病毒相关性肝细胞癌抗病毒治疗的临床意义

中国大陆地区80％的肝细胞癌(HCC)具有HBV感染背景,其中80％是基于肝硬化背景发生的,治疗方案设计要注意两个原则:(1)积极清除实体肿瘤;(2)积极改善肝脏微环境,防治肝硬化进展,减少HCC的复发和终末期肝病的发生.除了应用手术切除或非手术手段损毁HCC病灶之外,内科综合治疗具有重要意义.目前具有较多循证医学证据的辅助治疗措施为抗病毒治疗,故中华医学会肝病学分会肝癌学组提出了《HBV/HCV相关性肝细胞癌抗病毒治疗专家建议》(以下简称《建议》)[1].《建议》强调了针对HBV/HCV相关性肝细胞癌患者应用抗病毒治疗的必要性,抗病毒治疗的应用可提高患者生活质量,延长患者生存期.     

肝细胞癌多中心发生的诊断和治疗

在肝细胞癌(HCC)的治疗手段中，以HCC的治愈性切除为首选，但切除后的复发率可达50％～60％。我国HCC多合并慢性肝炎及肝硬化，85％的HCC合并肝硬化。慢性肝病多缘于HBV与HCV的感染，慢性肝病的存在既影响HCC的切除率，又是HCC多中心发生的基础因素。HCC切除后又出现多发性癌灶，一种是HCC经门静脉的肝内播散，另一种是HCC     

HBV相关肝细胞癌的危险因素

目前,HBV感染是全球公认的肝细胞癌(HCC)主要危险因素。然而,在乙型肝炎-肝硬化-肝癌的发展过程中,还有其他的辅助因素,如性别、年龄、家族史、ALT/AST、吸烟饮酒史、代谢综合征以及合并HCV、HIV感染等可能独立或与HBV协同促进HCC的发生。综述了HBV相关HCC的危险因素研究进展。     

2006年沪港国际肝病会议精选(肝癌部分)

2006年沪港国际肝病会议精选(肝癌部分)肝细胞癌的预防西班牙巴塞罗那大学JordiBruix教授指出,大多数诊断为肝癌的患者有慢性病毒性肝炎[丙型肝炎病毒(HCV)或乙型肝炎病毒(HBV)感染]相关基础疾病,某些地区与黄曲霉毒素摄入、酗酒或代谢状况如血色素沉着症有关。避开这些可导致慢性肝损伤甚至肝癌的危险因素为一级预防提供了机会。HBV疫苗已经在防止病毒传播和降低肝细胞癌(HCC)发生中显示其作用,所以肝癌是第一个用疫苗预防成功的肿瘤。目前还没有HCV疫苗,所以预防HCV传播只有通过避免接触有潜在污染危险的血液(不必要的输血、共用…     

乙型肝炎病毒感染史和大量吸烟对丙肝病毒相关性肝细胞癌的作用

日本Chiba报告称,世界范围的流行病学研究证明丙型肝炎病毒(HCV)大概是肝细胞癌(HCC)的病因,但目前能明确肯定导致HCV相关性慢性肝病病人发生HCC的危险因素的报道还没有。为此Chiba对导致HCV相关性慢性肝病病人发生肝癌的危险因素进行了研究。对412例HCV抗体阳性,但未合并乙肝     

HBV/HCV感染诱导肝细胞癌的病理机制

肝细胞癌(HCC)是最常见的恶性肿瘤之一。手术是小肝癌的首选治疗方法,但晚期以及术后复发转移仍然缺乏有效治疗手段,导致其病死率高居不下。持续性肝炎病毒感染以HBV和HCV感染为主,是诱导HCC发病的最主要原因。肝炎病毒通过多种信号转导机制改变肝细胞基因表达、阻止或改变免疫反应、调控肝组织微环境,从而促进HCC的发生发展。概述了HBV和HCV感染诱导HCC的病理机制,以期对HCC的防治新途径的开发有一定启示作用。     

丙型肝炎病毒感染的处理

丙型肝炎病毒(HCV)是输血后肝炎的主要原因,目前仍是世界范围内散发性肝炎的重要原因。 HCV感染常不引起暴发性肝炎,在原有慢性肝病的肝移植病人或合并HBV感染者常有严重的急性HCV感染。急性期HCV感染通常较轻,但其危害在于有较大比例的病人进展为慢性肝病,并伴有发生肝硬化和肝细胞癌的危险。一组135例输血后肝炎的研究显示77％发展为慢性肝病;65例病人作肝穿刺,在平均随访7.5年后32％发生肝硬化。     

嗜酒对慢性乙型肝炎促发肝细胞癌危险因素的影响

我国慢性乙型肝炎病毒（HBV）感染是肝癌的首要致病因素,HBV负荷和活跃复制与肝细胞癌（HCC）的发生密切相关[1-2]。近年来嗜酒人群增多,慢性乙型肝炎伴发酒精性肝病的发病率亦呈上升趋势。本文探讨嗜酒、HBV病毒感染对促发肝细胞癌主要危险因素,综合分析其协同作用,为临床提供预防策略。     

HBV、HCV和GBV-C/HGV对肝细胞癌的影响:欧洲多国协作研究

此研究目的是阐明HBV和HCV感染对欧洲肝细胞癌(HCC)的影响。 病人与方法:对503例HCC(来自法国、德国、意大利、西班牙、希腊、英国6个肝病中心)患者的血清及80份肝组织标本检测HBV DNA和HCV RNA,57份血清测GBV-C/HGV RNA。     

丙型肝炎与肝细胞癌

目前认为丙型肝炎病毒(HCV)感染是引发肝细胞癌(HCC)的主要危险因素。相当一部分HCC病人血中可检测到抗-HCV和HCV RNA。同时HCV感染的病人发展成肝硬化和肝癌,其潜伏期一般为20～30年。HCV感染可直接导致HCC,但通常经过肝硬化阶段。HCV基因型为1b、嗜酒及重叠感染HBV,可增加其发展成HCC的危险性。 1 流行病学     

Hepatocellular carcinoma in Egyptians with and without a history of hepatitis B virus infection: association with hepatitis C virus (HCV) infection but not with (HCV) RNA level.

The aim of this study was to analyze the association of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) in Egypt, using hepatitis B virus (HBV) and hepatitis E virus (HEV) as virus controls. In addition, the association of HCC with HCV RNA levels among persons seropositive for HCV was analyzed. We compared 131 patients with proven HCC, 247 with bladder cancer, and 466 healthy hospital employees. Age, sex, and place of residence were recorded to study confounding factors. Among the healthy controls, 16% were seropositive for HCV, 21% for HBV, and 31% for HEV. When healthy controls were age-matched with HCC patients, the latter were significantly (P < 0.001) more often HCV seropositive (67%) than were the controls (30%). The seropositivity for HBV and HEV did not differ significantly in frequency between the two groups. The seropositivity for HCV was also significantly (P < 0.001) more often found in HCC patients (76%) than in BC patients (47%), with seroprevalences for HBV and HEV not differing significantly in these age-matched groups. In HBV-negative HCC and bladder cancer patients, seroprevalence for HCV was significantly (P = 0.002) higher in HCC patients (68%) than in bladder cancer patients (36%). This difference was even more pronounced (P < 0.001) in HBV-positive HCC and bladder cancer patients (78% versus 52%, respectively). Of HCV-seropositive individuals, 49% were HCV RNA positive by branched DNA assay, and of these, 96% were infected by HCV genotype 4. No correlation between HCV RNA load and seropositivity of HBV or age or disease state was found. Infection with HCV and HCV-HBV double infection, but not HBV or HEV infection alone, is strongly correlated with HCC in Egypt.     

Roles of Alcohol, Hepatitis Virus Infection, and Gender in the Development of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

To assess the interaction of alcohol, hepatitis C virus (HCV), and hepatitis B virus (HBV) infection in hepatocarcinogenesis, we prospectively observed 449 patients with liver cirrhosis (LC) who presented to our outpatient clinics in 1 month; 164 patients with habitual drinking [alcoholic liver-liver cirrhosis (AL-LC)] who had taken ≥72 g alcohol/day (HCV-positive 81 cases: HCV + AL; HCV-negative 83 cases: AL); 176 patients with HCV infection, but without alcohol intake; 34 patients with HBV infection; 6 patients with HCV and HBV coinfection; and 82 patients with liver diseases from other etiologies, such as primary biliary cirrhosis. In the HCV group, the cumulative occurrence rate of hepatocellular carcinoma (HCC) was 9%, 18%, and 23% in the first, second, and third years, respectively. In the HCV + AL group, that was 13%, 17%, and 28%, respectively. There was no difference in the HCC occurrence rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 1% during the observation period of 3 years. The occurrence rate was significantly lower in the AL group, compared with the HCV and the HCV + AL groups. In the HBV group, the cumulative occurrence rate of HCC during the observation period of 3 years was 17%, which was similar to that of the HBV + AL group, 14%. We also examined some other variables that might be related to the development of HCC. The cumulative occurrence rate of HCC in male patients was 31%, whereas that was 18% in female patients. In the HCV group, there was a significant increase of HCC occurrence rate in male patients. In contrast, no difference was observed in the HCC occurrence rate between male and female patients in the HBV group. The present study suggests that alcohol alone may not be an independent risk factor for HCC, nor does it accelerate HCC development in LC patients with HCV and HBV infection during the prospective observation of 3 years.     

Minor Role of Hepatitis B and C Virus Infection in the Etiology of Hepatocellular Carcinoma in a Low-Endemic Area

Background: The etiologic role of hepatitis B (HBV) and C virus (HCV) for hepatocellular carcinoma (HCC) in a low-endemicity area is obscure. Methods: Patients suspected of having primary liver cancer (PLC) in Göteborg, Sweden (n = 113), were tested serologically for HBV surface antigen and antibodies to HBV surface and core antigens. The presence of HBV surface and core antigens in cancer and non-neoplastic liver tissue in HCC cases was investigated immunohistochemically. Antibodies to HCV were tested by third-generation tests. The prevalence of HBV and HCV infection was compared in 73 patients with HCC and 32 patients with a final diagnosis other than PLC. Results: No patient had signs of chronic HBV infection. Seven of 64 (11%) HCC patients were anti-HCV-positive, compared with 1 of 31 (3%) without PLC. All seven patients with HCC and HCV infection had liver cirrhosis, and two were alcoholics. Alcoholism was judged the commonest (42%) cause of cirrhosis. Conclusion: Contrary to areas with a high incidence of HCC, chronic viral hepatitis, particularly HBV, seems to play a minor etiologic role for HCC in Sweden compared with alcohol-related cirrhosis.     

HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。     

Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a Chinese experience

BACKGROUND: Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status. METHODS: The study population consisted of 413 patients undergoing a curative resection at Tianjin Cancer Hospital for small HCC (< or =3 cm) from January 1997 to December 2003. The patients were divided into four groups: HCV only (n = 75), HBV only (n = 251), HBV and HCV (n = 33), and neither HBV nor HCV (NBNC, n = 54). The preoperative status and postoperative HCC recurrence were recorded. Survival analyses were used to assess the impact of HBV/HCV status on HCC recurrence. RESULTS: Patients with HCV had a significant association with older age, lower mean preoperative platelet counts and albumin levels, higher mean prothrombin time, alanine aminotransferase and total bilirubin levels and multinodular tumors during diagnosis. Patients with HCV also had significantly less differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to the other groups. During the follow-up, the HCV group showed a higher incidence of intrahepatic recurrence and multiple recurrent lesions than the other patients. CONCLUSIONS: Patients with HCV infection tended to be older, and were characterized by more severe cirrhosis and higher incidence of tumor multicentricity. The statistically significant determinants for reoccurrence in patients with small HCC were HCV infection, presence of vascular invasion and multiple tumors.     

Risk factors and prevention of hepatocellular carcinoma in HCV infection

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Several risk factors for HCC development have been identified, including cirrhosis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection. With regard to cirrhosis, multivariate analysis indicates that alcohol abuse, HBsAg positivity, and anti-HCV seropositivity are independent variables associated with an increased risk for HCC in the cirrhotic patient. A close relationship between chronic HBV infection and HCC has been established by epidemiological studies and laboratory investigations. Evidence indicates that HCV also plays a leading role in development of HCC. Most patients with HCV-related HCC develop the tumor as a consequence of long-standing infection accompanied by chronic and progressive liver damage. In our study of 290 consecutive patients with cirrhosis, patients with persistently elevated or fluctuating ALT levels had a significantly greater rate of HCC development. The mechanism of HCC development in HCV infection remains to be elucidated. The annual cumulative risk of developing HCC is approximately 1% in patients without cirrhosis at inclusion and 3–10% in those with cirrhosis, depending on the stage of cirrhosis and presence of etiological cofactors. Although some evidence suggests that patients infected with the HCV genotype 1b are at increased risk for development of more severe liver disease, including HCC, results of our prospective study do not support a difference between cirrhotic and noncirrhotic patients in terms of the natural course of cirrhosis and the rate of developing HCC based on genotype. Strategies to prevent HCV-related HCC include blood screening and treatment of chronic HCV infection with interferon-α. Recent studies suggest that interferon-α treatment may prevent the development of HCC in HCV infection. Further research is warranted.     

Virushepatitis A–E

Five hepatotropic hepatitis viruses have been identified: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV). HAV and HEV are transmitted orally, HBV, HCV and HDV via blood and other body fluids. This review summarizes the biological characteristics of the different viruses and the established means of preventing infection.     

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area

AIMS/BACKGROUND: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. METHODS: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993-1997 were retrospectively studied. RESULTS: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9%) with HCV and 10% coinfection with HBV/HCV This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6%) had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5%) metastases in other organs be clinically diagnosed by chest X-ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 microg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. CONCLUSION: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.     

原发性肝癌与嗜肝病毒感染关系探讨

为探讨原发性肝癌与各种嗜肝病毒感染的关系,本文采用ELISA、SPRIA和PCR法对40例肝癌患者的HAV、HBV、HCV、HDV、HEV、CMV、EBV七种病毒的血清标志物进行了检测。结果,HBV感染率为100％,HCV感染率为20％,显著高于健康对照组。80％的HBV感染者表现为抗-HBe阳性和HBeAg阴性,表明持续抗-HBe阳性与肝癌发生关系密切。所有HCV感染者均伴有HBV感染,二者可能有协同致癌作用。说明河北省肝癌的发生除主要与HBV感染密切相关外,尚与HCV感染有关,而与其它病毒感染关系不大。