CYP2C19 Genotype,CagA Genotype and Antibiotic Resistant Strain of Helicobacter pylori Infection

Background: H. pylori is a class I carcinogen and major cause of gastric cancer. Few previous studies reportedrelationship between H. pylori infection, CYP2C19 genotype and functional dyspepsia (FD) subtype. The aim of thisstudy was to determine relationship between CYP2C19 genotype and FD subtype patients(host factor) with antibioticresistant strains of H. pylori infection and CagA genotype(bacterial factor). Methods: FD patients who were investigatedwith gastroscopy at Thammasat University Hospital, Thailand during March 2017-November 2017 were enrolled. Twoantral gastric biopsies were obtained for rapid urease test, E-test and cultures. CagA genotypes (CagA1a and CagA2a)were determined by PCR and CYP2C19 genotype was determined by PCR-RFLP. FD patients were categorized asepigastric pain syndrome(EPS) and postprandial distress syndrome (PDS). Results: 93 FD patients with H. pyloriinfection were enrolled (37 male, 56 female, mean age 54.5 years). There were 33 patients with EPS and 60 patientswith PDS. CYP2C19 genotype revealed 55.9% rapid metabolizer (RM), 40.9% intermediate metabolizer (IM) and3.2% poor metabolizer (PM) genotypes. Antibiotics susceptibility tests demonstrated 62.8% resistant to metronidazole,12.9% resistant to clarithromycin and 27.1% resistant to fluoroquinolone. CagA 1a and CagA 2a were demonstratedin 6 patients(11.5%) and 46 patients(88.5%). CagA2a genotype was more prevalent in PDS than EPS patients(94.3%vs.76.5%; P =0.08) without significance. In intermediate metabolizer (IM), CagA2a genotype was significanthigher in PDS than EPS(100% vs.25%; P=0.004). Conclusions: PDS, CYP2C19 RM genotype and CagA 2a gene ofH. pylori infection were the predominant type of FD in Thailand. Metronidazole remain the most common antibioticresistant strain of H. pylori infection in FD patients. PDS (host factor) was significantly related to CagA2a genotype(bacterial factors) only in patients with intermediate metabolizer. Appropriate dose of proton pump inhibitor (PPI) andcorrect regimens for H. pylori eradication in FD patients should be consider to improve clinical outcomes.     

Hepatitis B Virus DNA Negativity Acts as a Favorable Prognostic Factor in Hepatocellular Carcinoma Patients

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents inhepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine andentecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE wereanalyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBVDNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation andprogression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response.Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%,p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as comparedto those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significantvariables associated with virologic events. In addition, prophylaxis was the only independent protective factor forhepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver ItalianProgram score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudinedemonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention ofHBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayeda significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA andhepatitis B flares might be causes of tumor progression in these patients.     

Efficacy of Prophylactic Entecavir for Hepatitis B Virus- Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.     

Hepatitis C Virus Prevalence and Genotyping among Hepatocellular Carcinoma Patients in Baghdad

Hepatocellular carcinoma (HCC) is the third most common cause for cancer death in the world, now beingespecially linked to chronic hepatitis C virus (HCV) infection. This case-control study consisting of 65 HCCpatients and 82 patients with other malignant tumours as controls was conducted to determine the associationof HCV markers with HCC. Serum of each participant was obtained for detection of HCV Ab and RNA byDNA enzyme immunoassay (DEIA). Twenty six per cent (26.0%) of HCC patients had positive anti-HCV whichwas significantly greater than the control group (p=0.001). HCC patients significantly have a risk of exposure toHCV infection almost 3 times than the control group (OR=2.87, 95% C.I=1.1-7). Anti-HCV seropositive rate wassignificantly (p=0.03) higher among old age HCC patients and increases with age. Males with HCC significantlyshowed to have more than 9 times risk of exposure to HCV infection (OR=9.375, 95 % CI=1.299-67.647) thanfemales. HCV-RNA seropositive rate was (70.8%) significantly higher among HCC patients compared to (22.2%)the control group (p=0.019). The most prevalent genotype (as a single or mixed pattern of infection) was HCV-1b. This study detected a significantly higher HCV seropositive rate of antibodies and RNA in HCC patients.     

Increased Prevalence of HTLV-I Infection in Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age=51.7) and 43 patients with HCV-associated HCC (mean age=62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) ( P =0.001). The relative risk (RR) of association was 12.8 ( P =0.0004) among the males, however, no association was evident among the females, RR=1.3 ( P =0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.     

肝细胞癌组织中乙型肝炎病毒和丙型肝炎病毒的检测

目的检测肝细胞癌（hepatocellular carcinoma，HCC）组织中乙型病毒性肝炎（virus hepatitis type B）表面抗原（HB—sAg）和丙型病毒性肝炎（virus hepatitis type C）核心抗原（HCVAg）的表达。方法应用免疫组织化学法检测78例HCC及癌旁肝组织HBsAg和HCVAg的表达。同时比较患者的HBsAg和HCVAg血清学检测结果。结果HCC及癌旁肝组织中HBsAg和HCVAg阳性及HBsAg和HCVAg双重阳性表达率分别为9.1％、6．4％、2．6％和80．8％、44．9％、29．5％。HCC与癌旁肝组织HBsAg和HCVAg阳性及HBsAg和HCVAg双阳性表达率相互比较有非常显著性差异（P〈0．01）。合并肝硬化组和无肝硬HCC组中HCC与癌旁肝组织HBsAg和HCVAg阳性、HBsAg及HCVAg双阳性表达率相互比较也有非常显著性差异（P〈0．01）。HCC的HBsAg和HCVAg血清学检测的结果与手术标本HBsAg和HCVAg免疫组织化学检测的结果相吻合。结论HCC的发生与HBV和HCV的感染密切相关。     

The Putative Role of Natural Killer Cells in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

Background: Natural Killer (NK) cells have crucial roles in immune responses against malignant transformation including hepatocellular carcinoma (HCC). The NKG2D receptor has a critical role in the NK recognition of target cells. Aim: We assessed NKG2D receptor expression as a diagnostic biomarker for HCC detection and progression in Egyptian patients with hepatitis C virus (HCV)-related HCC. Methods: We classified 81 patients into three groups: chronic hepatitis (21), cirrhotic (30) and HCC (30) patients, with 36 individuals enrolled to the control group. We analyzed NK levels in peripheral blood and NKG2D receptor expression in NK cells using flow cytometry. Results: We observed a significant decrease in NKG2D (CD314) expression on circulating NK cells and frequency of NK cells expressing NKG2D (CD314) in HCC patients. Also, in patients, larger foci lesions significantly correlated with decreased NK cell numbers. Multiple foci numbers and patients with a Child score C significantly correlated with decreased circulating NK cells expressing NKG2D and decreased NKG2D expression. Conclusion: The percentage of NK cells in peripheral blood and NKG2D receptor expression could function as potential biomarkers for HCC detection and progression.     

Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis

Background: The role of hepatitis B surface antigen (HBsAg) levels in predicting the risk of developinghepatocellular carcinoma (HCC) has remained unclear. The aim of this study was to obtain the most up-to-date estimatedmeasure of the association between HBsAg levels and the development of HCC in patients. Methods: We performed asystematic review by searching for relevant studies on PubMed, Scopus, ProQuest and the Cochrane Central Registerof Controlled Trials from January 2002 to November 2017. We presented the effects of HBsAg levels at each cut-offvalue as the odds ratios (ORs) at 95% confidence interval (CI). We also investigated HCC and its potential risk factorsincluding HBeAg, and HBV DNA. We registered our protocol with the International Prospective Register of SystematicReviews (PROSPERO) with the registration number CRD42018081138. Results: We selected 10 studies representing12 541 cases. At the 100 IU/ml cut-off, the OR for HCC at the high HBsAg level versus the low level was 4.99 (95%CI, 3.01–8.29) with high inconsistency (I2=79%). At the 1,000 IU/ml threshold, the pooled OR for HCC at the highHBsAg versus the low level was 2.46 (95% CI, 2.15–2.83) with low variance. We also found correlations between therisk of HCC and male gender (OR=2.12), hepatitis B e-antigen positivity (OR=2.99), or hepatitis B (HBV) viral load≥ 2,000 IU/ml (OR=4.37). Conclusion: Our study revealed that HBsAg levels ≥ 100 IU/ml, and notably >1,000 IU/ml, are associated with an increased risk of HCC development.     

High Prevalence of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Thailand

Background: Chronic hepatitis B (CHB) infection is one of the important causes of hepatocellular carcinoma (HCC) in Thailand, involved in the pathogenesis and leading to a development of HCC with or without cirrhotic changes of the liver. This study was aimed to investigate the predictive factors for HCC among CHB patients in a tertiary care center in Thailand. Materials and Methods: We conducted a retrospective study of CHB patients with or without HCC during the period of January 2009 and December 2014 at Thammasat University Hospital, Pathumthani, Thailand. Data on clinical characteristics, biochemical tests and radiologic findings were collected from review of medical records. Results: A total of 266 patients were diagnosed with CHB in Thammasat university hospital during the study period. However, clinical information of only 164/266 CHB patients (98 males, 66 females with mean age of 49.4 years) could be completely retrieved in this study. The prevalence of HCC in CHB infection in this study was 38/164 (23.2%). CHB patients with HCC had a mean age older than those without HCC (59.5 vs 47 years, P-value = 0.01). Furthermore, history of upper GI bleeding, tattooing, blood transfusion, and chronic alcoholism were significantly more common in CHB patients with HCC than patients without HCC (13.2% vs 3.2% P-value 0.03, OR = 4.6, 95%CI = 1.2-18.1, 20% vs 3.9%, P-value = 0.01, OR= 6.1, 95% CI= 1.6-23.6, 20% vs 6.3%, P-value = 0.03, OR = 3.8, 95%CI =1.1-12.7, 62.2% vs 30.3%, P-value <0.0001, OR = 3.7, 95%CI= 1.7-8.1 respectively). Interestingly, more CHB patients with HCC had evidence of cirrhosis than those without HCC (78.9% vs 20.4%, P-value <0.0001, OR = 14.6, 95%CI = 5.8-36.7). In CHB patients with HCC, surgical therapy provided longer survival than radiofrequency ablation (RFA) (72 vs 46.5 months, P-value= 0.04). The mean survival time after HCC diagnosis was 17.2 months. Conclusions: HCC remains a major problem among patients with CHB infection in Thailand. Possible risk factors are male gender, history of upper GI bleeding, chronic alcoholism, tattooing, blood transfusion and evidence of cirrhosis. For early stage HCC patients, surgical treatment provided longer survival time than RFA. Most HCC patients presented with advanced disease and had a grave prognosis. Appropriate screening of CHB patients at risk for HCC might be an appropriate approach for early detection and improvement of long-term outcomes.     

Transition of Antibody to Hepatitis C Virus from Chronic Hepatitis to Hepatocellular Carcinoma

Fifty-eight patients with chronic hepatitis C were followed for more than 7 years. Of them, 10 patients were found to develop hepatocellular carcinoma, 14 to develop liver cirrhosis, 30 to sustain chronic hepatitis, and 4 to show subsidence of hepatitis. Antibody to hepatitis C virus (anti-HCV) disappeared from the 4 patients whose hepatitis subsided, but it persisted in the remaining 54 patients. The mean titer of anti-HCV was almost the same at the stages of chronic hepatitis and of cancer in the 10 patients who developed hepatocellular carcinoma. These results indicate that chronic infection of hepatitis C virus may lead to hepatocellular carcinoma.     

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factorsfor hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variationand the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infectedwith HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249Smutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP)in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basalcore promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group.R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was notsignificantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations wasindependently associated with the risk of HCC in Thai patients.     

Genetic Polymorphism of Epidermal Growth Factor Gene as a Predictor of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients

Background: In Egypt, the incidence of hepatocellular carcinoma (HCC) is approximately 4.7% of chronic liver disease patients due to (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration. A functional polymorphism in EGF 61A>G was identified; itwas associated with higher risk of HCC. Objectives: to investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV) cirrhotic patients as well as its relation to EGF protein expression in HCC tissue. Patients and methods: this casecontrol study was conducted on 75 HCV cirrhotic patients including 50 HCC patients (25 withresectable HCC and 25 with advanced unresectable HCC) and 25 healthy persons were included. EGF genotype was detected by restriction fragment length polymorphism. EGF expression in HCC tissue biopsiesfrom patientswhounderwent surgical resection was done by immunohistochemical examination. Results: The GG genotype was associated with significant increased risk of HCC compared to AA genotypes (P=0.031) in cirrhotic group. The G allele had a highly significant risk of HCC compared to allele Ain recessive model GG vs. AG+AA (P=0.036) rather than in the dominant model GG +AG vs. AA (P=0.66). There was significant increased expression of EGF in tumour tissues in patients with GG genotype compared to AG genotype and AA genotype p= 0.019. Conclusion: EGF gene polymorphism (GG genotype) had a significant risk of HCC development in cirrhotic patients. This is confirmed by increased EGF expression in liver tumor tissue from HCC patients.     

Current Trends and Recent Advances in Diagnosis,Therapy, and Prevention of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associatedmorbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis ofHCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin(DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2(TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), andsquamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC.The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US),dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some expertsadvocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced USas the promising imaging madalities of choice. With regard to recent advancements in tissue markers, manycuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostainingstudies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less thanhalf of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation,surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard ofcare with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads andradioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years,several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currentlythe only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCCpatients with well-preserved liver function who are not candidates for potentially curative treatments, suchas surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus(HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis Bvirus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is notyet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC,although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still areasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors,including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolongedaflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects againstHCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatmenthas proven to be a rational strategy.     

Correlation of Clinicopathologic Features of Resected Hepatocellular Carcinoma with Hepatitis C Virus Genotype

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.     

原发性肝细胞癌组织中乙肝病毒整合与p53基因突变关系研究

应用Ｓｏｕｔｈｅｒｎ杂交方法检测１５例原发性肝细胞癌及癌旁组织乙肝病毒（ＨＢＶ）存在状态，采用ＰＣＲ－ＳＳＣＰ（Ｐｏｌｙ－ｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ－ｓｉｎｇｌｅｓｔｒａｎｄｃｏｎｆｏｒｍａｔｉｏｎｐｏｌｙｍｏｒｐｈｉｓｍ）银染技术研究其ｐ５３基因突变。结果癌组织中１３例（８６．７％）有ＨＢＶＤＮＡ整合，同时３例伴游离ＨＢＶＤＮＡ；癌旁４例（２６．７％）有ＨＢＶＤＮＡ整合，而游离的ＨＢＶＤＮＡ却有６例。癌组织中ｐ５３基因变异８例（５３．３％），１例位于第５外显子，各有２例位于第６、第７外显子，３例位于第８外显子，癌旁组织未见ｐ５３基因异常，ｐ５３基因异常的癌组织中均有ＨＢＶＤＮＡ整合。研究结果表明，ＨＢＶＤＮＡ整合与ｐ５３基因突变密切相关，ＨＢＶＤＮＡ可能通过整合基因组后导致抑癌基因突变失去抑癌作用而引发肝癌。     

Relationship between Multicentric Occurrence of Hepatocellular Carcinoma and Histology of Noncancerous Hepatic Tissue in Patients with Chronic Hepatitis C

The relationship between multicentric occurrence of hepatocellular carcinoma (HCC) and the histology of noncancerous hepatic tissue was investigated in 252 patients infected with hepatitis C virus (HCV) and surgically treated for HCC. One type of multicentric HCC had at least one tumor consisting of well-differentiated HCC, together with moderately or poorly differentiated HCC located in a separate region. The other type had an area of well-differentiated component around HCC with less differentiation in all occurrences. Noncancerous hepatic tissues were assessed using a histologic activity index score. Serum alanine aminotransferase (ALT) activity, the concentration of type 4 collagen, the grading score (severity of active hepatitis), and the staging score (degree of fibrosis) were significantly higher in patients with multicentric HCCs than in those without them. Platelet count was significantly lower in patients with multicentric HCCs. The prevalence of multicentric HCCs increased as the grading score and staging score increased. On univariate analysis, a low platelet count and high grading and staging scores were risk factors for multicentric HCCs. A high ALT activity and a high concentration of type 4 collagen tended to be risk factors. On multivariate analysis, high grading score and high staging score were independent risk factors. These findings indicate that active hepatitis and extensive fibrosis are responsible for the development of multicentric HCCs. Measurement of platelet count, ALT activity, and the concentration of type 4 collagen, and histologic assessment of noncancerous hepatic tissue provide information useful for estimation of the potential for multicentric carcinogenesis.     

Significant SNPs Related to Telomere Length and Hepatocellular Carcinoma Risk in Chronic Hepatitis B Carriers

Chronic hepatitis B virus (HBV) infection increases the risk of developing cirrhosis and hepatocellular carcinoma(HCC) with suspected interactions between virus replication and host immune responses. A number of reports havesuggested that telomerase function may be involved in chronic hepatitis B (CHB) pathogenesis, but positive or negativeassociations with HCC risk remain for discussion. Mean telomere length is an indicator of biological aging and it hasbeen reported that reduction in NBV carriers compared to normal individuals. In somatic cells, telomeres containsimple, tandemly repeated G-rich sequences that frequently are reduced by 50 to 200 base pairs at each cell division.Several genome-wide association studies (GWAS) in diverse ethnic populations have revealed eleven single nucleotidepolymorphisms (SNPs) linked to telomere length. Two of these, rs398652 and rs621559, have prognostic value and couldbe used as genetic markers. This review describes current knowledge concerning telomerase activity and telomere lengthas well as significant polymorphisms in HBV-related HCC patients. In particular, to cast light on genotype-phenotypeinteractions, we used SNPnexus to evaluate effects of the two SNPs on risk of disease and complex disorders.     

The Biological Function of Hepatitis B Virus X Protein in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the major malignant tumors that lead to death. Chronic hepatitis B virus infection is an important risk factor for HCC initiation. HBx protein, encoded by the HBV X gene, is a significant factor that promotes HBV-related HCC, although the exact molecular mechanism remains unclear. This article summarizes the pathological roles and related mechanisms of HBx in HCC. HBx plays a carcinogenic role by promoting cell proliferation, metastasis, and angiogenesis and inhibiting apoptosis in HCC. A detailed study of the biological functions of HBx will help to elucidate the mechanism of hepatocarcinogenesis and lead to the development of novel therapeutic targets for the treatment of HBV-related HCC.