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Chang SH, Cabrera R, Heo J, Park C, Guo J, Park H. Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC. Clin Pharmacol Ther 2025; 117:1030-1038. [PMID: 39489881 DOI: 10.1002/cpt.3481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/08/2024] [Indexed: 11/05/2024]
Abstract
The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.
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Affiliation(s)
- Shao-Hsuan Chang
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Jihaeng Heo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Chanhyun Park
- Health Outcomes Division, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA
| | - Jingchuan Guo
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
| | - Haesuk Park
- Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA
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Maekawa S, Takano S, Enomoto N. Risk of hepatocellular carcinoma after viral clearance achieved by DAA treatment. J Formos Med Assoc 2024; 123:1124-1130. [PMID: 38245398 DOI: 10.1016/j.jfma.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/22/2024] Open
Abstract
The advent of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment, enabling most HCV-infected patients to achieve a sustained viral response (SVR) easily and safely in a short period. On the other hand, it is gradually being recognized that a significant proportion of patients are still at risk of developing de novo and recurrent hepatocellular carcinoma (HCC), even after HCV elimination, and therefore, elucidation of the risk of de novo and recurrent HCC, investigation of its molecular basis, and construction of accurate prediction models are emerging as new important clinical topics. In this review, we present recent advances regarding these issues.
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Affiliation(s)
- Shinya Maekawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
| | - Shinichi Takano
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuyuki Enomoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
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3
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Makhlouf NA, Abu-Elfatth A, Khaled T, El-Kassas M. The Interplay Between Schistosomiasis and Hepatitis C Virus: Battling on Two Fronts. INFECTIOUS DISEASES & IMMUNITY 2024; 4:187-193. [DOI: 10.1097/id9.0000000000000137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Indexed: 01/04/2025]
Abstract
Abstract
Schistosomiasis is a prevalent health issue in numerous countries in Africa, Asia, and South America. Data regarding the coinfection of schistosomiasis with hepatitis C virus (HCV) is limited, yet this coinfection is prevalent in regions where schistosomiasis is endemic. The extent of the coinfection issue is evident in countries with a high prevalence of both diseases, such as Egypt. Coinfections with schistosomiasis result in more pronounced liver damage compared with an HCV infection alone. Schistosomiasis has been found to disrupt HCV-specific T-cell responses, resulting in high viral load, increased likelihood of HCV chronicity, and accelerated development of comorbidities in individuals with coinfection. Introducing new, directly acting antivirals for HCV treatment resulted in a marked shift in the disease landscape. This shift may have an impact on the incidence of coinfection with schistosomiasis. This review emphasizes the notable influence of schistosomiasis on the vulnerability to HCV coinfection, the gravity of the consequent liver pathology, and the effectiveness of HCV antiviral therapy.
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Affiliation(s)
- Nahed A Makhlouf
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Ahmed Abu-Elfatth
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
- Department of Gastroenterology and Hepatology, Aljazeera Hospital, Riyadh 14236, Saudi Arabia
| | - Tasneem Khaled
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia
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Cabibbo G, Celsa C, Rimassa L, Torres F, Rimola J, Kloeckner R, Bruix J, Cammà C, Reig M. Navigating the landscape of liver cancer management: Study designs in clinical trials and clinical practice. J Hepatol 2024; 80:957-966. [PMID: 38307346 DOI: 10.1016/j.jhep.2024.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 12/28/2023] [Accepted: 01/18/2024] [Indexed: 02/04/2024]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide and its prognosis is highly heterogeneous, being related not only to tumour burden but also to the severity of underlying chronic liver disease. Moreover, advances in systemic therapies for HCC have increased the complexity of patient management. Randomised-controlled trials represent the gold standard for evidence generation across all areas of medicine and especially in the oncology field, as they allow for unbiased estimates of treatment effect without confounders. Observational studies have many problems that could reduce their internal and external validity. However, large prospective (well-conducted) observational real-world studies can detect rare adverse events or monitor the occurrence of long-term adverse events. How best to harness real world data, which refers to data generated from the routine care of patients, and real-world 'evidence', which is the evidence generated from real-world data, represents an open challenge. In this review article, we aim to provide an overview of the benefits and limitations of different study designs, particularly focusing on randomised-controlled trials and observational studies, to address important and not fully resolved questions in HCC research.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy; Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS London, UK
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Ferran Torres
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Liver Oncology Unit, Radiology Department, CDI, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Roman Kloeckner
- Institute of Interventional Radiology, University Hospital Schleswig-Holstein-Campus Lubeck, 23583 Lubeck, Germany
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
| | - Calogero Cammà
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Liver Oncology Unit, Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Barcelona University, Barcelona, Spain.
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Li L, Li ZZ, Pan LX, Su JY, Huang S, Ma L, Zhong JH. Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions. J Clin Transl Hepatol 2024; 12:525-533. [PMID: 38779519 PMCID: PMC11106350 DOI: 10.14218/jcth.2024.00030] [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] [Received: 01/19/2024] [Revised: 03/31/2024] [Accepted: 04/09/2024] [Indexed: 05/25/2024] Open
Abstract
Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.
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Affiliation(s)
- Le Li
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Guangxi Academy of Medical Sciences, Emergency Department, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
| | - Zhen-Zhen Li
- Pathology Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Li-Xin Pan
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jia-Yong Su
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Shan Huang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, Guangxi, China
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Miuma S, Miyaaki H, Ichikawa T, Matsuzaki T, Goto T, Kamo Y, Shigeno M, Hino N, Ario K, Yanagi K, Tsutsumi T, Fukushima N, Nakashiki S, Yamasaki K, Hamasaki K, Shibata H, Arima K, Yamamichi S, Yamashima M, Takahashi K, Nakao Y, Fukushima M, Haraguchi M, Sasaki R, Ozawa E, Taura N, Nakao K. Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history. J Med Virol 2024; 96:e29432. [PMID: 38509793 DOI: 10.1002/jmv.29432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 12/21/2023] [Accepted: 01/16/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND AND AIMS Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.
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Affiliation(s)
- Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tatsuki Ichikawa
- Department of Gastroenterology, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan
| | - Toshihisa Matsuzaki
- Department of Gastroenterology, Sasebo City General Medical Center, Sasebo, Japan
| | - Takashi Goto
- Department of Gastroenterology, Nagasaki Rosai Hospital, Sasebo, Japan
| | - Yasuhiro Kamo
- Department of Gastroenterology, Hakujujikai Sasebo Chuo Hospital, Sasebo, Japan
| | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Naoyuki Hino
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Keisuke Ario
- Department of Gastroenterology, National Hospital Organization Ureshino Medical Center, Ureshino, Japan
| | - Kenji Yanagi
- Department of Gastroenterology, Nijigaoka Hospital, Nagasaki, Japan
| | - Takuya Tsutsumi
- Department of Gastroenterology, Nijigaoka Hospital, Nagasaki, Japan
| | | | | | - Kazufumi Yamasaki
- Department of Gastroenterology, Saint Francis Hospital, Nagasaki, Japan
| | | | - Hidetaka Shibata
- Gastroenterology and Hepatology, Shibata Chokodo Hospital, Shimabara, Japan
| | - Kazuhiko Arima
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinobu Yamamichi
- Department of Gastroenterology, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan
| | - Mio Yamashima
- Department of Gastroenterology, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan
| | - Kosuke Takahashi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yasuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Department of Gastroenterology, Koebaru Chuo Hospital, Nagasaki, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Eisuke Ozawa
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Naota Taura
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Panneerselvam S, Wilson C, Kumar P, Abirami D, Pamarthi J, Reddy MS, Varghese J. Overview of hepatocellular carcinoma: from molecular aspects to future therapeutic options. Cell Adh Migr 2023; 17:1-21. [PMID: 37726886 PMCID: PMC10512929 DOI: 10.1080/19336918.2023.2258539] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 09/08/2023] [Indexed: 09/21/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the seventh most highly prevalent malignant tumor globally and the second most common cause of mortality. HCC develops with complex pathways that occur through multistage biological processes. Non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, alcoholic liver disease, autoimmune hepatitis, hepatitis B, and hepatitis C are the causative etiologies of HCC. HCC develops as a result of epigenetic changes, protein-coding gene mutations, and altered signaling pathways. Biomarkers and potential therapeutic targets for HCC open up new possibilities for treating the disease. Immune checkpoint inhibitors are included in the treatment options in combination with molecular targeted therapy.
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Affiliation(s)
- Sugan Panneerselvam
- Department of Hepatology and Transplant Hepatology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
| | - Cornelia Wilson
- Natural and Applied Sciences, School of Psychology and Life Sciences, Canterbury Christ Church University, Discovery Park, Sandwich, UK
| | - Prem Kumar
- Department of Hepatology and Transplant Hepatology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
| | - Dinu Abirami
- Department of Gastroenterology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
| | - Jayakrishna Pamarthi
- Multi-Disciplinary Research Unit, Madras Medical College, Chennai, Tamil Nadu, India
| | - Mettu Srinivas Reddy
- The Director and Head, Liver Transplant and HPB surgery, Gleneagles Global Health City, Chennai, Tamil Nadu, India
| | - Joy Varghese
- Department of Gastroenterology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
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Pelizzaro F, Trevisani F, Simeon V, Vitale A, Cillo U, Piscaglia F, Missale G, Sangiovanni A, Foschi FG, Cabibbo G, Caturelli E, Di Marco M, Azzaroli F, Brunetto MR, Raimondo G, Vidili G, Guarino M, Gasbarrini A, Campani C, Svegliati-Baroni G, Giannini EG, Mega A, Masotto A, Rapaccini GL, Magalotti D, Sacco R, Nardone G, Farinati F. Predictors of non-transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection. Liver Int 2023; 43:2762-2775. [PMID: 37753540 DOI: 10.1111/liv.15719] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 08/09/2023] [Accepted: 08/21/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non-transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. METHODS From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up-to-seven criteria were compared between patients with HCC <4 and ≥4 cm. RESULTS During a median follow-up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up-to-seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence-free survival and overall survival. HCC size ≥4 cm and high alpha-fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up-to-seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non-transplantable recurrence. CONCLUSIONS Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long-term survival. Non-transplantable recurrence is predicted by HCC size and AFP levels, among pre-operatively available variables. High-risk patients could be considered for frontline LT or listed for transplantation even before recurrence.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Franco Trevisani
- Unit of Semeiotics, Liver and Alcohol-related diseases, Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Vittorio Simeon
- Medical Statistics Unit, Mental, Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Napoli, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedale-Università di Padova, Padova, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gabriele Missale
- Department of Medicine and Surgery, Unit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | | | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizia R Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit, University of Pisa, Pisa, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Gianpaolo Vidili
- Department of Medicine Surgery and Pharmacy, Centralized Day Hospital of the medical area, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | | | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gian Ludovico Rapaccini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli 'Federico II', Napoli, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy
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9
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Chen R, Hou B, Zhou Y, Zhang T, Wang Z, Chen X, Zhang Y, Chen M. Recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors. Front Oncol 2023; 13:1018715. [PMID: 36910605 PMCID: PMC9997710 DOI: 10.3389/fonc.2023.1018715] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 02/01/2023] [Indexed: 02/25/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) frequently relapses after minimally invasive treatment. This study aimed to observe the influencing factors of different recurrence patterns after radiofrequency ablation (RFA) for the treatment of recurrence. Methods The medical records of HCC patients who underwent RFA between January 2010 and January 2019 were retrospectively reviewed. HCC recurrence is classified into three types: local tumour progression (LTP), intrahepatic distant metastasis, and extrahepatic metastasis. Risk factors, overall survival (OS), and disease-free survival (DFS) were assessed for each modality. Among the risk factors are age, gender, liver function tests, blood tests, and tumour size. The OS and DFS curves were measured by the Kaplan-Meier method. Results 406 patients who had undergone RFA were included in the study. The median survival for OS and DFS were 120 and 43.6 months. During follow-up, 39, 312, and 55 patients developed LTP, intrahepatic distant metastasis, and extrahepatic metastatic recurrence, respectively. The independent risk factors for each type were as follows: WBC > 5.55*109/L was an independent risk factor for local recurrence. Multiple tumours, extrahepatic metastases, and AFP > 200 ng/ml were used for intrahepatic metastases. Age (P = 0.030), recurrence pattern (P < 0.001) and Child-Pugh class B (P = 0.015) were independent predictors of OS. Conclusions According to our classification, each pattern of recurrence has different risk factors for recurrence, OS, and DFS.
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Affiliation(s)
- Rui Chen
- Department of Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China
| | - Beining Hou
- Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian, China
| | - Yanzhao Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Tuo Zhang
- Department of Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China
- Department of Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhengzheng Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Xun Chen
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
| | - Yingwei Zhang
- Beijing Key Laboratory of Mobile Computing and Pervasive Device, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
| | - Man Chen
- Department of Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China
- Department of Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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10
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Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR. J Gastroenterol 2022; 58:299-310. [PMID: 36585501 DOI: 10.1007/s00535-022-01940-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/05/2022] [Indexed: 12/31/2022]
Abstract
Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30 years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.
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11
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Comparisons of Viral Etiology and Outcomes of Hepatocellular Carcinoma Undergoing Liver Resection between Taiwan and Vietnam. Viruses 2022; 14:v14112571. [PMID: 36423180 PMCID: PMC9695296 DOI: 10.3390/v14112571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/17/2022] [Accepted: 11/19/2022] [Indexed: 11/22/2022] Open
Abstract
Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing liver resection. Vietnamese patients had a significantly higher ratio of hepatitis B virus (HBV) (p < 0.001) and a lower ratio of hepatitis C virus (HCV) (p < 0.001) and non-B non-C than Taiwanese patients. Among patients with HBV or non-B non-C, the mean age was younger in Vietnam than in Taiwan (p < 0.001, p = 0.001, respectively). The HCC patients in Vietnam had significantly higher serum alpha-fetoprotein (AFP) levels (p < 0.001), larger tumors (p < 0.001), and a higher ratio of macrovascular invasion (p < 0.001) and extrahepatic metastasis (p < 0.001), compared to those in Taiwan. Patients treated in Vietnam had a higher tumor recurrent rate (p < 0.001), but no difference in overall survival was found between both groups. In subgroup analysis, the recurrent rate of HCC was the highest in patients with dual HBV/HCV, followed by HCV or HBV, and non-B non-C (p < 0.001). In conclusion, although the viral etiology and clinicopathological characteristics of HCC differed, postoperative overall survival was comparable between patients in Taiwan and Vietnam.
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12
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Yi PS, Liu JN, Li Y, Wu B, Li JS. The priority of liver resection compared with transarterial chemoembolization in hepatocellular carcinoma at BCLC B1 stage: A single-center experience. Front Surg 2022; 9:920976. [PMID: 36439533 PMCID: PMC9681909 DOI: 10.3389/fsurg.2022.920976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 10/17/2022] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND This study aimed to compare the efficacy of liver resection (LR) and transarterial chemoembolization (TACE) in the treatment of Barcelona Clinic Liver Cancer B1 (BCLC B1) hepatocellular carcinoma. METHODS A total of 65 patients with BCLC B1 were divided into the radical (LR group) and TACE groups. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were carried out, and the prognostic factors for survival outcomes were identified using Cox proportional analysis. RESULTS The 1-, 3-, and 5-year survival rates and the 1-, 3-, and 5-year progression-free survival (PFS) rates in the LR group (P = 0.036) were significantly higher than those in the TACE group (P = 0.027). Results of the multivariate analysis demonstrated that tumor distribution (both lobes vs. semi-liver) and treatment strategy (LR vs. TACE) were independent risk factors for the overall survival (OS) [hazard ratios (HRs): 3.926 and 0.479; P < 0.05] and PFS (HR: 3.336 and 0.465, P < 0.05). LR was associated with increased OS and PFS compared with TACE in patients with BCLC B1 hepatocellular carcinoma.
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Affiliation(s)
- Peng-Sheng Yi
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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13
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Giuffrida P, Celsa C, Antonucci M, Peri M, Grassini MV, Rancatore G, Giacchetto CM, Cannella R, Incorvaia L, Corsini LR, Morana P, La Mantia C, Badalamenti G, Brancatelli G, Cammà C, Cabibbo G. The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints. Biomedicines 2022; 10:2827. [PMID: 36359347 PMCID: PMC9687474 DOI: 10.3390/biomedicines10112827] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/02/2022] [Indexed: 08/30/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.
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Affiliation(s)
- Paolo Giuffrida
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Ciro Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Michela Antonucci
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Marta Peri
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Maria Vittoria Grassini
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Gabriele Rancatore
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Carmelo Marco Giacchetto
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Roberto Cannella
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Lorena Incorvaia
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Lidia Rita Corsini
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Piera Morana
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Claudia La Mantia
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Badalamenti
- Department of Surgical, Oncological, and Oral Sciences (Di.Chir.On.S.), University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Brancatelli
- Section of Radiology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy
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Renzulli M, Pecorelli A, Brandi N, Brocchi S, Tovoli F, Granito A, Carrafiello G, Ierardi AM, Golfieri R. The Feasibility of Liver Biopsy for Undefined Nodules in Patients under Surveillance for Hepatocellular Carcinoma: Is Biopsy Really a Useful Tool? J Clin Med 2022; 11:4399. [PMID: 35956016 PMCID: PMC9369413 DOI: 10.3390/jcm11154399] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/14/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Background: The aim of the present study is to determine the feasibility of biopsy for atypical liver nodules in patients under surveillance for hepatocellular carcinoma (HCC), assessing which factors influence the decision to perform it. Methods: A total of 128 atypical liver nodules in 108 patients under surveillance for HCC, who underwent CT between September 2018 and September 2019, were included. All the images were saved digitally (on CD-ROM) and the two most representative images in the arterial and delayed phases were selected for each lesion and inserted into a digital atlas (on PDF). Two experienced radiologists (Readers 1 and 2) reviewed both the CD-ROM and the PDF to define the feasibility of biopsy in both scenarios, specifying the reasons for the unfeasibility of biopsy. The intra-observer variability and inter-observer variability were assessed. Results: When reviewing the PDF, 76 (59.4%) and 68 (53.1%) nodules were deemed unfeasible for biopsy by the less experienced radiologist (Reader 1) and the more experienced radiologist (Reader 2), respectively (p = 0.604). When reviewing the entire CT study, both percentages decreased slightly (Reader 1 = 70/128 (54.7%); Reader 2 = 61/128 (47.6%); p = 0.591). The intra-reader agreement on the PDF was substantial (k = 0.648 (95% CI = 0.513-0.783)). The inter-reader agreement on the PDF was slight (k = 0.185 (95% CI = 0.021-0.348)) and moderate on the entire CT study (k = 0.424 (95% CI = 0.269-0.579)). When assessing the PDF, the nodule size (10-20 mm) and location in segments six and eight were negatively and positively associated with the feasibility of liver biopsy, respectively. When assessing the CD-ROM, only the nodule dimension was associated with the unfeasibility of liver biopsy. Conclusions: The unfeasibility of liver biopsy is mainly due to the small size of the lesions and their location.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (S.B.); (R.G.)
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (S.B.); (R.G.)
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (S.B.); (R.G.)
| | - Stefano Brocchi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (S.B.); (R.G.)
| | - Francesco Tovoli
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.T.); (A.G.)
| | - Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.T.); (A.G.)
| | - Gianpaolo Carrafiello
- Diagnostic and Interventional Radiology Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20021 Milan, Italy; (G.C.); (A.M.I.)
| | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20021 Milan, Italy; (G.C.); (A.M.I.)
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (S.B.); (R.G.)
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15
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Innovations in education: A prospective study of storytelling narratives to enhance hepatitis C virus knowledge among substance users. World J Hepatol 2022. [DOI: 10.4254/wjh.v14.i5.973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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16
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Talal AH, Ding YX, Markatou M. Innovations in education: A prospective study of storytelling narratives to enhance hepatitis C virus knowledge among substance users. World J Hepatol 2022; 14:972-983. [PMID: 35721284 PMCID: PMC9157714 DOI: 10.4254/wjh.v14.i5.972] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/21/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Even though substance users have the highest hepatitis C virus (HCV) burden, many lack knowledge about the infection. Lack of knowledge is an important obstacle to pursuing HCV care. Although printed materials are conventionally utilized to disseminate HCV-related knowledge, narrative story-telling videos may be an alternative. Data are extremely limited, however, in the ability of storytelling videos to increase HCV knowledge among substance users. In this study, we hypothesized that a story-telling narrative video would increase substance user’s immediate and 1-month HCV-related knowledge compared to a printed format.
AIM To assess immediate and 1-month HCV-related knowledge retention among substance users comparing education delivered via a storytelling narrative video compared to a printed format.
METHODS We conducted a prospective matched, case-control study among substance users actively prescribed buprenorphine enrolled from two sites. The intervention site received the video and the control site, the brochure. Participants (n = 176) were matched on age, gender, and race. We obtained extensive patient and stakeholder input on the video’s design, validated the video’s content, and developed a recruitment plan to guide participant enrollment. Knowledge was assessed by administration of a 25-item instrument immediately before, immediately after, or one month after the intervention. Data were analyzed using nonparametric and generalized linear mixed-effects models.
RESULTS We recruited a total of 176 substance users, 90 and 86 individuals, from each site, respectively. One-month follow up occurred in 92% and 94% of enrollees in the control and intervention groups, respectively. In comparison with the pre-intervention scores, immediate knowledge recall increased significantly for both the intervention (P < 0.0001) and control (P < 0.0001) groups. Multivariate modeling revealed a significant improvement in HCV-related knowledge and retention (P = 0.033) among participants who viewed the storytelling video.
CONCLUSION Storytelling narratives emphasizing HCV education appear to be an effective method to increase HCV-related knowledge among substance users. They should become an educational cornerstone to promote HCV management among this population.
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Affiliation(s)
- Andrew H Talal
- Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY 14203, United States
| | - Yu-Xin Ding
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY 14214, United States
| | - Marianthi Markatou
- Department of Biostatistics, University at Buffalo, State University of New York, Buffalo, NY 14214, United States
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Wu Z, Lu H, Xie Q, Cheng J, Ma K, Hu X, Tan L, Zhang H, Liu C, Li X, Cai P. Preoperative Assessment of Abdominal Adipose Tissue to Predict Microvascular Invasion in Small Hepatocellular Carcinoma. J Clin Transl Hepatol 2022; 10:184-189. [PMID: 35528977 PMCID: PMC9039711 DOI: 10.14218/jcth.2021.00126] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/02/2021] [Accepted: 06/04/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Microvascular invasion (MVI) affects recurrence after treatment of small hepatocellular carcinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are associated with MVI in patients with sHCC. METHODS A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed. RESULTS Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analysis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (p<0.05), with an area under the receiver operating characteristic curve of 0.76 and 0.65, respectively. CONCLUSIONS The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.
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Affiliation(s)
- Zongqian Wu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hong Lu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qiao Xie
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jie Cheng
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kuansheng Ma
- Department of Hepatobiliary, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaofei Hu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Liang Tan
- Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China
- Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Macau, China
| | - Huarong Zhang
- Institute of Pathology and Southwest Cancer Center, Third Military Medical University (Army Military Medical University), Chongqing, China
| | - Chen Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaoming Li
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Correspondence to: Xiaoming Li and Ping Cai, Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China. Tel: +86-13594675445 (XL), +86-13228683331 (PC), Fax: +86-23-6546-3026, E-mail: (XL), (PC)
| | - Ping Cai
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
- Correspondence to: Xiaoming Li and Ping Cai, Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China. Tel: +86-13594675445 (XL), +86-13228683331 (PC), Fax: +86-23-6546-3026, E-mail: (XL), (PC)
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Bredt LC, Felisberto IBG, Felisberto DEG. Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver? World J Meta-Anal 2022; 10:46-51. [DOI: 10.13105/wjma.v10.i2.46] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/21/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
Whether liver transplantation (LT) plays a role in the treatment of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver (NCL) is a matter of debate. The recommendations for LT in this setting are extremely fragile and less well-defined than for cirrhosis-associated HCC. All reports of LT for NCL-HCC revealed that long-term outcomes of these patients are poor, and these dismal figures are justified by the advanced tumor stage at the time of LT, suggesting the presence of systemic micrometastatic disease. The decision-making regarding LT for NCL-HCC is difficult, since specific selection criteria are scarce, and basically the potential candidates are those with unresectable only-liver tumor at admission, or unresectable intrahepatic recurrence post-resection. Besides the surgical aspects regarding the tumor resectability, other phenotypic and genetic characteristics of the tumor should be considered for the indication of LT in this scenario. The present minireview aims to discuss and analyze the last series of LT for NCL-HCC, in order to help clinicians in the decision-making process regarding the role of LT in NCL-HCC treatment.
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Affiliation(s)
- Luis Cesar Bredt
- Surgical Oncology and Hepatobiliary Surgery, Unioeste University, Cascavel 85819-110, Paraná, Brazil
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Cost-Effectiveness Analysis of Follow-Up Schedule for Hepatocellular Carcinoma after Radiofrequency Ablation. JOURNAL OF ONCOLOGY 2022; 2022:3569644. [PMID: 35345515 PMCID: PMC8957434 DOI: 10.1155/2022/3569644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/13/2022] [Accepted: 02/14/2022] [Indexed: 11/29/2022]
Abstract
Methods A Markov model was established to evaluate the cost-effectiveness of every 2 months or 2-3 months (2- to 3-month group) versus every 3 months or 3-4 months (3- to 4-month group) posttreatment surveillance in the first two years for HCC after RFA. Transition probabilities and utility values were derived from the literature review. Costs of follow-up were estimated from our institution. The incremental cost-effectiveness ratio (ICER), which was less than $10888 per quality-adjusted life-year (QALY), was considered cost-effective. Sensitivity analyses were performed to determine the uncertainty of the model. Results The 2- to 3-month group gained 1.196 QALYs at a cost of $2212.66, while the effectiveness and cost of the 3- to 4-month group were 1.029 QALYs and $1268.92, respectively. The ICER of the 2- to 3-month group versus the 3- to 4-month group was $5651.14 per QALY gained, which was less than the willingness-to-pay threshold of 1-time gross domestic product per capita of China ($10888/QALY). One-way sensitivity analysis showed that the model was most sensitive to the utility of progression-free survival. The probabilistic sensitivity analysis demonstrated that the 2- to 3-month group had a higher probability of being more cost-effective than the 3- to 4-month group when willingness to pay was over $1088.8. Conclusions Every 2 months or 2-3 months of follow-up intervals were more cost-effective than 3 months or 3-4 months of follow-up intervals. Thus, the intensive follow-up interval in the first two years was recommended for Child-Pugh class A or B HCC patients within the Milan criteria following RFA.
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Kamal A, Elsheaita A, Abdelnabi M. Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate. World J Clin Cases 2022; 10:1764-1774. [PMID: 35317156 PMCID: PMC8891795 DOI: 10.12998/wjcc.v10.i6.1764] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 08/05/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
Since direct-acting antiviral agents (DAAs) have been introduced into hepatitis C virus treatment, the sustained viral response (SVR) rate has significantly increased to more than 95%. Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression, resulting in a reduction in the incidence of hepatocellular carcinoma (HCC). However, a significant debate exists related to DAA impact on HCC development. We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs. After a review of the published literature, we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy. More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.
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Affiliation(s)
- Ahmed Kamal
- Internal Medicine Department, Faculty of Medicine Alexandria University, Alexandria 21131, Egypt
| | - Ahmed Elsheaita
- Clinical and Experimental Internal Medicine Department, Medical Research Institute Alexandria University, Alexandria 21561, Egypt
| | - Mahmoud Abdelnabi
- Clinical and Experimental Internal Medicine Department, Medical Research Institute Alexandria University, Alexandria 21561, Egypt
- Internal Medicine Department, Texas Tech University Health Science Center, Lubbock, TX 79430, United States
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The Impact of Direct-Acting Antiviral Therapy on the Risk of Recurrence after Curative Resection in Patients with Hepatitis-C-Virus-Related Early Stage Hepatocellular Carcinoma. Medicina (B Aires) 2022; 58:medicina58020259. [PMID: 35208582 PMCID: PMC8875284 DOI: 10.3390/medicina58020259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/03/2022] [Accepted: 02/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background and Objectives: The impact of direct-acting antiviral (DAA)-based regimens on the recurrence of hepatocellular carcinoma (HCC) after successful curative hepatectomy is controversial. Aims: This study aimed to assess the association between DAAs treatment and recurrence risk in HCC after resection. Materials and Methods: We retrospectively assessed 152 cases of early stage (BCLC stage 0/A) hepatitis C virus (HCV)-related HCC (HCV-HCC) that underwent resection with curative intent between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital; 48 cases achieved a sustained virological response (SVR) by DAA, and 104 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative resection was analyzed by using the log-rank test and Kaplan–Meier method. A Cox proportional hazards model was used to analyze the factors that impacted RFS and OS. Results: Five patients (10.4%) experienced HCC recurrence after DAA therapy. The cumulative HCC recurrence rate was significantly lower in the DAA group than the non-treatment group (p < 0.001). Multivariate analysis revealed a significant difference in RFS between the non-treatment group and DAA group (p = 0.001; hazard ratio (HR), 4.978; 95% CI, 1.976–12.542); liver cirrhosis (p = 0.005; HR, 2.062; 95% CI, 1.247–3.410), microvascular invasion (p = 0.001; HR, 2.331; 95% CI, 1.408–3.860) and AFP > 15 ng/mL (p = 0.022; HR, 1.799; 95% CI, 1.089–2.970) were also independent factors for HCC recurrence. ALBI stage II/III (p = 0.005; HR, 3.249; 95% CI, 1.418–7.443) and microvascular invasion (p < 0.001; HR, 4.037 95% CI, 2.071–7.869) were independent factors for OS; no significant difference in OS was observed between the DAA and no DAA treatment groups. Conclusions: DAA treatment could reduce the risk of recurrence after curative treatment for early stage HCC.
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Pelizzaro F, Haxhi S, Penzo B, Vitale A, Giannini EG, Sansone V, Rapaccini GL, Di Marco M, Caturelli E, Magalotti D, Sacco R, Celsa C, Campani C, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Olivani A, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Trevisani F, Farinati F. Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment. Front Oncol 2022; 12:822507. [PMID: 35174092 PMCID: PMC8841805 DOI: 10.3389/fonc.2022.822507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/07/2022] [Indexed: 12/04/2022] Open
Abstract
Background Transarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy. Methods Data of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment. Results The proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC). Conclusions Despite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.
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Affiliation(s)
- Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Selion Haxhi
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Barbara Penzo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, University of Padova, Padova, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genova, Italy
| | - Vito Sansone
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gian Ludovico Rapaccini
- Gastroenterology Unit, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy
| | | | | | - Donatella Magalotti
- Internal Medicine Unit, Department of Medical and Surgical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Ciro Celsa
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties (PROMISE), Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Firenze, Firenze, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Gastroenterology Unit, University of Napoli “Federico II”, Napoli, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Università Cattolica del Sacro Cuore, Roma, Italy
| | | | | | - Andrea Olivani
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli “Federico II”, Napoli, Italy
| | - Giovanni Raimondo
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory and Internal Medicine Unit, University of Pisa, Pisa, Italy
| | - Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova, Italy
- *Correspondence: Fabio Farinati,
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Khajeh E, Moghadam AD, Eslami P, Ali-Hasan-Al-Saegh S, Ramouz A, Shafiei S, Ghamarnejad O, Dezfouli SA, Rupp C, Springfeld C, Carvalho C, Probst P, Mousavizadeh SM, Mehrabi A. Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery. BMC Cancer 2022; 22:91. [PMID: 35062904 PMCID: PMC8781082 DOI: 10.1186/s12885-022-09192-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery.
Methods
PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach.
Results
The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16–0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15–0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19–0.42; P < 0.001). The certainty of evidence for the outcomes was moderate.
Conclusion
Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.
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Trevisani F, Giannini EG. The ITA.LI.CA Consortium: How multicentre collaboration helped shape the management of patients with hepatocellular carcinoma on the basis of real-world evidence. Ann Hepatol 2022; 27 Suppl 1:100564. [PMID: 34688886 DOI: 10.1016/j.aohep.2021.100564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 02/04/2023]
Abstract
The growing diffusion of digitalisation and informatics has promoted the creation and analysis of large databases able to provide solid information. Analyses of "big data" generated by real-world practice are particularly useful for knowing incidence and mortality, disparities, temporal trends of diseases, identifying risk factors, predicting future scenarios, obtaining inputs for cost-effectiveness and treatment benefit modelling, designing new studies, and monitoring rare diseases. Although randomised controlled trials (RCTs) represent the gold-standard for generating evidence about new diagnostic, preventive or therapeutic procedures, their results should be integrated with real-world data to personalise patient management. Indeed, a substantial proportion of patients observed in field-practice have characteristics that prevent the access to RCTs or, when included, form sub-groups too small to provide robust post-hoc analyses. Furthermore, as RCTs are resource-consuming and designed to maximize the probability of success, they are generally performed in expert centres of high-income areas, excluding economically-deprived regions which could complementarily contribute to the medical progress as huge sources of real-world data. These considerations fuelled the creation in 1998 of the Italian Liver Cancer (ITA.LI.CA) consortium, with the aim to merge data of patients with hepatocellular carcinoma (HCC) managed in several centres. This cooperation permitted to analyse a multicentre, large cohort of HCC patients. Since then, the ITA.LI.CA group has progressively expanded to currently include 24 centres, and its database counts more than 9,000 patients. This article describes the history of the ITA.LI.CA consortium and presents its scientific production whose results greatly contributed to the incessant improvement of HCC management.
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Affiliation(s)
- Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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Celsa C, Stornello C, Giuffrida P, Giacchetto CM, Grova M, Rancatore G, Pitrone C, Di Marco V, Cammà C, Cabibbo G. Direct-acting antiviral agents and risk of Hepatocellular carcinoma: Critical appraisal of the evidence. Ann Hepatol 2022; 27 Suppl 1:100568. [PMID: 34699987 DOI: 10.1016/j.aohep.2021.100568] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023]
Abstract
Direct-acting antivirals (DAAs) revolutionized the treatment of chronic HCV-related disease achieving high rates of sustained virological response (SVR), even in advanced cirrhosis, with modest contraindications and a low rate of adverse events. However, the risk of hepatocellular carcinoma (HCC) persists due to the underlying chronic liver disease, both in patients with and without history of HCC. Although some initial studies reported a presumptive high risk of HCC development after DAA therapy, more recent observational studies denied this hypothesis. The residual risk for HCC occurrence after HCV eradication seems being progressively reduced with time after SVR. Data on recurrence of HCC after DAA exposure in patients with previously treated carcinoma initially reported conflicting results too, this being also due to methodological issues in analysis of retrospective multicenter studies. Anyway, current evidence support the use of DAAs in HCV-HCC treated patients, without any higher risk of tumor recurrence linked to antiviral therapy. Less effort has been made to evaluate the efficacy of DAA therapy in patients with untreated active HCC and it has been questioned whether a lower rate of SVR would be obtained among patients with active HCC. Studies conducted in this perspective concluded that HCC status does not influence the likelihood to obtain SVR with DAAs, making DAAs appropriate in HCC-active patients. As far as survival is concerned, recent studies conducted in cirrhotic HCV-related early-stage HCC found that DAAs improved overall survival, a benefit probably due to the reduction of hepatic decompensation.
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Affiliation(s)
- Ciro Celsa
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy; Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Sicilia, Italy
| | - Caterina Stornello
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Paolo Giuffrida
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Carmelo Marco Giacchetto
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Mauro Grova
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Gabriele Rancatore
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Concetta Pitrone
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy; Division of Medicine and Hepatology, University Hospital of Messina, Messina, Italy
| | - Vito Di Marco
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
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Pisano MB, Giadans CG, Flichman DM, Ré VE, Preciado MV, Valva P. Viral hepatitis update: Progress and perspectives. World J Gastroenterol 2021; 27:4018-4044. [PMID: 34326611 PMCID: PMC8311538 DOI: 10.3748/wjg.v27.i26.4018] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 04/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis, secondary to infection with hepatitis A, B, C, D, and E viruses, are a major public health problem and an important cause of morbidity and mortality. Despite the huge medical advances achieved in recent years, there are still points of conflict concerning the pathogenesis, immune response, development of new and more effective vaccines, therapies, and treatment. This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain to be solved, and future research directions. For hepatitis A virus we will address epidemiology, molecular surveillance, new susceptible populations as well as environmental and food detections. In the case of hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine improvement. On hepatitis C virus, we will focus on pathogenesis, immune response, direct action antivirals treatment in the context of solid organ transplantation, issues related to hepatocellular carcinoma development, direct action antivirals resistance due to selection of resistance-associated variants, and vaccination. Regarding hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy. Finally, for hepatitis E virus, we will address epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, the development of a vaccine, and environmental surveillance.
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Affiliation(s)
- María B Pisano
- Virology Institute, CONICET, School of Medical Sciences, National University of Córdoba, Cordoba X5016, Argentina
| | - Cecilia G Giadans
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
| | - Diego M Flichman
- Institute of Biomedical Investigations in Retrovirus and AIDS (INBIRS), School of Medicine, University of Buenos Aires, CONICET, CABA C1121ABG, Buenos Aires, Argentina
| | - Viviana E Ré
- Virology Institute, CONICET, School of Medical Sciences, National University of Córdoba, Cordoba X5016, Argentina
| | - María V Preciado
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
| | - Pamela Valva
- Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP) CONICET-GCBA, Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children’s Hospital, CABA C1425, Buenos Aires, Argentina
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Granito A, Forgione A, Marinelli S, Renzulli M, Ielasi L, Sansone V, Benevento F, Piscaglia F, Tovoli F. Experience with regorafenib in the treatment of hepatocellular carcinoma. Therap Adv Gastroenterol 2021; 14:17562848211016959. [PMID: 34104211 PMCID: PMC8165525 DOI: 10.1177/17562848211016959] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Regorafenib is a diphenylurea oral multikinase inhibitor, structurally comparable to sorafenib, which targets a variety of kinases implicated in angiogenic and tumor growth-promoting pathways. Regorafenib was the first agent to positively show significant survival advantage as a second-line therapy in patients with unresectable hepatocellular carcinoma (HCC) who had previously failed first-line treatment with sorafenib. Recent evidence has shown that its antitumor efficacy is due to a comprehensive spectrum of tumor neo-angiogenesis and proliferation inhibition and immunomodulatory effects on the tumor microenvironment, which plays a crucial role in tumor development. This review addresses the rationale and supporting evidence for regorafenib's efficacy in HCC that led to regorafenib's approval as a second-line therapy. In addition, we review proof from clinical practice studies that validate the RESORCE trial results. We discuss regorafenib's potential role in the newly emerging therapeutic strategy based on combination with immune checkpoint blockade and its possible extensibility to patient categories not enrolled in the registrative study.
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Affiliation(s)
- Alessandro Granito
- Department of Medical and Surgical Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Via Albertoni 15, Bologna, 40138, Italy
- Division of Internal Medicine IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Antonella Forgione
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Sara Marinelli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luca Ielasi
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Vito Sansone
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Francesca Benevento
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italia
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Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance. Cancers (Basel) 2021; 13:cancers13102454. [PMID: 34070067 PMCID: PMC8158142 DOI: 10.3390/cancers13102454] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/12/2021] [Accepted: 05/14/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Hepatitis B virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC). Understanding the unique features for HBV-induced HCC can shed new light on the unmet needs in its early diagnosis and effective therapy. During decades of chronic hepatitis B, hepatocytes undergoing repeated damage and regeneration accumulate genetic changes predisposing to HCC development. In addition to traditional mutations in viral and cellular oncogenes, HBV integration into the cell chromosomes is an alternative genetic change contributing to hepatocarcinogenesis. A striking male dominance in HBV-related HCC further highlights an interaction between androgen sex hormone and viral factors, which contributes to the gender difference via stimulating viral replication and activation of oncogenes preferentially in male patients. Meanwhile, a novel circulating tumor biomarker generated by HBV integration shows great potential for the early diagnosis of HCC. These unique HBV-induced hepatocarcinogenic mechanisms provide new insights for the future development of superior diagnosis and treatment strategies. Abstract Hepatitis B virus (HBV) infection is one of the important risk factors for hepatocellular carcinoma (HCC) worldwide, accounting for around 50% of cases. Chronic hepatitis B infection generates an inflammatory microenvironment, in which hepatocytes undergoing repeated cycles of damage and regeneration accumulate genetic mutations predisposing them to cancer. A striking male dominance in HBV-related HCC highlights the influence of sex hormones which interact with viral factors to influence carcinogenesis. HBV is also considered an oncogenic virus since its X and surface mutant proteins showed tumorigenic activity in mouse models. The other unique mechanism is the insertional mutagenesis by integration of HBV genome into hepatocyte chromosomes to activate oncogenes. HCC survival largely depends on tumor stages at diagnosis and effective treatment. However, early diagnosis by the conventional protein biomarkers achieves limited success. A new biomarker, the circulating virus–host chimera DNA from HBV integration sites in HCC, provides a liquid biopsy approach for monitoring the tumor load in the majority of HBV–HCC patients. To maximize the efficacy of new immunotherapies or molecular target therapies, it requires better classification of HCC based on the tumor microenvironment and specific carcinogenic pathways. An in-depth study may benefit both the diagnosis and treatment of HBV-related HCC.
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Tani J, Senoh T, Moriya A, Ogawa C, Deguchi A, Sakamoto T, Takuma K, Nakahara M, Oura K, Tadokoro T, Mimura S, Fujita K, Yoneyama H, Kobara H, Morishita A, Himoto T, Tsutsui A, Nagano T, Takaguchi K, Masaki T. Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study. Cancers (Basel) 2021; 13:cancers13092257. [PMID: 34066708 PMCID: PMC8125844 DOI: 10.3390/cancers13092257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/01/2021] [Accepted: 05/03/2021] [Indexed: 12/09/2022] Open
Abstract
There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924-8.207, p = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016-1.077, p = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively (p = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.
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Affiliation(s)
- Joji Tani
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
- Correspondence: ; Tel.: +81-87-891-2156
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa 760-8557, Japan; (T.S.); (A.T.); (T.N.); (K.T.)
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kagawa 769-1695, Japan;
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Kagawa 760-0017, Japan;
| | - Akihiro Deguchi
- Department of Gastroenterology, Kagawa Rosai Hospital, Kagawa 763-8502, Japan;
| | - Teppei Sakamoto
- Department of Internal Medicine, Yashima General Hospital, Kagawa 761-0816, Japan;
| | - Kei Takuma
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Mai Nakahara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Tomoko Tadokoro
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Shima Mimura
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Koji Fujita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Hideki Kobara
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
| | - Takashi Himoto
- Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa 761-0123, Japan;
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa 760-8557, Japan; (T.S.); (A.T.); (T.N.); (K.T.)
| | - Takuya Nagano
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa 760-8557, Japan; (T.S.); (A.T.); (T.N.); (K.T.)
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa 760-8557, Japan; (T.S.); (A.T.); (T.N.); (K.T.)
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan; (K.T.); (M.N.); (K.O.); (T.T.); (S.M.); (K.F.); (H.Y.); (H.K.); (A.M.); (T.M.)
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Reig M, Cabibbo G. Antiviral therapy in the palliative setting of HCC (BCLC-B and -C). J Hepatol 2021; 74:1225-1233. [PMID: 33582128 DOI: 10.1016/j.jhep.2021.01.046] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 01/06/2021] [Accepted: 01/28/2021] [Indexed: 02/07/2023]
Abstract
The potential impact of direct-acting antivirals (DAAs) in patients with Barcelona Clinic Liver Cancer (BCLC)-B/C stage hepatocellular carcinoma (HCC) is understudied. Patients with HCC have been systematically excluded from randomised controlled trials evaluating the effectiveness of DAAs. Thus, the benefits of DAAs in patients with HCC are less well defined. The presence of active HCC before the initiation of DAA treatment is reported to be a predictor of DAA failure, and studies in patients without HCC have demonstrated that improvements in cirrhosis complications were lower or absent after DAA failure. Even if viral eradication is achieved using DAAs, reversal of liver function impairment may take longer than the development of end-stage cancer status. Additionally, the impact of DAAs on HCC recurrence is still a controversial topic. Thus, the decision of whether to use DAAs should be made on a patient-by-patient basis, and each patient should be informed of all the potential risks and benefits associated with their usage. This document summarises the current data on the usage of DAAs in BCLC-B/C patients, discusses the concept of "the point of no return" in the setting of DAAs, and proposes tools for deciding the best option for each patient profile. If liver function improvement overlaps with symptomatic HCC progression, the benefits of DAAs could be minimised, worsened, or fully counterbalanced. If the BCLC stage is defined using only liver dysfunction, the decision to prioritise DAA treatment should be based on the option (or lack thereof) of liver transplantation and/or the HCC stage. We propose applying a shared decision-making approach, informing each patient of all the potential risks and benefits of the proposed medical intervention.
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Affiliation(s)
- Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, IMDiM, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, Palermo, Italy
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Gau RY, Yu MC, Tsai HI, Lee CH, Kuo T, Lee KC, Lee WC, Chan KM, Chiu CC, Lee CW. Laparoscopic Liver Resection Should Be a Standard Procedure for Hepatocellular Carcinoma with Low or Intermediate Difficulty. J Pers Med 2021; 11:266. [PMID: 33918197 PMCID: PMC8067022 DOI: 10.3390/jpm11040266] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 03/28/2021] [Accepted: 03/30/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND To investigate the feasibility of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC), we compared the outcome between LLR and conventional open liver resection (OLR) in patient groups with different IWATE criteria difficulty scores (DS). METHODS We retrospectively reviewed 607 primary HCC patients (LLR: 81, OLR: 526) who underwent liver resection in Linkou Chang Gung Memorial hospital from 2012 to 2019. By using 1:1 propensity score-matched (PSM) analysis, their baseline characteristics and the DS stratified by the IWATE criteria were matched between the LLR and OLR. Their perioperative and oncologic outcomes were compared. RESULTS After 1:1 PSM, 146 patients (73 in LLR, 73 in OLR) were analyzed. Among them, 13, 41, 13 and 6 patients were classified as low, intermediate, advanced and expert DS group, respectively. Compared to OLR, the LLR had shorter hospital stay (9.4 vs. 11.5 days, p = 0.071), less occurrence of surgical complications (16.4% vs. 30.1%, p = 0.049), lower rate of hepatic inflow control (42.5% vs. 65.8%, p = 0.005), and longer time of inflow control (70 vs. 51 min, p = 0.022). The disease-free survival (DFS) and overall survivals were comparable between the two groups. While stratified by the DS groups, the LLR tended to have lower complication rate and shorter hospital stay than OLR. The DFS of LLR in the intermediate DS group was superior to that of the OLR (p = 0.020). In the advanced and expert DS groups, there were no significant differences regarding outcomes between the two groups. CONCLUSION We have demonstrated that with sufficient experience and technique, LLR for HCC is feasible and the perioperative outcome is favorable. Based on the current study, we suggest LLR should be a standard procedure for HCC with low or intermediate difficulty. It can provide satisfactory postoperative recovery and comparable oncological outcomes. Further larger scale prospective studies are warranted to validate our findings.
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Affiliation(s)
- Ruoh-Yun Gau
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan; (R.-Y.G.); (W.-C.L.); (K.-M.C.)
| | - Ming-Chin Yu
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan 333, Taiwan
- Department of Surgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), Tu-Cheng, New Taipei City 236, Taiwan
| | - Hsin-I Tsai
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan 333, Taiwan
- Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan
| | - Cheng-Han Lee
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan
| | - Tony Kuo
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan
| | - Kuan-Chieh Lee
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan
| | - Wei-Chen Lee
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan; (R.-Y.G.); (W.-C.L.); (K.-M.C.)
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
| | - Kun-Ming Chan
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan; (R.-Y.G.); (W.-C.L.); (K.-M.C.)
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
| | - Chien-Chih Chiu
- Department of Nursing, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan;
| | - Chao-Wei Lee
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Guishan, Taoyuan 333, Taiwan; (R.-Y.G.); (W.-C.L.); (K.-M.C.)
- College of Medicine, Chang Gung University, Guishan, Taoyuan 333, Taiwan; (M.-C.Y.); (H.-I.T.); (C.-H.L.); (T.K.); (K.-C.L.)
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Guishan, Taoyuan 333, Taiwan
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Kuo MJ, Mo LR, Chen CL. Factors predicting long-term outcomes of early-stage hepatocellular carcinoma after primary curative treatment: the role of surgical or nonsurgical methods. BMC Cancer 2021; 21:250. [PMID: 33685409 PMCID: PMC7941925 DOI: 10.1186/s12885-021-07948-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open
Abstract
Background We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. Methods Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01–2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26–3.08), early recurrence (HR = 6.62, 95% CI:3.79–11.6) and late recurrence (HR = 3.75, 95% CI:1.99–7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. Conclusion Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07948-9.
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Affiliation(s)
- Ming-Jeng Kuo
- Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701, Taiwan. No. 670, Chon-De Road, Tainan, 701, Taiwan.
| | - Lein-Ray Mo
- Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan 701, Taiwan. No. 670, Chon-De Road, Tainan, 701, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, College of Medicine, and Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 100, 7 Chung-Shan South Road, Taipei, 100, Taiwan.
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Kamal A, Elmoety AAA, Rostom YA, Shater MS, Lashen SA. Hepatocellular carcinoma recurrence after directly acting antivirals for chronic hepatitis C: a 2-year follow-up study. Clin Exp Hepatol 2021; 7:66-73. [PMID: 34027117 PMCID: PMC8122091 DOI: 10.5114/ceh.2021.104397] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 11/20/2020] [Indexed: 02/06/2023] Open
Abstract
AIM OF THE STUDY Data regarding hepatocellular carcinoma (HCC) recurrence after directly acting antivirals for hepatitis C are contradictory. Our aim was to study the HCC recurrence in patients who received directly acting antivirals after tumor ablation. MATERIAL AND METHODS This retrospective study included all Child-Pugh A and B patients with hepatitis C related < 5 cm single or up to 3 HCC without any vascular or extrahepatic involvement whose lesions were managed using microwave or radiofrequency ablation at the Internal Medicine Department of Alexandria Faculty of Medicine, in the period from 1 January 2016 to 31 December 2016, and then received directly acting antivirals. RESULTS Data from 52 patients were analyzed. Throughout the 2 years from ablation, 42.3% of patients experienced tumor recurrence (22 out of 52 patients). In addition, two subjects died and 4 subjects were lost to follow-up before any tumor recurrence. CONCLUSIONS Although our study included both modified Child-Pugh A and B patients and included lesions up to 5 cm treated using thermal ablation, the 2-year HCC recurrence rate was similar to that previously reported after surgical resection or radiofrequency ablation of lesions up to 3 cm in Child-Pugh A patients before development of directly acting antivirals.
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Affiliation(s)
- Ahmed Kamal
- Hepatology Unit, Internal Medicine Department, Alexandria University, Egypt
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Park S, Rim CH, Jung YK, Yoon WS. Therapeutic Decision Making in Hepatocellular Carcinoma According to Age and Child-Pugh Class: A Nationwide Cohort Analysis in South Korea. Can J Gastroenterol Hepatol 2021; 2021:6640121. [PMID: 33505941 PMCID: PMC7811492 DOI: 10.1155/2021/6640121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 01/27/2023] Open
Abstract
Background We sought to analyze the preferred treatment modality by age and liver function in South Korea. Methods The Korean Liver Cancer Study Group randomly extracted the data of patients with hepatocellular carcinoma (HCC) enrolled in the Korean Central Cancer Registry from 2008 to 2014 from approximately 50 hospitals nationwide. After excluding distant and lymphatic metastases, the treatment preference for patients with a single lesion (excluding PVT (portal vein thrombosis), hepatic vessels, and bile duct invasion) and with PVT was evaluated in 7559 patients. Patients were grouped by age, and baseline liver function was divided based on the Child-Pugh class (CPC) A, B, and C. Results For a single HCC, the majority of patients selected transarterial therapy as the initial treatment, followed by surgical resection and local ablative therapy. The surgical resection rate decreased significantly with age (p < 0.001), and the transarterial therapy rate significantly increased (p < 0.001). For CPC C, liver transplantation was significantly increased to 11.5%, and 36.3% of patients received no treatment. In HCC with PVT, the transarterial therapy rate was the highest, followed by the rate of abandonment of treatment. The proportion of no treatment significantly increased with age (p < 0.001). In CPC C, transarterial therapy and systemic therapy were attempted in 15.4% and 5.8% of patients, respectively. Conclusions Age and liver function have a significant impact on the therapeutic decision-making of HCC patients in Korea. In unfavorable conditions, surgical resection was less favored in patients with single tumors, and no treatment was preferred in patients with PVT.
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Affiliation(s)
- Sunmin Park
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea
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Gao X, Zhan M, Wang L, Ding Y, Niu J. Timing of DAA Initiation After Curative Treatment and Its Relationship with the Recurrence of HCV-Related HCC. J Hepatocell Carcinoma 2020; 7:347-360. [PMID: 33299823 PMCID: PMC7720283 DOI: 10.2147/jhc.s279657] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus infection is a major cause of chronic hepatitis, leading to cirrhosis and hepatocellular carcinoma (HCC). Many studies agree that interferon (IFN)-based antiviral therapy can reduce the risk of HCC recurrence in patients with chronic hepatitis C who have achieved a sustained virological response (SVR). The recent introduction of direct-acting antivirals (DAA) has resulted in excitingly high SVR rates. However, as an IFN-free regimen, DAAs only exert antiviral activity without an immune response. The benefit of DAA-based regimens for HCC recurrence in patients with cirrhosis and following successful curative treatment remains controversial. Additionally, the time span between curative-intent therapy and the DAA regimen is an independent risk factor for HCC recurrence, irrespective of the DAA response. HCC patients who are eligible for potentially curative therapy by liver resection or ablation should defer DAA therapy; however, the accurate timing remains unclear. In this study, we reviewed the timing of DAA initiation after curative treatment and its effect on the recurrence of related HCC.
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Affiliation(s)
- Xiuzhu Gao
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China.,Phase I Clinical Research Center, The First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China
| | - Mengru Zhan
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China
| | - Liquan Wang
- Imaging Department, Jilin Province Occupational Disease Prevention and Treatment Hospital, Changchun, Jilin Province 130102, People's Republic of China
| | - Yanhua Ding
- Phase I Clinical Research Center, The First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China
| | - Junqi Niu
- Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China
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Mei YY, Chen YM, Wu YK, Zhang XH, Xu WX. Efficacy and Safety of Sofosbuvir-Based Direct-Acting Antiviral Agents Treatment for Patients with Genotype 3/6 Hepatitis C Virus Infection. Can J Gastroenterol Hepatol 2020; 2020:8872120. [PMID: 33194875 PMCID: PMC7648714 DOI: 10.1155/2020/8872120] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 10/12/2020] [Accepted: 10/16/2020] [Indexed: 02/07/2023] Open
Abstract
Aims The aim is to evaluate the efficacy and safety of Sofosbuvir- (SOF-) based direct-acting antiviral agents (DAAs) treatment for patients with genotype (GT) 3/6 hepatitis C virus (HCV) infection. Methods Patients infected with GT 3/6 HCV and treated with SOF-based DAAs were enrolled in this prospective, open, single-center, and real-world study. Drugs included Sofosbuvir (SOF), Velpatasvir (VEL), Daclatasvir (DCV), and Ribavirin (RBV). The treatment regimens included SOF + RBV for 24 weeks, SOF + DCV ± RBV for 12/24 weeks, and SOF/VEL ± RBV for 12 weeks. Results A total of 54 patients were included. Age was 42.5 ± 10.4 years. Baseline HCV RNA was 6.29 ± 0.89log10 IU/mL. The numbers of GT 3a, 3b, and 6a patients were 10, 12, and 32, respectively. The numbers of chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis patients were 39, 9, and 6, respectively. In patients with chronic hepatitis C and liver cirrhosis, sustained virological response 12 weeks after the end of treatment (SVR12) was 97.4% and 96.7%, respectively, and rapid virological response (RVR) was 75.0% and 57.1%, respectively. SVR12 of GT3a, GT3b, and GT6a was 100%, 83.3%, and 97%, respectively. ALT normality rate in chronic hepatitis group is higher than that in cirrhosis group at 4 weeks of treatment (89.7% versus 60.0%, p = 0.033) and at 12 weeks after EOT (94.9% versus 66.7%, p = 0.021). The overall incidence rate of adverse events was 44.4%, with fatigue being the most common (13.0%). Conclusion SOF-based DAAs regimen can achieve ideal SVR12 for Chinese patients with both GT3a and GT6a HCV infection. The tolerance and safety of SOF-based DAAs regimen are good.
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Affiliation(s)
- Yong-yu Mei
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - You-ming Chen
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Yuan-kai Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Xiao-hong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
| | - Wen-xiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong, China
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Sangiovanni A, Alimenti E, Gattai R, Filomia R, Parente E, Valenti L, Marzi L, Pellegatta G, Borgia G, Gambato M, Terreni N, Serio I, Belli L, Oliveri F, Maimone S, Brunacci M, D'Ambrosio R, Forzenigo LV, Russo FP, Rumi M, Barone M, Fracanzani AL, Raimondo G, Giannini EG, Brunetto MR, Villa E, Biganzoli E, Colombo M, Lampertico P. Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis. J Hepatol 2020; 73:593-602. [PMID: 32243959 DOI: 10.1016/j.jhep.2020.03.030] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 03/16/2020] [Accepted: 03/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIM An unexpected early increase in incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported (and refuted) in patients with HCV-related cirrhosis following direct-acting antiviral (DAA) treatment. To address this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients, with or without a history of HCC, undergoing DAA therapy. PATIENTS AND METHODS A total of 1,161 HCC-free cirrhotics (group 1) and 124 cirrhotics who had received a curative treatment for an HCC (group 2) were enrolled. Clinical features, including presence of undefined/non-malignant liver nodules (UNMNs), were analyzed with respect to HCC incidence and recurrence. RESULTS During a median study time of 17 months in group 1 and 16 months in group 2, de novo HCC developed in 48 patients (yearly incidence 3.1/100 patient-years, 75% BCLC 0-A) and recurred in 40 (mean yearly incidence 29.9/100 patient-years, 83% BCLC 0-A). A peak of HCC instant incidence was observed at 4.2 months in group 1 patients with UNMNs, and at 7.7 months in group 2. By multivariable Cox regression models, UNMNs (hazard ratio [HR] 3.11; 95% CI 1.47-6.57: p = 0.003), ascites detected any time before enrolment (HR 3.04; 95% CI 1.23-7.51; p = 0.02), and alpha-fetoprotein log-value (HR 1.90; 95% CI 1.05-3.44; p = 0.03) were the variables independently associated with the incidence of de novo HCC, while history of alcohol abuse (HR 2.10; 95% CI 1.08-4.09; p = 0.03) and history of recurrence of HCC (HR 2.87; 95% CI 1.35-6.09; p = 0.006) were associated with HCC recurrence. CONCLUSION An early high incidence of both de novo HCC, in patients with UNMNs, and recurrent HCC was observed in DAA-treated patients; this was not accompanied by increased tumor aggressiveness. LAY SUMMARY This prospective study focuses on the risk of developing de novo or recurrent hepatocellular carcinoma (HCC) after direct-acting antiviral (DAA) treatment in patients with hepatitis C-related cirrhosis. We found that DAA treatment was associated with an early high HCC incidence in patients with undefined or non-malignant nodules, as well as in those with a history of complete response to HCC treatment. Whether this is related to the presence of clinically undetectable nests of cancer cells or to precancerous lesions that may progress to overt HCC upon DAA treatment remains unanswered. No evidence of increased clinical aggressiveness was reported in de novo or recurrent HCC.
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Affiliation(s)
- Angelo Sangiovanni
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.
| | - Eleonora Alimenti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | - Riccardo Gattai
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy
| | - Roberto Filomia
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Elisabetta Parente
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Luca Valenti
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Luca Marzi
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Gaia Pellegatta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples 'Federico II', Naples, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Ilaria Serio
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Luca Belli
- UOC Epatologia e Gastroenterologia, Ospedale Niguarda, Milan, Italy
| | - Filippo Oliveri
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Matteo Brunacci
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Roberta D'Ambrosio
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | | | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Mariagrazia Rumi
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation (D.E.T.O.), University of Bari, Bari, Italy
| | - Anna Ludovica Fracanzani
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | | | - Maurizia Rossana Brunetto
- Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Pisa, Italy; Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Elia Biganzoli
- Department of Clinical Sciences and Community Health & DSRC, University of Milan, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Massimo Colombo
- Center of Translational Research in Hepatology, Humanitas Hospital, Rozzano, Italy
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico - Division of Gastroenterology and Hepatology - CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Asahina Y. JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis. Hepatol Res 2020; 50:775-790. [PMID: 32298527 DOI: 10.1111/hepr.13501] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 03/04/2020] [Accepted: 04/05/2020] [Indexed: 02/08/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.
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Kuo YH, Wang JH, Chang KC, Hung CH, Lu SN, Hu TH, Yen YH, Kee KM, Chen CH. The influence of direct-acting antivirals in hepatitis C virus related hepatocellular carcinoma after curative treatment. Invest New Drugs 2019; 38:202-210. [PMID: 31701431 DOI: 10.1007/s10637-019-00870-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 10/16/2019] [Indexed: 02/06/2023]
Abstract
This study was done to elucidate the influence of direct-acting antiviral (DAA) agents on the recurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC (HCV-HCC) after curative therapies. HCV-HCC patients who received curative therapies and obtained a complete response were analyzed. From January 2017 to September 2017, 112 HCV-HCC patients received DAA and obtained a sustained virological response (SVR). From January 2006 to December 2014, another 345 HCV-HCC patients received peg-interferon-based treatment and 118 obtained SVR. From January 2012 to December 2016, 248 HCV-HCC patients had complete HCC response and did not receive antiviral treatment. Patients were divided into DAA, IFN, and Untreated groups based on what antiviral treatment they received. There were 82 patients in the DAA group, 80 patients in the IFN group, and 160 patients in the Untreated group. During the follow-up period, the DAA group had 22 (26.8%) recurrent cases, whereas the IFN group had 46 (56.8%) cases after antiviral treatment. Among the 22 recurrent cases in the DAA group, 19 (86.9%) experienced HCC recurrence during 1 year after DAA initiation. Compared with the IFN group, the DAA group had poorer one-year recurrence-free survival (75.4% vs. 95%, p < 0.001), even after adjustment with propensity score matching (81.4% vs. 93.9%, p = 0.034). However, DAA was an improving factor for HCC recurrence compared with the Untreated group in the multivariate analysis. Among HCV-HCC patients with complete treatment, those with DAA-induced SVR had a higher one-year recurrence rate than those who received IFN-based antiviral therapy, but DAA did not seem to increase HCC recurrence compared to untreated patients.
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Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Rd, Niao-Sung, 833, Kaohsiung City, Taiwan.
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Cabibbo G, Cucchetti A, Cammà C, Casadei-Gardini A, Celsa C, Emanuele Maria Rizzo G, Johnson P, Ercolani G. Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials. Future Oncol 2019; 15:3411-3422. [PMID: 31588789 DOI: 10.2217/fon-2019-0287] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan-Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6-10.5), and median TTP was 4.1 months (95% CI: 3.8-4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-hepatic disease as predictors of longer OS. Conclusion: We provided a benchmark for future studies on sorafenib. The present results can be used in the decision making for the early shift to second-line strategy.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Alessandro Cucchetti
- Department of Medical & Surgical Sciences - DIMEC; Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Calogero Cammà
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Andrea Casadei-Gardini
- Department of Medical and Surgical Sciences for Children and Adults, Division of Medical Oncology, Policlinico di Modena Azienda Ospedaliera - Universitaria di Modena, Modena, Italy
| | - Ciro Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Giacomo Emanuele Maria Rizzo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Philip Johnson
- Department of Molecular & Clinical Cancer Medicine, The Duncan Building, Daulby Street, University of Liverpool, Liverpool, UK
| | - Giorgio Ercolani
- Department of Medical & Surgical Sciences - DIMEC; Alma Mater Studiorum - University of Bologna, Bologna, Italy
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Sanaka S, Kasarala GR, Tillmann HL. A Downside to Hepatitis C Virus Cure? Vigilance Is Needed Regarding Hepatitis B Virus Reactivation, Organ Rejection, or Hepatocellular Carcinoma Progression. J Infect Dis 2019; 217:857-860. [PMID: 29365131 DOI: 10.1093/infdis/jix659] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 12/19/2017] [Indexed: 02/06/2023] Open
Abstract
Cure of hepatitis C virus has become feasible in almost all patients. However, vigilance is needed in 3 scenarios: previous exposure to hepatitis B virus (HBV), history of organ transplantation, and history of cured hepatocellular carcinoma (HCC). The current data suggest that HBV reactivation occurs in about 10% of hepatitis B surface antigen (HBsAg)-positive patients and approximately 1% of hepatitis B core antibody-positive but HBsAg-negative patients. The risk of organ rejection is also around 1%, but can be fatal if not acted on immediately. Finally, the risk of early HCC recurrence may be increased but should not delay initiation of antiviral therapy in the setting of cured HCC; however, increased surveillance may be warranted.
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Affiliation(s)
- Sirish Sanaka
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
| | - George R Kasarala
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
- Vidant Medical Center, Greenville, North Carolina
| | - Hans L Tillmann
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, North Carolina
- Vidant Medical Center, Greenville, North Carolina
- Greenville Veterans Affairs Health Care Center, Greenville, North Carolina
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Hepatocellular carcinoma in the wait-listed patient with hepatitis C virus. Curr Opin Organ Transplant 2019; 23:237-243. [PMID: 29406448 DOI: 10.1097/mot.0000000000000505] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW To highlight the current data for treatment of hepatitis C virus (HCV) in patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplant and incorporation of various factors to decide the optimal time to initiate HCV therapy. RECENT FINDINGS Viral eradication on the waiting list has been found to lead to significant clinical improvement in approximately 20% of HCV-positive patients. However, there have been concerns raised for direct-acting antiviral (DAA) therapy in patients listed with HCC. DAA therapy leading to rapid HCV clearance has been reported to be associated with an increased risk of HCC recurrence, especially when DAA therapy is initiated in close proximity to HCC therapy. Additionally, the presence of viable HCC may significantly lower the chances of achieving sustained virologic response. Lastly, sustained virologic response can decrease the organ pool in HCV-positive waitlisted patients. SUMMARY The decision to treat HCV in patients listed for HCC pre vs. postliver transplant will require additional research.
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Mariño Z, Darnell A, Lens S, Sapena V, Díaz A, Belmonte E, Perelló C, Calleja JL, Varela M, Rodriguez M, Rodriguez de Lope C, Llerena S, Torras X, Gallego A, Sala M, Morillas RM, Minguez B, Llaneras J, Coll S, Carrion JA, Iñarrairaegui M, Sangro B, Vilana R, Sole M, Ayuso C, Ríos J, Forns X, Bruix J, Reig M. Time association between hepatitis C therapy and hepatocellular carcinoma emergence in cirrhosis: Relevance of non-characterized nodules. J Hepatol 2019; 70:874-884. [PMID: 30684506 DOI: 10.1016/j.jhep.2019.01.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 12/29/2018] [Accepted: 01/04/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC. METHODS This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years. RESULTS A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96-4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55-5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased. CONCLUSION These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation. LAY SUMMARY In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.
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Affiliation(s)
- Zoe Mariño
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Anna Darnell
- Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Victor Sapena
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Alba Díaz
- Barcelona Clinic Liver Cancer (BCLC) Group, Pathology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Ernest Belmonte
- Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Christie Perelló
- Liver Unit, Hospital Universitario Puerta de Hierro IDIPHIM, Universidad Autónoma de Madrid, Madrid, Spain
| | - Jose Luis Calleja
- Liver Unit, Hospital Universitario Puerta de Hierro IDIPHIM, Universidad Autónoma de Madrid, Madrid, Spain
| | - Maria Varela
- Liver Unit, Gastroenterology Department, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain
| | - Manuel Rodriguez
- Liver Unit, Gastroenterology Department, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain
| | - Carlos Rodriguez de Lope
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Susana Llerena
- Gastroenterology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Xavier Torras
- Gastroenterology and Hepatology Department, Hospital de la Santa Creu i Sant Pau, CIBERehd, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Adolfo Gallego
- Gastroenterology and Hepatology Department, Hospital de la Santa Creu i Sant Pau, CIBERehd, Barcelona, Spain
| | - Margarita Sala
- Liver Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Rosa María Morillas
- Liver Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Beatriz Minguez
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, Vall d'Hebron Institute of Research (VHIR), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jordi Llaneras
- Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, Vall d'Hebron Institute of Research (VHIR), Spain
| | - Susana Coll
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), UAB (Universitat Autonoma de Barcelona) Barcelona, Spain
| | - José Antonio Carrion
- Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), UAB (Universitat Autonoma de Barcelona) Barcelona, Spain
| | - Mercedes Iñarrairaegui
- Liver Unit, Clínica Universidad de Navarra, IDISNA, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra, IDISNA, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Ramón Vilana
- Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Manel Sole
- Barcelona Clinic Liver Cancer (BCLC) Group, Pathology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Carmen Ayuso
- Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - José Ríos
- Medical Statistics Core Facility, IDIBAPS, Hospital Clinic Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
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45
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Sanduzzi-Zamparelli M, Boix L, Leal C, Reig M. Hepatocellular Carcinoma Recurrence in HCV Patients Treated with Direct Antiviral Agents. Viruses 2019; 11:E406. [PMID: 31052463 PMCID: PMC6563506 DOI: 10.3390/v11050406] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 04/23/2019] [Accepted: 04/25/2019] [Indexed: 02/06/2023] Open
Abstract
The risk of hepatocellular carcinoma recurrence is universal regardless of the treatment modality applied, and secondary prevention is still an unmet issue even though the elimination of hepatitis C (HCV) with direct antiviral agents (DAAs) was expected to be one of the new options. Unfortunately, the impact of DAAs on hepatocellular carcinoma (HCC) development (de novo and recurrence) is still controversial. Since the first publication on the subject in 2016, almost all groups worldwide have carried out research in this field with hundreds of publications now available. This revision is focused on the impact of DAAs on HCC recurrence and aims to discuss the potential underlying mechanisms and host factors pointing out the time association phenomenon between DAA treatment and HCC recurrence. Moreover, we comment on the methodological issues that could affect the different interpretations of the published results. In conclusion, this is an area of research with potential in the understanding of the impact of factors not previously considered, and may also help change hepatocarcinogenesis tenets, such as the belief that the elimination of HCV should be used as a second prevention treatment.
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Affiliation(s)
- Marco Sanduzzi-Zamparelli
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - Loreto Boix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
- Centro de Investigación Médica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Cassia Leal
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain.
- Centro de Investigación Médica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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46
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Toyoda H, Kumada T, Tada T, Mizuno K, Sone Y, Akita T, Tanaka J, Johnson PJ. The impact of HCV eradication by direct-acting antivirals on the transition of precancerous hepatic nodules to HCC: A prospective observational study. Liver Int 2019; 39:448-454. [PMID: 30312003 DOI: 10.1111/liv.13987] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/25/2018] [Accepted: 10/05/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS It remains controversial whether the eradication of hepatitis C virus (HCV) by interferon (IFN)-free anti-HCV therapy using direct-acting antivirals (DAAs) suppresses or promotes hepatocellular carcinoma (HCC) development. We investigated the influence of HCV eradication by DAA therapy on HCC development, by observing changes of non-hypervascular hypointense nodules (NHHNs) by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). METHODS A total of 401 patients treated with DAA therapy who did not have a history of HCC were enrolled in this prospective cohort study. All patients underwent EOB-MRI prior to the start of DAA therapy and were followed up periodically after therapy. The progression of NHHNs detected at baseline to typical HCC, as indicated by hypervascularization and the incidence of newly emergent NHHNs, was analyzed. RESULTS In comparison of patients who achieved sustained virologic response (SVR) with propensity score-matched patients with persistent HCV infection, there was no difference in the incidence of hypervascularization of NHHNs to typical HCC among patients who had NHHNs at baseline. Among patients who did not have NHHNs at baseline, the incidence of the new emergence of NHHNs did not differ between study patients and propensity score-matched patients with persistent HCV infection. CONCLUSIONS During a 2-year observation period after SVR, the eradication of HCV by IFN-free DAA therapy did not suppress or enhance HCC development. (UMIN000017020).
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Philip J Johnson
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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47
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Nishibatake Kinoshita M, Minami T, Tateishi R, Wake T, Nakagomi R, Fujiwara N, Sato M, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Shiina S, Koike K. Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy. J Hepatol 2019; 70:78-86. [PMID: 30336183 DOI: 10.1016/j.jhep.2018.09.029] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 09/10/2018] [Accepted: 09/27/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS It remains controversial whether direct-acting antivirals (DAAs) accelerate the recurrence of hepatitis C-related hepatocellular carcinoma (HCC) after curative therapy. This study aimed to evaluate HCC recurrence after DAA treatment of chronic hepatitis C. METHODS We enrolled patients with a history of successful radiofrequency ablation treatment for hepatitis C-related HCC who received antiviral therapy with DAAs (DAA group: 147 patients) or with interferon (IFN)-based therapy (IFN group: 156 patients). We assessed HCC recurrence rates from the initiation of antiviral therapy using the Kaplan-Meier method and evaluated risk factors for HCC recurrence by multivariate Cox proportional hazard regression analysis. The recurrence pattern was categorized as follows: intrahepatic recurrence with a single tumor <2 cm (stage 0), a single tumor or up to 3 tumors ≤3 cm (stage A), multinodular (stage B), and extrahepatic metastasis or macrovascular invasion (stage C). RESULTS The recurrence rates at 1 and 2 years were 39% and 61% in the IFN group and 39% and 60% in the DAA group, respectively (p = 0.43). Multivariate analysis identified higher lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, a history of multiple HCC treatments, and a shorter interval between HCC treatment and initiation of antiviral therapy as independent risk factors for HCC recurrence. HCC recurrence in stage 0, A, B, and C was found in 56 (41%), 60 (44%), 19 (14%), and 1 (0.7%) patients in the IFN group and 35 (44%), 32 (40%), 11 (14%), and 2 (2.5%) patients in the DAA group, respectively (p = 0.70). CONCLUSIONS HCC recurrence rates and patterns after initiation of antiviral therapy did not differ between patients who received IFN-based therapy and DAA therapy. LAY SUMMARY We detected no significant difference in early hepatocellular carcinoma (HCC) recurrence rates and patterns between patients who received interferon-based and direct-acting antiviral therapy after HCC treatment. High lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, short recurrence-free period, and a history of multiple HCC treatments were independent risk factors for early HCC recurrence after the initiation of antiviral therapy.
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Affiliation(s)
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.
| | - Taijiro Wake
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Naoto Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | | | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
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48
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Cabibbo G, Celsa C, Cammà C, Craxì A. Should we cure hepatitis C virus in patients with hepatocellular carcinoma while treating cancer? Liver Int 2018; 38:2108-2116. [PMID: 29935096 DOI: 10.1111/liv.13918] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 06/19/2018] [Indexed: 12/11/2022]
Abstract
Direct acting antivirals stabilize or improve liver function in the majority of patients with hepatitis C virus cirrhosis. Hepatic decompensation is the main driver of death of patients with early, successfully treated hepatocellular carcinoma superimposed to cirrhosis. Treatment with direct acting antivirals could improve the prognosis of these subjects, independently from the subsequent course of hepatocellular carcinoma, if the efficacy in obtaining viral clearance is as high as in patients without a history of hepatocellular carcinoma, and if the risk of hepatocellular carcinoma recurrence is unaffected. When dealing with hepatocellular carcinoma patients, direct acting antivirals can be indicated in two different settings: (a) subjects in which hepatocellular carcinoma has been already successfully treated ("cured" hepatocellular carcinoma), or (b) subjects whose hepatocellular carcinoma is still untreated or untreatable ("active" hepatocellular carcinoma). Although there are abundant data on "cured" hepatocellular carcinoma, evidence supporting treatment decisions in patients with "active" hepatocellular carcinoma is at best scarce and controversial, since these patients as well as patients with hepatocellular carcinoma listed for liver transplantation are usually excluded from treatment.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Ciro Celsa
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
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49
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Yasui Y, Kurosaki M, Komiyama Y, Takada H, Tamaki N, Watakabe K, Okada M, Wang W, Shimizu T, Kubota Y, Higuchi M, Takaura K, Tsuchiya K, Nakanishi H, Takahashi Y, Itakura J, Enomoto N, Izumi N. Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts early occurrence of hepatocellular carcinoma after sustained virologic response by direct-acting antivirals for hepatitis C virus. Hepatol Res 2018; 48:1131-1139. [PMID: 30030872 DOI: 10.1111/hepr.13233] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 06/23/2018] [Accepted: 07/15/2018] [Indexed: 02/06/2023]
Abstract
AIM The aim of this study is to clarify the value of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) for predicting hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virologic response (SVR) by therapy with interferon-free, direct-acting antivirals (DAAs). METHODS This is a retrospective cohort study that included 567 patients who underwent antiviral therapy with an interferon-free DAA regimen and achieved SVR. Serum WFA+ -M2BP was measured after SVR. Factors predictive of HCC occurrence and recurrence were analyzed in the patients after stratification by previous treatment history of HCC. RESULTS Among 518 patients who had no history of HCC, 13 developed HCC. Post-SVR WFA+ -M2BP ≥1.75 cut-off index (C.O.I., P < 0.001) and α-fetoprotein (AFP) level ≥6 ng/mL (P = 0.01) were significant predictors of HCC development. Multivariate analysis showed that post-SVR WFA+ -M2BP ≥1.75 C.O.I. was an independent factor significantly associated with the development of HCC (hazard ratio [HR] 6.0; 95% confidence interval (CI), 1.8-19.4; P = 0.003). Among 49 patients who had a previous history of HCC, 22 had recurrence after SVR. Post-SVR AFP ≥6 ng/mL was the only factor associated with recurrence-free survival (HR 3.1; 95% CI, 1.3-7.5; P = 0.01). CONCLUSIONS Post-SVR WFA+ -M2BP is a predictive factor for the development of HCC in patients with no previous HCC history and treated with DAAs. Post-SVR AFP was predictive for HCC recurrence after DAA therapy.
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Affiliation(s)
- Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasuyuki Komiyama
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Hitomi Takada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mao Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Wan Wang
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takao Shimizu
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yohei Kubota
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- 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
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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50
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Guarino M, Viganò L, Ponziani FR, Giannini EG, Lai Q, Morisco F. Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis. Dig Liver Dis 2018; 50:1105-1114. [PMID: 30170908 DOI: 10.1016/j.dld.2018.08.001] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 07/26/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023]
Abstract
Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design.
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Affiliation(s)
- Maria Guarino
- Dept. of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| | - Luca Viganò
- Dept. of Surgery, Division of Hepatobiliary and General Surgery, Humanitas Clinical and Research Hospital, Humanitas University, Rozzano, Milan, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Polyclinic Foundation "Agostino Gemelli", IRCCS, Catholic University of Rome, Rome, Italy.
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Polyclinic Hospital "San Martino", Genoa, Italy.
| | - Quirino Lai
- Hepato-bilio-pancreatic and Liver Transplant Unit, Dept. of Surgery, Sapienza University of Rome, Rome, Italy
| | - Filomena Morisco
- Dept. of Clinical Medicine and Surgery, Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
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