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Abstract Background Severe alcoholic hepatitis is a catastrophic disease with a mortality rate of up to 35–50% at 30 days. Bacterial infection is an important prognostic factor in patients with severe alcoholic hepatitis, but it is difficult to detect the presence of infection immediately. Procalcitonin (PCT) is a well-known inflammatory marker that can detect bacterial infections in various diseases early. Therefore, we aimed to evaluate the diagnostic accuracy of PCT for bacterial infection in severe alcoholic hepatitis. Methods We prospectively enrolled patients with severe alcoholic hepatitis, defined as modified Maddrey’s Discriminant Function ≥ 32, from 10 medical centers. At admission, we performed an initial evaluation including physical examination, laboratory test, radiology, blood and urine culture, PCT, and C-reactive protein (CRP). We compared the receiver operating characteristic (ROC) curves of PCT and CRP for bacterial infection, systemic inflammatory response syndrome (SIRS), and sepsis among total patients. Results A total of 108 patients with severe alcoholic hepatitis were enrolled. The number of bacterial infections, SIRS, and sepsis were 31 (28.7%), 41 (38.0%), and 19 (17.6%), respectively. The patients with bacterial infection had significantly higher MELD scores (24.0 vs. 15.0), PCT levels (1.5 vs. 0.4 ng/mL), and CRP levels (4.9 vs. 2.5 mg/dL) compared to those without bacterial infection. The area under the ROC curve (AUROC) of PCT vs. CRP for bacterial infection was 0.752 and 0.655, respectively (P = 0.113). The AUROC of PCT vs. CRP for SIRS was 0.699 and 0.662, respectively (P = 0.490). The AUROC of PCT vs. CRP for sepsis was 0.780 and 0.630, respectively (P = 0.027). Conclusions Among patients with severe alcoholic hepatitis, PCT showed a trend of superior diagnostic performance in the early detection of bacterial infection and sepsis compared to CRP. Although PCT might have better potential to diagnose sepsis in the setting of severe alcoholic hepatitis, it is necessary to find more reliable diagnostic markers.

Abstract Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P

Renewable lignocellulosic biomass is a favorable energy resource since its co-pyrolysis with hydrogen-rich plastics can produce high-yield and high-quality biofuel. In contrast to earlier co-pyrolysis research that concentrated on increasing product yield, this study comprehends the synergistic effects of two distinct feedstocks that were not considered earlier. This work focuses on co-pyrolyzing wheat straw (WS) with non-reusable polyethylene terephthalate (PET) for the production of pyrolysis oil. WS and PET were blended in different ratios (100/0, 80/20, 60/40, 40/60, 20/80, and 0/100), and pyrolysis experiments were conducted in a fixed-bed reactor under different temperatures to assess their synergistic effect on oil yield. Synergy rates of up to 7.78 % were achieved on yield for the blends of plastic and biomass at a temperature of 500 °C. In comparison to individual biomass or plastics, co-pyrolyzing PET-biomass blends demonstrated good process interaction and promoted the yields of value-added products. The heating value of the pyrolysis oils was in the range of 16.45–28.64 MJ/kg, which depends on the amount of plastic present in the feedstock. The physical analysis of the oils shows that they can be used for heat production by direct combustion in boilers or furnaces. The correlation between WS and PET was validated with the aid of Fourier transform infrared spectroscopy (FT-IR) and gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS result demonstrated the presence of different compounds such as O-H compounds, esters, carbonyl group elements, acids, hydrocarbons, aromatics, and nitrogenated compounds in the pyrolysis oil, which differed based on the proportions of PET in the feedstock. The increased hydrocarbon and reduced oxygen percentages in the pyrolysis oil were implicitly caused by enhanced hydrocarbon pool mechanisms, in which the breakdown of PET may be supplied as a hydrogen donor. Overall, waste lignocellulosic biomass and plastics can be used to produce biofuels, which helps reduce the amount of solid waste that ends up in landfills. This study also revealed that future research should be focused on the reaction mechanisms of WS and PET co-pyrolysis in order to examine the synergistic interactions.

Background Differentiating between bacterial and nonbacterial colitis remains a challenge. We aimed to evaluate the value of serum procalcitonin (PCT) and C-reactive protein (CRP) in differentiating between bacterial and nonbacterial colitis. Methods Adult patients with three or more episodes of watery diarrhea and colitis symptoms within 14 days of a hospital visit were eligible for this study. The patients’ stool pathogen polymerase chain reaction (PCR) testing results, serum PCT levels, and serum CRP levels were analyzed retrospectively. Patients were divided into bacterial and nonbacterial colitis groups according to their PCR. The laboratory data were compared between the two groups. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results In total, 636 patients were included; 186 in the bacterial colitis group and 450 in the nonbacterial colitis group. In the bacterial colitis group, Clostridium perfringens was the commonest pathogen (n=70), followed by Clostridium difficile toxin B (n=60). The AUC for PCT and CRP was 0.557 and 0.567, respectively, indicating poor discrimination. The sensitivity and specificity for diagnosing bacterial colitis were 54.8% and 52.6% for PCT, and 52.2% and 54.2% for CRP, respectively. Combining PCT and CRP measurements did not increase the discrimination performance (AUC, 0.522; 95% confidence interval, 0.474–0.571). Conclusion Neither PCT nor CRP helped discriminate bacterial colitis from nonbacterial colitis.

Abstract This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020–2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars’ blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Background/Aims We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Methods Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. Results RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. Conclusions NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Objectives In this study, the applicability of dry condensate generated from food waste dry feed conversion process was evaluated as an external carbon source to increase the efficiency of the biological denitrification process. Methods The experiment was carried out in the form of a batch test, and dry condensate was injected into each reactor according to the COD and T/N ratio (C/N ratio). Then, the reactor was operated under anoxic conditions for 5 hours, and nitrate nitrogen was analyzed at intervals of 1 hour. Results and Discussion The dry condensate from food waste showed a low nitrogen content (T-N 220 mg/L) compared to a high organic matter content (TCOD 21,863 mg/L), and was analyzed to satisfy the conditions of an external carbon source in the denitrification process. And as a result of the experiment, it was found that the nitrate nitrogen removal efficiency was up to 76% after 5 hours at a C/N ratio 7.50:1, which was significantly increased compared to the control which was without condensed water (removal efficiency 4%). Moreover, the removal efficiency of 28% was exhibited even at the C/N ratio 0.95:1, which exhibited the lowest efficiency. In addition, as a result of calculating the specific denitrification rate (SDNR) for each C/N ratio, 7.50:1 was found to be as 0.0726 mg NO3-/mg VSS/d, which was significantly increased than that of control as 0.0038mg NO3-/mg VSS/d. Conclusion Based on these results, it is judged that it is possible to utilize the dried condensate of food waste as an external carbon source in the denitrification process.

Background: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. Method: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. Result: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. Conclusion: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

Background/Aims: Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods: We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results: Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID- 19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p

Abstract Background Previous studies of patients with liver cirrhosis have not considered the broad range of symptoms or the association between healthy behavior and quality of life. The purposes of this study were to examine the association between symptoms and adopting exercise and consuming fruits and vegetables and to identify factors associated with quality of life in patients with liver cirrhosis. Methods This cross-sectional study enrolled 91 consecutive patients with liver cirrhosis in one tertiary general hospital in South Korea between February 2016 and January 2017. Each study participant completed a self-administered questionnaire that measured symptom, stage of change in engaging in exercise and consumption of fruits and vegetables, and the Korean version of the 36-item Short-Form Health Survey. Multivariate ordinal logistic regression analysis and multiple regression models was used, respectively, to examine the association between each symptom with stage of change in engaging in exercise and consumption of fruits and vegetables and to evaluate factors affecting quality of life. Results Experiencing nausea was associated with more readiness for change in engaging in exercise, but experiencing shortness of breath was associated with less readiness for change in engaging in exercise. Experiencing right upper quadrant pain was associated with more readiness for change in engaging in consumption of fruits and vegetables. Muscle cramps, anorexia, right upper quadrant pain and body pain, itching, ascites or edema, bruising, and change in appearance negatively affected quality of life. Conclusions The results suggest that the types of symptoms experienced by a patient with liver cirrhosis hinder or promote the patient’s adoption of exercise and dietary behavior. Experiencing symptoms may negatively affect quality of life. Caregivers should provide supportive care to patients with liver cirrhosis, which includes assessing and managing symptoms to improve quality of life.

Background/Aims The risk factors for the development of primary biliary cholangitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. Methods Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A standardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. Results The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivariable analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. Conclusions A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.

Objectives: The present study was aimed to synthesize Silver nanoparticles (Ag NPs) from ethanol extract of Allium sativum to evaluate the in-vitro cytotoxicity effect on human lung adenocarcinoma cells (A549). Methods: Spetroscopic analysis were performed to determine the formation, stability, nature and the functional groups of the Ag NPs. Microscopic analysis were performed to ascertain the morphology and size of the particles. In-vitro MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was performed to determine the cytotoxic potential of the Ag NPs on A549 lung cancer cell lines. Results: The UV–Visble spectrum confirmed the formation of the particles. Fourier Transform Infrared (FTIR) spectrum revealed the presence of carbonyl, carboxyl, primary and secondary amine groups. Powder X-ray diffraction (PXRD) established the crystalline nature and FCC structure of Ag NPs. Morphological analysis performed using Field Emission-Scanning Electron Microscopy (FESEM), High-Resolution Transmission Electron Microscopy (HRTEM), Selected Area Electron Diffraction (SAED) pattern showed spherical and rod shaped bio synthesized Ag NPs with variable size ranging from 20 nm to 40 nm. The synthesized Ag NPs showed a significant cytotoxic potential against A549 human lung cancer cells at an IC50 of 22 μg/ml. Conclusion: The present study revealed a cost-effective, simple and effective method to synthesize Ag NPs using garlic extract and the cytotoxic activity on human adenocarcinoma cells (A549) demonstrated their future application as potential anti-cancer agent.

Background: Search for options that can overcome microorganism’s resistance to traditional drugs, has shifted the focus towards plant-based molecules and extracts. Latest developments in plant-based nanomaterials have further expanded the role of plant extracts since nano particle - plant extract combinations are shown to possess enhanced biological activity and reduced toxicity to human cells. In the present study, facile, one-pot synthesis of nearly monodispersed gold nanoparticles was developed using Clerodin enriched Clerodendrum infortunatum ethanolic leaf extract under ambient conditions. The synthesized gold nanoparticles were evaluated for broad spectrum anti-microbial activity as well as compatibility with human peripheral blood mononuclear cells. Methods: Clerodin enriched fraction from C. infortunatum leaves ethanol extract was used to synthesize gold nanoparticle from chloroauric acid. Synthesized gold nanoparticles were characterized and tested for broad spectrum anti-microbial activity against Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa using the standard broth dilution method. Cytotoxicity of the gold nanoparticles was evaluated against human monocyte leukemic cells (THP-I) and healthy peripheral blood mononuclear cells. MTT and FACS based Annexin V/FITC-PI assays were used to study its cytotoxic effect. Results: TEM analysis showed an average diameter of 33 ± 5 nm for the synthesized nanoparticles. EDX validated the presence of elemental Au (98.8%) and confirmed its nano form. Antimicrobial assay of gold nanoparticles showed significant inhibitory effect in all the tested pathogens. Additionally, MTT and Annexin-V/ PI assay demonstrated the cytotoxic activity of the nanoparticles against THP-I cells. Interestingly, nanoparticles did not show cytotoxicity against healthy human peripheral blood mononuclear cells. Conclusion: Gold nanoparticles generated in an eco-friendly process using Clerodin enriched fractions showed promising broad spectrum antibacterial activity. Simultaneously, they proved themselves to be benign against healthy human cells indicating potential therapeutic applications. Added benefit for the nanoparticles was, they had anti-proliferative effects against human leukemic monocyte cancer (THP-I) cells.

Background/Aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses. Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Background/Aims Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved. Methods A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed. Results Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P

Pedalium murex, a less-utilized traditional plant, has high lipid content, which ranges from 21 mg/gfw (milligram per gram fresh weight) in leaf, 32 mg/gfw in stem and 19 mg/gfw in callus. Lipids from different parts of the plant were extracted and employed for biodiesel production. Al2O3-CaO nanocatalyst was synthesized by the classical Sol-gel method, characterized by XRD, HR-SEM, and was applied for biodiesel production. In transesterification, the influence of methanol-lipid was evaluated by varying the ratio from 1:6 to 1:16, and the FAME converted yield was calculated to be 60% using Gas chromatography. The biomass was subjected to lipid extraction and was then used for the synthesis of AgNPs, analyzed through the UV–Visible absorption spectrum, XRD, HR-SEM, and SAED. AgNPs of Pedalium murex plant extract were examined for their antimicrobial activity against various bacterial pathogens such as Staphylococcus aureus, Klebsiella pneumonia, Bacillus subtilis and Escherichia coli. AgNPs showed the best antibacterial activity against E. coli at 5.0 mM concentration. This study is promising in the identification of a cheap source for biodiesel production with the added advantage of antimicrobial drug formulation from the medicinal plant Pedalium murex. Keywords: Pedalium murex, Nanocatalyst, Biodiesel, Lipid extraction, Antibacterial activity

Objectives: The objective of this work was to predict anti-colon and anti-hepatoma cancer activity of newly designed substituted 4-anilino coumarin derivatives using quantitative structure–activity relationship (QSAR). Methods: The optimization of the derivatives including molecular and electronic properties data to generate the QSAR were resulted from H-GGA DFT/BPV86 method calculation combined with Hartree-Fock 6-31G basis set. The QSAR models were delivered in multiple linear regression (MLR) and the drug design was accomplished by considering the descriptors constructing the best QSAR models for each biological activity. Results: This research accomplished two best validated QSAR models for predicting anti-colon cancer and anti-hepatoma activities of substituted 4-anilino coumarin derivatives. There were 17 of newly designed substituted 4-anilino coumarin derivatives which their anticancer activity (Log IC50) were predicted using our both QSAR models. The QSAR predictions inform that the compound 25 and compound 19 have the best predicted anti-colon cancer and anti-hepatoma activities, respectively. Conclusion: The results revealed that this approach can be used to assist in the action of anticancer drug discovery. Moreover, the retrosynthesis analysis of both compounds are also explained in a logic reverse of organic synthetic steps through Knoevenagel and Perkin reactions.

Objectives: Advancement in the biological process of nanoparticles synthesis is an important area of nanotechnology. The aim of this research is to utilize the root extract of Furcraea foetida as reduction and stabilization agents to biosynthesize. Silver nanoparticles (AgNPs) from AgNO3 via a simple green method. Methods: By utilizing UV–VIS spectroscopy, FTIR, XRD, Zeta potential, and HR-TEM techniques, the nanoparticles have been characterized. The anti-Candida properties of AgNPs were tested using the well-diffusion method in agar plates against five Candida species. Results: With an average diameter of 15 nm, the produced AgNPs are spherical. They were found to be stable and non-aggregated. The synthesized nanoparticles were active against all the tested organisms and showed better efficacy compared to Amphotericin B in most cases. The highest level of inhibition was found against C. albicans at 100 µg concentration. Conclusion: The results prove that F. foetida is a very good bioreductant and can be used for one-pot synthesis of stable AgNPs with good anti-Candida activity.

Objectives: The objective of this work was to develop a new pretreatment method to remediate processed cheese wastewater using calcium nanoparticles (CaNPs) synthesized from Senna auriculata L. flower extract. Methods: Processed cheese effluent was collected from a typical dairy factory and characterized the physical and chemical features such as color, odor, pH, total solids, total dissolved solids (TDS), total suspended solids and chemical oxygen demand (COD). The effluent was subjected to treatment using (CaNPs) synthesized from S. auriculata L. flower extract as a reducing agent. The NPs were characterized by X-ray diffraction, Fourier transformation spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy. Results: The crystalline nature of the synthesized CaNPs was found to be amorphous with a grain sizes 56 nm. The characterization studies confirmed the formation of CaNPs. The optimal dosage of NPs was 0.08 g, which reduced TDS and COD in the effluent by 73% and 82% respectively, within 2 h. The outcome of the investigation confirmed the reducing and stabilizing properties of from CaNPs synthesized from S. auriculata L plant flower extract and its effluent treatment efficiency. Conclusions: The results revealed that the treatment of processed cheese wastewater can be effective with the application of enhanced CaNPs. It can be also suggested as an eco-friendly material for wastewater remediation. Senna auriculata L plant flower extract is a good source for CaNPs synthesis, adopting eco-friendly methods. In future, biologically synthesized nanomaterials would be an extremely promising solution for food industry wastewater treatment.

The exponential expansion of industrial production during the past few decades has been detrimental to the environment owing to increased contamination with chemical pollutants such as heavy metals and dyes. Each year, large volumes of agricultural byproducts are generated as waste materials from various food crops, one which is wheat bran from wheat, the world’s largest food crop. Approximately 12% of dyes made from synthetic materials used by the textile industry are lost in the production and processing phases; similarly, 20% of the resulting dye reaches the ecosystem via industrial wastewater effluents. These dyes are highly radioactive and have potentially negative consequences; therefore, several federal and environmental authorities have enacted stringent regulations and restrictions prohibiting the dumping of dye-containing raw sewage into existing water bodies. Although there are several methods to remove dye from wastewater, the preferred approach is adsorption. Activated charcoal is one of the best adsorbents. However, its use in industrial water treatment, mainly in developing nations, is confined because of its high cost. Owing to the increasing price of activated carbon, researchers have been tasked with developing a low-cost, reliable adsorbent that can be substituted for activated carbon. Several adsorbents, such as biosorbents, carbon-based nano-adsorbents, transition metal-based oxides, Metal-organic frameworks MOFs, and polymer-based adsorbents, are used to treat dye-containing wastewater. This chapter compiles the results of various studies that analyzed the use of wheat bran as an absorbent for eliminating dyes and other toxic effluents from the textile industry. Dye removal via adsorption and nano-materials is expected to be a promising method for the treatment of dye-laden water.

AimsInduction of a durable viral response is difficult to achieve in patients with chronic hepatitis B (CHB), even from long-term use of a nucleos(t)ide analogue (NA). This study investigated whether switching to peginterferon (PegIFN) alfa-2a after long-term NA therapy induced a durable viral response.MethodsPatients with hepatitis B e antigen (HBeAg)-positive CHB who received any NA for at least 72 weeks and had a low level of HBV DNA (≤100 IU/mL) were randomized (1:1) to receive PegIFN alfa-2a (180 μg/week) or NA for 48 weeks. The primary endpoint was change in the hepatitis B surface antigen (HBsAg) titer during antiviral therapy.ResultsWe randomized 149 CHB patients to the two groups. Compared to baseline, the HBsAg levels in both groups were not lower at week 12, but were lower after 24, 36, and 48 weeks (all pConclusionsCHB patients who switched to PegIFN alfa-2a for 48 weeks had a significantly lower HBsAg titer and increased HBeAg seroconversion relative to those who remained on NA therapy.Trial registration(ClinicalTrials.gov; NCT01769833).

Background/Aims In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies. Methods This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or Child-Pugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA 5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs. Conclusions In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.

Background/Aims Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world. Methods We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure. Results The mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure. Conclusions DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

Background/Aim This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea. Methods A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted. Results The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naïve and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event. Conclusions EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.

Background and aimsThe low-salt diet is considered important for control of ascites in cirrhotic patients. To validate whether the spot urine sodium (Na)/potassium (K) ratio could replace 24-h urine Na (uNa) excretion in assessing low-salt diet compliance.MethodsWe prospectively studied 175 patients. 24-h urine collection and spot urine collection were performed. Subsequently, 24-h uNa, urine creatinine (uCr), and spot urine Na and K were assessed. A complete urine collection was confirmed based on 24-h uCr excretion levels of 15mg/kg/day for men and 10mg/kg/day for women. The area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the feasibility of spot urine Na/K ratio in predicting 24-h uNa greater than 78mmol/day.ResultsOut of 175 patients, 24-h urine samples were completely collected in 57 patients only. Moreover, urine samples were not completely collected in 118 patients because their 24-h uCr excretion level was less than the established criteria. In complete urine collection group, AUROC curve for spot urine Na/K ratio in predicting 24-h uNa greater than 78mmol/day was 0.874±0.051 (PConclusionsThe spot urine Na/K ratio reflects 24-h uNa, but the AUROC value obtained in this study is lower than that of a previous study. Considered the large number of patients with incomplete urine collection, validating 24-h complete urine collection criteria is necessary.

Objective The reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with severe infection of COVID-19.Design Retrospective multicentre cohort study.Setting Five tertiary hospitals of Daegu, South Korea.Participants 1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs.Methods The clinical and laboratory features of patients with COVID-19 receiving respiratory support were analysed to ascertain the risk factors for mortality using the Cox proportional hazards regression model. The relationship between overall survival and risk factors was analysed using the Kaplan-Meier method.Outcome In-hospital mortality for any reason within 56 days.Results Of the 1005 patients, 289 (28.8%) received respiratory support, and of these, 70 patients (24.2%) died. In multivariate analysis, high fibrosis-4 index (FIB-4; HR 2.784), low lymphocyte count (HR 0.480), diabetes (HR 1.917) and systemic inflammatory response syndrome (HR 1.714) were found to be independent risk factors for mortality in patients with COVID-19 receiving respiratory support (all p

Background/AimsThis study aimed to describe the health-related quality of life (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the impact of patient and virus-related factors on HRQoL.Methods : HRQoL was assessed in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary hospital, including those with liver cirrhosis and hepatocellular carcinoma (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life questionnaire-5 dimensions (EQ-5D-3L).Results : The SF-36 physical (48.8±8.3) and mental (46.2±11.7) component summary scores of the HCV-infected patients were below normal limits. Of the eight domains, general health, vitality, and mental health tended to show low scores. Patients with decompensated cirrhosis had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL results. The EQ-5D index was low (0.848±0.145) in the HCV infected patients. Multivariable analysis showed age ≤65 years, high monthly family income (>$2,641), low comorbidity score, and sustained virologic response (SVR) were independently associated with favorable HRQoL.Conclusion : sHRQoL in Korean patients with chronic HCV infection was low and was affected by cirrhosis severity, SVR, and comorbidity as well as income, which had the strongest effect. Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to prevent cirrhosis progression.

Background/Aims Endoscopic submucosal dissection (ESD) has been widely accepted as a method of treatment of early gastric tumor. This study aimed to identify the incidence and characteristics of multiple gastric tumors after ESD. Methods Patients with early gastric tumors who were treated by ESD from January 2004 to June 2012 and followed up with endoscopic examination periodically for at least 1 year were enrolled. All multiple gastric lesions were subsequently treated with ESD and the medical records of the patients were retrospectively reviewed. Results In total, 643 patients were included. The mean duration of endoscopic follow-up was 45.27±27.59 (range, 12–148) months. Overall, 144 patients (22.4%) showed multiple gastric tumors during the follow-up period (44 synchronous [6.8%] and 100 metachronous [15.5%]). The cumulative incidence rate steadily increased during the follow-up period. More than 50% of the tumors that developed at the same longitudinal location of the stomach were of the same macroscopic and histological type as the primary lesions. Conclusions Because synchronous and/or metachronous gastric tumors are common, considerable attention should be paid to detect multiple gastric lesions after ESD of early gastric neoplasm.

Imaging plays an important role in assessing the severity of COVID-19 pneumonia. Recent COVID-19 research indicates that the disease progress propagates from the bottom of the lungs to the top. However, chest radiography (CXR) cannot directly provide a quantitative metric of radiographic opacities, and existing AI-assisted CXR analysis methods do not quantify the regional severity. In this paper, to assist the regional analysis, we developed a fully automated framework using deep learning-based four-region segmentation and detection models to assist the quantification of COVID-19 pneumonia. Specifically, a segmentation model is first applied to separate left and right lungs, and then a detection network of the carina and left hilum is used to separate upper and lower lungs. To improve the segmentation performance, an ensemble strategy with five models is exploited. We evaluated the clinical relevance of the proposed method compared with the radiographic assessment of the quality of lung edema (RALE) annotated by physicians. Mean intensities of segmented four regions indicate a positive correlation to the regional extent and density scores of pulmonary opacities based on the RALE. Therefore, the proposed method can accurately assist the quantification of regional pulmonary opacities of COVID-19 pneumonia patients.

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.

Abstract Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells. Moreover, these chemokines were significantly increased in the sera of acute hepatitis A patients. The production of IFN-λs was also robustly induced by HAV infection, and the blocking of secreted IFN-λs partially abrogated the production of CCL4 and CCL5 in HAV-infected cells. However, CXCL10 production was not decreased by the blocking of IFN-λs. Instead, CXCL10 production was reduced by silencing the expression of RIG-I-like receptor (RLR) signal molecules, such as mitochondrial antiviral signaling protein and interferon regulatory factor 3, in HAV-infected cells. In conclusion, HAV infection strongly induces the production of helper 1 T cell-associated chemokines, particularly CXCL10 via RLR signaling, even without secreted IFNs.

Background/AimsTo evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon-based therapy in a real-world setting.Methods : This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy.Results : In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in non-genotype 1 patients.Conclusion : sApproximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs.

Background/Aims:Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. Methods:Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). Results:The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p

The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84-5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000).Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.ClinicalTrials.gov NCT01732367.

Background/AimsGiven the characteristic procedures involved in the endoscopy unit, the spread of pathogens is much more frequent in this unit than in other environments. However, there is a lack of data elucidating the existence of pathogens in the endoscopy unit. The aim of this study was to detect the presence of possible pathogens in the endoscopy unit.MethodsWe performed environmental culture using samples from the endoscopy rooms of 2 tertiary hospitals. We used sterile cotton-tipped swabs moistened with sterile saline to swab the surfaces of 197 samples. Then, we cultured the swab in blood agar plate. Samples from the colonoscopy room were placed in thioglycollate broth to detect the presence of anaerobes. After 2 weeks of culture period, we counted the colony numbers.ResultsThe most commonly contaminated spots were the doctor's keyboard, nurse's cart, and nurse's mouse. The common organisms found were non-pathogenic bacterial microorganisms Staphylococcus, Micrococcus, and Streptococcus spp.. No definite anaerobe organism was detected in the colonoscopy room.ConclusionsAlthough the organisms detected in the endoscopy unit were mainly non-pathogenic organisms, they might cause opportunistic infections in immunocompromised patients. Therefore, the environment of the endoscopy room should be managed appropriately; moreover, individual hand hygiene is important for preventing possible hospital-acquired infections.

Background/AimsThis retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.MethodsBetween January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.ResultsOf the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P

A major cause of cirrhosis related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Less common causes of gastrointestinal bleeding are peptic ulcers, malignancy, angiodysplasia, etc. Upper gastrointestinal bleeding has been classified according to the presence of a variceal or non-variceal bleeding. Although non-variceal gastrointestinal bleeding is not common in cirrhotic patients, gastroduodenal ulcers may develop as often as non-cirrhotic patients. Ulcers in cirrhotic patients may be more severe and less frequently associated with chronic intake of non-steroidal anti-inflammatory drugs, and may require more frequently endoscopic treatment. Portal hypertensive gastropathy (PHG) refers to changes in the mucosa of the stomach in patients with portal hypertension. Patients with portal hypertension may experience bleeding from the stomach, and pharmacologic or radiologic interventional procedure may be useful in preventing re-bleeding from PHG. Gastric antral vascular ectasia (GAVE) seems to be different disease entity from PHG, and endoscopic ablation can be the first-line treatment.

Article: Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients with Advanced Liver Disease (Gastroenterology 2015;149:649-659)

The pathogenesis of nonalcoholic steatohepatitis (NASH) is unclear, despite epidemiological data implicating FFAs. We studied the pathogenesis of NASH using lipoapoptosis models. Palmitic acid (PA) induced classical apoptosis of hepatocytes. PA-induced lipoapoptosis was inhibited by acyl-CoA synthetase inhibitor but not by ceramide synthesis inhibitors, suggesting that conversion products other than ceramide are involved. Phospholipase A2 (PLA2) inhibitors blocked PA-induced hepatocyte death, suggesting an important role for PLA2 and its product lysophosphatidylcholine (LPC). Small interfering RNA for Ca2+-independent phospholipase A2 (iPLA2) inhibited the lipoapoptosis of hepatocytes. PA increased LPC content, which was reversed by iPLA2 inhibitors. Pertussis toxin or dominant-negative Gαi mutant inhibited hepatocyte death by PA or LPC acting through G-protein-coupled receptor (GPCR)/Gαi. PA decreased cardiolipin content and induced mitochondrial potential loss and cytochrome c translocation. Oleic acid inhibited PA-induced hepatocyte death by diverting PA to triglyceride and decreasing LPC content, suggesting that FFAs lead to steatosis or lipoapoptosis according to the abundance of saturated/unsaturated FFAs. LPC administration induced hepatitis in vivo. LPC content was increased in the liver specimens from NASH patients. These results demonstrate that LPC is a death effector in the lipoapoptosis of hepatocytes and suggest potential therapeutic values of PLA2 inhibitors or GPCR/Gαi inhibitors in NASH.

Irisin is a recently found myokine that aids obesity control and improves glucose homeostasis by acting on white adipose tissue cells and increases total energy consumption. The aim of this study was to evaluate serum irisin levels in patients with non-alcoholic fatty liver disease (NAFLD) and to compare these levels with those of normal controls. Among 595 health screen examinees who had visited our institute between January 2013 to March 2013, 355 patients (84 NAFLD patients and 271 normal controls) were enrolled depending on whether they gave written informed consents and their history of alcohol intake, blood tests, and abdominal ultrasonographic findings. Age; sex; laboratory test parameters; homeostasis model assessment-insulin resistance; and levels of leptin, adiponectin, and irisin were assessed. Serum irisin levels (ng/ml) were significantly higher in the NAFLD group than in normal controls (63.4 ± 32.6 vs. 43.0 ± 29.7, p

Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis.LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (p = 0.039) and tended to be related with longer time to recurrence (TTR) (p=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; p-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33-0.90; p=0.017). Expression of LC3 in advanced stages of TNM (III) (p=0.045) and Edmonson-Steiner Grades (III and IV) (p=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.