The efficacy and safety profile of albumin administration for patients with cirrhosis at high risk of hepatorenal syndrome is dose dependent

Background:Albumin is a critical component in the standard therapeutic approach to acute renal failure(ARF)and spontaneous bacterial peritonitis(SBP)in the setting of ascites.However,data regarding the safety and minimumeffective dose are limited.Methods:We conducted a retrospective review of patients with decompensated cirrhosis who received albumin within the first 48 hours of hospitalization at Beth Israel Deaconess Medical Center between 2010 and 2013.Outcomes included 90-day risk of death or transplantation(primary)and(secondary)complications of albumin infusion(length of stay(LOS)and need for critical care),all adjusted for comorbidity and severity of illness.Results:We included 169 patients with ARF and 88 patients with SBP.The optimal doses of albumin for a survival benefit were found to be 87.5 g and 100 g in the ARF and SBP cohorts,respectively.The odds ratio(OR)for the 90-day risk of death or liver transplantation associated with the optimal loading dose was 0.36(95%CI:0.17-0.76,P=0.008)and 0.28(95%CI:0.07-0.97,P=0.04)for the ARF and SBP cohorts,respectively.This effect persisted for patients with ARF who had neither hepatorenal syndrome(HRS)nor SBP(OR:0.13,95%CI:0.007-0.79,P=0.02).LOS(beta coefficient per log albumin dose:1.69;95%CI:0.14-3.24,P=0.03)and risk of critical care(OR/g albumin:1.03;95%CI:1.01-1.05,P=0.01)were also dose dependent.Conclusion:Albumin has a dose-dependent effect on both survival and complications in patients with cirrhosis with ARF(HRS and otherwise)and/or SBP.

Interventions to improve physical function and prevent adverse events in cirrhosis

Cirrhosis is associated with debilitating complications that significantly impact on a patient’s physical function and reduce quality of life.Owing to highly prevalent sarcopenia,malnutrition and hepatic encephalopathy,functional impairment or frailty is a common complication of cirrhosis.Frailty in turn increases the patient’s risk of hospitalization,accidental falls and fractures,and death.The management of frailty and its associated adverse effects is imperative in improving the overall prognosis of patients with advanced liver disease.The cornerstone of therapy revolves around optimizing physical function with appropriate nutrition and exercise.Nutritional therapy with protein supplementation has shown significant benefit,while studies on exercise have been controversial.However,newly emerging studies trend towards a beneficial effect of physical exercise with improvement in quality of life.The implementation of technology in liver disease management shows future promise.Fitbits and other wearable devices can be used to help monitor a patient’s personal progress in physical exercise and nutritional optimization.Additionally,the progressive development of new smartphone applications to help aid in the diagnosis and monitoring of complications of cirrhosis provides a sophisticated avenue for improving care of patients with cirrhosis.

Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease

Background and aims.Non-alcoholic fatty liver disease(NAFLD)is a common,morbid disease with profound implications for the overall health of the patient.We set out to determine the clinical predictors of advanced histology in the referral population.Methods.We performed a retrospective review of all biopsy-proven NAFLD patients,including 358 unique patients first seen between 1996 and 2009.Liver histology and ultrasound images were reviewed prospectively by clinicians who were blinded to clinical information and test indication.Results.Compared with men,women tended to present at an older age(51.4-10.6 vs 45.3-11.2 years,P<0.001),were more likely to be Caucasian(P=0.003),less likely to present with an elevated alanine aminotransferase(ALT)(75.2%vs 88.8%),and more likely to have advanced non-alcoholic steatohepatitis(NASH)(44.7%vs 29.9%;P=0.04)and advanced fibrosis(23.3%vs 14.1%;P=0.03).In multivariate logistic regression,body mass index(BMI)-30 kg/m^(2)(odds ratio(OR)2.21;95%confidential interval(CI):1.23–4.08),female gender(OR 1.76;95%CI:1.01–3.10)and aspartate aminotransferase(AST)>40 IU/L(OR 2.00;95%CI:1.14–3.55)were associated with a NAFLD activity score>4.The sensitivity and specificity of an AST to platelet ratio index(APRI)>1 for significant fibrosis was 30.0%(95%CI:17.2–45.4%)and 92.8%(95%CI:88.2-95.8%),respectively;the likelihood ratio is 4.2.In multivariate logistic regression,APRI>1 was the most significant predictor of advanced fibrosis(OR 3.85;95%CI:1.55–9.59).In patients without ultrasound-detected steatosis,20%had advanced fibrosis and 16.7%had active NASH.Conclusion.Patients with suspected NAFLD should routinely be evaluated for advanced liver disease,including non-invasive indices of fibrosis such as APRI,and serious consideration given to liver biopsy.

The aspartate aminotransferase-to-platelet ratio and the evaluation of non-alcoholic fatty liver disease

Dear Editor,We thank Agilli et al.and Kayadibi et al.for their interest in our manuscript[1].Taken together,their letters raise points of clarification regarding the utility and general applicability of the‘aspartate aminotransferase-to-platelet ratio index’(APRI)test in the evaluation of liver fibrosis.Our first comment is that their concern over confounders of the APRI unrelated to liver disease is valid.Indeed,confounders would diminish the ability of APRI to predict advanced liver fibrosis,leading to false negatives.Given that our results were significant,this insight strengthens our findings.Also,in defense of APRI,most other non-invasive predictors of liver fibrosis are vulnerable to confounding by extraneous conditions,which could instead lead to false positives.The‘hepascore’and‘fibrotest’,for example,utilizes bilirubin(confounded by Gilbert’s)and Gamma-Glutamyl Transferase(GGT)(confounded by cholestasis)[2].

Design and rationale of a randomized-controlled trial of home-delivered meals for the management of symptomatic ascites:the SALTYFOOD trial

Background:When patients with cirrhosis develop ascites,it is associated with sharply increasedmortality and healthcare utilization with decreased quality of life.Dietary salt restriction is first-line therapy for ascites but it is limited by poor adherence.Methods:We will recruit 40 patients with cirrhosis and ascites who have received a recent paracentesis or hospitalization for a 1:1 randomized trial of standard care(education on salt restriction)versus home-delivered meals.Our primary outcome is the number of paracenteses needed over 12 weeks.Secondary outcomes include hospital-bed days,health-related quality of life(HRQOL,Ascites Symptom Inventory-7 and Visual Analogue Scale)and performance on batteries of physical function including hand grip(kg)and walk speed(m/s).All subjects follow up through a series of calls where any paracenteses,hospital readmissions,weight changes and diuretic dosage changes are recorded.In a final Week 12 visit,knowledge of dietary sodium intake,quality of life and frailty are reassessed,and satisfaction with the meal-delivery program is evaluated.Paired comparison testing will be conducted between the two arms.Discussion:A nutritionally standardized meal-delivery program for patients with cirrhosis and ascites post discharge has a variety of potential patient-based benefits,including the effective management of ascites,reduction of healthcare utilization and improvement of HRQOL.We have three core hypotheses.First,patients will report interest in and satisfaction with a home-delivered meals program.Second,subjects on a salt-restricted(2 g sodium)meal-delivery program will have fewer therapeutic paracenteses and all-cause readmissions than subjects receiving standard of care.Third,subjects on a saltrestricted(2 g sodium)meal-delivery program will report increased HRQOL compared to subjects receiving standard of care.

Medically tailored meals for the management of symptomatic ascites:the SALTYFOOD pilot randomized clinical trial

Background:Ascites is a costly,morbid complication of cirrhosis.Although a low-sodium diet is central to the clinical management of ascites,its efficacy is limited by poor adherence.We aimed to determine the feasibility and impact of lowsodium medically tailored meals(MTM)intervention.Methods:We enrolled 40 persons with cirrhosis and ascites at the time of a paracentesis in a 12-week,1:1 randomized trial of standard of care(SOC)(low-sodiumdiet educational handout)or MTM with<2,000mg of sodium,>2,100 kcal,and>80 g of protein including a nocturnal protein supplement.We determined the proportion of eligible candidates recruited and adherence to MTM.The primary outcome was the number of paracenteses performed during weeks 0-12.We also collected ascites-specific quality-of-life(ASI-7)scores.Results:The median age of the enrolled subjects was 54(IQR,47-63)years,46%were female,with median MELD-Na 18(IQR,11-23)and albumin 2.7(IQR,2.5-3.3)g/dL.At baseline,subjects reported a median of two(IQR,1-3)paracenteses in the prior 4 weeks.Adherence to the meal schedule was excellent save for when hospitalizations occurred.After 12 weeks,patients in the MTM arm required fewer paracenteses per week than those in the SOC group[median(IQR):0.34(0.14-0.54)vs 0.45(0.25-0.64)].During the trial,four(20%)SOC patients died,whereas two(10%)died and one(5%)was transplanted in the MTM arm.Ascites-specific quality of life improved to a greater degree in the MTM arm compared to the SOC arm,by 25%(IQR,-11%to 61%)vs 13%(IQR,-28%to 54%).Conclusion:A trial of MTM for persons with ascites is feasible and potentially effective.Both arms experienced benefits,highlighting the role for improved education and closer monitoring in this challenging condition.

Pill or procedure?Patient preferences on beta-blockers as an alternative to endoscopic variceal screening during the COVID-19 pandemic

Introduction Certain patients at low risk of clinically significant esophageal varices by Baveno criteria can safely avoid screening esophagogastroduodenoscopy(EGD)[1,2].However,regardless of variceal status,the PREDESCI study suggests that earlier betablocker(BB)use in compensated disease with clinically significant portal hypertension by hepatic venous pressure gradient may result in benefit by delaying the time to decompensated cirrhosis[3,4].This carries significant ramifications for future clinical guidelines and decision-making for whom we decide to initiate BB.