Hepatitis C virus antibody in hepatocellular carcinoma in Taiwan.

The prevalence of antibody to hepatitis C virus (anti-HCV) was investigated in patients with hepatocellular carcinoma (HCC), and correlated with the clinical features. Anti-HCV was detected in 129 histology or aspiration cytology proven HCC patients and 54 healthy controls. Anti-HCV was examined by the HCV EIA (Abbott Laboratories). All healthy controls were anti-HCV-negative. Nineteen of 81 (23.5%) hepatitis B surface antigen (HBsAg)-positive HCC patients were positive for anti-HCV. Anti-HCV was found among 60.4% (29/48) of HCC patients without detectable HB-sAg. Forty-eight of 129 (37.2%) HCC patients were positive for anti-HCV. There was a significant difference in the prevalence of anti-HCV between patients with HBsAg (23.5%) and those without HBsAg (60.4%, P = 0.0001). However, irrespective of the status of HBsAg, there was no statistical difference in sex, age, routine liver function tests, alpha-fetoprotein concentration, or associated cirrhosis between patients with anti-HCV and those without. The results imply that hepatitis C virus may play a role in the pathogenesis of HCC.     

X gene mutations in hepatitis B patients with cirrhosis,with and without hepatocellular carcinoma

Specific mutations in the hepatitis B virus (HBV) genome have been reported to be associated with the development of hepatocellular carcinoma (HCC). The goal of this study was to determine whether mutations in the HBV X gene are associated with the development of HCC in hepatitis B patients with cirrhosis. Forty‐two patients infected with HBV genotype C2 with cirrhosis and HCC were compared with 46 patients with cirrhosis but without HCC. X gene mutations were determined by direct sequencing in all patients. The HCC and non‐HCC groups were similar with respect to clinical characteristics, and the presence of T1762/A1764, T1653, and V1753 mutations was not significantly different between the two groups (P = 0.068, P = 0.097, P = 0.442, respectively). Only the B1499 mutation was associated significantly with HCC (P = 0.015) (odds ratio: 3.42, 95% CI: 1.24–9.48). In hepatitis Be antigen (HBeAg)‐positive patients, advanced age was associated significantly with HCC (P = 0.038), whereas in HBeAg‐negative patients, the B1499 mutation was associated more significantly with HCC (P = 0.01). Patients in the B1499 mutation group exhibited significantly higher AST and ALT levels compared with patients infected the wild‐type virus. In conclusion, B1499 is a novel mutation associated with HCC in Korean patients with cirrhosis infected with HBV genotype C2. J. Med. Virol. 81:1721–1725, 2009. © 2009 Wiley‐Liss, Inc.     

Relationship between codon 249 mutation in exon 7 of p53 gene and diagnosis of hepatocellular carcinoma

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC. Heat shock proteins have essential roles in protecting cells from the potentially lethal effects of stress. Among them, HSP70 are often overexpressed in cells of various cancers and have been suggested to contribute to tumourigenesis. p53 mutations in codon 249 have also been identified in HCC.

Material and methods

Fifty patients with liver disease were enrolled in this study compared to 10 healthy volunteers. The studied patients were divided into 2 groups: group I includes those suffering from HCC, group II includes those suffering from post-hepatitis B and C liver cirrhosis. The presence of p53 gene mutation was detected by DNA extraction from whole blood of patients and controls followed by polymerase chain reaction then restriction fragment length polymorphism (RFLP) analysis of codon 249 of exon 7. We also studied the genotypes of the HSP70 gene by PCR followed by RFLP analysis.

Results

Our results revealed no statistical difference between group I, group II, and the control group as regards exon 7 mutation of the p53 gene. Also the frequency of polymorphic genotypes of HSP70 showed no significant difference between the 3 studied groups.

Conclusions

The present study supports the view that the incidence of point mutation of p53 codon 249 mutations in exon 7 of the p53 gene may not play a role in carcinogenesis of HCC in Egyptian patients. Also, genetic polymorphism in HSP70 was not associated with high risk of future development of HCC.     

Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus

Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) in Asia. Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an interferon-induced, serine/threonine protein kinase. Recent studies have suggested that PKR is involved in the pathogenesis of HCC with hepatitis virus C infection by inhibiting viral and cellular proteins related to cell growth and proliferation. In the present study, PKR was examined in both tumor and non-tumor tissues from HCC livers infected with HBV. The expression of PKR was determined by TaqMan real-time PCR and immunohistochemical methods. The level of PKR was also analyzed in relation to pathological changes observed in HCC. The result showed that PKR was reduced in tumor tissues of HCC from HBV carriers with low serum viral load (<0.7 x 10(6) copies/ml) compared to those with higher serum viral load. However, the overall PKR level was much lower in tumor tissues than that in non-tumor tissues, irrespective of HBV carrier status or serum viral load. PKR level tended to be lower in HCC samples with alpha-fetoprotein (AFP) more than 500 ng/ml (mean: 4024.2 ng/ml) than those with AFP less than 500 ng/ml (mean: 50.6 ng/ml). There was no significant difference in the expression of PKR between tumor tissues with well differentiation and those with poor or moderate differentiation. In conclusion, the level of PKR was reduced in HCC tumor tissues, suggesting a possible role of PKR in promoting the growth of tumor. HBV may participate in altering the level of PKR, but factors other than HBV should play a more determining role in the regulation of PKR in HCC. The association between PKR and AFP levels may offer an alternative tumor marker for HCC.     

Serum antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma

Antibodies against hepatitis C virus (anti-HCV) were detected in 60.8% of 78 patients with hepatocellular carcinoma (HCC). Cirrhosis, present in most of the patients, as well as alcohol abuse, age, sex, and alpha-fetoprotein were equally distributed in the anti-HCV-positive and -negative groups. HBsAg positivity was significatively higher in negative anti-HCV group. By contrast, hepatitis B virus (HBV) antibodies were detected more frequently in positive anti-HCV patients than in the negative anti-HCV group. These data must be considered with caution because of the small number of HBsAg-positive patients. It is concluded that the high prevalence of anti-HCV in patients with HCC may suggest an etiological role of the hepatitis C virus, although in relationship to age, alcohol abuse and cirrhosis, the similarity in the two groups questions this hypothesis.     

Hepatitis-B virus infection in black children with hepatocellular carcinoma

The hepatitis B virus (HBV) status of six unselected South African Black children, aged 10 to 16 years, with hepatocellular carcinoma (HCC) was investigated. The characteristics of the tumor were similar to those seen in Black adults. Hepatitis B surface antigen and antibody to the core antigen were present in the serum of all the children, and hepatitis Be antigen was detected in four of the children. The serum of the two patients without e antigen was positive for e antibody, and all sera were negative for hepatitis B surface antibody. Taken in conjunction with the HBV status of southern African Black adults with HCC, these findings raise the possibility that nearly all, if not all, Black patients with this tumor are or have been infected with HBV. Moreover, if HBV is oncogenic, tumor formation may occur within 10 years of the initial infection, which occurs in early childhood in southern African Blacks.     

Hepatitis B virus DNA in primary hepatocellular carcinoma tissue.

Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.     

HBV-DNA hybridization in hepatocellular carcinoma associated with alcohol in Japan

To clarify the role of the hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) associated with alcohol consumption, HBV-DNA in the liver of 19 patients with HCC were investigated. HBV-DNA was examined by Southern blot hybridization. HBV-DNA was integrated into tumor cells from five out of six (83%) patients with HCC associated with HBs antigen (HBsAg)-positive post-hepatitic liver cirrhosis (LC), but this was not related to the history of alcohol intake. In 13 HCC patients of HBsAg-negative alcoholic LC, HBV-DNA integration was not detected in any patient. These findings suggest that HBV does not play a major role in the pathogenesis of HCC in HBsAg-negative alcoholics in Japan.     

Effects of hepatitis C and B viruses infection on the development of hepatocellular carcinoma

A case control study consisting of 102 patients with HCC, 102 sex-matched and age-matched patients with nonhepatic disease, and 204 matched healthy controls was carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The prevalence of antibody to HCV (anti-HCV) in HCC (34.3%) was higher than in nonhepatic disease (10.7%, P< 0.001) or in healthy controls (2.4%, P< 0.001). The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher than in nonhepatic disease (16.6%, P< 0.001) or in healthy controls (19.6%, P< 0.001). Anti-HCV positivity in nonhepatic disease was higher than in healthy controls (P<0.01). Using patients with nonhepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio, 3.4; 95% confidence interval, 2.1-5.6) and HBsAg (odds ratio, 5.6; 95% confidence interval, 3.6–8.5) are independent risk factors for HCC. Using healthy controls, the development of HCC was also strongly associated with anti-HCV (odds ratio, 8.0; 95% confidence interval, 4.3–14.6) and HBsAg (odds ratio, 5.5; 95% confidence interval, 3.7–8.2). Calculation of incremental odds ratio indicated that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are risk factors of HCC. They act independently and without interaction. © 1994 Wiley-Liss, Inc.     

Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular carcinoma

Fas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody. sFas levels were significantly higher in HCC patients (median 4.07 ng/ml; range 0.14–29.18 ng/ml) than levels in age-matched healthy donors (0.29 ng/ml; 0–4.90 ng/ml) (P < 0.0001) and HBsAg or anti-HCV antibody-positive patients with liver cirrhosis (LC) (2.16 ng/ml; 0.24–8.39 ng/ml) (P = 0.0015). An arbitrary cut-off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC, and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested contained transmembrane-deleted sFas and some contained another sFas lacking the Fas C-terminal. The positive frequency of either sFas (59.0%) or α-fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with multiple tumour foci (7.53 ng/ml; 1.40–29.18 ng/ml) had significantly higher sFas levels than did patients with a solitary tumour (2.70 ng/ml; 0.14–19.0 ng/ml) (P = 0.003). In all of the sFas-positive patients with a solitary tumour, surgical removal of the tumour reduced sFas levels to the negative in the first post-op week. These findings suggest that sFas may be closely linked with HCC and may be a candidate for a clinical parameter for HCC.     

肝细胞肝癌发病过程中HBVx及COX-2的作用

目的 研究HBVx和COX-2在肝细胞肝癌发病过程中的作用.方法 145例HCC、78例肝炎后肝硬化及16例来自尸检的正常肝组织标本经病理复查后制成组织芯片,进行HE及免疫组织化学染色,评定各指标的染色指数.结果 HCC组HBVx平均阳性表达指数高于肝硬化组(P<0.01).HBVx在高、中、低分化HCC组间表达差异有统计学意义.COX-2免疫组化染色在肝硬化组表达较强;在HCC组和正常人肝细胞胞质中表达较弱.HCC组肿瘤细胞胞质中COX-2阳性表达指数低于肝硬化组(P<0.01).COX-2在高、中、低HCC组间表达差异有统计学意义.相关性分析表明145例HCC中HBVx表达与COX-2表达存在正相关(P=0.000).结论HBVx可通过调节COX-2的表达参与HCC发病过程.     

URG4在肝癌组织中的表达及其与HBx的关系

目的:检测URG4在肝癌组织中的表达及意义。探讨URG4与HBx在肝癌组织表达之间的关系。方法:免疫组化方法检测URG4和HBx在正常组织、肝癌组织及癌旁组织中的表达分布,并分析其表达的意义及表达之间的相关性。结果:URG4在肝癌组织及肝癌细胞系中的阳性表达率分别为48%和54%,而在正常组织中仅22.2%弱表达,其与HBx表达的相关系数分别为0.38和0.45(P0.05)。结论:URG4在肝癌组织及癌旁组织中的表达高于正常组织,且与HBx密切相关。     

Association between the Interleukin-10 -1082 G/A polymorphism and risk of hepatocellular carcinoma

BackgroundInconsistent results have been reported from studies investigating the relationship of the interleukin-10 (IL-10) -1082 G/A polymorphism and the susceptibility of hepatocellular carcinoma (HCC). Therefore, a thorough literature review of relatedstudies was performed in this meta-analysis to examine the association of the interleukin-10(IL-10) -1082 G/A polymorphism with HCC susceptibility.MethodsElectronic databases were searched for literature on the relationship between interleukin-10(IL-10) -1082 G/A polymorphism and the risk of HCC in accordance with the inclusion and exclusion criteria. The selected studies were analyzed using the Stata 12.0 software. Finally, the strength of the associations was evaluated using the odds ratio (OR) and 95% confidence intervals (95% CI).ResultsA total of six case-control studies were enrolled into the current meta-analysis, which included a total of 911 patients and 1889 control subjects. Our data revealed no association between the IL-10 -1082 G/A polymorphism and the risk of HCC (GG vs AA:OR=0.84, 95%CI=0.57–1.25; AG vs AA:OR=0.85, 95%CI=0.70–1.05; Dominant model: OR=0.85, 95%CI=0.70–1.03; and Recessive model: OR=0.92, 95%CI = 0.64–1.32). Similarly, no association was found in sub-group analysis based on ethnicity.ConclusionThe results of our study suggest no association between IL-10 -1082 G/A polymorphism and the risk of HCC.     

Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma

Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross‐sectional case–control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age‐, sex‐, and hepatitis B e antigen (HBeAg) status‐matched patients without HCC (non‐ HCC group). Age and sex were also matched between HBeAg‐positive and ‐negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box α region, the A1689 mutation in between the box α and β regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non‐HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg‐negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the A1689, and T1762/A1764 mutations was higher in the HCC group than in the non‐HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, A1689, and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or A1689 mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, A1689, and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2. J. Med. Virol. 81:1002–1008, 2009. © 2009 Wiley‐Liss, Inc.     

Primary hepatocellular carcinoma and hepatitis B virus infection in korea

Serological evidence of hepatitis B virus (HBV) infection and serum alphafetoprotein (AFP) were assayed in sera from 112 Korean patients with primary hepatocellular carcinoma (PHC) and from 63 age- and sex-matched controls. Serological evidence of HBV infection was found in 100% of PHC patients and in 97% of controls. The majority of PHC patients (87%) were positive for hepatitis B surface antigen (HBsAg). In contrast, only 14% of control individuals were positive for HBsAg, but 82% were positive for antibody to HBsAg (anti-HBs). Hepatitis B e antigen (HBeAg) was detected in a high percentage (38%) of HBsAg-positive PHC patients, but in none of the nine HBsAg-positive control individuals. Serum AFP was detectable in 83% of PHC patients but in only one of 63 controls (1.5%). These results document that HBV infection may be the mjor factor in the development of PHC in this country.     

白细胞介素10基因启动子区多态性与乙型肝炎病毒感染预后的关联研究

目的探讨中国汉族人白细胞介素10基因(interleukin10gene,IL10)启动子区单核苷酸多态性与乙型肝炎病毒(hepatitisBvirus,HBV)感染、转归的关联。方法采用聚合酶链反应-限制性片段长度多态性分析方法,检测231例HBV感染者,165例HBV感染康复者和135名正常对照者IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型。结果IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型和等位基因在HBV感染组、HBV感染康复组和正常对照组之间的分布频率比较差异无统计学意义(P>0.05),在血清HBV-DNA<1×103拷贝/mL的HBV感染者组和HBV-DNA≥1×103拷贝/mL组之间的分布频率比较差异亦无统计学意义(P>0.05);但IL10基因启动子-819T/C和-592A/C位点基因型和等位基因在HBV无症状携带组和慢性乙型肝炎组之间的分布差异有统计学意义(P<0.05),-819T/C位点TT型和-592A/C位点AA型在慢性乙型肝炎组的频率明显较高。结论汉族人IL10基因启动子多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性;但IL10启动子-819T/C和-592A/C位点基因多态性与HBV感染后的肝脏炎症反应有关。     

Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma

Hepadnaviruses share properties of virion structure, genome structure and replication, epidemiologic behavior, and pathogenic effects, including an association with hepatocellular carcinoma (HCC). Epidemiologic evidence implicating hepadnavirus infection in HCC includes the observation that the geographic distributions of HBV infection and HCC are similar, that the incidence of HCC is much higher in hepadnavirus infected than uninfected hosts, and that viral DNA sequences are integrated in the cellular DNA of most (e.g., 80-90%) but not all hepadnavirus-associated HCC. Cirrhosis further increases the risk of HCC in HBV infected humans. The precise role of hepadnaviruses in development of most HCC is unclear, although the finding of viral integrations within or near protooncogenes in a few cases suggests the possibility that these integrations may play a direct role in these HCC. However, in the great majority of HCC associated with HBV infections, viral integrations are in different cellular DNA sites in different HCC, integrations are not within domains of known protooncogenes, and integrations are not found in some 10-15% hepadnavirus-associated HCC, suggesting that persisting viral sequences are not directly involved in the development of these HCC as viral sequences are for tumors caused by viruses with oncogenes or viruses that act by a "promoter-insertion" mechanism. It is possible, however, that oncogenic mutations could arise via other mutagenic mechanism that may operate in chronic hepatitis B and/or cirrhosis and which do not involve persisting viral integrations. For example, liver regeneration, which is a feature of the cirrhosis associated with chronic HBV infection (and sometimes with chronic hepatitis B) involves proliferation of many cells with HBV integrations, and such integrations have been shown to be unstable and may lead to mutations through post-integration rearrangements of cellular sequences at sites of viral integrations. Viral sequences appear to be lost or deleted at some such sites of rearranged cell DNA. Chronic HBV infection shares pathologic features of liver cell injury and reactive inflammation, liver regeneration, and in man sometimes cirrhosis with other important risk factors for HCC including chronic alcoholic liver disease, chronic non-A, non-B hepatitis, hemochromatosis, and crypogenic cirrhosis, suggesting that this common pathologic process may be carcinogenic by a mechanism that does not depend specifically on the factor which initiates liver cell injury. The pathogenetic role of chronic hepadnavirus infection in such a process would be in causing liver cell injury with reactive inflammation and hepatocyte proliferation (regeneration).(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatitis B viral loads in southern African Blacks with hepatocellular carcinoma

Although viral loads are known to influence the development of hepatitis B virus‐induced hepatocellular carcinoma in a number of populations, little information is available in the Black African population. Black African patients with hepatocellular carcinoma differ from those in other populations in having a lower frequency of e antigen‐positivity and in other respects that might affect viral loads. Hepatitis B viral loads were measured using real‐time polymerase chain reaction assay in 124 Black Africans with hepatocellular carcinoma and compared with those in 125 Black adult asymptomatic viral carriers. The geometric mean viral load in the cancer patients was 553,618 copies/ml (95% CI 301,953–1,015,033 copies/ml), with 62.1% having loads >1 × 10⁵ copies/ml and 87.1% >1 × 10⁴ copies/ml, whereas that in the carriers was 16,084 copies/ml (95% CI 9,184–28,168 copies/ml), with only 15.2% having values >1 × 10⁵ copies/ml and 49.6% >1 × 10⁴ copies/ml (P < 0.001 in each instance). Mean viral load was significantly higher in e antigen‐positive than e antigen‐negative cancer patients (5,905,357 copies/ml [1,362,847–25,588,520] cf 238,173 copies/ml [97,200–685,730]: P < 0.001) after adjusting for age and sex. No statistically significant difference existed between patients in different age groups, in men and women, or in patients infected with genotype A or D after adjusting for the other variables. Conclusion: Black Africans with hepatocellular carcinoma have high hepatitis B viral loads in spite of the relative infrequency of e antigen‐positivity. J. Med. Virol. 81:1525–1530, 2009. © 2009 Wiley‐Liss, Inc.     

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009. © 2009 Wiley‐Liss, Inc.