A case of the usage of entecavir to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patient

Hepatitis B virus(HBV)reactivation is a serious clinical problem for HBV infected patients, and one of its possible causes is chemotherapy for malignant disease. At the onset of active hepatitis, planned chemotherapy should be discontinued and acute or fetal fulminant hepatitis must be induced in some cases. Therefore, it is desirable to prevent virus reactivation during chemotherapy in HBV-positive patients. We report a case in which adjuvant chemotherapy for a breast cancer patient was accomplished safely by using entecavir. The patient was a 48-year-old woman with breast cancer whose HBV infection had been pointed out when she was 20 years old. Breast reconstruction was performed, followed by mastectomy. Pathological findings were invasive ductal carcinoma, three positive nodes, estrogen and progesterone receptor-positive, and HER2-negative. An adjuvant chemotherapy with anthracycline followed by taxane was planned. Blood chemistry revealed the seroconversion of HBV and the quantity of HBV-DNA was 2. 8 log copies/mL. Administration of the anti-virus agent, entecavir, was started three weeks before chemotherapy. The HBV-DNA was decreased under the titer of detection and no re-increase in HBV-DNA was found during chemotherapy. Planned chemotherapy was accomplished safely without HBV reactivation.     

术前抗病毒治疗对HBV-DNA 阴性肝细胞癌患者术后病毒再激活及肝功能的影响*

目的:评估术前抗病毒治疗对术后乙肝病毒再激活以及肝功能的影响。方法:2012年7 月至2016年3 月将广西医科大学附属肿瘤医院肝胆胰脾外科乙肝病毒DNA 阴性的HCC 患者分成抗病毒组（66例）及对照组（108 例）,抗病毒组术前给予恩替卡韦分散片抗病毒治疗,对照组未给予抗病毒治疗。统计分析术后HBV 再激活及肝功能指标变化情况。结果:抗病毒组HBV 激活率为3%（2/ 66）,对照组为27.8%（30/ 108）。 多因素分析显示小部分肝切术（HR= 4.695;95%CI:1.257- 17.537,P = 0.021）及术前未抗病毒治疗（HR= 8.164;95%CI:1.831- 36.397,P = 0.006）是术后HBV 再激活的危险因素。抗病毒组与未抗病毒组,激活组与未激活组术后7 天内肝功能指标差异无统计学意义（P > 0.05）,术后30天比较,ALT 及ALB 差异有统计学意义（P < 0.05）。 结论:对于DNA阴性的HCC 患者,肝切除术可导致HBV 再激活,术前抗病毒治疗能有效降低HBV 再激活风险及保护肝功能。      

肝细胞癌患者围手术期病毒载量及肝功能变化

目的:探讨肝细胞癌患者围手术期乙肝病毒DNA载量及肝功能的变化。方法:选取2013年4月-2015年4月本院收治的肝细胞癌患者78例作为研究对象。按照术前血清中HBV-DNA载量的不同,将其分为阴性组14例,低复制组48例,高复制组16例。三组患者均行手术治疗,记录三组患者手术前后7天静脉血清中HBV-DNA载量和术后1天肝功能［谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（TBIL）以及白蛋白（ALB）］变化。结果:手术治疗7天后,阴性组和低复制组患者血清中HBV-DNA载量较治疗前7天有所下降,高复制组患者血清中HBV-DNA载量较治疗前7天有所上升,但无统计学意义（P>0.05）。三组患者手术后的ASL、ALT、TBIL指标较手术前均有明显上升（P＜0.05）,三组术后ALB指标较治疗前下降（P＜0.05）,且阴性组、低复制组、高复制组术后ASL、ALT、TBIL指标比较有递增变化,ALB指标比较有递减变化。结论:肝细胞癌患者行肝癌根除术后仍然存在HBV复制活跃的问题,HBV活跃程度和术前HBV-DNA载量高水平复制会影响到患者术后肝功能恢复。     

Efficacy of Prophylactic Entecavir for Hepatitis B Virus- Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.     

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.     

Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy.

BACKGROUND: Cancer patients who are hepatitis B virus (HBV) carriers and undergoing chemotherapy (CT) may be complicated by HBV reactivation. Over 80% of hepatocellular carcinoma (HCC) patients are HBV carriers; however, the incidence of HBV reactivation during CT has not been well-reported. A prospective study was conducted to determine the incidence of HBV reactivation, the associated morbidity and mortality, and possible risk factors. PATIENTS AND METHODS: 102 HBsAg-positive patients with inoperable HCC underwent systemic CT. Patients received either combination cisplatin, interferon, doxorubicin and fluorouracil (PIAF) or single-agent doxorubicin. They were followed up during and for 8 weeks after CT. RESULTS: In 102 patients, 59 (58%) developed hepatitis amongst whom 37 (36%) were attributable to HBV reactivation. Twelve (30%) died of HBV reactivation. CT was interrupted in 32 patients (86%) with reactivation and 54 (83%) without reactivation (P>0.05). The median survivals were 6.00 and 5.62 months, respectively (P=0.694). Elevated baseline alanine aminotransferase (ALT) was found to be a risk factor. CONCLUSION: HBV reactivation is a common cause of liver damage during CT in HBsAg-positive HCC patients. The only identifiable associated risk factor was elevated pre-treatment ALT. Further studies into the role of antiviral and novel anticancer therapies are required to improve the prognosis of these patients.     

恩替卡韦预防肺癌携带 HBV 患者化疗后HBV 再激活的临床研究

目的：探讨化疗引起的肺癌患者乙肝病毒再激活与肝功能损害的相关性及恩替卡韦对化疗后乙肝病毒再激活的预防作用。方法收集2011年1月-2012年12月,在哈尔滨医科大学附属肿瘤医院经病理证实的160例携带乙型肝炎病毒的肺癌患者的临床资料进行回顾性分析,按照治疗方法的不同分为两组：预防组80例,对照组80例。预防组在化疗前给予口服恩替卡韦（0．5 mg/d）,至化疗后6个月,对照组患者给予化疗未接受恩替卡韦治疗。比较两组化疗后乙肝病毒再激活、肝功能损害、化疗延迟、化疗的毒性反应等指标变化。结果预防组乙肝病毒再激活发生率为5％,对照组为25％,两组比较差异有统计学意义（P＜0．01）,乙肝病毒再激活与HBV-DNA载量有关,HBV-DNA≥104copies/mL容易发生乙肝病毒再激活,而与肺癌的病理类型、临床分期、是否含铂方案化疗及是否HBeAg阳性无关（ P＞0．05）;肝功能损害方面,预防组肝功能损害率为40％,对照组为70％,两组比较差异有统计学意义（ P＜0．01）,具体分级中,预防组Ⅲ、Ⅳ度肝功能损害率为5％,对照组为30％,两组比较差异有统计学意义（P＜0．05）,而Ⅰ、Ⅱ度预防组为35％,对照组为40％,两组比较差异无统计学意义（P＞0．05）;肝功能损害所致的化疗延迟率比较,预防组为5％,对照组为20％,两组比较差异有统计学意义（ P＜0．05）;两组化疗的主要毒性反应为骨髓抑制、恶心、呕吐、疲乏等,多为1～2级,经支持对症处理可以恢复。结论预防性口服恩替卡韦可以降低携带乙肝病毒的肺癌患者乙肝病毒再激活的风险。     

Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: Analysis from the Asia Lymphoma Study Group

BackgroundHepatitis B virus (HBV) reactivation is increasing, as rituximab has become widely used for B-cell lymphoma. Thus, prevention and management of HBV reactivation are important in HBV-endemic areas.MethodsHepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-positive patients and HBsAg-negative/HBV core antibody (HBcAb)-positive patients who received rituximab-containing chemotherapy was investigated by the Asia Lymphoma Study Group via retrospective (n = 340), and the results were compared to cross-sectional analysis with patients who were prospectively monitored in a single institute (n = 127). The goal of the study was to define the frequency of HBV reactivation and the efficacy of antiviral prophylaxis.ResultsHBV reactivation was found in 27.8% of HBsAg-positive patients (45/162) in the retrospective analysis, being significantly less frequent in patients receiving antiviral prophylaxis than those not (22.9%, 32/140 versus 59.1%, 13/22; p < 0.001). Lamivudine was most commonly used (96/162, 59.3%), but more than 20% of HBsAg-positive patients showed breakthrough HBV reactivation. In the cross-sectional analysis, a reduced rate of HBV reactivation occurred for entecavir as compared with lamivudine prophylaxis (6.3% versus 39.3%; p < 0.05). HBV DNA monitoring of HBsAg-negative/HBcAb-positive patients in the cross-sectional analysis showed HBV reactivation in only 2.4% of cases.ConclusionsThis is the largest study of HBV reactivation in patients receiving rituximab-containing chemotherapy to date, and we defined the probability of HBV reactivation in an HBV-endemic region.     

Hepatitis B virus reactivation in patients receiving chemotherapy for cancer treatment: role of Lamivudine prophylaxis

Hepatitis B virus (HBV) reactivation is a frequent complication in inactive HBV carriers at time of chemotherapy or following this chemotherapy. This complication appeared during or after chemotherapy and was not increased by the use of rituximab alone or combined with chemotherapy. This is a severe complication most frequently seen in lymphoma patients. Lamivudine have efficacy to treat the patients once the clinical disease is present. However, lamivudine prophylaxis beginning before chemotherapy and until at least 6 months after the end of chemotherapy is recommended for all HBV carriers. Hepatitis C virus is usually not associated with reactivation and prophylaxis should not be used.     

拉米夫定预防B细胞非霍奇金淋巴瘤患者利妥昔单抗化疗后乙型肝炎病毒再激活的临床分析

 【摘要】　目的　研究利妥昔单抗联合化疗治疗B细胞非霍奇金淋巴瘤（B-NHL）合并乙型肝炎病毒（HBV）携带患者的安全性,探讨拉米夫定预防性治疗的价值。方法　回顾性分析含利妥昔单抗联合化疗前后B-NHL患者乙型肝炎五项、HBV-DNA和肝功能指标变化。将39例HBV核心抗体（HBcAb）（+）／HBV表面抗体（HBsAb）（-）的B-NHL患者分为拉米夫定预防组和对照组,比较两组化疗后HBV再激活、肝功能损害等指标。结果　108例接受利妥昔单抗联合化疗的B-NHL患者中,15例患者为HBV表面抗体（HBsAg）（+）,占所有患者的13.89 %;39例为HBsAg（-）／HBcAb（+）患者,占所有患者的36.11 %。15例HBsAg（+）的患者中HBV再激活率为13.3 %,13例拉米夫定预防患者中1例（7.7 %）HBV再激活,2例未预防的患者中1例HBV再激活。39例HBsAg（-）／HBcAb（+）患者中HBV再激活率为7.7 %（3例）,14例拉米夫定预防组HBV再激活率为0,25例未预防的患者中3例（12 %）HBV再激活。结论　B-NHL合并HBV携带患者在利妥昔单抗联合化疗导致HBV再激活的风险是可控的,预防性使用拉米夫定能明显降低HBV再激活。     

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.     

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。     

A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma

Purpose

We studied the safety and effectiveness of TSU-68, an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor and fibroblast growth factor receptor, in patients with advanced hepatocellular carcinoma (HCC).

Methods

Patients with unresectable or metastatic HCC were eligible for enrollment. In phase I, the safety, tolerability and pharmacokinetics were assessed in patients stratified based on liver function, from no cirrhosis to Child?CPugh class B. The safety and effectiveness were assessed in phase II at the dose determined in phase I.

Results

Twelve patients were enrolled in phase I. Dose-limiting toxicities were found with TSU-68 at the dose of 400?mg bid in Child?CPugh B patients, and 200?mg bid was established as the phase II dose. Phase II included 23 additional patients, and the safety and efficacy were evaluated in a total of 35 patients. One patient (2.9%) had a complete response. Two patients (5.7%) had a partial response, and 15 patients (42.8%) showed a stable disease. The median time to progression was 2.1?months, and the median overall survival was 13.1?months. Common adverse events were hypoalbuminemia, diarrhea, anorexia, abdominal pain, malaise, edema and AST/ALT elevation. The analysis of angiogenesis-related parameters suggests that serum-soluble vascular cell adhesion molecule-1 is a possible marker to show the response.

Conclusions

TSU-68 at a dose of 200?mg bid determined by stratification into liver function, showed promising preliminary efficacy with a high safety profile in patients with HCC who had been heavily pre-treated.     

长、短疗程口服抗病毒药预防急性髓系白血病患者乙型肝炎病毒再激活的观察研究

背景与目的：乙型肝炎病毒(hepatitis B virus,HBV)再激活是急性髓系白血病(acute myeloid leukemia,AML)合并HBV感染的患者接受诱导和巩固化疗期间严重并发症之一,核苷类抗HBV药物(包括拉米夫定和恩替卡韦等)已成为预防和抢先治疗HBV再激活主要抗病毒药物。该研究观察并探究AML合并HBV感染患者化疗前后长疗程和短疗程口服核苷类抗HBV药物预防病毒再激活的临床疗效和安全性。方法：回顾性分析29例AML合并HBV感染并接受至少4个疗程化疗患者的临床资料。根据患者口服核苷类抗HBV药物预防治疗前HBV表面抗原(hepatitis B surface antigen,HBsAg)含量以及抗HBV药物持续服用时间分为4个亚组,系统分析和比较不同亚组患者HBV再激活情况和药物不良反应。结果：长疗程预防(long course prophylaxis group,LCP)组,即口服抗HBV药物持续至化疗结束后6个月以上,该组患者的HBV再激活率和HBV相关性肝炎发生率分别为5.56%(1/18)和0%(0/18),明显低于短疗程预防(short course prophylaxis group,SCP)组患者(即口服抗HBV药物持续至化疗结束后1个月以内)的45.45%(5/11)和36.36%(4/11),差异有统计学意义(P=0.018和P=0.014),而LCP和SCP组患者的HBV原发耐药率分别为11.11%(2/18)和9.09%(1/11),差异无统计学意义(P>0.05)。进一步亚组分析显示,预防治疗前HBsAg阳性患者(HBsAg大于等于0.05 IU/mL)经长疗程预防,其HBV再激活率和HBV相关性肝炎发生率分别为8.33%(1/12)和0%(0/12),明显低于SCP组,66.67%(4/6)和66.67%(4/6),差异有统计学意义(P=0.022和P=0.005);同时,LCP和SCP组中HBsAg(+)患者的HBV原发耐药率分别为8.33%(1/12)和16.67%(1/6),差异无统计学意义(P>0.05)。此外,LCP组中HBsAg阴性患者(HBsAg小于0.05 IU/mL)的HBV再激活率、肝炎发生率和原发耐药率与SCP组中HBsAg(-)患者比较,差异无统计学意义(P>0.05)。LCP和SCP组患者均未发生3级以上药物毒性反应。结论：长疗程口服核苷类抗HBV药物是降低AML合并HBsAg(+)感染患者化疗后病毒再激活以及病毒相关事件发生率有效而且安全性良好的预防治疗方案。     

Retrospective and prospective studies of hepatitis B virus reactivation in malignant lymphoma with occult HBV carrier

BackgroundIn surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients.Patients and methodsForty-eight of 127 (37.8%) lymphoma patients were HBsAg negative and HBcAb positive, and 24 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months.ResultsHBV reactivation was observed in two patients (4.1%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test.ConclusionsRituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAg-negative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection.     

Reactivation of chronic hepatitis B infection following intensive chemotherapy and successful treatment with lamivudine: A case report and review of the literature

Background:Hepatitis B virus reactivation has been reported incancer patients following administration of chemotherapy or immunosuppressivetherapy and may result in liver damage of varying degrees of severity.Although treatment is supportive in nature, lamivudine, a nucleoside analoguehas been found to suppress HBV replication as evidenced by reports of 13 casesin the medical literature. Patients and methods:We report a patient who achieved asuccessful outcome with lamivudine following reactivation of HBV duringcombination chemotherapy for non-Hodgkins lymphoma, and provide a briefoverview of the literature including the 13 published case reports. Results:Lamivudine therapy resulted in clinical improvement aswell as in normalization of liver function tests and coagulation profile. Conclusions:Lamivudine has been found to suppress HBV replicationmanifested both by histology and serum HBV-DNA levels in chronic carriers ofHBV who developed reactivation of hepatic disease following chemotherapy.Physicians caring for such patients should be able to recognize this clinicalchallenge, and lamivudine should be considered.     

原发性肝癌与HBV DNA的关系分析

目的：探讨原发性肝癌（PHCC）与患者血清乙肝病毒（HBV）的关系。方法：对286例PHCC患者进行HBV DNA检测。结果：在286例肝癌患者中，HBV DNA阳性率为62．59％，其中85．47％的感染者血清HBV DNA水平≤10^6。结论：乙肝病毒感染仍是肝癌的主要发病因素，而且这类患者的血清HBV DNA水平大多较低。     

术前HBV-DNA载量对肝细胞癌术后肝功能衰竭的影响

目的 探讨术前HBV-DNA载量对肝细胞癌（hepatocellular carcinoma,HCC）术后肝功能衰竭（posthepatectomy liver failure,PHLF）的影响。方法 回顾性分析342例术前肝功能Child-Pugh A级HCC患者行肝切除术的临床资料,根据术前HBV-DNA不同载量进行分组,比较术前HBV-DNA载量与PHLF发生的关系。结果 术后发生PHLF 99例（29.0％）。PHLF总发生率≥10⁶ IU/mL组为42.6%（20/47）、10⁵ IU/mL组为29.2%（21/72）、10⁴ IU/mL组为34.9%（22/63）、10³ IU/mL组为19.7%（11/56）、＜10³ IU/mL组为24.0%（25/104）,差异无统计学意义（X²=8.900,P=0.064）;PHLF-B级及以上的发生率分别为21.3%（10/47）、16.7%（12/72）、19.0%（12/63）、10.7%（6/56）、13.5%（14/104）,差异亦无统计学意义（X²=3.118, P=0.538）。根据术前HBV-DNA不同载量进一步行亚组分析PHLF-B级及以上发生率,各亚组间比较差异均无统计学意义（P＞0.05）。结论 术前HBV-DNA载量对PHLF-B级及以上发生无明显影响,对于肝功能Child-Pugh A级患者,术前经简单抗病毒治疗后应尽快手术。     

Level of hepatitis B surface antigen might serve as a new marker to predict hepatocellular carcinoma recurrence following curative resection in patients with low viral load

To investigate the association between preoperative HBsAg (hepatitis B surface antigen) level and risk of HCC (hepatocellular carcinoma) recurrence following curative resection, we enrolled 826 HBV-related HCC patients who underwent curative resection and received long-term follow-up at the Eastern Hepatobiliary Surgery Hospital (Shanghai, China). Multivariate analyses showed that serum HBsAg ≥ 2000 S/CO, seropositive hepatitis B e antigen (HBeAg), γ-glutamyl transpeptidase > 61 U/L, prothrombin time > 13 s, multinodularity, lager tumor size, and major portal vein invasion were independently associated with a increased risk of HCC recurrence. Compared with HCC patients with HBsAg level < 2000 S/CO, HCC patients with HBsAg level ≥ 2000 S/CO had a higher prevalence of seropositive HBeAg, antiviral therapy, and cirrhosis; were younger; and had a higher levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and HBV viral load. Multivariable stratified analyses showed HCC patients with HBsAg level < 2000 S/CO tended to have a lower incidence of HCC recurrence in following subgroups of patients, including for noncirrhotic (HR, 0.561; 95% CI, 0.345-0.914), HBV DNA < 2000 IU/mL (HR, 0.604; 95% CI, 0.401-0.912), ALT ≤ 41 U/L (HR, 0.643; 95% CI, 0.440-0.942), AST ≤ 37 U/L (HR, 0.672; 95% CI, 0.459-0.983), and seronegative HBeAg (HR, 0.682; 95% CI, 0.486-0.958). When we evaluated HBeAg-negative patients with HBV DNA < 2000 IU/mL, HBsAg level still determined risk of HCC recurrence (p = 0.014), but not HBV DNA (p = 0.550) and ALT (p = 0.186). These results suggest high levels of HBsAg increase risk of HCC recurrence following curative resection. HBsAg level might serve as a new marker to complement HBV DNA level in predicting HCC recurrence, especially in HBeAg-negative patients with low viral load.     

A randomised phase II study of TSU-68 in patients with hepatocellular carcinoma treated by transarterial chemoembolisation

BackgroundTSU-68 is an antitumour drug that acts by inhibiting angiogenesis. We evaluated the efficacy and safety of TSU-68 in combination with transarterial chemoembolisation (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC).Patients and MethodsIn this multicenter, open-label phase II study, we randomised patients with HCC who had been treated with a single session of TACE to receive either 200 mg TSU-68 twice daily or no medication. The primary end-point was progression-free survival (PFS).ResultsA total of 103 patients were enrolled. Median PFS was 157.0 days (95% confidence interval [CI], 124.0–230.0 days) in the TSU-68 group and 122.0 days (95% CI, 73.0–170.0 days) in the control group. The hazard ratio was 0.699 (95% CI, 0.450–1.088). Fatigue, elevated aspartate aminotransferase (AST), elevated alkaline phosphatase, oedema and anorexia were more frequent in the TSU-68 group than in the control group. The most frequent grade 3/4 adverse events were AST elevation (46% of patients in the TSU-68 group and 12% of controls) and alanine aminotransferase elevation (26% of patients in the TSU-68 group and 8% of controls). Two deaths, grade 5 hepatic failure and melena were noted in the TSU-68 group.ConclusionThis exploratory study shows a trend towards prolonged PFS with TSU-68 treatment after a single session of TACE, but this observation was not statistically significant. The two deaths were related to the study treatment. These results suggest that further examination of the study design is necessary to determine whether TSU-68 has any clinical benefits when combined with TACE.