alcohol‐related liver disease is one of the most common diseases worldwide. The gut–liver axis plays an important role in the pathogenesis of liver disease. Small intestinal bacterial overgrowth, dysbiosis, leaky bowel, bacterial translocation, and imbalanced metabolites are related to the progression of chronic liver disease. Recently, novel therapeutic approaches for microbiota modulation such as personalized diet, probiotics, prebiotics, antibiotics, engineered microbiotas, phage therapy, stomach operation, and fecal microbiota transplantation (FMT) have been proposed with numerous promising results in the effectiveness and clinical application. Although the evidence is still lacking, FMT, a type of fecal bacteriotherapy, has been known as a candidate for the treatment of liver disease. This review article focuses on the most recent advances in our understanding of FMT in chronic liver disease such as non‐alcoholic and alcohol‐related liver disease. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. Methods: A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. Results: Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 ± 0.02, 1.02 ± 0.18, 2.86 ± 0.77, and 6.56 ± 1.46 EU/mL, p < 0.001) and LBP (7026 ± 3336, 11,445 ± 1247, 11,947 ± 1164, and 13,791 ± 2032 ng/mL, p = 0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83 ± 0.17, 2.62 ± 0.22, 3.69 ± 0.28, and 4.29 ± 0.34 pg/mL, p < 0.001), demonstrating a significant difference between each grade ( p < 0.05). Conclusions: HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Kim et al paper. To view these articles, visit https://doi.org/10.1111/apt.16200 [ABSTRACT FROM AUTHOR]

Abstract: Anti-oxidative and immunologic effects of the Korea red ginseng (KRG; Panax ginseng) and urushiol (Rhus vernicifera Stokes) on non-alcoholic fatty liver disease (NAFLD) were evaluated. Forty-five rats (five Long-Evans Tokushima Otsuka and 40 Otsuka Long-Evans Tokushima Fatty [OLETF] rats) received chew diets for 10months; after this period. The OLETF rats were divided into the following four groups according to diet for 2months: NAFLD (chew), KRG (chew+KRG [200mg/kg/day]), urushiol (chew+urushiol [0.5mg/kg/day]), and ursodeoxycholic acid (UDCA) (chew+UDCA [15mg/kg/day]) groups. Liver function, lipid profiles and anti-oxidant activity of liver and serum, natural killer (NK) cell activity, and pathology were compared. In KRG and urushiol groups, the level of serum triglyceride ([302.0±70.4 and 275.2±63.8] vs. 527.7±153.3mg/dL) were lower compared with that of NAFLD group (p <0.05). The levels of HDL-cholesterol (liver tissue: [4.8±0.2 and 4.8±0.5] vs. 4.2±0.2mg/g) and NK cell activity ([3485±910 and 3559±910] vs. 2486±619 counts) were significantly higher than those of the NAFLD group (p <0.001). Inflammation with neutrophil infiltration was observed in only two rats in the NAFLD group. These results suggest that 2months of oral KRG or urushiol administration improves lipid profiles and stimulates NK cell activity, while inhibiting steatohepatitis in OLEFT rats. [Copyright &y& Elsevier]

OBJECTIVES:To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.METHODS:From May 2005 to May 2007, cases of DILI (alanine transferase >3 × upper normal limit or total bilirubin >2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.RESULTS:A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included 'herbal medications' (102, 27.5%), 'prescription or non-prescription medications' (101, 27.3%), 'health foods or dietary supplements' (51, 13.7%), 'medicinal herbs or plants' (35, 9.4%), 'folk remedies' (32, 8.6%), 'combined' (30, 8.2%), 'herbal preparations' (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.CONCLUSIONS:DILI appears to be a highly relevant health problem in Korea. 'Herbal medications' are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The accuracies of biomarkers checked in the hepatic vein (HV) and peripheral vein (PV) were compared in the prediction of advanced fibrosis (AF) of liver. Methods: Patients with chronic viral hepatitis (n=101) who underwent hepatic venous pressure gradient, liver biopsy, and paired HV–PV samples (6 biomarkers: hyaluronic acid [HA], haptoglobin, matrix metalloproteinase-2 [MMP2], tissue inhibitor of metalloproteinases-1 [TIMP1], procollagen III N-terminal peptide [PIIINP], and apolipoprotein-A1 [Apo-A1]) were enrolled. Results: Differences were displayed between the HV and PV in the predictive logit-models for predicting AF (−3.13+0.017×MMP2−0.019×haptoglobin and −0.270+0.007×HA−0.018×haptoglobin, respectively). In the area under the receiver operating characteristic curves, PIIINP (0.74/0.68, p =0.03), MMP2 (0.72/0.63, p =0.04), HA (0.79/0.76, p =0.94), Apo-A1 (0.56/0.48, p =0.73), and predictive logit-model (0.81/0.78, p =0.68) showed higher diagnostic value in the HV sample. Conclusions: While most biomarkers were correlated better with hepatic fibrosis in HV than in PV, individually and in predictive logit-models, they were inadequate to determine the degree of advanced fibrosis. [Copyright &y& Elsevier]

Background: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. Materials and Methods: Monomer and 2-4 polymer urushiol were used. In the in vitro study, pH- and concentration-dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro-inflammatory cytokines was checked. Results: All strains survived within a pH 6.0-9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064-0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL × 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori-induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin-1β in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication ( p = .014). Conclusions: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model. [ABSTRACT FROM AUTHOR]

Primary liver cancer is a heterogeneous disease. Liver cancer metabolism includes both the reprogramming of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment and fluctuations in regular tissue metabolism. Currently, metabolomics and metabolite profiling in liver cirrhosis, liver cancer, and hepatocellular carcinoma (HCC) have been in the spotlight in terms of cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecules, chemicals, and metabolites. Metabolomics technologies can provide critical information about the liver cancer state. Here, we review how liver cirrhosis, liver cancer, and HCC therapies interact with metabolism at the cellular and systemic levels. An overview of liver metabolomics is provided, with a focus on currently available technologies and how they have been used in clinical and translational research. We also list scalable methods, including chemometrics, followed by pathway processing in liver cancer. We conclude that important drivers of metabolomics science and scientific technologies are novel therapeutic tools and liver cancer biomarker analysis. [ABSTRACT FROM AUTHOR]

Background and Aim: The Model for End‐Stage Liver Disease (MELD) is a reliable prognostic tool for short‐term outcome prediction in patients with end‐stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD‐Na, in patients with alcoholic liver cirrhosis. Methods: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD‐Na, and MELD 3.0, for 30‐day and 90‐day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. Results: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD‐Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD‐Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90‐day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. Conclusion: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

Over the last decade, increased research into the cognizance of the gut–liver–brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut–brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut–liver–brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut–liver–brain axis. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson's disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis. [ABSTRACT FROM AUTHOR]

Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low. Methods: This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts. Results: The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. Conclusion: This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low. [ABSTRACT FROM AUTHOR]

This document, published in the Journal of Translational Medicine, discusses the potential therapeutic benefits of Salinosporamides (SSAs) in treating cancer. The study aims to identify the key SSAs and their mechanisms of action using systems biology concepts. Through database-driven analysis and computer screening tools, the researchers identified 11 SSAs with drug-like properties and common targets. The study highlights the importance of the NOD-like receptor signaling pathway and specific targets, such as STAT3, MAPK1, TBK1, and P2RX7, in the anti-cancer effects of SSAs. The research suggests that incorporating biological data can help uncover the potential of marine organic molecules in cancer medicine. [Extracted from the article]

This document, published in the Journal of Translational Medicine, discusses the potential use of short positively charged peptides (SPCPs) as a therapy for hepatocellular carcinoma (HCC). SPCPs have been identified as having anti-cancer properties and the ability to penetrate cancer cell membranes. The study identifies specific SPCPs that have stable physicochemical properties and can target key proteins and signaling pathways associated with HCC. The two key SPCPs identified, KFAH and HFAK, show strong affinity for the targets and have the potential to be developed into a localized injection therapy for HCC. [Extracted from the article]

This document explores the potential of Cephalotaxus alkaloids (CAs) as anti-cancer agents. Through data analysis using various tools and software, the study identifies heat shock protein 90 alpha family class A member 1 (HSP90AA1) as a potential target for inhibiting cancer progression and the NOD-like receptor (NLR) signaling pathway as a promising pathway for cancer treatment. The compound Nordeoxyharringtonine is identified as a potential anti-cancer mediator, and its toxicity is found to be manageable. The study suggests that Nordeoxyharringtonine can be used to validate its anti-pan-cancer effects by targeting multiple pathways. The research was supported by multiple funding sources and has been approved by all authors. [Extracted from the article]

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti‐OB efficacy of the non‐fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein–protein interaction (PPI), PAF‐signaling pathways‐targets‐compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti‐OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1‐gamma‐tocopherol, PPARA‐fucosterol, PPARD‐stigmasterol, (PPARG)‐fucosterol, (NR1H3)‐campesterol, and ILK‐alpha‐tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB. [ABSTRACT FROM AUTHOR]

Background/aims: Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis.Methods: A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS.Results: Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 ± 0.02, 1.02 ± 0.18, 2.86 ± 0.77, and 6.56 ± 1.46 EU/mL, p < 0.001) and LBP (7026 ± 3336, 11,445 ± 1247, 11,947 ± 1164, and 13,791 ± 2032 ng/mL, p = 0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83 ± 0.17, 2.62 ± 0.22, 3.69 ± 0.28, and 4.29 ± 0.34 pg/mL, p < 0.001), demonstrating a significant difference between each grade (p < 0.05).Conclusions: HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS. [ABSTRACT FROM AUTHOR]

A response from the author of the article "A prospective nationwide study of drug-induced liver injury in Korea" in the 2012 issue is presented.

Background: Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue globally, currently, the treatment of NAFLD lies still in the labyrinth. In the inchoate stage, the combinatorial application of food regimen and favorable gut microbiota (GM) are considered as an alternative therapeutic. Accordingly, we integrated secondary metabolites (SMs) from GM and Avena sativa (AS) known as potent dietary grain to identify the combinatorial efficacy through network pharmacology. Methods: We browsed the SMs of AS via Natural Product Activity & Species Source (NPASS) database and SMs of GM were retrieved by gutMGene database. Then, specific intersecting targets were identified from targets related to SMs of AS and GM. The final targets were selected on NAFLD-related targets, which was considered as crucial targets. The protein–protein interaction (PPI) networks and bubble chart analysis to identify a hub target and a key signaling pathway were conducted, respectively. In parallel, we analyzed the relationship of GM or AS─a key signaling pathway─targets─SMs (GASTM) by merging the five components via RPackage. We identified key SMs on a key signaling pathway via molecular docking assay (MDA). Finally, the identified key SMs were verified the physicochemical properties and toxicity in silico platform. Results: The final 16 targets were regarded as critical proteins against NAFLD, and Vascular Endothelial Growth Factor A (VEGFA) was a key target in PPI network analysis. The PI3K-Akt signaling pathway was the uppermost mechanism associated with VEGFA as an antagonistic mode. GASTM networks represented 122 nodes (60 GM, AS, PI3K-Akt signaling pathway, 4 targets, and 56 SMs) and 154 edges. The VEGFA-myricetin, or quercetin, GSK3B-myricetin, IL2-diosgenin complexes formed the most stable conformation, the three ligands were derived from GM. Conversely, NR4A1-vestitol formed stable conformation with the highest affinity, and the vestitol was obtained from AS. The given four SMs were no hurdles to develop into drugs devoid of its toxicity. Conclusion: In conclusion, we show that combinatorial application of AS and GM might be exerted to the potent synergistic effects against NAFLD, dampening PI3K-Akt signaling pathway. This work provides the importance of dietary strategy and beneficial GM on NAFLD, a data mining basis for further explicating the SMs and pharmacological mechanisms of combinatorial application (AS and GM) against NAFLD. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease. [ABSTRACT FROM AUTHOR]

The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research. [ABSTRACT FROM AUTHOR]

Background/Aims: The management of hepatic hydrothorax (HH) remains a challenging clinical scenario with suboptimal options. We investigated the effect and safety of pigtail catheter drainage compared to intermittent thoracentesis. Methods: This multicenter, retrospective study included 164 cirrhotic patients with recurrent pleural effusion from March 2012 to June 2017. Patients with neoplasms, cardiopulmonary disease, and infectious conditions were excluded. We compared the clinical outcomes of pigtail catheter drainage versus thoracentesis for variables including complications related to procedures, overall survival, and re-admission rates. Results: A total of 164 patients were divided into pigtail catheter (n = 115) and thoracentesis (n = 49) groups. During the follow-up period of 6.93 months after discharge, 98 patients died (pigtail; n = 47 vs. thoracentesis; n = 51). The overall survival (p = 0.61) and 30-day mortality (p = 0.77) rates were similar between the pigtail catheter and thoracentesis groups. Only MELD scores were associated with overall survival (adjusted HR, 1.08; p < 0.01) in patients with HH. Spontaneous pleurodesis occurred in 59 patients (51.3%) in the pigtail catheter group. Re-admission rates did not differ between the pigtail catheter and thoracentesis groups (13.2% vs 19.6% p = 0.7). A total of five complications occurred, including four total cases of bleeding (one patient in the pigtail catheter group and three in the thoracentesis group) and one case of empyema in the pigtail catheter group. Conclusions: Pigtail catheter drainage is not inferior to that of intermittent thoracentesis for the management of HH, proving it may be an effective and safe clinical option. [ABSTRACT FROM AUTHOR]

The platelet-to-white blood cell ratio (PWR) has been reported to predict the severity of patients with various diseases. However, no previous studies have assessed the use of the PWR as a prognostic marker for pyogenic liver abscesses (PLA). This observational retrospective study was performed between January 2008 and December 2017, including 833 patients with PLA from multiple centers. The enrolled patients, on average, had a PWR of 17.05, and 416 patients had a PWR lower than 17.05. A total of 260 patients (31.2%) with PLA showed complications of metastatic infection, pleural effusion and abscess rupture. A low PWR level was identified as a strong risk factor for metastatic infection and pleural effusion. The low PWR group also had a longer hospital stay. In the multivariate analysis, old age, anemia, albumin and CRP levels and unidentified pathogens were significant factors for low PWR levels. A low PWR, old age, male sex, abscess size, albumin, ALP and unidentified causative pathogens showed significant associations with a hospital stay longer than 28 days. As a result, PLA patients presenting with a low PWR were shown to have more complications and a poor prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict a prognosis of PLA. [ABSTRACT FROM AUTHOR]

The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota–substrate–metabolite–target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein–protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut–hepatic–brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy. [ABSTRACT FROM AUTHOR]

Alcohol consumption is a global healthcare problem. Chronic alcohol consumption generates a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, fibrosis, and cirrhosis. Alcoholic liver diseases (ALD) refer to liver damage and metabolomic changes caused by excessive alcohol intake. ALD present several clinical stages of severity found in liver metabolisms. With increased alcohol consumption, the gut microbiome promotes a leaky gut, metabolic dysfunction, oxidative stress, liver inflammation, and hepatocellular injury. Much attention has focused on ALD, such as alcoholic fatty liver (AFL), alcoholic steatohepatitis (ASH), alcoholic cirrhosis (AC), hepatocellular carcinoma (HCC), a partnership that reflects the metabolomic significance. Here, we report on the global function of inflammation, inhibition, oxidative stress, and reactive oxygen species (ROS) mechanisms in the liver biology framework. In this tutorial review, we hypothetically revisit therapeutic gut microbiota-derived alcoholic oxidative stress, liver inflammation, inflammatory cytokines, and metabolic regulation. We summarize the perspective of microbial therapy of genes, gut microbes, and metabolic role in ALD. The end stage is liver transplantation or death. This review may inspire a summary of the gut microbial genes, critical inflammatory molecules, oxidative stress, and metabolic routes, which will offer future promising therapeutic compounds in ALD. [ABSTRACT FROM AUTHOR]

Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Abbreviations AFP alpha-foetoprotein ALT alanine aminotransferase AVT antiviral therapy CHB chronic hepatitis B CI confidence interval HBeAg hepatitis B virus e antigen HBV hepatitis B virus HCC hepatocellular carcinoma HR hazard ratio IQR interquartile range kPa kilopascals LS liver stiffness OR odds ratio TE transient elastography INTRODUCTION Potent antiviral therapy (AVT) against chronic hepatitis B (CHB) can induce regression of liver fibrosis, thereby reducing the development of cirrhosis and hepatocellular carcinoma (HCC) among CHB patients.1 While the prognostic significance of hepatitis B virus (HBV)-DNA levels have diminished because of potent AVT, fibrotic burden, not HBV-DNA level or type of AVT, remains the strongest predictor of HCC development.2 Fibrotic burden is undoubtedly the most critical predictor of HCC development.3 Considering that ALT rapidly normalizes up to 49% after 1-year AVT,4 the prognostic significance of alanine aminotransferase (ALT) levels may be unclear. [Extracted from the article]

Background and Aim Although transnasal endoscopy ( TNE) is generally a comfortable and safe procedure, it has some disadvantages, such as complicated preprocessing and occasional repulsion reaction during catheterization. In an attempt to simplify the preprocessing method, the efficacy of a catheter-free method in which a catheter is not inserted into the nasal cavity was assessed. Methods The present study was a prospective, open-label, single-center, randomized controlled study with parallel assignment allocation 1:1. Between March 2009 and August 2009, a total of 93 TNE-naïve patients were enrolled and randomized. Patients were prospectively randomized into two groups (catheter-free vs catheter-insertion method). Patients who prepared according to the catheter-free method and who were unsuccessful underwent the catheter-insertion method. Clinical characteristics, success rate, complications, vital signs, acceptability, and tolerability were assessed and compared. Results Success rates of the catheter-free and catheter-insertion methods were 88% ( n = 44) and 88% ( n = 38) ( P > 0.05), respectively. Causes of failure in the catheter-free method included severe rhinalgia ( n = 1, 2%) and narrowing of the nasal cavity ( n = 5, 10%). Causes of failure in the catheter-insertion method included narrowing of the nasal cavity ( n = 5, 11%). Six patients whose TNE failed with the catheter-free method also experienced failed TNE with the catheter-insertion method. There were no statistical differences in vital signs, acceptability, and tolerability. Conclusion The catheter-free method is sufficient for preparation for TNE. The success rate of TNE depends more on the structure of the nasal cavity than the preprocessing method. [ABSTRACT FROM AUTHOR]

Drynaria rhizome (DR) is used as a natural remedy to ameliorate obesity (OB) in East Asia; in parallel, the gut microbiota (GM) might exert a positive impact on OB through their metabolites. This study elucidates the orchestrated effects of DR and GM on OB. DR–GM, − a key signaling pathway–target–metabolite (DGSTM) networks were used to unveil the relationship between DR and GM, and Molecular Docking Test (MDT) and Density Functional Theory (DFT) were adopted to underpin the uppermost molecules. The NR1H3 (target) − 3-Epicycloeucalenol (ligand), and PPARG (target) − Clionasterol (ligand) conjugates from DR, FABP3 (target) − Ursodeoxycholic acid, FABP4 (target) − Lithocholic acid (ligand) or Deoxycholic acid (ligand), PPARA (target) − Equol (ligand), and PPARD (target) − 2,3-Bis(3,4-dihydroxybenzyl)butyrolactone (ligand) conjugates from GM formed the most stable conformers via MDT and DFT. Overall, these findings suggest that DR-GM might be a promising ameliorator on PPAR signaling pathway against OB. • GM (4 molecules) and DR (2 molecules) exert combinational effects against obesity. • The 6 targets are significant protein-coding genes to alleviate obesity. • DR and GM effectors are agonists on the PPAR signaling pathway in treating obesity. [ABSTRACT FROM AUTHOR]

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD. [ABSTRACT FROM AUTHOR]

Background: Wireless capsule endoscopy allows the identification of small intestinal protruded lesions, such as polyps, tumors, or venous structures. However, reading wireless capsule endoscopy images or movies is time-consuming, and minute lesions are easy to miss. Computer-aided diagnosis (CAD) has been applied to improve the efficacy of the reading process of wireless capsule endoscopy images or movies. However, there are no studies that systematically determine the performance of CAD models in diagnosing gastrointestinal protruded lesions. Objective: The aim of this study was to evaluate the diagnostic performance of CAD models for gastrointestinal protruded lesions using wireless capsule endoscopic images. Methods: Core databases were searched for studies based on CAD models for the diagnosis of gastrointestinal protruded lesions using wireless capsule endoscopy, and data on diagnostic performance were presented. A systematic review and diagnostic test accuracy meta-analysis were performed. Results: Twelve studies were included. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD models for the diagnosis of protruded lesions were 0.95 (95% confidence interval, 0.93–0.97), 0.89 (0.84–0.92), 0.91 (0.86–0.94), and 74 (43–126), respectively. Subgroup analyses showed robust results. Meta-regression found no source of heterogeneity. Publication bias was not detected. Conclusion: CAD models showed high performance for the optical diagnosis of gastrointestinal protruded lesions based on wireless capsule endoscopy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Finding the metabolites risk and metabolic phenotyping in MCF-7 cells with GO nanosheets. • Our understanding of metabolomics profiling is evolving the therapeutic metabolites and quantified. • An energy and several amino acid pathways can be affected and impacted. In this study, we investigated the graphene oxide (GO) nanosheets of specific interaction with metabolome in breast cancer cells. The edge-oxidized form of GO nanosheets have multiple applications in biomedical research. At present, the actual metabolic mechanisms of GO nanosheets is not yet clearly understood. Here, we describe the effects of GO exposure on MCF-7 breast cancer cells using 1H nuclear magnetic resonance (1H-NMR) profiling. We treated MCF-7 cells with different GO concentrations and examined the metabolic distributions. Interestingly, we found that the treatment affected arginine metabolism, proline metabolism, and aminoacyl-tRNA biosynthesis, including anabolism and catabolism. GO dose-dependently increased the number of metabolic disturbances in cancer steroids. Therefore, these data suggest that GO can significantly potentiate the metabolic effect in MCF-7 cells. These results demonstrate that using targeted metabolomics profiling and pattern recognition analysis display the potential metabolic changes and underlying metabolic impacts in human breast cancer cells. [ABSTRACT FROM AUTHOR]

An antibacterial effect of fermented‐Rhus verniciflua extract (FRVE), an urushiol‐free extract fermented by Fomitella fraxinea, on Helicobacter pylori was evaluated in mice. Minimal inhibitory concentration of FRVE against H. pylori eradication was checked with serial dilution method in vitro. H. pylori infection‐induced mice were utilized to determine the effect of oral administration of FRVE with/without standard triple therapy (STT: metronidazole, omeprazole, and clarithromycin) on H. pylori colonization and gastric inflammation. H. pylori was clearly eradicated by FRVE at a concentration of ≥2 mg/ml in vitro. In animal study, FRVE at a concentration of ≥6 mg/ml significantly reduced colonized H. pylori grading (0.2 vs. 2.2, p <.01) and improved gastric inflammation (0.4 vs. 1.6, p <.01) compared to control. STT with FRVE (3 mg/ml) exerted synergistic effect on both H. pylori colonization grade (STT, 0.6 ± 0.9; FRVE, 1.4 ± 0.5; STT + FRVE, 0.8 ± 0.4) and gastric inflammation (STT, 0.4 ± 0.5; FRVE, 1.4 ± 0.5; STT + FRVE,1.0 ± 0.1) compared with single therapy (p <.01). H. pylori eradication rate of FRVE (6 mg/ml) was higher than that of STT (60% vs. 20%). FRVE has potential antibacterial activity against H. pylori infection and can be used as an additional therapy on STT. [ABSTRACT FROM AUTHOR]

Background and Aims: This prospective observational study aimed to evaluate the best serum and urine markers to assess predictability for the prognosis of patients with decompensated cirrhosis. Methods: Serum creatinine and cystatin C (CysC), and urinary N‐acetyl‐beta‐D glucosaminidase (uNAG) and neutrophil gelatinase‐associated lipocalin (uNGAL) levels were measured from hospitalized patients with decompensated cirrhosis. Results: In total, 328 patients (mean age, 57.2 ± 12.0 years; 237 men) with decompensated cirrhosis were included. Alcoholic liver disease was the most frequent underlying liver disease (68.0%). Acute kidney injury (AKI) was concomitantly present in 41 patients (12.5%) at baseline. INR, serum creatinine and CysC levels, and uNAG and uNGAL levels were significantly higher in patients with AKI. During hospitalization, AKI had progressed in 37 patients (11.3%). In 287 patients without AKI, the incidence of AKI at 3, 6, 9 and 12 months was 15.4%, 22.2%, 28.6% and 32.5% respectively. On multivariate analysis, serum CysC and uNAG levels were independent predictors of AKI, and their optimal cut‐off values were 1.055 mg/L and 23.1 U/g urinary Cr respectively. When patients were classified into three groups with these cut‐off values of serum CysC and uNAG levels (group 1, both low; group 2, one of two high; and group 3, both high), progression of AKI during hospitalization (P =.001), incidence of AKI in patients without AKI at baseline (P =.001) and mortality rate (P <.001) differed significantly according to serum CysC and uNAG levels. Conclusion: Serum CysC and uNAG levels are useful prognostic markers for renal outcomes and mortality in patients with decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6‐monthly ultrasonography (US). However, sensitivities of US to detect early‐stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very‐early‐stage HCC in two groups: group A, undergoing 6‐monthly US versus group B, undergoing 6‐monthly US alternating with dynamic computed tomography (CT). Methods: This retrospective multicenter study assessed 1235 cirrhotic patients with CHB under entecavir/tenofovir therapy from 2007 to 2016. The primary endpoint was overall survival rates between the two groups. The Cox proportional hazards model and propensity score matching analyses were used to assess the effect of surveillance modalities on overall survival and detection of Barcelona Clinic Liver Cancer stage 0 HCC after balancing. Results: During a median follow‐up of 4.5 years, 10‐year cumulative HCC incidence rates of 16.3% were significantly higher in group B (n = 576) than 13.7% in group A (n = 659; P < 0.001). However, in patients with HCC, 10‐year overall survival rates of 85.1% were significantly higher in group B than 65.6% in group A (P = 0.001 by log‐rank test). CT exam alternating with US was independently associated with reduced overall mortality (hazard ratio 0.47, P = 0.02). Cumulative incidence of Barcelona Clinic Liver Cancer stage 0 HCC was significantly higher in group B than in group A (hazard ratio 2.82, P < 0.001). Conclusion: In cirrhotic patients with CHB, dynamic CT exam alternating with US led to higher detection rates of very‐early‐stage HCC and benefit of overall survival than did US exams. [ABSTRACT FROM AUTHOR]

Backgrounds & Aims: The Baveno VI guidelines proposed criteria including liver stiffness (LS) and platelet count to avoid screening endoscopy in patients with compensated advanced chronic liver disease (cACLD). This study was performed to validate the Baveno IV criteria and to compare its diagnostic accuracy with other non‐invasive models. Methods: Patients with cACLD who underwent laboratory tests, upper gastrointestinal endoscopy and abdominal ultrasound within 6 months of transient elastography were included. Results: A total of 1218 patients with cACLD were included. VNT occurred in 249 patients (20.4%). With the Baveno VI criteria, the VNT miss rate was 1.9% with a 25.7% saved endoscopy rate. Using two criteria of LS <20 kPa and platelet count >110 × 109 cells/L or LS <25 kPa and platelet count >120 × 109 cells/L, the saved endoscopy rate was 39.1% while maintaining the VNT miss rate <5%. The optimal LS and platelet count‐based criteria for predicting VNT differed according to the underlying liver disease. The area under the receiver operating characteristic curve of LS‐spleen diameter to platelet score (LSPS) was 0.780 (95% confidence interval: 0.774‐0.820), which was significantly higher than other models. The optimal cut‐off value of the LSPS for predicting VNT was 1.47. Conclusion: Liver stiffness and platelet count‐based criteria are useful for discriminating patients with very low risk of having VNT among patients with cACLD and are partly affected by the type of underlying liver disease. Conversely, the LSPS is a predictor of VNT in patients with cACLD regardless of the type of underlying liver disease. [ABSTRACT FROM AUTHOR]

Background: The forward-viewing endoscope has been increasingly used to perform endoscopic retrograde cholangiopancreatography (ERCP) in patients who underwent Billroth II gastrectomy. This study intended to assess efficacy and safety of the forward-viewing endoscope for ERCP in Billroth II gastrectomy patients compared with conventional side-viewing endoscope using a systematic review and meta-analysis.Methods: A systematic review was conducted for studies that evaluated the outcomes of ERCP for patients with Billroth II gastrectomy. Random-effect model meta-analyses with subgroup analyses were conducted. The methodological quality of the included publications was evaluated using the risk of bias assessment tool for non-randomized studies. The publication bias was assessed.Results: In total, 25 studies (1 randomized, 18 retrospective, 1 prospective, and 5 case series studies) with 2446 patients (499 forward-viewing and 1947 side-viewing endoscopes) were analyzed. The pooled afferent loop intubation rate was higher with the forward-viewing endoscope (90.3%, 95% confidence interval (CI) 85.6-93.6 vs. 86.8%, 95% CI 82.8-89.9%). The pooled selective cannulation rate was higher with the side-viewing endoscope (92.3%, 95% CI 88.0-95.2 vs. 91.1%, 95% CI 87.2-93.9%). The pooled bowel perforation rate was higher with the side-viewing endoscope (3.6%, 95% CI 2.3-5.7 vs. 3.0%, 95% CI 1.7-5.3%). The pooled pancreatitis rate was higher with the forward-viewing endoscope (5.4%, 95% CI 3.6-8.0 vs. 2.5%, 95% CI 2.3-5.7%). The pooled bleeding rate was higher with the forward-viewing endoscope (3.0%, 95% CI 1.6-5.5 vs. 2.0%, 95% CI 1.4-3.0%). The heterogeneity among the studies was not significant. The publication bias was minimal.Conclusion: This meta-analysis indicates that the forward-viewing endoscope is as safe and effective as conventional side-viewing endoscope for ERCP in patients with Billroth II gastrectomy. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP). However, the involvement of PAD2 and cit-GFAP in hepatic fibrosis remains unclear. To determine the expression of PAD2 and cit-GFAP in hepatic fibrosis, C57BL/6 mice underwent bile duct ligation (BDL) or a sham operation. In BDL livers, the expression of PAD2 and its enzyme activity were significantly increased compared with controls. In addition, PAD2-postitive cells were rarely observed in only the portal vein and the small bile duct in sham-operated livers, whereas an increased number of PAD2-positive cells were detected in the bile duct and Glisson’s sheath in BDL livers. Interestingly, PAD2 was colocalized with α-SMA-positive cells and CK19-positive cells in BDL livers, indicating upregulated PAD2 in activated HSCs and portal fibroblasts of the livers of BDL mice. We also found that citrullinated proteins were highly accumulated in the livers of BDL mice compared with controls. Moreover, the expression level of GFAP and the amount of cit-GFAP were higher in BDL livers than in control livers. In correlation with PAD2 localization, cit-GFAP was observed in α-SMA-positive and CK19-positive cells in the livers of BDL mice. These results suggest that the increased expression and activation of PAD2 along with increased citrullinated proteins, specifically cit-GFAP, may play important roles in the pathogenesis of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532–27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548–18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. Methods: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS‐1). Results: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS‐1. Serum creatinine level was not significantly associated with mortality and development of HRS‐1 on multivariate analysis. Conclusion: Serum cystatin C level was an independent predictor of mortality and development of HRS‐1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The aim of this study was to validate the chronic liver failure‐sequential organ failure assessment score (CLIF‐SOFAs), CLIF consortium organ failure score (CLIF‐C OFs), CLIF‐C acute‐on‐chronic liver failure score (CLIF‐C ACLFs), and CLIF‐C acute decompensation score in Korean chronic liver disease patients with acute deterioration. Methods: Acute‐on‐chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF‐C criteria. The diagnostic performances for short‐term mortality were compared by the area under the receiver operating characteristic curve. Results: Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF‐C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs were significantly higher than those of the Child–Pugh, model for end‐stage liver disease, and model for end‐stage liver disease‐Na scores in ACLF patients according to the CLIF‐C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF‐C definition, but not in ACLF patients according to the AARC definition. Conclusions: The CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF‐C definition, but not the AARC definition. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is becoming more common and severe. Individuals with NAFLD have an altered composition of gut- microbial metabolites. We used metabolomics profiling to identify microbial metabolites that could indicate gut-liver metabolic severity. Noninvasive biomarkers are required for NAFLD, especially for patients at high risk of disease progression. We compared the stool metabolomes, untargeted metabolomics, and clinical data of 80 patients. Patients with nonalcoholic fatty liver (NAFL: n = 16), nonalcoholic steatohepatitis (NASH: n = 26), and cirrhosis (n = 19) and healthy control individuals (HC: n = 19) were enrolled. The identified metabolites in NAFLD were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Gas chromatography–mass spectrometry (GC–MS) and liquid chromatography coupled to time-of-flight–mass spectrometry (LC–TOF-MS) were used to analyze metabolites. Untargeted metabolomics was used to identify and quantify 103 metabolites. Principal component analysis (PCA) was used to assess the metabolic discrimination of NAFL, NASH, and cirrhosis. Short-chain fatty acids (SCFA) levels were significantly lower in NAFLD patients, including those of acetate (p = 0.03), butyrate (p = 0.0008), and propionate. The stool cholic acid (p = 0.001) level was significantly increased in NAFLD patients. Palmitoylcarnitine and l -carnitine levels were significantly increased in NASH and cirrhosis patients. The phenotypic expression of these metabolites was linked to β-oxidation. We demonstrated a distinct metabolome profile in NAFLD patients with NAFL, NASH, and cirrhosis. We also discovered that the expression of certain metabolites and metabolic pathways was linked to NAFLD. • A workflow was developed for NAFLD through untargeted metabolomics analysis. • The effect of non-alcohol consumption on the metabolome was quantified and investigated. • Metabolic injuries of NAFL, NASH, and cirrhosis were analyzed. • Fatty acids, bile acids, amino acids, and organic molecules could significantly alter human stool samples. • Short-chain fatty acids, linolenic acid, and indole metabolites were identified and recommended for clinical therapeutics. [ABSTRACT FROM AUTHOR]

Objectives. Terlipressin is safely used for acute variceal bleeding. However, side effects, such as hyponatremia, although very rare, can occur. We investigated the development of hyponatremia in cirrhotic patients who had acute variceal bleeding treated with terlipressin and the identification of the risk factors associated with the development of hyponatremia. Design and Methods. This retrospective, case-control study investigated 88 cirrhotic patients who developed hyponatremia and 176 controls that did not develop hyponatremia and were matched in terms of age and gender during the same period following terlipressin administration. Results. The overall change in serum sodium concentration and the mean lowest serum sodium concentration were 3.44 ± 9.55 and 132.44 ± 8.78 mEq/L during treatment, respectively. Multivariate analysis revealed that baseline serum sodium was an independent positive predictor, and the presence of baseline serum creatinine, HBV, DM, creatinine, and shock on admission was independent negative predictors of hyponatremia (P<0.05). Conclusion. The presence of HBV, DM, the baseline serum sodium, shock on admission, and especially baseline creatinine may be predictive of the development of hyponatremia after terlipressin treatment. Therefore, physicians conduct vigilant monitoring associated with severe hyponatremia when cirrhotic patients with preserved renal function are treated with terlipressin for variceal bleeding. [ABSTRACT FROM AUTHOR]

Background: Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD.Methods: Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL.Results: In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27-6.06), mosapride (OR: 1.99, 95% credible interval: 0.87-4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92-4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29-6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43-6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07-1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04-2.18).Conclusions: Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD. [ABSTRACT FROM AUTHOR]

Background: There have been limited studies directly comparing the long-term efficacy between entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study was aimed to compare the long-term efficacy between them in treatment-naïve chronic hepatitis B (CHB).Methods: Out of 345 CHB patients who received first line therapy with ETV (n = 200) or TDF (n = 145) in a cohort, 210 patients were analyzed using propensity score matching, at a ratio of 1:1.Results: Two groups showed no difference in baseline characteristics. During the follow-up of 12 months, HBV DNA levels were similarly suppressed in both groups (ETV vs. TDF; -5.01 vs. -5.242 log10IU/mL, P = 0.559). At month 12, both groups showed no difference in terms of the serologic, biochemical and virologic (VR) response. In multivariate analysis, the initial virologic response at 3 months (IVR-3) was independent factor for VR at 1 year. During the long-term follow-up, HBV DNA levels were more strongly suppressed by TDF than ETV in hepatitis B e antigen (HBeAg) positive patients (P = 0.035), especially with high viral load (P = 0.012), although there was no significant difference in overall VR between two groups. The type of antivirals was not an independent factor for long-term VR.Conclusions: Although either ETV or TDF, overall, may show a comparable long-term antiviral efficacy in treatment-naïve CHB, TDF might be better regimen than ETV in the subgroup of HBeAg-positive CHB, especially with a higher HBV DNA levels. [ABSTRACT FROM AUTHOR]

Background: Portal hypertensive gastropathy (PHG) is a frequently overlooked complication of liver cirrhosis (LC). The clinical implications of PHG as a prognostic factor of LC or a predictive factor for the development of hepatocellular carcinoma (HCC) have not been established. The aim of this study was to assess the clinical significance of PHG in patients with LC.Methods: Patients with LC were prospectively enrolled and followed in a single tertiary hospital in the Republic of Korea. Baseline hepatic vein pressure gradient (HVPG) was measured, and esophagogastroduodenoscopy (EGD) was performed. The associations of PHG with HVPG, survival and the development of HCC were evaluated.Results: A total of 587 patients were enrolled. The mortality rate was 20.3 % (n = 119), and HCC developed in 9.2 % (n = 54) during the follow-up period (32.6 ± 27.8 months). The grade of PHG was well correlated with HVPG (no PGH: median 9.2 [IQR: 7.2-16.7], mild PHG: 14.6 [10.1-19.3], and severe PHG: 17.3 [12.3-21.5], P < 0.001), as well as with Child-Pugh class, MELD score or survival. However, it was not associated with the development of HCC. The grade of PHG (HR 3.29, 95 % CI: 1.12-9.63, severe vs. no PHG) and Child-Pugh class (HR 3.53, 95 % CI: 1.79-6.97, Child C vs A) showed significant associations with mortality.Conclusion: PHG was well correlated with portal hypertension and could be used as a prognostic factor for LC but not for the prediction of HCC. [ABSTRACT FROM AUTHOR]