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Cheo FY, Chan KS, Shelat VG. Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis. World J Virol 2024; 13:88946. [PMID: 38616852 PMCID: PMC11008402 DOI: 10.5501/wjv.v13.i1.88946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/10/2023] [Accepted: 12/28/2023] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). AIM To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. RESULTS Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. CONCLUSION This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.
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Affiliation(s)
- Feng Yi Cheo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Kai Siang Chan
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Gao X, Zuo S. Immune landscape and immunotherapy of hepatocellular carcinoma: focus on innate and adaptive immune cells. Clin Exp Med 2023; 23:1881-1899. [PMID: 36773210 PMCID: PMC10543580 DOI: 10.1007/s10238-023-01015-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 01/27/2023] [Indexed: 02/12/2023]
Abstract
Hepatocellular carcinoma (HCC) is responsible for roughly 90% of all cases of primary liver cancer, and the cases are on the rise. The treatment of advanced HCC is a serious challenge. Immune checkpoint inhibitor (ICI) therapy has marked a watershed moment in the history of HCC systemic treatment. Atezolizumab in combination with bevacizumab has been approved as a first-line treatment for advanced HCC since 2020; however, the combination therapy is only effective in a limited percentage of patients. Considering that the tumor immune microenvironment (TIME) has a great impact on immunotherapies for HCC, an in-depth understanding of the immune landscape in tumors and the current immunotherapeutic approaches is extremely necessary. We elaborate on the features, functions, and cross talk of the innate and adaptive immune cells in HCC and highlight the benefits and drawbacks of various immunotherapies for advanced HCC, as well as future projections. HCC consists of a heterogeneous group of cancers with distinct etiologies and immune microenvironments. Almost all the components of innate and adaptive immune cells in HCC have altered, showing a decreasing trend in the number of tumor suppressor cells and an increasing trend in the pro-cancer cells, and there is also cross talk between various cell types. Various immunotherapies for HCC have also shown promising efficacy and application prospect. There are multilayered interwoven webs among various immune cell types in HCC, and emerging evidence demonstrates the promising prospect of immunotherapeutic approaches for HCC.
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Affiliation(s)
- Xiaoqiang Gao
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Guiyang, 550000, Guizhou, China
- Guizhou Medical University, Guiyang, Guizhou, China
| | - Shi Zuo
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Guiyang, 550000, Guizhou, China.
- Guizhou Medical University, Guiyang, Guizhou, China.
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Hsu PY, Liang PC, Huang CI, Hsieh MH, Tsai YS, Lin TC, Yeh ML, Huang CF, Wang CW, Jang TY, Lin YH, Lin ZY, Chuang WL, Dai CY. Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR. Viruses 2022; 14:2412. [PMID: 36366510 PMCID: PMC9693099 DOI: 10.3390/v14112412] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/27/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR.
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Affiliation(s)
- Po-Yao Hsu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- College of Medicine, National Sun Yat-sen University, Kaohsiung 807, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tzu-Chun Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chih-Wen Wang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Tyng-Yuan Jang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912, Taiwan
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Takaura K, Kurosaki M, Inada K, Kirino S, Yamashita K, Muto T, Osawa L, Sekiguchi S, Hayakawa Y, Higuchi M, Kaneko S, Maeyashiki C, Tamaki N, Yasui Y, Itakura J, Tsuchiya K, Nakanishi H, Takahashi Y, Izumi N. The impact of background liver disease on the long-term prognosis of very-early-stage HCC after ablation therapy. PLoS One 2022; 17:e0264075. [PMID: 35196341 PMCID: PMC8865683 DOI: 10.1371/journal.pone.0264075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 02/02/2022] [Indexed: 12/24/2022] Open
Abstract
Background and aim The long-term prognosis of hepatocellular carcinoma (HCC) treated at a very-early-stage (the Barcelona Clinical Liver Cancer (BCLC) classification stage 0) was unclear, especially in terms of background liver disease. Methods This single-center, retrospective study included 302 patients with BCLC stage 0 HCC treated with radiofrequency ablation (RFA) and followed for at least six months. We examined the impact of background liver disease on overall survival and recurrence. Results The median age was 72 (range; 36–91) years; the median tumor diameter was 15 (range; 8–20) mm. The etiologies of background liver disease were hepatitis B virus infection (HBV) in 24 cases, hepatitis C virus infection (HCV) in 195 cases, and non-viral (NBNC) in 83 cases. Among the patients with HCV, 63 had achieved sustained virological response (SVR) by antiviral therapy (HCV SVR) before developing HCC (n = 37) or after HCC treatment (n = 26), and 132 had active HCV infection (HCV non-SVR). The median overall survival was 85 (95% CI; 72–98) months, and the median recurrence-free survival was 26 (95% CI; 20–30) months. Active infection with hepatitis C virus negatively contributed to overall survival (HR 2.91, 95% CI 1.31–3.60, p = 0.003) and recurrence-free survival (HR 1.47, 95% CI 1.06–2.05, p = 0.011). Conclusions The prognosis of RFA treatment for very early-stage HCC was favorable. Achieving SVR in hepatitis C was important for further prognosis improvement.
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Affiliation(s)
- Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Sakura Kirino
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kouji Yamashita
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tomohiro Muto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Leona Osawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shuhei Sekiguchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Hayakawa
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shun Kaneko
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- Division of Medicine, NAFLD Research Center, University of California, San Diego, La Jolla, California, United States of America
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
- * E-mail:
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Lu L, Zhuang Z, Fan M, Liu B, Yang Y, Huang J, Da X, Mo J, Li Q, Lu H. Green formulation of Ag nanoparticles by Hibiscus rosa-sinensis: Introducing a navel chemotherapeutic drug for the treatment of liver cancer. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2021.103602] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Kaibori M, Yoshii K, Kashiwabara K, Kokudo T, Hasegawa K, Izumi N, Murakami T, Kudo M, Shiina S, Sakamoto M, Nakashima O, Matsuyama Y, Eguchi S, Yamashita T, Takayama T, Kokudo N, Kubo S. Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey. Hepatol Res 2021; 51:890-901. [PMID: 34041804 DOI: 10.1111/hepr.13676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/13/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
AIM We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.
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Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Kansai Medical University, Osaka, Japan
| | - Kengo Yoshii
- Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kosuke Kashiwabara
- Biostatistics Division, Clinical Research Support Center, Central Coordinating Unit, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takamichi Murakami
- Department of Diagnostic and Interventional Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Yutaka Matsuyama
- Department of Biostatics, School of Public Health University of Tokyo, Tokyo, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuya Yamashita
- Advanced Preventive Medical Research Center, Kanazawa University, Kanazawa, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Esagian SM, Kakos CD, Giorgakis E, Burdine L, Barreto JC, Mavros MN. Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers (Basel) 2021; 13:2984. [PMID: 34203692 PMCID: PMC8232114 DOI: 10.3390/cancers13122984] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/07/2021] [Accepted: 06/09/2021] [Indexed: 02/07/2023] Open
Abstract
The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.
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Affiliation(s)
- Stepan M. Esagian
- Oncology Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Christos D. Kakos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Lyle Burdine
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - J. Camilo Barreto
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Michail N. Mavros
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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10
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Wang CC, Tseng KC, Tzeng IS, Kao JH. The impact of cytokine change after hepatitis C virus clearance by direct antiviral agents on the risk of hepatocellular carcinoma. J Formos Med Assoc 2021; 120:965-973. [PMID: 33129621 DOI: 10.1016/j.jfma.2020.10.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/30/2020] [Accepted: 10/16/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/PURPOSE De novo and early recurrent hepatocellular carcinoma (HCC) have been observed in clinical practice after direct antiviral agents (DAA) treatment. The study aims to investigate the change of cytokines and growth factors after hepatitis C virus (HCV) clearance by DAAs and their impact on the risk of HCC development. METHODS The chronic hepatitis C (CHC) patients with or without HCC who received DAA treatment were prospectively enrolled. The cytokines and growth factors were measured using Bio-Plex Pro™ Human Cytokine 27-plex Assay before and 12 weeks off DAA treatment. RESULTS A total of 37 patients were enrolled for final analysis. There were 11 males (29.7%) and 26 females (70.3%). The mean age was 67.39 ± 10.48 years. 11 (29.7%) patients were HCV-related HCC patients. The HCV genotype included genotype 2 in 26 patients and genotype 1b in 10 patients, and genotype 6 in 1. Among them, 35 (94.6%) patients achieved sustained virologic response (SVR). Two patients with HCC failed to DAA treatment. In HCV-related HCC patients, serum IP-10 level significantly declined after HCV clearance, but no difference in five growth factors including G-CSF, GM-CSF, basic FGF, PDGF-BB, and VEGF. Several cytokines including IP-10 significantly declined after HCV clearance in CHC patients. CONCLUSION This study showed only serum IP-10 level, a risk factor of HCC, was significantly declined after HCV clearance and no change in the markers of growth factors in HCV-related HCC patients, suggesting no promotion of HCC using DAA treatment for HCV-related HCC patients.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Da-Lin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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11
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Sarno G, Montalti R, Giglio MC, Rompianesi G, Tomassini F, Scarpellini E, De Simone G, De Palma GD, Troisi RI. Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment. Surg Oncol 2021; 36:42-50. [PMID: 33307490 DOI: 10.1016/j.suronc.2020.11.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 11/15/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.
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Affiliation(s)
- Gerardo Sarno
- General Surgery and Transplantation Unit - "San Giovanni di Dio e Ruggi D'Aragona" -University Hospital, Scuola Medica Salernitana, Salerno, Italy.
| | - Roberto Montalti
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy
| | - Mariano Cesare Giglio
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy
| | | | - Federico Tomassini
- Department of Human Structure and Repair, Ghent University Faculty of Medicine, Belgium
| | - Emidio Scarpellini
- Internal Medicine Unit, San Benedetto General Hospital, San Benedetto Del Tronto, Italy
| | - Giuseppe De Simone
- Department of Anesthesiology, Federico II University of Naples, Naples, Italy
| | - Giovanni Domenico De Palma
- Department of Clinical Medicine and Surgery, Interuniversity Center for Technological Innovation Interdepartmental Center for Robotic Surgery, Federico II University Naples, Italy
| | - Roberto Ivan Troisi
- Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Naples, Italy; Oxford University Hospitals NHS Foundation Trust, UK; Department of Human Structure and Repair, Ghent University Faculty of Medicine, Belgium
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12
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Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma. Molecules 2021; 26:molecules26020295. [PMID: 33435572 PMCID: PMC7827668 DOI: 10.3390/molecules26020295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 01/06/2021] [Accepted: 01/06/2021] [Indexed: 01/01/2023] Open
Abstract
The high rates of hepatocellular carcinoma (HCC) recurrence after initially successful curative therapy emphasize ongoing unmet needs to prevent or reduce HCC recurrence. Retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development. Here we present an updated summary of the molecular pathogenesis of HCC and of preclinical and clinical findings with peretinoin, including its clinical characteristics, safety and tolerability profile and future perspectives for clinical use.
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13
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Abstract
Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population starting from birth dose, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective, the cancer preventive efficacy support it as the first successful example of cancer preventive vaccine in human. Addition of hepatitis B immunoglobulin immediately after birth and antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are existing or possible emerging strategies to enhance the prevention efficacy of HBV infection and its related liver cancer. Secondary prevention with current antiviral agents may reduce the risk or delay the onset of HCC development, but could not eradicate HBV infection and HCC. Better antiviral therapeutic agents are needed for better secondary prevention.
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Affiliation(s)
- Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
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14
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Joko K, Mashiba T, Ochi H, Yano R, Sato K, Okujima Y, Aono M, Azemoto N, Takechi S, Yokota T, Jinoka R, Moriyama Y, Nishiyama M. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepatogastroenterol 2020; 9:78-83. [PMID: 32117695 PMCID: PMC7047307 DOI: 10.5005/jp-journals-10018-1305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. How to cite this article Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78–83.
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Affiliation(s)
- Kouji Joko
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan; Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Toshie Mashiba
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Hironori Ochi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryo Yano
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Kaori Sato
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yusuke Okujima
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Michiko Aono
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Nobuaki Azemoto
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Shunji Takechi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Tomoyuki Yokota
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryosuke Jinoka
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yasunori Moriyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Masataka Nishiyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
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15
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [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: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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16
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Singal AG, Rich NE, Mehta N, Branch AD, Pillai A, Hoteit M, Volk M, Odewole M, Scaglione S, Guy J, Said A, Feld JJ, John BV, Frenette C, Mantry P, Rangnekar AS, Oloruntoba O, Leise M, Jou JH, Bhamidimarri KR, Kulik L, Ioannou GN, Huang A, Tran T, Samant H, Dhanasekaran R, Duarte-Rojo A, Salgia R, Eswaran S, Jalal P, Flores A, Satapathy SK, Kagan S, Gopal P, Wong R, Parikh ND, Murphy CC. Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma. Gastroenterology 2019; 157:1253-1263.e2. [PMID: 31374215 PMCID: PMC6815711 DOI: 10.1053/j.gastro.2019.07.040] [Citation(s) in RCA: 153] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 06/24/2019] [Accepted: 07/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.
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Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas.
| | - Nicole E Rich
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas
| | - Neil Mehta
- Division of Gastroenterology, University of California San Francisco, San Francisco, California
| | - Andrea D Branch
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, Illinois
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael Volk
- Transplantation Institute and Division of Gastroenterology, Loma Linda University Health, Loma Linda, California
| | - Mobolaji Odewole
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas
| | - Steven Scaglione
- Division of Hepatology, Loyola University Medical Center and Edward Hines Veterans Affairs, Hines, Illinois
| | - Jennifer Guy
- Department of Transplantation, California Pacific Medical Center, San Francisco, California
| | - Adnan Said
- Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine, Madison, Wisconsin
| | - Jordan J Feld
- Toronto Center for Liver Disease, Toronto General Hospital, Toronto, Ontario, Canada
| | - Binu V John
- Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia
| | - Catherine Frenette
- Division of Organ Transplantation, Scripps Green Hospital, San Diego, California
| | | | - Amol S Rangnekar
- Division of Gastroenterology, Georgetown University Hospital, Washington, District of Columbia
| | - Omobonike Oloruntoba
- Division of Gastroenterology and Hepatology, Duke University Health Center, Durham, North Carolina
| | - Michael Leise
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Janice H Jou
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon
| | | | - Laura Kulik
- Division of Hepatology, Northwestern University, Chicago, Illinois
| | - George N Ioannou
- Division of Gastroenterology and Research and Development, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington
| | - Annsa Huang
- Division of Gastroenterology, University of California San Francisco, San Francisco, California
| | - Tram Tran
- Liver Disease and Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Hrishikesh Samant
- Division of Gastroenterology and Hepatology, Louisiana State University Health Sciences Center, New Orleans, Louisiana
| | | | - Andres Duarte-Rojo
- Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Reena Salgia
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan
| | - Sheila Eswaran
- Division of Gastroenterology, Rush Medical College, Chicago, Illinois
| | - Prasun Jalal
- Division of Abdominal Transplantation, Baylor College of Medicine, Houston, Texas
| | - Avegail Flores
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri
| | - Sanjaya K Satapathy
- Division of Hepatology, Donald and Barbara Zucker School of Medicine, Northshore University Hospital, Northwell Health, Manhasset, New York
| | - Sofia Kagan
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas
| | - Purva Gopal
- Department of Pathology, UT Southwestern Medical Center, Dallas, Texas
| | - Robert Wong
- Division of Gastroenterology and Hepatology, Alameda Health System, Oakland, California
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Caitlin C Murphy
- Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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18
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de Jesus VHF, Felismino TC, de Barros e Silva MJ, de Souza e Silva V, Riechelmann RP. Current approaches to immunotherapy in noncolorectal gastrointestinal malignancies. Clinics (Sao Paulo) 2018; 73:e510s. [PMID: 30365605 PMCID: PMC6173942 DOI: 10.6061/clinics/2018/e510s] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 07/02/2018] [Indexed: 11/24/2022] Open
Abstract
Noncolorectal gastrointestinal (GI) malignancies are among the most frequently diagnosed cancers. Despite the undeniable progress in systemic treatments in recent decades, further improvements using cytotoxic chemotherapy seem unlikely. In this setting, recent discoveries regarding the mechanism underlying immune evasion have prompted the study of molecules capable of inducing strong antitumor responses. Thus, according to early data, immunotherapy is a very promising tool for the treatment of patients with GI malignancies. Noncolorectal GI cancers are a major public health problem worldwide. Traditional treatment options, such as chemotherapy, surgery, radiation therapy, monoclonal antibodies and antiangiogenic agents, have been the backbone of treatment for various stages of GI cancers, but overall mortality remains a major problem. Thus, there is a substantial unmet need for new drugs and therapies to further improve the outcomes of treatment for noncolorectal GI malignancies. "Next-generation" immunotherapy is emerging as an effective and promising treatment option in several types of cancers. Therefore, encouraged by this recent success, many clinical trials evaluating the efficacy of immune checkpoint inhibitors and other strategies in treating noncolorectal GI malignancies are ongoing. This review will summarize the current clinical progress of modern immunotherapy in the field of noncolorectal GI tumors.
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Affiliation(s)
| | | | | | | | - Rachel P Riechelmann
- Departamento de Oncologia Médica, A.C. Camargo Cancer Center, Sao Paulo, SP, BR
- Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR
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19
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Wen T, Jin C, Facciorusso A, Donadon M, Han HS, Mao Y, Dai C, Cheng S, Zhang B, Peng B, Du S, Jia C, Xu F, Shi J, Sun J, Zhu P, Nara S, Millis JM. Multidisciplinary management of recurrent and metastatic hepatocellular carcinoma after resection: an international expert consensus. Hepatobiliary Surg Nutr 2018; 7:353-371. [PMID: 30498711 DOI: 10.21037/hbsn.2018.08.01] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40-70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients' prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.
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Affiliation(s)
- Tianfu Wen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chen Jin
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Antonio Facciorusso
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Matteo Donadon
- Department of Hepatobiliary & General Surgery, Humanitas University, Humanitas Clinical and Research Center, Milan, Italy
| | - Ho-Seong Han
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Baogang Peng
- Department of Liver Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Changjun Jia
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110000, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Juxian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200433, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Satoshi Nara
- Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan
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Tong MJ, Theodoro CF, Salvo RT. Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance. J Dig Dis 2018; 19:411-420. [PMID: 29889353 DOI: 10.1111/1751-2980.12615] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/25/2018] [Accepted: 06/07/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies. METHODS We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years. RESULTS Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04). CONCLUSIONS The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.
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Affiliation(s)
- Myron J Tong
- Liver Center, Huntington Medical Research Institutes, Pasadena, California, USA.,Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | | | - Rebecca T Salvo
- Liver Center, Huntington Medical Research Institutes, Pasadena, California, USA
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Ding H, Liu J, Liu B, Zeng Y, Chen P, Su Y. Long noncoding RNA PVT1 inhibits interferon-α mediated therapy for hepatocellular carcinoma cells by interacting with signal transducer and activator of transcription 1. Biochem Biophys Res Commun 2018; 500:973-980. [PMID: 29715456 DOI: 10.1016/j.bbrc.2018.04.219] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/27/2018] [Indexed: 02/07/2023]
Abstract
Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC) and hsigh expression of oncogenic PVT1 is associated with poor prognosis of HCC. Interferon-α (IFN-α) has been used in clinic for HCC therapy. However, whether PVT1 is involved in the IFN-α therapy for HCC is completely unknown. Our study found that high PVT1 expression in HCC cells is associated with high unmethylation in PVT1 promoter region. IFN-α treatment further increases PVT1 expression in HCC cells by enhancing H3K4me3 modification on the promoter. Furthermore, PVT1 knockdown enhances IFN-α-induced HCC cell apoptosis by promoting phosphorylation of signal transducer and activator of transcription 1 (STAT1) and upregulating IFN-stimulated genes expression. Moreover, PVT1 specifically interacts with STAT1 in HCC cells. Taken together, these results for the first time indicate that IFN-α treatment promotes oncogenic PVT1 expression in HCC cells, which interacts with STAT1 to inhibit IFN-α signaling, ultimately blocking IFN-α-induced cells apoptosis, suggesting that lncRNA PVT1 may be a potential target to improve IFN-α-mediated HCC immunotherapies.
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Affiliation(s)
- Hongda Ding
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China
| | - Junpeng Liu
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China
| | - Baiming Liu
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China
| | - Yongchao Zeng
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China
| | - Pengrui Chen
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China
| | - Yang Su
- Department of the Fifth General Surgery, ShengJing Hospital of China Medical University, No. 36 Sanhao Road, Shenyang, 110004, China.
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22
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Mashiba T, Joko K, Kurosaki M, Ochi H, Osaki Y, Kojima Y, Nakata R, Goto T, Takehiro A, Kimura H, Mitsuda A, Kawanami C, Uchida Y, Ogawa C, Kusakabe A, Narita R, Ide Y, Abe T, Tsuji K, Kitamura T, Okada K, Sohda T, Shigeno M, Satou T, Izumi N. Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group. PLoS One 2018; 13:e0194704. [PMID: 29659591 PMCID: PMC5901785 DOI: 10.1371/journal.pone.0194704] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 03/07/2018] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIM This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. METHODS This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. RESULTS AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. CONCLUSIONS There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.
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Affiliation(s)
- Toshie Mashiba
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Ehime, Japan
- * E-mail:
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yukio Osaki
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Mie, Japan
| | - Ryo Nakata
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Tohru Goto
- Department of Gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
| | - Akahane Takehiro
- Department of Gastroenterology, Ishinomaki Red Cross Hospital, Miyagi, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | - Chiharu Kawanami
- Department of Gastroenterology, Otsu Red Cross Hospital, Shiga, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Matsue Red Cross Hospital, Shimane, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Aichi, Japan
| | - Ryuichi Narita
- Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | - Takehiko Abe
- Department of Gastroenterology, Maebashi Red Cross Hospital, Gunma, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Tadashi Kitamura
- Department of Gastroenterology, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan
| | - Kazuhiko Okada
- Department of Gastroenterology, Toyama Red Cross Hospital, Toyama, Japan
| | - Tetsuro Sohda
- Hepatology Division, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Takashi Satou
- Department of Gastroenterology, Nasu Red Cross Hospital, Tochigi, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Sasaki K, Shindoh J, Nishioka Y, Sugawara T, Margonis GA, Andreatos N, Pawlik TM, Hashimoto M. Postoperative low hepatitis C virus load predicts long-term outcomes after hepatectomy for hepatocellular carcinoma. J Surg Oncol 2018; 117:902-911. [PMID: 29473962 DOI: 10.1002/jso.25015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 01/12/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Preoperative hepatitis C virus (HCV) viral load is known to predict long-term outcomes after hepatectomy for HCV-related hepatocellular carcinoma (HCC). This study sought to examine the hypothesis that postoperative and preoperative HCV viral-load have similar prognostic implications, as well as determine a target viral-load that will improve long-term postoperative outcomes. METHOD One hundred and eighty-one patients who underwent curative hepatectomy for HCV-related HCC were divided into five groups according to time-weighted average viral load. The cumulative-recurrence curves of the five groups were compared to identify prognostic trends. The optimal cut-off viral load value related to recurrence was also investigated. RESULTS The five cumulative-recurrence curves were separated into two clusters according to viral load. Patients with a negative viral load had comparable recurrence curves to patients with the lowest viral-load (P = 0.907); both of these patient groups had more favorable outcomes than patients with a viral load categorized in the other groups (all P < 0.050). The optimal cut-off based on maximum HR method (> or ≤4.0 log10 IU/mL) was a strong prognostic indicator of recurrence in multivariate analysis (HR 3.09; 95%CI 1.96-5.04; P < 0.001). CONCLUSION Postoperative HCV viral load correlated with long-term surgical outcomes. A low viral load (≤4.0 log10 IU/mL) independently predicted better long-term outcomes.
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Affiliation(s)
- Kazunari Sasaki
- Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland
| | - Junichi Shindoh
- Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
| | - Yujiro Nishioka
- Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
| | - Toshitaka Sugawara
- Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
| | | | | | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland
| | - Masaji Hashimoto
- Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan
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Management consensus guideline for hepatocellular carcinoma: 2016 updated by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. J Formos Med Assoc 2017; 117:381-403. [PMID: 29074347 DOI: 10.1016/j.jfma.2017.09.007] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/16/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan produced the management consensus guideline for HCC. METHODS The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention. RESULTS The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation. CONCLUSION With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality.
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25
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Huang Y, Li MH, Hou M, Xie Y. Peginterferon alfa-2a for the treatment of chronic hepatitis C in the era of direct-acting antivirals. Hepatobiliary Pancreat Dis Int 2017; 16:470-479. [PMID: 28992878 DOI: 10.1016/s1499-3872(17)60044-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 06/23/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND The availability of novel direct-acting antivirals (DAAs) represents a new era of curative hepatitis C virus (HCV) treatment, with over 95% of patients infected with HCV genotype 1 achieving sustained virological response (SVR). Nevertheless, the majority of patients globally are unable to access these treatments because of cost and infrastructure constraints and, thus, remain untreated and uncured. DATA SOURCE Relevant articles of peginterferon (PegIFN)-based treatments in HCV and sofosbuvir-based treatments, simeprevir, daclatasvir/asunaprevir, ritonavir-boosted paritaprevir/ombitasvir/dasabuvir, and grazoprevir/elbasvir, were searched in PubMed database, including general population and special population. RESULTS PegIFN in combination with ribavirin remains an important and relevant option for some patients, achieving SVR rates of up to 79% in genotype 1 and 89% in genotype 2 or 3 infections, which increases for patients with favorable IL28B genotypes. Triple therapy of DAA plus PegIFN/ribavirin is effective in treating difficult-to-cure patients infected with HCV genotype 3 or with resistance-associated variants. Owing to its long history in HCV management, the efficacy, tolerability and long-term outcomes associated with PegIFN alfa-2a are well established and have been validated in large-scale studies and in clinical practice for many populations. Furthermore, emerging data show that IFN-induced SVR is associated with lower incidences of hepatocellular carcinoma compared with DAAs. On the contrary, novel DAAs have yet to be studied in special populations, and long-term outcomes, particularly tumor development and recurrence in patients with cirrhosis and/or hepatocellular carcinoma, and reactivation of HBV in dually infected patients, are still unclear. CONCLUSION In this interferon-free era, PegIFN-based regimens remain a safe and effective option for selected HCV patients.
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Affiliation(s)
- Yan Huang
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Ming-Hui Li
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Min Hou
- Shanghai Roche Pharmaceuticals Ltd., Shanghai 201203, Beijing, China
| | - Yao Xie
- Liver Disease Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
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Sim HW, Knox J, Dawson LA. An Update on Randomized Clinical Trials in Hepatocellular Carcinoma. Surg Oncol Clin N Am 2017; 26:647-666. [PMID: 28923223 DOI: 10.1016/j.soc.2017.05.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is a common malignancy that typically occurs in the setting of comorbid liver disease. Optimal management is challenging, especially given the assortment of available treatment modalities. This article reviews the randomized clinical trials that have formed the basis of contemporary hepatocellular carcinoma management.
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Affiliation(s)
- Hao-Wen Sim
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
| | - Jennifer Knox
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
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27
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Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo. Toxicol Appl Pharmacol 2017; 332:64-74. [PMID: 28755860 DOI: 10.1016/j.taap.2017.07.019] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 07/22/2017] [Accepted: 07/25/2017] [Indexed: 12/14/2022]
Abstract
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration.
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28
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Yang Y, Zhou Y, Hou J, Bai C, Li Z, Fan J, Ng IOL, Zhou W, Sun H, Dong Q, Lee JMF, Lo CM, Man K, Yang Y, Li N, Ding G, Yu Y, Cao X. Hepatic IFIT3 predicts interferon-α therapeutic response in patients of hepatocellular carcinoma. Hepatology 2017; 66:152-166. [PMID: 28295457 DOI: 10.1002/hep.29156] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 02/14/2017] [Accepted: 03/09/2017] [Indexed: 12/27/2022]
Abstract
UNLABELLED Adjuvant interferon-α (IFN-α) therapy is used to control certain types of cancer in clinics. For hepatocellular carcinoma (HCC), IFN-α therapy is effective in only a subgroup of patients; therefore, identifying biomarkers to predict the response to IFN-α therapy is of high significance and clinical utility. As the induced IFN-stimulated gene expression following IFN-α treatment plays pivotal roles in IFN-α effects, we screened IFN-stimulated gene expression in HCC tissues and found that several IFN-stimulated genes were significantly decreased in HCC. Interestingly, expression of IFN-induced protein with tetratricopeptide repeats (IFIT) family members, including IFIT1, IFIT2, IFIT3, and IFIT5, was decreased in HCC tissues. We further analyzed the expression of IFIT family members in HCC and their roles in patients' responses to IFN-α therapy in two independent randomized controlled IFN-α therapy clinical trials of HCC patients. We found that higher expression of IFIT3, but not other IFITs, in HCC tissues predicts better response to IFN-α therapy, suggesting that IFIT3 may be a useful predictor of the response to IFN-α therapy in HCC patients. Mechanistically, IFIT3 enhanced the antitumor effects of IFN-α by promoting IFN-α effector responses both in vitro and in vivo. IFIT3 could bind signal transducer and activator of transcription 1 (STAT1) and STAT2 to enhance STAT1-STAT2 heterodimerization and nuclear translocation upon IFN-α treatment, thus promoting IFN-α effector signaling. CONCLUSION Higher IFIT3 expression in HCC tissues predicts better response to IFN-α therapy in HCC patients; IFIT3 promotes IFN-α effector responses and therapeutic effects by strengthening IFN-α effector signaling in HCC. (Hepatology 2017;66:152-166).
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Affiliation(s)
- Yingyun Yang
- Department of Oncology, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
- Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Ye Zhou
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
| | - Jin Hou
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
| | - Chunmei Bai
- Department of Oncology, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhenyang Li
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
| | - Jia Fan
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, China
| | - Irene O L Ng
- Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Weiping Zhou
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, China
| | - Qiongzhu Dong
- Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai, China
| | - Joyce M F Lee
- Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Chung-Mau Lo
- Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Kwan Man
- Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong, China
| | - Yun Yang
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Nan Li
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
| | - Guoshan Ding
- Department of Organ Transplantation, Shanghai Changzheng Hospital, Shanghai, China
| | - Yizhi Yu
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
| | - Xuetao Cao
- Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China
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Kim KA. [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 67:123-6. [PMID: 26996180 DOI: 10.4166/kjg.2016.67.3.123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment.
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Affiliation(s)
- Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
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30
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Keshvari M, Alavian SM, Behnava B, Pouryasin A, Craig JC, Sharafi H. Impact of IFNL4 rs12979860 and rs8099917 polymorphisms on response to Peg-Interferon-α and Ribavirin in patients with congenital bleeding disorder and chronic hepatitis C. J Clin Lab Anal 2016; 31. [PMID: 27735085 DOI: 10.1002/jcla.22063] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 08/16/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). METHODS This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV). Baseline patient and viral parameters were measured and analyzed statistically to assess their combined and individual contributions to SVR prediction. RESULTS The most prevalent variants of rs12979860 and rs8099917 identified among the study patients were CT (45.9%) and TT (57.6%), respectively. Overall, SVR was achieved in 69% of the study patients. The rate of SVR was lower in patients with HCV genotype-1 than in those with HCV genotype-3 (62% vs 88%; P<.001; OR=0.23). Multivariate analysis of SVR predictors in patients with HCV genotype-1 infection included age (<24 years), BMI (<25), absence of cirrhosis, HCV RNA level (<400 000 IU/mL), rs8099917 TT and rs12979860 CC, all of which were associated with a higher SVR rate. In HCV genotype-3 infection, only rs12979860 CC was significantly associated with SVR. CONCLUSION These results demonstrate that polymorphisms of the IFNL4 gene are highly associated with SVR to PegIFN and RBV combination therapy in patients with a congenital bleeding disorder and CHC. Assessment of rs12979860 and rs8099917 genotypes can guide physicians in choosing an optimal treatment regimen, including less expensive therapies that may only be available in many geographic locales.
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Affiliation(s)
- Maryam Keshvari
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Middle East Liver Diseases (MELD) Center, Tehran, Iran
| | - Bita Behnava
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Middle East Liver Diseases (MELD) Center, Tehran, Iran
| | - Ali Pouryasin
- Armin Pathobiology Laboratory, Tehran, Iran.,Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran
| | - Johanna C Craig
- GATACA, LLC, Corporate Research Center, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Heidar Sharafi
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.,Middle East Liver Diseases (MELD) Center, Tehran, Iran.,Armin Pathobiology Laboratory, Tehran, Iran
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31
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Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, Díaz A, Vilana R, Darnell A, Varela M, Sangro B, Calleja JL, Forns X, Bruix J. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016; 65:719-726. [PMID: 27084592 DOI: 10.1016/j.jhep.2016.04.008] [Citation(s) in RCA: 798] [Impact Index Per Article: 88.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 03/31/2016] [Accepted: 04/08/2016] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS The success of direct-acting antivirals (DAA) against hepatitis C is a major breakthrough in hepatology. Until now, however, there are very few data on the effect of hepatitis C virus (HCV) eradication in patients who have already developed hepatocellular carcinoma. METHODS The study included patients with HCV infection and prior history of treated hepatocellular carcinoma who achieved complete response and lacked 'non-characterized nodules' at the time they underwent anti-HCV treatment with all-oral DAAs in 4 hospitals. Patients receiving interferon as part of the antiviral regimen were excluded. The baseline characteristics, laboratory and radiologic tumor response were registered in all patients before starting antiviral therapy and during the follow-up according to the clinical practice policy. RESULTS Between 2014 and 2015, 103 patients with prior hepatocellular carcinoma received DAA, 58 of them met the inclusion criteria. After a median follow-up of 5.7months, 3 patients died and 16 developed radiologic tumor recurrence (27.6%). The pattern of recurrence was: intrahepatic growth (3 patients), new intrahepatic lesion (1 nodule in 5 patients, up to 3 nodules less or equal to 3cm in 4 cases and multifocal in one patient) and infiltrative ill-defined hepatocellular carcinoma and/or extra-hepatic lesions in 3 patients. CONCLUSIONS Our data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, although based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity. LAY SUMMARY High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.
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Affiliation(s)
- María Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain
| | - Christie Perelló
- Liver Unit, Hospital Universitario Puerta de Hierro, CIBERehd, IDIPHIM, Madrid, Spain
| | - Mercedes Iñarrairaegui
- Unidad de Hepatología, Clínica Universidad de Navarra, IDISNA, CIBERehd, Pamplona, Spain
| | - Andrea Ribeiro
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain
| | - Alba Díaz
- Department of Pathology, BCLC Group, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Ramón Vilana
- Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Spain
| | - Anna Darnell
- Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Spain
| | - María Varela
- Liver Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Bruno Sangro
- Unidad de Hepatología, Clínica Universidad de Navarra, IDISNA, CIBERehd, Pamplona, Spain
| | - José Luis Calleja
- Liver Unit, Hospital Universitario Puerta de Hierro, CIBERehd, IDIPHIM, Madrid, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
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Takami T, Yamasaki T, Saeki I, Matsumoto T, Suehiro Y, Sakaida I. Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function. World J Gastroenterol 2016; 22:7252-7263. [PMID: 27621572 PMCID: PMC4997645 DOI: 10.3748/wjg.v22.i32.7252] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/07/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.
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33
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How I treat hepatitis C virus infection in patients with hematologic malignancies. Blood 2016; 128:1449-57. [PMID: 27443290 DOI: 10.1182/blood-2016-05-718643] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 07/12/2016] [Indexed: 12/20/2022] Open
Abstract
Hepatitis C virus (HCV) infection is not uncommon in cancer patients. Over the past 5 years, treatment of chronic HCV infection in patients with hematologic malignancies has evolved rapidly as safe and effective direct-acting antivirals (DAAs) have become the standard-of-care treatment. Today, chronic HCV infection should not prevent a patient from receiving cancer therapy or participating in clinical trials of chemotherapy because most infected patients can achieve virologic cure. Elimination of HCV from infected cancer patients confers virologic, hepatic, and oncologic advantages. Similar to the optimal therapy for HCV-infected patients without cancer, the optimal therapy for HCV-infected patients with cancer is evolving rapidly. The choice of regimens with DAAs should be individualized after thorough assessment for potential hematologic toxic effects and drug-drug interactions. This study presents clinical scenarios of HCV-infected patients with hematologic malignancies, focusing on diagnosis, clinical and laboratory presentations, complications, and DAA therapy. An up-to-date treatment algorithm is presented.
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Peng W, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ. Postoperative aspartate aminotransferase to platelet ratio index change predicts prognosis for hepatocellular carcinoma. Medicine (Baltimore) 2016; 95:e4160. [PMID: 27472685 PMCID: PMC5265822 DOI: 10.1097/md.0000000000004160] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
An elevated preoperative aspartate aminotransferase (AST) to platelet ratio index (APRI) is reported to be a prognostic factor for patients with hepatocellular carcinoma (HCC) after treatment. However, delta APRI (ΔAPRI), which represents the change from preoperative to postoperative APRI, has received little attention. The present study was designed to evaluate the prognostic value of ΔAPRI in patients with small HCC after liver resection.A retrospective cohort study analyzing 244 patients with small HCC who had undergone liver resection was conducted. Medical data were retrieved from our prospectively maintained database. Patients were divided into 2 groups according to ΔAPRI as follows: group A (ΔAPRI ≥0.02) and group B (ΔAPRI <0.02). The association of demographic and clinical data, overall survival (OS), and recurrence-free survival (RFS) were statistically compared in the 2 groups, and a multivariate analysis was used to identify prognostic factors.The 1, 3, and 5-year OS of patients in group A were 94.2%, 79.5%, and 62.3%, respectively, and 95.1%, 87.9%, and 84.6%, respectively, for patients in group B (P = 0.001). The corresponding 1, 3, and 5-year RFS was 69.0%, 44.7 %, and 28.1%, and 77.4%, 57.0%, and 54.2% for patients in the 2 groups, respectively (P = 0.009). The results of a multivariate analysis indicated that ΔAPRI was an independent prognostic factor for both OS (P = 0.001, hazard ratio 3.115, 95% confidence interval 1.642-5.912) and RFS (P = 0.006, hazard ratio 1.689, 95% confidence interval 1.163-2.452).A positive ΔAPRI after liver resection predicts decreased OS and RFS in patients with small HCC.
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Affiliation(s)
- Wei Peng
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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35
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Qi X, Zhao Y, Li H, Guo X, Han G. Management of hepatocellular carcinoma: an overview of major findings from meta-analyses. Oncotarget 2016; 7:34703-34751. [PMID: 27167195 PMCID: PMC5085185 DOI: 10.18632/oncotarget.9157] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023] Open
Abstract
This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
| | - Yan Zhao
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
- Department of Gastroenterology, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, 710000 China
| | - Hongyu Li
- Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
| | - Xiaozhong Guo
- Department of Gastroenterology and Meta-analysis Study Interest Group, General Hospital of Shenyang Military Area, Shenyang, 110840 China
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032 China
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Forner A, Reig M, Varela M, Burrel M, Feliu J, Briceño J, Sastre J, Martí-Bonmati L, Llovet JM, Bilbao JI, Sangro B, Pardo F, Ayuso C, Bru C, Tabernero J, Bruix J. [Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. Med Clin (Barc) 2016; 146:511.e1-511.e22. [PMID: 26971984 DOI: 10.1016/j.medcli.2016.01.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/22/2016] [Accepted: 01/28/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.
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Affiliation(s)
- Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Oviedo, España
| | - Marta Burrel
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Jaime Feliu
- Servicio de Oncología Médica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Sociedad Española de Oncología Médica, Madrid, España
| | - Javier Briceño
- Unidad de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, España
| | - Luis Martí-Bonmati
- Departamento de Radiología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Josep María Llovet
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, Estados Unidos
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Unidad de Hepatología, Departamento de Medicina Interna, Clínica Universidad de Navarra, Pamplona, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Carmen Ayuso
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Concepció Bru
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebrón, Barcelona, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
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Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. This cancer commonly arises against a background of chronic liver disease. As a result, a patient with HCC requires multidisciplinary care. Treatment options vary widely based on tumor burden and metastases. The most widely utilized staging system is the Barcelona Clinic Liver Cancer staging system, which recommends treatments based on tumor size and the underlying liver disease and functional status of the patient. Treatment options range from surgical resection or transplantation to locoregional therapies with modalities such as radiofrequency ablation and transarterial chemoembolization to systemic chemotherapies. Future care involves the development of combination therapies that afford the best tumor response, further clarification of the patients best suited for therapies and the development of new oral chemotherapeutic agents.
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Affiliation(s)
- Jennifer S Au
- Division of Gastroenterology and Hepatology, Scripps Clinic
| | - Catherine T Frenette
- Liver Transplantation, Center for Organ and Cell Transplantation, Scripps Clinic, La Jolla, CA, USA
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38
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Blackadar CB. Historical review of the causes of cancer. World J Clin Oncol 2016; 7:54-86. [PMID: 26862491 PMCID: PMC4734938 DOI: 10.5306/wjco.v7.i1.54] [Citation(s) in RCA: 168] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/31/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer.
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Qiao W, Yu F, Wu L, Li B, Zhou Y. Surgical outcomes of hepatocellular carcinoma with biliary tumor thrombus: a systematic review. BMC Gastroenterol 2016; 16:11. [PMID: 26822229 PMCID: PMC4730620 DOI: 10.1186/s12876-016-0427-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 01/25/2016] [Indexed: 02/08/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) with biliary tumor thrombus (BTT) is rare and its impact on postoperative prognosis remains controversial. The aim of this study was to evaluate the published evidence concerning the outcome of surgical resection of HCC with BTT. Methods Eligible studies were identified by searching PubMed and reviewed systematically. Comparisons of the clinicopathologic features and surgical outcomes for HCC patients with or without BTT were analyzed using meta-analytical techniques. Results Twenty retrospective studies containing 598 patients that met the selection criteria were included for review. The perioperative mortality was 2.1 % (range, 0–10 %), and the median 5-year overall survival (OS) was 24 % (range, 0–48 %) with a recurrence rate of 63.9 % (range, 42–91 %). Pooled analysis of 13 comparative studies showed that HCC patients with BTT had a higher incidence of vascular invasion (odds ratio [OR]: 4.70, 95 % CI: 2.90–7.60; P <0.001), a higher frequency of poor differentiation (OR: 2.07, 95 % CI: 1.23–3.49; P = 0.006), and a shorter 5-year OS rate (OR: 0.31, 95 % CI: 0.21–0.64; P <0.001) than those without BTT. Conclusions Although HCC with BTT has more aggressive biological characteristics and is an indicator of poor prognosis, surgical resection can still provide long-term survival for some patients.
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Affiliation(s)
- Wenhui Qiao
- Department of General Surgery, First Hospital of Lanzhou University, Lanzhou, China.
| | - Feng Yu
- Department of Hepatobiliary Surgery, No.101 Hospital of CPLA, Wuxi, China.
| | - Lupeng Wu
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
| | - Bin Li
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
| | - Yanming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First affiliated Hospital of Xiamen University, Xiamen, China.
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Liu GM, Huang XY, Shen SL, Hu WJ, Peng BG. Adjuvant antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after curative treatment: A systematic review and meta-analysis. Hepatol Res 2016; 46:100-10. [PMID: 26331530 DOI: 10.1111/hepr.12584] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 08/10/2015] [Accepted: 08/25/2015] [Indexed: 12/23/2022]
Abstract
AIM To investigate whether adjuvant antiviral treatment could improve prognosis and entecavir is the optimal nucleoside/nucleotide analog (NA) regimen after curative therapy of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A comprehensive electronic search was performed. All controlled trials comparing antiviral treatment with placebo or no treatment for HBV-related HCC after curative treatment were included. The pooled hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Stata 12.0 software. An indirect treatment comparison method was used to compare the relative efficacy of different NA strategies. RESULTS Twenty-one studies containing 8072 patients were included. NA was found to significantly improve recurrence-free survival (RFS) and overall survival (OS). Alternatively, for interferon, a non-significant benefit was found. By adjusted indirect comparisons among entecavir, lamivudine and adefovir, entecavir were found to display almost but not significant superiority to the other NA in improving RFS. No tendency favoring a specific NA regimen was found for OS. CONCLUSION In HBV-HCC patient after curative treatment, NA improve the prognosis significantly but the role of interferon remains to be elucidated; entecavir was not found to be superior to other NA based on available data.
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Affiliation(s)
- Gao-Min Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, China
| | - Xiao-Yong Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shun-Li Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wen-Jie Hu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bao-Gang Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1929] [Impact Index Per Article: 214.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Qu LS, Zhang HF. Significance of viral status on prognosis of hepatitis B-related hepatocellular carcinoma after curative resection in East Asia. Hepatol Res 2016; 46:40-9. [PMID: 25858122 DOI: 10.1111/hepr.12523] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Revised: 03/23/2015] [Accepted: 04/05/2015] [Indexed: 12/20/2022]
Abstract
Tumor recurrence remains one major obstacle for further improving the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after curative liver resection. It has been widely reported that tumor size, positive surgical margin, macroscopic vascular invasion, tumor-node-metastasis stage and Edmondson's grade were significantly related to HCC recurrence. However, the association between HCC recurrence and important viral factors, including the HBV DNA levels, status of hepatitis B surface antigen and hepatitis B e-antigen, levels of cccDNA and hepatitis B core-related antigen, viral genotypes and specific viral sequence mutations remained controversial. Meanwhile, studies on the effect of postoperative adjuvant antiviral therapy on HCC recurrence have been relatively limited and have yielded conflicting results. Identification of certain viral risk factors for HCC recurrence and stratification of patient risk are very important to perform future surveillance programs. As a HBV hyperendemic region, the majority of HBV-related HCC patients develop in East Asia. In this article, we thus systematically reviewed the risk of important viral factors involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy in preventing tumor recurrence in this area.
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Affiliation(s)
- Li-Shuai Qu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China
| | - Hai-Feng Zhang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China
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Antiviral therapy decreases recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection: a meta-analysis. World J Surg 2015; 38:2395-402. [PMID: 24791945 DOI: 10.1007/s00268-014-2586-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The long-term outcome after curative resection of hepatocellular carcinoma (HCC) remains unsatisfactory because of the high incidence of recurrence. The present study was intended to assess the impact of hepatitis B virus (HBV) DNA level and nucleos(t)ide analog therapy on posthepatectomy recurrence of HBV-related HCC. METHODS Eligible studies were identified through a computerized literature search. The pooled relative risk ratio (RR) with 95 % confidence interval (CI) was calculated using Review Manager 5.1 Software. RESULTS Twenty studies with a total of 8,204 participants were included for this meta-analysis. Pooled analysis showed that high viral load was significantly associated with risk of recurrence (RR: 1.85, 95 % CI: 1.41-2.42; P < 0.001), poorer disease-free survival (DFS) (RR: 1.96, 95 % CI: 1.62-2.38; P < 0.001), and poorer overall survival (OS) (RR: 1.47, 95 % CI: 1.22-1.77; P < 0.001) of HBV-related HCC after surgical resection. Nucleos(t)ide analog therapy significantly decreased the recurrence risk (RR: 0.69, 95 % CI: 0.59-0.80; P < 0.001) and improved both DFS (RR: 0.70, 95 % CI: 0.58-0.83; P < 0.001) and OS (RR: 0.46, 95 % CI: 0.32-0.68; P < 0.001). CONCLUSIONS High DNA level is associated with posthepatectomy recurrence of HBV-related HCC. Nucleos(t)ide analog therapy improves the prognosis of HBV-related HCC after resection.
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Kubo S, Takemura S, Tanaka S, Shinkawa H, Nishioka T, Nozawa A, Kinoshita M, Hamano G, Ito T, Urata Y. Management of hepatitis B virus infection during treatment for hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 2015; 21:8249-8255. [PMID: 26217076 PMCID: PMC4507094 DOI: 10.3748/wjg.v21.i27.8249] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 03/16/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
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.
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45
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Zhu GQ, Shi KQ, Yu HJ, He SY, Braddock M, Zhou MT, Chen YP, Zheng MH. Optimal adjuvant therapy for resected hepatocellular carcinoma: a systematic review with network meta-analysis. Oncotarget 2015; 6:18151-18161. [PMID: 26061709 PMCID: PMC4627241 DOI: 10.18632/oncotarget.4098] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 05/26/2015] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES Major adjuvant therapies (ATs) for resected hepatocellular carcinoma (HCC) include chemotherapy, internal radiation therapy (IRT), interferon therapy (IFNT) and immunotherapy but the optimum regimen remains inconclusive. We aim to compare these therapies in terms of patient survival and recurrence rates. METHODS We searched PubMed, EMBASE and Cochrane library databases for randomized trials comparing the above four therapies until 31 March 2014. We estimated the HRs for survival and ORs for overall recurrence among different therapies. Toxic effects were also evaluated. RESULTS Fourteen eligible articles were included. IFNT improved 5-year survival greatly (HR 1.81, 95% CI 1.01-3.81, P = 0.034), whereas chemotherapy (HR 0.33, 95% CI 0.03-2.02), IRT (HR 0.31, 95% CI 0.02-3.33) and immunotherapy (HR 0.73, 95% CI 0.05-9.12) all provided a poorer survival outcome after 1-year. Similarly, for 5-year survival rates, although differing, IRT did not provide a significant improvement in survival (HR 1.38, 95% CI 0.34-5.19) compared with IFNT. Chemotherapy (HR 0.49, 95% CI 0.18-1.14) and immunotherapy (HR 0.56, 95% CI 0.17-1.59) did not appear to provide benefit over IFNT. Chemotherapy was ranked the worst in overall recurrence (OR 0.99, 95% CI 0.18-5.38) and most likely to cause toxic effects. CONCLUSIONS IFNT was the most efficacious AT regimen both for short and long term survivals. Immunotherapy and IFNT were the most two effective in preventing overall relapse for resected HCC.
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Affiliation(s)
- Gui-Qi Zhu
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Ke-Qing Shi
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Hua-Jian Yu
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Sun-Yue He
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Martin Braddock
- Global Medicines Development, AstraZeneca R&D, Loughborough, United Kingdom
| | - Meng-Tao Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yong-Ping Chen
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
| | - Ming-Hua Zheng
- Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
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46
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Abstract
Primary liver cancer, mostly hepatocellular carcinoma, remains a difficult-to-treat cancer. Incidence of liver cancer varies geographically and parallels with the geographic prevalence of viral hepatitis. A number of staging systems have been developed, reflecting the heterogeneity of primary liver cancer, regional preferences, and regional variations in resectability or transplant eligibility. Multimodality treatments are available for this heterogeneous malignancy, and there are variations in the management recommendations for liver cancers across specialties and geographic regions. Novel treatment strategies have merged with the advance of new treatment modalities. This work focuses on reviewing the incidence, staging, and treatment of liver cancer.
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Affiliation(s)
- Chun-Yu Liu
- Department of Medicine, Division of Hematology and Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan School of Medicine, National Yang-Ming University, Taipei 112, Taiwan Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
| | - Kuen-Feng Chen
- Department of Medical Research, National Taiwan University College of Medicine, Taipei 112, Taiwan National Center of Excellence for Clinical Trial and Research, National Taiwan University College of Medicine, Taipei 112, Taiwan
| | - Pei-Jer Chen
- Department of Medical Research, National Taiwan University College of Medicine, Taipei 112, Taiwan National Center of Excellence for Clinical Trial and Research, National Taiwan University College of Medicine, Taipei 112, Taiwan Graduate Institute of Molecular Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 112, Taiwan
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47
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Sommer CM, Stampfl U, Kauczor HU, Pereira PL. [National S3 guidelines on hepatocellular carcinoma]. Radiologe 2015; 54:642-53. [PMID: 25047521 DOI: 10.1007/s00117-014-2656-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CLINICAL/METHODICAL ISSUE Evidence-based therapeutic and diagnostic algorithm for hepatocellular carcinoma. STANDARD RADIOLOGICAL METHODS Ultrasound, computed tomography, magnetic resonance imaging, image-guided percutaneous biopsy, percutaneous thermal ablation and transarterial chemoembolization. METHODICAL INNOVATIONS Diagnostic and therapy of hepatocellular carcinoma according to the official German interdisciplinary guidelines. PERFORMANCE The formulation of the German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma was performed under special consideration of quality indicators and standardized quality improvement methods. ACHIEVEMENTS In 2013 the German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma were published and clinically implemented as part of the nationwide guideline program in oncology of the Deutsche Krebsgesellschaft (German Cancer Society). PRACTICAL RECOMMENDATIONS The German S3 guidelines on diagnosis and therapy of hepatocellular carcinoma have to be considered as the national gold standard with the goal of optimization of patient care.
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Affiliation(s)
- C M Sommer
- Abteilung für Diagnostische und Interventionelle Radiologie, Radiologische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
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Shindoh J, Hashimoto M, Watanabe G. Surgical approach for hepatitis C virus-related hepatocellular carcinoma. World J Hepatol 2015; 7:70-77. [PMID: 25624998 PMCID: PMC4295196 DOI: 10.4254/wjh.v7.i1.70] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Revised: 10/30/2014] [Accepted: 11/17/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma (HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC, adequate management of co-existing infection with hepatitis C virus (HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection, perioperative anti-viral treatment is recommended, since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease, the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy, new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.
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Affiliation(s)
- Junichi Shindoh
- Junichi Shindoh, Masaji Hashimoto, Goro Watanabe, Hepatobiliary-pancreatic Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Masaji Hashimoto
- Junichi Shindoh, Masaji Hashimoto, Goro Watanabe, Hepatobiliary-pancreatic Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
| | - Goro Watanabe
- Junichi Shindoh, Masaji Hashimoto, Goro Watanabe, Hepatobiliary-pancreatic Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo 105-8470, Japan
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49
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Sharafi H, Alavian SM, Keshvari M. Efficacy of 24-week pegylated interferon alpha and ribavirin combination therapy in highly selected patients infected with hepatitis C virus genotype 1. HEPATITIS MONTHLY 2015; 15:e24955. [PMID: 25741374 PMCID: PMC4330713 DOI: 10.5812/hepatmon.24955] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 12/03/2014] [Accepted: 12/31/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Previous studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate. OBJECTIVES The current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR. PATIENTS AND METHODS In this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group. RESULTS The majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99). CONCLUSIONS The current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.
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Affiliation(s)
- Heidar Sharafi
- Iran Hepatitis Network, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
| | - Seyed Moayed Alavian
- Iran Hepatitis Network, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
| | - Maryam Keshvari
- Iran Hepatitis Network, Tehran, IR Iran
- Middle East Liver Diseases Center (MELD), Tehran, IR Iran
- Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran
- Corresponding Author: Maryam Keshvari, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran. Tel: +98-2188601501-30, Fax: +98-2166900386, E-mail:
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50
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Okita K, Izumi N, Ikeda K, Osaki Y, Numata K, Ikeda M, Kokudo N, Imanaka K, Nishiguchi S, Kondo S, Nishigaki Y, Shiomi S, Ueshima K, Isoda N, Karino Y, Kudo M, Tanaka K, Kaneko S, Moriwaki H, Makuuchi M, Okusaka T, Hayashi N, Ohashi Y, Kumada H, The Peretinoin Study Group. Survey of survival among patients with hepatitis C virus-related hepatocellular carcinoma treated with peretinoin, an acyclic retinoid, after the completion of a randomized, placebo-controlled trial. J Gastroenterol 2015; 50:667-74. [PMID: 25209978 PMCID: PMC4460291 DOI: 10.1007/s00535-014-0996-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 08/24/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND This study examined the effects of peretinoin, an acyclic retinoid, on the survival of patients with hepatitis C virus-related hepatocellular carcinoma (HCC) who had completed curative therapy and participated in a randomized, placebo-controlled trial. METHODS This study was an investigator-initiated retrospective cohort study. Subjects were all patients who were administered the investigational drug (peretinoin 600 mg/day, peretinoin 300 mg/day, or placebo) in the randomized trial. Survivals between the groups were compared using the log-rank test, and hazard ratios were estimated by Cox regression. RESULTS Survey data were collected from all patients (n = 392) who participated in the randomized trial, all of whom were then divided into the peretinoin 600 mg/day (n = 132), peretinoin 300 mg/day (n = 131), and placebo (n = 129) groups. At the median follow-up of 4.9 years, 5-year cumulative survival rates for patients in the 600 mg/day, 300 mg/day, and placebo groups were 73.9, 56.8, and 64.3 %, respectively. Comparison of overall survival among patients classified as Child-Pugh A revealed that survival of the 600 mg/day group (n = 105) was significantly longer than that of the placebo group (n = 108) (hazard ratio 0.575, 95 % CI 0.341-0.967; P = 0.0347). CONCLUSIONS Administration of 600 mg/day peretinoin to patients with hepatitis C virus-related HCC who have completed curative therapy may improve survival for those classified as Child-Pugh A, for whom liver function is relatively stable.
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Affiliation(s)
- Kiwamu Okita
- Shimonoseki Kohsei Hospital, Kamishinchi-Machi 3-3-8, Shimonoseki, Yamaguchi 750-0061 Japan
| | - Namiki Izumi
- Musashino Red Cross Hospital, Sakai-minami-cho 1-26-1, Musashino, Tokyo 180-8610 Japan
| | - Kenji Ikeda
- Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo 105-8470 Japan
| | - Yukio Osaki
- Osaka Red Cross Hospital, Fudegasaki-cho 5-30, Tennoji-ku, Osaka 543-8555 Japan
| | - Kazushi Numata
- Yokohama City University Medical Center, Urafune-cho 4-57, Minami-ku, Yokohama 232-0024 Japan
| | - Masafumi Ikeda
- National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa, Chiba 277-8577 Japan
| | - Norihiro Kokudo
- The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655 Japan
| | - Kazuho Imanaka
- Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi 1-3-3 Higashinari-ku, Osaka, 537-8511 Japan
| | - Shuhei Nishiguchi
- Hyogo College of Medicine Hospital, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501 Japan
| | - Shunsuke Kondo
- National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045 Japan
| | | | - Susumu Shiomi
- Osaka City University Hospital, Asahi-machi 1-5-7, Abeno-ku, Osaka 545-8585 Japan
| | - Kazuomi Ueshima
- Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 Japan
| | - Norio Isoda
- Jichi Medical University, Yakushiji 3311-1, Shimotsuke-shi, Tochigi 329-0498 Japan
| | - Yoshiyasu Karino
- Sapporo Kosei General Hospital, Kita 3-jo Higashi 8-choume-5, Chuo-ku, Sapporo, Hokkaido 060-0033 Japan
| | - Masatoshi Kudo
- Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 Japan
| | - Katsuaki Tanaka
- Yokohama City University Medical Center, Urafune-cho 4-57, Minami-ku, Yokohama 232-0024 Japan
| | - Shuichi Kaneko
- Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, Ishikawa 920-8641 Japan
| | | | - Masatoshi Makuuchi
- Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, 150-8935 Japan
| | - Takuji Okusaka
- National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045 Japan
| | - Norio Hayashi
- Kansai Rosai Hospital, Inabaso 3-1-69, Amagasaki, Hyogo 660-8511 Japan
| | - Yasuo Ohashi
- Chuo University, Kasuga 1-13-27, Bunkyo-ku, Tokyo, 112-8551 Japan
| | - Hiromitsu Kumada
- Toranomon Hospital, Toranomon 2-2-2, Minato-ku, Tokyo 105-8470 Japan
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