湖北地区乙型肝炎病毒基因型分布与临床的相关性

目的 了解湖北地区乙型肝炎病毒(HBV)基因型的分布及其与临床的相关性。 方法 选择湖北地区HBV DNA阳性的慢性HBV感染者190例,其中乙型肝炎表面抗原(HBsAg)携带者52例、慢性乙型肝炎56例、重型肝炎32例、肝硬化22例、原发性肝癌28例,应用多对型特异性引物-聚合酶链反应检测HBV的基因型。 结果 多对HBV型特异性引物法可快速准确鉴定HBV的基因型。190份HBV DNA阳性血清标本中,B基因型140例(73.7％),C基因型42例(22.1％),BC混合型8例(4.2％),未发现A、D和E基因型;B基因型在重型肝炎和肝癌患者中占绝对优势,分别为87.5％和89.3％,显著高于HBsAg携带者的67.3％;B基因型患者血清丙氨酸氨基转移酶水平(253.1±306.7)U／L高于C基因型患者的(154.1±192.9)U／L,差异有统计学意义(P<0.05);除HBsAg携带者外的慢性HBV感染者中,B基因型患者血清抗-HBe阳性率50.5％(53／105)显著高于C基因型的18.5％(5／27),P<0.01。 结论 多对型特异性引物同时进行聚合酶链反应的基因分型方法可用于HBV基因型的流行病学调查;湖北地区存在HBV的B、C和BC混合基因型,B型为本地区的优势基因型并在严重肝病和肝癌中的比例较高,基因型的分布可能有较大的地区差异。     

乙型肝炎病毒基因型与病情轻重的关系

目的研究乙型肝炎病毒(HBV)基因型与肝脏损伤程度的相关性。方法随机选取87例慢性无症状乙型肝炎表面抗原携带者(ASC)、157例慢性乙型肝炎(CHB)、22例肝硬化(LC)和18例肝细胞癌(HCC)患者外周血测定HBV S基因序列以明确其基因型。结果基因型以B型和C型为主,分别为26.1％和73.2％。在B型与C型中,ASC、CHB、LC和HCC的构成比差异有非常显著性(X2=15.09,P<0.001),C型与B型相比,C型发展致CHB和HCC所占百分比显著高于B型,分别为59.6％比43.2％,X2=10.87,P<0.001;和7.7％比1.4％,X2=7.41,P<0.001。而LC所占百分比差异无显著性。结论基因型C型与B型相比,C型HBV感染易引起较重肝脏损伤。     

Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan

BACKGROUND: Hepatitis B virus (HBV) infection is a major health problem. HBV genotypes may be associated with progression of liver disease. The distribution and clinical implications of HBV genotypes in southern Taiwan are evaluated. METHODS: We used a polymerase chain reaction-restriction fragment length polymorphism genotyping method to determine HBV genotypes. RESULTS: The genotype distribution for 265 patients with chronic HBV infection was as follows: A, 3 (1%); B, 158 (60%); C, 90 (34%); D, 7 (2.5%); E, 0: F, 0; and unclassified, 7 (2.5%). Compared with genotype B patients, genotype C patients had a higher hepatitis B e antigen positive rate and higher fibrosis score. There was no significant difference in the mean age between genotype B and genotype C patients with hepatocellular carcinoma (HCC). However, when patients were stratified by age, the prevalence of genotype C was significantly higher in young HCC patients (<50 years of age) than in age-matched asymptomatic carriers (40% versus 10%, P < 0.001). Using multivariate analysis, the significant risk factors for advanced liver disease (cirrhosis or HCC) for patients with chronic HBV infection were old age, male gender and genotype C. CONCLUSIONS: These results suggest that genotype C is associated with more severe liver diseases than the B variant.     

Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B

BACKGROUND & AIMS: Six genotypes (A-F) of hepatitis B virus (HBV) have been identified; however, the genotype-related differences in the pathogenicity of HBV remain unknown. Therefore, we investigated the prevalence of HBV genotypes in Taiwan and the association between distinct genotypes and severity of liver disease in a cross-sectional study. METHODS: Using a molecular method, HBV genotypes were determined in 100 asymptomatic carriers and in 170 patients with histologically verified chronic liver disease and hepatocellular carcinoma (HCC). RESULTS: All genotypes except genotype E were identified in Taiwan, and genotypes B and C were predominant. Genotype C was prevalent in patients with cirrhosis and in those with HCC who were older than 50 years compared with age-matched asymptomatic carriers (60% vs. 23%, P < 0.001, and 41% vs. 15%, P = 0.005, respectively). Genotype B was significantly more common in patients with HCC aged less than 50 years compared with age-matched asymptomatic carriers (80% vs. 52%, P = 0.03). This predominance was more marked in younger patients with HCC (90% in those aged 相似文献   

Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand

AIM: The role of hepatitis B virus (HBV) genotypes on the clinical features and prognosis of patients with hepatocellular carcinoma (HCC) is currently unknown. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thai patients. METHODS: HBV genotypes were determined by PCR-RFLP in stored sera of 93 asymptomatic carriers, 103 patients with chronic hepatitis, 60 patients with cirrhosis and 76 patients with HCC. The clinical data were analyzed in relation to the HBV genotype. RESULTS: HBV genotypes C and B were predominant in Thailand, accounting for 73% and 21%, respectively. The distributions of genotypes B and C were similar in HCC patients compared to the other groups. Genotype C was significantly more common in HCC patients who were under 40 years old than genotype B (18% vs 0%, P= 0.03), but was significantly less common in patients older than 60 years (26% vs 56.5%, P= 0.01). The positive rate of hepatitis B e antigen (HBeAg) in patients with genotype C was significantly higher than that in patients with genotype B (71.6% vs 44.4%, P= 0.03 in chronic hepatitis; 56.8% vs 11.1%, P= 0.01 in cirrhosis). There were no differences between HCC patients with genotypes B and C regarding tumor staging by CLIP criteria and the overall median survival. Multivariate analyses showed that HBV genotype was not an independent prognostic factor of survival in HCC patients. CONCLUSION: Patients with genotype C had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC than those with genotype B. However, there were no differences in the risk of developing HCC and its prognosis between patients with these genotypes.     

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

AIM： To identify the distribution of hepatitis B virus （HBV） subgenotype and basal core promoter （BCP） mutations among patients with HBV-associated liver disease in Indonesia.
METHODS： Patients with chronic hepatitis （CH, n =61）, liver cirrhosis （LC, n = 62）, and hepatocellular carcinoma （HCC, n = 48） were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS： HBV genotype B （subgenotypes B2, B3, B4, 85 and B7） the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C （subgenotypes C1, C2 and C3） was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 （84.9%） and C1 （82.2%） were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 （84.9%） and adrq＋ （89.4%） were the most prevalent in HBV genotype B and C, respectively. Double mutation （A1762T/G1764A） in the BCP was significantly higher in LC （59.7%） and HCC （54.2%） than in CH （19.7%）, suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC （46.8%）, but lower in HCC （22.9%） and CH （18.0%）, suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION： HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.     

慢性乙型肝炎和肝硬化患者血清HBV基因型分析

目的 分析慢性乙型肝炎和肝硬化患者血清乙型肝炎病毒(HBV)分型分布情况。方法 2015年6月～2018年5月南京中医药大学附属南京市第二医院就诊的慢性乙型肝炎患者261例,乙型肝炎肝硬化患者30例,肝细胞癌4例,采用测序法检测血清HBV基因型。结果 在295例HBV感染者中,有132例(44.7%)为B型感染,161例(54.6%)为C型感染,2例(0.7%)为D型感染;慢性乙型肝炎患者与肝硬化患者血清TBIL、ALT和AST水平比较差异均无统计学意义(P>0.05);肝硬化患者血清肝纤维化指标(P<0.05)、血清HBV DNA载量(P<0.05)和血清HBeAg阳性率(x²=5.798,P<0.05)均显著高于慢性乙型肝炎患者;乙型肝炎肝硬化患者和肝细胞癌患者C型感染比例均显著高于慢性乙型肝炎患者,差异具有统计学意义(P<0.05)结论 慢性乙型肝炎和肝硬化患者HBV感染以B基因型和C基因型为主,而肝硬化患者以C型感染居多,提示C型感染患者可能比B型患者更容易出现严重的肝损伤,并产生严重的临床结局。     

慢性乙型肝炎病毒感染者病毒前C区和基本核心启动子区变异检测及意义

目的 探讨乙型肝炎病毒（HBV）前C区和基本核心启动子（BCP）区变异与基因型及疾病进展间的关系。方法 收集HBV携带者（ASC）、慢性乙型肝炎（CHB）、肝炎肝硬化（LC）、肝细胞肝癌（HCC）患者血清148份，用半巢式聚合酶链反应扩增HBV前C／C基因部分片段，产物纯化后直接测序，检测前C区A1896及BCP区T1762／A1764变异。用S基因聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）方法确定HBV基因型。结果 有128份血清能够成功分型和测序，其中B基因型60份，C基因型68份。在B基因型感染者中前C区A1896变异检出率（48．33％）明显高于C基因型感染者（29．41％，X^2=4．83，P〈0．05）；而BCP区T1762／A1764变异检出率却明显低于C基因型感染者，差异亦有统计学意义（30．00％：73．54%，X^2=24．25。P〈0．05）。前C区A1896变异在CHB、LC、HCC中的阳性检出率分别为46．88％（15/32）、39．39％（13／33）、51．52％（17／33）。与ASC的13．33％（4／30）相比，P分别〈0．05，差异有统计学意义。BCP区T1762／A1764变异检出率在HCC、LC组分别为87．88％（29／33）和72．73％（24／33）．明显高于CHB组的37．50％（12／32）及ASC组10.00％（3／30）（P〈0．05）。结论 前C区A1896变异常见于B基因型感染者，而BCP区T1762/A1764变异C基因型感染者多见。除ASC外．前C区A1896变异与疾病进展关系不大．而BCP区T1762/A1764变异与乙型肝炎进展及顶后相关。     

Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong

OBJECTIVE: We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection. METHODS: Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin > 50 IU/L or elevated bilirubin plus PT > 3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child's A liver cirrhosis plus HBV DNA > 106 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child's B or C liver cirrhosis with complications. Restriction fragment length polymorphism was used for genotyping. RESULTS: Only genotype B and C HBV were identified in our studied cohort. Ninety-one percent of patients suffering from IF were infected by genotype B HBV (p < 0.001 vs asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients). On the contrary, genotype C HBV was the predominant strain at different stages of chronic liver disease; no statistical difference was found on the relative prevalence of genotype B/C HBV among asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients. CONCLUSIONS: Genotype B HBV is associated with IF among chronic HBV-infected patients in Hong Kong, whereas genotype C HBV is more prevalent at all stages of chronic liver disease. Our findings suggested that the two different HBV genotypes might have different pathogenic mechanisms of liver damage.     

Hepatitis B viral genotypes: clinical relevance and molecular characteristics

Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.     

贵州地区慢性乙型肝炎病毒感染者病毒基因亚型研究

目的调查贵州省B、C基因型慢性HBV感染者的病毒基因亚型。方法PCR扩增HBV P区长309 bp的基因片段,扩增产物分别经限制性内切酶NciⅠ、VspⅠ、BstEⅡ酶切,琼脂糖凝胶电泳,根据酶切图谱多态性,用限制性片段长度多态性分析（PCR-RFLP）检测HBV C基因亚型。直接测序确定B基因亚型、对178例用S基因限制性片段长度多态性鉴定为B、C基因型的不同临床类型慢性HBV感染者进行亚型分析。结果84例C基因型HBV感染者中,27例（32.14%）为C1亚型、56例（66.67%）为C2亚型,1例为C1、C2亚型混合感染。94例B基因型HBV感染者中,93例（98.94%）为Ba、1例为Bj亚型感染。从无症状乙型肝炎表面抗原携带者、CHB到肝硬化/肝癌,C1亚型在各组中的比例逐渐降低,分别为60.00%、30.65%和16.67%;而C2亚型在各对应组中的分布逐渐增高,分别为40.00%、67.74%和83.33%。结论贵州地区B、C基因型慢性HBV感染者中,以Ba、C2亚型为主。C1、C2亚型在疾病中的分布有一定差异。PCR-RFLP分析HBV C1、C2亚型,方法简便、特异性强,适合较大样本分析,可用于流行病学调查。     

The Effect of HBV Genotype C on the Development of HCC Differs Between Wild-Type Viruses and Those With BCP Double Mutations (T1762A1764)

Background:

Association of hepatitis B virus (HBV) genotype C with hepatocellular carcinoma (HCC) development remains controversial. HBV basal core promoter (BCP) double mutations (T¹⁷⁶²A¹⁷⁶⁴) are very strong confounding factors of genotypes B and C in HCC development.

Objectives:

To investigate the association of HBV genotype C with HCC development after controlling for BCP double mutations.

Materials and methods:

Four hundred and two serum samples from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH) and also from asymptomatic HBsAg carriers were analyzed.

Results:

Genotypes B (31.1%), C (62.8%), and I (6.1%) were detected. With the severity of liver disease the prevalence of genotype B decreased, but genotype C increased. No trend was found for genotype I. The prevalence of BCP double mutations in genotypes C and I viruses was significantly higher than genotype B. BCP double mutations are risk factors for CH, LC and HCC. Genotype C was not identified as a particular risk factor for HCC prior to the stratification analysis but after that genotype C viruses with BCP double mutations were found to be a particular risk factor for HCC (P = 0.008, OR = 17.19 [95% CI: 2.10 - 140.41]), but those with the wild-type BCP were not. In the interaction analysis, genotype C and BCP double mutations were found to have a synergistic effect on HCC development (P < 0.0001, OR = 52.56 [95% CI: 11.49-240.52]).

Conclusions:

The effect of HBV genotype C on the development of HCC differs between wild-type viruses and those with BCP double mutations, suggesting that not all individuals infected with genotype C HBV are at increased risk of HCC.     

Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection

We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.     

Mutations in <Emphasis Type="Italic">preS</Emphasis> genes of genotype C hepatitis B virus in patients with chronic hepatitis B and hepatocellular carcinoma

Background Hepatitis B virus (HBV) preS mutations are frequently isolated from patients with severe forms of liver disease. Meanwhile, genotype C has been shown to cause more serious liver disease than genotype B. This study assesses the frequency of preS mutation in Chinese patients with genotype C chronic HBV infection and its relation to liver damage. Methods Seventy-nine persistently infected patients (25 asymptomatic carriers, 28 with chronic hepatitis, and 26 with hepatocellular carcinoma) with genotype C HBV were analyzed. Levels of HBV DNA, hepatitis B e antigen (HBeAg), alanine aminotransferase, and aspartate transaminase and mutations in the preS region were determined. Results The correlations of preS deletion with disease progression were distinct: preS deletion mutations were more commonly found in the hepatocellular carcinoma (HCC) group than in the chronic hepatitis B (CHB) or asymptomatic carrier (ASC) groups, with the frequencies of 38.46% (10/26) in the HCC, 7.14% (2/28) in the CHB, and 4.00% (1/25) in the ASC (P = 0.001) groups. The HBeAg-positive rate and HBV DNA levels were comparable between patients with the preS mutation and those without. Conclusions PreS deletion mutations of genotype C HBV might play a role in HBV-related hepatocarcinogenesis.     

Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients

AIM: To identify the prevalence of pre-S2 start codon mutations and to assess their association with liver disease progression. METHODS: The mutations were identified by direct sequencing from 73 asymptomatic carriers, 66 chronic hepatitis (CH), 66 liver cirrhosis (LC) and 63 hepatocellular carcinoma (HCC) patients. Statistical significances were determined using Fisher's exact test, χ 2 test, and t -test analyses whenever appropriate. Pre-S mutation as a risk factor for advanced liver disease was estimated by unconditional logistic regression model adjusted with age, sex, and hepatitis B e antigen (HBeAg). P 0.05 was considered significant. RESULTS: Mutation of the hepatitis B virus (HBV) pre-S2 start codon was found in 59 samples from 268 subjects (22.0%), with higher prevalence in patients with cirrhosis 27/66 (40.9%) followed by HCC 18/63 (28.6%), chronic hepatitis 12/66 (18.2%) and asymptomatic carriers 2/73 (2.7%) (P 0.001). Logistic regression analysis showed that pre-S2 start codon mutation was an independent factor for progressive liver disease. Other mutations, at T130, Q132, and A138, were also associated with LC and HCC, although this was not statistically significant when adjusted for age, sex, and HBeAg. The prevalence of pre-S2 start codon mutation was higher in HBV/B than in HBV/C (23.0% vs 19.1%), whilst the prevalence of T130, Q132, and A138 mutation was higher in HBV/C than in HBV/B. The prevalence of pre-S2 start codon mutation was higher in LC (38.9%) and HCC (40.0%) than CH (5.6%) in HBeAg(+) group, but it was similar between CH, LC and HCC in HBeAg(-) group. CONCLUSION: Pre-S2 start codon mutation was higher in Indonesian patients compared to other Asian countries, and its prevalence was associated with advanced liver disease, particularly in HBeAg(+) patients.     

Subgenotypes of hepatitis B virus genotype C do not correlate with disease progression of chronic hepatitis B in Taiwan.

BACKGROUND: Hepatitis B virus (HBV) genotype C (HBV/C) has two subgenotypes: HBV/Cs and Ce. The prevalence and clinical implications of subgenotype Cs and Ce in Taiwanese HBV carriers remain unknown. METHODS: Subgenotypes of HBV/C were determined in 242 Taiwanese HBV carriers with various stages of liver disease. The clinical as well as virologic features between patients with HBV/Cs and HBV/Ce infection were further compared. RESULTS: HBV/Ce was the predominant subgenotype in Taiwan. The prevalence of HBV/Ce was 93.6% in the inactive carriers group, 84.2% in chronic hepatitis patients, 81.2% in cirrhosis patients, 92.5% in hepatocellular carcinoma (HCC) patients without cirrhosis and 91.9% in HCC patients with cirrhosis. There was no significant difference in the distribution of the HBV/C subgenotypes among patients with different stages of liver disease. CONCLUSIONS: Subgenotypes of HBV/C may not have a clinical impact on the disease progression of chronic hepatitis B in Taiwan.     

HBV genotypes in India: do they influence disease severity?

Aims:  Association of HBV genotypes (especially A and D) with severity of liver disease is controversial. We studied the influence of HBV genotypes on liver disease severity among Indian patients.
Methods:  We selected 247 HBV infected patients (42 acute hepatitis, 87 carriers, 44 chronic hepatitis B [CHB], 35 liver cirrhosis [LC] and 40 hepatocellular carcinoma [HCC]). Genotyping of stored sera was performed using genotype-specific enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism (RFLP). The distribution of genotypes in disease states of differing clinical, histological and biochemical severity were compared.
Results:  The most common genotype was D (162/237, 68.3%), followed by A (61, 25.7%) and C (14, 5.9%). The distribution of HBV genotypes between patients with acute hepatitis and CHB (carriers + CHB + LC + HCC), or between carriers and disease states (CHB + LC + HCC), or between mild chronic infection (carriers + CHB) and complications of chronic HBV infection (LC + HCC) was similar. Eighty-seven patients had liver biopsy; the median histological activity index (HAI) and fibrosis stage at baseline were similar between genotype groups (four [1–9] genotype A [ n  = 28]), three (2–4) genotype C ( n  = 4) and four (1–10) genotype D ( n  = 55); P  = 0.33 for HAI score; (0.5 [0–6] genotype A, 0.5 [0–4] genotype C and 1 [0–6] genotype D; P  = 0.92 for fibrosis stage). The response to therapy was similar between the genotypes.
Conclusion:  Clinical, histological severity and therapeutic responses are similar among patients with HBV genotypes A and D.     

Alteration of serum cytokine balances among different phases of chronic hepatitis B virus infection.

To understand the pathogenesis of chronic hepatitis B virus (HBV) infection, we examined the serum levels of IL-10, TNF-alpha IL-12 p70, and IL-12 p40 in 77 patients chronically infected with HBV and 19 controls. The patients were classified into four groups: asymptomatic carriers (ASC), patients with chronic hepatitis (CH), patients with liver cirrhosis (LC), and patients with hepatocellular carcinomas (HCC). The cytokine values among these groups were compared and their relations to clinical parameters were investigated. All these cytokine values were higher in the patient groups than in controls. IL-10 and TNF-alpha became higher in accordance with the progress of the disease phases, from ASC to LC, and lowest when the patients had HCC. IL-12 p40 was also lowest in HCC, however, the group with highest levels was CH. IL-12 p70 was unchanged among ASC, CH, and LC, but were raised in HCC. Serial analyses for the cytokine values in the same patients showed the similar tendencies. Regression analysis showed the significant correlations between ALT and IL-10. Serum cytokine values well reflected the pathological differences of the individual disease phases, and may become useful indices to understand the pathogenesis of chronic HBV infection.     

HBV基因型、变异、X蛋白与HCC相关性的研究

【摘要】 目的  了解HBV病毒基因型、变异位点1762/1764和1896、X蛋白与肝细胞癌的关系,进一步探讨肝癌的发病机理,为肝癌的防治及早期诊断提供理论依据。 方法  采用核酸扩增荧光定量及测序法检测慢性HBV携带者、慢性乙型肝炎、乙肝肝硬化和乙肝合并肝癌患者共159例血清标本的HBV基因型及变异位点,采用免疫组织化学方法检测上述4组肝组织中X蛋白的表达情况,用半定量积分法进行结果判断。 结果  1. 在159例慢性HBV感染者中基因型B型为56例,占35.2％（56/159）,基因型C型为103例,占64.8％（103/159）,基因C型在ASC、CHB、LC、HCC四组中所占比例分别为44.0%（11/25）,63.2%（36/57）,85.7%（36/46）,64.5%（20/31）,差异有统计学意义（χ2 =8.462,P=0.037）。2. 在ASC、CHB、LC、HCC四组中,基因C型HBV感染者发生BCP变异的病例数所占比例分别为36.4%（4/11）,75.0%（27/36）,80.6%（29/36）,75.0%（15/20）,发生PC变异的病例数所占比例分别为45.5%（5/11）,66.7%（24/36）,77.8%（28/36）,70.0%（14/20）,两种变异均多于基因B型感染者,除ASC组外,差异均有统计学意义（P <0.05）。3. X蛋白的表达,以LC组最高（阳性率71.7%）,其次是HCC组（71.0%）、CHB组（59.6%）、ASC组（52.0%）,组间比较差异有统计学意义（P<0.05）。4. ASC组、CHB组、LC组和HCC组基因C型HBV感染者X蛋白的阳性表达率分别为81.8%（9/11）,72.2%（26/36）,86.1%（31/36）和85.0%（17/20）,大于基因B型感染者X蛋白的阳性表达率,即28.6%（4/14）,38.1%（8/21）,20.0%（2/10）,45.5%（5/11）,差异有统计学意义（P<0.05）。ASC、CHB、LC和HCC组中X蛋白阳性表达的HBV感染者BCP变异阳性的比例分别为61.5%,73.5%,69.7%,81.8%,均高于BCP变异阴性感染者所占比例,PC变异阳性的比例分别为46.2%,67.6%,78.8%,63.6%,除了ASC组外均高于PC变异阴性感染者所占比例,但差异无统计学意义。 结论  HBV基因型、变异位点1762/1764和1896、X蛋白之间存在相互关系,与肝细胞癌的发生与发展有关。