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.

Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

AIM: To evaluate the efficacy and safety of tolvaptan to treat refractory ascites in decompensated liver cirrhosis patients with or without further complications, such as hepatorenal syndrome and/or hepatocellular carcinoma.

Evaluation and management of patients with refractory ascites

Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis, malignancy or infection and non-compliance with medications and low sodium diet have been excluded, the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis （LVP） and transjugular intrahepatic portasystemic stent-shunt （TIPS） are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morlJidity and mortality （most surgical options） rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study

BACKGROUND Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis.However,few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIM To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODS A total of 75 cirrhotic patients with refractory ascites were enrolled in the study(50 in a rifaximin and 25 in a control group).Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics(19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics).All patients received conventional treatment for refractory ascites,while patients in the rifaximin group received oral rifaximin-α200 mg four times daily for at least 2 wk.The ascites grade,fasting weight,liver and kidney function,and inflammatory factors in the plasma were evaluated before and after treatment.In addition,the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment.The patients were followed for 6 mo.RESULTS Compared with the control group,the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin(P=0.011 and 0.009,respectively).The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group(P=0.048).The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group(P=0.024).The abundance of Roseburia,Haemophilus,and Prevotella was significantly reduced after rifaximin treatment,while the abundance of Lachnospiraceae_noname,Subdoligranulum,and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics.The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSION Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites.A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria,thus improving the systemic inflammatory state.

Alfapump®implantable device in management of refractory ascites:An update

Refractory ascites(RA)is a frequent and life-threatening complication of cirrhosis.In selected patients with RA,transjugular intrahepatic portosystemic shunt(TIPS)placement and liver transplantation(LT)are currently considered the best therapeutic alternatives to repeated large volume paracentesis.In patients with a contraindication to TIPS or LT,the alfapump®system(Sequana Medical,Ghent,Belgium)has been developed to reduce the need for iterative paracentesis,and consequently to improve the quality of life and nutritional status.We report here recent data on technical progress made since the first implantation,the efficacy and tolerance of the device,the position of the pump in the therapeutic arsenal for refractory ascites,and the grey areas that remain to be clarified regarding the optimal selection of patients who are potential candidates for this treatment.

Constrictive pericarditis as a cause of refractory ascites after liver transplantation:A case report

BACKGROUND Refractory ascites is a rare complication following orthotopic liver transplantation(OLT).The broad spectrum of differential diagnosis often leads to delay in diagnosis.Therapy depends on recognition and treatment of the underlying cause.Constrictive pericarditis is a condition characterized by clinical signs of right-sided heart failure.In the advanced stages of the disease,hepatic congestion leads to formation of ascites.In patients after OLT,cardiac etiology of ascites is easily overlooked and it requires a high degree of clinical suspicion.CASE SUMMARY We report a case of a 55-year-old man who presented with a refractory ascites three months after liver transplantation for alcoholic cirrhosis.Prior to transplantation the patient had a minimal amount of ascites.The transplant procedure and the early postoperative course were uneventful.Standard posttransplant work up failed to reveal any typical cause of refractory post-transplant ascites.The function of the graft was good.Apart from atrial fibrillation,cardiac status was normal.Eighteen months post transplantation the patient developed dyspnea and severe fatigue with peripheral edema.Ascites was still prominent.The presenting signs of right-sided heart failure were highly suggestive of cardiac etiology.Diagnostic paracentesis was suggestive of cardiac ascites,and further cardiac evaluation showed typical signs of constrictive pericarditis.Pericardiectomy was performed followed by complete resolution of ascites.On the follow-up the patient remained symptom-free with no signs of recurrent ascites and with normal function of the liver graft.CONCLUSION Refractory ascites following liver transplantation is a rare complication with many possible causes.Broad differential diagnosis needs to be considered.

Portal Hypertension Refractory Ascites Caused by Secondary Hemochromatosis

We report a patient with refractory ascites because of portal hypertension caused by hemochromatosis secondary to osteopetrosis.To our knowledge,this is the first well-documented case of this association.A 46-year-old male patient who was repeatedly infused with red blood cells for anemia secondary to osteopetrosis suffered from refractory ascites.The serum-ascites albumin gradient was 29.9 g/L.Abdominal computed tomography(CT)showed a large amount of ascites,hepatomegaly,and splenomegaly.Bone marrow biopsy showed a small bone marrow cavity with no hematopoietic tissue.A peripheral blood smear showed tear drop red blood cells and metarubricytes.Serum ferritin was 8,855.0 ng/mL.Therefore,we considered that the ascites resulted from portal hypertension caused by hemochromatosis secondary to osteopetrosis.We simultaneously performed the transjungular intrahepatic portal-systemic shunt(TIPS)and obtained a transjungular liver biopsy.The portal pressure gradient before TIPS was 28 mmHg,and iron staining was strongly positive on liver biopsy,which confirmed our diagnosis.After TIPS,both abdominal distention and ascites gradually resolved,and no recurrence as observed after the 12-month postoperative follow-up was observed.This case indicated that regular monitoring of iron load is important for patients with osteopetrosis.TIPS is safe and effective for portal hypertension complications due to osteopetrosis.

Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites

BACKGROUND Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis.The transjugular intrahepatic portosystemic shunt(TIPS)is an efficacious intervention,but there is a lack of reliable tools for postoperative pro-gnosis assessment.Previously utilized clinical biochemical markers,such as the serum albumin concentration(Alb),sodium(Na+)concentration,and serum creatinine(Scr),have limited predictive value.Therefore,the quest for novel,specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance.A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021.These patients were followed up regularly for two years,and the death toll was meticulously documented.The patients were allocated into a survival group(n=45 patients)or a deceased group(n=30 patients)based on their prognosis status.The clinical data of the two groups were collected,and Child-Pugh scores and MELD scores were calculated for analysis.Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade,MELD score,and Cys C level.Additionally,a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites.The receiver operating characteristic curve(ROC)ascertained the predictive value of the Cys C concen-tration,Child-Pugh grade,and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients.RESULTS During a 2-year follow-up period,among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment,30 patients(40.00%)passed away.The deceased cohort exhibited heightened aspartate aminotrans-ferase,alanine aminotransferase,total bilirubin,Scr,prothrombin time,Cys C,international normalized ratio,Child-Pugh,and MELD scores compared to those of the survival cohort,while Alb and Na+levels were attenuated in the deceased group(P<0.05).Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score,MELD score,and Cys C level(r=0.709,0.749,0.671,P<0.05).Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C(HR=3.802;95%CI:1.313-11.015),Child-Pugh(HR=3.030;95%CI:1.858-4.943),and MELD(HR=1.222;95%CI:1.073-1.393)scores.ROC analysis confirmed that,compared to those of the classic prognostic models for Child-Pugh and MELD scores,the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower.This analysis yielded sensitivity and specificity values of 83.33%and 82.22%,respectively.The area under the curve value at this juncture was 0.883,with an optimal cutoff value set at 1.95 mg/L.CONCLUSION Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites.Predictive models based on serum Cys C levels,as opposed to Scr levels,are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

Clinical research on navel application of Shehuang Paste combined with Chinese herbal colon dialysis in treatment of refractory cirrhotic ascites complicated with azotemia

AIM: To explore the efficacy and mechanism of a novel therapeutic method of traditional Chinese medicine in patients with refractory cirrhotic ascites complicated with azotemia. METHODS: Seventy-five cases of refractory cirrhotic ascites complicated with azotemia were randomly divided into 3 groups: comprehensive treatment (n = 29), simple treatment (n = 24), and control (n = 22). The basic treatment methods were the same in all groups, including liver protecting medicines, diuretics and supportive drugs. The control group underwent only the basic treatment. Shehuang Paste (SHP) was applied to the navels of the two treatment groups once a day for 30 d. Colon dialysis with Chinese herbs was administered to the comprehensive treatment group once every two days. Before and after treatment, we measured abdominal circumference, BUN, Cr, serum Na+, urine Na+/K+, liver function, endotoxin content, NO, and ET-1. Color Doppler ultrasonography was conducted to measure the portal vein blood flow. RESULTS: The total effective rate for ascites was 72.4% in the comprehensive treatment group, 45.8% in the simple treatment, contrasting with 18.2% in the controls. Between the two treatment groups and the controls, there were significant differences in the effective rates (P < 0.01, and P < 0.05). There was also a significant difference (P < 0.05) between the two treatment groups. Measurements of Cr and BUN showed higher values for the treatment groups, with the comprehensive better than the simple group (P < 0.05). Sera Na, urineNa/K were different, P < 0.01 between pre- and post- treatment in the comprehensive group, and P < 0.05 in the simple group. The treatment groups’ endotoxin content was also significantly reduced (P < 0.01, and P < 0.05), with the comprehensive group better than the simple group (P < 0.05). Portal vein blood flow and NO content significantly reduced (P < 0.05), as did ET-1 content (P < 0.01). There were no significant changes in the control group (P > 0.05). The comprehensive treatment group’s pre- and post-treatment portal vein and splenic vein blood flows showed a positive correlation to NO, ET-1 and endotoxin contents.CONCLUSION: When treating refractory cirrhotic ascites complicated with azotemia, Shehuang Paste combined with Chinese herbal dialysis is better than Shehuang Paste alone for ascites resolution, azotemia, and endotoxin elimination. However, both methods on their own were also effective for reducing portal and splenic vein blood flow, and lowering the contents of NO, ET-1 in the two treatment groups.

Road to recompensation:BavenoⅦcriteria and transjugular intrahepatic portosystemic shunt in liver cirrhosis

Liver cirrhosis has long been considered a point of no return,with limited hope for recovery.However,recent advancements,particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt(TIPS),have illuminated the concept of hepatic recompensation.In this editorial we comment on the article by Gao et al published in the recent issue.This editorial provides a comprehensive overview of the evolution of understanding cirrhosis,the criteria for recompensation,and the efficacy of TIPS in achieving recompensation.We discuss key findings from recent studies,including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion.While further research is needed to validate these findings and elucidate the mechanisms underlying recompensation,the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites:A systematic review and meta-analysis

BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.Atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(P<0.01).Moreover,natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites(P<0.01).ANP infusions increased renal water excretion,although without reaching a statistically significant dose-response gradient.Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders(P<0.01).Blood pressure decreases occurred less frequently when ANP doses≤30 ng/kg/min were applied.The quality of evidence for a natriuretic response to ANP was low,mainly due to small sample sizes and considerable between-study heterogeneity.Data were sparse for the other natriuretic peptides;B-type natriuretic peptide and urodilatin.CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites.Continuous infusion rates>30 ng/kg/min are the most effective.However,safety increases with infusion rates≤30 ng/kg/min.

Reduction of portosystemic gradient during transjugular intrahepatic portosystemic shunt achieves good outcome and reduces complications

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is placed important role in the therapy of complications of portal hypertension,there is still no suitable criterion for a reduction in portosystemic gradient(PSG),which can both reduce PSG and maximize clinical results and minimize hepatic encephalopathy(HE).AIM To compare the clinical outcomes and incidence of HE after one-third PSG reduction during TIPS in patients with variceal bleeding and refractory ascites.METHODS A total of 1280 patients with portal-hypertension-related complications of refractory ascites or variceal bleeding who underwent TIPS from January 2016 to January 2019 were analyzed retrospectively.Patients were divided into group A(variceal hemorrhage and PSG reduced by one third,n=479);group B(variceal hemorrhage and PSG reduced to<12 mmHg,n=412);group C(refractory ascites and PSG reduced by one third,n=217);and group D(refractory ascites and PSG reduced to<12 mmHg of PSG,plus medication,n=172).The clinical outcomes were analyzed.RESULTS By the endpoint of follow-up,recurrent bleeding was no different between groups A and B(χ^(2)=7.062,P=0.374),but recurrent ascites did differ significantly between groups C and D(χ^(2)=14.493,P=0.006).The probability of total hepatic impairment within 3 years was significantly different between groups A and B(χ^(2)=11.352,P=0.005)and groups C and D(χ^(2)=13.758,P=0.002).The total incidence of HE differed significantly between groups A and B(χ^(2)=7.932,P=0.016),groups C and D(χ^(2)=13.637,P=0.007).There were no differences of survival rate between groups A and B(χ^(2)=3.376,P=0.369,log-rank test),but did differ significantly between groups C and D(χ^(2)=13.582,P=0.014,log-rank test).CONCLUSION The PSG reduction by one third may reduce the risk of HE,hepatic function damage and achieve good clinical results.

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding,the transjugular intrahepatic portosystemic shunt(TIPS)procedure continues to remain a focus of intense clinical and biomedical research.By the impressive reduction in portal pressure achieved by this intervention,coupled with its minimally invasive nature,TIPS has gained increasing acceptance in the treatment of complications of portal hypertension.The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy.Moreover,the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions,which was occasionally severe.While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents,hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS.It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS.The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax,portal hypertensive gastropathy,ectopic varices,hepatorenal and hepatopulmonary syndromes,non-tumoral portal vein thrombosis and chylous ascites.It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality.The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.

Orthotopic liver transplantation for giant liver haemangioma: A case report

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease(lab MELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the lab MELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low lab MELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

Effects of Shehuang Paste (麝黄膏) on Hemodynamics, Endotoxin, Nitric Oxide and Endothelin-1 in Patients with Refractory Cirrhotic Ascites

Objective： To explore the influence of Shehuang Paste （麝黄膏, SHP） to the hemodynamics, endotoxin, nitric oxide （NO）, and endothelin-1 （ET-1） in patients with refractory cirrhotic ascites. Methods： Fifty-nine cases of refractory cirrhotic ascites were randomly assigned to two groups, 32 cases in the treatment group and 27 cases in the control group. The basic treatment was the same for both groups, including liver protecting medicines, diuretics and supportive drugs, but SHP navel sticking was applied for the treatment group additionally once a day. A course of one month of treatment was applied and the general efficacy on ascites was observed by the end of the therapeutic course. Before and after the treatment, examinations by limulus lysate chromogenic test was conducted to measure plasma endotoxin content; colorimetry to measure plasma content of NO indirectly, radioimmunoassay to measure plasma ET-1 content; and color Doppler ultrasonography to measure the blood flow of portal vein and splenic vein. The relationship between the blood flow of portal vein and splenic vein and endotoxin, NO and ET-1 in the treatment group was analyzed as well. Results： The total effective rate on ascites was 84.4% in the treatment group, and 48. 1% in the control group, with significant difference shown between them （P〈0.01）. In the treatment group the blood flow of portal vein and splenic vein, contents of endotoxin, NO and ET-1 all got significantly reduced after treatment （ P〈0.05 or P〈0.01）; while these indexes in the control group were not significantly changed （P〉0.05）. Moreover, it was found that in the treatment group, the blood flow of portal vein and splenic vein had a positive correlation to the levels of NO, ET-1, and endotoxin, either before or after treatment. Conclusion： Application of SHP navel sticking could clearly reduce the blood flow of portal vein and splenic vein, and lower the content of endotoxin, NO and ET-1. The blood flow of portal vein and splenic vein in the treatment group showed a positive correlation with the contents of endotoxin, NO and ET-1.

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.

Hepatic sinusoidal obstruction syndrome induced by tacrolimus following liver transplantation:Three case reports

BACKGROUND Hepatic sinusoidal obstruction syndrome(HSOS)is a rare complication in solid organ transplant recipients,especially in liver transplantation recipients.However,the consequences of HSOS occurrence are pernicious,which could result in severe liver or renal failure,and even death.In addition to previously reported azathioprine and acute rejection,tacrolimus is also considered as one predisposing factor to induce HSOS after liver transplantation,although the underlying mechanism remains unclear.CASE SUMMARY In this study,we reported three cases of tacrolimus-related HSOS after liver transplantation.The diagnosis of HSOS was firstly based on the typical symptoms including ascites,painful hepatomegaly and jaundice.Furthermore,the features of patchy enhancement on portal vein and delayed phase of abdominal enhanced computed tomography were suspected of HSOS and ultimately confirmed by liver biopsy and histological examination in two patients.A significant decrease in ascites and remission of clinical symptoms of abdominal distention and pain were observed after withdrawal of tacrolimus.CONCLUSION Tacrolimus-induced HSOS is a scarce but severe complication after liver transplantation.It lacks specific symptoms and diagnostic criteria.Timely diagnosis of HSOS is based on clinical symptoms,radiological and histological examinations.Discontinuation of tacrolimus is the only effective treatment.Transplantation physicians should be aware of this rare complication potentially induced by tacrolimus.

Spontaneous bacterial empyema in cirrhosis:A systematic review and meta-analysis

BACKGROUND Spontaneous bacterial empyema(SBE)occurs when a hepatic hydrothorax becomes infected and runs a course similar to spontaneous bacterial peritonitis(SBP).It remains underdiagnosed as patients with cirrhosis do not routinely undergo diagnostic thoracentesis.Current understanding is limited by small cohorts,while studies reporting its association with ascites/SBP are conflicting.AIM To explore the incidence of SBE,to determine its association with ascites,and to summarize what is known regarding treatment and outcomes for patients with SBE.METHODS Major databases were searched until June 2021.Outcomes include the incidence of SBE in pleural effusions,SBP in peritoneal fluid,and SBE in patients without ascites within our cohort of patients with cirrhosis.We performed a meta-analysis using a randomeffects model with pooled proportions and 95%confidence intervals(CI).We assessed heterogeneity using I^(2)and classic fail-safe to determine bias.RESULTS Eight studies with 8899 cirrhosis patients were included.The median age ranged between 41.2 to 69.7 years.The majority of the patients were Child-Pugh B and C.Mean MELD score was 18.6±8.09.A total of 1334 patients had pleural effusions and the pooled incidence of SBE was 15.6%(CI 12.6-19;I^(2)50).Amongst patients diagnosed with SBE,the most common locations included right(202),left(64),and bilateral(8).Amongst our cohort,a total of 2636 patients had ascites with a pooled incidence of SBP of 22.2%(CI 9.9-42.7;I^(2)97.8).The pooled incidence of SBE in patients with cirrhosis but without concomitant ascites was 9.5%(CI 3.6-22.8;I^(2)82.5).CONCLUSION SBE frequently occurs with concurrent ascites/SBP;our results suggest high incidence rates of SBE even in the absence of ascites.The pleura can be an unrecognized nidus and our findings support the use of diagnostic thoracentesis in patients with decompensated cirrhosis after exclusion of other causes of pleural effusion.Thoracentesis should be considered particularly in patients without ascites and when there is a high suspicion of infection.The need for diagnostic thoracentesis will continue to be important as rates of multi-drug resistant bacterial infections increase and antibiotic susceptibility information is required for adequate treatment.

Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction:A Concise Review

Annually,10%of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis(LVP)is a frequently used therapeutic procedure.LVP,although a safe method,is associated with circulatory dysfunction in a significant percentage of patients,which is termed para-centesis-induced circulatory dysfunction(PICD).PICD results in faster reaccumulation of ascites,hyponatremia,renal impairment,and shorter survival.PICD is diagnosed through laboratory results,with increases of>50%of baseline plasma renin activity to a value≥4 ng/mL/h on the fifth to sixth day after paracentesis.In this review,we discuss the pathophysi-ology and prevention of PICD.