Amebic liver abscess: An update

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.

Renal resistive index measurements by ultrasound in patients with liver cirrhosis:Magnitude and associations with renal dysfunction

BACKGROUND The hemodynamic alterations seen in liver cirrhosis lead to renal vasoconstriction,ultimately causing acute kidney injury(AKI).The renal resistive index(RRI)is the most common Doppler ultrasound variable for measuring intrarenal vascular resistance.AIM To evaluate the association of the RRI with AKI in patients with liver cirrhosis and to identify risk factors for high RRI.METHODS This was a prospective observational study,where RRI was measured using Doppler ultrasound in 200 consecutive hospitalized patients with cirrhosis.The association of RRI with AKI was studied.The receiver operating characteristic(ROC)curve analysis was utilized to determine discriminatory cut-offs of RRI for various AKI phenotypes.Multivariate analysis was conducted to determine the predictors of high RRI.RESULTS The mean patient age was 49.08±11.68 years,with the majority(79.5%)being male;the predominant etiology of cirrhosis was alcohol(39%).The mean RRI for the study cohort was 0.68±0.09,showing a progressive increase with higher Child-Pugh class of cirrhosis.Overall,AKI was present in 129(64.5%)patients.The mean RRI was significantly higher in patients with AKI compared to those without it(0.72±0.06 vs 0.60±0.08;P<0.001).A total of 82 patients(41%)had hepatorenal syndrome(HRS)-AKI,29(22.4%)had prerenal AKI(PRA),and 18(13.9%)had acute tubular necrosis(ATN)-AKI.The mean RRI was significantly higher in the ATN-AKI(0.80±0.02)and HRS-AKI(0.73±0.03)groups than in the PRA(0.63±0.07)and non-AKI(0.60±0.07)groups.RRI demonstrated excellent discriminatory ability in distinguishing ATN-AKI from non-ATN-AKI(area under ROC curve:93.9%).AKI emerged as an independent predictor of high RRI(adjusted odds ratio[OR]:11.52),and high RRI independently predicted mortality among AKI patients(adjusted OR:3.18).CONCLUSION In cirrhosis patients,RRI exhibited a significant association with AKI,effectively differentiated between AKI phenotypes,and predicted AKI mortality.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

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.

Intestinal lymphangiectasia:Understanding the bigger picture

Intestinal lymphangiectasia(IL)is characterized by the dilation of intestinal lymphatic vessels,which can rupture and cause loss of lymph into the intestine.Due to the high content of proteins,lipoproteins,and lymphocytes in the intestinal lymph,loss of lymph might result in hypoproteinemia,hypoalbuminemia,hypogammaglobulinemia,and lymphocytopenia.In addition,there may be a depletion of minerals,lipids,and fat-soluble vitamins.IL can be primary due to inherent malfunctioning of the lymphatic system,or secondly,a result of various factors that may hinder lymphatic drainage either directly or indirectly.This condition has emerged as a subject of significant clinical interest.Given that the intestinal lymphatic system plays an important role in the body’s fluid homeostasis,adaptive immunity,nutrient and drug absorption,intestinal transport,and systemic metabolism,its dysfunction may have wider implications.Although primary IL is rare,with varied clinical features,complications,treatment response,and outcomes,secondary IL is more common than previously believed.The definitive diagnosis of IL requires endoscopic demonstration of whitish villi(which frequently resemble snowflakes)and histological confirmation of dilated lacteals in the small intestinal mucosa.Treatment of IL is challenging and involves dietary modifications,managing underlying medical conditions,and using medications such as sirolimus and octreotide.Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition.This article provides a comprehensive exploration of the clinical implications associated with IL.In addition,it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.

Chronic hepatitis B:Prevent,diagnose,and treat before the point of no return

Hepatitis B remains a significant global health challenge,contributing to substantial morbidity and mortality.Approximately 254 million people world-wide live with Chronic hepatitis B(CHB),with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions.Alarmingly,only about 13.4%of the individuals infected with this disease have been diagnosed,and awareness of hepatitis B virus(HBV)infection status is as low as 1%in sub-Saharan Africa.In 2022,CHB led to 1.1 million deaths globally.The World Health Organization(WHO)has set a target of eliminating hepatitis B as a public health concern by 2030;however,this goal appears increasingly unattainable due to multiple challenges.These challenges include low vaccination coverage;a large number of undiagnosed cases;a low proportion of patients eligible for treatment under current guidelines;limited access to healthcare;and the costs associated with lifelong treatment.Treatment of HBV can yield significant clinical benefits within a long window of opportunity.However,the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage.This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.

Vascular complications of liver abscess: A literature review

Extensive vascular network and proximity to the gastrointestinal tract make the liver susceptible to abscess formation.While pyogenic liver abscesses account for the majority of liver abscesses in the Western world,amebic liver abscesses are more prevalent in tropical and developing nations.Most liver abscesses heal without complications.However,various vascular complications can occur in these patients,including compression of the inferior vena cava,thrombosis of the portal vein and/or hepatic veins,hepatic artery pseudoaneurysm,direct rupture into major vessels or the pericardium,and biliovascular fistula.These compli-cations can present significant clinical challenges due to the potential for hae-morrhage,ischemia,and systemic embolism,thereby increasing the risk of morbidity and mortality.Mechanical compression,flow stasis,inflammation,endothelial injury,and direct invasion are some of the proposed mechanisms that can cause vascular complications in the setting of a liver abscess.For the diag-nosis,thorough assessment,and therapeutic planning of vascular complications,more sophisticated imaging techniques such as multidetector computed tomo-graphy angiography or magnetic resonance angiography may be necessary.Although most vascular complications resolve with abscess treatment alone,additional interventions may be required based on the nature,severity,and course of the complications.This article aims to provide a systematic update on the spectrum of vascular complications of liver abscesses,offering insights into their pathogenesis,diagnosis,and management strategies.

Current therapeutic modalities and chemopreventive role of natural products in liver cancer:Progress and promise

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.

Compensated liver cirrhosis:Natural course and disease-modifying strategies

Compensated liver cirrhosis(CLC)is defined as cirrhosis with one or more decompensating events,such as ascites,variceal haemorrhage,or hepatic encephalopathy.Patients with CLC are largely asymptomatic with preserved hepatic function.The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors.The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis,as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years.Furthermore,early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition.With the advent of effective non-invasive tools for detecting hepatic fibrosis,more and more patients with CLC are currently being recognised.This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or,at the very least,prevent its progression.There are numerous emerging approaches for preventing or delaying decompensation in CLC patients.A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression,and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension.Additionally,address-ing various cofactors(such as obesity,diabetes,dyslipidaemia,and alcoholism)and precipitating factors(such as infection,viral hepatitis,and hepatotoxic drugs)that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC.However,high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these diseasemodifying techniques for CLC patients.This article discussed the natural history of CLC,risk factors for its progression,and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.

Modulatory effect of caffeic acid in alleviating diabetes and associated complications

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.

Prevalence and risk factors of lymphatic dysfunction in cirrhosis patients with refractory ascites:An often unconsidered mechanism

BACKGROUND The lymphatic system is crucial in maintaining the body fluid homeostasis.A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in cirrhosis patients.Therefore,assessment of lymphatic dysfunction in cirrhosis patients with refractory ascites(RA)can be crucial as it would call for using different strategies for fluid mobilization.AIM To assessing the magnitude,spectrum,and clinical associations of lymphatic dysfunction in liver cirrhosis patients with RA.METHODS This observational study included 155 consecutive cirrhosis patients with RA.The presence of clinical signs of lymphedema,such as peau d’orange appearance and positive Stemmer sign,intestinal lymphangiectasia(IL)on duodenal biopsy seen as dilated vessels in the lamina propria with strong D2-40 immunohistochemistry,and chylous ascites were used to diagnose the overt lymphatic dysfunctions.RESULTS A total of 69(44.5%)patients out of 155 had evidence of lymphatic dysfunction.Peripheral lymphedema,found in 52(33.5%)patients,was the most common manifestation,followed by IL in 42(27.0%)patients,and chylous ascites in 2(1.9%)patients.Compared to patients without lymphedema,those with lymphedema had higher mean age,median model for end-stage liver disease scores,mean body mass index,mean ascitic fluid triglyceride levels,and proportion of patients with hypoproteinemia(serum total protein<5 g/dL)and lymphocytopenia(<15%of total leukocyte count).Patients with IL also had a higher prevalence of lymphocytopenia and hypoproteinemia(28.6%vs.9.1%,P=0.004).Seven(13%)patients with lymphedema had lower limb cellulitis compared to none in those without it.On multivariate regression analysis,factors independently associated with lymphatic dysfunction included obesity[odds ratio(OR):4.2,95%confidence intervals(95%CI):1.1–15.2,P=0.027],lymphocytopenia[OR:6.2,95%CI:2.9–13.2,P<0.001],and hypoproteinemia[OR:3.7,95%CI:1.5–8.82,P=0.003].CONCLUSION Lymphatic dysfunction is common in cirrhosis patients with RA.Significant indicators of its presence include hypoproteinemia and lymphocytopenia,which are likely due to the loss of lymphatic fluid from the circulation.Future efforts to mobilize fluid in these patients should focus on methods to improve lymphatic drainage.

Dietary salt in liver cirrhosis:With a pinch of salt!

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.

Heat-tolerant maize for rainfed hot,dry environments in the lowland tropics:From breeding to improved seed delivery

Climate change-induced heat stress combines two challenges:high day-and nighttime temperatures,and physiological water deficit due to demand-side drought caused by increase in vapor-pressure deficit.It is one of the major factors in low productivity of maize in rainfed stress-prone environments in South Asia,affecting a large population of smallholder farmers who depend on maize for their sustenance and livelihoods.The International Maize and Wheat Improvement Center(CIMMYT)maize program in Asia,in partnership with public-sector maize research institutes and private-sector seed companies in South Asian countries,is implementing an intensive initiative for developing and deploying heat-tolerant maize that combines high yield potential with resilience to heat and drought stresses.With the integration of novel breeding tools and methods,including genomics-assisted breeding,doubled haploidy,fieldbased precision phenotyping,and trait-based selection,new maize germplasm with increased tolerance to heat stress is being developed for the South Asian tropics.Over a decade of concerted effort has resulted in the successful development and release of 20 high-yielding heat-tolerant maize hybrids in CIMMYT genetic backgrounds.Via public–private partnerships,eight hybrids are presently being deployed on over 50,000 ha in South Asian countries,including Bangladesh,Bhutan,India,Nepal,and Pakistan.

Surveying the genomic landscape of silage-quality traits in maize(Zea mays L.)

Despite the longstanding importance of silage as a critical feed source for ruminants,its quality improvement has been largely overlooked.Although numerous quantitative trait loci(QTL)and genes affecting silage quality in maize have been reported,only a few have been effectively incorporated into breeding programs.Addressing this gap,the present study undertook a comprehensive meta-QTL(MQTL)analysis involving 523 QTL associated with silage-quality traits collected from 14 published studies.Of the 523 QTL,405 were projected onto a consensus map comprising 62,424 genetic markers,resulting in the identification of 60 MQTL and eight singletons.The average confidence interval(CI)of the MQTL was 3.9-fold smaller than that of the source QTL.Nine of the 60 identified MQTL were classified as breeder’s MQTL owing to their small CIs,involvement of more QTL,and large contribution to phenotypic variation.One-third of the MQTL co-localized with DNA marker-trait associations identified in previous genomewide association mapping studies.A set of 78 high-confidence candidate genes influencing silage quality were identified in the MQTL regions.These genes and associated markers may advance marker-assisted breeding for maize silage quality.

Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome:A comprehensive review

Irritable bowel syndrome(IBS)is a chronic functional disorder which alters gastrointestinal(GI)functions,thus leading to compromised health status.Pathophysiology of IBS is not fully understood,whereas abnormal gut brain axis(GBA)has been identified as a major etiological factor.Recent studies are suggestive for visceral hyper-sensitivity,altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients.Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors,such as microbiota population and diversity,microbial metabolites,dietary uptake,and psychological abnormalities.Strategic efforts focused to study these interactions including probiotics,antibiotics and fecal transplantations in normal and germfree animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology.Additionally,neurotransmitters act as communication tools between enteric microbiota and brain functions,where serotonin(5-hydroxytryptamine)plays a key role in pathophysiology of IBS.It regulates GI motility,pain sense and inflammatory responses particular to mucosal and brain activity.In the absence of a better understanding of various interconnected crosstalks in GBA,more scientific efforts are required in the search of novel and targeted therapies for the management of IBS.In this review,we have summarized the gut microbial composition,interconnected signalling pathways and their regulators,available therapeutics,and the gaps needed to fill for a better management of IBS.

Chronic renal dysfunction in cirrhosis:A new frontier in hepatology

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.

Clinical implications of diabetes in chronic liver disease:Diagnosis,outcomes and management,current and future perspectives

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.

Amebic liver abscess:Clinico-radiological findings and interventional management

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.

Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation

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.

Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease

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.

Hepatogenous diabetes:Knowledge,evidence,and skepticism

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.