Efficacy and complications of transarterial chemoembolization alone or in combination with different protocols for hepatocellular carcinoma: A Bayesian network meta-analysis of randomized controlled trials

Background and aims:Transarterial chemoembolization(TACE)is the standard treatment for most intermediate-toadvanced stage hepatocellular carcinoma.With the ongoing development of interventional therapies,TACE in combination with different protocols is being explored.A network meta-analysis to collect recent evidence in this field is required.Methods:We searched PubMed,Web of Science,Cochrane Central Register of Controlled Trials,Embase,Chinese National Knowledge Infrastructure database,Cochrane Library,and Wanfang database from their inception to May 2022 for randomized controlled trials(RCTs)that reported TACE in combination with different protocols for hepatocellular carcinoma.Results:In total,67 RCTs assessing eight combination treatments were included.The quality of primary outcomes was from moderate to low.The Bayesian network meta-analysis confirmed that TACE combined with iodine-125 seed implantation had the highest probability of 1-year survival rate and TACE combined with sorafenib had the highest probability of 2-year survival rate.TACE alone had the highest probability of incidence of fever,TACE combined with sorafenib had the highest probability of incidence of pain and TACE combined with percutaneous ethanol injection had the highest probability of incidence of nausea and vomiting.Conclusion:This Bayesian network meta-analysis found that TACE combined with iodine-125 seed and TACE combined with sorafenib may benefit patients in terms of 1-year survival and 2-year survival,respectively.To confirm this conclusion,high-quality and well-designed RCTs with a larger sample size are needed.

Free fatty acid-induced miR-22 inhibits gluconeogenesis via SIRT-1-mediated PGC-1α expression in nonalcoholic fatty liver disease

Background and aims:Free fatty acids(FFAs)are one of the important regulators of the progression of nonalcoholic fatty liver disease.The FFAs are shown to modulate the metabolic status of the liver by modulating several cellular pathways in hepatocytes.Here,we elucidated the role of miR-22 in modulating FFAs-mediated gluconeogenesis.Methods:Huh7 and WRL68 cells were transfected with nonspecific miRNA,miR-22 premiRs or anti-miR-22 oligos followed by incubation with palmitic acid,oleic acid,and linoleic acid(300μM each)for 48 and 72 h after transfection.The expression of miR-22 was performed using real-time polymerase chain reaction and Western blots were performed for SIRT-1,PGC-1α,PEPCK,and glucose-6-phosphatase.Three groups of C57BL/6 mice(6 mice per group)were fed with standard diet,choline sufficient L-amino acid defined diet or choline-deficient L-amino acid defined(CDAA)diet for 6,18,32,or 54 weeks.Triglycerides content was measured in the serum.Expression of miR-22 and the protein expression of gluconeogenic enzymes were analyzed in the tissue samples.Results:Incubation of miR-22-transfected cells with FFAs inhibited the expression of SIRT-1,PGC-1α,PEPCK,and glucose-6-phosphatase,while miR-22 expression was increased.These changes were reversed when the cells were transfected with anti-miR-22 oligos.CDAA-fed mice showed the significant increase in triglycerides content and miR-22 expression,while there was an inhibition of SIRT-1,PGC-1α,PEPCK,and glucose-6-phosphatase expression in CDAA-fed mice.

Evaluating Tislelizumab, Lenvatinib, and FOLFOX4-HAIC as a Conversion Therapy for Unresectable Hepatocellular Carcinoma

Background and aims:Conversion therapy downstages tumors and renders patients with unresectable hepatocel-lular carcinoma(HCC)eligible for radical resection.This study aimed to evaluate the efficacy and safety of tislelizumab plus lenvatinib and hepatic artery infusion chemotherapy with oxaliplatin,fluorouracil,and leuco-vorin(FOLFOX4-HAIC)as a first-line conversion therapy.Methods:Clinical data from HCC patients who were treated with the triple therapy between April 2021 and April 2022 were retrospectively analyzed.The primary outcome included objective response rate(ORR),disease control rate(DCR),conversion resection rate(CRR),and treatment-related adverse events(TRAEs).Results:A total of 18 patients completed conversion therapy assessment,which ended on March 27,2023.The patients had a median age of 55.5(37–72)years,and 94.4%were male.According to mRECIST,tumor shrinkage was observed in all patients,with an ORR of 94.4%(17/18),a DCR of 94.4%(17/18),and a median time to response of 1.4(0.7–3.0)months.Successful conversion was observed in 61.1%(11/18)of patients(mRECIST).The CRR and pathological complete response were 38.9%(7/18)and 57.1%(4/7),respectively.The median progression-free survival(PFS)was 17.8 months,while median overall survival was not reached.The 6-and 9-month PFS rates were 83.3%and 66.7%,respectively.The most common TRAE(16/18 patients,88.9%)was an increase in aspartate aminotransferase levels.Conclusion:Tislelizumab combined with lenvatinib and FOLFOX4-HAIC achieved a high conversion rate and acceptable toxicity in patients with unresectable HCC,suggesting that this combination may represent a new conversion strategy for this population.

When liver disease diagnosis encounters deep learning:Analysis,challenges,and prospects

The liver is the second-largest organ in the human body and is essential for digesting food and removing toxic substances.Viruses,obesity,alcohol use,and other factors can damage the liver and cause liver disease.The diagnosis of liver disease used to depend on the clinical experience of doctors,which made it subjective,difficult,and time-consuming.Deep learning has made breakthroughs in various fields;thus,there is a growing interest in using deep learning methods to solve problems in liver research to assist doctors in diagnosis and treatment.In this paper,we provide an overview of deep learning in liver research using 139 papers from the last 5 years.We also show the relationship between data modalities,liver topics,and applications in liver research using Sankey diagrams and summarize the deep learning methods used for each liver topic,in addition to the relations and trends between these methods.Finally,we discuss the challenges of and expectations for deep learning in liver research.

Hepatic allograft rejection after liver transplantation: Clinicopathological debates

Liver transplantation(LT)represents a life-saving surgical procedure and is considered the current standard of care for the majority of patients having end-stage liver disease.As known,significant progress in organ preservation techniques,perioperative care,and strict immunosuppression protocols are associated with favorable patient/graft survival post-LT.Hence,proper evaluation of liver allograft-related complications among survivors has paid great attention,particularly the rejection sequel after LT.It is a seriously underestimated cause of allograft injury,which pushes researchers for understanding the exact pathogenesis of different types and proper time diagnosis for better management of such complications.However,it still represents a challenge because of the complexities related to diagnosis and histopathology.Hence,increasing clinical awareness with earlier diagnosis of post-LT rejection is essential through stimulating further studies.Therefore,our review will focus on the clinicopathological debates regarding liver allograft loss after transplantation.

Hepatocellular Carcinoma Gene Expression: The New Era, Where It goes?

Hepatocellular carcinoma is known to be a common primary liver malignancy and a serious leading cause of cancerrelated mortality globally.Hence,ongoing recent advances in the genetic field regarding hepatocellular carcinoma paid researchers great attention to identifying various biomarkers to act as diagnostic and prognostic tools for the early detection of hepatocellular carcinoma and also developing targeted therapeutic agents that are indicated and available for advanced stages of hepatocellular carcinomas,however,their antitumor efficacy remains limited and under investigations.Therefore,our review summarized the genetic studies of liver cancer focusing on the somatic mutations,copy number variations,and epigenetic modifications that represent early alterations and oncodrivers in hepatocarcinogenesis,Moreover,the identification of genetic signatures and proteomic targets through hepatocellular carcinoma-related genome-wide screening,to show the ongoing clinical application of such analysis to facilitate diagnosis,prognosis and management of patients with hepatocellular carcinoma for a better outcome.

The transjugular intrahepatic portosystemic shunt: Smaller stent diameters are required to optimize pressure response

Background and aims:The present treatment goal of the transjugular intrahepatic portosystemic shunt(TIPS)is a portosystemic pressure gradient of
12 mmHg or its reduction by>50%.This study relates the stent diameter to the reduction of the pressure gradient and attempts to predict the appropriate stent diameter necessary to reach the treatment goal.Methods:Pressure response,super response,and poor response were investigated in 208 de-novo TIPS patients and defined as post-TIPS gradients between>6 and 12 mmHg,
6 mmHg,or not reaching the goal(>12 mmHg,reduction<50%),respectively.Pressures were related to the smallest stent diameters measured by planimetry of the radiographic image.Results:Responders(65%),super responders(26%),or poor responders(9%)had comparable stent diameters of 7.21.0 mm,but different post-TIPS gradients(9.71.9 mmHg,4.51.5 mmHg,and 14.21.4 mmHg,p<0.001),relative reduction of pre-TIPS gradients(51.711.4%,73.611.1%,and 34.09.1%,p<0.001),and specific reduction per mm of stent diameter(7.52.0%/mm,10.12.0%/mm,and 4.81.4%/mm,p<0.001).Prediction of the stent diameter required to reach response was not possible.Only two super responders had a stent diameter of<6 mm.Super and poor responders differed by the increase in the right atrial pressure(+5.0 mmHg vs.+3.1 mmHg,p=0.026)and reduction in the portal vein pressure(-8.6 mmHg vs.-4.6 mmHg,p<0.001).Conclusion:Most patients reached the treatment goal with stent diameters of<8 mm.Overtreatment(super response,gradient ≤6 mmHg)can be prevented by stent diameters as small as 6 mm.The individual response was not related to the stent diameter and not predictable.Cardiac dysfunction may play an important role by its effect on the right atrial(preload)and portal pressure(afterload).

General-motors diet: A quick fix for steatotic live liver donors

Background and aims:GM(General-Motors)diet is a low-calorie 7-day diet plan using complex carbohydrates used for quick weight loss.Dietary optimisation is known to decrease steatosis and improve outcomes in liver donors.We evaluated the efficacy and feasibility of using GM diet in steatotic live liver donors(LLD).Methods:LLDs who either had BMI>30 kg/m^(2),Computerised tomography liver attenuation index(CT-LAI)<0 HU,Magnetic resonance(MR)fat-fraction of>10%were started on GM diet for 1 week.Records of these LLDs and their recipients were retrieved retrospectively and analysed.Weight,liver function tests(LFT),MR fat-frac-tion,CT-LAI,hospital-stay and complications were analysed in LLDs while early graft dysfunction(EGD)and complications were assessed in recipients.Results:A total of 51 LLDs with mean age of 34.6?9.5 years with baseline mean weight of 80.6±10.8 kg and BMI of 29.1±2.78 kg/m^(2) were started on GM diet.After a week of following the GM diet,there was an average weight loss of 3.46±2.1 kg,a decrease in fat-fraction by 3.8%±2.7,and an improvement in CT-LAI by 6.7?3.7 HU.All patients could successfully undergo donor hepatectomy with an average postoperative ICU stay of 2.86±0.8 days and hospital stay of 6.82?0.81 days.No donor had steatosis>10% on intraoperative Tru-cut biopsy and their post-operative outcomes were similar to normal liver donors.There were intra-abdominal collections in 2 donors requiring drainage and one required re-exploration for intestinal obstruction.There was EGD in 8 recipients(15.6%)and mortality in 1(1.9%)recipients.Conclusion:GM diet is safe and effective regimen to reduce steatosis and increase healthy LLD pool without compromising donor or recipient safety.

A retrospective cohort study to examine the association between the persistence of abdominal pain after cholecystectomy and ejection fraction on HIDA scan in patients with biliary dyskinesia

Background and aims:The persistence of pain in patients who underwent cholecystectomy primarily for biliary dyskinesia has been associated with gall bladder ejection fraction(GBEF)found on hepatobiliary iminodiacetic acid(HIDA)scan.Cholecystectomy is a definitive treatment for cholelithiasis but is questionable in biliary dyskinesia.During the postoperative follow-up,gastroenterologists and surgeons often found that some patients with biliary dyskinesia continue to experience biliary pain even after surgery.This study aims to investigate whether the value of GBEF found on the HIDA scan predicts the persistence of pain after cholecystectomy in patients with biliary dyskinesia(EF<35%on HIDA scan).Methods:It is a retrospective cohort study conducted at Kern Medical by recruiting patients from November 2019 to October 2022 in consecutive manner.It is a single sample study consisting of post-cholecystectomy biliary dyskinesia patients with dichotomous outcomes,i.e.,persistent typical recurrent epigastric or right upper quadrant pain with/without meals versus no pain.The primary outcome was the presence of pain 30 days after the cholecystectomy.Univariate analysis was performed with some of the bivariate indicators and continuous predictors,which contained fewer missing elements and had more variation.Results:Univariate logistic regression suggested that HIDA GBEF as a continuous variable does not suggest a relationship with pain after surgery(p=0.3951).A ROC analysis suggested a cutoff of HIDA GBEF=16(AUC=0.60,Specificity=0.5455,Sensitivity=0.7333).Conclusion:Our study does not support the relationship between GBEF found on HIDA scan to improved outcomes after the surgery.But larger controlled trials comparing outcomes of the patients with biliary dyskinesia who did and didn't undergo cholecystectomy are needed to look for other factors.

The analysis of the adherence of liver transplant recipients to immunosuppressant treatment, their self-control, and self-management in the post-transplantation period

Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Methods:The sample of this descriptive and cross-sectional study was composed of liver transplant recipients.The personal information form,Immunosuppressant Therapy Adherence Scale,and the Liver Self-Control and SelfManagement Scale were used to collect data,and descriptive statistical methods,independent samples t-test and one-way analysis of variance analysis was used to analyze the collected data.Results:In light of the data collected in this study,it was identified that,of all recipients,73.6%were 45–64 years old,72.5%were male,25.2%were workers,and 44.6%had equivalent income and expenses.It was observed that the recipients did not fully adhere to the immunosuppressant therapy regimen,and their self-control and selfmanagement levels were below the medium level.Conclusion:The social support system of liver transplant recipients is very important.Recipients with a good social support system can receive caregiver support from their relatives,thereby supporting their self-control and selfmanagement.Both liver transplant patients and the people providing care to them should be simultaneously provided with training programs and given information,and both groups should be supported in treatment and care processes.

Prednisolone therapy accelerates recovery of severe drug-induced liver injury: A prospective, randomized controlled study

Background and aims:Drug-induced liver injury(DILI)is one of the most serious adverse drug reactions and its incidence has been increasing rapidly.Accumulating evidence suggests that immune activation and systemic inflammatory responses are very important in the progression of DILI.Corticosteroids are often used in DILI,but their clinical usefulness remains controversial.We therefore conducted a prospective,randomized controlled study to investigate whether corticosteroid therapy can accelerate recovery and reduce mortality in severe DILI(SDILI).Methods:SDILI patients with total bilirubin?171μmol/L who presented to the Fifth Medical Center of Chinese PLA General Hospital,Beijing from 2016 to 2019 were randomly allocated to prednisolone and control groups.The endpoints were resolution of SDILI,defined as a decrease in total bilirubin of at least 35μmol/L to<171μmol/L,and overall survival at 6 months.Patients in the prednisolone group received prednisolone 60 mg/day therapy for the first 7 days.Patients with a decrease in total bilirubin of more than 35μmol/L on day 8 continued on tapering doses of prednisolone;otherwise,prednisolone was discontinued.Results:On day 8,50.75%(34/67)and 26.47%(18/68)of the participants in the prednisolone and control groups,respectively,achieved the primary endpoint(p¼0.002).However,there was no significant difference in overall survival at 6 months:95.52%(64/67)vs.91.18%(62/68)in the prednisolone and control groups,respectively(p¼0.3).All deaths in both groups occurred in patients who failed to achieve SDILI resolution on day 8.Conclusion:Prednisolone therapy may accelerate the recovery of SDILI.

A high level of secreted phosphoprotein 1 is associated with macrophage infiltration and poor prognosis in hepatocellular carcinoma

Background and aims:Secreted phosphoprotein 1(SPP1)functions in several physiological processes.The role of SPP1 expression in the prognosis and tumor immunity of hepatocellular carcinoma(HCC)is unknown.The aim of this study was to investigate the expression pattern of SPP1 in HCC and its correlation with prognosis and tumor immunity.Methods:Clinical and gene expression data of The Cancer Genome Atlas-liver hepatocellular carcinoma(LIHC)cohort and 11 other HCC datasets were collected.The Kaplan–Meier method and Cox regression analysis were used to analyze the prognostic value of SPP1.The DESeq2 package in R was used to analyze SPP1-related genes.Gene Ontology analysis and gene set enrichment analysis were used to determine the biological function of SPP1 in HCC.The single sample Gene Set Enrichment Analysis(ssGSEA)method was used to analyze the immune infiltrates of HCC.Illumina human methylation 450 data and level 3 HTSeq-FPKM data from The Cancer Genome Atlas-LIHC were used to analyze the effects of DNA methylation level on SPP1 expression.Results:SPP1 was overexpressed in HCC and correlated with T stage,histological grade,adjacent hepatic tissue inflammation,and vascular invasion in HCC.The analysis of survival rates indicated that high SPP1 levels were associated with poor overall survival in HCC.Functional analysis showed that SPP1 is related to tumor immunity,especially macrophage infiltration.Aberrant demethylation of the promoter region is one of the mechanisms underlying the increase of SPP1 in HCC.Conclusion:Our results indicate that SPP1 is an independent prognostic factor for HCC and is correlated with the clinical features and macrophage infiltration in HCC.

Laparoscopic cholecystectomy based on Laennec approach via the cystic plate with lymphadenectomy in Calot's triangle for gallbladder neoplasms:Initial experience and technical details

Background:It is still challenging to define the exact stage of early gallbladder carcinoma with preoperative imaging.Generally,subserous gallbladder is dissected for the potential early gallbladder carcinoma,which may cause incomplete tumor resection or tumor spread especially for the patients with T2 stage.Here,we reported our experience and safety of Laennec approach via the cystic plate to dissect the whole gallbladder with lymphadenectomy in Calot's triangle for accurate diagnosis and stage in gallbladder neoplasms.Methods:The anatomical gap between Laennec capsule and the cystic plate serves as the landmark to dissect the whole gallbladder through Laennec approach.Laparoscopic cholecystectomy based on Laennec approach via the cystic plate,together with lymphadenectomy in Calot's triangle,was performed in 17 patients with gallbladder neoplasms.Results:All patients had less intraoperative bleeding,no gallbladder breakage,no bile leakage,and accurate intraoperative rapid pathological staging under the corresponding strategies.The duration of surgery was comparable to that of traditional laparoscopic cholecystectomy.Conclusion:Laparoscopic cholecystectomy based on Laennec approach via the cystic plate,together with lymphadenectomy in Calot's triangular is safe for gallbladder neoplasms.In the future,the prospective clinical trial is going on to confirm the feasibility and effectiveness of this approach.

Systematic review and meta-analysis: Comparing hepatocellular and cholestatic patterns of drug-induced liver injury

Background and aims:Drug-induced liver injury(DILI)is a leading cause of death from acute liver failure(ALF).Hy's law warns that a hepatocellular pattern of injury accompanied by jaundice and normal alkaline phosphatase(ALP)levels is associated with a 10%or greater chance of progression to transplant or liver-related death.This meta-analysis of DILI studies evaluates acute and chronic outcomes of DILI according to clinical pattern of injury.Methods:We conducted a systematic search using electronic databases PubMed and EMBASE through to 8 March 2022.Our primary outcome was to compare acute outcomes including ALF,liver-related death,and liver transplant between patients experiencing hepatocellular,cholestatic,and mixed patterns of DILI.Our secondary outcome was to compare the rate of DILI chronicity between patients of these three differing patterns of injury.Pooled odds ratios(ORs)and 95%confidence intervals(CIs)were calculated using a random-effects model.Results:Overall,12 studies comprising 4290 patients were included.Patients with cholestatic DILI demonstrated similar rates of ALF(OR:0.80,95%CI:0.46–1.40,p=0.429)and liver-related death(OR:0.92,95%CI:0.50–1.69,p=0.792)compared to patients with hepatocellular DILI.Patients with cholestatic DILI were significantly more likely to experience chronicity compared to patients with hepatocellular DILI(OR:2.53,95%CI:1.34–4.79,p=0.004).

Investigation of perceived stress and psychological well-being in liver recipients having immunosuppressive therapy

Background and aims:In this study,the relationship between perceived stress and psychological well-being was analyzed in liver transplant recipients having immunosuppressive therapy.Methods:This study was performed as descriptive research with 134 patients who had liver transplantation at the organ transplantation institute of a training and research hospital(n?134).The Perceived Stress Scale and the Psychological Well-Being Scale were used for the data collection.The research data were analyzed by using the Statistical Package for Social Science 25.0.Results:Of all participant liver transplant recipients,22.4%were aged 18–27 years and 48–57 years and 80.6%were males.Besides,the participant liver transplant recipients used immunosuppressive drugs such as prednisolone(92.53%),tacrolimus(61.9%),and mycophenolate mofetil(52.98%).It was found that there was a statistically significant relationship between psychological well-being and perceived stress.Conclusion:In this study,it was discerned that perceived stress affected psychological well-being negatively.It is of importance to realize the stress experienced by liver transplant recipients and enhance their psychological wellbeing.In the process following transplant surgery,the liver transplant recipients should be carefully followed and efforts to improve patient outcomes should be made.

Feasibility of surgical application of the ligamentum teres hepatis:a review

Ligamentum teres hepatis(LTH),a normal anatomical tissue in the liver,is frequently observed during abdominal surgery.Its unique positional and structural characteristics give it a wide range of potential clinical applications,including but not limited to repairing peptic perforation,preventing hemorrhage,treating hiatal hernia,and strengthening the biliary/pancreatic intestine anastomosis to prevent biliary and pancreatic leak.The current review summarizes kinds of methods of using LTH in abdominal surgery,especially some new clinical applications in recent years,involving various organs and fields.At the same time,domestic and foreign literature and research in the past five years are cited to demonstrate the feasibility of these applications.This review may guide surgeons to think and explore more new applications of LTH in all surgery fields.

Advances in diagnostic ultrasound techniques for assessing liver steatosis in nonalcoholic fatty liver disease

The incidence of nonalcoholic fatty liver disease(NAFLD),a common chronic liver disease,is increasing yearly.With increasing degrees of liver steatosis,NAFLD can progress to varying degrees of hepatic fibrosis,cirrhosis,and even hepatocellular carcinoma(HCC),with a concomitant increase in the risk of metabolic syndrome and cardiovascular disease.Therefore,early diagnosis and accurate assessment of NAFLD are particularly significant.Although liver biopsy is regarded as the standard for evaluating the degree of hepatic steatosis in NAFLD,it is not frequently utilized due to its invasiveness.Ultrasound technology as a noninvasive diagnostic method has the advantages of operating simplicity and economy.It can effectively diagnose and assess the disease of NAFLD.This article mainly summarizes the current status and progress of research on the assessment of NAFLD and liver steatosis by two main types of ultrasound techniques,semi-quantitative and quantitative ultrasound,as well as other emerging techniques,and briefly describes the strengths and limitations of B-mode ultrasound,controlled attenuation parameters(CAP),and attenuation imaging(ATI)in this field.

Intrahepatic cholestasis of pregnancy is associated with increased risk of hepatobiliary disease and adverse fetal outcomes: A systematic review and meta-analysis

Background and aims:The aim of this study was to review the literature and perform a meta-analysis to clarify the association between intrahepatic cholestasis of pregnancy and risks of long-term maternal hepatobiliary disease as well as adverse fetal outcomes including preterm birth,meconium-stained amniotic fluid,and stillbirth.Methods:This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.A comprehensive literature search was performed using Cochrane,Embase,and PubMed databases to identify observational or cohort studies comparing pregnant women with intrahepatic cholestasis of pregnancy(ICP)to pregnant women without ICP.Data from the included studies were analyzed using the Review Manager 5.4.1 software.Results:The meta-analysis showed a significant association between ICP and the risk of hepatobiliary diseases(pooled risk ratio[RR]:2.81,95%confidence interval[CI]:2.66–2.97,p<0.00001),hepatitis C(HC):a significant association between ICP and risk of HC(pooled RR:4.02,95%CI:3.12–5.19,p<0.00001),meconium-stained amniotic fluid(MSAF):ICP was significantly associated with an increased risk of MSAF(pooled RR:1.91,95%CI:1.65–2.21,p<0.00001),and preterm birth:the meta-analysis demonstrated a significant association between ICP and preterm birth(pooled RR:2.11,95%CI:2.01–2.21,p<0.00001).Conclusion:ICP demonstrated statistically significant associations with increased risks of hepatobiliary disease,HC,MSAF,and preterm birth.

Identification of positive cofactor 4 as a diagnostic and prognostic biomarker associated with immune infiltration in hepatocellular carcinoma

Background and aims:Human positive cofactor 4(PC4)is associated with the development and therapeutic resistance of several malignancies.However,the role of PC4 in hepatocellular carcinoma(HCC)remains obscure.Methods:The expression status of PC4 was explored in Gene Expression Omnibus and The Cancer Genome Atlas datasets.Subsequently,the prognostic and diagnostic significance of PC4 in HCC patients was analyzed.Functional enrichment analyses were conducted to explore biological functions and potential mechanisms.The CIBERSORT algorithm was used for immune infiltration analysis.The risk signature was constructed by LASSO-Cox regression and was validated with the International Cancer Genome Consortium dataset.Quantitative real-time polymerase chain reaction was used to verify the expression levels of all genes.Tumor Immune Dysfunction and Exclusion analysis evaluated immunotherapy response.Finally,using online databases,PC4-related competing endogenous RNA networks were constructed.Results:PC4 levels were significantly upregulated in HCC and positively correlated with the pathological grade and clinical stage.The PC4-high expression group showed worse prognosis.In addition,PC4 could distinguish between tumor and normal tissues with an area under the curve of 0.965.The PC4 level was associated with immune checkpoints and immune cell infiltration.In the training and validation sets,the eight-gene risk signature strongly correlated with HCC patient prognosis.Tumor Immune Dysfunction and Exclusion analysis showed that patients in both the PC4-low and low-risk groups were more likely to benefit from immunotherapy.Finally,an lncRNA/microRNA-101-3p/PC4 network was constructed.Conclusion:We confirmed PC4 as a diagnostic and prognostic biomarker in HCC patients.We also developed and validated an eight-gene risk signature,which will help in clinical decision-making.The competing endogenous RNA network could help explore the regulatory mechanisms of PC4 in HCC.

Efficiency and safety of sofosbuvir in Bangladeshi children with chronic hepatitis C virus

Background and aims:Currently,treatment with oral direct-acting antivirals is recommended for all hepatitis C virus(HCV)-infected pediatric patients.The aim of this study was to evaluate the efficacy and safety of sofosbuvir and ribavirin combination ther apy for children and adolescents in Bangladesh who are living with chronic HCV in fection.Methods:An experimental study was performed from January 2021 to December 2022.HCV polymerase chain reaction(PCR)-positive thalassemic children,who were 6–18 years of age,were enrolled by consecutive non-probability sampling.Clinical features were recorded,and investigations were performed.All patients were initially treated with sofosbuvir(200 mg for 6-to 11-year-olds and 400 mg for 12-to 18-year-olds)and ribavirin(10–15 mg/kg/day)and were assessed clinically on a four-weekly basis,along with liver-function testing.The total duration of therapy was 24 weeks.HCV PCR was done at the end of treatment and 12 weeks after the completion of treatment to see the sustained virological response.Results:There were 26 cases in total,with a mean age of 9.26?2.82 years;14 were males(53.8%),and 12 females(46.2%).Twenty-five(96.15%)patients achieved a sustained virological response,and the end-of-treatment PCR was negative.One patient(3.85%)was a nonresponder even after 24 weeks of treatment.The medication was well received,with only four patients(15.3%)reporting headaches that were reported untreated.Conclusion:The combination of sofosbuvir and ribavirin is effective in treating chronic HCV infection and is not accompanied by any major negative side effects.