Patients with advanced liver cirrhosis and liver failure frequently experience abnormalities in their serum electrolyte levels.In such patients,hyponatremia has been identified as a predictor of poor outcomes.However,...Patients with advanced liver cirrhosis and liver failure frequently experience abnormalities in their serum electrolyte levels.In such patients,hyponatremia has been identified as a predictor of poor outcomes.However,emerging evidence suggests that serum chloride may provide even better prognostic information in similar situations.Hypochloremia,characterised by low serum chloride levels,has been linked to increased mortality,exacerbated organ dysfunction,and higher requirements for renal replacement therapy and vasopressors in various critical conditions,including advanced liver diseases.The pathophysiological mecha-nisms underlying the association between low serum chloride levels and poor outcomes in liver disease appear to involve complex interactions among electro-lyte imbalances,renal function,and systemic hemodynamics.Chloride dysregu-lation can influence renal salt-sensing mechanisms,disrupt acid-base homeostasis,and exacerbate complications such as hepatic encephalopathy and hepatorenal syndrome.This article aims to elucidate the prognostic significance of lower serum chloride levels in patients with advanced liver disease.By reviewing recent literature and analysing clinical data,we seek to establish serum chloride as an underutilised but valuable prognostic marker.Understanding the role of serum chloride in liver disease could enhance prognostic accuracy,refine treatment strategies,and ultimately improve patient outcomes.展开更多
Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of...Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.展开更多
Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets it...Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets itself apart from existing research by applying a novel optimization technique to a basic ideal Rankine cycle,focusing on a specific power plant that has not been previously analyzed.Currently,this cycle operates at 41%efficiency and a steam quality of 76%,constrained by fixed operational parameters.The primary objectives are to increase thermal efficiency beyond 46%and raise steam quality above 85%,while adhering to operational limits:a boiler pressure not exceeding 15 MPa,condenser pressure not dropping below 10 kPa,and turbine temperature not surpassing 500℃.This study utilizes numerical simulations to model the effects of varying boiler pressure(Pb)and condenser pressure(Pc)within the ranges of 12MPa<Pb<15 MPa and 5 kPa<Pc<10 kPa.By systematically adjusting these parameters,the proposed aimto identify optimal conditions that maximize efficiency and performance within specified constraints.The findings will provide valuable insights for power plant operators seeking to optimize performance under real-world conditions,contributing to more efficient and sustainable power generation.展开更多
Nodal pricing is a critical mechanism in electricity markets,utilized to determine the cost of power transmission to various nodes within a distribution network.As power systems evolve to incorporate higher levels of ...Nodal pricing is a critical mechanism in electricity markets,utilized to determine the cost of power transmission to various nodes within a distribution network.As power systems evolve to incorporate higher levels of renewable energy and face increasing demand fluctuations,traditional nodal pricing models often fall short to meet these new challenges.This research introduces a novel enhanced nodal pricing mechanism for distribution networks,integrating advanced optimization techniques and hybrid models to overcome these limitations.The primary objective is to develop a model that not only improves pricing accuracy but also enhances operational efficiency and system reliability.This study leverages cutting-edge hybrid algorithms,combining elements of machine learning with conventional optimization methods,to achieve superior performance.Key findings demonstrate that the proposed hybrid nodal pricing model significantly reduces pricing errors and operational costs compared to conventional methods.Through extensive simulations and comparative analysis,the model exhibits enhanced performance under varying load conditions and increased levels of renewable energy integration.The results indicate a substantial improvement in pricing precision and network stability.This study contributes to the ongoing discourse on optimizing electricity market mechanisms and provides actionable insights for policymakers and utility operators.By addressing the complexities of modern power distribution systems,our research offers a robust solution that enhances the efficiency and reliability of power distribution networks,marking a significant advancement in the field.展开更多
Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of fi...Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of first-line anti-TB drugs(ATDs)-particularly isoniazid,rifampicin,and pyrazinamide-poses a considerable risk,as these agents are associated with a significant incidence of ATD-induced liver injury(AT-DILI).The clinical presentation of AT-DILI can range from asymptomatic elevations in serum transaminases,which may resolve spontaneously due to hepatic adaptation,to acute liver failure(ALF),a potentially life-threatening condition.A recent meta-analysis reported a global incidence of AT-DILI of 11.5%,with rates varying from 2%to 28%.Approximately 7%of patients with AT-DILI progress to ALF,a condition characterized by a poor survival rate with medical therapy.ATD-induced ALF(AT-ALF)is clinically indistinguishable from ALF due to other causes and disproportionately affects young female patients,typically within eight weeks of treatment initiation.Emergency liver transplantation has become an effective therapeutic option for AT-ALF,although outcomes are generally poorer compared to elective transplantation.This minireview provides a comprehensive overview of AT-ALF,covering its epidemiology,risk factors,clinical presentation,prognosis,and treatment options.展开更多
The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications direct...The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications directly addressing the research problem at hand.Similarly,while the body of work on optimal location and sizing of renewable energy generators(REGs)in balanced distribution systems is substantial,only the most pertinent sources are cited,aligning closely with the study’s objective function.A comprehensive literature review reveals several key research areas:RES integration,RES-related optimization techniques,strategic placement of wind and solar generation,and RES promotion in deregulated powermarkets,particularly within transmission systems.Furthermore,the optimal location and sizing of REGs in both balanced and unbalanced distribution systems have been extensively studied.RESs demonstrate significant potential for standalone applications in remote areas lacking conventional transmission and distribution infrastructure.Also presents a thorough review of current modeling and optimization approaches for RES-based distribution system location and sizing.Additionally,it examines the optimal positioning,sizing,and performance of hybrid and standalone renewable energy systems.This paper provides a comprehensive review of current modeling and optimization approaches for the location and sizing of Renewable Energy Sources(RESs)in distribution systems,focusing on both balanced and unbalanced networks.展开更多
In liver cirrhosis patients,acute kidney injury(AKI)is a common and severe complication associated with significant morbidity and mortality,often leading to chronic kidney disease(CKD).This progression reflects a comp...In liver cirrhosis patients,acute kidney injury(AKI)is a common and severe complication associated with significant morbidity and mortality,often leading to chronic kidney disease(CKD).This progression reflects a complex interplay of renal and hepatic pathophysiology,with AKI acting as an initiator through maladaptive repair mechanisms.These mechanisms—such as tubular cell cycle arrest,inflammatory cascades,and fibrotic processes—are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis.Following AKI episodes,persistent kidney dysfunction or acute kidney disease(AKD)often serves as a bridge to CKD.AKD represents a critical phase in renal deterioration,characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI.The progression from AKD to CKD is further influenced by recurrent AKI episodes,impaired renal autoregu-lation,and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease,which compound kidney damage.The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury,the application of novel biomarkers,and precision interventions.Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression,necessitating novel biomarkers for early detection and intervention.展开更多
Acute liver failure(ALF)and acute-on-chronic LF(ACLF)are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections(BI),despite significant systemic inflammation.Literature indi...Acute liver failure(ALF)and acute-on-chronic LF(ACLF)are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections(BI),despite significant systemic inflammation.Literature indicates that 30%–80%of ALF patients and 55%–81%of ACLF patients develop BI,attributed to immu-nological dysregulation.Bacterial sepsis in these patients is associated with adverse clinical outcomes,including prolonged hospitalization and increased mortality.Early detection of bacterial sepsis is critical;however,distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis.Conventional sepsis biomarkers,such as procalcitonin and C-reactive protein,have shown limited utility in LF patients due to inconsistent results.In contrast,novel biomarkers like presepsin and sTREM-1 have demonstrated promising discrim-inatory performance in this population,pending further validation.Moreover,emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization.Although preliminary findings are encouraging,further studies are necessary to validate these results across diverse patient cohorts,including those with LF.This article provides a compre-hensive review of the magnitude,impact,and diagnostic challenges associated with BI in LF patients,focusing on novel advancements in early sepsis detection and characterization.展开更多
Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects ...Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.展开更多
Chronic kidney disease(CKD)in patients with liver cirrhosis has become a new frontier in hepatology.In recent years,a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis.The rising p...Chronic kidney disease(CKD)in patients with liver cirrhosis has become a new frontier in hepatology.In recent years,a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis.The rising prevalence of risk factors,such as diabetes,hypertension and nonalcoholic fatty liver disease,appears to have contributed significantly to the high prevalence of CKD.Moreover,the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of<60 mL/min over more than 3 mo.This definition has resulted in a better differentiation of CKD from acute kidney injury(AKI),leading to its greater recognition.It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis.CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances.The available literature on combined cirrhosis-CKD is extremely limited,as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI.Due to problems related to glomerular filtration rate estimation in cirrhosis,the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis,CKD in cirrhosis can present many challenges for clinicians.With combined hepatorenal dysfunctions,fluid mobilization becomes problematic,and there may be difficulties with drug tolerance,hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation.This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis,with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.展开更多
Patients with liver cirrhosis are advised to limit their sodium consumption to control excessive fluid accumulation.Salt is the most common form in which sodium is consumed daily.Consequently,various recommendations u...Patients with liver cirrhosis are advised to limit their sodium consumption to control excessive fluid accumulation.Salt is the most common form in which sodium is consumed daily.Consequently,various recommendations urge patients to limit salt intake.However,there is a lack of consistency regarding salt restriction across the guidelines.Moreover,there is conflicting evidence regarding the efficacy of salt restriction in the treatment of ascites.Numerous studies have shown that there is no difference in ascites control between patients with restriction of salt intake and those without restriction.Moreover,patients with cirrhosis may have several negative effects from consuming too little salt,although there are no recommendations on the lower limit of salt intake.Sodium is necessary to maintain the extracellular fluid volume;hence,excessive salt restriction can result in volume contraction,which could negatively impact kidney function in a cirrhotic patient.Salt restriction in cirrhotic patients can also compromise nutrient intake,which can have a negative impact on the overall outcome.There is insufficient evidence to recommend restricted salt intake for all patients with cirrhosis,including those with severe hyponatremia.The existing guidelines on salt restriction do not consider the salt sensitivity of patients;their nutritional state,volume status and sodium storage sites;and the risk of hypochloremia.This opinion article aims to critically analyze the existing literature with regard to salt recommendations for patients with liver cirrhosis and identify potential knowledge gaps that call for further research.展开更多
Amebic liver abscess(ALA)is still a common problem in the tropical world,where it affects over three-quarters of patients with liver abscess.It is caused by an anaerobic protozoan Entamoeba hystolytica,which primarily...Amebic liver abscess(ALA)is still a common problem in the tropical world,where it affects over three-quarters of patients with liver abscess.It is caused by an anaerobic protozoan Entamoeba hystolytica,which primarily colonises the cecum.It is a non-suppurative infection of the liver consisting primarily of dead hepatocytes and cellular debris.People of the male gender,during their reproductive years,are most prone to ALA,and this appears to be due to a poorly mounted immune response linked to serum testosterone levels.ALA is more common in the right lobe of the liver,is strongly associated with alcohol consumption,and can heal without the need for drainage.While majority of ALA patients have an uncomplicated course,a number of complications have been described,including rupture into abdomino-thoracic structures,biliary fistula,vascular thrombosis,bilio-vascular compression,and secondary bacterial infection.Based on clinico-radiological findings,a classification system for ALA has emerged recently,which can assist clinicians in making treatment decisions.Recent research has revealed the role of venous thrombosis-related ischemia in the severity of ALA.Recent years have seen the development and refinement of newer molecular diagnostic techniques that can greatly aid in overcoming the diagnostic challenge in endemic area where serology-based tests have limited accuracy.Metronidazole has been the drug of choice for ALA patients for many years.However,concerns over the resistance and adverse effects necessitate the creation of new,safe,and potent antiamebic medications.Although the indication of the drainage of uncomplicated ALA has become more clear,high-quality randomised trials are still necessary for robust conclusions.Percutaneous drainage appears to be a viable option for patients with ruptured ALA and diffuse peritonitis,for whom surgery represents a significant risk of mortality.With regard to all of the aforementioned issues,this article intends to present an updated review of ALA.展开更多
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes...Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.展开更多
BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a...BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.展开更多
In its classic form,amebic liver abscess(ALA)is a mild disease,which responds dramatically to antibiotics and rarely requires drainage.However,the two other forms of the disease,i.e.,acute aggressive and chronic indol...In its classic form,amebic liver abscess(ALA)is a mild disease,which responds dramatically to antibiotics and rarely requires drainage.However,the two other forms of the disease,i.e.,acute aggressive and chronic indolent usually require drainage.These forms of ALA are frequently reported in endemic areas.The acute aggressive disease is particularly associated with serious complications,such as ruptures,secondary infections,and biliary communications.Laboratory parameters are deranged,with signs of organ failure often present.This form of disease is also associated with a high mortality rate,and early drainage is often required to control the disease severity.In the chronic form,the disease is characterized by low-grade symptoms,mainly pain in the right upper quadrant.Ultrasound and computed tomography(CT)play an important role not only in the diagnosis but also in the assessment of disease severity and identification of the associated complications.Recently,it has been shown that CT imaging morphology can be classified into three patterns,which seem to correlate with the clinical subtypes.Each pattern depicts its own set of distinctive imaging features.In this review,we briefly outline the clinical and imaging features of the three distinct forms of ALA,and discuss the role of percutaneous drainage in the management of ALA.展开更多
BACKGROUND Platelet transfusion in acute variceal bleeding(AVB)is recommended by few guidelines and is common in routine clinical practice,even though the effect of thrombocytopenia and platelet transfusion on the out...BACKGROUND Platelet transfusion in acute variceal bleeding(AVB)is recommended by few guidelines and is common in routine clinical practice,even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear.AIM To determine how platelet counts,platelets transfusions,and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control,rebleeding,and mortality.METHODS Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB.The outcomes were assessed as the risk of rebleeding at days 5 and 42,and risk of death at day 42,considering the platelet counts and platelet transfusion.Propensity score matching(PSM)was used to compare the outcomes in those who received platelet transfusion.Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Coxproportional hazard model for rebleeding and for 42-d mortality.RESULTS The study included 913 patients,with 83.5%men,median age 45 years,and Model for End-stage Liver Disease score 14.7.Platelet count<20×10^(9)/L,20-50×10^(9)/L,and>50×10^(9)/L were found in 23(2.5%),168(18.4%),and 722(79.1%)patients,respectively.Rebleeding rates were similar between the three platelet groups on days 5 and 42(13%,6.5%,and 4.7%,respectively,on days 5,P=0.150;and 21.7%,17.3%,and 14.4%,respectively,on days 42,P=0.433).At day 42,the mortality rates for the three platelet groups were also similar(13.0%,23.2%,and 17.2%,respectively,P=0.153).On PSM analysis patients receiving platelets transfusions(n=89)had significantly higher rebleeding rates on day 5(14.6%vs 4.5%;P=0.039)and day 42(32.6%vs 15.7%;P=0.014),compared to those who didn't.The mortality rates were also higher among patients receiving platelets(25.8%vs 23.6%;P=0.862),although the difference was not significant.On multivariate analysis,platelet transfusion and not platelet count,was independently associated with 42-d rebleeding.Hepatic encephalopathy was independently associated with 42-d mortality.CONCLUSION Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB;however,platelet transfusion increased rebleeding on days 5 and 42,with a higher but nonsignificant effect on mortality.展开更多
BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.MET...BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.展开更多
Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,ne...Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,nephropathy,retinopathy,cardiovascular disorders,and diabetic foot ulcers.Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications.Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase,heme oxygenase-1,superoxide dismutase,and catalase that are essential in maintaining redox balance,and ameliorate oxidative stress.Caffeic acid(CA)is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties including antioxidant,anti-inflammatory,anti-atherosclerotic,immune-stimulatory,cardioprotective,antiproliferative,and hepatoprotective activities.CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets.These include various transcription factors such as nuclear factor-B,tumor necrosis factor-α,interleukin-6,cyclooxygenase-2,and nuclear factor erythroid 2-related factor 2.Therefore,this review summarizes the pharmacological properties,molecular mechanisms,and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications.The bioavailability,drug delivery,and clinical trials of CA have also been discussed.展开更多
The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a conse...The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.展开更多
Acute liver failure(ALF)refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease.ALF has different causes,but the clinical characteristics...Acute liver failure(ALF)refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease.ALF has different causes,but the clinical characteristics are strikingly similar.In clinical practice,however,inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas.ALF mortality rates used to be over 80%in the past;however,survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management.The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates.Given that liver transplantation(LT)is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression,it is very important to select accurate patients who may benefit from it.Still,emergency LT remains a lifesaving procedure for many ALF patients.However,there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner.The other problems associated with LT in ALF are the shortage of graft,development of contraindications on the waiting list,vaguely defined delisting criteria,time constraints for pre-transplant evaluation,ethical concerns,and comparatively poor post-transplant outcomes in ALF.Therefore,there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies,such as liver support systems,plasma exchange,stem cells,auxiliary LT,and so on,to enhance transplant-free survival and to fill the void created by the graft shortage.展开更多
文摘Patients with advanced liver cirrhosis and liver failure frequently experience abnormalities in their serum electrolyte levels.In such patients,hyponatremia has been identified as a predictor of poor outcomes.However,emerging evidence suggests that serum chloride may provide even better prognostic information in similar situations.Hypochloremia,characterised by low serum chloride levels,has been linked to increased mortality,exacerbated organ dysfunction,and higher requirements for renal replacement therapy and vasopressors in various critical conditions,including advanced liver diseases.The pathophysiological mecha-nisms underlying the association between low serum chloride levels and poor outcomes in liver disease appear to involve complex interactions among electro-lyte imbalances,renal function,and systemic hemodynamics.Chloride dysregu-lation can influence renal salt-sensing mechanisms,disrupt acid-base homeostasis,and exacerbate complications such as hepatic encephalopathy and hepatorenal syndrome.This article aims to elucidate the prognostic significance of lower serum chloride levels in patients with advanced liver disease.By reviewing recent literature and analysing clinical data,we seek to establish serum chloride as an underutilised but valuable prognostic marker.Understanding the role of serum chloride in liver disease could enhance prognostic accuracy,refine treatment strategies,and ultimately improve patient outcomes.
文摘Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.
文摘Enhancing the efficiency of Rankine cycles is crucial for improving the performance of thermal power plants,as it directly impacts operational costs and emissions in light of energy transition goals.This study sets itself apart from existing research by applying a novel optimization technique to a basic ideal Rankine cycle,focusing on a specific power plant that has not been previously analyzed.Currently,this cycle operates at 41%efficiency and a steam quality of 76%,constrained by fixed operational parameters.The primary objectives are to increase thermal efficiency beyond 46%and raise steam quality above 85%,while adhering to operational limits:a boiler pressure not exceeding 15 MPa,condenser pressure not dropping below 10 kPa,and turbine temperature not surpassing 500℃.This study utilizes numerical simulations to model the effects of varying boiler pressure(Pb)and condenser pressure(Pc)within the ranges of 12MPa<Pb<15 MPa and 5 kPa<Pc<10 kPa.By systematically adjusting these parameters,the proposed aimto identify optimal conditions that maximize efficiency and performance within specified constraints.The findings will provide valuable insights for power plant operators seeking to optimize performance under real-world conditions,contributing to more efficient and sustainable power generation.
文摘Nodal pricing is a critical mechanism in electricity markets,utilized to determine the cost of power transmission to various nodes within a distribution network.As power systems evolve to incorporate higher levels of renewable energy and face increasing demand fluctuations,traditional nodal pricing models often fall short to meet these new challenges.This research introduces a novel enhanced nodal pricing mechanism for distribution networks,integrating advanced optimization techniques and hybrid models to overcome these limitations.The primary objective is to develop a model that not only improves pricing accuracy but also enhances operational efficiency and system reliability.This study leverages cutting-edge hybrid algorithms,combining elements of machine learning with conventional optimization methods,to achieve superior performance.Key findings demonstrate that the proposed hybrid nodal pricing model significantly reduces pricing errors and operational costs compared to conventional methods.Through extensive simulations and comparative analysis,the model exhibits enhanced performance under varying load conditions and increased levels of renewable energy integration.The results indicate a substantial improvement in pricing precision and network stability.This study contributes to the ongoing discourse on optimizing electricity market mechanisms and provides actionable insights for policymakers and utility operators.By addressing the complexities of modern power distribution systems,our research offers a robust solution that enhances the efficiency and reliability of power distribution networks,marking a significant advancement in the field.
文摘Tuberculosis(TB)is still a major public health issue in developing countries,where it causes a heavy disease burden.Although current anti-TB treatment regimens demonstrate high efficacy,the hepatotoxic potential of first-line anti-TB drugs(ATDs)-particularly isoniazid,rifampicin,and pyrazinamide-poses a considerable risk,as these agents are associated with a significant incidence of ATD-induced liver injury(AT-DILI).The clinical presentation of AT-DILI can range from asymptomatic elevations in serum transaminases,which may resolve spontaneously due to hepatic adaptation,to acute liver failure(ALF),a potentially life-threatening condition.A recent meta-analysis reported a global incidence of AT-DILI of 11.5%,with rates varying from 2%to 28%.Approximately 7%of patients with AT-DILI progress to ALF,a condition characterized by a poor survival rate with medical therapy.ATD-induced ALF(AT-ALF)is clinically indistinguishable from ALF due to other causes and disproportionately affects young female patients,typically within eight weeks of treatment initiation.Emergency liver transplantation has become an effective therapeutic option for AT-ALF,although outcomes are generally poorer compared to elective transplantation.This minireview provides a comprehensive overview of AT-ALF,covering its epidemiology,risk factors,clinical presentation,prognosis,and treatment options.
文摘The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications directly addressing the research problem at hand.Similarly,while the body of work on optimal location and sizing of renewable energy generators(REGs)in balanced distribution systems is substantial,only the most pertinent sources are cited,aligning closely with the study’s objective function.A comprehensive literature review reveals several key research areas:RES integration,RES-related optimization techniques,strategic placement of wind and solar generation,and RES promotion in deregulated powermarkets,particularly within transmission systems.Furthermore,the optimal location and sizing of REGs in both balanced and unbalanced distribution systems have been extensively studied.RESs demonstrate significant potential for standalone applications in remote areas lacking conventional transmission and distribution infrastructure.Also presents a thorough review of current modeling and optimization approaches for RES-based distribution system location and sizing.Additionally,it examines the optimal positioning,sizing,and performance of hybrid and standalone renewable energy systems.This paper provides a comprehensive review of current modeling and optimization approaches for the location and sizing of Renewable Energy Sources(RESs)in distribution systems,focusing on both balanced and unbalanced networks.
文摘In liver cirrhosis patients,acute kidney injury(AKI)is a common and severe complication associated with significant morbidity and mortality,often leading to chronic kidney disease(CKD).This progression reflects a complex interplay of renal and hepatic pathophysiology,with AKI acting as an initiator through maladaptive repair mechanisms.These mechanisms—such as tubular cell cycle arrest,inflammatory cascades,and fibrotic processes—are exacerbated by the hemodynamic and neurohormonal disturbances characteristic of cirrhosis.Following AKI episodes,persistent kidney dysfunction or acute kidney disease(AKD)often serves as a bridge to CKD.AKD represents a critical phase in renal deterioration,characterized by prolonged kidney injury that does not fully meet CKD criteria but exceeds the temporal scope of AKI.The progression from AKD to CKD is further influenced by recurrent AKI episodes,impaired renal autoregu-lation,and systemic comorbidities such as diabetes and metabolic dysfunction-associated steatotic liver disease,which compound kidney damage.The clinical management of AKI and CKD in cirrhotic patients requires a multidimensional approach that includes early identification of kidney injury,the application of novel biomarkers,and precision interventions.Recent evidence underscores the inadequacy of traditional biomarkers in predicting the AKI-to-CKD progression,necessitating novel biomarkers for early detection and intervention.
文摘Acute liver failure(ALF)and acute-on-chronic LF(ACLF)are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections(BI),despite significant systemic inflammation.Literature indicates that 30%–80%of ALF patients and 55%–81%of ACLF patients develop BI,attributed to immu-nological dysregulation.Bacterial sepsis in these patients is associated with adverse clinical outcomes,including prolonged hospitalization and increased mortality.Early detection of bacterial sepsis is critical;however,distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis.Conventional sepsis biomarkers,such as procalcitonin and C-reactive protein,have shown limited utility in LF patients due to inconsistent results.In contrast,novel biomarkers like presepsin and sTREM-1 have demonstrated promising discrim-inatory performance in this population,pending further validation.Moreover,emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization.Although preliminary findings are encouraging,further studies are necessary to validate these results across diverse patient cohorts,including those with LF.This article provides a compre-hensive review of the magnitude,impact,and diagnostic challenges associated with BI in LF patients,focusing on novel advancements in early sepsis detection and characterization.
文摘Diabetes mellitus(DM)is common in liver cirrhosis(LC).The pathophysiological association is bidirectional.DM is a risk factor of LC and LC is a diabetogenic condition.In the recent years,research on different aspects of the association DM and LC has been intensified.Nevertheless,it has been insufficient and still exist many gaps.The aims of this review are:(1)To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis;(2)To evaluate the impact of DM on outcomes of LC patients;and(3)To select the most adequate management benefiting the two conditions.Literature searches were conducted using Pub Med,Ovid and Scopus engines for DM and LC,diagnosis,outcomes and management.The authors also provided insight from their own published experience.Based on the published studies,two types of DM associated with LC have emerged:Type 2 DM(T2 DM)and hepatogenous diabetes(HD).High-quality evidences have determined that T2 DM or HD significantly increase complications and death pre and post-liver transplantation.HD has been poorly studied and has not been recognized as a complication of LC.The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure.In conclusion,the clinical impact of DM in outcomes of LC patients has been the most studied item recently.Nevertheless many gaps still exist particularly in the management.These most important gaps were highlighted in order to propose future lines for research.
文摘Chronic kidney disease(CKD)in patients with liver cirrhosis has become a new frontier in hepatology.In recent years,a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis.The rising prevalence of risk factors,such as diabetes,hypertension and nonalcoholic fatty liver disease,appears to have contributed significantly to the high prevalence of CKD.Moreover,the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of<60 mL/min over more than 3 mo.This definition has resulted in a better differentiation of CKD from acute kidney injury(AKI),leading to its greater recognition.It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis.CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances.The available literature on combined cirrhosis-CKD is extremely limited,as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI.Due to problems related to glomerular filtration rate estimation in cirrhosis,the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis,CKD in cirrhosis can present many challenges for clinicians.With combined hepatorenal dysfunctions,fluid mobilization becomes problematic,and there may be difficulties with drug tolerance,hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation.This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis,with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.
文摘Patients with liver cirrhosis are advised to limit their sodium consumption to control excessive fluid accumulation.Salt is the most common form in which sodium is consumed daily.Consequently,various recommendations urge patients to limit salt intake.However,there is a lack of consistency regarding salt restriction across the guidelines.Moreover,there is conflicting evidence regarding the efficacy of salt restriction in the treatment of ascites.Numerous studies have shown that there is no difference in ascites control between patients with restriction of salt intake and those without restriction.Moreover,patients with cirrhosis may have several negative effects from consuming too little salt,although there are no recommendations on the lower limit of salt intake.Sodium is necessary to maintain the extracellular fluid volume;hence,excessive salt restriction can result in volume contraction,which could negatively impact kidney function in a cirrhotic patient.Salt restriction in cirrhotic patients can also compromise nutrient intake,which can have a negative impact on the overall outcome.There is insufficient evidence to recommend restricted salt intake for all patients with cirrhosis,including those with severe hyponatremia.The existing guidelines on salt restriction do not consider the salt sensitivity of patients;their nutritional state,volume status and sodium storage sites;and the risk of hypochloremia.This opinion article aims to critically analyze the existing literature with regard to salt recommendations for patients with liver cirrhosis and identify potential knowledge gaps that call for further research.
文摘Amebic liver abscess(ALA)is still a common problem in the tropical world,where it affects over three-quarters of patients with liver abscess.It is caused by an anaerobic protozoan Entamoeba hystolytica,which primarily colonises the cecum.It is a non-suppurative infection of the liver consisting primarily of dead hepatocytes and cellular debris.People of the male gender,during their reproductive years,are most prone to ALA,and this appears to be due to a poorly mounted immune response linked to serum testosterone levels.ALA is more common in the right lobe of the liver,is strongly associated with alcohol consumption,and can heal without the need for drainage.While majority of ALA patients have an uncomplicated course,a number of complications have been described,including rupture into abdomino-thoracic structures,biliary fistula,vascular thrombosis,bilio-vascular compression,and secondary bacterial infection.Based on clinico-radiological findings,a classification system for ALA has emerged recently,which can assist clinicians in making treatment decisions.Recent research has revealed the role of venous thrombosis-related ischemia in the severity of ALA.Recent years have seen the development and refinement of newer molecular diagnostic techniques that can greatly aid in overcoming the diagnostic challenge in endemic area where serology-based tests have limited accuracy.Metronidazole has been the drug of choice for ALA patients for many years.However,concerns over the resistance and adverse effects necessitate the creation of new,safe,and potent antiamebic medications.Although the indication of the drainage of uncomplicated ALA has become more clear,high-quality randomised trials are still necessary for robust conclusions.Percutaneous drainage appears to be a viable option for patients with ruptured ALA and diffuse peritonitis,for whom surgery represents a significant risk of mortality.With regard to all of the aforementioned issues,this article intends to present an updated review of ALA.
文摘Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.
基金financial support from University Grants Commission, New Delhi, India in the form of UGC-Junior Research Fellowship and Senior Research Fellowshipfinancial support from Council of Scientific & Industrial Research, New Delhi, India in the form of CSIR Junior Research Fellowship and Senior Research Fellowship
文摘BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors.Long-term fluoxetine treatment results in hepatotoxicity.Baicalin,a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant,hepatoprotective and anti-inflammatory effects.However,the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODS Male albino Wistar rats were divided into seven groups.Group 1 was the normal control.Oral fluoxetine was administered at 10 mg/kg body weight to groups 2,3,4 and 5.In addition,groups 3 and 4 were also co-administered oral baicalin(50 mg/kg and 100 mg/kg,respectively)while group 5 received silymarin(100 mg/kg),a standard hepatoprotective compound for comparison.Groups 6 and 7 were used as a positive control for baicalin(100 mg/kg)and silymarin(100 mg/kg),respectively.All treatments were carried out for 28 d.After sacrifice of the rats,biomarkers of oxidative stress[superoxide dismutase(SOD),catalase(CAT),reduced glutathione(GSH),glutathione-S-transferase(GST),advanced oxidation protein products(AOPP),malondialdehyde(MDA)],and liver injury[alanine transaminase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),total protein,albumin,bilirubin]were studied in serum and tissue using standard protocols and diagnostic kits.Inflammatory markers[tumor necrosis factor(TNF-α),interleukin(IL)-6,IL-10 and interferon(IFN)-γ]in serum were evaluated using ELISA-based kits.The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers(total bilirubin,ALT,AST,and ALP)and inflammatory markers(TNF-α,IL-6,IL-10 and IFN-γ),with a decline in total protein and albumin levels.Biochemical markers of oxidative stress such as SOD,CAT,GST,GSH,MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage.Histological examination of liver tissue also showed degeneration of hepatocytes.Concurrent administration of baicalin(50 and 100 mg/kg)restored the biomarkers of oxidative stress,inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage.Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.
文摘In its classic form,amebic liver abscess(ALA)is a mild disease,which responds dramatically to antibiotics and rarely requires drainage.However,the two other forms of the disease,i.e.,acute aggressive and chronic indolent usually require drainage.These forms of ALA are frequently reported in endemic areas.The acute aggressive disease is particularly associated with serious complications,such as ruptures,secondary infections,and biliary communications.Laboratory parameters are deranged,with signs of organ failure often present.This form of disease is also associated with a high mortality rate,and early drainage is often required to control the disease severity.In the chronic form,the disease is characterized by low-grade symptoms,mainly pain in the right upper quadrant.Ultrasound and computed tomography(CT)play an important role not only in the diagnosis but also in the assessment of disease severity and identification of the associated complications.Recently,it has been shown that CT imaging morphology can be classified into three patterns,which seem to correlate with the clinical subtypes.Each pattern depicts its own set of distinctive imaging features.In this review,we briefly outline the clinical and imaging features of the three distinct forms of ALA,and discuss the role of percutaneous drainage in the management of ALA.
文摘BACKGROUND Platelet transfusion in acute variceal bleeding(AVB)is recommended by few guidelines and is common in routine clinical practice,even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear.AIM To determine how platelet counts,platelets transfusions,and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control,rebleeding,and mortality.METHODS Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB.The outcomes were assessed as the risk of rebleeding at days 5 and 42,and risk of death at day 42,considering the platelet counts and platelet transfusion.Propensity score matching(PSM)was used to compare the outcomes in those who received platelet transfusion.Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Coxproportional hazard model for rebleeding and for 42-d mortality.RESULTS The study included 913 patients,with 83.5%men,median age 45 years,and Model for End-stage Liver Disease score 14.7.Platelet count<20×10^(9)/L,20-50×10^(9)/L,and>50×10^(9)/L were found in 23(2.5%),168(18.4%),and 722(79.1%)patients,respectively.Rebleeding rates were similar between the three platelet groups on days 5 and 42(13%,6.5%,and 4.7%,respectively,on days 5,P=0.150;and 21.7%,17.3%,and 14.4%,respectively,on days 42,P=0.433).At day 42,the mortality rates for the three platelet groups were also similar(13.0%,23.2%,and 17.2%,respectively,P=0.153).On PSM analysis patients receiving platelets transfusions(n=89)had significantly higher rebleeding rates on day 5(14.6%vs 4.5%;P=0.039)and day 42(32.6%vs 15.7%;P=0.014),compared to those who didn't.The mortality rates were also higher among patients receiving platelets(25.8%vs 23.6%;P=0.862),although the difference was not significant.On multivariate analysis,platelet transfusion and not platelet count,was independently associated with 42-d rebleeding.Hepatic encephalopathy was independently associated with 42-d mortality.CONCLUSION Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB;however,platelet transfusion increased rebleeding on days 5 and 42,with a higher but nonsignificant effect on mortality.
基金This study was reviewed and approved by the Ethics Committee of the All India Institute of Medical Sciences,New Delhi(Approval No.IEC/NP-458/12.12.2014,RP 22-2015).
文摘BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.
基金financial support from University Grants Commission/Council of Scientific and Industrial Research,New Delhi,India in the form of UGC/CSIR-Senior Research Fellowships.Shiv Vardan Singh acknowledges UGC for Dr DS Kothani Fellowship.Kntika Jaiswal acknowledges financial support from University Grants Commission,New Dellhi,India in the form of UGC-CRET Fellowship.
文摘Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,nephropathy,retinopathy,cardiovascular disorders,and diabetic foot ulcers.Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications.Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase,heme oxygenase-1,superoxide dismutase,and catalase that are essential in maintaining redox balance,and ameliorate oxidative stress.Caffeic acid(CA)is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties including antioxidant,anti-inflammatory,anti-atherosclerotic,immune-stimulatory,cardioprotective,antiproliferative,and hepatoprotective activities.CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets.These include various transcription factors such as nuclear factor-B,tumor necrosis factor-α,interleukin-6,cyclooxygenase-2,and nuclear factor erythroid 2-related factor 2.Therefore,this review summarizes the pharmacological properties,molecular mechanisms,and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications.The bioavailability,drug delivery,and clinical trials of CA have also been discussed.
文摘The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.
文摘Acute liver failure(ALF)refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease.ALF has different causes,but the clinical characteristics are strikingly similar.In clinical practice,however,inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas.ALF mortality rates used to be over 80%in the past;however,survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management.The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates.Given that liver transplantation(LT)is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression,it is very important to select accurate patients who may benefit from it.Still,emergency LT remains a lifesaving procedure for many ALF patients.However,there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner.The other problems associated with LT in ALF are the shortage of graft,development of contraindications on the waiting list,vaguely defined delisting criteria,time constraints for pre-transplant evaluation,ethical concerns,and comparatively poor post-transplant outcomes in ALF.Therefore,there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies,such as liver support systems,plasma exchange,stem cells,auxiliary LT,and so on,to enhance transplant-free survival and to fill the void created by the graft shortage.
