恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术预后的影响

目的探讨恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术(TACE)预后的影响。方法选取2011年1月—2018年3月在南方医院肝肿瘤中心首次接受TACE治疗的HCC患者170例,包括恩替卡韦治疗组114例,对照组(未抗病毒治疗)56例。记录治疗前基线的人口学资料,ALT、AST、TBil、Alb、PLT和Child-Pugh分级,HBeAg和HBV DNA水平,AFP、BCLC分期,以及治疗后4~8周的HBV DNA水平,ALT、AST、TBil、Alb和Child-Pugh分级变化和治疗后长期的生存状况。观察患者的短期和长期临床获益(总生存期)。计量资料两组间比较采用t检验或Mann-Whitney U检验;计数资料两组间比较采用χ2检验。对治疗前临床相关指标进行多因素logistic分析,以发现与乙型肝炎再活动的相关危险因素。Kaplan-Meier法分析总生存期的生存曲线,log-rank检验生存曲线间差异性。结果恩替卡韦治疗组患者乙型肝炎再活动的发生率与对照组比较无差异(15.79%vs 16.07%,χ2=0.002,P=0.962)。PLT水平在乙型肝炎再活动组与无乙型肝炎再活动组间差异有统计学意义(Z=-2.183,P=0.029)。多因素分析结果显示,HBV DNA水平是乙型肝炎再活动的独立危险因素(HR=1.000,P=0.015)。恩替卡韦组的1、3和5年生存率分别是56.20%、30.30%和13.20%,对照组的1、3和5年生存率分别是60.60%、27.20%和16.30%,两组在总体生存率上差异无统计学意义(χ2=0.049,P=0.755)。结论抗病毒治疗可以抑制乙型肝炎相关HCC患者TACE术后HBV复制,从而减少TACE治疗的肝毒性。     

Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma

Aim: Reports concerning changes in hepatitis B virus (HBV) status and liver function in hepatocellular carcinoma (HCC) during or after transcatheter arterial chemoembolization (TACE) have been rare and the results inconsistent. The objective of this retrospective study was to evaluate these parameters in a large cohort of HBV‐related HCC patients. Methods: One hundred and seventy‐two hepatitis B surface antigen positive HCC patients with Child–Pugh grade A or B liver disease who underwent 228 sessions of TACE were enrolled, and related clinical and laboratory data were analyzed. Results: In total, HBV reactivated in 33 (14.5%), remained stable in 152 (66.7%) and decreased in 43 (18.8%) sessions. Univariate analysis revealed that sex and HBV DNA levels correlated with changes in HBV DNA status after TACE, while hepatitis B e‐antigen (HBeAg), prothrombin time and chemotherapeutic agents were marginally significant factors. Multivariate analysis demonstrated that the major factors that influenced the HBV DNA status were baseline HBV DNA levels(P = 0.0002) and HBeAg (P = 0.0387). A comparison of the post‐TACE (30–90 days) liver function to the baseline revealed no significant differences. The reactivation group has the highest rate of exacerbation (12.1%) compared with the stable group (5.9%) and downregulation group (4.7%). Conclusion: HBV DNA changes after TACE included reactivated, decreased and stable HBV DNA levels. Although HBV reactivation did not necessarily result in exacerbation of liver damage and most HCC patients with Child–Pugh grade A and B tolerated TACE well, careful post‐procedure monitoring and managing is needed.     

原发性肝癌局部化疗后肝炎及乙型肝炎抗病毒治疗的临床研究

目的分析肝癌化疗后肝炎发生的病因,探讨核苷类似物抗病毒治疗对化疗后乙肝病毒再激活肝炎疗效。方法收集明确诊断乙型肝炎后肝细胞癌患者120例,男108例,女12例,年龄28~85岁,平均（53.88±12.16）岁。肝癌患者均接受1次经导管肝动脉化疗栓塞（TACE）治疗;并分为抗病毒治疗组35例;未行抗病毒治疗组85例。抗病毒组中TACE前2周23例服拉米夫定;12例服阿德福韦酯,维持抗病毒治疗TACE后4周为观察终点。随访4周后,监测2组患者TACE前后肝功能及HBV载量水平变化和肝炎发生情况,观察核苷类似物抗病毒治疗HBV再激活肝炎的疗效。结果肝细胞癌患者化疗后HBV再激活33例,化疗后未再激活87例,HBV再激活发生率为27.50%。HBV再激活肝炎23例,发生率为69.70%;化疗药物性肝炎11例,发生率为12.64%,2种肝炎的发生之间差异有统计学意义（P=0.00）。抗病毒治疗组与未抗病毒组之间HBV再激活肝炎的发生差异有统计学意义（2χ=5.78,P〈0.05）,2组间药物性肝炎的发生差异无统计学意义。结论肝细胞癌化疗后发生HBV再激活肝炎和化疗药物性肝炎;HBV再激活肝炎的发生较化疗药物性肝炎多。核苷类似物（拉米夫定/阿德福韦酯）抗病毒治疗可明显降低肝细胞癌患者化疗后HBV再激活肝炎的发生。     

恩替卡韦抗病毒对TACE治疗的HBV DNA阴性乙型肝炎相关性肝癌的影响

目的 探讨应用恩替卡韦预防治疗接受肝动脉化疗栓塞术（TACE）的乙型肝炎病毒（HBV）DNA阴性的乙型肝炎相关性肝细胞癌（HCC）患者对病毒激活的影响。方法 将45例HBV DNA阴性乙型肝炎相关性HCC患者随机分为观察组23例和对照组22例。两组患者均在常规护肝治疗基础上接受TACE治疗,观察组于TACE治疗前1周开始应用恩替卡韦分散片抗病毒治疗,对照组未行抗病毒治疗。采用荧光定量PCR法检测血清HBV DNA,采用微粒发光法检测血清HBV标志物,使用全自动生化分析仪检测血生化指标。观察并比较两组TACE后血清HBV DNA转阳和肝衰竭发生率及生存率情况。结果 在治疗24 w,观察组血清HBV DNA水平仍为<2 lg IU/mL,明显低于对照组的（4.10±2.86） lg IU/mL（P<0.01）,观察组HBV DNA转阳率为8.7%,明显低于对照组的36.4%（P<0.05）;观察组肝衰竭发生率为0.0%,对照组为22.7%,但两组差异无统计学意义（P>0.05）;在治疗12 w,观察组血清ALT为（56.75±20.74） IU/L,明显低于对照组的（125.78±42.75） IU/L,PTA为（48.65±8.26）%,明显高于对照组的（42.74±7.42）%（P<0.05）;在24 w,观察组血清ALT水平和Child-Pugh评分分别为（50.73±18.45）IU/L和（6.26±1.46）分,明显低于对照组的（97.48±30.56） IU/L和（7.84±1.65） 分,PTA为（52.45±9.10）%,明显高于对照组的（39.56±6.78）%（均P<0.01）;两组近期临床疗效差异无统计学意义(P>0.05);观察组2 a生存率为69.6%,明显高于对照组的36.4%（P<0.05）。结论 对接受TACE治疗的HBV DNA阴性的乙型肝炎相关性HCC患者,给予恩替卡韦抗病毒预防性治疗可以抑制HBV再激活,改善肝功能。     

A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization

Reactivation of hepatitis B virus (HBV) during chemotherapy is well documented. However, there are limited data on this complication in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemotherapy. The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization (TACL) and to seek predictors of this event. A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospectively and randomly assigned to receive lamivudine 100 mg daily from the start of TACL (preemptive group) or not (control group). During the study, 11 (29.7%) of 37 patients in the control group and 1 (2.8%) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation (P = .002). In addition, there were significantly more incidences of overall hepatitis (P = .021) and severe grade of hepatitis (P = .035) in the control group. With multivariate Cox regression model, a baseline HBV DNA level of more than 10(4) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization (P = .046). In conclusion, preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL. Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia.     

A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial

Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P < 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation-related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-na?ve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation. CONCLUSION: Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.     

Quantitative analysis of plasma HBV DNA for early evaluation of the response to transcatheter arterial embolization for HBV-related hepatocellular carcinoma

AIM: To assesse changes in plasma HBV DNA after TAE in HBV-related HCC and correlate the levels with the pattern of lipiodol accumulation on CT. METHODS: Between April and June 2001,14 patients with HBV-associated HCC who underwent TAE for inoperable or recurrent tumor were studied. Levels of plasma HBV DNA were measured by real-time quantitative PCR daily for five consecutive days after TAE. More than twofold elevation of circulating HBV DNA was considered as a definite elevation. Abdominal CT was performed 1-2 mo after TAE for the measurement of lipiodol retention. RESULTS: Circulating HBV DNA in 10 out of 13 patients was elevated after TAE, except for one patient whose plasma HBV DNA was undetectable before and after TAE. In group Ⅰ patients (n = 6), the HBV DNA elevation persisted for more than 2 d, while in group Ⅱ (n = 7), the HBV DNA elevation only appeared for 1 d or did not reach a definite elevation. There were no significant differences in age or tumor size between the two groups. Patients in group Ⅰ had significantly better lipiodol retention (79.31±28.79%) on subsequent abdominal CT than group Ⅱ (18.43±10.61%) (P=0.02). CONCLUSION: Patients with durable HBV DNA elevation for more than 2 d correlated with good lipiodol retention measured 1 mo later, while others associated with poor lipiodol retention. Thus, circulating HBV DNA may be an early indicator of the success or failure of TAE.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.     

Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Reactivation of hepatitis B virus (HBV) replication is a well-known complication in cancer patients receiving chemotherapy. The aims of this study were to determine the incidence of HBV reactivation in hepatocellular carcinoma (HCC) patients undergoing transarterial chemo-lipiodolization, and to clarify factors contributing to HBV reactivation. METHODS: From April 2001 to September 2002, 146 HBsAg positive patients newly diagnosed as HCC were enrolled in the study. Among these, 83 patients underwent transarterial chemo-lipiodolization using epirubicin and/or cisplatin, and 63 received other treatments. RESULTS: In total, HBV reactivation occurred in 30 (20.5%) patients (28 with chemo-lipiodolization and 2 with other treatments), and of the 30 patients, 19 (13.0%) (18 with chemo-lipiodolization and 1 with other treatments) developed hepatitis. Chemo-lipiodolization was significantly correlated with a higher incidence of hepatitis attributed to HBV reactivation than other treatments (21.7% vs. 1.6%, P<0.001), irrespective of HBeAg or HBV DNA. Among 83 patients undergoing chemo-lipiodolization, HBV reactivation occurred in 28 (33.7%) patients, and HBeAg seropositivity was the only independent predictor of HBV reactivation (P=0.013). Three (10.7%) of them died of hepatic decompensation resulting from HBV reactivation. CONCLUSIONS: Transarterial chemo-lipiodolization can reactivate HBV, and HBeAg-positive HCC patients receiving chemo-lipiodolization should be closely monitored for HBV reactivation.     

Management of hepatitis B virus infection during treatment for hepatitis B virus-related hepatocellular carcinoma

Although liver resection is considered the most effective treatment for hepatocellular carcinoma (HCC), treatment outcomes are unsatisfactory because of the high rate of HCC recurrence. Since we reported hepatitis B e-antigen positivity and high serum hepatitis B virus (HBV) DNA concentrations are strong risk factors for HCC recurrence after curative resection of HBV-related HCC in the early 2000s, many investigators have demonstrated the effects of viral status on HCC recurrence and post-treatment outcomes. These findings suggest controlling viral status is important to prevent HCC recurrence and improve survival after curative treatment for HBV-related HCC. Antiviral therapy after curative treatment aims to improve prognosis by preventing HCC recurrence and maintaining liver function. Therapy with interferon and nucleos(t)ide analogs may be useful for preventing HCC recurrence and improving overall survival in patients who have undergone curative resection for HBV-related HCC. In addition, reactivation of viral replication can occur after liver resection for HBV-related HCC. Antiviral therapy can be recommended for patients to prevent HBV reactivation. Nevertheless, further studies are required to establish treatment guidelines for patients with HBV-related HCC.     

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.     

Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma

AIM: The aim of this study was to determine whether antiviral therapy with lamivudine is beneficial in patients after initial treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Forty-nine consecutive patients with HBV-related HCC completely treated by hepatic resection or radiofrequency ablation were retrospectively enrolled in this study. Comparison was made between 16 patients who received lamivudine therapy at a dose of 100 mg/day after treatment for HCC (lamivudine group) and 33 patients who did not (control group) in terms of changes in remnant liver function, HCC recurrence and survival. RESULTS: Cumulative recurrence rates of HCC did not significantly differ between the two groups (P = 0.622). However, median Child-Pugh score at the time of HCC recurrence was significantly different; 5 (range 5-6) in the lamivudine group versus 7 (range 5-12) in the control group (P = 0.005). All patients in the lamivudine group were able to receive curative treatment for recurrent HCC. In contrast, 10 of 15 patients in the control group were unable to receive curative optimal therapy for recurrent HCC due to deterioration of remnant liver function. The cumulative survival rates of patients in the lamivudine group tended to be higher than those of patients in the control group (P = 0.063). CONCLUSION: It is suggested that lamivudine therapy is beneficial for patients after initial treatment for HBV-related HCC because it contributes to improving remnant liver function, thus decreasing the risk of liver failure and increasing the chances of receiving available treatment modalities for recurrent HCC.     

Perioperative reactivation of hepatitis B virus replication in patients undergoing partial hepatectomy for hepatocellular carcinoma

Background and Aim: Reactivation of hepatitis B virus (HBV) replication happens in patients who receive transarterial chemoembolization or systemic chemotherapy for hepatocellular carcinoma (HCC). The incidence and risk factors of HBV reactivation during the perioperative period in HCC patients receiving hepatic resection is unknown. Methods: Between May 2009 and November 2010, 164 consecutive patients with HBV‐related HCC who underwent hepatic resection were prospectively enrolled in the study. Among these, 126 patients received antiviral treatment before the operation (the antiviral group) and 38 patients did not receive any antiviral treatment (the non‐antiviral group). Results: Ten patients (6.1%) developed HBV reactivation perioperatively (within 1 month after hepatectomy). The incidence of HBV reactivation in the antiviral group and non‐antiviral group were 1.6% (2/126) and 21.1% (8/38), respectively (P < 0.001). On univariate analysis, preoperative HBV DNA < 1.0 × 10³ copies/mL and non‐antiviral therapy were significantly correlated with the occurrence of HBV reactivation (P = 0.044 and P < 0.001, respectively). Only non‐antiviral therapy remained as a predictive factor on multivariate analysis (odds ratio, 15.46; 95% confidence interval, 2.80–85.46, P = 0.002). The recovery of liver function (defined as a decrease of alanine aminotransferase back to normal) was achieved in 86.8% (132/152) patients without HBV reactivation and in 37.5% (3/8) patients with HBV reactivation when evaluated on day 30 after hepatectomy (P < 0.001). Conclusion: Hepatectomy could reactivate HBV replication during the perioperative period, especially in patients who did not receive any antiviral therapy. A close monitoring of HBV DNA during the perioperative period was necessary irrespective of the preoperative HBV DNA level. Once HBV was reactivated, antiviral therapy should be given.     

Transcatheter arterial chemoembolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

AIM:To evaluate the efficacy of transcatheter arterial chemoembolization(TACE) using a suspension of a fine-powder formulation of cisplatin(DDPH) for hepatocellular carcinoma(HCC).METHODS:The study population was comprised of 164 patients who were treated by TACE alone.Of these patients,76 underwent TACE using a suspension of DDPH in lipiodol(LPD)(DDPH group),and the remaining 88 underwent TACE with an emulsion of doxorubicin(ADM) with LPD(ADM group).We compared the DDPH group with the ADM group in terms of...     

血清HBV DNA与肝动脉化疗栓塞术后肝癌复发的相关性研究

目的观察肝癌患者血清HBV DNA载量与肝动脉化疗栓塞术(TACE)后肿瘤复发的关系。方法检测193例乙型肝炎病毒标记物阳性的肝癌患者在TACE治疗前血清HBV DNA载量,分析患者血清HBV DNA载量与栓塞术后肿瘤复发的关系。结果在193例患者中,介入治疗术后2年内共有169例(87.6%)患者肿瘤复发;血清HBV DNA阳性(≥5×102copies/ml)138例,平均血清病毒载量为6.20±1.12lg copies/ml;单因素及多因素分析显示,肝功能Child-Pugh B级或C级、多发肿瘤、肿瘤最长径大于3cm、血清HBV DNA≥5×102copies/ml患者肿瘤复发的相对危险性较高,无肿瘤复发生存期较短。结论肝癌患者血清HBV DNA≥5×102copies/ml是TACE治疗后肿瘤复发的危险因素之一。     

Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma

Chronic hepatitis B virus(HBV) infection is a critical risk factor for the carcinogenesis and progression of hepatocellular carcinoma(HCC). It promotes HCC development by inducing liver fibrogenesis, genetic and epigenetic alterations, and the expression of active viral-coded proteins. Effective antiviral treatments inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis B e antigen serum conversion. Timely initiation of antiviral treatment is not only essential for preventing the incidence of HCC in chronic hepatitis B patients, but also important for reducing HBV reactivation, improving liver function, reducing or delaying HCC recurrence, and prolonging overall survival of HBV-related HCC patients after curative and palliative therapies. The selection of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B surface antigen, and timely rescue treatment when necessary, are essential in antiviral therapies for HBVrelated HCC.     

Potential risk factors for the reactivation of the replication of hepatitis B and C viruses after transcatheter arterial chemoembolization of hepatocellular carcinoma

The purpose of this study was to investigate the potential risk factors for the reactivation of the replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma. Forty-four hepatocellular carcinoma patients treated by TACE using epirubicin plus mitomycin C were studied. Serum HBV DNA (n=17) and HCV RNA (n=27) levels were measured 1 day before and 3 months after TACE. Plasma concentrations of chemotherapeutic agents were determined at 1 hour and 72 hours after TACE. A total of 29 patients (n=13 for chronic hepatitis Band n=16 for chronic hepatitis C) showed significant changes of the viral loads after TACE. Patients with increased viral loads after TACE were older (p=0.041), had higher incidence of pre-TACE white blood cell counts being less than normal limit (p=0.023), and had higher plasma mitomycin C concentrations (p=0.039) than those in patients with decreased viral loads. Analysis by multiple logistic regressions using age, decreased or normal pre-TACE white blood cell counts, mitomycin C concentrations >3.95 ng/mL adopted by receiver operating characteristic curve (p=0.037), and epirubicin concentrations have shown that decreased pre-TACE white blood cell counts was the only significant factor associated with increased viral loads after TACE (p=0.048). In conclusion, patients with decreased pre-TACE white blood cell counts have a potential risk for the reactivation of the replication of HBV or HCV after TACE.     

中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。     

Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma

Background/AimsAntiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear.MethodsA retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled.ResultsThe median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new-onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort.ConclusionsOverall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients.     

Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy

BACKGROUND & AIMS: De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy. METHODS: Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion. RESULTS: Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001). CONCLUSIONS: Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.