Wilson's disease:Revisiting an old friend

Wilson's disease(WD)is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs,such as the central nervous system.It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter.This protein facilitates the incorporation of copper into ceruloplasmin.More than 800 mutations associated with WD have been described.The onset of the disease frequently includes manifestations related to the liver(as chronic liver disease or acute liver failure)and neurological symptoms,although it can sometimes be asymptomatic.Despite it being more frequent in young people,WD has been described in all life stages.Due to its fatal prognosis,WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms.The diagnosis is established with a combination of clinical signs and tests,including the measurement of ceruloplasmin,urinary copper excretion,copper quantification in liver biopsy,or genetic assessment.The pharmacological therapies include chelating drugs,such as D-penicillamine or trientine,and zinc salts,which are able to change the natural history of the disease,increasing the survival of these patients.In some cases of end-stage liver disease or acute liver failure,liver transplantation must be an option to increase survival.In this narrative review,we offer an overview of WD,focusing on the importance of clinical suspicion,the correct diagnosis,and treatment.

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.

Impact of COVID-19 on liver disease: From the experimental to the clinic perspective

Coronavirus disease 2019(COVID-19)has caused a global pandemic unprecedented in over a century.Although severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a predominantly respiratory infection,various degrees of liver function abnormalities have been reported.Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies,but it can critically compromise survival and trigger hepatic decompensation.The collapse of the healthcare services has negatively impacted the diagnosis,monitoring,and treatment of liver diseases in non-COVID-19 patients.In this review,we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.

Glutaminolysis-ammonia-urea Cycle Axis,Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies

The prevalence of non-alcoholic fatty liver disease(NAFLD)is increasing worldwide,reflecting the current epidemics of obesity,insulin resistance,type 2 diabetes mellitus,and metabolic syndrome.NAFLD is characterized by the accumulation of fat in the liver,and is known to be a cause of cirrhosis.Although many pathways have been proposed,the cause of NAFLD-linked fibrosis progression is still unclear,which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma.Cirrhosis is associated with activation of hepatic stellate cells(HSC)and accumulation of excess extracellular matrix proteins,and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis.Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation.Both mechanisms are plausible antifibrotic targets in NASH,as the activation of HSCs the proliferation of myofibroblasts depend on those processes.This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression,and shows how the axis could be a novel therapeutic target.

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.