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Jang JW, Yoo SH, Nam HC, Jang BH, Sung Sung PS, Lee W, Kwon JH, Nam SW, Bae SH, Yoon SK, Choi JY. Association of Prophylactic Anti-Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy. Clin Infect Dis 2021; 71:546-555. [PMID: 31504352 DOI: 10.1093/cid/ciz860] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 08/30/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). METHODS Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. RESULTS A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. CONCLUSIONS Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.Hepatitis B virus-associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.
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Affiliation(s)
- Jeong Won Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Sun Hong Yoo
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Hee Chul Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Bo Hyun Jang
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Pil Soo Sung Sung
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Won Lee
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jung Hyun Kwon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Soon Woo Nam
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
| | - Jong Young Choi
- Department of Internal Medicine, College of Medicine, World Health Organization Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul
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Gane E, Verdon DJ, Brooks AE, Gaggar A, Nguyen AH, Subramanian GM, Schwabe C, Dunbar PR. Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: A pilot study. J Hepatol 2019; 71:900-907. [PMID: 31306680 DOI: 10.1016/j.jhep.2019.06.028] [Citation(s) in RCA: 236] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 06/26/2019] [Accepted: 06/27/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS To evaluate the hypothesis that increasing T cell frequency and activity may provide durable control of hepatitis B virus (HBV), we administered nivolumab, a programmed death receptor 1 (PD-1) inhibitor, with or without GS-4774, an HBV therapeutic vaccine, in virally suppressed patients with HBV e antigen (HBeAg)-negative chronic HBV. METHODS In a phase Ib study, patients received either a single dose of nivolumab at 0.1 mg/kg (n = 2) or 0.3 mg/kg (n = 12), or 40 yeast units of GS-4774 at baseline and week 4 and 0.3 mg/kg of nivolumab at week 4 (n = 10). The primary efficacy endpoint was mean change in HBV surface antigen (HBsAg) 12 weeks after nivolumab. Safety and immunologic changes were assessed through week 24. RESULTS There were no grade 3 or 4 adverse events or serious adverse events. All assessed patients retained T cell PD-1 receptor occupancy 6-12 weeks post-infusion, with a mean total across 0.1 and 0.3 mg/kg cohorts of 76% (95% CI 75-77), and no significant differences were observed between cohorts (p = 0.839). Patients receiving 0.3 mg/kg nivolumab without and with GS-4774 had mean declines of -0.30 (95% CI -0.46 to -0.14) and -0.16 (95% CI -0.33 to 0.01) log10 IU/ml, respectively. Patients showed significant HBsAg declines from baseline (p = 0.035) with 3 patients experiencing declines of >0.5 log10 by the end of study. One patient, whose HBsAg went from baseline 1,173 IU/ml to undetectable at week 20, experienced an alanine aminotransferase flare (grade 3) at week 4 that resolved by week 8 and was accompanied by a significant increase in peripheral HBsAg-specific T cells at week 24. CONCLUSIONS In virally suppressed HBeAg-negative patients, checkpoint blockade was well-tolerated and led to HBsAg decline in most patients and sustained HBsAg loss in 1 patient. LAY SUMMARY Chronic hepatitis B virus infection (CHB) is characterized by a dysfunctional immune response. In patients with CHB, inhibitory receptors, such as programmed death receptor 1 (PD-1) are overexpressed on T cells, leading to an ineffective immune response in the liver. Herein, we show that the PD-1 inhibitor, nivolumab, is safe and effective for the treatment of virally suppressed patients with CHB. Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) number: ACTRN12615001133527.
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Affiliation(s)
- Edward Gane
- Auckland Clinical Studies, Auckland, New Zealand.
| | - Daniel J Verdon
- School of Biological Sciences, and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
| | - Anna E Brooks
- School of Biological Sciences, and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
| | | | | | | | | | - P Rod Dunbar
- School of Biological Sciences, and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
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Zhang L, Xie XY, Chen Y, Ge NL, Chen RX, Gan YH, Zhang BH, Wang YH, Ren ZG. Hepatitis B surface antigen predicts recurrence after radiofrequency ablation in patients with low hepatitis B virus loads. Medicine (Baltimore) 2017; 96:e9377. [PMID: 29384914 PMCID: PMC6392890 DOI: 10.1097/md.0000000000009377] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Radiofrequency ablation (RFA) is a first-line option for the treatment of small liver cancers, but the recurrence remains a problem affecting long-term survival. Hepatitis B virus (HBV) activity is associated with the prognosis of hepatocellular carcinoma (HCC). We investigated the significance of hepatitis B surface antigen (HBsAg) in HCC recurrence after curative RFA treatment in HBV-related small HCC.We enrolled 404 HBV-related patients with small HCC (≤3 cm) who underwent curative RFA. We used univariate and multivariate analyses to investigate the baseline levels of HBsAg, in addition to other known risk factors for HCC recurrence, for association with HCC tumor recurrence after curative RFA.The overall 1-, 2-, and 3-year recurrence-free survival (RFS) rates were 75%, 50%, and 34%, respectively. The median recurrence-free time was 25 months. The level of HBsAg was an independent risk factor for recurrence in patients with lower HBV-DNA levels. In hepatitis Be antigen (HBeAg)-negative patients, the 1-, 2-, and 3-year RFS rates were 79%, 64%, and 44%, respectively, for that with low HBsAg levels, compared with 73%, 50%, and 37%, respectively, for that with high HBsAg levels (P = .039).HBsAg might serve as a valuable marker to evaluate the risk of HCC recurrence in HBeAg-negative patients with low HBV viral load.
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Feasibility and Efficacy of S-Adenosyl-L-methionine in Patients with HBV-Related HCC with Different BCLC Stages. Gastroenterol Res Pract 2016; 2016:4134053. [PMID: 28003820 PMCID: PMC5149688 DOI: 10.1155/2016/4134053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 10/26/2016] [Indexed: 02/06/2023] Open
Abstract
Aims. To understand the feasibility and efficacy of treatment with SAMe in patients with hepatitis B-related HCC with different Barcelona Clinic Liver Cancer (BCLC) stages. Methods. We retrospectively enrolled 697 patients with BCLC early-stage (stages 0-A) and advanced-stage (stages B-C) HCC who underwent SAMe therapy (354 cases) or no SAMe therapy (343 cases). The baseline characteristics, postoperative recoveries, and 24-month overall survival rates of the patients in the 2 groups were compared. Cox regression model analysis was performed to confirm the independent variables influencing the survival rate. Results. For patients in the early-stage (BCLC stages A1–A4) group, little benefit of SAMe therapy was observed. For advanced-stage (BCLC B-C) patients, SAMe therapy reduced alanine aminotransferase (ALT) and aspartate transaminase (AST) levels and effectively delayed the recurrence time and enhanced the 24-month survival rate. Cox regression model analysis in the advanced-stage group revealed that treatment with SAMe, preoperative viral load, and Child-Pugh grade were independent variables influencing survival time. Conclusion. SAMe therapy exhibited protective and therapeutic efficacy for BCLC advanced-stage HBV-related HCC patients. And the efficacy of SAMe therapy should be further explored in randomized prospective clinical trials.
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Lin XJ, Lao XM, Shi M, Li SP. Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment. Dig Dis Sci 2016; 61:2465-76. [PMID: 27105647 DOI: 10.1007/s10620-016-4167-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 04/13/2016] [Indexed: 02/07/2023]
Abstract
Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE.
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Affiliation(s)
- Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Xiang-Ming Lao
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China.
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Sheng-Ping Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Southern China, Guangzhou, 510060, Guangdong, People's Republic of China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
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Chen X, Wu F, Liu Y, Lou J, Zhu B, Zou L, Chen W, Gong J, Wang Y, Zhong R. The contribution of serum hepatitis B virus load in the carcinogenesis and prognosis of hepatocellular carcinoma: evidence from two meta-analyses. Oncotarget 2016; 7:49299-49309. [PMID: 27384478 PMCID: PMC5226509 DOI: 10.18632/oncotarget.10335] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Accepted: 06/13/2016] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIM The meta-analysis aimed to quantify and summarize the contribution of serum hepatitis B virus (HBV) DNA load in the carcinogenesis and prognosis of hepatocellular carcinoma (HCC). RESULTS Nine independent studies with a total of 1162 cases and 9365 participants on risk of HCC and seventeen studies with 1342 cases and 2891 participants on recurrence of HCC were finally included. The non-liner dose-response association between HBV DNA level and HCC risk was observed, with P value equal to 0.02 for linear test. Compared with 2 log10copies/ml HBV DNA level carriers, the summary relative risk of HCC were 1.65(95% CI: 0.94-2.92) for 4.5 log10copies/ml, 2.20(95% CI: 1.00-4.85) for 5.5 log10copies/ml, 3.06(95% CI: 1.11-8.44) for 6.5 log10copies/ml. Moreover, individuals with high viral load (HBV DNA levels > 105copies/ml) presented significant association with increased risk of HCC recurrence, with the pooled RR of 1.69 (95% CI: 1.49-1.92). MATERIALS AND METHODS Pertinent studies were identified by searching PubMed, Embase and ISI Web of science databases up to January 2016 and by reviewing the references of retrieved articles. The dose-response meta-analysis was precisely performed to calculate the summary relative risks (RRs) by quantizing the association between HBV load and risk of HCC. Besides, the contribution of HBV load on recurrence of HCC was further clarified by general meta-analysis. CONCLUSIONS These findings indicated a non-linear dose-response relationship between serum HBV DNA level and risk of HCC, and confirmed the significant contribution of serum HBV DNA level in the prognosis of HCC.
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Affiliation(s)
- Xueqin Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of Medical Quality Management, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| | - Fan Wu
- Abdominal Surgery Department, Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yanmei Liu
- Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jiao Lou
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Beibei Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Zou
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing Gong
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ying Wang
- Department of Virology, Wuhan Centers for Disease Prevention and Control, Wuhan, Hubei, China
| | - Rong Zhong
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Chen JL, Lin XJ, Zhou Q, Shi M, Li SP, Lao XM. Association of HBV DNA replication with antiviral treatment outcomes in the patients with early-stage HBV-related hepatocellular carcinoma undergoing curative resection. CHINESE JOURNAL OF CANCER 2016; 35:28. [PMID: 26992891 PMCID: PMC4799530 DOI: 10.1186/s40880-016-0089-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 02/25/2016] [Indexed: 02/07/2023]
Abstract
Background It remains unclear what the antiviral therapy affects disease-free survival (DFS) and overall survival (OS) of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) at different tumor stages and baseline HBV DNA levels. In this study, we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage (stages I and II) HCC patients. Methods We included 445 patients with early-stage HBV-related HCC who underwent curative resection, and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification. The Kaplan–Meier and Cox regression analyses were performed to determine the association of clinical characteristics with survival. Results The median follow-up period was 74 months. For all patients, cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group (log-rank test, P = 0.023), whereas no significant differences in DFS rates were observed. High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients. In patients with baseline HBV DNA levels ≥2000 IU/mL, antiviral treatment was significantly associated with prolonged DFS and OS (log-rank test, P = 0.041 and 0.001, respectively). In patients with HBV DNA levels <2000 IU/mL or undetectable, antiviral treatment did not show a significant benefit in prolonging DFS and OS. Conclusions High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC, and the antiviral treatment could generate survival benefits for the patients. Therefore, antiviral treatment should be given for these patients. However, the effect of antiviral treatment on the patients with low viral load remains unclear, and further investigation is warranted.
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Affiliation(s)
- Jian-Lin Chen
- Department of Hepatobiliary Oncology, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Xiao-Jun Lin
- Department of Hepatobiliary Oncology, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Qian Zhou
- Epidemiology Research Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P. R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Sheng-Ping Li
- Department of Hepatobiliary Oncology, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Xiang-Ming Lao
- Department of Hepatobiliary Oncology, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
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Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma. PLoS One 2016; 11:e0148493. [PMID: 26901762 PMCID: PMC4762706 DOI: 10.1371/journal.pone.0148493] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 12/08/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking. METHODS We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated. RESULTS Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52-207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09-2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75-4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82-4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08-2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01-0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12-3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6-0.78) and 0.746 (95% C.I.: 0.69-0.82) respectively. CONCLUSION Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence.
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Jiang E, Shangguan AJ, Chen S, Tang L, Zhao S, Yu Z. The progress and prospects of routine prophylactic antiviral treatment in hepatitis B-related hepatocellular carcinoma. Cancer Lett 2015; 379:262-7. [PMID: 26272181 DOI: 10.1016/j.canlet.2015.07.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 07/07/2015] [Accepted: 07/16/2015] [Indexed: 02/07/2023]
Abstract
Liver cancer is a common cancer and a leading cause of cancer-related deaths. Among all types of primary liver cancers, hepatocellular carcinoma (HCC) is the major histological subtype, and hepatitis B virus (HBV) infection is the leading cause of HCC. Treatments for hepatitis B related HCC include hepatectomy, liver transplantation, transarterial chemoembolization (TACE), ablative therapy, and Sorafenib treatment. However, HBV reactivation can occur in patients who receive these treatments, resulting in poor clinical outcomes. However, prophylactic antiviral treatment in patients with hepatitis B-related HCC, can reduce the copies of HBV DNA, prevent HBV reactivation, reduce hepatic inflammation, reverse liver fibrosis, decrease tumor recurrence and metastasis, and extend survival time. Prophylactic antiviral treatment should be routinely performed as an important adjuvant therapy in HBV-related HCC patients.
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Affiliation(s)
- Enze Jiang
- Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | | | - Shuangshuang Chen
- Department of Medical Oncology, Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lin Tang
- Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Shuang Zhao
- Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Zhenghong Yu
- Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
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Zhou ZG, Zheng XR, Zhou Q, Shi M, Zhang YJ, Guo RP, Yuan YF, Chen MS, Lin XJ, Lao XM, Li SP. Impact of oral anti-hepatitis B therapy on the survival of patients with hepatocellular carcinoma initially treated with chemoembolization. CHINESE JOURNAL OF CANCER 2015; 34:205-16. [PMID: 26058595 PMCID: PMC4593372 DOI: 10.1186/s40880-015-0017-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 01/04/2015] [Indexed: 02/07/2023]
Abstract
Introduction Most hepatocellular carcinomas (HCC) develop in a background of underlying liver disease including chronic hepatitis B. However, the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus (HBV)-related HCC treated with chemoembolization is unclear. This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC. Methods A total of 224 HCC patients who successfully underwent chemoembolization were identified, and their survival and other relevant clinical data were reviewed. Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival (OS). Results The median survival time (MST) was 15.9 (95% confidence interval [CI], 9.5–27.7) months in the antiviral group and 9.6 (95% CI, 7.8–13.7) months in the non-antiviral group (log-rank test, P = 0.044). Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS (P = 0.008). Additionally, a further analysis was based on the stratification of the TNM tumor stages. In the subgroup of early stages, MST was significantly longer in the antiviral-treatment group than in the non-antiviral group (61.8 months [95% CI, 34.8 months to beyond the follow-up period] versus 26.2 [95% CI, 14.5–37.7] months, P = 0.012). Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup (P = 0.006). However, in the subgroup of advanced stages, MST of the antiviral-treated group was comparable to that of the non-antiviral group (8.4 [95% CI, 5.2–13.5] months versus 7.4 [95% CI, 5.9–9.3] months, P = 0.219). Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup. Conclusion Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC, especially in patients with early-stage tumors.
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Affiliation(s)
- Zhong-Guo Zhou
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Xing-Rong Zheng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, Peoples Republic of China.
| | - Qian Zhou
- Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, Peoples Republic of China.
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Yun-Fei Yuan
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Min-Shan Chen
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Xiang-Ming Lao
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
| | - Sheng-Ping Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, Peoples Republic of China.
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11
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Chen C, Chen DP, Gu YY, Hu LH, Wang D, Lin JH, Li ZS, Xu J, Wang G. Vascular invasion in hepatitis B virus-related hepatocellular carcinoma with underlying cirrhosis: possible associations with ascites and hepatitis B viral factors? Tumour Biol 2015; 36:6255-63. [PMID: 25833692 DOI: 10.1007/s13277-015-3311-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 03/05/2015] [Indexed: 02/06/2023] Open
Abstract
Vascular invasion is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). The objective of the current, retrospective study was to determine the associations of ascites and hepatitis B viral factors (HBeAg and anti-HBe status and HBV DNA levels), as well as tumor-related factors (size, tumor number, grade, and location) with micro- or macroscopic vascular invasion in patients with HCC that developed as a result of hepatitis B virus (HBV)-related cirrhosis. A total of 336 consecutive patients were included. Potential factors associated with micro- or macroscopic vascular invasion were analyzed by logistic regression. Ascites were more commonly detected in patients with micro- or macroscopic vascular invasion, and the presence of ascites was independently associated with vascular invasion. Among patients with mild-to-moderate or severe ascites, the odds ratio for macroscopic vascular invasion was 4.83 (95 % confidence interval [CI] 2.29-10.16) and 11.87 (95 % CI 4.53-31.07), respectively. Similarly, the presence of ascites was associated with microscopic vascular invasion (OR 5.00; 95 % CI 1.23-20.31). In contrast, hepatitis B viral factors were not significantly associated with vascular invasion. The presence of ascites was associated with vascular invasion in patients with HBV-related cirrhotic HCC. Thus, patients with ascites, vascular invasion should be considered and more frequent surveillance should be performed after curative treatment.
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Affiliation(s)
- Chuan Chen
- Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, No. 10 Changjiang Zhi Rd, Chongqing, 400042, China
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12
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Yu SJ, Kim YJ. Hepatitis B viral load affects prognosis of hepatocellular carcinoma. World J Gastroenterol 2014; 20:12039-12044. [PMID: 25232241 PMCID: PMC4161792 DOI: 10.3748/wjg.v20.i34.12039] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/20/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself. The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function. Hepatitis B virus (HBV) is an established major risk factor of HCC development, and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC. High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways. First, it is associated with more frequent recurrence of HBV-related HCC after treatment. Second, it is associated with more occurrence and severity of potentially life-threatening HBV reactivation. Last, it is associated with more worsened liver function, which limits the therapeutic options for HBV-related HCC. HBV, directly or indirectly, can induce hepatocarcinogenesis. In patients with a high HBV DNA level and subsequent active hepatitis, adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis. HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes. Thus, high HBV viral load can affect the prognosis of patients with HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression. Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC. Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression, it is expected that long-term antiviral therapy results in the sustained HBV suppression, control of inflammation, reduction in HCC progression, and eventually in improved overall survival.
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13
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Nishikawa H, Nishijima N, Arimoto A, Inuzuka T, Kita R, Kimura T, Osaki Y. Effect of nucleoside analog use in patients with hepatitis B virus-related hepatocellular carcinoma. Hepatol Res 2014; 44:608-20. [PMID: 23701455 DOI: 10.1111/hepr.12169] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2013] [Revised: 04/15/2013] [Accepted: 05/20/2013] [Indexed: 01/06/2023]
Abstract
AIM To examine the effect of nucleoside analog (NA) therapy on clinical outcome in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent curative therapy. METHODS A total of 131 patients with HBV-related HCC who underwent curative therapy were analyzed. They were divided into an NA group who received NA therapy (n = 99, group A) and a control group (n = 32, group B). Group A was further classified into two groups of patients who either received NA therapy before HCC therapy (n = 34, group Aa) or who received NA therapy with initial HCC therapy (n = 65, group Ab). Overall survival (OS) and recurrence-free survival (RFS) were compared in the three groups. RESULTS The 1- and 3-year cumulative OS rates were both in group Aa, 100% and 88.0% in group Ab, and 100% and 75.7% in group B (overall significance, P = 0.002), respectively. The corresponding RFS rates were 93.1% and 36.0% in group Aa, 78.3% and 45.7% in group Ab, and 78.0% and 38.0% in group B (overall significance, P = 0.734), respectively. Multivariate analysis revealed that being part of group Aa (P < 0.001) or group Ab (P < 0.001) and having albumin levels of 4.0 g/dL or more (P = 0.040) were significantly associated with OS, while HCC stage (P = 0.001) and hepatitis B e-antigen positivity (P < 0.001) were independent predictors linked to RFS. CONCLUSION NA therapy in patients with HBV-related HCC may improve survival after curative therapy.
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Affiliation(s)
- Hiroki Nishikawa
- Departments of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka
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14
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Song IH, Kim SM, Choo YK. Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy. World J Gastroenterol 2013; 19:8867-8872. [PMID: 24379609 PMCID: PMC3870537 DOI: 10.3748/wjg.v19.i47.8867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/23/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a grave primary liver cancer that has a limited therapeutic option because it is generally diagnosed later in an advanced stage due to its aggressive biologic behavior. The early detection of HCC has a great impact on the treatment efficacy and survival of patients at high risk for cancer. Potential host, environmental, and virus-related risk factors have been introduced. Hepatitis B virus (HBV) is a major cause of end-stage liver diseases such as liver cirrhosis or HCC in endemic areas, and its serologic or virologic status is considered an important risk factor. HCC risk prediction derived from the identification of major risk factors is necessary for providing adequate screening/surveillance strategies to high-risk individuals. Several risk prediction models for HBV-related HCC have been presented recently with simple, efficient, and readily available to use parameters applicable to average- or unknown-risk populations as well as high-risk individuals. Predictive scoring systems of risk estimation to assess HCC development can provide the way to an evidence-based clinical approach for cost- and effort-effective outcomes, capable of inducing a personalized surveillance program according to risk stratification. In this review, the concepts and perspectives of the risk prediction of HCC are discussed through the analysis of several risk prediction models of HBV-related HCC.
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Huang L, Li J, Yan J, Sun J, Zhang X, Wu M, Yan Y. Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial. J Viral Hepat 2013; 20:336-42. [PMID: 23565616 DOI: 10.1111/jvh.12036] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Accepted: 09/01/2012] [Indexed: 02/07/2023]
Abstract
This prospective randomized controlled trial investigated whether antiviral therapy decreases the risk of perioperative viral reactivation in patients with hepatitis B virus-induced hepatocellular carcinoma. Patients with hepatitis B virus-related hepatocellular carcinoma undergoing liver resection were screened. Eighty-four patients with low viral load were randomly assigned to receive either antiviral treatment with telbivudine or no therapy. The primary outcome was reactivation of viral replication. Secondary outcomes included liver function recovery and postoperative liver insufficiency. A total of 15 patients developed HBV reactivation during the perioperative period, of which 8 (57.1%) were within the first week after hepatectomy. The incidence of viral reactivation during the perioperative period was 2.5% (1/40) in the antiviral-treated group, compared with 31.8% (14/44) in the control group [HR 0.07 (95%CI 0.01-0.65); P = 0.001]. Liver function recovery was achieved in 82.5% (33/40) patients in the antiviral group on day 30 after hepatectomy, compared with 91.0% (40/44) in the nonantiviral group [HR 1.23 (95%CI 0.98-2.55); P = 0.109]. A total of 7 patients (8.9%) had postoperative liver insufficiency in both groups, but there was no relevant difference between the two groups. Antiviral therapy with telbivudine can significantly decrease the perioperative reactivation of viral replication in patients with hepatitis B virus-related hepatocellular carcinoma undergoing liver resection. Antiviral therapy is an appropriate option for all patients with viral replication undergoing liver resection. (Chinese Clinical Trial Registry, number ChiCTR-TRC-0900615).
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Affiliation(s)
- L Huang
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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16
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Kwon JH, Jang JW, Choi JY, Park CH, Yoo SH, Bae SH, Yoon SK. Should lamivudine monotherapy be stopped or continued in patients infected with hepatitis B with favorable responses after more than 5 years of treatment? J Med Virol 2013; 85:34-42. [PMID: 23154874 DOI: 10.1002/jmv.23421] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Regarding the limited evidence for determining the optimal duration of antiviral treatment for hepatitis B, the long-term outcome of patients with favorable responses to over 5 years of lamivudine monotherapy was investigated. Two hundred seventy-one patients who had received lamivudine for at least 5 years were enrolled. Ultimately, 72 patients without YMDD mutations and showing hepatitis B virus (HBV) DNA levels <2.5 pg/ml after 5 years of treatment were analyzed. Mean treatment duration with lamivudine was 9.1 ± 2.6 years. During the treatment, HBeAg and HBsAg loss/seroconversion rates were 95 and 6.9%, respectively. Decompensation and hepatocellular carcinoma (HCC) developed in 2.8 and 6.9% of patients, respectively. Old age and cirrhosis were risk factors for HCC development. Finally, 11.1% of patients developed YMDD mutations after 8.3 ± 2.4 years of treatment. There was no hepatic decompensation among the patients who developed delayed YMDD mutations. Sixteen patients who achieved a complete response stopped lamivudine and four patients showed relapses 10.3 ± 8.5 months after stopping lamivudine. Relapsed patients had more cirrhotic livers and higher rates of HBeAg positivity at 5 years than patients who maintained complete response. The present study suggests that patients who do not develop YMDD mutations over 5 years of treatment with lamivudine may continue lamivudine monotherapy until the loss of HBsAg. However, even for the patients showing favorable response over 5 years of treatment, those in older ages, with cirrhosis or who show poor HBeAg responses should be on careful monitoring to detect the development of viral mutations, relapse and even HCC.
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Affiliation(s)
- Jung Hyun Kwon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
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Yu SJ, Lee JH, Jang ES, Cho EJ, Kwak MS, Yoon JH, Lee HS, Kim CY, Kim YJ. Hepatocellular carcinoma: high hepatitis B viral load and mortality in patients treated with transarterial chemoembolization. Radiology 2013; 267:638-47. [PMID: 23440326 DOI: 10.1148/radiol.13121498] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE To determine the relationship between hepatitis B virus (HBV) DNA level and the survival of patients with hepatocellular carcinoma treated by means of transarterial chemoembolization (TACE). MATERIALS AND METHODS This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. From January 2005 to March 2007, 183 patients with HBV-related hepatocellular carcinoma who underwent TACE but never received antiviral therapy were consecutively enrolled in our cohort. All patients were tested for pre-TACE serum level of HBV DNA, and overall survival was measured from date of enrollment until death from any cause. Radiologic progression was evaluated by using the modified response evaluation criteria in solid tumors by means of independent radiologic assessment. RESULTS The median overall survival was 19 months (95% confidence interval: 13.7, 24.3) and median time to progression was 4 months (95% confidence interval: 3.03, 4.97). Multivariate analysis revealed that a high pre-TACE serum level of HBV DNA (> 2000 IU/L) was an independent risk factor for reduced overall survival (P = .021; hazard ratio [HR], 1.725), high cancer progression-related mortality (P = .014; HR, 1.936), and hepatic failure-related mortality associated with cancer progression (P = .005, HR, 3.908). Pre-TACE level of HBV DNA did not significantly affect hepatic failure-related mortality that was not caused by cancer progression. CONCLUSION A high pre-TACE serum level of HBV DNA was associated with poor overall survival and rapid progression of hepatocellular carcinoma after TACE, and the cause of mortality was not hepatitis exacerbation but cancer progression.
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Affiliation(s)
- Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
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Chen L, Zhang Q, Chang W, Du Y, Zhang H, Cao G. Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma. Eur J Cancer 2012; 48:1977-87. [DOI: 10.1016/j.ejca.2012.01.015] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Revised: 01/08/2012] [Accepted: 01/16/2012] [Indexed: 02/06/2023]
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Yang T, Lu JH, Zhai J, Lin C, Yang GS, Zhao RH, Shen F, Wu MC. High viral load is associated with poor overall and recurrence-free survival of hepatitis B virus-related hepatocellular carcinoma after curative resection: a prospective cohort study. Eur J Surg Oncol 2012; 38:683-91. [PMID: 22621971 DOI: 10.1016/j.ejso.2012.04.010] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 04/02/2012] [Accepted: 04/29/2012] [Indexed: 12/12/2022] Open
Abstract
PURPOSE The aim of this prospective cohort study was to investigate the impact of preoperative hepatitis B viral load, as well as postoperative antiviral therapy, on the risk of long-term survival after curative resection of hepatitis B virus-related hepatocellular carcinoma (HCC). METHODS A prospective cohort of hepatitis B virus-related HCC patients undergoing curative resection from 2002 to 2008 was studied. According to preoperative viral load (using 10,000 copies/mL of hepatitis B virus DNA level as cut-off value), two groups were compared. Prognostic factors for overall survival and recurrence-free survival were evaluated. Additionally, subgroup analysis was conducted in patients with high viral load to investigate prediction of postoperative antiviral therapy on the long-term prognosis. RESULTS With a median follow-up of 49.1 months, patients with high viral load had lower median overall survival (78.3 months vs. 111.4 months, P<0.001) and RFS (44.6 months vs. 94.8 months, P<0.001) compared with those with low viral load. Multivariate analysis revealed that preoperative high viral load was an independent risk factor affecting both overall survival and recurrence-free survival (both P<0.001). The subgroup analysis revealed that postoperative antiviral therapy independently improved recurrence-free survival for patients with high viral load (P=0.001). CONCLUSIONS Hepatitis B virus-related HCC patients with preoperative high viral load led to poorer overall and recurrence-free survival than those with low viral load after curative resection. To prevent postoperative recurrence, antiviral therapy should be initiated in those patients with hepatitis B virus DNA ≥ 10,000 copies/ml.
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Affiliation(s)
- T Yang
- The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Yangpu District, Shanghai 200438, PR China
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Chakravarty R. Role of molecular diagnostics in the management of viral hepatitis B. ACTA ACUST UNITED AC 2012; 6:395-406. [PMID: 23480805 DOI: 10.1517/17530059.2012.690391] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Despite the availability of a safe and effective vaccine, chronic hepatitis B virus (HBV) infection continues to be a global health concern with an estimated 350 - 400 million people infected worldwide. Globally, HBV is the leading cause of chronic liver disease that may progress to cirrhosis and hepatocellular carcinoma. Therefore, accurate diagnosis and classification of the disease are important to determine whether therapy is needed. AREAS COVERED The review contains an overview of recent data on the existing and emerging developments in the molecular diagnostic and monitoring tools for chronic liver disease. EXPERT OPINION Monitoring of HBV viral load is the most widely used method in assessing liver disease severity, predicting development of cirrhosis and hepatocellular carcinoma, deciding initiation of antiviral therapy, assessing treatment response as well as early detection of emergence of drug resistance. Some recent studies have downplayed the importance of viral load in HBV management. Phenotyping/genotyping methods can establish emergent resistance to antivirals. Increasing number of reports suggest that clinical outcome and efficacy of antiviral treatment might vary with HBV genotype and precore/core promoter mutants. The importance of covalently closed circular DNA is also becoming apparent in this regard. Further studies on the development of newer molecular methods for a better management of chronic hepatitis B (CHB) will minimize morbidity in CHB.
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Affiliation(s)
- Runu Chakravarty
- ICMR Virus Unit , GB 4, 1st Floor, ID & BG Hospital Campus, 57, Dr. Suresh Chandra Banerjee Road, Kolkata 700010 , India +91 33 2353 7425 ; +91 33 2353 7424 ;
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Han YF, Zhao J, Ma LY, Yin JH, Chang WJ, Zhang HW, Cao GW. Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma. World J Gastroenterol 2011; 17:4258-70. [PMID: 22090781 PMCID: PMC3214700 DOI: 10.3748/wjg.v17.i38.4258] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2011] [Revised: 07/12/2011] [Accepted: 07/19/2011] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus (HBV) infection contributes to > 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged > 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8+ T cells and regulatory T cells or Th1 and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC.
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Yang M, Guo Z, Li BG. Risk factors for early recurrence after cryoablation for hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2011; 19:960-963. [DOI: 10.11569/wcjd.v19.i9.960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate risk factors for early recurrence after cryoablation for hepatocellular carcinoma (HCC).
METHODS: The clinical data for 90 HCC patients with recurrence after cryoablation were analyzed retrospectively. Risk factors associated with tumor early recurrence were assessed.
RESULTS: During a median follow-up of 21.9 mo ± 10.1 mo (range, 8 to 47 mo), early recurrences were observed in 57 out of 90 patients (63.4%) and late recurrences in 29 patients (32.2%). The median survival time was significant lower in the early recurrence group than in the late recurrence group (21 mo vs 36 mo, P < 0.05). Univariate analysis demonstrated that risk factors associated with early recurrence after cryoablation for HCC were preoperative serum α-fetoprotein (AFP) level >200 μg/L, hepatitis B virus (HBV) DNA level >5 log10 copies/mL, maximum tumor diameter >3 cm, and adjacency of the tumor to large blood vessels (diameter ≥6 mm). Multivariate analysis showed that preoperative HBV DNA level >5 log10 copies/mL, maximum tumor diameter >3 cm, and adjacency of the tumor to large blood vessels were independent risk factors for early recurrence after cryoablation for HCC (all P < 0.05).
CONCLUSION: Preoperative HBV DNA level >5 log10 copies/mL, maximum tumor diameter >3 cm and adjacency of the tumor to large blood vessels are independent risk factors for early recurrence after cryoablation for HCC.
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Yu LH, Li N, Cheng SQ. The Role of Antiviral Therapy for HBV-Related Hepatocellular Carcinoma. Int J Hepatol 2011; 2011:416459. [PMID: 21994855 PMCID: PMC3170809 DOI: 10.4061/2011/416459] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2010] [Revised: 03/15/2011] [Accepted: 04/08/2011] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer worldwide; despite the curative treatment for HCC, the rate of tumor recurrence after hepatectomy remains high. Tumor recurrence can occur early (<2 years) or late (>2 years) as metastases or de novo tumors. Several tumor factors were associated with HCC recurrence; high hepatitis B virus (HBV) load is the major risk factor for late recurrence of HCC after resection. Preoperative antiviral therapy improves liver function, and postoperative reduce HCC recurrence. In this paper, we focus on antiviral treatment to improve the liver function, prevent recurrence, and lengthen the overall survival for HBV-related HCC.
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Affiliation(s)
- Liang-He Yu
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China
| | - Nan Li
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China
| | - Shu-Qun Cheng
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China,Tumor Comprehensive Treatment Department, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai 200438, China,*Shu-Qun Cheng:
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Fung J, Lai CL, Yuen MF. Hepatitis B virus DNA and hepatitis B surface antigen levels in chronic hepatitis B. Expert Rev Anti Infect Ther 2010; 8:717-26. [PMID: 20521898 DOI: 10.1586/eri.10.45] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Despite universal vaccination, chronic hepatitis B (CHB) continues to be a major health burden worldwide, with an estimated 350-400 million people infected with the virus. Over the past decade, rapid progress has been made with regards to antiviral therapy for CHB, from conventional interferon to pegylated interferon, and with the earliest oral agent lamivudine to the current, more potent drugs such as entecavir and tenofovir. There have also been new developments in the diagnostic and monitoring tools for CHB. Qualitative hepatitis B surface antigen (HBsAg) testing has been used to diagnose patients infected with CHB. More recently, quantitative HBsAg titers have been used to predict treatment outcome when measured at baseline or early into treatment. The progress on the use of hepatitis B virus (HBV) DNA levels has been more rapid. Serum HBV DNA levels have been shown to be important in the natural history of CHB infection, with higher levels being significantly associated with the development of cirrhosis and hepatocellular carcinoma. For patients receiving antiviral therapy, the baseline and early on-treatment HBV DNA levels are important in determining treatment outcomes. Monitoring of HBV DNA levels during therapy will allow for early detection of drug resistance. The end-of-treatment and post-treatment HBV DNA levels have been demonstrated to be important indicators of treatment success and relapse, respectively. With newer and more powerful antiviral agents, and with the development of quantitative assays that are highly sensitive, further studies are needed to optimize the use of these tools and agents in the modern management of CHB.
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Affiliation(s)
- James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR.
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Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death, and chronic hepatitis B is a serious worldwide problem. The epidemiology of HCC is distinctive. Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis. Prevention of HBV-related HCC is a key issue in current hepatology. This paper describes the prevention and clinical features of HBV-related HCC, along with a short review of the disease.
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Song IH, Kim KS. Current status of liver diseases in Korea: hepatocellular carcinoma. THE KOREAN JOURNAL OF HEPATOLOGY 2010; 15 Suppl 6:S50-9. [PMID: 20037280 DOI: 10.3350/kjhep.2009.15.s6.s50] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. During the last two decades, the incidence rate of primary liver cancer has shown a modest decrease, but its mortality rate has slightly increased. The incidence of HCC, according to age, peaks in the late sixth decade in men and in the early seventh decade in women. Hepatitis B virus (HBV) is the most important risk factor, which represents approximately 70% of all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10 years earlier than HCV-associated HCC due to a more prolonged exposure to HBV, which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic area. National Cancer Control Institute, which was reorganized in 2005, is now working for several national projects such as National Cancer Registration Program, National R&D Program for Cancer Control and National Cancer Screening Program. International collaboration for the clinico-epidemiologic research would be needed to provide the specific measures for managing HCC in diverse etiologic situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular carcinogenesis might be clarified to provide insights into the advanced therapeutic and preventive approaches for HCC in Korea, where the majority of HCC originate from chronic HBV and HCV infections.
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Affiliation(s)
- Il Han Song
- Division of Hepatology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
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Chuma M, Hige S, Kamiyama T, Meguro T, Nagasaka A, Nakanishi K, Yamamoto Y, Nakanishi M, Kohara T, Sho T, Yamamoto K, Horimoto H, Kobayashi T, Yokoo H, Matsushita M, Todo S, Asaka M. The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma. J Gastroenterol 2009; 44:991-999. [PMID: 19554391 DOI: 10.1007/s00535-009-0093-z] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2009] [Accepted: 05/23/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Prediction and prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) recurrence is an important clinical issue. We investigated whether HBV DNA level and antiviral therapy are associated with HCC recurrence. METHODS This retrospective study involved 103 patients who underwent hepatic resection or radiofrequency ablation for initial HCC. Patients were divided into four groups. Thirty had high serum HBV DNA levels (>4 log(10) copies/mL) and had not received antiviral therapy (high virus group; HVG). Thirty-four had low HBV DNA levels (< or =4 log(10) copies/mL) and had not received antiviral therapy (low virus group; LVG). Twenty received antiviral therapy after HCC developed (therapeutic group A, TG-A). Nineteen received antiviral therapy before HCC developed (therapeutic group B, TG-B). RESULTS Cumulative HCC recurrence rates at 3 years in the HVG, LVG, TG-B, and TG-A were 71.1%, 42.2%, 42.3%, and 52.0%, respectively. Recurrence rates differed significantly between the HVG and LVG (P = 0.016) and between the HVG and TG-B (P = 0.008). Recurrence rate in the TG-A was marginally lower than in the HVG (P = 0.10). On multivariate analysis, high serum hepatitis B virus DNA levels (hazard ratio: HR 2.67; 95% CI 1.31-5.47; P = 0.007) and absence of antiviral therapy (HR 2.57; 95% CI 1.34-4.94; P = 0.005) were independent risk factors for hepatocellular carcinoma recurrence. CONCLUSION HBV DNA level and antiviral therapy are associated with HCC recurrence. For patients with high HBV DNA levels, antiviral therapy before the development of HCC is important for prevention of recurrence.
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Affiliation(s)
- Makoto Chuma
- Department of Gastroenterology and Hematology, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.
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Abstract
Serum hepatitis B virus (HBV) DNA levels can fluctuate markedly during the course of chronic HBV infection. Both case-control and cohort studies have shown a significant, dose-response association between serum HBV DNA levels measured at the time of initial evaluation and the subsequent risk of cirrhosis. A similar direct relationship has been shown for the risk of hepatocellular carcinoma (HCC) in cross-sectional, case-control, and cohort studies. Interventional studies have shown a strong correlation between the indices of disease activity seen on liver biopsy and levels of serum HBV DNA. These studies have also shown that reduction in HBV DNA levels correlate strongly with improvements in liver histology. For patients with HCC, prognosis (including risk of death, metastasis, and recurrence following surgery) is worse with higher serum HBV DNA levels. The preponderance of the evidence in the published literature demonstrates that serum HBV DNA level is an important and independent risk factor for disease progression in chronic hepatitis B. The relative importance of serial HBV DNA measurements, the loss of hepatitis B e and surface antigens, as well as the emergence of HBV mutants in the progression of chronic hepatitis B, especially in young patients, is an important need for future research.
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Affiliation(s)
- Chien-Jen Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan.
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Ji SK, Cho YK, Ahn YS, Kim MY, Park YO, Kim JK, Kim WT. Multivariate analysis of the predictors of survival for patients with hepatocellular carcinoma undergoing transarterial chemoembolization: focusing on superselective chemoembolization. Korean J Radiol 2009; 9:534-40. [PMID: 19039270 PMCID: PMC2627241 DOI: 10.3348/kjr.2008.9.6.534] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Objective While the prognostic factors of survival for patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) are well known, the clinical significance of performing selective TACE for HCC patients has not been clearly documented. We tried to analyze the potential factors of disease-free survival for these patients, including the performance of selective TACE. Materials and Methods A total of 151 patients with HCC who underwent TACE were retrospectively analyzed for their disease-free survival (a median follow-up of 23 months, range: 1-88 months). Univariate and multivariate analyses were performed for 20 potential factors by using the Cox proportional hazard model, including 19 baseline factors and one procedure-related factor (conventional versus selective TACE). The parameters that proved to be significant on the univariate analysis were subsequently tested with the multivariate model. Results Conventional or selective TACE was performed for 40 and 111 patients, respectively. Univariate and multivariate analyses revealed that tumor multiplicity, venous tumor thrombosis and selective TACE were the only three independent significant prognostic factors of disease-free survival (p = 0.002, 0.015 and 0.019, respectively). Conclusion In our study, selective TACE was a favorable prognostic factor for the disease-free survival of patients with HCC who underwent TACE.
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Affiliation(s)
- Suk Kyeong Ji
- Department of Radiology, Seoul Veterans Hospital, Seoul, Korea
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Abstract
PURPOSE OF REVIEW This review primarily focuses on new developments in the field of hepatocellular carcinoma. RECENT FINDINGS Potential preventive strategies in the development of hepatocellular carcinoma are being recognized. Novel molecular markers identified may aid in the diagnosis of early hepatocellular carcinoma in patients with chronic hepatitis C virus. Prognostic information gained by preoperative tumor biopsy is being investigated. Treatment of early hepatocellular carcinoma with resection versus primary or salvage transplantation continues to be debated. Expansion of selection criteria beyond the Milan criteria appears feasible. The role of living donor liver transplantation in hepatocellular carcinoma will require further study to determine the risk of recurrence. Improvements in chemoembolization with drug eluting beads appear promising. SUMMARY Further insight into the pathogenesis of hepatocellular carcinoma will result in the continued evolution of our approach and management of the disease. Tailored therapies based on tumor biology are needed to improve treatment response and ultimately patient survival.
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