Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication

The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.

Predictive value of NLR, Fib4, and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma

BACKGROUND Neutrophil-lymphocyte ratio(NLR),fibrosis index based on four factors(Fib4),aspartate aminotransferase-to-platelet ratio index(APRI)can be used for prognostic evaluation of hepatocellular carcinoma.However,no study has established an individualized prediction model for the prognosis of hepatocellular carcinoma based on these factors.AIM To screen the factors that affect the prognosis of hepatocellular carcinoma and establish a nomogram model that predicts postoperative liver failure after hepatic resection in patients with hepatocellular carcinoma.METHODS In total,220 patients with hepatocellular carcinoma treated in our hospital from January 2022 to January 2023 were selected.They were divided into 154 participants in the modeling cohort,and 66 in the validation cohort.Comparative analysis of the changes in NLR,Fib4,and APRI levels in 154 patients with hepatocellular carcinoma before liver resection and at 3 mo,6 mo,and 12 mo postoperatively was conducted.Binary logistic regression to analyze the influencing factors on the occurrence of liver failure in hepatocellular carcinoma patients,roadmap prediction modeling,and validation,patient work characteristic curves(ROCs)to evaluate the predictive efficacy of the model,calibration curves to assess the consistency,and decision curve analysis(DCA)to evaluate the model’s validity were also conducted.RESULTS Binary logistic regression showed that Child-Pugh grading,Surgical site,NLR,Fib4,and APRI were all risk factors for liver failure after hepatic resection in patients with hepatocellular carcinoma.The modeling cohort built a column-line graph model,and the area under the ROC curve was 0.986[95%confidence in terval(CI):0.963-1.000].The patients in the validation cohort utilized the column-line graph to predict the probability of survival in the validation cohort and plotted the ROC curve with an area under the curve of the model of 0.692(95%CI:0.548-0.837).The deviation of the actual outcome curves from the calibration curves of the column-line plots generated by the modeling and validation cohorts was small,and the DCA confirmed the validity.CONCLUSION NLR,Fib4,and APRI independently influence posthepatectomy liver failure in patients with hepatocellular carcinoma.The column-line graph prediction model exhibited strong prognostic capability,with substantial concordance between predicted and actual events.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Non-anatomical liver resection for hepatocellular carcinoma:the SegSubTe classification to overcome the problem of heterogeneity

Background:The superiority of anatomical resection(AR)vs.non-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is debated.ARs are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous outcomes.This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor.Methods:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted.The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section(segmental,subsegmental or terminal next to the tumor)of vascular pedicles feeding the HCCs;then,the population was divided in“SegSubTe-IN”or“SegSubTe-OUT”groups,and the tumor recurrence and survival were analyzed.Results:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were SegSubTe-OUT.Total disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN vs.SegSubTe-OUT groups were 50%vs.83%(P=0.006),20%vs.52%(P=0.003)and 16%vs.39%(P=0.020),respectively.SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis.One-,three-,and five-year disease-free survival rates in the SegSubTe-IN vs.SegSubTe-OUT groups were 81%,58%and 35%vs.46%,21%and 11%,respectively(P<0.001).Conclusions:The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC,aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging

BACKGROUND The liver imaging reporting and data system(LI-RADS)diagnostic table has 15 cells and is too complex.The diagnostic performance of LI-RADS for hepatocellular carcinoma(HCC)is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging(EOB-MRI).AIM To evaluate the ability of the simplified LI-RADS(sLI-RADS)to diagnose HCC on EOB-MRI.METHODS A total of 331 patients with 356 hepatic observations were retrospectively analysed.The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLIRADS.The algorithms of sLI-RADS A-D are as follows:The single threshold for sLI-RADS A and B was 10 mm,that is,classified observations≥10mm using an algorithm of 10-19 mm observations(sLI-RADS A)and≥20 mm observations(sLI-RADS B)in the diagnosis table of LI-RADS v2018,respectively,while the classification algorithm remained unchanged for observations<10 mm;the single threshold for sLI-RADS C and D was 20 mm,that is,for<20 mm observations,the algorithms for<10 mm observations(sLI-RADS C)and 10-19 mm observations(sLI-RADS D)were used,respectively,while the algorithm remained unchanged for observations≥20 mm.With hepatobiliary phase(HBP)hypointensity as a major feature(MF),the final sLI-RADS(F-sLI-RADS)was formed according to the optimal sLI-RADS,and its diagnostic performance was evaluated.The times needed to classify the observations according to F-sLIRADS and LI-RADS v2018 were compared.RESULTS The optimal sLI-RADS was sLI-RADS D(with a single threshold of 20 mm),because its sensitivity was greater than that of LI-RADS v2018(89.8%vs 87.0%,P=0.031),and its specificity was not lower(89.4%vs 90.1%,P>0.999).With HBP hypointensity as an MF,the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018(93.0%vs 87.0%,P<0.001)and sLI-RADS D(93.0%vs 89.8%,P=0.016),without a lower specificity(86.5%vs 90.1%,P=0.062;86.5%vs 89.4%,P=0.125).Compared with that of LI-RADS v2018,the time to classify lesions according to FsLI-RADS was shorter(51±21 s vs 73±24 s,P<0.001).CONCLUSION The use of sLI-RADS with HBP hypointensity as an MF may improve the sensitivity of HCC diagnosis and reduce lesion classification time.

Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion:A case report

BACKGROUND Surgical resection and liver transplantation(LT)are the most effective curative options for hepatocellular carcinoma(HCC).However,few patients with huge HCC(>10 cm in diameter),especially those with portal vein tumor thrombus(PVTT),can receive these treatments.Selective internal radiation therapy(SIRT)can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume.However,in patients with huge HCC,high lung absorbed dose often prevents them from receiving SIRT.CASE SUMMARY A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month.The computed tomography scan showed a 20.2 cm×19.8 cm tumor located in the right lobe–left medial lobes with right portal vein and right hepatic vein invasion.After the pathological type of HCC was confirmed by biopsy,two conversions were presented.The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab,converted to SIRT,and the second one was sequential SIRT with continued systemic treatment.The tumor size significantly decreased from 20.2 cm×19.8 cm to 16.2 cm×13.8 cm,then sequentially to 7.8 cm×6.8 cm.In the meantime,the ratio of spared volume to total liver volume increased gradually from 34.4%to 55.7%,then to 62.9%.Furthermore,there was visualization of the portal vein,indicating regression of the tumor thrombus.Finally,owing to the new tumor in the left lateral lobe,the patient underwent LT instead of resection without major complications.CONCLUSION Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.

Coexistence of liver abscess, hepatic cystic echinococcosis and hepatocellular carcinoma: A case report

BACKGROUND Human cystic echinococcosis(CE)is a life-threatening zoonosis caused by the Echinococcus granulosus(sensu lato).Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality in the world.The coexistence of CE and HCC is exceedingly rare,and only several well-documented cases have been reported.In addition to this coexistence,there is no report of the coexistence of CE,HCC,and liver abscess to date.Herein,we aimed to report a case of coexistence of liver abscess,hepatic CE,and HCC.CASE SUMMARY A 65-year-old herdsman presented to the department of interventional therapy with jaundice,right upper abdominal distension and pain for 10 d.Laboratory test showed that he had positive results for HBsAg,HBeAb,HBcAb,and echino-coccosis IgG antibody.The test also showed an increased level of alpha fetopro-tein of 3400 ng/mL.An abdominal computed tomography(CT)scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver.In addition,CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images,the diagnoses of hepatic CE(CE4 subtype)and HCC were established.Initially,transarterial chemoembolization was performed for HCC.In the follow-up,liver abscess occurred in addition to CE and HCC;thus,percutaneous liver puncture drainage was performed.In the next follow-up,CE and HCC were stable.The liver abscess was completely resolved,and the patient was discharged with no evidence of recurrence.CONCLUSION This is the first reported case on the coexistence of liver abscess,hepatic CE,and HCC.Individualized treatment and multidisciplinary discussions should be performed in this setting.Therefore,treatment and diagnosis should be based on the characteristics of liver abscess,hepatic CE,and HCC,and in future clinical work,it is necessary to be aware of the possibility of this complex composition of liver diseases.

Liver abscess and tracheal fistula induced by transcatheter arterial chemoembolization for hepatocellular carcinoma:A case report

BACKGROUND Transarterial chemoembolization(TACE)is a standard treatment for intermediate-stage hepatocellular carcinoma(HCC).The complications of TACE include biliary tract infection,liver dysfunction,tumor lysis syndrome,biloma,partial intestinal obstruction,cerebral lipiodol embolism,etc.There are few reports about tracheal fistula induced by TACE.CASE SUMMARY A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC.Laboratory test results showed abnormalities of albumin,hemoglobin,prothrombin time,C-reactive protein,D-dimer,and prothrombin.Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens.Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver.Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal.Drainage for liver abscess by needle puncture under ultrasonic guidance was performed.After 1 month of drainage and anti-infection therapy,the abscess in the liver and the infection in the lung were reduced obviously,and the symptom of expectoration was relieved.CONCLUSION Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC.Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients:Hepatitis B virus infection and transaminases should be considered

BACKGROUND Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma(HCC),but a convenient and comprehensive method to assess liver condition is lacking.Liver stiffness(LS)measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition.Chronic hepatitis B(CHB)is an important risk factor for HCC progression,but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication.We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition.AIM To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB.METHODS A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus(HBV)-DNA levels[HBV-DNA≥100.00 IU/mL as Pos group(n=200)and<100.00 IU/mL as Neg group(n=84)].Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition.RESULTS A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition(P<0.05).When alanine aminotransferase(ALT)concentrations were normal(≤40 U/L),LS was correlated with liver condition indices(P<0.05),but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group(9.30 kPa)than the Pos group(7.40 kPa).When ALT levels were elevated(>40 U/L),the correlations between LS and liver condition indices were not significant(P>0.05).CONCLUSION LS was significantly correlated with most liver condition indices in patients with CHB and HCC.However,these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease

BACKGROUND Prevalence of hepatocellular carcinoma(HCC)is increasing,especially in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD).AIM To investigate rifaximin(RIF)effects on epigenetic/autophagy markers in animals.METHODS Adult Sprague-Dawley rats were randomly assigned(n=8,each)and treated from 5-16 wk:Control[standard diet,water plus gavage with vehicle(Veh)],HCC[high-fat choline deficient diet(HFCD),diethylnitrosamine(DEN)in drinking water and Veh gavage],and RIF[HFCD,DEN and RIF(50 mg/kg/d)gavage].Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained.RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis,and cirrhosis,but three RIF-group did not develop HCC.Comparing animals who developed HCC with those who did not,miR-122,miR-34a,tubulin alpha-1c(Tuba-1c),metalloproteinases-2(Mmp2),and metalloproteinases-9(Mmp9)were significantly higher in the HCC-group.The opposite occurred with Becn1,coactivator associated arginine methyltransferase-1(Carm1),enhancer of zeste homolog-2(Ezh2),autophagy-related factor LC3A/B(Map1 Lc3b),and p62/sequestosome-1(p62/SQSTM1)-protein.Comparing with controls,Map1 Lc3b,Becn1 and Ezh2 were lower in HCC and RIF-groups(P<0.05).Carm1 was lower in HCC compared to RIF(P<0.05).Hepatic expression of Mmp9 was higher in HCC in relation to the control;the opposite was observed for p62/Sqstm1(P<0.05).Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control(P=0.024).There was no difference among groups for Tuba-1c,Aldolase-B,alpha-fetoprotein,and Mmp2(P>0.05).miR-122 was higher in HCC,and miR-34a in RIF compared to controls(P<0.05).miR-26b was lower in HCC compared to RIF,and the inverse was observed for miR-224(P<0.05).There was no difference among groups regarding miR-33a,miR-143,miR-155,miR-375 and miR-21(P>0.05).CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

Exploring predictive markers for liver failure post-hepatectomy in hepatocellular carcinoma patients

This letter to the editor addresses the study titled“Predictive value of NLR,Fib4,and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma”by Kuang et al in the World Journal of Gastrointestinal Surgery.The study acknowledges the comprehensive patient data analysis while suggesting that there is a need for further discussion on the clinical applicability of these markers across diverse patient populations.This letter recommends prospective studies for validation and considers the influence of confounding factors.This finding underscores the significance of this study in improving hepatocellular carcinoma management.

Predicting liver function after hemihepatectomy in patients with hepatocellular carcinoma using different modalities

In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)represent the predominant histological types of primary liver cancer,comprising over 99%of cases.Given their differing biological behaviors,prognoses,and treatment strategies,accurately differentiating between HCC and ICC is crucial for effective clinical management.Radiomics,an emerging image processing technology,can automatically extract various quantitative image features that may elude the human eye.Reports on the application of ultrasound(US)-based radiomics methods in distinguishing HCC from ICC are limited.METHODS In our retrospective study,we included a total of 280 patients who were diagnosed with ICC(n=140)and HCC(n=140)between 1999 and 2019.These patients were divided into training(n=224)and testing(n=56)groups for analysis.US images and relevant clinical characteristics were collected.We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models.We compared the diagnostic performances of these ultrasomics models with that of radiologists.RESULTS Four distinct ultrasomics models were constructed,with the number of selected features varying between models:13 features for the US model;15 for the contrast-enhanced ultrasound(CEUS)model;13 for the combined US+CEUS model;and 21 for the US+CEUS+clinical data model.The US+CEUS+clinical data model yielded the highest area under the receiver operating characteristic curve(AUC)among all models,achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort.This performance exceeded even the most experienced radiologist(AUC=0.964).The AUC for the US+CEUS model(training cohort AUC=0.964,test cohort AUC=0.955)was significantly higher than that of the US model alone(training cohort AUC=0.822,test cohort AUC=0.816).This finding underscored the significant benefit of incorporating CEUS information in accurately distin-guishing ICC from HCC.CONCLUSION We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC,which outperformed experienced radiologists.

Systemic treatment of hepatocellular carcinoma secondary to nonalcoholic fatty liver disease

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death globally,with 15%of cases arising on a background of non-alcoholic fatty liver disease(NAFLD).NAFLD is a heterogenous condition ranging from fatty liver to cirrhosis and is itself a growing global problem,with estimated worldwide prevalence of 50%in 2040.Pathophysiology of NAFLD-HCC is not well understood,there are no dedicated screening programs,and there have been no clinical studies of anticancer treatments in this population specifically.However,the NAFLD-HCC population appears different than other aetiologies-patients tend to be older,diagnosed at more advanced stages,have more comorbidities,and overall worse prognosis.Understanding of best treatment options for this group of patients is an urgent unmet clinical need.This narrative review discusses NAFLD-HCC pathophysiology and systemic treatment,and offers suggestions for future directions in this therapy area.