Hyperammonemia induced oxidative stress in cirrhotic rats without promoting differential protein expression in the brain cortex: A 2D-DIGE analysis

Oxidative stress induced by a high ammonia concentration could modify protein expression in the brain. This study was undertaken in order to investigate the impact of hyperammonemia, caused by thioacetmide (TAA) in rats, on brain cortex protein expression using 2D-DIGE, and analyzing its role in the pathogenesis of HE. Hyperammonemia was induced with TAA. Ammonia and active oxidants were measured by L-glutamate dehydrogenase and dichlorodihydrofluorescein diacetate methods, respectively. Lipid peroxidation and protein oxidation biomarkers were also studied. Differential protein expression in the cortex of TAA- and control-rats was studied by 2D-DIGE. Image analysis was performed using the DeCyder? Software. Ammonia concentration in plasma and brain tissue was higher in TAA-rats compared to control-rats, 3.12 and 2.43 fold higher, respectively. Active oxidants production in TAA-rats was increased by 2.7 fold compared to control-rats. Measurements of MDA, HNE and carbonyl groups, biomarkers of lipid peroxidation and protein oxidation respectively, were found to be statistically significantly increased in TAA-rats compared to control-rats (3.16-, 2.44- and 1.95-fold, respectively), reflecting the presence of oxidative stress in the brain of TAA-rats. 2D-DIGE analysis of brain cortex protein allowed the detection of 2896 spots, however, image analysis showed no statistically significant differential protein expression between the proteins expressed in TAA- and control-rats. No statistical significant differential protein expression in the cortex of TAA-rats was observed, although oxidative stress biomarkers for lipid and proteins were higher in the brain of TAA-rats than in control-rats. These results support the idea that oxidative post-translational modifications are implicated in HE physiopathology.

Combination of squamous cell carcinoma antigen immunocomplex and alpha-fetoprotein in mid-and long-term prediction of hepatocellular carcinoma among cirrhotic patients

BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

What Has the COVID-19 Pandemic Taught Us so Far?Addressing the Problem from a Hepatologist's Perspective

As of today, March 30, 2020, when this Editorial is being written, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19) has been confirmed in more than 745,000 cases worldwide and has claimed the lives of more than 35,000 people.1 In addition to the morbidity and mortality associated with COVID-19, this betacoronavirus has placed several of the world's major economies in strife, mainly in Western Europe and North America, paralyzing travel and regular social interactions, making COVID-19 undoubtedly one of the most important pandemics in human history.