Current aspects of renal dysfunction after liver transplantation

The development of chronic kidney disease(CKD)after liver transplantation(LT)exerts a severe effect on the survival of patients.The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure,as several patients are transplanted with previously deteriorated renal function.Due to its multifactorial nature,encompassing pre-transplantation conditions,perioperative events,and nephrotoxic immunosuppressor therapies,the accurate identification of patients under risk of renal disease,and the implementation of preventive approaches,are extremely important.Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate,to non-invasive markers,although no option has yet proved efficient in early detection of kidney injury.Considering the nephrotoxicity of calcineurin inhibitors(CNI)as a factor of utmost importance after LT,early nephroprotective strategies are highly recommended.They are based mainly on delaying the application of CNI during the immediate postoperativeperiod,reducing their dosage,and associating them with other less nephrotoxic drugs,such as mycophenolate mofetil and everolimus.This review provides a critical assessment of the causes of renal dysfunction after LT,the methods of its evaluation,and the interventions aimed at preserving renal function early and belatedly after LT.

Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

AIM:To study the association between genetic ancestry,non-alcoholic fatty liver disease(NAFLD) metabolic characteristics in two cohorts of patients,from Brazil and Portugal. METHODS:We included 131 subjects from Brazil [(n = 45 with simple steatosis(S. Steatosis) and n = 86 with nonalcoholic steatohepatitis(NASH)] and 90 patients from Portugal(n = 66,S. Steatosis; n = 24,NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis:simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers(AT3-I/D,LPL,Sb19.3,APO,FYNull,PV92,and CKMM) with the greatest ethnicgeographical differential frequencies(≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP onlineand the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant(P < 0.05). RESULTS:In the Brazilian sample,NASH was significantly more frequent among the elderly patients with diabetes(NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old,P = 3.7 x 10-9),dyslipidemia(NASH 63% vs S. Steatosis 37%,P = 0.009),higher fasting glucose levels(NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3,P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3(70.8%) vs S. Steatosis 4.6(29.2%) P = 0.04]. In the Portuguese study population,dyslipidemia was present in all patients with NASH(P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group(P = 0.003,respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort(Brazilian cohort:P = 0.75; Portuguese cohort:P = 0.97). Nonetheless,the genetic ancestry contribution of the Brazilian and Portuguese population were different,and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups.CONCLUSION:There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil

BACKGROUND Hepatitis C virus(HCV)treatment has undergone major changes in recent years.Previous interferon-based therapies have been replaced by oral direct-acting antivirals(DAA)regimens,with high sustained virologic response(SVR)rates,and a lower incidence of adverse events(AEs).AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.METHODS This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C(CHC),undergoing treatment with interferon-free regimens from November 2015 to November 2019.The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment.Demographic,anthropometric,clinical,and laboratory variables were evaluated.SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat(ITT),and modified ITT(m-ITT)analysis.AEs and serious adverse events(SAEs)were registered.In the statistical analysis,a P value of<0.05 was considered significant.RESULTS The mean age was 56.88 years,with 415(78.5%)being HCV genotype 1,followed by genotype 3(20.1%).Moreover,306(57.5%)subjects had cirrhosis,and a third of them had decompensated cirrhosis.Sofosbuvir(SOF)plus daclatasvir±ribavirin was the most frequently used treatment(66.9%),followed by SOF plus simeprevir(21.2%).The overall ITT SVR was 92.6%(493/532),while the m-ITT SVR was 96.8%(493/509).Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy(OR:4.320;95%CI:1.920-9.721,P=0.0004),presence of esophageal varices(OR:2.381;95%CI:1.137-4.988,P=0.0215),previous portal hypertensive bleeding(OR:2.756;95%CI:1.173-6.471,P=0.02),higher model for end-stage liver disease scores(OR:1.143,95%CI:1.060–1.233,P=0.0005),lower serum albumin levels(OR:0.528,95%CI:0.322-0.867,P=0.0115),higher serum creatinine(OR:1.117,95%CI:1.056-1.312,P=0.0033),and international normalized ratio(INR)levels(OR:5.542,95%CI:2.023-15.182,P=0.0009).AEs were reported in 41.1%(211/514)of patients,and SAEs in 3.7%.The female gender,higher body mass index,esophageal varices,higher INR values,and longer treatment duration were independently associated with AE occurrence.CONCLUSION Treatment with oral DAAs attains a high SVR rate,with fewer SAEs in a real-life cohort of subjects with CHC,from two tertiary university centers in Brazil.