Long-term albumin infusion in decompensated cirrhosis:A review of current literature

Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction.Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis,large-volume paracentesis and hepatorenal syndrome.Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients.We review the current literature on both the established and potential role of albumin,and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.

Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis:A meta-analysis

BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma globally.Sofosbuvir/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatment of chronic HCV infection.While the addition of ribavirin(RBV)to SOF/VEL improved sustained virological response(SVR12)in genotype 3(GT3)decompensated cirrhosis patients,the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.AIM To evaluate the efficacy and safety of SOF/VEL,with or without RBV in GT3 compensated cirrhosis patients.METHODS We searched four electronic databases(PubMed/Medline,Embase,Cochrane Library and Web of Science)from inception up to June 2021 using both free text and MeSH terms.There was no restriction on language,geography,publication dates and publication status(full text or abstracts).All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL,with or without RBV,were included,regardless of age,gender or prior treatment experience.The primary outcome was sustained virological response 12-wk posttreatment(SVR12).The secondary outcome was treatment-related adverse events,as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL.The pooled relative risk(RR),95%CI and heterogeneity(I^(2))were estimated using Review Manager version 5.3.RESULTS From 1752 citations,a total of seven studies(2 randomized controlled trials,5 cohort studies)with 1088 subjects were identified.The SVR12 was similar in GT3 compensated cirrhosis patients,regardless of the use of RBV,for both the intention-to-treat RR 1.03,95%CI:0.99-1.07;I^(2)=0%)and the per-protocol analysis(RR:1.03,95%CI:0.99-1.07;I^(2)=48%).The overall pooled rate of treatment-related adverse events was 7.2%.Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL(RR:4.20,95%CI:1.29-13.68;I^(2)=0%).Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions.However,addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients.CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL.Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Real-world Effectiveness and Tolerability of Interferonfree Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C:A Multinational Cohort Study

Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).

Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society Consensus Conference: towards better clinical care in transplant hepatology

Liver transplantation(LT)was first performed over six decades ago and is currently the standard of care for patients with end-stage liver disease and life-threatening complications.There have been significant advances in the area of LT;however,it remains a highly morbid,restrictive,expensive and resource-intensive intervention(1).Early recovery for LT(ERAS4OLT.org)is a multimodal concept aimed at promoting faster recovery in patients undergoing LT.The development of a dedicated protocol for early recovery following LT has been challenging due to the complexity of developing a treatment approach,patient comorbidities associated with decompensated cirrhosis,and low case volume.

Antibiotic prophylaxis in cirrhosis patients with upper gastrointestinal bleeding:An updated systematic review and meta‐analysis

Objective:Emerging evidence suggest that antibiotic prophylaxis may be omitted in early cirrhosis patients with upper gastrointestinal bleeding(UGIB),which question the benefits of antibiotic prophylaxis on rebleeding,mortality related to ongoing bleeding,and the need for salvage therapy.As the management of UGIB has improved over time since the last review a decade ago,we performed an updated meta‐analysis to review the benefits of antibiotic prophylaxis in cirrhosis patients with UGIB.Method:Six electronic databases including PubMed/MEDLINE,EMBASE,Scopus,Web of Science,Cochrane library,and ClinicalTrial.gov were systematically searched up to December 1,2021.The primary outcome was 6 weeks mortality.Secondary outcomes include the risk of infection,rebleeding at 7 days and 6 weeks,mortality related to ongoing bleeding,need for salvage therapy,and infection‐related mortality.Result:Eighteen studies(12 randomized controlled trials[RCT],6 non‐RCT)from 3180 subjects were identified among 2129 citations.Antibiotic prophylaxis reduces mortality at 6 weeks,risk of infection,and infectionrelated mortality(pooled relative risk:0.72,0.39,and 0.41,respectively).Although antibiotics reduce the risk of rebleeding and the amount of blood transfusion,they did not reduce the risk of mortality from ongoing bleeding nor the need for salvage therapy.Antibiotic prophylaxis may shorten the length of stay in the intensive care unit.Conclusion:Antibiotic prophylaxis reduces rebleeding,6‐week mortality,and infection‐related mortality.Due to the low risk of infection and death,dedicated studies are warranted to evaluate the benefit of antibiotic prophylaxis in early cirrhosis with UGIB.

Pre-emptive TIPSS in Acute Variceal Bleeding:Current Status,Controversies,and Future Directions

Acute variceal bleeding(AVB)is associated with signifi-cant short-term morbidity and mortality.Pre-emptive tran-sjugular intrahepatic portosystemic shunt(p-TIPSS)is recommended to prevent rebleeding in AVB patients with a high risk of rebleeding.Despite the benefit of prevent-ing rebleeding and de-novo ascites,the uptake of p-TIPSS remains low because logistic challenges in the real-world setting.In this review,we summarize the current evidence and controversies on p-TIPSS including patient selection for p-TIPSS,particularly in the setting of NASH cirrhosis and acute-on-chronic liver failure,the role of sarcopenia,renal impairment in the setting of p-TIPSS.Finally,we summarize both pharmacological and nonpharmacological strategies to optimize outcomes in patients undergoing p-TIPSS.