Quantum key distribution(QKD)is recognized as an unconditionally secure method of communication encryption,relying solely on the principles of quantum mechanics.A key performance metric for QKD systems is secure key r...Quantum key distribution(QKD)is recognized as an unconditionally secure method of communication encryption,relying solely on the principles of quantum mechanics.A key performance metric for QKD systems is secure key rate(SKR),which is a critical factor for real-world applications.Herein,we report a practical QKD system,equipped with compact gated InGaAs/InP single-photon detectors(SPDs),that can generate a high SKR of 15.2 Mb/s with a channel loss of 2 dB.This exceptional performance stems from the ultra-low afterpulsing probability of the SPDs,which significantly reduces the bit error rate in the QKD system.The typical quantum bit error rate is 1.3%.The results validate the feasibility of an integrated,practical QKD system and offer a reliable solution for the future development of real-world QKD networks.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padu...Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital.The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample.The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results.Three months after the injury,at the second step of followup,a relevant increase in transaminases with a low viral replication activity(350 IU/mL) was observed in the student,indicating HCV infection.The patient tested positive for the same genotype(1b) of HCV as the injured student.A rapid decline in transaminases,which was not accompanied by viral clearance,and persistently positive HCV-RNA was described 1 mo later.Six months after testing positive for HCV,the student was treated with pegylated interferon plus ribavirin for 24 wk.A rapid virological response was observed after 4 wk of treatment,and a sustained virological response(SVR) was evident 6 mo after therapy withdrawal,confirming that the patient was definitively cured.Despite the favourable IL28B gene(rs12979860) CC-polymorphism observed in the patient,which is usually predictive of a spontaneous clearance and SVR,spontaneous viral clearance did not take place;however,infection with this genotype was promising for a sustained virological response after therapy.展开更多
De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two ...De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.展开更多
Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between ac...Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma(HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.展开更多
Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis vir...Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.展开更多
Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic...Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival.Thromboembolism during OLT is characterized not only by a complex aetiology,but also by unpredictable onset and evolution of the disease.The initiation of a procoagulant process may be triggered by various factors,such as inflammation,venous stasis,ischemia-reperfusion injury,vascular clamping,anatomical and technical abnormalities,genetic factors,deficiency of profibrinolytic activity,and platelet activation.The involvement of the arterial system,intracardiac thrombosis,pulmonary emboli,portal vein thrombosis,and deep vein thrombosis,are among the most serious thrombotic events in the perioperative period.The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis,particularly when these events occur intraoperatively or early after OLT.Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting,many institutions recommend such an approach especially in the subset of patients at high risk.However,the decision of when,how and in what doses to use the various chemical anticoagulants is still a difficult task,since there is no common consensus,even for highrisk cases.The risk of postoperative thromboembolism causing severe hemodynamic events,or even loss of graft function,must be weighed and compared with the risk of an important bleeding.In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurringin the perioperative period,as well as their incidence and clinical features.Moreover,the indications to pharmacological prophylaxis and the current treatment strategies are also summarized.展开更多
AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult pa...AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectivelyupdated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/hepatocellular carcinoma(HCC)] and into two interval times(2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS One thousand one hundred and ninty-four [male(M)/female(F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration(490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction(from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst decHCV(from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time(289/666, 43.4%), there was a trend towards a decrease after DAAs introduction(from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients(M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival(log-rank test P = 0.02) and delisting rate(P = 0.002) than untreated HCV patients. CONCLUSION Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis.展开更多
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has m...Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.展开更多
Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased suscep...Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcareassociated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.展开更多
The design of remediation works for the mitigation and prevention of the associated risk is needed where these geological hazards affect anthropized areas. Remedial measures for landslides commonly include slope resha...The design of remediation works for the mitigation and prevention of the associated risk is needed where these geological hazards affect anthropized areas. Remedial measures for landslides commonly include slope reshaping, plumbing, drainage, retaining structures and internal slope reinforcement, while debris flow control works consist in open or closed control structures. The effectiveness of the remedial works implemented must be assessed by evaluating the reduction of the risk over time. The choice of the most appropriate and cost-effective intervention must consider the type of hazard and environmental issues, and selects, wherever possible, naturalistic engineering operations that are consequently implemented according to the environmental regulations or the design and specification standards imposed by the competent public administrations. The mitigation procedures consist of five basic steps:(a) acquisition of the knowledge of the hazard process;(b) risk assessment with identification of possible disaster scenarios;(c) planning and designing of specific remedial measures to reduce and/or eliminate the potential risk;(d) slope monitoring after application of remedial measures,(e) transfer of knowledge to the stakeholders. This paper presents two case studies describing the practice for the design of the mitigation measures adopted for debris flow and active landslide sites in North-Eastern Italy. The first case study is a debris flow site, for which, based on observation of past events and numerical simulations using the software FLOW-2D, the most suitable mitigation measures were found to be the construction of a debris basin, barriers and breakers. The second case study deals with an active landslide threatening a village. Based on the landslide kinematics and the results of numerical simulations performed with the code FLAC, hard engineering remedial works were planned to reduce the driving forces with benching and by increasing the available resisting forces using jet grout piles and deep drainage.展开更多
Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic fail...Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.展开更多
Non-selective beta blockers(NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics.Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with...Non-selective beta blockers(NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics.Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.展开更多
Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk...Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.展开更多
Objectives: To analyze the association between alexithymia and alcohol intake during adolescence, also in relation to psychopathology, in order to identify psychological risk factors for alcohol misuse. Method: 3556 s...Objectives: To analyze the association between alexithymia and alcohol intake during adolescence, also in relation to psychopathology, in order to identify psychological risk factors for alcohol misuse. Method: 3556 students [mean age (range) 14.5 years (11-18)] were recruited in the Padua area. Each was administered a set of three questionnaires: the Toronto Alexithymia Scale for children (TAS-20) to measure alexithymia, the Questionnaire Adolescent Saturday evening (QAS) to estimate of alcohol intake, and the Youth Self-Report (YSR 11-18) to value psychopathology. Results: Externalizing problems appeared to increase with age and with the amount of alcohol consumed, unlike internalizing problems. The prevalence of alexithymia was 18%, decreasing with age, and it was not associated with alcohol consumption, and used except in younger subjects (≤13), for whom a positive correlation was observed between alexithymia, internalizing problems and alcohol intake. Conclusions: Younger adolescents are more psycho-emotionally vulnerable (internalizing problems and alexithymia) and at a greater risk of alcohol misuse.展开更多
The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being "auto-anticoagulated", prone only to bleeding c...The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being "auto-anticoagulated", prone only to bleeding complications, and protected from thrombotic events. With greater attention to clinical thrombotic events, their impact on the natural history of cirrhosis, and with the emergence and increased use of point-of-care and global assays, it is now understood that cirrhosis results in profound hemostatic alterations that can lead to thrombosis as well as to bleeding complications. Although many clinical decisions are still based on traditional coagulation parameters such as prothrombin(PT), PT, and international normalized ratio, it is increasingly recognized that these tests do not adequately predict the risk of bleeding, nor they should guide pre-emptive interventions. Moreover, altered coagulation tests should not be considered as a contraindication to the use of anticoagulation, although this therapeutic or prophylactic approach is not at present routinely undertaken. Gastroesophageal variceal bleeding continues to be one of the most feared and deadly complications of cirrhosis and portal hypertension, but great progresses have been made in prevention and treatment strategies. Other bleeding sites that are frequently part of end-stage liver disease are similar to clinical manifestations of thrombocytopenia, with gum bleeding and epistaxis being very common but fortunately only rarely a cause of life-threatening bleeding. On the contrary, manifestations of coagulation factor deficiencies like soft tissue bleeding and hemartrosis are rare in patients with cirrhosis. As far as thrombotic complications are concerned, portal vein thrombosis is the most common event in patients with cirrhosis, but venous thromboembolism is not infrequent, and results in important morbidity and mortality in patients with cirrhosis, especially those with decompensated disease. Future studies and the more widespread use of point-ofcare tests in evaluating hemostasis will aid the clinician in decision making when facing the patient with bleeding or with thrombotic complications, with both ends of a continuum being potentially fatal.展开更多
Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list f...Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.展开更多
The evolution of liver diseases to end-stage liver disease or to acute hepatic failure, the evaluation process for liver transplantation, the organ allocation decisionmaking, as well as the post-transplant outcomes ar...The evolution of liver diseases to end-stage liver disease or to acute hepatic failure, the evaluation process for liver transplantation, the organ allocation decisionmaking, as well as the post-transplant outcomes are different between female and male genders. Women's access to liver transplantation is hampered by the use of model for end-stage liver disease(MELD) score, in which creatinine values exert a systematic bias against women due to their lower values even in the presence of variable degrees of renal dysfunction. Furthermore, even when correcting MELD score for gender-appropriate creatinine determination, a quantifiable uneven access to transplant prevails, demonstrating that other factors are also involved. While some of the differences can be explained from the epidemiological point of view, hormonal status plays an important role. Moreover, the pre-menopausal and post-menopausal stages imply profound differences in a woman's physiology, including not only the passage from the fertile age to the non-fertile stage, but also the loss of estrogens and their potentially protective role in delaying liver fibrosis progression, amongst others. With menopause, the tendency to gain weight may contribute to the development of or worsening of pre-existing metabolic syndrome. As an increasing number of patients are transplanted for non-alcoholic steatohepatitis, and as the average age at transplant increases, clinicians must be prepared for the management of this particular condition, especially in post-menopausal women, who are at particular risk of developing metabolic complications after menopause.展开更多
The current attempt is aimed to outline the geometrical framework of a well known statistical problem, concerning the explicit expression of the arithmetic mean standard deviation distribution. To this respect, after ...The current attempt is aimed to outline the geometrical framework of a well known statistical problem, concerning the explicit expression of the arithmetic mean standard deviation distribution. To this respect, after a short exposition, three steps are performed as 1) formulation of the arithmetic mean standard deviation, , as a function of the errors, , which, by themselves, are statistically independent;2) formulation of the arithmetic mean standard deviation distribution, , as a function of the errors,;3) formulation of the arithmetic mean standard deviation distribution, , as a function of the arithmetic mean standard deviation, , and the arithmetic mean rms error, . The integration domain can be expressed in canonical form after a change of reference frame in the n-space, which is recognized as an infinitely thin n-cylindrical corona where the symmetry axis coincides with a coordinate axis. Finally, the solution is presented and a number of (well known) related parameters are inferred for sake of completeness.展开更多
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 program...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.展开更多
基金supported by the Innovation Program for Quantum Science and Technology(Grant No.2024ZD0302500)the National Natural Science Foundation of China(Grant No.62250710162)the Beijing Natural Science Foundation(Grant No.Z230005)。
文摘Quantum key distribution(QKD)is recognized as an unconditionally secure method of communication encryption,relying solely on the principles of quantum mechanics.A key performance metric for QKD systems is secure key rate(SKR),which is a critical factor for real-world applications.Herein,we report a practical QKD system,equipped with compact gated InGaAs/InP single-photon detectors(SPDs),that can generate a high SKR of 15.2 Mb/s with a channel loss of 2 dB.This exceptional performance stems from the ultra-low afterpulsing probability of the SPDs,which significantly reduces the bit error rate in the QKD system.The typical quantum bit error rate is 1.3%.The results validate the feasibility of an integrated,practical QKD system and offer a reliable solution for the future development of real-world QKD networks.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
文摘Hepatitis C virus(HCV) infection after biological accident(needlestick injury) is a rare event.This report describes the first case of acute HCV infection after a needlestick injury in a female nursing student at Padua University Hospital.The student nurse was injured on the second finger of the right hand when recapping a 23-gauge needle after taking a blood sample.The patient who was the source was a 72-year-old female with weakly positive anti-HCV test results.Three months after the injury,at the second step of followup,a relevant increase in transaminases with a low viral replication activity(350 IU/mL) was observed in the student,indicating HCV infection.The patient tested positive for the same genotype(1b) of HCV as the injured student.A rapid decline in transaminases,which was not accompanied by viral clearance,and persistently positive HCV-RNA was described 1 mo later.Six months after testing positive for HCV,the student was treated with pegylated interferon plus ribavirin for 24 wk.A rapid virological response was observed after 4 wk of treatment,and a sustained virological response(SVR) was evident 6 mo after therapy withdrawal,confirming that the patient was definitively cured.Despite the favourable IL28B gene(rs12979860) CC-polymorphism observed in the patient,which is usually predictive of a spontaneous clearance and SVR,spontaneous viral clearance did not take place;however,infection with this genotype was promising for a sustained virological response after therapy.
文摘De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma(HCC) recurrence have been reported with the use of m TOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs m TOR-inhibitorfree immunosuppression is more efficacious in reducing HCC recurrence.
文摘Hepatitis B virus(HBV) infection is a dynamic state ofinteractions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B(CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma(HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.
文摘Liver transplantation(LT) is a life-saving treatment forpatients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus(HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus(HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
文摘Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation(OLT),the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival.Thromboembolism during OLT is characterized not only by a complex aetiology,but also by unpredictable onset and evolution of the disease.The initiation of a procoagulant process may be triggered by various factors,such as inflammation,venous stasis,ischemia-reperfusion injury,vascular clamping,anatomical and technical abnormalities,genetic factors,deficiency of profibrinolytic activity,and platelet activation.The involvement of the arterial system,intracardiac thrombosis,pulmonary emboli,portal vein thrombosis,and deep vein thrombosis,are among the most serious thrombotic events in the perioperative period.The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis,particularly when these events occur intraoperatively or early after OLT.Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting,many institutions recommend such an approach especially in the subset of patients at high risk.However,the decision of when,how and in what doses to use the various chemical anticoagulants is still a difficult task,since there is no common consensus,even for highrisk cases.The risk of postoperative thromboembolism causing severe hemodynamic events,or even loss of graft function,must be weighed and compared with the risk of an important bleeding.In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurringin the perioperative period,as well as their incidence and clinical features.Moreover,the indications to pharmacological prophylaxis and the current treatment strategies are also summarized.
文摘AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectivelyupdated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/hepatocellular carcinoma(HCC)] and into two interval times(2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS One thousand one hundred and ninty-four [male(M)/female(F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration(490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction(from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst decHCV(from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time(289/666, 43.4%), there was a trend towards a decrease after DAAs introduction(from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients(M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival(log-rank test P = 0.02) and delisting rate(P = 0.002) than untreated HCV patients. CONCLUSION Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis.
文摘Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.
文摘Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcareassociated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.
文摘The design of remediation works for the mitigation and prevention of the associated risk is needed where these geological hazards affect anthropized areas. Remedial measures for landslides commonly include slope reshaping, plumbing, drainage, retaining structures and internal slope reinforcement, while debris flow control works consist in open or closed control structures. The effectiveness of the remedial works implemented must be assessed by evaluating the reduction of the risk over time. The choice of the most appropriate and cost-effective intervention must consider the type of hazard and environmental issues, and selects, wherever possible, naturalistic engineering operations that are consequently implemented according to the environmental regulations or the design and specification standards imposed by the competent public administrations. The mitigation procedures consist of five basic steps:(a) acquisition of the knowledge of the hazard process;(b) risk assessment with identification of possible disaster scenarios;(c) planning and designing of specific remedial measures to reduce and/or eliminate the potential risk;(d) slope monitoring after application of remedial measures,(e) transfer of knowledge to the stakeholders. This paper presents two case studies describing the practice for the design of the mitigation measures adopted for debris flow and active landslide sites in North-Eastern Italy. The first case study is a debris flow site, for which, based on observation of past events and numerical simulations using the software FLOW-2D, the most suitable mitigation measures were found to be the construction of a debris basin, barriers and breakers. The second case study deals with an active landslide threatening a village. Based on the landslide kinematics and the results of numerical simulations performed with the code FLAC, hard engineering remedial works were planned to reduce the driving forces with benching and by increasing the available resisting forces using jet grout piles and deep drainage.
文摘Wilson's disease(WD), which results from the defective ATP7 B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury.
文摘Non-selective beta blockers(NSBB) are commonly used to prevent portal hypertensive bleeding in cirrhotics.Nevertheless, in the last years, the use of NSBB in critically decompensated patients, especially in those with refractory ascites, has been questioned, mainly for an increased risk of mortality and worsening of systemic hemodynamics. Moreover, even if NSBB have been reported to correlate with a higher risk of renal failure and severe infection in patients with advanced liver disease and hypotension, their use has been associated with a reduction of risk of spontaneous bacterial peritonitis, modification of gut permeability and reduction of bacterial translocation. This manuscript systematically reviews the published evidences about harms and benefits of the use of NSBB in patients with decompensated cirrhosis.
基金provided by Mary Hines and Sheridan Henness of Springer Healthcare Communications,and funded by Gilead Sciences Srl
文摘Chronic hepatitis C(CHC) is the most common indication for liver transplantation(LT). Aggressive treatment of hepatitis C virus(HCV) infection before cirrhosis development or decompensation may reduce LT need and risk of HCV recurrence post-LT. Factors associated with increased HCV risk or severity of recurrence include older age, immunosuppression, HCV genotype 1 and high viral load at LT. HCV recurrence post-LT leads to accelerated liver disease and cirrhosis development with reduced graft and patient survival. Currently, interferon(IFN)-based regimens can be used in dualagent regimens with ribavirin, in triple-agent antiviral strategies with direct-acting antivirals(e.g., protease inhibitors telaprevir or boceprevir), or before transplant in compensated patients to reduce HCV viral load to prevent or reduce the risk of post-LT recurrence and complications; they cannot be used in patients with decompensated cirrhosis. IFN-based regimens are used in less than half of HCV-infected patients waiting for LT due to extremely low efficacy and poor tolerability. However, antiviral therapy is indicated after LT in patients with histologically confirmed CHC despite tolerability issues. Improvements in side effect management have increased survival in patients achieving therapeutic targets. HCV treatment pre- and post-LT results in significant health care costs especially when lack of efficacy leads to disease worsening, although studies have shown sofosbuvir treatment before LT vs conventional post-LT dual antiviral is cost effective. The suboptimal efficacy and tolerability of IFN-based therapies, plus the significant economic burden, means the need for effective and well tolerated IFN-free antiHCV therapy for pre- and post-LT remains high.
文摘Objectives: To analyze the association between alexithymia and alcohol intake during adolescence, also in relation to psychopathology, in order to identify psychological risk factors for alcohol misuse. Method: 3556 students [mean age (range) 14.5 years (11-18)] were recruited in the Padua area. Each was administered a set of three questionnaires: the Toronto Alexithymia Scale for children (TAS-20) to measure alexithymia, the Questionnaire Adolescent Saturday evening (QAS) to estimate of alcohol intake, and the Youth Self-Report (YSR 11-18) to value psychopathology. Results: Externalizing problems appeared to increase with age and with the amount of alcohol consumed, unlike internalizing problems. The prevalence of alexithymia was 18%, decreasing with age, and it was not associated with alcohol consumption, and used except in younger subjects (≤13), for whom a positive correlation was observed between alexithymia, internalizing problems and alcohol intake. Conclusions: Younger adolescents are more psycho-emotionally vulnerable (internalizing problems and alexithymia) and at a greater risk of alcohol misuse.
文摘The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being "auto-anticoagulated", prone only to bleeding complications, and protected from thrombotic events. With greater attention to clinical thrombotic events, their impact on the natural history of cirrhosis, and with the emergence and increased use of point-of-care and global assays, it is now understood that cirrhosis results in profound hemostatic alterations that can lead to thrombosis as well as to bleeding complications. Although many clinical decisions are still based on traditional coagulation parameters such as prothrombin(PT), PT, and international normalized ratio, it is increasingly recognized that these tests do not adequately predict the risk of bleeding, nor they should guide pre-emptive interventions. Moreover, altered coagulation tests should not be considered as a contraindication to the use of anticoagulation, although this therapeutic or prophylactic approach is not at present routinely undertaken. Gastroesophageal variceal bleeding continues to be one of the most feared and deadly complications of cirrhosis and portal hypertension, but great progresses have been made in prevention and treatment strategies. Other bleeding sites that are frequently part of end-stage liver disease are similar to clinical manifestations of thrombocytopenia, with gum bleeding and epistaxis being very common but fortunately only rarely a cause of life-threatening bleeding. On the contrary, manifestations of coagulation factor deficiencies like soft tissue bleeding and hemartrosis are rare in patients with cirrhosis. As far as thrombotic complications are concerned, portal vein thrombosis is the most common event in patients with cirrhosis, but venous thromboembolism is not infrequent, and results in important morbidity and mortality in patients with cirrhosis, especially those with decompensated disease. Future studies and the more widespread use of point-ofcare tests in evaluating hemostasis will aid the clinician in decision making when facing the patient with bleeding or with thrombotic complications, with both ends of a continuum being potentially fatal.
文摘Liver transplant for hepatitis B virus(HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28(2%) received the graft from hepatitis B surface antigen positive(HBs Ag)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3-and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBs Agpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.
文摘The evolution of liver diseases to end-stage liver disease or to acute hepatic failure, the evaluation process for liver transplantation, the organ allocation decisionmaking, as well as the post-transplant outcomes are different between female and male genders. Women's access to liver transplantation is hampered by the use of model for end-stage liver disease(MELD) score, in which creatinine values exert a systematic bias against women due to their lower values even in the presence of variable degrees of renal dysfunction. Furthermore, even when correcting MELD score for gender-appropriate creatinine determination, a quantifiable uneven access to transplant prevails, demonstrating that other factors are also involved. While some of the differences can be explained from the epidemiological point of view, hormonal status plays an important role. Moreover, the pre-menopausal and post-menopausal stages imply profound differences in a woman's physiology, including not only the passage from the fertile age to the non-fertile stage, but also the loss of estrogens and their potentially protective role in delaying liver fibrosis progression, amongst others. With menopause, the tendency to gain weight may contribute to the development of or worsening of pre-existing metabolic syndrome. As an increasing number of patients are transplanted for non-alcoholic steatohepatitis, and as the average age at transplant increases, clinicians must be prepared for the management of this particular condition, especially in post-menopausal women, who are at particular risk of developing metabolic complications after menopause.
文摘The current attempt is aimed to outline the geometrical framework of a well known statistical problem, concerning the explicit expression of the arithmetic mean standard deviation distribution. To this respect, after a short exposition, three steps are performed as 1) formulation of the arithmetic mean standard deviation, , as a function of the errors, , which, by themselves, are statistically independent;2) formulation of the arithmetic mean standard deviation distribution, , as a function of the errors,;3) formulation of the arithmetic mean standard deviation distribution, , as a function of the arithmetic mean standard deviation, , and the arithmetic mean rms error, . The integration domain can be expressed in canonical form after a change of reference frame in the n-space, which is recognized as an infinitely thin n-cylindrical corona where the symmetry axis coincides with a coordinate axis. Finally, the solution is presented and a number of (well known) related parameters are inferred for sake of completeness.
基金Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos Ⅲ to support ángela Rojas postdoctoral contract,Consejería de Salud y Familias,Junta de Andalucía supporting Antonio Gil-Gómez contract,PI19/01404 Grant from Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,PI19/00589/Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,and the Xeptagen,Italy,provided the ELISA kits for the measurements of SCCA-IgM.
文摘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.