AFP增高与乙肝各种血清学指标模式的关系及癌变风险分析

目的：探讨乙肝各血清学模式中发生癌变的风险。方法：应用ELISA法对436例AFP介于20-400ng/mL的乙型肝炎患者及64例有乙肝感染史的肝细胞癌患者（AFP：431-897ng/mL)进行了乙肝血清学指标和HBV-DNA测定。结果：乙肝血清学指标各模式间存在相当大的差异，436例乙肝患者中HBsAg( ),HBeAg( ),HBcAg( )模式占27.3%,HBsAg( ),HBeAb( ),HBcAb( )模式占48.1%,HBsAb( ),HBeAb( ),HBcAb( )模式占6%，HBeAb( ),HBcAb( )模式占18.6%;64例肝细胞癌患者中HBsAg( ),HBeAg( ),HBcAb( )模式占25.0%,HBsAg( ),HBeAb( ),HBcAb( )模式占45.3%,HBsAb( ),HBeAb( ),HBcAb( )模式占10.9%,HBeAb( ),HBcAb( )模式占18.8%。结论：乙肝各种模式AFP的增高有高度相关性。     

肝癌与肝炎标志物及相关肿瘤标志物的相关性分析

目的探讨乙肝五项、HCV抗体、血清甲胎蛋白(AFP)、CA19-9、CA125、CEA对原发性肝癌的诊断价值。方法对75例原发性肝癌患者分别测定乙肝五项、HCV抗体、肝脏肿瘤血清标志物AFP、CA199、CA125、CEA。结果 5例原发性肝癌患者中,HBsAg阳性45例(60.0%),HCV抗体阳性16例(21.3%),HBsAg并HCV抗体双阳性3例(4.0%);乙肝五项(HBV-M)不同组合模式中,HBsAg、HBeAb、HBcAb三项阳性(小三阳)20例,HBsAg、HBeAg、HBcAb阳性(大三阳)9例,HBsAg、HBcAb两项阳性14例。AFP、CA19-9、CA125、CEA对肝癌诊断的灵敏度依次为AFP(68.0%),CA19-9(34.6%),CA125(33.3%),CEA(30.7%),四项联合检测对肝癌诊断的灵敏度可提高至80.0%。结论肝癌的发生与HBV有着非常密切的关系,HBsAg、HBeAb、HBcAb三项阳性(小三阳)患者应视为的高危人群。在肝癌患者中,肝癌的单项肿瘤标志物检测应首选阳性率最高的AFP,多种肿瘤标志物联合检测对肝癌的诊断具有重要价值。     

肝细胞肝癌血清AFP值与HBV感染的关系

目的:探索肝细胞肝癌患者血清AFP值与HBV感染模式的关系.方法:回顾性分析2009年1月到2011年6月于我院就诊并手术的所有肝脏恶性肿瘤患者的临床资料.结果:共有217例肝脏恶性肿瘤患者纳入研究:肝细胞肝癌(HCC)组176例,非HCC组41例.HCC组中HBV感染模式前三位的分别是HBsAg,HBeAb和HBcAb阳性(小三阳)(30.7％),HBsAg和HBcAb阳性(25.6％)及HBsAg,HBeAg和HBcAb阳性(大三阳)(20.5％).HCC组血清AFP值高于非HCC组血清AFP值(P ＜0.001),但HCC组内HBV感染组与非HBV感染组之间血清AFP水平无统计学差异(P =0.147),三种主要HBV感染模式之间血清AFP值也无统计学差异(P=0.578).同样的,无论在AFP阴性组(＜20ng/ml)还是AFP阳性组(≥20ng/ml),三种主要的HBV感染模式之间的血清AFP值均无统计学差异.结论:HCC的血清AFP值明显高于其他类型的肝脏恶性肿瘤血清AFP值,但HCC组内HBV的各种感染模式之间AFP值水平无差异.     

原发性肝癌患者HBV感染血清学模式调查

目的 :研究HBV感染血清学模式与原发性肝癌的关系。方法 :分析 1996年 6月～ 2 0 0 0年 9月我院收治的 50 0例原发性肝癌患者的HBV感染血清学模式 ,与同期收治的 50 0例其他恶性肿瘤患者的HBV感染血清学模式进行比较。结果 :原发性肝癌患者HBV感染率为 89 6% ,显著高于其他恶性肿瘤患者。HBsAg和HBcAb同时阳性者占HBV感染肝癌的 79 9% ,占HBV感染其他恶性肿瘤的13 3% ,差异有极显著性 (P <0 0 1)。出现HBsAb者占原发性肝癌中HBV感染病例的 8 5% ,其他恶性肿瘤中HBV感染病例的 75 1% ,两者差异亦有极显著性 (P <0 0 1)。“大三阳”、“小三阳”和 (HBsAg HBcAb )者与肝癌相关的OR分别为 13 85、6 95和 14 69。结论 :HBsAg和HBcAb同时阳性的患者患肝癌的危险性最高 ;血清出现HBsAb的HBV感染者不易发展成肝癌     

乙肝病毒阳性的实体瘤患者化疗期间肝功能变化

目的　观察乙肝病毒阳性的实体瘤患者化疗期肝功能变化 ,了解肝功能损伤与疾病种类及乙肝标志物的关系。方法　 2 0 0例乙肝病毒阳性的住院实体瘤患者接收全身化疗或动脉插管化疗 ,化疗前后检测肝功能变化。结果　Ⅰ度以上肝功能损害占 4 0 5 % (81/ 2 0 0 ) ,病种以恶性淋巴瘤和原发性肝癌居多 ,乙肝标志物中以HBsAg( )及HBeAb( )者肝功能损害发生率高 ,HBsAb( )者发生率低。结论　乙肝病毒阳性的实体瘤患者化疗期肝功能损伤发生率较高 ,尤其恶性淋巴瘤及HBsAg、HBeAb阳性患者 ,化疗前常规检测乙肝标志物十分必要。     

HBsAg阴性HBcAb阳性肿瘤患者化疗后HBV再激活3例报道并文献复习

目的：探讨乙肝表面抗原（HBsAg）（-）核心抗体（HBcAb）（+）肿瘤患者化疗后引起乙型肝炎病毒（HBV）再激活的治疗与监控。方法：报道3例HBsAg（-）HBsAg（+）的肿瘤患者化疗过程中出现HBV再激活的病例,针对可行的治疗监控措施进行文献复习。结果：1例最初乙肝表面抗体（HBsAb）（+）、HBcAb（+）的非霍奇金淋巴瘤（NHL）患者经过多次化疗后转变为HBsAg（+）、e抗原（HBeAg）(+)、HBcAb（+）;1例乙肝e抗体（HBsAb）（+）、HBcAb(+)的霍奇金淋巴瘤（NL）患者化疗后乙肝模式未改变,乙肝病毒载量（HBV-NDA）定量结果增高;1例HBsAb(+)、HBeAb(+)、HBcAb(+)的肝癌患者性肝动脉化疗栓塞术（TACE）后出现HBV-DNA定量结果增高。3例HBsAg(-)患者化疗后均出现HBV再激活,经抗病毒治疗后获得良好转归。结论：不仅对于HBsAg（+）的患者,对于即使处于康复期的既往有急性或慢性乙肝病史的HBsAg(-)、HBcAb（+）患者,在应用化疗或免疫抑制剂治疗时均需严密监测血清HBsAg、肝功能及HBV-DNA定量的动态变化,必要时实施预防性抗病毒治疗,以免中止原有治疗计划延误病情。     

原发性肝癌患者HBV感染血清学模式调查

目的：研究HBV感染血清学模式与原发性肝癌的关系。方法：分析1996年6月－2000年9月我院收治的500例原发性肝癌患者的HBV感染血清学模式，与同期收治的500例其他恶性肿瘤患者的HBV感染血清学模式进行比较，结果：原发性肝癌患者HBV感染率为89．6％，显著高于其他恶性肿瘤患者，HBsAg和HBcAb同时阳性者占HBV感染肝癌的79．9％，占HBV感染其他恶性肿瘤的13．3％，差异有极显著性（P＜0．01），出现HBsAb者占原发性肝癌中HBV感染病例的8．5％，其他恶性肿瘤中HBV感染病例的75．1％，两者差异亦有极显著性（P＜0．01），大三阳，小三阳和（HBsAg HBcAb )者与肝癌相关的OR分别为13．85，6．95和14．69。结论：HBsAg和HBcAb同时阳性的患者患肝癌的危险性最高；血清出现HBsAb的HBV感染者不易发展成肝癌。     

乙肝病毒阳性的实体瘤患者化疗期间肝功能变化

目的 观察乙肝病毒阳性的实体瘤患者化疗期肝功能变化。了解肝功能损伤与疾病种类及乙肝标志物的关系。方法 200例乙肝病毒阳性的住院实体瘤患者接收全身化疗或动脉插管化疗，化疗前后检测肝功能变化。结果 Ⅰ度以上肝功能损害占40.5%(81/200)，病种以恶性淋巴瘤和原发性肝癌居多，乙肝标志物中以HBsAg( )及HBeAb( )者肝功能损害发生率高，HBsAb( )者发生率低。结论 乙肝标志物中以HBsAg( )及HBeAb( )者肝功能损害发生率高，HBsAb( ）者发生率低。结论 乙肝病毒阳性的实体瘤患者化疗期肝功能损伤发生率较高。尤其恶性淋巴瘤及HBsAg,HBeAb阳性患者，化疗前常规检测乙肝标志物十分必要。     

青、中、老年肝癌患者AFP HBV—M值的对比分析

目的 对HBV—M检测结果进行分析和比较,以探讨AFP及HBV在不同年龄组PHC病人中的特点和诊断价值。方法 AFP用放射免疫双抗法,HBV—M检测包括HBsAg、HBsAb、HBeAg、HBcAb、HBeAb。结果 青年组>中年组>老年组,青年组与中年组间无统计学意义,青年组、中年组与老年组间均有非常显著性差异(P<0.001)。结论 青年PHC病人AFP异常率较老年组高,老年PHC患者AFP阴性率低,有助于AFP阴性的老年PHC的早期诊断。     

恶性淋巴瘤伴乙型肝炎病毒感染率调查分析

目的:了解初诊恶性淋巴瘤患者中乙型肝炎病毒(hepatitis B virus,HBV)的感染状况。方法:2008-01-2008-12对459例患者(恶性淋巴瘤276例,肺癌183例)临床资料进行回顾性分析。采用电化学发光技术检测患者血清标本的HBV表面抗原(HBsAg)、HBV表面抗体(HBsAb)、HBVe抗原(HBeAg)、HBVe抗体(HBeAb)及HBV核心抗体(HBcAb)的阳性率。结果:恶性淋巴瘤组HBsAg阳性率为11.95%(33/276),明显高于肺癌组患者(4.92%,9/183),P=0.010 4。其中B细胞淋巴瘤组HBsAg阳性率最高(14.77%,26/176),P=0.005 2。结论:恶性淋巴瘤患者HBsAg阳性率较高,与其他肿瘤化疗相比,恶性淋巴瘤患者化疗中更需要对HBV进行监测,更要重视乙型肝炎发作的预防和治疗。     

Reactivation of hepatitis B virus after rituximab‐containing treatment in patients with CD20‐positive B‐cell lymphoma

BACKGROUND:

Reactivation of hepatitis B virus (HBV) after rituximab‐containing chemotherapy in patients with B‐cell lymphoma has been recognized as a potentially serious complication in HBV immune patients.

METHODS:

To determine the HBV reactivation in patients treated with rituximab, a retrospective study of HBV‐related markers was performed before and after rituximab‐containing treatment in 261 consecutive patients with CD20‐positive B‐cell lymphoma.

RESULTS:

Of the 261 patients, 230 patients were tested for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti‐HBc) before treatment. Fifty‐six (24.3%) of 230 patients were anti‐HBc positive, and the remaining 174 (75.6%) patients were anti‐HBc negative. Among the 56 anti‐HBc–positive patients, 5 (8.9%) became HBsAg positive (HBV reactivation), whereas none of the 174 anti‐HBc–negative patients became HBsAg positive with a median follow‐up of 24 months (P = .001). Among the 5 patients with HBV reactivation, 4 were negative for antibody to HBsAg (anti‐HBs), and 1 patient was positive for anti‐HBs. All 5 of these patients were treated successfully with entecavir on detection of HBsAg, although 4 of the 5 patients exhibited mild to moderate elevation of alanine aminotransferase. Among 56 anti‐HBc–positive patients, those negative for anti‐HBs had a higher probability of developing HBV reactivation compared with those positive for anti‐HBs (4 of 19; 21.1% vs 1 of 37; 2.7%, P = .014).

CONCLUSIONS:

Patients with isolated anti‐HBc are at high risk of HBV reactivation and should be monitored closely for HBsAg, anti‐HBs, HBV‐DNA, and transaminase levels during and after rituximab‐containing treatment. Although preemptive use of entecavir enabled successful management of HBV reactivation, mild to moderate hepatic flare was still observed. These approaches should be further evaluated in a prospective study with regard to clinical usefulness, safety, and cost‐effectiveness. Cancer 2010. © 2010 American Cancer Society.     

肝癌高发区抗-HBc阳性慢性乙肝患者HBVDNA血清学分析

目的：了解启东肝癌高发区抗－HBc阳性慢性乙肝患者HDVDNA分布 情况。方法：采用ELISA法筛选慢性乙肝患者中抗－HBc阳性者，再用聚合酶链反应（PCR）检测这些血清中的HBVDNA。结果：HBVDNA总检出率为75．24％（158／210）。抗－HBc与HBsAg、HBeAg同在时HBVDNA阳性率最高，达97．26％（71／73），显著高于其它模式（P＜0．005）。抗－HBc/HBsAg阳性血清中HBVDNA检出率为81．08％（150／185），单纯抗HBc/HBsAg阳性血清中HBVDNA检出率为80．77％（42／52），单纯抗－HBc阳性血清中检出率为20％（1／5）。结论：抗－HBc是乙肝病毒感染的一个直接标志。判断患者的传染性应通过免疫学和基因学两种方法来检测。启东慢性乙肝患者中HBVDNA整合现象可能要高于其它地区，这或许是启东肝癌高发的机制之一，值得进一步研究。基因学和免疫学方法检测乙肝病毒感染情况各有利弊，应互补共存。     

HBsAg阳性的肝细胞癌患者血清乙肝标志物的分析

目的观察HBsAg阳性的肝细胞癌(HCC)患者的血清乙肝标志物,并探讨不同标志物在评价慢性乙肝患者转归方面的意义.方法应用ELISA法分别检测HBsAg+的300例HCC和1000例慢性乙肝患者的血清HBV的5项标志物.结果HCC组的抗-HBe阳性率明显高于慢性乙肝组,而HBeAg阳性率明显低于慢性乙肝组,经统计学U检验,结果均具有显著性差异(P均＜0.01).结论HBeAg阳性的成年慢性乙肝患者血清HBeAg减弱、消失及向抗HBe的慢性转化在理论上虽有预示病情好转的可能,但实际上往往是肝细胞癌发生的一个前期危险信号.     

Hepatitis B virus reactivation in hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization therapy

Aim: The effect of transcatheter arterial chemoembolization (TACE) therapy on hepatitis B virus (HBV) reactivation in hepatocellular carcinoma (HCC) patients with prior resolved hepatitis B is not fully understood. Methods: From January 2006 to December 2010, 43 hepatitis B surface antigen (HBsAg)‐negative/anti‐hepatitis B core antigen (HBc) positive patients with newly diagnosed unresectable HCC were enrolled in the study. All underwent TACE therapy. Results: Four patients (9.3%) developed HBV reactivation with mild/moderate hepatitis. The median number of TACE cycles received was 3.5 (range 3–4 cycles). The median time interval between the occurrence of HBV reactivation and the completion of TACE therapy was 3 months (range 1–5 months) and their median HBV DNA level was 1.58 × 10⁴ IU/mL (range, 1.65 × 10³–6.42 × 10⁴ IU/mL). After the introduction of lamivudine at the occurrence of HBV reactivation, all had resolution of hepatitis. An exploratory analysis indicated that significant predictors of HBV reactivation included increased serum total bilirubin coexisting with cirrhosis and the total number of cycles of TACE received. Conclusion: The administration of TACE therapy may increase the risk of HBV reactivation in HBsAg‐negative/anti‐HBc‐positive patients diagnosed with unresectable HCC. Further studies are warranted to explore the optimal management of HBV reactivation in patients with prior resolved hepatitis B.     

AFP与HBsAg混合多肽负载树突状细胞治疗HBV阳性肝癌的研究

目的：以AFP和HBsAg为双靶标,以树突状细胞（DCs）为抗原载体与佐剂,探讨其激发特异性（CTL）反应的能力及其在HBV阳性肝癌（HCC）患者应用的可行性。方法：采集20例HLA—A201＋HBV＋AFP＋HCC患者外周血,分离单核细胞（Mo）和外周淋巴细胞（PBLs）,将Mo诱导为成熟DCs（mDC）;人工合成AFP和HBsAg多肽,负载mDC后体外致敏,检测其体外杀伤活性;同时于患者皮内注射负载AFP和HBsAg混合多肽的DCs,监测接种前后患者外周血中细胞因子和特异性CTL水平变化,并进行DTH试验,治疗后跟踪检测患者AFP水平和乙肝两对半水平的变化。结果l患者外周PBLs经DCs致敏后,对负载AFP和HBsAg多肽的T2靶细胞杀伤率明显增高,P〈0．05。接种负载AFP和HBsAg多肽的DCs后,血清中IL-2、IL-12、IFN-γ水平较治疗前显著升高,P〈0．05,TNF-a和IL-10水平较治疗前均差异不大,P〉0．05;DTH试验阳性率为41．7％（5／12）,患者外周血中特异性CTLs比例明显上升的有4例（4／12）。治疗后有4例患者AFP水平下降,9例HBeAg阳性的患者中有3例HBeAg下降,2例患者出现血清学应答。结论：负载AFP和HBsAg多肽的Dcs体内、体外均具有激发特异性cTLs反应能力,可诱导Thl型细胞因子的分泌,有望成为一种HCC治疗的新方法。     

Induction of immune tolerance toward tumor-associated-antigens enables growth of human hepatoma in mice.

Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) was previously shown to facilitate suppression of experimental human hepatocellular carcinoma (HCC) expressing HBsAg in athymic mice. We have shown that oral tolerance induces antigen‐specific immune suppression of HBsAg by feeding hepatitis B virus (HBV) antigens. In the present study we evaluated the effect of oral tolerance induction toward HBV or HCC antigens on the growth of experimental HCC‐expressing HBsAg in mice. Tolerance induction was induced in mice by 5 oral feedings of 1 μg HBV antigens or HCC‐extracted proteins (50 μg protein) before vaccination with recombinant HBsAg. Splenocytes (2 × 10⁶) from these mice were transferred to sublethally irradiated athymic BALB/c mice previously transplanted subcutaneously with 10⁷ human hepatoma Hep3B cells. Adoptive transfer of splenocytes immunized toward HBsAg prevented tumor growth. At 4 weeks after splenocyte transplantation, tumor volume and serum alpha‐fetoprotein (AFP) levels in athymic mice transplanted with splenocytes immunized to HBsAg were undetectable as compared with 1,048 ± 738 mm³ and 2,500 ± 1,431 ng/ml in recipients of naïve splenocytes (p < 0.0001). Mice receiving splenocytes tolerized toward Hep3B cells, as manifested by reduced serum HBs antibody levels, reduced HBV‐specific stimulation index and reduced HBV‐specific‐IFNγ spot‐forming cells, had early tumor growth evident by elevated AFP serum levels, weight loss and mortality, which were suppressed at 6 weeks. Mice transplanted with splenocytes tolerized toward HBV antigens did not have direct evidence of tumor growth. Induction of oral tolerance toward HCC‐extracted proteins enabled transient tumor growth in this model. This effect was mediated through downregulation of the anti‐HBV immune response. © 2002 Wiley‐Liss, Inc.     

肝细胞癌患者庚型肝炎病毒的感染

 目的：探讨庚型肝炎病毒感染与肝癌的关系。方法：检测128例肝细胞癌(HCC)患者和55例健康对照者血清中庚型肝炎病毒抗体(Anti-HGV)，另外采用ELISA法检测本实验检出18例Anti-HGV+血清的乙肝表面抗原(HBsAg)和丙肝抗体(Anti-HCV)。结果：Anti-HGV阳性率分别为12.5%(16/128)和36%(2/55)，两者差异显著(P<0.01)。18例Anti-HGV+血清中，HBsAg阳性率77.7%(14/18)，Anti-HGV阳性率22.2%(4/18)。表明HGV、HBV、与HCV有重叠感染现象。结论：提示广西地区HCC病毒致癌因素中，HGV感染可能是仅次于HBV及HCV的又一重要因素。     

Association of hepatitis B virus infection with hepatocellular carcinoma in American patients

Thirty-four patients from the Philadelphia area with hepatocellular carcinoma (HCC) were matched with colon cancer patients, lung cancer patients and blood donors according to age and sex. Sera from the four groups were tested to determine the prevalence of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). Five of the HCC patients (14.7%) and none of the controls were positive for HBsAg. At least one of the three serologic markers of hepatitis B virus (HBV) infection was found in 51.5% of the HCC patients, 5.3% of the colon cancer patients, 11.1% of the lung cancer patients, and 10.7% of the blood donors. Twelve of the seventeen seropositive HCC patients (70.6%) were positive for anti-HBc alone, while all of the seropositive lung cancer patients and donors were positive for anti-HBs alone. Sera positive for any HBV marker were also tested for e antigen (HBeAg) and its antibody (anti-HBe). Four of the HCC patients (23.5% of the seropositives) had anti-HBe, while none of the sera tested had HBeAg. A history of alcoholism did not appear to influence HBV seropositivity in the HCC patients. This study supports the hypothesis that HBV infection is closely associated with HCC even in areas where both conditions are uncommon. The wide disparity between seropositivity for HBsAg and anti-HBc in the HCC patients is an unusual feature, for which an age effect may be the best explanation.     

Frequency of Hepatitis B Markers in Systemic Lupus Erythematosus Patients in Iran

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Hepatitis B virus is the causative agent for chronic, acute, cirrhosis, and hepatocellular carcinoma.  SLE patients with chronic or occult hepatitis B infection undergoing immunosuppressive drugs may become reactive and develop fatal hepatitis. Therefore, this study was conducted to determine HBV markers in SLE patients before the administration of immunosuppressive drugs in Ahvaz city, Iran. Materials and methods: The sera of 92 SLE patients were  tested for HBs Ag and anti-HBc using ELISA, HBV DNA (by Nested PCR) testes. Real-time PCR was performed for the patients with positive anti-HBc and negative HBsAg. The positive HBV DNA samples were checked for HBV genotype and HBV subtypes. Results: Among the 92 SLE patients, three (3.3%) were males and 89 (96.7%) females . The patients’ ages ranged from 14 to 70 years [mean age of 38.9±10.1]. Three of 92 (3.26%) subjects [2/3 males and 1/89 female] were positive for HBsAg, anti-HBc Ab, and HBV DNA detected with PCR (p=0.000003)].  Five of 89 (5.61%) subjects [1 male and 4/88 females were only positive for anti-HBc and negative for HBs Ag, HBV DNA(PCR) using Real-time PCR (p=0.05).  The results of the nucleotide data and phylogenetic tree showed all three HBV patients were genotype D1. The results of amino acid sequencing revealed all three HBV patients were HBV subtype ayw2. Conclusion: This study proved that 3.26% of SLE patients were positive for overt HBV infection (positive for anti-HBc, HBsAg and HBV-DNA using PCR). All the three isolated HBV were genotype D1 and subtype ayw2. The fact that 5.61% of  the patients were only positive for anti-HBc characterized the occult hepatitis B infection (OBI) although further investigation is needed. To prevent HBV or OBI reactivation for SLE patients before immunosuppression treatment, HBV markers including anti-HBc, HBsAg, HBV-DNA should be implemented using PCR and Real-time PCR .     

乙肝病毒相关的肝癌p16异常甲基化

Objective： To investigate the potential linkage between high rate of p16 methylation and hepatitis B virus （HBV） infection, methylation status of p16, HBV infection markers in serum and HBV-DNA replication level in cancerous and non-cancerous tissue of 32 cases of hepatocellular carcinomas （HCC） with HBV infection and 12 HCCs without HBV infection were examined. Methods： p16 methylation was detected with methylation-specific polymerase Chain reaction （PCR）, and HBV markers were examined with real-time PCR and immunologic method. Results： Methylation of p16 promoter was found in 31 （70.5%） of 44 cancerous tissues of HCC, 2 （16.7%） of 12 HCC without HBV infection, 29 （90.6%） of 32 HCCs with HBV infection marker, p16 methylation was detected in 5 （83.3%） of 6 HCCs positive for HBsAg and HBeAg, 17 （94.4%） of 18 HCCs positive for HBsAg and negative for HBeAg, 7/8 （87.5%） of HCCs positive for other HBV infection markers, such as HBsAB, HBcAb, HBeAb. p16 methylation products were also found in non-cancerous tissues of 4 cases of HCCs with HBV infection, not detected in non-cancerous tissues without HBV infection. HBV-DNA was detected in cancerous tissues of 29/32 （90%） HCCs with HBV infection. Surprisingly, Methylation product of p16 promoter was found in all cases （29/29） of HCCs with detectable HBV-DNA in neoplastic tissue. Conclusion： Persistent HBV infection may promote p16 hypermethylation, suggesting that HBV, via enhancing the aberrant methylation of p16, indirectly involved in development of HCC.