肝癌病人乙肝病毒状态及对外科干预的反应

对收治的９７例肝癌病人（其中３１例经手术治疗）采用定性ＰＣＲ方法，并进一步采用定量ＰＣＲ方法对１４例乙肝阳性癌病人外科处理前后配对，研究了病毒活动状态及外科干预对病毒活动变化的影响。结果显示：肝癌乙肝病毒仍然在一大部分病人体内进行着活跃的复制活动；外科干预更加激发乙肝病毒的复制过程。建议在肝癌外科干预的同时应当防范乙肝的活动。     

感染乙型肝炎病毒肝癌患者体内病毒活动状态及对外科治疗的反应

目的了解乙型肝炎病毒标志物阳性肝癌患者体内乙肝病毒的活动状态及外科治疗肝癌对其的影响。方法ＨＢＶＤＮＡ定性ＰＣＲ及免疫学方法检测９７例肝癌患者的血清乙肝病毒ＤＮＡ及其标志物,９７例患者分为２组,术前组６６例,术后组３１例;ＨＢＶＤＮＡ定量ＰＣＲ方法对２０例乙肝病毒阳性肝癌患者外科治疗前后血清中病毒的存在状态及血清中病毒ＤＮＡ复制数进行对比研究。结果术前组及术后组均有部分肝癌患者血清中可以发现复制型乙肝病毒,两组阳性率分别为４０９％、６４５２％,术后组较术前组有显著意义的升高（Ｐ＜００５）;２０例乙肝病毒阳性患者经外科治疗后血清中乙肝病毒ＤＮＡ复制数较术前有显著意义增加（Ｐ＜００１）。结论部分乙肝病毒阳性肝癌患者体内乙肝病毒仍然活跃复制;外科干预更加激发乙肝病毒的复制过程。建议在肝癌外科干预的同时应当防范乙肝的活动     

乙肝阳性肝癌患者乙肝病毒活动状态及对外科干预的反应

背景:乙肝与肝癌有确定关系的观点早已确立,但是人们对肝癌阶段肝病毒的活动状态评价不一;并且对肝癌的主要治疗手段-外科干预是否对病毒活动造成影尚无定论。目的:明确肝癌阶段HBV的存在状态;探讨外科干预 对HBV的可能影。方法:采用常规PCR方法,对收治的97例肝癌病人,进行手术前后(其中31例经手术治疗)血清HBV DNA阳性情况调查;进一步采用定量PCR方法对14例乙肝阳性肝癌病人配对研究了外科处理前后病毒血清HBV DNA拷贝变化。结果:1)97次检查阳性率为48.45％(47/97),其中术前检查阳性率为40.9％(27/66),术后阳性率为64.52％(20/31);2)14例肝癌患者术后血清HBV DNA拷贝数较术前增加(P<0.01)。结论:肝癌阶段乙肝病毒仍然在一大部分病人体内进行着活跃地复制活动;外科干预更加激发乙肝病毒的复制过程。建议在肝癌外科干预的同时应当防范乙肝的活动。     

乙肝相关性肝癌抗病毒治疗研究进展

在我国肝细胞癌的主要病因之一是乙型肝炎病毒感染,主要的治疗方法是手术切除,但是预后不佳。病毒复制影响术后肝功能恢复、肿瘤复发;应用抗病毒治疗能显著抑制乙肝病毒复制,改善术后的肝功能损伤,提高乙肝相关性肝癌治疗的疗效。本文对乙型肝炎相关性肝癌抗病毒治疗的研究进展作一综述。     

应用聚合酶链反应探讨乙肝病毒感染与胆石症的关系

目的探讨乙肝病毒感染在胆石症发病中的作用。方法应用聚合酶链式反应技术（ＰＣＲ）,对３２例血清乙肝标志物阳性的胆石症患者和２０例乙肝标志物阳性的非胆石症患者的石蜡包埋胆囊标本进行ＨＢＶ－ＤＮＡ检测。结果３２例胆石症患者的胆囊标本ＨＢＶ－ＤＮＡ阳性检出率为４０．６３％,２０例非胆石症患者的胆囊标本ＨＢＶ－ＤＮＡ阳性检出率为１５％。结论提示乙肝病毒感染与胆石症发生有关。用ＰＣＲ技术检测石蜡包埋胆囊组织中的ＨＢＶ－ＤＮＡ是一种简便、可靠的方法。     

转乙型肝炎病毒x基因肝癌细胞株的建立

目的 建立表达转乙型肝炎病毒Ｘ基因（ＨＢＸ）的人肝癌细胞株,为研究ＨＢＸ基因与肝癌生物学行为间的关系提供模型。方法 以聚合酶链反应（ＰＣＲ）法从３．２ｋｂ 型肝炎病毒（ＨＢＶ）全基因组中主增ＨＢＸ基因,亚克隆至逆转 功体,磷酸钙共沉淀法将其导入包装细胞系,以含病毒的培养上清感染人肝癌细胞系ＱＧＹ７７０１,新霉素（Ｇ４１８）筛选,ＰＣＲ与反转录ＰＣＲ（ＲＴ－ＰＣＲ）鉴定。结果 ＰＣＲ法从ＨＢＶ基因     

慢性乙肝病人HBeAg的存在对其肝细胞肝癌肝切除预后的影响

在慢性乙型肝炎的自然进程中血清HBeAg的存在与不断发展炎症活性及肝疾病发展的致病乙肝病毒 (HBV)复制相关 ,从HBeAg阳性到抗HBe抗体阳性的转化 ,通常有效的HBV复制活性的减少相联系。并且保持低 (ALT)低血清活性 ,和从免疫清除期到疾病静止期的变化相符合。Tsai等报道HBeAg和乙肝表面抗原 (HBsAg)是附加并且是肝细胞肝癌 (HCC)进展的独立危险因素 ,在此项研究中 ,检查血清HBeAg阳性对临床病理发现和乙型肝炎病人肝癌肝切除后预后的临床影响。病人和方法　病人 :从 1 989～ 1 999,总共有 5 6例HBeAg阳性病人 (HCV抗体阴性 )…     

合并乙肝病毒感染的心脏病人体外循环手术适应证探讨

目的 探讨合并乙肝病毒感染的心脏病人的体外循环手术适应证。方法 回顾分析近6年来合并乙开肝病毒感染并进行了体外循环手术的心脏病人42例,其中男20例,女22例;平均年龄29．3岁。综合乙肝5项及HBV DNA结果,其中病毒活跃复制者11例,占26．2％,结合临床表现,对比分析手术前后GPT和GOT结果。结果 体外循环手术前后GPT差异无显著性（P＞0．05）,术后GOT异常率显著高于术前（P＜0．05）。1例病人因低心排死亡,1例病人肝功能损害加重,41例病人随访1－2年,心功能均恢复到I－Ⅱ级。结论 对于肝功能损害轻微的轻度慢性乙型肝炎及乙肝病毒携带者,体外循环手术是安全的;对病毒活跃复制的慢性肝炎,建议治疗肝炎后择期手术。     

根治切除术联合抗病毒治疗肝癌合并乙肝病毒感染

探讨根治切除术联合抗病毒治疗肝癌合并乙肝病毒(HBV)感染的临床效果。100例肝癌合并乙肝病毒感染患者,按照HBV-DNA水平不同分成高病毒复制组和低病毒复制组(以HBV-DNA载量为105拷贝/ml为标准),每组又分为抗病毒组和未抗病毒治疗组,比较4组在肝功能、HBV-DNA水平、并发症和住院时间、住院费用差异性。结果显示,抗病毒治疗后患者肝功能明显好转,HBV-DNA水平明显低于未抗病毒治疗,住院时间、费用费用和并发症均优于未抗病毒者;但低病毒复制组在并发症和住院时间、住院费用上优于高病毒复制组。结果表明,抗病毒结合根治切除术能改善肝癌合并HBV感染肝功能和病毒指标,缩短住院时间。     

抗乙肝病毒治疗与原发性肝癌术后生存关系研究分析

目的探讨乙肝病毒DNA复制及抗病毒治疗与原发性肝癌病人术后复发及生存率的关系。方法通过对过去5年前在我院经病理确诊为原发性肝癌(均合并乙肝病毒感染)、未提示出现远处转移,并在我院行外科手术切除后的32例病人的生存率观察,根据其乙肝病毒DNA复制情况及是否抗病毒治疗、抗病毒治疗时机的选择等因素进行分析。结果 32例患者中,抗病毒治疗22例,未进行抗病毒治疗10例;术前开始抗病毒治疗14例,术后开始抗病毒治疗8例。结果提示抗病毒治疗组较未进行抗病毒治疗组有较高生存率,差异有统计学意义(P0.05),术前开始抗病毒治疗组与术后开始抗病毒治疗组生存率无明显差异。结论积极抗病毒治疗可有效控制原发性肝癌的复发、提高原发性肝癌患者生活质量。     

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目的 探讨拉米夫定防治乙肝病毒在肝癌围手术期活跃的效果。方法 对７２例肝癌合并ＨＢＶ感染者随机分组,研究组的３８例在围手术期每日１次给予拉米夫定１００mg,进行定量ＨＢＶ ＤＮＡ及其它检查。对照组在围手术期不进行抗乙肝病毒治疗。结果 对照组的ＨＢＶ ＤＮＡ量,在术后１周内、２周内较术前的增高值具显著性意义（Ｐ＜０.０１）,研究组中术后１周内、２周内ＨＢＶ ＤＮＡ量较术前的ＨＢＶ ＤＮＡ量低值亦有显著性意义（Ｐ＜０.０１）,皆低于安全治愈阈值;两组的术前、术后Ｃhild分级,术前、术后ＡＬＴ比较差异无显著性意义（Ｐ＞０.０5）。术后２周内并发症发生率比较,差异有显著性意义（Ｐ＜０.０５）。结论 外科治疗可激活ＨＢＶ的复制能力,须加强肝癌围手术期对ＨＢＶ的防范。拉米夫定有强大的抗ＨＢＶ功能,可短期内迅速降低ＨＢＶ ＤＮＡ的量至安全范围,应用拉米夫定可以预防和治疗肝癌围手术期乙肝病毒的活跃。但其短期内改善肝脏功能的效果不明显。     

Hepatitis serology predicts tumor and liver-disease characteristics but not prognosis after resection of hepatocellular carcinoma

The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on survival rates after resection of hepatocellular carcinoma (HCC) is controversial. The objective of this study was to determine whether serologic evidence of HBV or HCV infection ("hepatitis serology") can predict underlying liver disease, tumor factors, and survival rates in patients with HCC. Using a multicenter international database, we identified 446 patients with complete HBV and HCV serology. One hundred twenty-six patients were negative for HBV and HCV, 163 patients had HBV infection only, 79 patients had HCV infection only, and 78 patients had coinfection with HBV and HCV. Patients with hepatitis were more likely to have tumors smaller than 5 cm and bilateral HCC involvement. Hepatitis status (negative vs. HBV vs. HCV vs. coinfection with HBV and HCV) did not predict tumor grade or the presence of multiple tumor nodules. Patients with HCV or coinfection with HBV and HCV exhibited a lower incidence of vascular invasion, but worse fibrosis than patients with negative serology or HBV. The median survival rate was 47.9 months. The presence of hepatitis did not significantly affect the survival rate, but hepatic fibrosis and vascular invasion predicted a decreased survival rate. The prognosis after resection of HCC is influenced by tumor factors and liver disease, but not by HBV or HCV infection. The treatment for HCC should be dictated by the extent of underlying liver disease rather than by hepatitis serology. Presented at the Forty-Fifth Annual Meeting of the Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 (oral presentation).     

乙肝相关性肝癌和丙肝相关性肝癌的临床病理特征及意义

目的探讨乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。方法收集2003年12月~2010年10月在南方医科大学附属南方医院行手术治疗C-HCC标本18例和2011年3月~2012年12月行手术治疗的B-HCC标本34例,以及这些肝癌患者的临床病理资料。分析乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。结果乙肝相关性肝癌平均年龄(46.9±10.5)显著低于丙肝相关性肝癌组(59.0±9.9),平均住院天数(17.9±6.8)显著低于丙肝相关性肝癌组(34.9±16.5),平均术后住院天数(11.5±4.3)显著低于丙肝相关性肝癌组(19.4±11.9),肝功能分级中A级肝功明显较丙肝相关性肝癌组多,最大肿瘤直径明显大于丙肝相关性肝癌组,差异均有统计学意义(P0.05)。B-HCC组患者中位无瘤生存时间为13个月,1年、2年无瘤生存率分别为56.3%和32.0%;C-HCC组患者中位无瘤生存时间为16.5个月,1年、2年无瘤生存率分别为75%和75%。Cox模型分析提示肝炎类型是肝细胞癌术后复发的独立影响因素。乙肝相关肝细胞癌术后复发的风险是丙肝相关性肝癌的2.35倍(P=0.108)。结论乙肝病毒与丙肝病毒相关肝细胞癌的临床病理特征及预后有显著差异。乙肝相关性肝癌术后恢复较丙肝相关性肝癌快,而丙肝相关肝细胞癌术后复发风险低于乙肝相关肝细胞癌。     

Transplantation of hepatitis B surface antigen-positive livers into hepatitis B virus-positive recipients and the role of hepatitis delta coinfection.

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV-infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients.     

Clinicopathologic Features and Outcome After Liver Resection for Hepatocellular Carcinoma in Patients with Concurrent Versus Previous Chronic Hepatitis B

Purpose We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B.Methods Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome.Results The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors.Conclusion Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.     

Comparison of Surgical Outcomes for Hepatocellular Carcinoma in Patients With Hepatitis B Versus Hepatitis C: A Western Experience

Background: We reviewed our experience in patients with hepatocellular carcinoma (HCC) and chronic hepatitis to determine if differences exist in preoperative status and postoperative survival between those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.Methods: We reviewed the records of 240 consecutive patients with HCC who underwent hepatic resection or liver transplantation at Mount Sinai Hospital between February 1990 and February 1998. Patients who tested negative for hepatitis B antigen and hepatitis C antibody (74 patients) as well as those who tested positive for both (2 patients) were excluded. Age as well as preoperative platelet count, prothrombin time (PT), albumin, and total bilirubin were measured in all patients. The presence of encephalopathy or ascites also was noted. Explanted livers and resection specimens were examined for size, number, and differentiation of tumors as well as the presence of vascular invasion and cirrhosis in the surrounding parenchyma.Results: One hundred twenty-one patients with HCC tested positive for HCV, and 43 tested positive for HBV. A significantly higher proportion of patients with HCV required transplant for the treatment of their HCC when compared to those with HBV. In the resection group, patients with HCV were significantly older that those with HBV. They also had significantly lower mean preoperative platelet counts and albumin levels and higher mean PT and total bilirubin levels. Resected patients with HCV had significantly less-differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to those with HBV. There was no statistical difference in the multicentricity and size of tumors between the two groups. The 5-year disease-free survival was significantly higher for HBV patients treated with resection when compared to those with HCV (49% vs. 7%, P 5 .0480). Patients with HCC and HCV had significantly longer 5-year disease-free survival with transplant when compared to resection (48% vs. 7%, P 5 .0001).Transplanted patients with HBV and HCC had preoperative status, pathological findings, and survival similar to those of patients with HCV.Conclusions: Based on preoperative liver function and tumor location, a much higher proportion of HCC patients with HBV were candidates for resection. Significant differences in preoperative status, tumor characteristics and disease-free survival exist between HCC patients with chronic HBV and HCV infection who have not yet reached end-stage liver disease. Serious consideration should be given to transplanting resectable HCC with concomitant HCV, especially in cases with small tumors.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

肝移植术后肝癌复发对HBV再感染的影响

目的 探讨肝移植术后肝癌复发对HBV再感染的影响.方法 回顾性分析285例原发病为乙肝相关性疾病且术后随访超过半年的原位肝移植患者资料.结果 285例肝移植患者随访时间为6～59个月,术后HBV再感染10例,再感染率为3.5%.其中9例患者合并肝癌复发,HBV再感染发生于肝癌复发后1～7个月.肝癌复发患者与肝癌未复发和良性肝病患者HBV再感染的差异具有统计学意义.13例肝癌复发或转移灶切除标本中有1例免疫组化染色HBsAg阳性、HBcAg弱阳性.结论 乙肝免疫球蛋白联合核苷类似物是预防肝移植术后乙肝复发的有效治疗措施,肝癌复发是肝移植术后HBV再感染的重要原因.     

Significance of HBV DNA in the Hepatic Parenchyma from Patients with Non-B, Non-C Hepatocellular Carcinoma

Introduction The etiologic and prognostic factors for non-B, non-C hepatocellular carcinoma (HCC), which is defined by its seronegativity for both hepatitis B surface antigen and hepatitis C virus (HCV) antibody, remain unclear. Methods Nonneoplastic liver tissue from 46 patients with non-B, non-C HCC were examined for hepatitis B virus (HBV) DNA and HCV RNA using in situ hybridization. Recurrence-free survival rates were compared between patients showing high or low HBV DNA expression. Other potential prognostic factors were examined as well. Results HBV DNA was detected in nonneoplastic liver specimens from 35 patents (76.1%), whereas HCV RNA was not detected in any case. In patents with high HBV DNA group expression, recurrence-free survival rates at 1 and 5 years after onset were 68.8% and 13.8%, respectively; those with low expression had higher rates of 89.2% and 59.2%, respectively. Multivariate analysis identified high tumor stage (P = 0.042) and high HBV DNA expression (p = 0.014) as independent negative prognostic factors. Conclusions In many patients with non-B, non-C HCC, HBV DNA in the liver appears to be involved in the carcinogenesis, with intense HBV DNA expression predicting poor outcome for patients with these cancers.