Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, N...Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.展开更多
Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis...Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.展开更多
AIM: To compare the outcomes of pediatric patients weighing less than or more than 10 kg who underwent liver transplantation.METHODS: Data for 196 pediatric patients who underwent living donor liver transplantation be...AIM: To compare the outcomes of pediatric patients weighing less than or more than 10 kg who underwent liver transplantation.METHODS: Data for 196 pediatric patients who underwent living donor liver transplantation between June 1994 and February 2011 were reviewed retrospectively.The information for each patient was anonymized and de-identified before analysis. The data included information regarding the pre-transplant conditions, intraoperative fluid replacement and outcomes for each patient. The 196 patients were divided into two groups: those with body weights of less than 10 kg were included in group 1(G1; n =101), while those with body weights of more than 10 kg were included in group 2(G2; n = 95). For each group, the patients' ages, body weights, heights,pediatric end stage liver disease scores, anesthesia times, and warm and cold ischemic times were analyzed. In addition, between-group comparisons were also made. Mann-Whitney U tests were used to compare all the variables except for complications and survival rates, which were analyzed using χ 2 tests and Kaplan-Meier tests, respectively.RESULTS: The general medical conditions of the G1patients were worse than those of the G2 patients, as shown by the higher pediatric end stage liver disease scores and poorer Z-scores. In addition, the preoperative Hb and serum albumin levels were all lower for the G1 patients than for the G2 patients. The G1 patients also had significantly more intraoperative blood loss than the G2 patients. In addition, the intraoperative fluid requirements for the G1 patients,including leukocyte poor red blood cell transfusions,5% albumin infusions and crystalloid infusions, were significantly higher than those for the G2 patients. The risk of intraoperative portal vein thrombosis was higher for the patients in G1 than for those in G2. However,the one-year survival rates(95.9% and 96.8% for G1 and G2, respectively) and three-year survival rates(94.9% and 94.6% for G1 and G2, respectively) for both groups were similar.CONCLUSION: Patients weighing less than 10 kg typically have poorer conditions, but their survival rates are comparable to those of children weighing more than 10 kg.展开更多
AIM: Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the...AIM: Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the blood glucose levels in transfused and non-transfused patients during LT. METHODS: A retrospective study on 60 biliary pediatric patients and 16 adult patients undergoing LT was carried out. Transfused pediatric patients were included in Group Ⅰ (GⅠ), those not transfused in Group Ⅱ (GⅡ). Twelve adult patients were not given transfusion and assigned to Group Ⅲ(GⅢ); whereas, four adult patients who received massive transfusion were assigned to Group Ⅳ (GⅣ). The blood glucose levels, volume of blood transfused, and the volume of crystalloid infused were recorded, compared and analyzed. RESULTS: Results showed that the changes in blood glucose levels during LT for both non-transfused and minimally transfused pediatric groups and non-transfused and massively-transfused adult groups were almost the same. CONCLUSION: We conclude that blood transfusion does not cause significant changes in the blood glucose levels in this study.展开更多
AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A...AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.展开更多
Living donor liver transplantation (LDLT) is now performed with high rates of success due to judicious recipient and donor selection,careful preoperative planning, excellent anesthesia management, and prompt detection...Living donor liver transplantation (LDLT) is now performed with high rates of success due to judicious recipient and donor selection,careful preoperative planning, excellent anesthesia management, and prompt detection and treatment of complications. The indications for LDLT for adult and pediatric recipients should be the same as for deceased donor liver transplantation. Early postoperative complications are often defined as complications occurring within the first 3 months展开更多
The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics,virtual surgery s...The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics,virtual surgery simulation and using the created scenarios in real-time surgery using mixed reality.In this article,we described our experience on developing a dedicated 3 dimensional visualization and reconstruction software for surgeons to be used in advanced liver surgery and living donor liver transplantation.Furthermore,we shared the recent developments in the field by explaining the outreach of the software from virtual reality to augmented reality and mixed reality.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare e...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower healthrelated quality of life.To date,there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis(NASH).Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.AIM To investigate the efficacy and safety of semaglutide in patients with NAFLD.METHODS MEDLINE,CENTRAL,and EMBASE were searched from inception to May 1,2023,to identify eligible randomized controlled trials(RCTs).Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences(MD)or standardized MDs(SMD),and dichotomous outcomes as odds ratios(OR)with 95%confidence intervals(CI).Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic.RESULTS Three RCTs involving 458 patients were included.Semaglutide increased the likelihood of NASH resolution(OR:3.18,95%CI:1.70,5.95;P<0.001),improvement in steatosis(OR:2.83,95%CI:1.19,6.71;P=0.03),lobular inflammation(OR:1.81,95%CI:1.11,2.96;P=0.02),and hepatocellular ballooning(OR:2.92,95%CI:1.83,4.65;P<0.001),but not fibrosis stage(OR:0.71,95%CI:0.15,3.41;P=0.67).Radiologically,semaglutide reduced liver stiffness(SMD:-0.48,95%CI:-0.86,-0.11;P=0.01)and steatosis(MD:-4.96%,95%CI:-9.92,0.01;P=0.05).It also reduced alanine aminotransferase(MD:-14.06 U/L,95%CI:-22.06,-6.07;P<0.001)and aspartate aminotransferase(MD:-11.44 U/L,95%CI:-17.23,-5.65;P<0.001).Semaglutide led to improved cardiometabolic outcomes,including decreased HgA1c(MD:-0.77%,95%CI:-1.18,-0.37;P<0.001)and weight loss(MD:-6.53 kg,95%CI:-11.21,-1.85;P=0.006),but increased the occurrence of GIrelated side effects(OR:3.72,95%CI:1.68,8.23;P=0.001).Overall risk of serious adverse events was similar compared to placebo(OR:1.40,95%CI:0.75,2.62;P<0.29).CONCLUSION Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile.Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.展开更多
Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogen...Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.展开更多
AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009...AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.展开更多
AIM:To study the hemodynamics in the immediate post transplant period and compare patients with alcoholic vs viral cirrhosis. METHODS:Between 2000-2003,38 patients were transplanted for alcoholic cirrhosis and 28 for ...AIM:To study the hemodynamics in the immediate post transplant period and compare patients with alcoholic vs viral cirrhosis. METHODS:Between 2000-2003,38 patients were transplanted for alcoholic cirrhosis and 28 for postviral cirrhosis.Heart rate(HR),central venous pressure(CVP), mean arterial pressure(MAP),pulmonary capillary wedge pressure(PCWP),cardiac index(CI),systemic vascular resistance index(SVRI),pulmonary artery pressure(PAP),and pulmonary vascular resistance index(PVRI)were measured immediately and 24 h post transplantation. RESULTS:Hyperdynamic circulation persisted at 24 hfollowing transplantation with an elevated CI of 5.4± 1.3 L/(min×m 2 )and 4.9±1.0 L/(min×m 2 )in the viral and alcoholic groups,respectively,and was associated with a decreased SVRI.Within the first 24 h, there was a significant decrease in HR and increase in MAP;the extent of the change was similar in both groups.The CVP,PCWP,and SVRI increased,and CI decreased in the viral patients,but not the alcoholic patients.Alcoholics showed a lower PVRI(119±52 dynes/(cm 5 ×m 2 )vs 166±110 dynes/(cm5×m2),P< 0.05)and PAP(20±7 mmHg vs 24±7 mmHg,P< 0.05)compared to the viral group at 24 h. CONCLUSION:Hyperdynamic circulation persists in the immediate post-transplant period with a faster improvement in the viral group.Alcoholic patients have a more pronounced pulmonary vasodilatation.展开更多
Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality.It is a multisystem disease that is precipitated by ingesting large quantities o...Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality.It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role.Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy.Primary therapy remains abstinence and supportive care,as continued alcohol abuse is the most important risk factor for disease progression.The cornerstone of supportive care remains aggressive nutritional support,and although acute alcoholic hepatitis has been extensively studied,few specific medical therapies have been successful.Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis;however,the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary.While liver transplantation for acute alcoholic hepatitis have demonstrated promising results,this practice remains controversial and has not been advocated universally,with most transplant centers requiring a prolonged period of abstinence before considering transplantation.Extracorporeal liver support devices,although still experimental,have been developed as a form of liver support to give additional time for liver regeneration.These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.展开更多
Background:The immediate challenges during microvascular reconstruction of hepatic artery(HAR)during liver transplantation(LT)can be many.Hence,in order to give a cross sectional view of these problems this study over...Background:The immediate challenges during microvascular reconstruction of hepatic artery(HAR)during liver transplantation(LT)can be many.Hence,in order to give a cross sectional view of these problems this study over a period of 1 year,showing our routine practice,was taken up.Methods:From January 2015 to December 2015,a total of 133 LTs were performed in Kaohsiung Chang Gung Memorial Hospital,Taiwan.All hepatic artery(HA)reconstructions were performed by a microvascular surgeon under an operating microscope.Results:In the 133 patients,one artery was anastomosed in 123(92.5%)patients,two in 9(6.8%)patients and three in 1(0.7%)of the patient.Eleven(8.3%)arteries were less than 2 mm in size(1–1.9 mm).There were intimal dissections(IDs)involving either the donor or the recipient arteries of mild to severe nature in 9(6.8%)patients.Immediately following graft arterial anastomosis,either there was no flow or an intraoperative hepatic artery thrombosis(HAT)was found in nine(7.1%—8 LDLT,4.8%—1 DDLT)patients.Immediate re-do anastomosis was done in all of these patients who did well in the follow-up.The overall post-operative success rate was 99.2%.One patient(0.8%)developed postoperative HAT due to infection during follow up and died due to sepsis.Conclusions:Small vessels or HA injury are the frequently encountered problems by a micro vascular surgeon.The other problems could be ID,need to do multiple reconstructions,immediate HAT and ability to re-do the HAR immediately.展开更多
Background:We investigated the prognostic value of preoperative fibrinogen levels in hepatocellular carcinoma patients receiving liver transplantation by building a scoring model for predicting tumor recurrence.Method...Background:We investigated the prognostic value of preoperative fibrinogen levels in hepatocellular carcinoma patients receiving liver transplantation by building a scoring model for predicting tumor recurrence.Methods:Cox regression analysis was used to identify factors that predicted tumor recurrence,and a scoring model was generated by assigning a value of 0 or 1 to each independent risk factor.The cut-off value for fibrinogen was determined by receiver operating characteristic curve analysis.Results:Preoperative fibrinogen concentration was significantly higher in patients with vs.without tumor recurrence(3.27 g/L vs.2.34 g/L,P<0.001),with vs.without macrovascular invasion(3.54 g/L vs.2.82 g/L,P?0.007),and with>400 vs.400 ng/mL plasma alpha-fetoprotein concentration(3.43 g/L vs.2.76 g/L,P?0.007).The 5-year disease-free survival rate was significantly lower for patients with elevated(2.68 g/L)vs.normal(<2.68 g/L)fibrinogen concentration(37.2%vs.78.4%,P?0.001).Macrovascular invasion,>3 tumor nodules,and elevated fibrinogen concentration were independent risk factors for tumor recurrence.A scoring model based on these risk factors predicted recurrence with a sensitivity of 68.3%and a specificity of 87.5%.Conclusions:Elevated preoperative plasma fibrinogen concentration is associated with tumor recurrence in HCC patients after liver transplantation.A new scoring model predicted recurrence with good sensitivity and specificity.展开更多
AIM： Autologous blood donation （ABD） is mainly used to reduce the use of banked blood. In fact, ABD can be regarded as acute blood loss. Would ABD 2-3 d before operation affect the CVP level and subsequently result...AIM： Autologous blood donation （ABD） is mainly used to reduce the use of banked blood. In fact, ABD can be regarded as acute blood loss. Would ABD 2-3 d before operation affect the CVP level and subsequently result in less blood loss during liver resection was to be determined.METHODS： Eighty-four patients undergoing living donor left hepatectomy were retrospectively divided as group Ⅰ （GⅠ） and group Ⅱ （GⅡ） according to have donated 250-300 mL blood 2-3 d before living donor hepatectomy or not. The changes of the intraoperative CVP, surgical blood loss,blood products used and the changes of perioperative hemoglobin （Hb） between groups were analyzed and compared by using Mann-Whitney Utest.RESULTS： The results show that the intraoperative CVP changes between GⅠ （n = 35） and GⅡ （n = 49） up to graft procurement were the same, subsequently the blood loss,but ABD resulted in significantly lower perioperative Hb levels in GI.CONCLUSION： Since none of the patients required any blood products perioperatively, all the predonated bloods were discarded after the patients were discharged from the hospital. It indicates that ABD in current series had no any beneficial effects, in term of cost, lowering the CVP, blood loss and reduce the use of banked blood products, but resulted in significant lower Hb in perioperative period.展开更多
Introduction: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and usually appears as part of liver cirrhosis (LC). Its management in the presence of LC is ideally with orthotopic liver tra...Introduction: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and usually appears as part of liver cirrhosis (LC). Its management in the presence of LC is ideally with orthotopic liver transplantation. Surgical resection is indicated only in the presence of a tumor in a patient with a very good liver function and who for medical reasons cannot be carried to transplantation. Materials and Methods: A descriptive study of a prospective and consecutive series of patients undergoing surgery (resection or liver transplantation) for HCC in a hospital in the city of Medellin was performed, from June 2004 to January 2015. A multivariate analysis was carried out of factors associated with survival during the follow-up. Results: 116 surgical interventions for the management of HCC between June 2004 and January 2015 were performed. The analysis included 107 patients, of which 73% were men. The median age of all patients was 60 years. The factors that showed better survival were: patients undergoing transplantation, the presence of cirrhosis, tumor less than 5 cm in diameter, a unique and well-differentiated tumor;however, none of these factors achieved statistical significance. Conclusion: Both resection and liver transplantation, when well indicated achieve good 5-years of survival in patients with HCC.展开更多
Aim:The aim was to analyze the feasibility of salvage liver transplant after liver resection in hepatocellular carcinoma(HCC)with hepatitis C virus(HCV)etiology.Methods:All the patients diagnosed with HCC with HCV eti...Aim:The aim was to analyze the feasibility of salvage liver transplant after liver resection in hepatocellular carcinoma(HCC)with hepatitis C virus(HCV)etiology.Methods:All the patients diagnosed with HCC with HCV etiology who underwent living donor liver transplant from July 2002 to November 2012 were studied.Their recurrence rate,mortality,and prognostic factors were analyzed and compared between primary transplant and salvage transplant for up to 5 years post-transplant.Results:One hundred and nine patients underwent a liver transplant for HCC associated with HCV etiology within the University of California,San Francisco criteria.Eighteen were post-hepatectomy salvage transplants and 91 were primary transplants.Median follow-up time was 31 months.One,3 and 5 years overall survival rates were 76%,76%and 65%in the salvage group,and 92%,85%and 85%in primary transplant group respectively.The difference in overall survival rates was statistically signifi cant(P=0.031).However,recurrence-free survivals for 1,3 and 5 years were 72%,72%and 46%for salvage group,and 91%,73%and 46%for primary transplant group;which were not statistically signifi cant(P=0.328).Conclusion:Salvage transplantation for post-hepatectomy recurrence for patients with HCC associated with HCV-related chronic liver disease seems to offer inferior overall survival rates than primary transplantation.展开更多
Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we ...Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.展开更多
In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasv...In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.展开更多
Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expres...Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment.展开更多
文摘Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.
文摘Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.
文摘AIM: To compare the outcomes of pediatric patients weighing less than or more than 10 kg who underwent liver transplantation.METHODS: Data for 196 pediatric patients who underwent living donor liver transplantation between June 1994 and February 2011 were reviewed retrospectively.The information for each patient was anonymized and de-identified before analysis. The data included information regarding the pre-transplant conditions, intraoperative fluid replacement and outcomes for each patient. The 196 patients were divided into two groups: those with body weights of less than 10 kg were included in group 1(G1; n =101), while those with body weights of more than 10 kg were included in group 2(G2; n = 95). For each group, the patients' ages, body weights, heights,pediatric end stage liver disease scores, anesthesia times, and warm and cold ischemic times were analyzed. In addition, between-group comparisons were also made. Mann-Whitney U tests were used to compare all the variables except for complications and survival rates, which were analyzed using χ 2 tests and Kaplan-Meier tests, respectively.RESULTS: The general medical conditions of the G1patients were worse than those of the G2 patients, as shown by the higher pediatric end stage liver disease scores and poorer Z-scores. In addition, the preoperative Hb and serum albumin levels were all lower for the G1 patients than for the G2 patients. The G1 patients also had significantly more intraoperative blood loss than the G2 patients. In addition, the intraoperative fluid requirements for the G1 patients,including leukocyte poor red blood cell transfusions,5% albumin infusions and crystalloid infusions, were significantly higher than those for the G2 patients. The risk of intraoperative portal vein thrombosis was higher for the patients in G1 than for those in G2. However,the one-year survival rates(95.9% and 96.8% for G1 and G2, respectively) and three-year survival rates(94.9% and 94.6% for G1 and G2, respectively) for both groups were similar.CONCLUSION: Patients weighing less than 10 kg typically have poorer conditions, but their survival rates are comparable to those of children weighing more than 10 kg.
文摘AIM: Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the blood glucose levels in transfused and non-transfused patients during LT. METHODS: A retrospective study on 60 biliary pediatric patients and 16 adult patients undergoing LT was carried out. Transfused pediatric patients were included in Group Ⅰ (GⅠ), those not transfused in Group Ⅱ (GⅡ). Twelve adult patients were not given transfusion and assigned to Group Ⅲ(GⅢ); whereas, four adult patients who received massive transfusion were assigned to Group Ⅳ (GⅣ). The blood glucose levels, volume of blood transfused, and the volume of crystalloid infused were recorded, compared and analyzed. RESULTS: Results showed that the changes in blood glucose levels during LT for both non-transfused and minimally transfused pediatric groups and non-transfused and massively-transfused adult groups were almost the same. CONCLUSION: We conclude that blood transfusion does not cause significant changes in the blood glucose levels in this study.
基金Supported by A grant from Chang Gung Memorial Hospital,CMRPG8A0631 to Chiu KW of Taiwan
文摘AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.
文摘Living donor liver transplantation (LDLT) is now performed with high rates of success due to judicious recipient and donor selection,careful preoperative planning, excellent anesthesia management, and prompt detection and treatment of complications. The indications for LDLT for adult and pediatric recipients should be the same as for deceased donor liver transplantation. Early postoperative complications are often defined as complications occurring within the first 3 months
文摘The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics,virtual surgery simulation and using the created scenarios in real-time surgery using mixed reality.In this article,we described our experience on developing a dedicated 3 dimensional visualization and reconstruction software for surgeons to be used in advanced liver surgery and living donor liver transplantation.Furthermore,we shared the recent developments in the field by explaining the outreach of the software from virtual reality to augmented reality and mixed reality.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower healthrelated quality of life.To date,there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis(NASH).Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.AIM To investigate the efficacy and safety of semaglutide in patients with NAFLD.METHODS MEDLINE,CENTRAL,and EMBASE were searched from inception to May 1,2023,to identify eligible randomized controlled trials(RCTs).Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences(MD)or standardized MDs(SMD),and dichotomous outcomes as odds ratios(OR)with 95%confidence intervals(CI).Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic.RESULTS Three RCTs involving 458 patients were included.Semaglutide increased the likelihood of NASH resolution(OR:3.18,95%CI:1.70,5.95;P<0.001),improvement in steatosis(OR:2.83,95%CI:1.19,6.71;P=0.03),lobular inflammation(OR:1.81,95%CI:1.11,2.96;P=0.02),and hepatocellular ballooning(OR:2.92,95%CI:1.83,4.65;P<0.001),but not fibrosis stage(OR:0.71,95%CI:0.15,3.41;P=0.67).Radiologically,semaglutide reduced liver stiffness(SMD:-0.48,95%CI:-0.86,-0.11;P=0.01)and steatosis(MD:-4.96%,95%CI:-9.92,0.01;P=0.05).It also reduced alanine aminotransferase(MD:-14.06 U/L,95%CI:-22.06,-6.07;P<0.001)and aspartate aminotransferase(MD:-11.44 U/L,95%CI:-17.23,-5.65;P<0.001).Semaglutide led to improved cardiometabolic outcomes,including decreased HgA1c(MD:-0.77%,95%CI:-1.18,-0.37;P<0.001)and weight loss(MD:-6.53 kg,95%CI:-11.21,-1.85;P=0.006),but increased the occurrence of GIrelated side effects(OR:3.72,95%CI:1.68,8.23;P=0.001).Overall risk of serious adverse events was similar compared to placebo(OR:1.40,95%CI:0.75,2.62;P<0.29).CONCLUSION Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile.Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.
文摘Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.
文摘AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.
基金Supported by Research grants from the Canadian Liver Foundation
文摘AIM:To study the hemodynamics in the immediate post transplant period and compare patients with alcoholic vs viral cirrhosis. METHODS:Between 2000-2003,38 patients were transplanted for alcoholic cirrhosis and 28 for postviral cirrhosis.Heart rate(HR),central venous pressure(CVP), mean arterial pressure(MAP),pulmonary capillary wedge pressure(PCWP),cardiac index(CI),systemic vascular resistance index(SVRI),pulmonary artery pressure(PAP),and pulmonary vascular resistance index(PVRI)were measured immediately and 24 h post transplantation. RESULTS:Hyperdynamic circulation persisted at 24 hfollowing transplantation with an elevated CI of 5.4± 1.3 L/(min×m 2 )and 4.9±1.0 L/(min×m 2 )in the viral and alcoholic groups,respectively,and was associated with a decreased SVRI.Within the first 24 h, there was a significant decrease in HR and increase in MAP;the extent of the change was similar in both groups.The CVP,PCWP,and SVRI increased,and CI decreased in the viral patients,but not the alcoholic patients.Alcoholics showed a lower PVRI(119±52 dynes/(cm 5 ×m 2 )vs 166±110 dynes/(cm5×m2),P< 0.05)and PAP(20±7 mmHg vs 24±7 mmHg,P< 0.05)compared to the viral group at 24 h. CONCLUSION:Hyperdynamic circulation persists in the immediate post-transplant period with a faster improvement in the viral group.Alcoholic patients have a more pronounced pulmonary vasodilatation.
文摘Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality.It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role.Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy.Primary therapy remains abstinence and supportive care,as continued alcohol abuse is the most important risk factor for disease progression.The cornerstone of supportive care remains aggressive nutritional support,and although acute alcoholic hepatitis has been extensively studied,few specific medical therapies have been successful.Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis;however,the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary.While liver transplantation for acute alcoholic hepatitis have demonstrated promising results,this practice remains controversial and has not been advocated universally,with most transplant centers requiring a prolonged period of abstinence before considering transplantation.Extracorporeal liver support devices,although still experimental,have been developed as a form of liver support to give additional time for liver regeneration.These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.
文摘Background:The immediate challenges during microvascular reconstruction of hepatic artery(HAR)during liver transplantation(LT)can be many.Hence,in order to give a cross sectional view of these problems this study over a period of 1 year,showing our routine practice,was taken up.Methods:From January 2015 to December 2015,a total of 133 LTs were performed in Kaohsiung Chang Gung Memorial Hospital,Taiwan.All hepatic artery(HA)reconstructions were performed by a microvascular surgeon under an operating microscope.Results:In the 133 patients,one artery was anastomosed in 123(92.5%)patients,two in 9(6.8%)patients and three in 1(0.7%)of the patient.Eleven(8.3%)arteries were less than 2 mm in size(1–1.9 mm).There were intimal dissections(IDs)involving either the donor or the recipient arteries of mild to severe nature in 9(6.8%)patients.Immediately following graft arterial anastomosis,either there was no flow or an intraoperative hepatic artery thrombosis(HAT)was found in nine(7.1%—8 LDLT,4.8%—1 DDLT)patients.Immediate re-do anastomosis was done in all of these patients who did well in the follow-up.The overall post-operative success rate was 99.2%.One patient(0.8%)developed postoperative HAT due to infection during follow up and died due to sepsis.Conclusions:Small vessels or HA injury are the frequently encountered problems by a micro vascular surgeon.The other problems could be ID,need to do multiple reconstructions,immediate HAT and ability to re-do the HAR immediately.
基金supported by Science and Technology Planning Project of Guangdong Province,China(2017B020209004)Major State Research Development Program of China(2017ZX10203205-006-001,2017ZX10203205-001-003).
文摘Background:We investigated the prognostic value of preoperative fibrinogen levels in hepatocellular carcinoma patients receiving liver transplantation by building a scoring model for predicting tumor recurrence.Methods:Cox regression analysis was used to identify factors that predicted tumor recurrence,and a scoring model was generated by assigning a value of 0 or 1 to each independent risk factor.The cut-off value for fibrinogen was determined by receiver operating characteristic curve analysis.Results:Preoperative fibrinogen concentration was significantly higher in patients with vs.without tumor recurrence(3.27 g/L vs.2.34 g/L,P<0.001),with vs.without macrovascular invasion(3.54 g/L vs.2.82 g/L,P?0.007),and with>400 vs.400 ng/mL plasma alpha-fetoprotein concentration(3.43 g/L vs.2.76 g/L,P?0.007).The 5-year disease-free survival rate was significantly lower for patients with elevated(2.68 g/L)vs.normal(<2.68 g/L)fibrinogen concentration(37.2%vs.78.4%,P?0.001).Macrovascular invasion,>3 tumor nodules,and elevated fibrinogen concentration were independent risk factors for tumor recurrence.A scoring model based on these risk factors predicted recurrence with a sensitivity of 68.3%and a specificity of 87.5%.Conclusions:Elevated preoperative plasma fibrinogen concentration is associated with tumor recurrence in HCC patients after liver transplantation.A new scoring model predicted recurrence with good sensitivity and specificity.
文摘AIM： Autologous blood donation （ABD） is mainly used to reduce the use of banked blood. In fact, ABD can be regarded as acute blood loss. Would ABD 2-3 d before operation affect the CVP level and subsequently result in less blood loss during liver resection was to be determined.METHODS： Eighty-four patients undergoing living donor left hepatectomy were retrospectively divided as group Ⅰ （GⅠ） and group Ⅱ （GⅡ） according to have donated 250-300 mL blood 2-3 d before living donor hepatectomy or not. The changes of the intraoperative CVP, surgical blood loss,blood products used and the changes of perioperative hemoglobin （Hb） between groups were analyzed and compared by using Mann-Whitney Utest.RESULTS： The results show that the intraoperative CVP changes between GⅠ （n = 35） and GⅡ （n = 49） up to graft procurement were the same, subsequently the blood loss,but ABD resulted in significantly lower perioperative Hb levels in GI.CONCLUSION： Since none of the patients required any blood products perioperatively, all the predonated bloods were discarded after the patients were discharged from the hospital. It indicates that ABD in current series had no any beneficial effects, in term of cost, lowering the CVP, blood loss and reduce the use of banked blood products, but resulted in significant lower Hb in perioperative period.
文摘Introduction: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and usually appears as part of liver cirrhosis (LC). Its management in the presence of LC is ideally with orthotopic liver transplantation. Surgical resection is indicated only in the presence of a tumor in a patient with a very good liver function and who for medical reasons cannot be carried to transplantation. Materials and Methods: A descriptive study of a prospective and consecutive series of patients undergoing surgery (resection or liver transplantation) for HCC in a hospital in the city of Medellin was performed, from June 2004 to January 2015. A multivariate analysis was carried out of factors associated with survival during the follow-up. Results: 116 surgical interventions for the management of HCC between June 2004 and January 2015 were performed. The analysis included 107 patients, of which 73% were men. The median age of all patients was 60 years. The factors that showed better survival were: patients undergoing transplantation, the presence of cirrhosis, tumor less than 5 cm in diameter, a unique and well-differentiated tumor;however, none of these factors achieved statistical significance. Conclusion: Both resection and liver transplantation, when well indicated achieve good 5-years of survival in patients with HCC.
文摘Aim:The aim was to analyze the feasibility of salvage liver transplant after liver resection in hepatocellular carcinoma(HCC)with hepatitis C virus(HCV)etiology.Methods:All the patients diagnosed with HCC with HCV etiology who underwent living donor liver transplant from July 2002 to November 2012 were studied.Their recurrence rate,mortality,and prognostic factors were analyzed and compared between primary transplant and salvage transplant for up to 5 years post-transplant.Results:One hundred and nine patients underwent a liver transplant for HCC associated with HCV etiology within the University of California,San Francisco criteria.Eighteen were post-hepatectomy salvage transplants and 91 were primary transplants.Median follow-up time was 31 months.One,3 and 5 years overall survival rates were 76%,76%and 65%in the salvage group,and 92%,85%and 85%in primary transplant group respectively.The difference in overall survival rates was statistically signifi cant(P=0.031).However,recurrence-free survivals for 1,3 and 5 years were 72%,72%and 46%for salvage group,and 91%,73%and 46%for primary transplant group;which were not statistically signifi cant(P=0.328).Conclusion:Salvage transplantation for post-hepatectomy recurrence for patients with HCC associated with HCV-related chronic liver disease seems to offer inferior overall survival rates than primary transplantation.
基金supported in part by grants from the GuangdongGuang-dong Natural Science Foundation(Nos.2015A030313038,2015A030312013)Science and Technology Program of Guangzhou City(No.201607010024)Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027).
文摘Background and Aims:Numerous studies have explored the important role of N6-methyladenosine(m^(6)A)in cancer.Nonetheless,the interaction between m^(6)A and long noncoding RNAs(lncRNAs)is poorly investigated.Herein,we systematically analyzed the role and prognostic value of m^(6)A-related lncRNAs in hepatocellular carcinoma(HCC).Methods:The m^(6)A-related lncRNAs were identified based on the correlation coefficients with m^(6)A-related genes in HCC from The Cancer Genome Atlas.Subsequently,a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses.Univariate and multivariate Cox analyses were used to identify independent prog-nostic factors for overall survival(OS)of HCC;thereafter,a prognostic nomogram was constructed.Results:A total of 259 lncRNAs showed significant correlations with m^(6)A in HCC,while 29 lncRNAs had prognostic significance.Further,six critical m^(6)A-related lncRNAs(NRAV,SNHG3,KDM4A-AS1,AC074117.1,AC025176.1,and AL031985.3)were screened out to construct a novel risk score model which classified HCC patients into high-and low-risk groups.Survival analy-ses revealed that patients in the high-risk group exhibited worse OS,both in the training and validation groups.The risk score was also identified as an independent prognostic factor of OS,and a nomogram was established and verified with superior prediction capacity.Besides,the risk score signifi-cantly correlated with the expression of immune checkpoint genes and immune subtypes.Conclusions:These findings indicated the significant role of m^(6)A-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.
文摘In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.
基金supported in part by grants from the Guangdong Natural Science Foundation(Nos.2015A030313038 and 2015A030312013)Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027)National Natural Science Foundation of China(Nos.81770648 and 81972286).
文摘Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment.
