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.

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.

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.

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.

Lymphatic dysfunction in advanced cirrhosis:Contextual perspective and clinical implications

The lymphatic system plays a very important role in body fluid homeostasis,adaptive immunity,and the transportation of lipid and waste products.In patients with liver cirrhosis,capillary filtration markedly increases,primarily due to a rise in hydrostatic pressure,leading to enhanced production of lymph.Initially,lymphatic vasculature expansion helps to prevent fluid from accumulating by returning it back to the systemic circulation.However,the lymphatic functions become compromised with the progression of cirrhosis and,consequently,the lymphatic compensatory mechanism gets overwhelmed,contributing to the development and eventual worsening of ascites and edema.Neurohormonal changes,low-grade chronic inflammation,and compounding effects of predisposing factors such as old age,obesity,and metabolic syndrome appear to play a significant role in the lymphatic dysfunction of cirrhosis.Sustained portal hypertension can contribute to the development of intestinal lymphangiectasia,which may rupture into the intestinal lumen,resulting in the loss of protein,chylomicrons,and lymphocyte,with many clinical consequences.Rarely,due to high pressure,the rupture of the subserosal lymphatics into the abdomen results in the formation of chylous ascites.Despite being highly significant,lymphatic dysfunctions in cirrhosis have largely been ignored;its mechanistic pathogenesis and clinical implications have not been studied in depth.No recommendation exists for the diagnostic evaluation and therapeutic strategies,with respect to lymphatic dysfunction in patients with cirrhosis.This article discusses the perspectives and clinical implications,and provides insights into the management strategies for lymphatic dysfunction in patients with cirrhosis.

Liver transplantation in acute liver failure:Dilemmas and challenges

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.

Association of COVID-19 with hepatic metabolic dysfunction

The coronavirus disease 2019(COVID-19)pandemic continues to be a global problem with over 438 million cases reported so far.Although it mostly affects the respiratory system,the involvement of extrapulmonary organs,including the liver,is not uncommon.Since the beginning of the pandemic,metabolic comorbidities,such as obesity,diabetes,hypertension,and dyslipidemia,have been identified as poor prognostic indicators.Subsequent metabolic and lipidomic studies have identified several metabolic dysfunctions in patients with COVID-19.The metabolic alterations appear to be linked to the course of the disease and inflammatory reaction in the body.The liver is an important organ with high metabolic activity,and a significant proportion of COVID-19 patients have metabolic comorbidities;thus,this factor could play a key role in orchestrating systemic metabolic changes during infection.Evidence suggests that metabolic dysregulation in COVID-19 has both short-and long-term metabolic implications.Furthermore,COVID-19 has adverse associations with metabolic-associated fatty liver disease.Due to the ensuing effects on the renin-angiotensin-aldosterone system and ammonia metabolism,COVID-19 can have significant implications in patients with advanced chronic liver disease.A thorough understanding of COVID-19-associated metabolic dysfunction could lead to the identification of important plasma biomarkers and novel treatment targets.In this review,we discuss the current understanding of metabolic dysfunction in COVID-19,focusing on the liver and exploring the underlying mechanistic pathogenesis and clinical implications.

Non-alcoholic Fatty Liver Disease:Growing Burden, Adverse Outcomes and Associations

Nonalcoholic fatty liver disease(NAFLD)is a systemic disor-der with a complex multifactorial pathogenesis and hetero-genous clinical manifestations.NAFLD,once believed to be an innocuous condition,has now become the most common cause of chronic liver disease in many countries worldwide.NAFLD is already highly prevalent in the general population,and owing to a rising incidence of obesity and diabetes mellitus,the incidence of NAFLD and its impact on global healthcare are expected to increase in the future.A subset of patients with NAFLD develops progressive liver disease lead-ing to cirrhosis,hepatocellular carcinoma,and liver failure.NAFLD has emerged as one of the leading causes of cirrhosis and hepatocellular carcinoma in recent years.Moreover,HCC can occur in NAFLD even in absence of cirrhosis.Compared with the general population,NAFLD increases the risk of liver-related,cardiovascular and all-cause mortality.NAFLD is bidirectionally associated with metabolic syndrome.NAFLD increases the risk and contributes to aggravation of the pathophysiology of atherosclerosis,cardiovascular diseases,diabetes mellitus,and chronic kidney disease.In addition,NAFLD is linked to colorectal polyps,polycystic ovarian syndrome,osteoporosis,obstructive sleep apnea,stroke,and various extrahepatic malignancies.Extended resection of steatotic liver is associated with increased risk of liver failure and mortality.There is an increasing trend of NAFLD-related cirrhosis requiring liver transplantation,and the recurrence of NAFLD in such patients is almost universal.This review discusses the growing burden of NAFLD,its outcomes,and adverse associations with various diseases.

Sarcopenia in Chronic Liver Disease:A Metabolic Perspective

Sarcopenia,a condition of low muscle mass,quality,and strength,is commonly found in patients with chronic liver disease(CLD)and is associated with adverse clinical out-comes including reduction in quality of life,increased mor-tality,and complications.A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover wherein changes in various metabolic factors such as hyperammone-mia,amino acid deprivation,hormonal imbalance,gut dys-biosis,insulin resistance,chronic inflammation,etc.have important roles.In particular,hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to sarcopenia by various mechanisms including increased ex-pression of myostatin,increased phosphorylation of eukary-otic initiation factor 2a,cataplerosis ofα-ketoglutarate,mi-tochondrial dysfunction,increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis.Skeletal muscle is a major organ of insulin-induced glucose metabolism,and sarcopenia is closely linked to insulin resistance and metabolic syndrome.Patients with liver cirrhosis are in a hypermetabolic state that is associated with catabolism and depletion of amino acids,particularly branched-chain amino acids.Sarcopenia can have significant implications for nonalcoholic fatty liver disease,the most common form of CLD worldwide,because of the close link between metabolic syndrome and sarcope-nia.This review discusses the potential metabolic derange-ment as a cause or effect of sarcopenia in CLD,as well as interorgan crosstalk,which that might help identifying a novel therapeutic strategies.