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Tran NH, Muñoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology 2022; 76:1203-1218. [PMID: 35765265 DOI: 10.1002/hep.32613] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.
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Affiliation(s)
- Nguyen H Tran
- Division of Medical OncologyDepartment of OncologyMayo ClinicRochesterMinnesotaUSA
| | - Sergio Muñoz
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Scott Thompson
- Division of Vascular and Interventional RadiologyDepartment of RadiologyMayo ClinicRochesterMinnesotaUSA
| | | | - Jordi Bruix
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
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2
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Chen QF, Li W, Yu SCH, Chou YH, Rhim H, Yang X, Shen L, Dong A, Huang T, Huang J, Zhang F, Fan W, Zhao M, Gu Y, Huang Z, Zuo M, Zhai B, Xiao Y, Kuang M, Li J, Han J, Song W, Ma J, Wu P. Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations. Front Oncol 2021; 11:621834. [PMID: 34277397 PMCID: PMC8284077 DOI: 10.3389/fonc.2021.621834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 06/15/2021] [Indexed: 12/24/2022] Open
Abstract
In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.
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Affiliation(s)
- Qi-Feng Chen
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wang Li
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Simon Chun-Ho Yu
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong, China
| | - Yi-Hong Chou
- Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, China.,Department of Radiology, Taipei General Hospital and School of Medicine, National YangMing University, Taipei, China.,Department of Radiology, Yeezen General Hospital, Taoyuan, China
| | - Hyunchul Rhim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Xiaoming Yang
- Image-Guided Bio-Molecular Intervention Research and Division of Vascular and Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, United States
| | - Lujun Shen
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Annan Dong
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tao Huang
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.,State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.,Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jinhua Huang
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fujun Zhang
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Weijun Fan
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ming Zhao
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yangkui Gu
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhimei Huang
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mengxuan Zuo
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Bo Zhai
- Department of Surgery, Shanghai Jiaotong University School of Medicine Renji Hospital, Shanghai, China
| | - Yueyong Xiao
- Department of Radiology, The First Medical Centre, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Ming Kuang
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jianjun Han
- Department of Intervention, Shandong Cancer Hospital, Jinan, China
| | - Wei Song
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jie Ma
- Department of Biotherapy, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Peihong Wu
- Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
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Ayuso C, Rimola J, Vilana R, Burrel M, Darnell A, García-Criado Á, Bianchi L, Belmonte E, Caparroz C, Barrufet M, Bruix J, Brú C. Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines. Eur J Radiol 2018; 101:72-81. [PMID: 29571804 DOI: 10.1016/j.ejrad.2018.01.025] [Citation(s) in RCA: 240] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 01/10/2018] [Accepted: 01/27/2018] [Indexed: 12/20/2022]
Abstract
One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96-100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions.
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Affiliation(s)
- Carmen Ayuso
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain.
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ramón Vilana
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Anna Darnell
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ángeles García-Criado
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Luis Bianchi
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ernest Belmonte
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Carla Caparroz
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Marta Barrufet
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group: Liver Unit. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Concepción Brú
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
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Fong ZV, Tanabe KK. The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: A comprehensive and evidence-based comparison and review. Cancer 2014; 120:2824-38. [DOI: 10.1002/cncr.28730] [Citation(s) in RCA: 188] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Revised: 02/18/2014] [Accepted: 03/21/2014] [Indexed: 12/12/2022]
Affiliation(s)
- Zhi Ven Fong
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital; Harvard Medical School; Boston Massachusetts
| | - Kenneth K. Tanabe
- Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital; Harvard Medical School; Boston Massachusetts
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Yang HJ, Lee JH, Lee DH, Yu SJ, Kim YJ, Yoon JH, Kim HC, Lee JM, Chung JW, Yi NJ, Lee KW, Suh KS, Lee HS. Small single-nodule hepatocellular carcinoma: comparison of transarterial chemoembolization, radiofrequency ablation, and hepatic resection by using inverse probability weighting. Radiology 2014; 271:909-18. [PMID: 24520944 DOI: 10.1148/radiol.13131760] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE To compare the effectiveness of transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and hepatic resection (HR) in patients with small single-nodule hepatocellular carcinoma by using inverse probability weighting to control selection bias. MATERIALS AND METHODS This retrospective cohort study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study included 197 consecutive patients (146 men and 51 women; mean age ± standard deviation, 57.4 years ± 9.7) with single-nodule hepatocellular carcinomas measuring 3 cm or smaller and no vascular invasion who were treated initially with HR (n = 52), RFA (n = 79), or TACE (n = 66) from January 2005 to December 2006 at a single tertiary hospital. The primary endpoint was overall survival. RESULTS The baseline liver status of the groups differed significantly and was most favorable for the HR group, followed by the RFA group, and then the TACE group. The 5-year overall survival rates were 93.6% in the HR group, 86.6% in the RFA group, and 74.2% in the TACE group (P = .023). However, after inverse probability weighting, weighted survival rates among the three groups were similar (5-year overall survival: 85.6% with HR, 87.6% with RFA, and 80.7% with TACE; P = .834). In multivariate Cox regression analysis, TACE showed a hazard ratio of 0.978 (95% confidence interval: 0.407, 2.347; P = .960) compared with HR and of 1.335 (95% confidence interval: 0.619, 2.879; P = .461) compared with RFA. CONCLUSION TACE is an effective treatment that allows achievement of long-term survival rates comparable to those with HR and RFA in patients with small single-nodule hepatocellular carcinoma.
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Affiliation(s)
- Hyo-Joon Yang
- From the Department of Internal Medicine and Liver Research Institute (H.J.Y., J.H.L., D.H.L., S.J.Y., Y.J.K., J.H.Y., H.S.L.), Department of Radiology (H.C.K., J.M.L., J.W.C.), and Department of Surgery (N.J.Y., K.W.L., K.S.S.), Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-744, Korea
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Abdo AA, Hassanain M, AlJumah A, Al Olayan A, Sanai FM, Alsuhaibani HA, Abdulkareem H, Abdallah K, AlMuaikeel M, Al Saghier M, Babatin M, Kabbani M, Bazarbashi S, Metrakos P, Bruix J. Saudi guidelines for the diagnosis and management of hepatocellular carcinoma: technical review and practice guidelines. Ann Saudi Med 2012; 32:174-99. [PMID: 22366832 PMCID: PMC6086640 DOI: 10.5144/0256-4947.2012.174] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [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
Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi Arabia, and the difficulties often faced in early and accurate diagnoses, evidence-based management, and the need for appropriate referral of HCC patients, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) formed a multi-disciplinary task force to evaluate and update the previously published guidelines by the Saudi Gastroenterology Association. These guidelines were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as its official HCC guidelines as well. The committee assigned to revise the Saudi HCC guidelines was composed of hepatologists, oncologists, liver surgeons, transplant surgeons, and interventional radiologists. Two members of the task force served as guidelines editors. A wide based search on all published reports on all aspects of the epidemiology, natural history, risk factors, diagnosis, and management of HCC was performed. All available literature was critically examined and available evidence was then classified according to its strength. The whole document and the recommendations were then discussed in detail by members and consensus was obtained. All recommendations in these guidelines were based on the best available evidence, but were tailored to the patients treated in Saudi Arabia. We hope that these guidelines will improve HCC patient care and enhance the multidisciplinary care needed for these patients.
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Affiliation(s)
- Ayman A Abdo
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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7
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Bruix J, Reig M, Rimola J, Forner A, Burrel M, Vilana R, Ayuso C. Clinical decision making and research in hepatocellular carcinoma: pivotal role of imaging techniques. Hepatology 2011; 54:2238-44. [PMID: 21932394 DOI: 10.1002/hep.24670] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Jordi Bruix
- Barcelona Clinic Liver Cancer group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain.
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8
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Kumar A, Dwivedi M, Misra SP, Narang S, Tiwari BK, Pandey R. Clinical profile, genotype and management updates of hepatitis B virus. INDIAN JOURNAL OF VIROLOGY : AN OFFICIAL ORGAN OF INDIAN VIROLOGICAL SOCIETY 2011; 22:1-10. [PMID: 23637496 PMCID: PMC3550728 DOI: 10.1007/s13337-011-0037-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2010] [Accepted: 05/07/2011] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) is a well known agent of acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Around 400 million people worldwide carrier of HBV of which more than 250 million reside in Asia, and 1-2 million people have died from it. It has a partially double-stranded DNA, having 3.2-kb genome size and replicate via reverse transcription of RNA intermediate. In the natural history or during the antiviral therapy of chronic HBV infection, seroconversion from HBeAg to anti-HBeAg is usually accompanied by a decrease in viral replication and remission of liver disease. Based on genomic sequence data HBV is classified into eight genotypes A-H and four major serotypes ayw, ayr, adw and adr on the basis of complete genome and S gene sequence analysis. Genotypes and serotypes are useful tools in understanding the epidemiology of HBV infection. HBV genotypes have distinct geographical distributions. The HBV variants appear during HBeAg seroconversion and they bring mutations in the precore region (PC) that prevent HBeAg synthesis. Another common HBeAg variant is the basal core promoter mutant (BCP) characterized by point mutation in the promoter of both HBeAg mRNA and core protein mRNA. The most frequent core promoter mutation is the double A1762T and G1764A nucleotide exchange, which results in a substantial decrease in HBeAg expression but enhanced viral genome replication. The approved antiviral drugs such as Interferon, lamivudine, adefovir dipivoxil, entecavir and telbivudine for purpose of treating chronic HBV infection is to prevent or stop the progression of liver injury by suppressing viral replication or eliminating infection. Sustained losses of viral markers of active viral replication (HBeAg and HBV DNA) are the standard end point of the therapies.
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Affiliation(s)
- Ajay Kumar
- />Centre for Biotechnology, Allahabad Central University, Allahabad, India
- />Department of Gastroenterology, MLN Medical College, Allahabad, India
| | - Manisha Dwivedi
- />Department of Gastroenterology, MLN Medical College, Allahabad, India
| | - S. P. Misra
- />Department of Gastroenterology, MLN Medical College, Allahabad, India
| | - Sushil Narang
- />Department of Gastroenterology, MLN Medical College, Allahabad, India
| | | | - Renu Pandey
- />Centre for Biotechnology, Allahabad Central University, Allahabad, India
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Sun JH, Wang LG, Bao HW, Lou JL, Cai LX, Wu C, Chen LM, Zheng SS. Usefulness of C-arm angiographic computed tomography for detecting iodized oil retention during transcatheter arterial chemoembolization of hepatocellular carcinoma. J Int Med Res 2010; 38:1259-65. [PMID: 20925998 DOI: 10.1177/147323001003800407] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Transcatheter arterial chemoembolization (TACE) with iodized oil and anticancer agents is widely used for hepatocellular carcinoma (HCC) treatment. To assess C-arm angiographic computed tomography (CCT) for detecting iodized oil retention during TACE, CCT images were obtained of 40 tumours (24 HCC patients). The primary CCT images showed complete iodized oil retention patterns (type I) in 29/40 (73%) tumours, at which point embolization was terminated; incomplete iodized oil retention requiring further iodized oil embolization occurred in 11/40 (28%) tumours and, of these, complete iodized oil retention patterns were achieved in eight tumours. Conventional CT scanning employed 1 week later showed the same iodized oil retention patterns as demonstrated in the latest CCT images (37/40 [93%] tumours). In 24 additional HCC patients who underwent TACE but not CCT (control group), conventional CT scans obtained 1 week after TACE showed complete iodized oil retention in 32/42 (76%) tumours. The rate of complete iodized oil retention pattern was significantly higher in patients undergoing CCT. It is concluded that the distribution of iodized oil within HCC lesions can be demonstrated on CCT images during TACE, helping to achieve complete iodized oil filling of tumours and, thereby, improving therapeutic effects.
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Affiliation(s)
- J-H Sun
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Abstract
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
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Ariff B, Lloyd CR, Khan S, Shariff M, Thillainayagam AV, Bansi DS, Khan SA, Taylor-Robinson SD, Lim AKP. Imaging of liver cancer. World J Gastroenterol 2009; 15:1289-300. [PMID: 19294758 PMCID: PMC2658841 DOI: 10.3748/wjg.15.1289] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identification and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality.
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12
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Yang P, Liang M, Zhang Y, Shen B. Clinical application of a combination therapy of lentinan, multi-electrode RFA and TACE in HCC. Adv Ther 2008; 25:787-94. [PMID: 18670743 DOI: 10.1007/s12325-008-0079-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide and there is a clear need for further treatment options. In this study, we assessed the efficacy of a combination of lentinan (a fungal extract), transcatheter arterial chemoembolisation (TACE) and radiofrequency ablation (RFA) in HCC patients. METHODS Seventy-eight patients with HCC confirmed by pathology and iconographical checks were used in this study. A total of 136 tumours with a mean diameter of 6.5 cm were detected (standard deviation [SD]+/-0.7). Subjects were divided into four groups, receiving either TACE only, RFA only, RFA and TACE, or the combination group - receiving lentinan, RFA and TACE. RESULTS The tumour necrosis was significantly higher in the combination group (88.6%), compared to the TACE group (37.5%), the RFA group (47.8%) and the TACE/RFA group (60.3%; P<0.05). The tumour recurrence rate was significantly lower in the combination group (17.8%), compared to the TACE group (45.8%), the RFA group (34.7%) and the TACE/RFA group (29.0%; P<0.05). Finally, mean survival duration was significantly higher in the combination group (28.2 months; P<0.05). CONCLUSION Combination therapy involving lentinan, RFA and TACE was beneficial in terms of increasing mean survival duration, tumour necrosis and reducing the recurrence rate. Lentinan may therefore be of benefit to HCC patients.
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13
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Varela M, Forner A, Bruix J. Diagnosis and staging of hepatocellular carcinoma prior to transplantation: expertise or failure. Liver Transpl 2006; 12:1445-7. [PMID: 17004255 DOI: 10.1002/lt.20909] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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14
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Affiliation(s)
- Pierre Deltenre
- Service d'Hépato-Gastroentérologie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
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15
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Affiliation(s)
- Jordi Bruix
- BCLC Group. Liver Unit. Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
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16
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Zheng XH, Guan YS, Zhou XP, Huang J, Sun L, Li X, Liu Y. Detection of hypervascular hepatocellular carcinoma: Comparison of multi-detector CT with digital subtraction angiography and Lipiodol CT. World J Gastroenterol 2005; 11:200-3. [PMID: 15633215 PMCID: PMC4205401 DOI: 10.3748/wjg.v11.i2.200] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The purpose of this study was to compare the diagnostic accuracy of biphasic multi-detector row helical computed tomography (MDCT), digital subtraction angiography (DSA) and Lipiodol computed tomography (CT) in detection of hypervascular hepatocellular carcinoma (HCC).
METHODS: Twenty-eight patients with nodular HCC underwent biphasic MDCT examination: hepatic arterial phase (HAP) 25 s and portal venous phase (PVP) 70 s after injection of the contrast medium (1.5 mL/kg). They also underwent hepatic angiography and intra-arterial infusion of iodized oil. Lipiodol CT was performed 3-4 wk after infusion. MDCT images were compared with DSA and Lipiodol CT images for detection of hepatic nodules.
RESULTS: The three imaging techniques had the same sensitivity in detecting nodules >20 mm in diameter. There was no significant difference in the sensitivity among HAP-MDCT, Lipiodol CT and DSA for nodules of 10-20 mm in diameter. For the nodules <10 mm in diameter, HAP-MDCT identified 47, Lipiodol CT detected 27 (χ2 = 11.3, P = 0.005<0.01, HAP-MDCT vs Lipiodol CT) and DSA detected 16 (χ2 = 9.09, P = 0.005<0.01 vs Lipiodol CT and χ2 = 29.03, P = 0.005<0.01vs HAP-MDCT). However, six nodules <10 mm in diameter were detected only by Lipiodol CT.
CONCLUSION: MDCT and Lipiodol CT are two complementary modalities. At present, MDCT does not obviate the need for DSA and subsequent Lipiodol CT as a preoperative examination for HCC.
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Affiliation(s)
- Xiao-Hua Zheng
- Department of Radiology, Huaxi Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Abstract
The diagnosis of hepatocellular carcinoma (HCC) includes detection of the index lesion, staging of the lesion within the liver, and assessment for extrahepatic metastasis. HCC is a highly vascular neoplasm usually arising in a cirrhotic liver. Based on this concept, consensus criteria have been developed for the radiographic diagnosis of HCC. These include: (1) identification of a mass >2 cm in diameter in a cirrhotic liver in 2 imaging modalities, and (2) contrast enhancement on computed tomography, magnetic resonance, or angiography. A mass lesion within a cirrhotic liver in the presence of a serum alpha-fetoprotein level >400 ng/mL also is diagnostic. For lesions <2 cm in diameter, histological confirmation is required. Serum markers for the diagnosis of early HCC (<2 cm in diameter) have not been established. Staging HCC for metastases is insensitive and is based on conventional criteria (eg, pulmonary nodules, skeletal metastases, and lymphadenopathy). Additional diagnostic techniques based on cytological advances, genomics, and proteomics are needed for the diagnosis and staging of this highly malignant neoplasm.
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Affiliation(s)
- Jayant A Talwalkar
- William J. von Liebig Transplantation Center, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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18
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França AVC, Elias Junior J, Lima BLG, Martinelli ALC, Carrilho FJ. Diagnosis, staging and treatment of hepatocellular carcinoma. Braz J Med Biol Res 2004; 37:1689-705. [PMID: 15517086 DOI: 10.1590/s0100-879x2004001100015] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.
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Affiliation(s)
- A V C França
- Divisão de Gastroenterologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo Brasil
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Fung KTT, Li FTW, Raimondo ML, Maudgil D, Mancuso A, Tibballs JM, Watkinson AA, Patch D, Burroughs AK. Systematic review of radiological imaging for hepatocellular carcinoma in cirrhotic patients. Br J Radiol 2004; 77:633-40. [PMID: 15326039 DOI: 10.1259/bjr/31556748] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
We systematically reviewed the evidence for determining the best radiological imaging for characterizing hepatocellular carcinoma (HCC) in cirrhotic patients in 997 articles between 1995 and 2001. We selected only prospective and retrospective cohorts of patients, excluding both case reports and studies without separate data on HCC. Only 29 studies, comprising 918 patients, fulfilled the inclusion criteria: 10 used the explanted liver as the reference standard of diagnosis. All except one, either found no statistically significant difference between imaging modalities or had no direct comparison of sensitivity between different modalities of imaging; 16 studies evaluated HCC among cirrhotic patients and had biopsy or imaging as the reference standard for diagnosis. However, no one imaging technique was shown to be superior. In two studies, data of a HCC subgroup was derived from the studies evaluating different kinds of focal hepatic lesions. No conclusion could be drawn because of the small sample size. One study addressed the issue of therapeutic impact. The evidence for choosing the best modality of imaging for characterizing HCC in cirrhotic patients is inadequate. Large multicentre studies with defined reference standards for diagnosis, and studies evaluating therapeutic impact are needed.
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Affiliation(s)
- K T T Fung
- Liver Transplantation and Hepatobiliary Medicine, The Royal Free Hospital, Pond Street, London, UK
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20
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Mok TSK, Yu SCH, Lee C, Sung J, Leung N, Lai P, Leung TWT, Chan ATC, Yeo W, Koh J, Johnson P. False-Negative Rate of Abdominal Sonography for Detecting Hepatocellular Carcinoma in Patients with Hepatitis B and Elevated Serum α-Fetoprotein Levels. AJR Am J Roentgenol 2004; 183:453-8. [PMID: 15269040 DOI: 10.2214/ajr.183.2.1830453] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Routine screening for hepatocellular carcinoma among chronic carriers of hepatitis B virus using a combination of abdominal sonography and serum alpha-fetoprotein levels is widely practiced. Negative results on an abdominal sonogram generally indicate the absence of hepatocellular carcinoma despite the elevation of alpha-fetoprotein levels, but the false-negative rate of abdominal sonography has not been established prospectively. SUBJECTS AND METHODS In our screening program, we routinely investigated patients with Lipiodol (iodized oil) CT when they presented with alpha-fetoprotein levels above 20 ng/mL or a focal lesion as depicted on abdominal sonography. Lipiodol CT comprised a hepatic angiogram with injection of Lipiodol selectively in the hepatic arteries, followed by an unenhanced CT scan 10 days later. Positive findings on Lipiodol CT were confirmed histologically by biopsy or surgical resection. We defined false-negative as histologic diagnosis of hepatocellular carcinoma within 3 months of normal findings on screening abdominal sonography. RESULTS One hundred three patients with elevated alpha-fetoprotein levels were investigated with Lipiodol CT within 2 months of abdominal sonography. Of these, three of 70 patients with negative abdominal sonography had histologically confirmed hepatocellular carcinoma. Thus, abdominal sonography has a false-negative rate of 4.3%. Lipiodol CT is associated with a significant false-positive rate of 43.7%. The sensitivity, specificity, and positive predictive value of abdominal sonography for early detection of hepatocellular carcinoma among hepatitis B virus carriers with elevated alpha-fetoprotein levels was 85.7%, 81.7%, and 54.5%, respectively. CONCLUSION Negative results on a screening abdominal sonogram among hepatitis B virus carriers with elevated alpha-fetoprotein levels does not rule out the presence of small hepatocellular carcinoma. Routine use of Lipiodol CT as a supplementary screening tool is not recommended.
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Affiliation(s)
- Tony S K Mok
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
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21
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Bhattacharjya S, Bhattacharjya T, Quaglia A, Dhillon AP, Burroughs AK, Patch DW, Tibballs JM, Watkinson AF, Rolles K, Davidson BR. Liver transplantation in cirrhotic patients with small hepatocellular carcinoma: an analysis of pre-operative imaging, explant histology and prognostic histologic indicators. Dig Surg 2004; 21:152-9; discussion 159-60. [PMID: 15166485 DOI: 10.1159/000078741] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2003] [Accepted: 12/11/2003] [Indexed: 12/21/2022]
Abstract
BACKGROUND In recent years, liver transplantation in patients with hepatocellular cancers and cirrhosis has been restricted to those with small cancers (<5 cm for solitary and <3 cm for multifocal HCC with <3 nodules). The selection of patients for liver transplantation is based on pre-operative imaging. The accuracy of imaging correlated with explant histology and the effect of tumour stage has not been evaluated in this selected population. METHODS In this study, prospectively collected data for 30 patients who underwent orthotopic liver transplantation for cirrhosis complicated by small hepatocellular carcinoma (HCC) at a single centre have been reviewed with the aim of correlating radiological findings, explant histology and patient outcome. Patients who underwent orthotopic liver transplantation between 1995 and 1999 had plain and contrast-enhanced dual-phase spiral CT (DCT) scans of the liver. Patients suspected of having HCC on CT scan or due to elevated serum alpha-fetoprotein underwent iodized oil CT (IOCT). Following transplantation, the explanted liver was serially sectioned at 10-mm intervals and examined by a pathologist blinded to the results of imaging. Data collected prospectively on imaging and histology were compared with outcome data. The median period of follow-up was 1,139 days (range 690-1,955 days) after transplantation. All patients were followed up by clinical assessment, assessment of serum alpha-protein levels and imaging when indicated. RESULTS All the patients transplanted fulfilled the selective criteria on the basis of imaging (solitary HCC <5 cm in diameter or multifocal HCC <3 cm in diameter with <3 nodules). Of the 30 patients transplanted, 46 HCCs were detected on explant histology with a median size of 24 mm (range 6-75 mm). Ten patients had multifocal disease (median number of lesions 2, range 2-4). No significant difference was observed between IOCT and DCT with regards to the sensitivity (67.4 vs. 68%) and specificity (78.97 vs. 88.6%) of detecting HCCs. IOCT had a positive predictive value of 78.9% as compared to 82.8% for DCT. IOCT had an overall sensitivity of 40% as compared to 30% for DCT in detecting multifocal disease (not significant). Histological assessment of the explanted livers showed that 8 patients had well-, 17 moderate and 5 poorly differentiated HCCs. Tumour size and the presence of multifocal disease did not influence survival in this study. Microvascular invasion was more common with larger tumours (from 38% with lesions less than 40 mm in diameter to 60% with lesions >40 mm in diameter; p < 0.01) and with moderately (29.4%) or poorly differentiated (60%) HCCs than well-differentiated HCC (12.5%) (p < 0.04 and 0.01 for well- vs. moderately and poorly differentiated HCC, respectively). Microvascular invasion on explant histology was associated with poor survival. Of the 17 transplant recipients without vascular invasion, 15 were alive at 1 and 2 years in comparison to 7 of 9 with microscopic vascular invasion (p < 0.01). Four patients died in the post-transplant period due to recurrent HCC. Overall survival [after excluding early post-transplant sepsis-induced deaths (n = 4)] at 1 year was 83.3%. CONCLUSIONS Selective criteria for transplantation of HCC in cirrhosis are associated with a 1-year and 3-year survival rate of 73.3% (including early post-transplant sepsis-induced deaths). IOCT and DCT are similar in their ability to detect unifocal or multifocal HCC. Tumour size and number are not predictive of recurrence with these selective criteria, but microscopic vascular invasion is a bad prognostic factor.
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Affiliation(s)
- Shantanu Bhattacharjya
- Department of Surgery, Royal Free Hospital, Royal Free and University College School of Medicine, London, UK
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22
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N/A, 房 静. N/A. Shijie Huaren Xiaohua Zazhi 2003; 11:1416-1419. [DOI: 10.11569/wcjd.v11.i9.1416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
Affiliation(s)
| | - 房静远
- 上海第二医科大学附属仁济医院消化疾病研究所 上海市 200001
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23
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Fontana RJ, Hamidullah H, Nghiem H, Greenson JK, Hussain H, Marrero J, Rudich S, McClure LA, Arenas J. Percutaneous radiofrequency thermal ablation of hepatocellular carcinoma: a safe and effective bridge to liver transplantation. Liver Transpl 2002; 8:1165-74. [PMID: 12474157 DOI: 10.1053/jlts.2002.36394] [Citation(s) in RCA: 139] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Although liver transplantation is an effective means of treating selected patients, pretransplantation tumor progression may preclude some patients from undergoing transplantation. The aim of this study is to determine the safety and efficacy of percutaneous radiofrequency thermal ablation (RFA) in 33 consecutive patients with nonresectable HCC and advanced cirrhosis. Mean subject age was 57.2 +/- 10.6 years, mean Child-Turcotte-Pugh score was 7.0 +/- 1.4, and mean maximal tumor diameter was 3.6 +/- 1.1 cm. Using contrast-enhanced computed tomography and magnetic resonance imaging, 22 patients (66%) had a complete radiological response at 3 months post-RFA, whereas 11 patients (33%) had an incomplete radiological response. During follow-up, 18 patients (54%) experienced tumor progression and 9 subjects underwent repeated ablation for either residual disease or tumor progression. The overall actuarial patient survival rate of the 33 patients was 58% at 2 years, whereas the transplantation-free patient survival rate was 34% at 2 years. Fifteen of 23 transplant candidates were successfully bridged to liver transplantation after a mean post-RFA follow-up of 7.9 +/- 6.7 months. The extent of tumor necrosis in the explant varied, but no subjects had evidence of tumor seeding on post-RFA imaging, at liver transplantation, or in the explant. The 3-year actuarial posttransplantation patient survival rate was 85%. Two patients have developed posttransplantation recurrence, and both had microscopic vascular invasion in their explants. In summary, our data show that RFA is a safe and effective treatment modality for patients with advanced cirrhosis and nonresectable HCC. Although the ability of RFA to prevent or delay tumor progression requires further prospective study, its favorable safety profile and promising efficacy make it an attractive treatment option for liver transplant candidates with nonresectable HCC.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
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24
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, responsible for an estimated one million deaths annually. The incidence in the United States has steadily increased over the past two decades. Although HCC has historically had a dismal prognosis, it is now being detected earlier as a result of improved radiologic imaging and surveillance. This affords the opportunity to treat patients with curative intent, and may improve survival. Partial hepatectomy and transplantation each provide potentially curative therapy for selected patients with HCC. Transplantation is indicated when there is severe underlying liver dysfunction. Local ablative therapy, such as ethanol injection, hepatic artery embolization, and radiofrequency ablation, offer palliation for patients when surgery is not feasible. The rational application of the myriad of therapies to a patient with HCC is designed to maximize both quality of life and survival.
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Affiliation(s)
- Charles Cha
- Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
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25
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Mori K, Scheidler J, Helmberger T, Holzknecht N, Schauer R, Schirren CA, Bittmann I, Dugas M, Reiser M. Detection of malignant hepatic lesions before orthotopic liver transplantation: accuracy of ferumoxides-enhanced MR imaging. AJR Am J Roentgenol 2002; 179:1045-51. [PMID: 12239063 DOI: 10.2214/ajr.179.4.1791045] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate the diagnostic accuracy of ferumoxides-enhanced MR imaging for screening malignant hepatic lesions before orthotopic liver transplantation. MATERIALS AND METHODS The study comprised 48 patients who underwent MR imaging within 6 months before transplantation. Imaging techniques included unenhanced and ferumoxides-enhanced T1-weighted gradient-echo and T2-weighted fast spin-echo sequences and ferumoxides-enhanced T2(*)-weighted gradient-echo sequences. Qualitative and quantitative analyses were performed; the gold standard was the histopathologic reports of explanted livers. RESULTS Twenty patients had malignant hepatic lesions, and 24 hepatocellular carcinomas were histopathologically proven. The mean area under the receiver operating characteristic curve and the mean sensitivity were significantly greater for the image sets with ferumoxides-enhanced gradient-echo sequences than for those without these sequences. The mean sensitivity and specificity of all sequences were 85% and 74% on a per-patient basis, respectively. The mean contrast-to-noise ratio was significantly greater for the ferumoxides-enhanced T2(*)-weighted gradient-echo sequences than for any other sequences and for the ferumoxides-enhanced T1-weighted gradient-echo sequences than for unenhanced sequences and the ferumoxides-enhanced T2-weighted fast spin-echo sequences. CONCLUSION Ferumoxides-enhanced gradient-echo sequences improved the diagnostic accuracy and the sensitivity for detecting malignant hepatic lesions in patients with end-stage cirrhosis of the liver. However, the specificity was not improved even after the administration of ferumoxides because of the false-positive lesions that were mainly the result of fibrotic changes.
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Affiliation(s)
- Kensaku Mori
- Department of Clinical Radiology, Klinikum Grosshadern, Ludwig Maximilias University of Munich, Marchioninistr. 15, D-81377 Munich, Germany
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26
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Papatheodoridis GV, Dimou E, Papadimitropoulos V. Nucleoside analogues for chronic hepatitis B: antiviral efficacy and viral resistance. Am J Gastroenterol 2002; 97:1618-28. [PMID: 12135009 DOI: 10.1111/j.1572-0241.2002.05819.x] [Citation(s) in RCA: 98] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Nucleoside analogues have been recently introduced in the management of chronic hepatitis B virus (HBV) infection. They mainly act by inhibition of HBV polymerase activity resulting in decrease of viral replication. They are administered orally, and most of them have an excellent tolerance and safety profile. Lamivudine is the only nucleoside analogue licensed for chronic hepatitis B. It has potent activity against HBV, and a 12-month course achieves clearance of hepatitis B e antigen (HBeAg) in 20-30% of HBeAg-positive patients and both biochemical and virological remission in more than 65-70% of HBeAg-negative chronic hepatitis B patients. Famciclovir and ganciclovir are less effective, whereas other nucleoside or nucleotide analogues, such as adefovir, entecavir, and emtricitabine, are currently under evaluation. Prolonged effective antiviral therapy is required for eradication of chronic HBV infection, but long-term treatment with nucleoside analogues has been found to be associated with progressively increasing rates of viral resistance because of emergence of resistant HBV mutant strains. Virological breakthroughs usually develop after the first 6 months of lamivudine monotherapy, and their rate ranges between 15% and 30% at 12 months and exceeds 50% after 3 yr of therapy. Resistant HBV mutant strains harbor point mutations in the HBV polymerase gene and predominantly in the well-conserved YMDD motif. Although resistant HBV strains may have impaired replication capacity compared with the wild HBV, their clinical significance has not been completely clarified yet. No significant biochemical or clinical event may develop in some cases, whereas severe biochemical breakthroughs with or without deterioration of liver function may develop in others. To date, there is no proven effective therapy for the resistant HBV mutant strains, although adefovir and entecavir seem to be interesting candidates.
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27
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Delaugerre C, Marcelin AG, Thibault V, Peytavin G, Bombled T, Bochet MV, Katlama C, Benhamou Y, Calvez V. Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine. Antimicrob Agents Chemother 2002; 46:1586-8. [PMID: 11959607 PMCID: PMC127167 DOI: 10.1128/aac.46.5.1586-1588.2002] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2001] [Revised: 11/06/2001] [Accepted: 01/22/2002] [Indexed: 11/20/2022] Open
Abstract
Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65 and 70 or any other particular HIV-1 reverse transcriptase resistance profile.
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28
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Chen MS, Li JQ, Zhang YQ, Lu LX, Zhang WZ, Yuan YF, Guo YP, Lin XJ, Li GH. High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol 2002; 8:74-8. [PMID: 11833075 PMCID: PMC4656630 DOI: 10.3748/wjg.v8.i1.74] [Citation(s) in RCA: 79] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To conduct a randomized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization(TACE) in the treatment of large hepatocellular carcinoma (HCC).
METHODS: From January 1993 to June 1998, 473 patients with unresectable hepatocellular carcinoma were divided into two groups: 216 patients in group A received more than 20mL iodized oil during the first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the same way. The Child’s classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment. During the TACE procedure the catheters was inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography. The anticancer drug mixed with iodized oil (Lipiodol) were Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10 mL Lipiodol, 138 cases received 11-15 mL, and the average dose was 11.8 mL.
RESULTS: High-dose Lipiodol chemoembolization caused tolerable side effects and a little hurt to the liver function in the patients with Child grade A or ICG-R15 < 20. But the patients with child grade B or ICG-R15 > 20 had higher risk of liver failure after high-dose TACE. More type I and type II lipiodol accumulations in CT scan after 4 weeks of TACE were seen in the group A patients than those in the group B patients (P < 0.01). The resection rate and complete tumor necrosis rate in group A were higher than those of group B (P < 0.05). The 1-,2-,3-year survival rates of group A patients with Child grade A were 79.2%, 51.8% and 34.9%, respectively, better than those of group B (P < 0.001).
CONCLUSION: High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor. High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose. For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol is recommended.
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Affiliation(s)
- Min-Shan Chen
- Department of Hepatobiliary Cancer Center of Sun Yet-sen University of Medical Sciences, 651 Dongfeng Road East, Guangzhou 510060, China.
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30
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Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodés J. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35:421-30. [PMID: 11592607 DOI: 10.1016/s0168-8278(01)00130-1] [Citation(s) in RCA: 3228] [Impact Index Per Article: 134.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Affiliation(s)
- J Bruix
- Liver Unit, Digestive Disease Institute, Hospital Clinic, IDIBAPS, Barcelona, Catalonia, Spain.
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31
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Nakayama A, Imamura H, Matsuyama Y, Kitamura H, Miwa S, Kobayashi A, Miyagawa S, Kawasaki S. Value of lipiodol computed tomography and digital subtraction angiography in the era of helical biphasic computed tomography as preoperative assessment of hepatocellular carcinoma. Ann Surg 2001; 234:56-62. [PMID: 11420483 PMCID: PMC1421948 DOI: 10.1097/00000658-200107000-00009] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To compare the diagnostic accuracies of Lipiodol computed tomography (CT) and helical biphasic CT as preoperative imaging modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA Lipiodol CT after digital subtraction angiography has long been used as a highly sensitive imaging modality for HCC. The recent advent of helical CT has allowed scanning the entire liver during both the arterial and portal venous phase of contrast enhancement. METHODS The authors analyzed data from 164 patients who underwent hepatic resection for HCC to calculate the sensitivity and specificity of these modalities. Findings of intraoperative ultrasonography followed by histologic confirmation were set as the gold standard. RESULTS Although sensitivity decreased with both modalities as tumors became small and well differentiated, helical CT showed a higher sensitivity than Lipiodol CT in detecting well-differentiated HCC nodules smaller than 2 cm. In contrast, Lipiodol CT was superior to helical CT for the detection of small but moderately to poorly differentiated nodules. The overall sensitivity of helical CT was higher than that of Lipiodol CT. These findings suggest that helical CT is superior in delineating early HCC, whereas Lipiodol CT is specific to the detection of intrahepatic metastases. In terms of specificity, helical CT was superior to Lipiodol CT. CONCLUSIONS Helical CT and Lipiodol CT are complementary modalities. At present, helical biphasic CT does not obviate the need for invasive techniques such as angiography and Lipiodol CT as preoperative examinations for HCC.
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Affiliation(s)
- A Nakayama
- First Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
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32
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Rode A, Bancel B, Douek P, Chevallier M, Vilgrain V, Picaud G, Henry L, Berger F, Bizollon T, Gaudin JL, Ducerf C. Small nodule detection in cirrhotic livers: evaluation with US, spiral CT, and MRI and correlation with pathologic examination of explanted liver. J Comput Assist Tomogr 2001; 25:327-36. [PMID: 11351179 DOI: 10.1097/00004728-200105000-00001] [Citation(s) in RCA: 248] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The purpose of this work was to evaluate the detection and characterization of nodules > or = 8 mm and small hepatocellular carcinomas (HCCs) in liver cirrhosis. METHOD Pathologic examination and results of US, helical CT, and dynamic MRI with gadolinium were compared after orthotopic liver transplantation (OLT) of 43 cirrhotic patients. Nodules were classified as macroregenerative nodules (MRNs), borderline nodules (BNs), and HCC. RESULTS Pathologic examination classified 69 nodules: 50 MRNs, 6 BNs, and 13 HCCs. Sensitivities of MRN, BN, and HCC detection were, respectively, for US imaging 2% (1/50), 33.3% (2/6), and 46.2% (6/13); for helical CT 2% (1/50), 50% (3/6), and 53.8% (7/13); and for MRI 42% (21/50), 50% (3/6), and 76.9% (10/13). MRI detected 21 MRNs. They presented on T1/T2-weighted images as hyperintense/hypointense (n = 8), hyperintense/isointense (n = 7), hypointense/hypointense (n = 4), hypointense/isointense (n = 1), and hypointense depicted only on echo planar imaging (n = 1). The three detected BNs were hyperintense/hypointense nodules. The 10 detected HCCs appeared hyperintense/isointense (n = 7), hyperintense/hypointense (n = 2), and hypointense/isointense (n = 1). None of the MRNs but eight HCCs and one BN were enhanced after gadolinium injection. CONCLUSION Contrast-enhanced MRI is the most sensitive technique for detecting liver nodules. No MR signal intensity pattern characteristic of small HCCs enables differentiation from benign nodules, however. Gadolinium enhancement is the most sensitive and specific characteristic of HCC.
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Affiliation(s)
- A Rode
- Department of Radiology, Hôpital de la Croix Rousse, Lyon, France
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Abstract
The incidence of hepatocellular carcinoma is increasing world-wide. Although there are no randomized controlled trials showing benefits from surveillance programmes, these strategies have been widely practised by hepatologists, and most early tumours are diagnosed in the setting of such a policy. In this chapter we summarize the surveillance schedule and recall the policy applied in our Unit. Diagnosis at an early stage is crucial to allow the application of curative treatments that are the only hope for increasing the life expectancy of the patient. Surgical resection and liver transplantation are considered the first-line options for early tumours, although there is no agreement on which is the best approach. Resection is limited by the high recurrence rate, whereas the increasing waiting times have decreased the intention-to-treat outcomes of transplantation. Percutaneous treatments are reserved for patients with single non-surgical tumours. Clinical trials assessing treatments for patients with advanced tumours have not shown any survival benefits.
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Affiliation(s)
- J M Llovet
- Liver Unit, Institut de Malalties Digestives, Catalonia, Spain
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Abstract
Hepatocellular carcinoma (HCC) has ranked second in cancer mortality in China since the 1990s and is increasing in frequency among males in many countries. Hepatitis B and C viruses, aflatoxin and algal toxin in the contaminated drinking water remain major aetiological factors and hepatitis G virus and transfusion-transmitted virus can not be excluded. A prospective randomized control trial screening for HCC in a high-risk population using alpha fetoprotein (AFP) and ultrasonography has demonstrated a decrease in HCC mortality. Rapidly progressing medical imaging has continuously contributed to the improving treatment results. Surgical resection still plays a major role in influencing prognosis of HCC. Studies on recurrence and metastasis after curative resection have become a key issue for further improvement of the surgical outcome. Regional cancer therapies are progressing rapidly, based on the advances in early diagnosis. The advantages and disadvantages of these are noted. Multimodality combination and sequential treatment has been accepted as an important approach for unresectable HCC and cytoreduction and sequential resection have attracted attention. Conformal radiotherapy has shown important potential for HCC treatment. Intra-arterial chemotherapy has been repeatedly proved effective; however, systemic chemotherapy for HCC remains disappointing. The effects of tamoxifen are questionable, whereas alpha-interferon has been shown to have significant potential, particularly in prevention of recurrence. All of these treatments have resulted in continuing improvement of HCC prognosis in some centres.
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Affiliation(s)
- Z Y Tang
- Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, China.
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Suarez Y, França AC, Llovet JM, Fuster J, Bruix J. The current status of liver transplantation for primary hepatic malignancy. Clin Liver Dis 2000; 4:591-605. [PMID: 11232163 DOI: 10.1016/s1089-3261(05)70128-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Several advances have been achieved during the last years in the management of patients with liver cancer. The refinement of the imaging techniques and the better knowledge of the biology of this neoplasm have facilitated the establishment of useful criteria to select patients for transplantation. Following a strict selection policy (solitary tumors < or = 5 cm or up to 3 foci each one < or = 3 cm) patients with liver cancer may achieve the same survival as nonneoplastic subjects. Currently, the main problem is how to diminish the risk of tumor progression while waiting for a liver. Although at present the benefits of invasive treatments are ill-defined, the ongoing studies exploring new treatment options hopefully will succeed in preventing this complication and further improve the current results.
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Affiliation(s)
- Y Suarez
- Barcelona-Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, University of Barcelona, Catalonia, Spain
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Abstract
Chronic hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Its prevalence approaches 10% in hyperendemic areas, such as southeast Asia, China, and Africa. Although chronic HBV infection is seen less frequently in North America and Europe, an estimated 1.25 million persons in the United States are infected. In the past decade, revolutionary strides have been made toward the treatment of chronic HBV infection. Interferon-alpha was once the only available therapy but has recently been joined by the nucleoside analogues, the most extensively studied of which is lamivudine. Interferon therapy continues to have a role in the treatment of a carefully selected group of patients. Lamivudine therapy, which has less stringent selection criteria, suppresses HBV DNA in almost all treated patients: Seventeen percent to 33% experience loss of hepatitis B e antigen, and 53% to 56% have a histologic response. Extended lamivudine treatment leads to the development of a specific lamivudine-resistant virus with base-pair substitutions at the YMDD locus of the DNA polymerase. Newer nucleoside analogues and other immunomodulator therapies are being investigated. In the future, combination therapy with different classes of agents may yield improved response rates and delay the development of resistance.
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Affiliation(s)
- A H Malik
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas 75390-9151, USA
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37
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Abstract
Improvements in diagnostic techniques have enhanced our understanding of the natural history of hepatocellular carcinoma (HCC). This has facilitated a proper evaluation of the available treatment options for this neoplasm through both phase II studies and randomized controlled trials. Surgical resection and liver transplantation constitute the first two radical options, and when they are contra-indicated, patients may benefit from percutaneous ethanol injection or thermal ablation by radiofrequency current. These options may also achieve a complete response and constitute the last potentially radical therapies for small HCC. In contrast, for large multinodular tumours, the available treatment options have not been shown to improve survival. Arterial embolization with or without associated chemotherapy has been widely used. However, randomized controlled trials have failed to show a survival benefit, emphasizing the need to develop new treatment strategies.
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Affiliation(s)
- J Bruix
- Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Catalonia, Spain
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Bartolozzi C, Donati F, Cioni D, Crocetti L, Lencioni R. Computed Tomography of Hepatocellular Carcinoma. LIVER MALIGNANCIES 1999. [DOI: 10.1007/978-3-642-58641-5_6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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