Occurrence Of HCC Research Articles

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Background & AimsPatients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events. MethodsWe performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months). ResultsBased on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02). ConclusionsIn patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.

Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients

Background: Hepatocellular carcinoma is one of the most fatal malignancies worldwide and is related to many risk factors. Chronic HCV is associated with a 20–30-fold increased risk for HCC. Angiotensin-converting enzyme (ACE) is overexpressed in many cancers and plays a major role in angiogenesis and carcinogenesis. Aim: We aimed to elucidate the effect of the ACE I/D gene polymorphism in patients with HCV-related liver cirrhosis and HCC, and its relationship to clinical parameters. Patients and Methods: The study included 180 participants, cirrhotic (n=60), HCC (n=60) and control healthy subjects (n=60). Liver and renal function tests, alpha-fetoprotein, HCV antibodies and triphasic CT were assessed. ACE Gene polymorphism was assessed by Nested PCR. Results: We observed higher frequencies of DD (36.7%) and DI (51.7%) genotypes, along with the D allele (62.5%), in HCC patients compared to those of cirrhotic cases (10%, 40% and 30%, respectively) and control subjects (6.7%, 38.3%, and 25.8%, respectively). DD and DI genotypes increased the risk and predicted the occurrence of HCC by OR 25.932 and OR 6.354, respectively. The D allele conveys significant risk for HCC compared to control and cirrhotic groups with OR 4.785 and OR 3.889, respectively. Both DD genotype and D allele are significantly correlated with larger tumor size and metastasis. Conclusion: The ACE I/D polymorphism (DD genotype and D allele) is significantly associated with HCC risk in HCV patients and is correlated with increased tumor growth and advanced stage.

Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma

SMYD3 (SET and MYND domain-containing protein 3) is involved in histone modification, which initiates oncogenesis by activating transcription of multiple downstream genes. To investigate associations of variable numbers of tandem repeats (VNTR) variants in the SMYD3 gene promoter, SMYD3 serum levels and SMYD3 mRNA expression in hepatitis B virus (HBV) infection and clinical progression of related liver disease. SMYD3 VNTRs were genotyped in 756 HBV patients and 297 healthy controls. SMYD3 serum levels were measured in 293 patients and SMYD3 mRNA expression was quantified in 48 pairs of hepatocellular tumor and adjacent non-tumor liver tissues. Genotype SYMD3 VNTR 3/3 was more frequent among HCC patients than in controls (Padjusted = 0.037). SMYD3 serum levels increased according to clinical progression of liver diseases (P = 0.01); HCC patients had higher levels than non-HCC patients (P = 0.04). Among patients with SMYD3 VNTR 3/3, HCC patients had higher SMYD3 levels than others (P < 0.05). SMYD3 mRNA expression was up-regulated in HCC tumor tissues compared to other tissues (P = 0.008). In conclusion, upregulation of SMYD3 correlates with the occurrence of HCC and SMYD3 VNTR 3/3 appears to increase the risk of HCC through increasing SMYD3 levels. SMYD3 may be an indicator for HCC development in HBV patients.

Bioinformatics-based screening of key genes for transformation of liver cirrhosis to hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms.MethodsGSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein–protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan–Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.ResultsIn total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes.ConclusionCDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

Cell Surface Proteins in Hepatocellular Carcinoma: From Bench to Bedside.

Cell surface proteins act as the go-between in carrying the information from the extracellular environment to the intracellular signaling proteins. However, these proteins are often deregulated in neoplastic diseases, including hepatocellular carcinoma. This review discusses several recent studies that have investigated the role of cell surface proteins in the occurrence and progression of HCC, highlighting the possibility to use them as biomarkers of the disease and/or targets for vaccines and therapeutics.

LncRNA SNHG11 Promotes Proliferation, Migration, Apoptosis, and Autophagy by Regulating hsa-miR-184/AGO2 in HCC.

BackgroundThe most common malignant tumor of the digestive system is HCC. However, the mechanism and pathogenesis of HCC occurrence and progress are still unknown. LncRNA is closely related to the occurrence and progress of HCC. It is important to investigate the effect and role of lncRNA in HCC.Materials and MethodsLncRNA microarray assay was used to screen the differential expression profile of lncRNA. SNHG11, miR-184 and GO2 expression was analyzed by RT-PCR. The ability of SNHG11 to serve as a sponge for miRNA and the fact that miR-184 directly targets mRNA were revealed by dual luciferase assay and RIP. Apoptosis and autophagy related proteins were detected by Western blot. Cell proliferation, invasion, migration, and apoptosis were detected by CCK-8 assay, wound healing assay, transwell assay, and flow cytometry.ResultsLncRNA microarray assay and RT-PCR results revealed that the expression of SNHG11 was increased in HCC tumor tissues and also upregulated in HCC cells. SNHG11 had a connection with poor survival rate in HCC. In addition, dual luciferase assay and RIP results revealed that SNHG11 serves as a sponge for miR-184 and miR-184 directly targets AGO2. Pearson correlation analysis showed that SNHG11 with miR-184 and miR-184 with AGO2 were negative correlations, and SNHG11 with AGO2 was a positive correlation. Cell function assay and Western blot showed SNHG4/miR-184/AGO2 regulatory loop was critical for HCC cell proliferation, migration, apoptosis, and autophagy.ConclusionOur study demonstrated that the expression of SNHG11 is higher in HCC; moreover, SNHG11 promotes proliferation, migration, apoptosis, and autophagy by regulating AGO2 via miR-184 in HCC. Our verification of the role of SNHG11 may provide a novel biomarker for the diagnosis, therapy, and prognosis of HCC.

Circulating exosome-derived bona fide long non-coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma.

Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell‐free plasma was applied. The risk score analysis was employed to screen the potential exosome‐derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi‐stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer‐free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer‐free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.

Effect of chronic hepatitis B virus DNA negative transformation and HBsAg clearance on the occurrence of hepatocellular carcinoma

Achieving HBV DNA negative transformation and HBsAg clearance with effective antiviral therapy can reduce the incidence of HCC, but some patients are still at risk of developing HCC. Therefore, screening high-risk patients for close monitoring is essential to reduce the incidence of HCC. This paper reviews the occurrence of HCC, risk factors and risk prediction models of HBV DNA negative transformation and HBsAg clearance, and provides a basis for screening and follow-up management of high-risk group of HCC with chronic hepatitis B.

1045 BMI Is an Independent Predictor for the Occurrence of HCC Following DAA Therapy in HCV Related Cirrhosis

INTRODUCTION: Treatment for Hepatitis C Virus (HCV) has made a significant stride with the advent of direct-acting antiviral (DAA) therapy with SVR rates higher than 95%. Despite such a big feat, questions have been raised regarding the rate of occurrence and recurrence of HCC following treatment with DAA, especially in those with cirrhosis. METHODS: Using our database, we first identified all patients with liver cirrhosis secondary to HCV with no prior history of HCC, who were treated with DAA between 01/01/2014 to 04/01/2018 at our institution. We then performed a detailed review of their electronic medical records and obtained relevant clinical data. Patients who developed HCC in the follow-up period were identified. HCC screening was carried out every 3-6 months with US or CT abdomen. Categorical variables were calculated as frequencies(percentages), and continuous variables were calculated as median (range). Cumulative incidence of de novo HCC was calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was performed to identify predictors for the development of HCC. RESULTS: We identified 254 patients meeting the criteria mentioned above. The basic demographics and key variables were identified and computed for those with and without the occurrence of HCC, as shown in Table 1. The two groups were quite similar in terms of the different variables that were studied. The patients had a median follow up of 21 months (3-55 months) following the start of DAA therapy. Sixteen patients subsequently developed de novo HCC with an occurrence rate of 6.3%. The cumulative incidence of HCC at 1,2 and 3 years of follow up are 1.6%, 6.6 %, and 11.3 %, respectively (Figure 1). Univariate analysis revealed a higher BMI of &gt; 30, was statistically significant (P value = 0.047) for an association with the occurrence of HCC ( HR of 4.06 with a CI of 0.9-18.19) (Figure 2). The median time to the occurrence of HCC following DAA therapy was 17 months. Multivariate analysis was performed to analyze the interaction between different variables on HCC occurrence, namely BMI, CHILD class, AFP, and Viral load, which did not reveal any significant association. CONCLUSION: Of the various risk factors that have been identified for de novo HCC occurrence, our study identified higher BMI as an independent risk factor for HCC occurrence. Further large-scale prospective studies should be performed to identify and confirm these risk factors associated with increased HCC occurrence.

Hepatocellular carcinoma with a direct right atrial extension in an HCV patient previously treated with direct-acting antiviral therapy: a case report

BackgroundHepatocellular carcinoma (HCC) is considered the third-leading cause of cancer-related mortality worldwide. Most cases of HCC are usually associated with liver cirrhosis due to various causes such as alcohol or more commonly viral hepatitis. Usually, patients remain asymptomatic for a long time, and symptoms are usually related to the cirrhosis itself or secondary to tumor extension. Intra-cardiac involvement with HCC rarely develops with a very poor prognosis. The occurrence and recurrence of HCC in cirrhotic patients treated with direct-acting antiviral (DAA) therapy (sofosbuvir) have been discussed in a few trials so far with no valid answer.Case presentationWe are reporting a case of recurrent HCC with an accidentally discovered direct right atrial extension with tumor thrombus through the inferior vena cava (IVC) in a cirrhotic patient previously treated with DAA. Unfortunately, due to his critical general condition, he died within days.ConclusionCardiac involvement in HCC rarely occurs and usually develops in advanced stages of HCC with very poor reported prognosis. Data regarding the relation between DAA and HCC development is controversial.

Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study

BackgroundAn unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals.MethodsAccording to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up.ResultsNine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455–13.169).ConclusionsOur data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.

Abstract LB-150: Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection

Abstract Background: Direct acting antiviral medications (DAA) have become the mainstay for treatment of chronic hepatitis C virus (HCV) infection. However, some studies have suggested an increased risk of HCC development following use of DAAs for HCV compared with use of interferon-based medications (IFN), while other studies, mostly in Veterans Administration population in the United States, did not show an increase in HCC risk after the use of DAA in patients with HCV. To address these conflicting reports, we investigated the association between use of DAA for HCV and subsequent development of HCC in a large, longitudinal data with broad representation of individuals from various ages, ethnicities, and geographic regions across the United States. Methods: A retrospective cohort study was performed using medical and pharmacy claims from the OptumLabs® Data Warehouse. The study included 9,532 incident HCV cases (2010-2016) of ages 18 years or older treated with DAA or IFN and did not have a prior diagnosis of HCC before initiation of the antiviral therapy. The participants were categorized into DAA-only or IFN-only groups. To account for confounding by indication, inverse probability of treatment weighting (IPTW) was performed to ensure balance in sociodemographic and treatment related factors between treatment groups. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC risk, comparing DAA-only regimen with IFN-only regimen (reference). Results: Median follow-up for the entire study cohort was 1.4 years, with a slightly longer follow-up for individuals in the IFN-only group (1.8 years) than for those in the DAA-only group (1.4 years). One hundred and seventy-one incident HCC cases developed during follow-up, with a higher occurrence of HCC in the DAA-only group (n=155; 11.9 cases per 1,000 person-years) than in the IFN-only group (n=16; 8.3 cases per 1,000 person-years). Compared with IFN-only treatment, use of DAA-only for HCV was not associated with an increase in HCC risk (HR=1.47, 95% CI: 0.89-2.42). Similarly, no association was found between use of DAA-only regimen and HCC risk among individuals with cirrhosis (HR=1.28, 95% CI: 0.71-2.31) or those without cirrhosis (HR =1.80, 95% CI: 0.64-5.03). When stratified by sustained virologic response (SVR), a measure of complete viral clearance, we noted a higher HCC risk associated with DAA-only regimen among individuals with SVR (HR=7.83, 95% CI: 1.54-39.88) and a lower risk for DAA-only regimen among those without SVR (HR=0.12, 95% CI: 0.02-0.95); however, the CIs are substantially wide, reflecting the small numbers in these subgroup analyses. Conclusion: Despite some prior reports of increased risk of HCC development following use of DAA for HCV, this ethnically and geographically diverse study did not find compelling evidence indicating an increased HCC risk associated with use of DAA in patients with HCV when compared with use of IFN. Citation Format: Samuel O. Antwi, Holly K. Van Houten, Lindsey R. Sangaralingham, Tushar Patel. Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-150.

Analysis of potential key genes in very early hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the major pathological type of primary liver cancer, one of the leading causes of cancer death worldwide. In addition, the long-term survival rates of HCC still remain low. Therefore, we attempted to identify the potential key genes in the occurrence of HCC by comparing the expression profiles of very early HCC tissue samples with that of chronic cirrhotic tissue samples by integrating the bioinformatics analysis in this study.MethodsGene expression profiles of 19 very early HCC and 19 cirrhotic tissue samples were selected from GSE63898. Differentially expressed genes (DEGs) were also identified by using online tool GEO2R. Furthermore, the GO and KEGG enrichment analysis of the DGEs were conducted on DAVID datasets. Then a protein–protein interaction (PPI) network was constructed and the modules were analyzed based on STRING database and Cytoscape software. The hub genes were screened by applying the cytoHubba plugin and then analyzed with the Kaplan Meier plotter.ResultsA total of 118 DEGs were identified between very early HCC and cirrhotic tissue samples. These DGEs were strongly associated with several biological processes, such as negative regulation of growth and p53 signaling pathway. A PPI network was constructed and top eight hub genes, including CDKN3, CDK1, CCNB1, TOP2A, CCNA2, CCNB2, PRC1, and RRM2, were determined. High expressions of CDK1, CCNB1, TOP2A, CCNA2, PRC1, RRM2, CDKN3, and CCNB2 were associated with poorer overall survivals (OS) in HCC patients.ConclusionWe had compared the expression profiles between the very early HCC and cirrhotic tissue samples by using bioinformatics analysis tools, which might help us better to understand the molecular mechanism of the initiation of HCC and even to find novel targets for HCC therapy.

Current Knowledge of Occult Hepatitis B Infection and Clinical Implications.

Occult hepatitis B infection (OBI) is a status of undetectable serum hepatitis B surface antigen (HBsAg) yet detectable serum and/or intrahepatic hepatitis B virus (HBV) DNA. Mutations in the preS1, preS2, and S regions of the HBsAg gene may result in undetectable HBsAg. OBI may either result from a self-limiting acute hepatitis, or in patients with chronic hepatitis B who achieved HBsAg seroclearance, which refers to the loss of detectability of serum HBsAg with or without antibody to HBsAg (anti-HBs) in chronic hepatitis B (CHB) patients. HBsAg seroclearance contributes to a significant proportion of population in seropositive OBI. Both spontaneous and antiviral treatment-induced HBsAg seroclearance rarely happens; yet both types of HBsAg seroclearance are durable. CHB patients who achieve HBsAg seroclearance generally have a favorable clinical course. There is still a low yet definite risk of HCC occurrence, particularly in male CHB patients who achieve HBsAg seroclearance after being 50 years old. Clinical implications of OBI include occurrence of cirrhosis and HCC, liver transplantation, blood products transfusion, hemodialysis, and so on. A potentially life-threatening condition would be OBI reactivation in patients during immunosuppression therapy, especially in the setting of intensified immunosuppression including in onco-hematological patients (those receiving hematopoietic stem cell transplantation and treated with the anti-CD20 monoclonal antibody [e.g., rituximab]). With more new insights into these two conditions, CHB patients who achieved HBsAg seroclearance generally have benign clinical course and good prognosis. Sensitive assay for serum HBV DNA should be considered to establish the presence of OBI in the clinical settings mentioned earlier, which will affect the management plan.

Direct-acting antiviral agents and risk of hepatocellular carcinoma: is it still a clinical dilemma?

Direct-acting antivirals (DAAs) revolutionised the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), also in more advanced patients, with a good safety profile and a proven positive effect on the reduction of risk of HCC occurrence. Nevertheless, patients with an history of successfully treated early HCC were initially excluded from pivotal trials. Although some initial retrospective studies, affected by several methodological issues, raised concerns regarding a possible harmful effect on the risk of HCC recurrence after antiviral therapy, more recent prospective studies and meta-analyses provided evidence that risk of HCC recurrence after DAA therapy is similar, or even lower, than that observed in patients treated with interferon or in DAA-untreated controls. In the future, a meta-analyses of individual patient data would be necessary to definitively close this clinical debate, as well as prospective studies assessing ‘true endpoints’, such as overall survival.

Effect of Metabolic Syndrome on the Clinical Outcomes of Chronic Hepatitis B Patients with Nucleos(t)ide Analogues Treatment.

No data are available about the effect of MS on oral nucleos(t)ide analogues (NUCs) treatment and clinical outcomes in chronic hepatitis B (CHB) patients. We aimed to elucidate whether coexistence of MS and CHB affects the long-term prognosis of CHB patients with oral NUCs treatment. We performed a retrospective data analysis for a total of 587 CHB patients who started oral NUCs treatment for the first time in our institution from January 2006 to March 2016. Among the 587 patients, 70 (11.9%) had MS, but 517 (88.1%) had no evidence of MS when oral NUCs treatment was initiated. Cumulative occurrence rates of viral breakthrough, genotypic resistance, HCC, disease progression (PD), and overall adverse outcomes (OAO) were significantly higher in CHB patients with MS than in those without MS, although HBV-DNA suppression and cumulative occurrence rates of HBeAg negative conversion and seroconversion were not significantly different between the two groups. The overall survival (OS) was also significantly shorter in CHB patients with MS than in those without MS. Multivariate analysis indicated that the MS was an independent, poor prognostic factor for occurrence of genotypic resistance (adjusted hazard ratio [aHR], 22.3; 95% confidence interval [CI] 6.61-75.02; P < 0.001), HCC (aHR, 3.98; 95% CI 2.07-7.66; P < 0.001), PD (aHR, 6.18; 95% CI 3.43-11.14; P < 0.001), OAO (aHR, 8.10; 95% CI 4.68-14.02; P < 0.001), and OS (aHR, 12.29; 95% CI 2.25-67.24; P < 0.001). MS is an independent determinant of poor prognosis in CHB patients receiving oral NUCs treatment.

The SMYD3 VNTR 3/3 polymorphism confers an increased risk and poor prognosis of hepatocellular carcinoma in a Chinese population

ObjectiveHepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC. MethodsA total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. ResultsThe family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. ConclusionThis study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir.

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65426 infected patients receiving entecavir or tenofovir for at least 3months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end-stage renal failure or a diagnosis of HCC within 3months of starting treatment. Eligible patients (N=27820) were followed until HCC occurrence, completion of the allowed 3-year regimen or 31 December 2013. During a median follow-up of 25.1 (12.1-35.6) months, 802 patients developed HCC, with 1-, 2- and 3-year cumulative incidence of 1.82% (95% CI, 1.66-1.99%), 3.05% (95% CI, 2.82-3.28%) and 4.06% (95% CI, 3.77-4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66-0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00-16.90 in age <40years; 4.69; 95% CI, 3.94-5.59 in age ≧40years), age (IRR, 3.38; 95% CI, 2.10-5.47 for 40-50years; 6.92; 95% CI, 4.27-11.21 for 50-60years; 12.50; 95% CI, 7.71-20.25 for ≧60years; <40years as reference), male sex (IRR, 1.71; 95% CI, 1.44-2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02-1.58) and diabetes (IRR, 1.24; 95% CI, 1.05-1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.

VIRAL HEPATITIS

Objectives: Diabetes mellitus has been shown to be an independent risk factorfor hepatocellular carcinoma in populations at risk. Different anti-diabetic drugs have beenshown to have different effects on incidence of cancers in diabetic patients. Data Source:Outpatient and inpatient hospital records as well as fresh cases. Design of Study: Hospitalbased retrospective case control study. Setting: DHQ, Sargodha. Period: Fifteen years (10years retrospective, 5 years prospective, from the starting date of study). Materials &amp; Methods:In a hospital based study we recorded the incidence of HCC in patients otherwise consideredto be at risk. We also observed whether anti-diabetic monotherapy has any effects on HCCoccurrence in our target population. Results: We found out that incidence of HCC in diabeticpatients with a concomitant HBV or HCV infection was at least 1.5 times higher than non-diabetichepatitis patients. The incidence of HCC reduced in patients using metformin as compared tosulfonylureas. Conclusion: Diabetes is an independent risk factor for hepatocellular carcinomaand metformin use is correlated with reduced HCC occurrence in risk groups.

DIABETICS PATIENTS INFECTED WITH HEPATITIS B OR C VIRUS; METFORMIN INTAKE IS ASSOCIATED WITH DECREASED INCIDENCE OF HEPATOCELLULAR CARCINOMA

Objectives: Diabetes mellitus has been shown to be an independent risk factorfor hepatocellular carcinoma in populations at risk. Different anti-diabetic drugs have beenshown to have different effects on incidence of cancers in diabetic patients. Data Source:Outpatient and inpatient hospital records as well as fresh cases. Design of Study: Hospitalbased retrospective case control study. Setting: DHQ, Sargodha. Period: Fifteen years (10years retrospective, 5 years prospective, from the starting date of study). Materials &amp; Methods:In a hospital based study we recorded the incidence of HCC in patients otherwise consideredto be at risk. We also observed whether anti-diabetic monotherapy has any effects on HCCoccurrence in our target population. Results: We found out that incidence of HCC in diabeticpatients with a concomitant HBV or HCV infection was at least 1.5 times higher than non-diabetichepatitis patients. The incidence of HCC reduced in patients using metformin as compared tosulfonylureas. Conclusion: Diabetes is an independent risk factor for hepatocellular carcinomaand metformin use is correlated with reduced HCC occurrence in risk groups.