Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following hepatectomy.But traditional single clinical variables are still insufficient to predict recurrence.We still lack effective prediction models for recent recurrence(time to recurrence<2 years)after hepatectomy for HCC.AIM To establish an interventable prediction model to estimate recurrence-free survival(RFS)after hepatectomy for HCC based on sarcopenia.METHODS We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time,and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography.94 of these patients were enrolled for external validation.Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was validated.The predictive efficacy of this model was evaluated using the receiver operating characteristic curve.RESULTS Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,P<0.05],alpha-fetoprotein≥40 ng/mL(HR=1.984,95%CI:1.307-3.011,P<0.05),the maximum diameter of tumor>5 cm(HR=2.222,95%CI:1.285-3.842,P<0.05),and hepatitis B virus DNA level≥2000 IU/mL(HR=2.1,95%CI:1.407-3.135,P<0.05)were independent risk factors associated with postoperative recurrence of HCC.Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease(SAMD)was established combined with other the above risk factors.The area under the curve of the SAMD model was 0.782(95%CI:0.705-0.858)in the training cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation cohort.Besides,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of HCC.CONCLUSION Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC.A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC,which is superior to other models and contributes to prognosis prediction.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.

Hepatitis B virus X protein-mediated upregulation of miR-221 activates the CXCL12-CXCR4 axis to promote NKT cells in HBVrelated hepatocellular carcinoma

Both hepatitis B virus X protein(HBx)and microRNA-221(miR-221)have been implicated in the development of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).The present study demonstrates that HBx promotes HCC cell proliferation via the C-X-C motif chemokine ligand 12-C-X-C chemokine receptor type 4(CXCL12-CXCR4)axis.We predict that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.Methods:After miR-221 mimic,miR-221 mimic negative control,miR-221 inhibitor,miR-221 inhibitor negative control were transfected into cells,the expression of CXCL12 and miR-221 was detected by qPCR and western blot.Then we constructed a stable HBV-HCC cell line.HBV-HCC cells were injected into the nude mice,thus a HBV-HCC mouse model was constructed.Q-PCR and western blot were used to detect the expression of HBx,miR-221,CXCL12 and CXCR4 in tumor tissues.The expression of CXCL12 was detected by immunohistochemistry,and the expression of CXCR4,CD3 and CD56 was detected by immunofluorescence.The levels of CXCL12,IL-2 and TNF-αin serum of mice were detected by ELISA.Sixty-one patients with HBV-related HCC,61 patients with HBV-related cirrhosis,61 patients with chronic hepatitis B(CHB)and 30 healthy people were enrolled.CXCL12,cytokine levels,and clinicopathological parameters were tested.Results:Hepatitis B virus X protein upregulates the expression of miR-221 and CXCL12 in lentivirus(LV5)-HBx-transfected HepG2 cells.HBx protein promotes HepG2 cell proliferation in vitro.HBx protein promoted tumor growth via the miR-221/CXCL12/CXCR4 pathway in a mouse tumor model.HBx protein upregulated natural killer T cell expression via the CXCR4/CXCL12 pathway to promote tumor growth.The data demonstrated a positive correlation between CXCL12 concentration with Cre levels and Child-Pugh scores.CXCL12 had an inferior diagnostic efficiency compared to IL-2 and IL-6 for HBV-related HCC.Conclusions:We present evidence that HBx/miR-221-mediated CXCL12/CXCR4 signaling induces NKT cells to promote HBV-related HCC.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B

BACKGROUND Research exploring the influence of healthier lifestyle modification(LSM)on the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB)is limited.AIM To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data.METHODS Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1,2009,and December 31,2017,those aged≥20 years who drank alcohol,smoked cigarettes,and were sedentary were analyzed.Exposure included at least one LSM,including alcohol abstinence,smoking cessation,and regular exercise.The primary outcome was HCC development,and the secondary outcome was liver-related mortality.We used 2:1 propensity score matching to account for covariates.RESULTS With 48766 patients in the LSM group and 103560 in the control group,the adjusted hazard ratio(HR)for incident HCC and liver-related mortality was 0.92[95%confidence interval(CI):0.87-0.96]and 0.92(95%CI:0.86-0.99)in the LSM group,respectively,compared with the control group.Among the LSM group,the adjusted HR(95%CI)for incident HCC was 0.84(0.76-0.94),0.87(0.81-0.94),and 1.08(1.00-1.16)for alcohol abstinence,smoking cessation,and regular exercise,respectively.The adjusted HR(95%CI)for liver-related mortality was 0.92(0.80-1.06),0.81(0.72-0.91),and 1.15(1.04-1.27)for alcohol abstinence,smoking cessation,and regular exercise,respectively.CONCLUSION LSM lowered the risk of HCC and mortality in patients with CHB.Thus,active LSM,particularly alcohol abstinence and smoking cessation,should be encouraged in patients with CHB.

Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis

BACKGROUND Type 2 diabetes mellitus(T2DM)has been shown to be correlated with hepatocellular carcinoma(HCC)development.However,further investigation is needed to understand how T2DM characteristics affect the prognosis of chronic hepatitis B(CHB)patients.AIM To assess the effect of T2DM on CHB patients with cirrhosis and to determine the risk factors for HCC development.METHODS Among the 412 CHB patients with cirrhosis enrolled in this study,there were 196with T2DM.The patients in the T2DM group were compared to the remaining 216patients without T2DM(non-T2DM group).Clinical characteristics and outcomes of the two groups were reviewed and compared.RESULTS T2DM was significantly related to hepatocarcinogenesis in this study(P=0.002).The presence of T2DM,being male,alcohol abuse status,alpha-fetoprotein>20ng/mL,and hepatitis B surface antigen>2.0 log IU/mL were identified to be risk factors for HCC development in the multivariate analysis.T2DM duration of more than 5 years and treatment with diet control or insulin±sulfonylurea significantly increased the risk of hepatocarcinogenesis.CONCLUSION T2DM and its characteristics increase the risk of HCC in CHB patients with cirrhosis.The importance of diabetic control should be emphasized for these patients.

Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma

BACKGROUND Hepatitis B virus(HBV)is a major cause of hepatocellular carcinoma(HCC).HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis.However,the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated.AIM To analyze the features of HBV integration in HCC using a new reference database and integration detection method.METHODS Published data,consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples,were re-analyzed to identify the integration sites.Genome Reference Consortium Human Build 38(GRCh38)and Telomere-to-Telomere Consortium CHM13(T2T-CHM13(v2.0))were used as the human reference genomes.In contrast,human genome 19(hg19)was used in the original study.In addition,GRIDSS VIRUSBreakend was used to detect HBV integration sites,whereas high-throughput viral integration detection(HIVID)was applied in the original study(HIVID-hg19).RESULTS A total of 5361 integration sites were detected using T2T-CHM13.In the tumor samples,integration hotspots in the cancer driver genes,such as TERT and KMT2B,were consistent with those in the original study.GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19.Enrichment of integration was observed at chromosome 11q13.3,including the CCND1 pro-moter,in tumor samples.Recurrent integration sites were observed in mitochondrial genes.CONCLUSION GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration.Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development.

Construction of an immune-related prognostic model to predict prognosis and immunotherapy in liver cancer patients with hepatitis B virus-infected

Background:Hepatocellular carcinoma(HCC)appears to be strongly associated with immune-related genes.However,immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus(HBV).The purpose of this study was to investigate the prognostic significance of immune-related genes in HBV-infected HCC.Methods:Gene expression data from 114 HBV-infected HCC and 50 normal tissues were integrated into The Cancer Genome Atlas.Differentially expressed immune-associated genes were analyzed to identify immune-associated differential genes associated with overall survival.Least Absolute Shrinkage and Selection Operator and multivariate Cox regressions were used to constructing immunoprognostic models.An independent prognostic factor analysis using multiple Cox regressions was also performed for HBV-infected HCCs.Immunocorrelation analysis markers and immune cell infiltration were also investigated.Results:We found 113 differentially expressed immune-associated genes.Immune-related differential genes were significantly correlated with the overall survival of HCC patients.We constructed an immune-based prognostic model using multivariate Cox regression analysis including seven immune-related genes.According to further analysis,immune-related prognostic factors may serve as independent prognostic indicators in the clinical setting.There is also evidence that the 7-gene prognostic model reflects the tumor immune microenvironment as a result of the risk score model and immune cell infiltration.Conclusions:As a result of our study,we screened immune-related genes for prognosis in HBV-infected HCC and developed a novel immune-based prognostic model.The research not only provides new prognostic biomarkers but also offers insight into the tumor immune microenvironment and lays the theoretical groundwork for immunotherapy.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Hemocholecyst caused by accidental injury associated with radiofrequency ablation for hepatocellular carcinoma:A case report

BACKGROUND Radiofrequency ablation(RFA)is an effective and safe treatment for hepatocellular carcinoma that features a lower incidence of serious complications than surgical resection.Hemocholecyst caused by RFA is a rare complication of secondary damage to the intrahepatic bile duct that results in hemobilia.CASE SUMMARY Here we report on a case of a hemocholecyst caused by accidental injury during RFA that induced hematemesis and melena.Digital subtraction angiography revealed no gallbladder arterial injuries.After conservative treatment and transcatheter arterial chemoembolization,the patient’s condition stabilized,and she was discharged 1 wk later.CONCLUSION Therefore,when performing interventional procedures such as RFA,clinicians must be vigilant because even minor injuries can lead to serious complications such as hemocholecyst.

Barcelona Clinic Liver Cancer Classification and Treatment of Hepatocellular Carcinoma in a Côte d’Ivoire University Hospital

Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the treatment of hepatocellular carcinoma. The aim of this retrospective study was to describe the Barcelona Clinic Liver Cancer classification and the treatment of hepatocellular carcinoma in a University Hospital in Côte d’Ivoire. Methods: Patients with hepatocellular carcinoma hospitalized in the hepato-gastroenterology unit of the University Hospital of Yopougon from 01 January 2012 to 30 June 2017 were included. The diagnosis of hepatocellular carcinoma was based on the presence of hepatic nodules on the abdominal ultrasound scan, typical images with the helical scanner associated or not with an increase of the α-fetoprotein higher than 200 ng/ml or with histology. Demographic, clinical, biological and radiological data were determined at the time of diagnosis. Patients were classified according to the Barcelona Clinic Liver Cancer classification. Their treatment was specified. Results: There were 258 patients whose median age was 48.1 years. Viral hepatitis B virus was the primary cause of hepatocellular carcinoma in 64.7% of cases. The severity of the underlying cirrhosis was Child-Pugh A in 12.1%, B in 63.6% and C in 24.3% of cases. The median size of the tumor was 63 mm. The α-fetoprotein level was higher than 200 mg/ml in 56.03% of cases. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) system was ≥2 in 82.9%. The Barcelona Clinic Liver Cancer classification was A in 1.3%, B in 0%, C in 55.2% and D in 43.5% of patients. There was no transplantation or hepatic resection. Very few patients (1.9%) received radio-frequency curative therapy. The treatment was predominantly symptomatic in 97.8% of patients. During hospitalization 43.7% of patients died. Conclusion: Hepatocellular carcinoma occurs on a liver with severe cirrhosis at a late stage. This does not allow cure treatment and explains a high mortality rate during hospitalization. Hepatitis B virus is the main risk factor and immunization at birth will reduce the incidence of this cancer in Africa.

Diagnostic value of PIVKA-Ⅱ and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P < 0.05), especially when cirrhosis was present(P < 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA

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MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma

Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.

Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma

Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus(HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1(IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance.

Hepatitis B viral load affects prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies,respectively.Seven HCV-related studies,three HBV-related studies and three studies on HBV or HCV-related HCC were identified.RESULTS:A total of 1224 patients were included in this analysis.The estimated odds ratios(OR) for the 1-,2-,3-and 5-year recurrence were 0.54 [15.4% vs 24.1%,95% confidence interval(CI):0.32-0.89,P=0.02],0.42(36.9% vs 58.0%,95% CI:0.19-0.90,P=0.03),0.37(47.9% vs 63.8%,95% CI:0.19-0.71,P=0.003),and 0.32(66.7% vs 74.3%,95% CI:0.15-0.66,P=0.002),respectively;and the OR for the 1-,2-,3-,5-and 7-year mortality were 0.23(1.2% vs 9.1%,95% CI:0.07-0.71,P=0.01),0.31(6.4% vs 22.1%,95% CI:0.12-0.79,P=0.01),0.43(12.7% vs 20.8%,95% CI:0.21-0.89,P=0.02),0.42(25.1% vs 42.0%,95% CI:0.27-0.66,P=0.0002) and 0.28(31.9% vs 52.2%,95% CI:0.13-0.59,P=0.0008).CONCLUSION:This meta-analysis indicates the postoperative antiviral therapy,interferon in particular,may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.