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Nagaoki Y, Yamaoka K, Fujii Y, Uchikawa S, Fujino H, Ono A, Murakami E, Kawaoka T, Miki D, Aikata H, Hayes CN, Tsuge M, Oka S. Impact of viral eradication by direct-acting antivirals on clinical outcomes after curative treatment for hepatitis C virus-associated hepatocellular carcinoma. Therap Adv Gastroenterol 2025; 18:17562848251324094. [PMID: 40078327 PMCID: PMC11898033 DOI: 10.1177/17562848251324094] [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: 10/15/2024] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Background It is not clear that antiviral therapy for hepatitis C virus (HCV) after recovery from curative treatment for hepatocellular carcinoma (HCC) has an effect on suppressing recurrence or improving survival rates. Objectives We analyzed the impact of eradication by interferon (IFN)-free direct-acting antiviral (DAA) therapy on clinical outcomes of patients with HCV-associated HCC who underwent curative treatment. Design This was a retrospective study. Methods We retrospectively reviewed 109 consecutive patients with sustained virologic response with DAA therapy after HCC treatment and analyzed HCC recurrence and overall survival (OS). Among these patients are those with a history of HCC recurrence and curative HCC treatments administered as definitive HCC treatments prior to initiation of DAA therapy. Results Among 109 patients, 64 received DAA therapy after curative treatment for HCC; the remaining 45 received ⩾2 subsequent treatments for HCC. Cumulative HCC recurrence rates at 1, 3, and 5 years were 23%, 47%, and 56%, respectively. Multivariate analysis identified predictive factors for suppression of HCC recurrence as tumor number (hazard ratio (HR) 2.293 for multiple; p = 0.006) and number of HCC treatments before DAA therapy (HR 2.928 for ⩾2; p = 0.001). Among 64 patients who received curative treatment for HCC, cumulative first HCC recurrence rates at 1, 3, and 5 years were 12%, 34%, and 44%, respectively, second recurrence rates were 11%, 28%, and 39%, and third recurrence rates were 0%, 22%, and 53%, respectively; recurrence tended to be suppressed until 3 years. Cumulative OS rates at 3 and 5 years were 87% and 75%, respectively. On multivariate analysis, tumor number (HR 2.452 for single; p = 0.026) was the only independent predictor of OS. Conclusion DAA therapy after curative treatment for HCC suppresses HCC recurrence in the long term, but recurrence was higher in patients with a history of many HCC treatments.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology, Mazda Hospital, Mazda Motor Corporation, 2-15 Aosakiminami, Fuchu-cho, Aki-gun, Hiroshima 735-8585, Japan
| | - Kenji Yamaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551, Japan Liver Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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El-Azab GI, El-Helw GAA, Elsabaawy MMA, Kohla MAS, Omar YAM. Evaluation of screening program for hepatocellular carcinoma at a single center. EGYPTIAN LIVER JOURNAL 2025; 15:2. [DOI: 10.1186/s43066-025-00404-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 01/16/2025] [Indexed: 03/04/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and is a form of liver cancer that starts in the cells of the liver. The best way to increase the chances of survival for people at high risk for HCC is to detect it early through regular monitoring. For monitoring purposes, it is recommended to conduct ultrasound exams every 4 to 6 months, sometimes in combination with alpha-fetoprotein tests.
Aim of the work
Assess the HCC surveillance and its ability to detect HCC patients early on and improve their management.
Patients and methods
The study involved 300 patients of hepatocellular carcinoma (HCC) investigated at Menoufia University’s Institute of National Liver in Egypt. Patients were evaluated using the Liver Cancer of Barcelona Clinic (BCLC) staging system. Furthermore, the patients were classified into three surveillance categories: no surveillance, routine surveillance, and sporadic surveillance.
Results
A substantial difference statistically among the groups that received and did not receive surveillance with consideration for the stage of hepatocellular carcinoma (HCC) in particular was found. Patients who were observed usually got their diagnoses earlier. Those who were not under surveillance frequently had advanced cases of hepatocellular carcinoma upon diagnosis (HCC).
Conclusion
High-risk patients were regularly investigated for having HCC is necessary for early disease detection, appropriate therapy, and improved survival. Consistent monitoring with AFP and ultrasound allows for early detection of HCC.
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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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Ríos J, Sapena V, Mariño Z, Bruix J, Forns X, Morros R, Reig M, Torres F, Pontes C. Incidence of Liver and Non-liver Cancers After Hepatitis C Virus Eradication: A Population-Based Cohort Study. Drugs Real World Outcomes 2024; 11:389-401. [PMID: 38874848 PMCID: PMC11365915 DOI: 10.1007/s40801-024-00437-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Direct-acting antivirals (DAAs) offer a high rate of hepatitis C virus (HCV) eradication. However, concerns on the risk of cancer after HCV eradication remain. Our study aimed at quantifying the incidence of cancer in patients treated with anti-HCV therapies in Catalonia (Spain) and their matched controls. METHODS This was a population-based study using real-world data from the public healthcare system of Catalonia between 2012 and 2016. Propensity score matching was performed in patients with HCV infection treated with interferon-based therapy (IFN), sequential IFN and DAA (IFN+DAA), and DAA only (DAA) with concurrent controls. We estimated the annual incidence of overall cancer, hepatocellular carcinoma, and non-liver cancer of HCV-treated patients and their corresponding rate ratios. RESULTS The study included 11,656 HCV-treated patients and 49,545 controls. We found statistically significant increases in the rate of overall cancer for IFN+DAA-treated (rate ratio [RR] 1.77, 95% confidence interval [CI] 1.27-2.46) and DAA-treated patients (RR 1.90, 95% CI 1.66-2.19) and in the rate of HCC for IFN-treated (RR 1.50, 95% CI 1.02-2.22), IFN+DAA-treated (RR 3.89, 95% CI 2.26-6.69), and DAA-treated patients (RR 6.45, 95% CI 4.90-8.49) compared with their corresponding controls. Moreover, DAA-treated patients with cirrhosis showed an increased rate of overall cancer versus those without cirrhosis (RR 1.92, 95% CI 1.51-2.44). CONCLUSIONS Results showed that overall cancer and hepatocellular carcinoma incidence in Catalonia was significantly higher among HCV-treated patients compared with matched non-HCV-infected controls, and risks were higher in patients with cirrhosis. An increased awareness of the potential occurrence of uncommon malignant events and monitoring after HCV eradication therapy may benefit patients.
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Affiliation(s)
- José Ríos
- Department of Clinical Pharmacology, Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Campus, Cerdanyola, 08193, Barcelona, Spain
| | - Víctor Sapena
- Department of Clinical Pharmacology, Hospital Clinic and Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Rosa Morros
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Clinical Pharmacology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
| | - María Reig
- Barcelona Clinic Liver Cancer (BCLC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERHED), University of Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Campus, Cerdanyola, 08193, Barcelona, Spain.
| | - Caridad Pontes
- Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Department of Clinical Pharmacology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain
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Kamal A, Metawea M, Omar H, Ghallab M, Kassem A, Naguib H. Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial. J Gastrointest Cancer 2024; 55:913-923. [PMID: 38436921 DOI: 10.1007/s12029-024-01035-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2024] [Indexed: 03/05/2024]
Abstract
PURPOSE Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/virology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Hepatocellular/drug therapy
- Male
- Liver Neoplasms/virology
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/surgery
- Female
- Middle Aged
- Antiviral Agents/therapeutic use
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/virology
- Neoplasm Recurrence, Local/prevention & control
- Hepacivirus/isolation & purification
- Hepacivirus/drug effects
- Sofosbuvir/therapeutic use
- Aged
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Carbamates/therapeutic use
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Affiliation(s)
- Ahmed Kamal
- Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
| | - Marwa Metawea
- Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Heba Omar
- Pulmonology Clinical Pharmacy, Alexandria University Hospitals, Alexandria University, Alexandria, Egypt
- Fellow of Microbiology, Alexandria University, Alexandria, Egypt
| | - Mahmoud Ghallab
- Radiodiagnosis and Intervention Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Ahmed Kassem
- Radiology Department, Faculty of Medicine, Port Said University, Port Said, Egypt
| | - Hend Naguib
- Hepatology Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Elgazzar M, Salman T, Abdelsameea E, Akl M, Omar N, Abdel-Samiee M, Abas S, Elsakhawy M, Elsherif A, Abdelkader I, Elazab D, Ehsan N, Mohamady M, El-Kassas M, Omar HM. Hepatocellular carcinoma in hepatitis C virus patients treated with direct acting antivirals (DAAs) and patients not exposed to DAAs: a large center comparative study. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2024; 55:88. [DOI: 10.1186/s43055-024-01249-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Accepted: 04/02/2024] [Indexed: 04/03/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the first cause of cancer in Egypt. Recently, HCC developed post direct-acting antivirals (DAAs) differ in some characteristics from those developed without DAAs exposure regarding the biological features and behavior of HCC. We aimed to assess the epidemiological, clinical, laboratory, and radiological findings besides the biological behavior of HCC patients post DAAs in comparison to HCC not exposed to DAAs. An analytic cross-sectional research was performed at the National Liver Institute which is a tertiary multidisciplinary HCC center. Subjects included hepatitis C virus patients and were allocated into two groups: group I included 2036 HCC cases post-DAA treatment and group II included 6338 HCC cases who did not receive DAAs. Subjects were examined to evaluate clinical, laboratory, and radiological findings. Tumor staging was done using the BCLC staging system.
Results
Group II showed a more advanced Child–Pugh score, FIB-4 index, and MELD score than Group I (P = 0.001). The multiplicity of hepatic focal lesions was elevated in group I than in group II (P = 0.033). AFP level was significantly elevated in group I than in group II (p = 0.012). Portal vein invasion was significantly elevated in group I than in group II patients (P = 0.001). Extrahepatic spread of HCC was significantly elevated in group I than in group II (P = 0.001). Infiltrative lesions were significantly elevated in group I than in group II (P = 0.002).
Conclusion
Our study detected that the behavior in HCC post DAAs treatment is more aggressive in respect of the number of lesions, PV invasion; local and distant metastasis, and serum AFP level than in patients unexposed to DAAs. Strict surveillance in cirrhotic patients treated with DAA should be followed according to the international guidelines for early diagnosis and treatment of HCC.
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Luan CH, Su PS, Chu CJ, Lin CC, Su CW, Luo JC, Lee IC, Chi CT, Lee SD, Wang YJ, Lee FY, Huang YH, Hou MC. Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients. J Chin Med Assoc 2024; 87:357-368. [PMID: 38180018 DOI: 10.1097/jcma.0000000000001051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence. METHODS Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models. RESULTS The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors. CONCLUSION This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes.
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Affiliation(s)
- Chih-Hsuan Luan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Pin-Shuo Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jiing-Chyuan Luo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chen-Ta Chi
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Ichikawa S, Motosugi U, Sawai Y, Ishida H, Imai Y, Kozaka K, Tsurusaki M, Sofue K, Murakami T, Kawai N, Matsuo M, Fukukura Y, Mawatari S, Shimizu T, Morisaka H, Inoue T, Goshima S. Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study. Hepatol Res 2024; 54:43-53. [PMID: 37676063 DOI: 10.1111/hepr.13964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 08/28/2023] [Accepted: 08/30/2023] [Indexed: 09/08/2023]
Abstract
AIM To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.
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Affiliation(s)
- Shintaro Ichikawa
- Department of Radiology, Hamamatsu University School of Medicine, Hamamatsu, Japan
- Department of Radiology, University of Yamanashi, Chuo, Japan
| | - Utaroh Motosugi
- Department of Radiology, University of Yamanashi, Chuo, Japan
- Department of Diagnostic Radiology, Kofu Kyoritsu Hospital, Kofu, Japan
| | - Yoshiyuki Sawai
- Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Japan
| | - Hisashi Ishida
- Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Japan
| | - Yasuharu Imai
- Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Japan
| | - Kazuto Kozaka
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Masakatsu Tsurusaki
- Department of Radiology, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | | | | | - Yoshihiko Fukukura
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan
| | - Tatsuya Shimizu
- Department of Radiology, University of Yamanashi, Chuo, Japan
| | | | - Taisuke Inoue
- First Department of Internal Medicine, University of Yamanashi, Chuo, Japan
| | - Satoshi Goshima
- Department of Radiology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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9
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Fatima I, Parikh ND, Likhitsup A. Controversies of Direct-Acting Antivirals in Hepatocellular Carcinoma. Surg Oncol Clin N Am 2024; 33:43-58. [PMID: 37945144 DOI: 10.1016/j.soc.2023.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Therapy for chronic hepatitis C virus infection with direct-acting antiviral agents (DAAs) has been highly successful in achieving sustained virological response (SVR) with associated improvements in liver dysfunction, liver-related mortality, and transplant-free survival. There is a high risk of hepatocellular carcinoma (HCC) with an annual incidence of 2% to 4% in patients with cirrhosis. Following DAAs treatment and achievement of SVR, the risk of incident and recurrent HCC drops significantly over time, with risk associated with demographic and liver disease-related factors. Several risk factors have been described including age, male, diabetes comorbidities, alcohol abuse, hepatitis B virus or human immunodeficiency virus-coinfection, and advanced liver disease or increased liver fibrosis. Recurrence risk after DAA therapy has been associated with baseline tumor burden, with increased risk with larger lesion(s), multifocal disease, elevated alpha-fetoprotein level, treatment type (curative vs palliative), and shorter interval between HCC complete response and DAA initiation. Overall, due to the heterogeneity among individual patient data and lack of adequately controlled data, there are no conclusive statements that can be drawn that DAAs exposure is directly associated with HCC occurrence or recurrence. However, the best available data suggest a decreased risk of incident HCC with DAA therapy and no increased risk of recurrence with DAAs after complete tumor response.
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Affiliation(s)
- Ifrah Fatima
- University of Missouri-Kansas City, 2301 Holmes Street, Kansas City, MO 64108, USA
| | - Neehar D Parikh
- University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
| | - Alisa Likhitsup
- University of Michigan, 3912 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
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10
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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11
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Ali S, Naveed A, Hussain I, Qazi J. Diagnosis and monitoring of hepatocellular carcinoma in Hepatitis C virus patients using attenuated total reflection Fourier transform infrared spectroscopy. Photodiagnosis Photodyn Ther 2023; 43:103677. [PMID: 37390855 DOI: 10.1016/j.pdpdt.2023.103677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND Current diagnostic methods for assessment of hepatitis C virus related hepatocellular carcinoma and subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, to establish appropriate treatment strategies, are costly, invasive and requires multiple screening steps. This demands alternative diagnostic approaches that are cost-effective, time-efficient, and minimally invasive, while maintaining their efficacy for screening of hepatitis c virus related hepatocellular carcinoma. In this study, we propose that attenuated total reflection Fourier transform infrared in conjunction with principal component analysis - linear discriminant analysis and support vector machine multivariate algorithms holds a potential as a sensitive tool for the detection of hepatitis C virus-related hepatocellular carcinoma and the subsequent categorization of hepatocellular carcinoma into non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma. METHODS Freeze-dried sera samples collected from 31 hepatitis c virus related hepatocellular carcinoma patients and 30 healthy individuals, were used to acquire mid-infrared absorbance spectra (3500-900 cm-1) using attenuated total reflection Fourier transform infrared. Chemometric machine learning techniques were utilized to build principal component analysis - linear discriminant analysis and support vector machine discriminant models for the spectral data of hepatocellular carcinoma patients and healthy individuals. Sensitivity, specificity, and external validation on blind samples were calculated. RESULTS Major variations were observed in the two spectral regions i.e., 3500-2800 and 1800-900 cm-1. IR spectral signatures of hepatocellular carcinoma were reliably different from healthy individuals. Principal component analysis - linear discriminant analysis and support vector machine models computed 100% accuracy for diagnosing hepatocellular carcinoma. To classify the non-angio-invasive hepatocellular carcinoma/ angio-invasive hepatocellular carcinoma status, diagnostic accuracy of 86.21% was achieved for principal component analysis - linear discriminant analysis. While the support vector machine showed a training accuracy of 98.28% and a cross-validation accuracy of 82.75%. External validation for support vector machine based classification observed 100% sensitivity and specificity for accurately classifying the freeze-dried sera samples for all categories. CONCLUSIONS We present the specific spectral signatures for non-angio-invasive hepatocellular carcinoma and angio-invasive hepatocellular carcinoma, which were prominently differentiated from healthy individuals. This study provides an initial insight into the potential of attenuated total reflection Fourier transform infrared to diagnose hepatitis C virus related hepatocellular carcinoma but also to further categorize into non-angio-invasive and angio-invasive hepatocellular carcinoma.
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Affiliation(s)
- Salmann Ali
- Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Ammara Naveed
- Department of gastroenterology and hepatology, Pakistan Kidney and Liver Institute, Lahore, Pakistan
| | - Irshad Hussain
- Department of Chemistry &Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences (LUMS), DHA, Lahore Cantt 54792, Pakistan
| | - Javaria Qazi
- Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
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12
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Abe H, Ushijima Y, Bikangui R, Ondo GN, Pemba CM, Zadeh VR, Mpingabo PI, Ueda H, Agnandji ST, Lell B, Yasuda J. Genetic Diversity of Hepatitis B and C Viruses Revealed by Continuous Surveillance from 2015 to 2021 in Gabon, Central Africa. Microorganisms 2023; 11:2046. [PMID: 37630606 PMCID: PMC10458803 DOI: 10.3390/microorganisms11082046] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/03/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C virus (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the "Gabon-specific" HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. The HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region.
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Affiliation(s)
- Haruka Abe
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan;
- Vietnam Research Station, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan
| | - Yuri Ushijima
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan;
- Division of Biomedical Science, Institute of Medicine, University of Tsukuba, Tsukuba 305-8577, Japan
| | - Rodrigue Bikangui
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné BP. 242, Gabon; (R.B.); (G.N.O.); (S.T.A.); (B.L.)
| | - Georgelin Nguema Ondo
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné BP. 242, Gabon; (R.B.); (G.N.O.); (S.T.A.); (B.L.)
| | - Christelle M. Pemba
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
| | - Vahid R. Zadeh
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
| | - Patrick I. Mpingabo
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
| | - Hayato Ueda
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
| | - Selidji T. Agnandji
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné BP. 242, Gabon; (R.B.); (G.N.O.); (S.T.A.); (B.L.)
- Institute for Tropical Medicine, University of Tübingen, 72074 Tübingen, Germany
| | - Bertrand Lell
- Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné BP. 242, Gabon; (R.B.); (G.N.O.); (S.T.A.); (B.L.)
- Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Jiro Yasuda
- Department of Emerging Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, Nagasaki 852-8523, Japan; (H.A.); (C.M.P.); (V.R.Z.); (P.I.M.); (H.U.)
- Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan;
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
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13
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma and hepatitis C virus treatments: The bold and the beautiful. J Viral Hepat 2023; 30:148-159. [PMID: 36461645 DOI: 10.1111/jvh.13778] [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: 06/22/2022] [Revised: 10/07/2022] [Accepted: 11/26/2022] [Indexed: 12/04/2022]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is one of the most serious complications of hepatitis C virus (HCV) infection. Recently, effective antiviral medications have made sustained viral response (SVR) or cure a realistic therapeutic goal for most chronic HCV patients. Given HCV's tumorigenic propensity, it is not surprising that achieving SVR is helpful in preventing HCC. This review briefly summarizes and discusses the existing evidence on the relationship between hepatic carcinogenesis and viral eradication by antivirals, which is mainly divided into interferon-based and direct-acting antivirals (DAAs) based therapy. DAAs have changed the treatment landscape of chronic HCV, reaching high rates of SVR even in patients with advanced cirrhosis, with few contraindications and little side effects. Although some early reports suggested that DAA treatment increased the chance of HCC occurrence, more subsequent observational studies have refuted this theory. The probability of HCC recurrence after HCV eradication appears to be decreasing over time following SVR. Despite virological suppression/cure, individuals with liver cirrhosis are still at risk of HCC and should be monitored. There is a considerable need for markers/scores to predict the long-term risk of HCC in patients with HCV-related liver disease who attain SVR with direct-acting antivirals.
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Affiliation(s)
- Walaa Abdelhamed
- Endemic Medicine Department, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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14
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Jean K, Tawheed A, Luong Nguyen LB, Heikal T, Eldaly U, Elhadidy N, Elghaieb A, Aboudonia A, Tondeur L, Dublineau A, Fontanet A, El-Kassas M. Changes in Presentation, Treatment, and Survival of Patients with Hepatocellular Carcinoma in Damietta, Egypt, 2007-2019: A Retrospective Monocentric Cohort Study. J Hepatocell Carcinoma 2023; 10:99-111. [PMID: 36721637 PMCID: PMC9884455 DOI: 10.2147/jhc.s391511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 01/12/2023] [Indexed: 01/26/2023] Open
Abstract
INTRODUCTION We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally. METHODS We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients' final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan-Meier curves and differences in restricted mean survival time (RMST). RESULTS Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p<10-3). Overall patient's survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months. DISCUSSION Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.
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Affiliation(s)
- Kévin Jean
- Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France
- Unité PACRI, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Liem Binh Luong Nguyen
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France
| | - Tarek Heikal
- Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt
| | - Usama Eldaly
- Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt
| | - Neveen Elhadidy
- Pharmaceutical Services Department, Damietta Oncology Center, Damietta, Egypt
| | - Ahmed Elghaieb
- Radiology Department, Damietta Oncology Center, Damietta, Egypt
| | - Ahmed Aboudonia
- Radiology Department, Damietta Oncology Center, Damietta, Egypt
| | - Laura Tondeur
- Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France
| | - Amélie Dublineau
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France
| | - Arnaud Fontanet
- Unité PACRI, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France
- Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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15
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Campos LB, de Almeida NAA, de Santana CG, Barbosa ENP, Horta MAP, Amendola Pires M, Brandão Mello CE, de Paula VS, de Barros JJF. Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV. Viruses 2023; 15:187. [PMID: 36680226 PMCID: PMC9863677 DOI: 10.3390/v15010187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 01/11/2023] Open
Abstract
Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples.
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Affiliation(s)
- Letícia Bomfim Campos
- Laboratory of Molecular Virology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro 21040-900, Brazil
| | | | - Catarina Góis de Santana
- Gaffrée and Guinle University Hospital, Ambulatory of Liver Disease, Rio de Janeiro State Federal University/UniRio, Rio de Janeiro 20270-004, Brazil
| | | | | | - Márcia Amendola Pires
- Gaffrée and Guinle University Hospital, Ambulatory of Liver Disease, Rio de Janeiro State Federal University/UniRio, Rio de Janeiro 20270-004, Brazil
| | - Carlos Eduardo Brandão Mello
- Gaffrée and Guinle University Hospital, Ambulatory of Liver Disease, Rio de Janeiro State Federal University/UniRio, Rio de Janeiro 20270-004, Brazil
| | - Vanessa Salete de Paula
- Laboratory of Molecular Virology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro 21040-900, Brazil
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16
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Xie C, Hu J, Hu Q, Jiang L, Chen W. Classification of the mitochondrial ribosomal protein-associated molecular subtypes and identified a serological diagnostic biomarker in hepatocellular carcinoma. Front Surg 2023; 9:1062659. [PMID: 36684217 PMCID: PMC9853988 DOI: 10.3389/fsurg.2022.1062659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 12/12/2022] [Indexed: 01/07/2023] Open
Abstract
Purpose The objective of this study was to sort out innovative molecular subtypes associated with mitochondrial ribosomal proteins (MRPs) to predict clinical therapy response and determine the presence of circulating markers in hepatocellular carcinoma (HCC) patients. Methods Using an unsupervised clustering method, we categorized the relative molecular subtypes of MRPs in HCC patients. The prognosis, biological properties, immune checkpoint inhibitor and chemotherapy response of the patients were clarified. A signature and nomogram were developed to evaluate the prognosis. Enzyme-linked immunosorbent assay (ELISA) measured serum mitochondrial ribosomal protein L9 (MRPL9) levels in liver disease patients and normal individuals. Receiver operating characteristic (ROC) curves were conducted to calculate the diagnostic effect. The Cell Counting Kit 8 was carried out to examine cell proliferation, and flow cytometry was used to investigate the cell cycle. Transwell assay was applied to investigate the potential of cell migration and invasion. Western blot detected corresponding changes of biological markers. Results Participants were classified into two subtypes according to MRPs expression levels, which were characterized by different prognoses, biological features, and marked differences in response to chemotherapy and immune checkpoint inhibitors. Serum MRPL9 was significantly higher in HCC patients than in normal individuals and the benign liver disease group. ROC curve analysis showed that MRPL9 was superior to AFP and Ferritin in differentiating HCC from healthy and benign patients, or alone. Overexpressed MRPL9 could enhance aggressiveness and facilitate the G1/S progression in HCC cells. Conclusion We constructed novel molecular subtypes based on MRPs expression in HCC patients, which provided valuable strategies for the prediction of prognosis and clinical personalized treatment. MRPL9 might act as a reliable circulating diagnostic biomarker and therapeutic target for HCC patients.
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Affiliation(s)
| | | | | | | | - Weixian Chen
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Elbadry M, Moussa AM, Eltabbakh M, Al Balakosy A, Abdalgaber M, Abdeen N, El Sheemy RY, Afify S, El-Kassas M. The art of managing hepatitis C virus in special population groups: a paradigm shift. EGYPTIAN LIVER JOURNAL 2022; 12:61. [DOI: 10.1186/s43066-022-00226-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 11/08/2022] [Indexed: 11/17/2022] Open
Abstract
AbstractThe first direct-acting antiviral (DAA) medications were approved for the treatment of chronic hepatitis C virus (HCV) in 2011. Later, the appearance of novel DAAs had revolutionized the landscape of HCV treatment whose early treatment options were limited to interferon (IFN) either alone or in combinations. This review discusses the paradigm shift in legibility for treating different groups of patients with HCV after the introduction of DAAs, along with the consequent changes in treatment guidelines. IFN-based therapy was the firstly used for treating chronic HCV. Unfortunately, it exhibited many pitfalls, such as low efficacy in some patients and unsuitability for usage in lots of patients with some specific conditions, which could be comorbidities such as autoimmune thyroiditis, or liver related as in decompensated cirrhosis. Furthermore, IFN failed to treat all the extrahepatic manifestations of HCV. Nowadays, the breakthroughs brought by DAAs have benefited the patients and enabled the treatment of those who could not be treated or did not usually respond well to IFN. DAAs achieve a high success rate of HCV eradication in addition to avoiding unfavorable harms and, sometimes, adverse effects related to the previously used PEGylated IFN regimens.
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Dawood RM, El-Meguid MA, Shousha HI, Elsayed A, Nabeel MM, Yosry A, Abdelaziz A, Salum GM. Seven gene signature explores the impact of DAAs on the appearance of hepatocellular carcinoma in HCV infected patients. Heliyon 2022; 8:e10119. [PMID: 36033258 PMCID: PMC9404272 DOI: 10.1016/j.heliyon.2022.e10119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/30/2022] [Accepted: 07/25/2022] [Indexed: 11/03/2022] Open
Abstract
UNLABELLED HCV damages the hepatocytes ending with hepatocellular carcinoma (HCC). The direct-acting antivirals (DAAs) treatment has raised hopes for reducing the incidence of HCC. However, several scientific debate regarding the impact of DAAs on the occurrence of HCC in patients with cirrhosis. We aimed to study the Cirrhosis Risk Score (CRS), several clinical factors and tumor characteristics between patients who developed HCC either with or without DAAs treatment "DAA-exposed HCC patients" and "DAA-unexposed HCC patients". METHODS CRS was assessed via genotyping by allelic discrimination assays in HCV patients who developed de novo HCC (with DAAs (DAA-exposed HCC patients, n = 50), and without DAAs treatment (DAA-unexposed HCC patients, n = 40)). APRI, FIB-4 scores, and tumor characteristics were assessed. RESULTS Around 60% and 48% of DAA-exposed HCC patients and DAA-unexposed HCC patients; respectively had high CRS scores without significant difference. DAA-exposed HCC patients showed elevated Albumin, Hemoglobin and decreased ALT, AST compared with DAA-unexposed HCC patients (P = 0.002, 0.04, <0.001 and 0.006; respectively). FIB4 and APRI didn't reach the statistical difference between the studied groups. DAA-exposed HCC patients have higher overall survival (OS) than DAA-unexposed HCC patients (median: 30 & 15 months; respectively (p = 0.019)). Moreover, no significant differences were observed between the two groups in their focal lesion characteristics. CONCLUSION All studied patients are genetically predisposed to develop HCC. Moreover, DAAs significantly improved the OS and the biochemical parameters. No differences between the two groups were detected regarding their tumor characteristics. Accordingly, the appearance of HCC after treatment is attributed to the natural course of cirrhosis.
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Affiliation(s)
- Reham M. Dawood
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt
| | - Mai Abd El-Meguid
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt
| | - Hend Ibrahim Shousha
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Egypt
| | - Ahmed Elsayed
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Egypt
| | - Mohamed Mahmoud Nabeel
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt
| | - Ayman Yosry
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Egypt
| | - Ashraf Abdelaziz
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Egypt
| | - Ghada M. Salum
- Department of Microbial Biotechnology, Biotechnology Research Institute, National Research Centre, 33 EL Bohouth Street Dokki, Giza, 12622, Egypt
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El Kassas M, Eltabbakh M, Elbadry M, Tawheed A, Elbaz T. Establishing a research production line in real-life settings: the case of Hepatitis C management in a viral hepatitis specialized Egyptian center. Curr Med Res Opin 2022; 38:553-563. [PMID: 35118916 DOI: 10.1080/03007995.2022.2038489] [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: 10/12/2021] [Revised: 01/23/2022] [Accepted: 02/02/2022] [Indexed: 11/03/2022]
Abstract
Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Elbadry
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatogastroenterology, Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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20
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Sapena V, Enea M, Torres F, Celsa C, Rios J, Rizzo GEM, Nahon P, Mariño Z, Tateishi R, Minami T, Sangiovanni A, Forns X, Toyoda H, Brillanti S, Conti F, Degasperi E, Yu ML, Tsai PC, Jean K, El Kassas M, Shousha HI, Omar A, Zavaglia C, Nagata H, Nakagawa M, Asahina Y, Singal AG, Murphy C, Kohla M, Masetti C, Dufour JF, Merchante N, Cavalletto L, Chemello LL, Pol S, Crespo J, Calleja JL, Villani R, Serviddio G, Zanetto A, Shalaby S, Russo FP, Bielen R, Trevisani F, Cammà C, Bruix J, Cabibbo G, Reig M. Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis. Gut 2022; 71:593-604. [PMID: 33741640 DOI: 10.1136/gutjnl-2020-323663] [Citation(s) in RCA: 70] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/12/2021] [Accepted: 01/29/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. DESIGN We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. RESULTS Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.
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Affiliation(s)
- Victor Sapena
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Marco Enea
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy
| | - Ferran Torres
- Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain
| | - Ciro Celsa
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, Sicilia, Italy
| | - Jose Rios
- Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain
| | - Giacomo Emanuele Maria Rizzo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", F-93206 Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeurs solides", F-75000, Bondy, France
| | - Zoe Mariño
- Liver Unit, Hospital Clinic de Barcelona, IDIBAPS, University of Barcelona, CIBEREHD, Barcelona, Spain
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
- CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | - Xavier Forns
- Liver Unit, Hospital Clinic de Barcelona, IDIBAPS, University of Barcelona, CIBEREHD, Barcelona, Spain
| | - Hidenori Toyoda
- Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Stefano Brillanti
- Department of Medical and Surgical Sciences (DIMEC), Research Centre for the Study of Hepatitis, University of Bologna, Bologna, Italy
| | - Fabio Conti
- Department of Medical and Surgical Sciences (DIMEC), Research Centre for the Study of Hepatitis, University of Bologna, Bologna, Italy
| | - Elisabetta Degasperi
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
- CRC "A.M. and A. Migliavacca" Center for Liver Disease, Milan, Italy
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis, Center Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis, Center Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Kevin Jean
- Laboratoire MESuRS (EA 4628), Conservatoire National Des Arts et Métiers, Paris, France
- Unité PACRI, Institut Pasteur, Conservatoire National des Arts et Métiers, Paris, France
| | - Mohamed El Kassas
- Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Hend Ibrahim Shousha
- Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf Omar
- Endemic Medicine and Hepato-Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Claudio Zavaglia
- Department of Hepatology and Gastroenterology, Liver Unit, Niguarda Hospital, Milano, Lombardia, Italy
| | - Hiroko Nagata
- Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
- Institute of Education, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Liver Disease Control, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Caitlin Murphy
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Mohamed Kohla
- Hepatology, National Liver Institute, Shebin El-Kom, Egypt
| | - Chiara Masetti
- Liver and Transplant Unit, Policlinico Tor Vergata, Rome, Italy
| | - Jean-François Dufour
- Hepatology, Department of Clinical Research, University Clinic for Visceral Surgery and Medicine Inselspital, Bern, Switzerland
- Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Nicolas Merchante
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Seville, Spain
| | - Luisa Cavalletto
- Department of Medicine-DIMED, Padua University, University Hospital, Clinica Medica 5, Refering Center for Liver Diseases, Padova, Italy
| | - Liliana Lc Chemello
- Department of Medicine-DIMED, Padua University, University Hospital, Clinica Medica 5, Refering Center for Liver Diseases, Padova, Italy
| | - Stanislas Pol
- l'Agence de recherche ANRS (France REcherche Nord&Sud Sida-HIV Hépatites), Paris, France
| | - Javier Crespo
- Gastroenterology and Hepatology Service, Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain
- Facultad de Medicina, Universidad de Cantabria, Santander, Cantabria, Spain
| | - Jose Luis Calleja
- Gastroenterology and Hepatology, IDIPHIM, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain
- (CIBEREHD), Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Madrid, Spain
| | - Rosanna Villani
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gaetano Serviddio
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Alberto Zanetto
- Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology Unit, University of Padova, Padova, Italy
| | - Sarah Shalaby
- Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology Unit, University of Padova, Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology/Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology Unit, University of Padova, Padova, Italy
| | - Rob Bielen
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Limburg, Belgium
- Department of Gastro-Enterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Limburg, Belgium
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Calogero Cammà
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy
| | - Maria Reig
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain
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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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Elbaz T, Waked I, El-Akel W, Shaker MK, Abdelaziz AO, Yousif M, El-Bendary M, Zaky S, AbdAllah M, Hassany M, Esmat G, Doss W. Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma. Expert Rev Anti Infect Ther 2022; 20:307-314. [PMID: 34253123 DOI: 10.1080/14787210.2021.1951230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/30/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.
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Affiliation(s)
- Tamer Elbaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Hepatology, National Liver Institute, Menoufiya University, Menoufiya, Egypt
| | - Wafaa El-Akel
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Monkez Yousif
- Internal Medicine Department, Zagazig University, Sharkia, Egypt
| | - Mahmoud El-Bendary
- Department of Tropical Medicine and Hepatology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Samy Zaky
- Department of Hepatogastroenterology and Infectious Diseases, Al-Azhar University, Cairo, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Center, Giza, Egypt
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wahid Doss
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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23
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Lithy RM, Elbaz T, H Abdelmaksoud A, M Nabil M, Rashed N, Omran D, Kaseb AO, O Abdelaziz A, I Shousha H. Survival and recurrence rates of hepatocellular carcinoma after treatment of chronic hepatitis C using direct acting antivirals. Eur J Gastroenterol Hepatol 2022; 34:227-234. [PMID: 33208688 DOI: 10.1097/meg.0000000000001972] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Conflicting studies were proposed either suggested or denied the relationship between early hepatocellular carcinoma (HCC) recurrence and the use of direct-acting antivirals (DAAs) for chronic hepatitis C management. AIM OF THE STUDY To evaluate HCC recurrence rate post-DAAs and potential predictive factors.Study This prospective cohort study included all HCC patients achieved complete response attending our multidisciplinary HCC clinic, Cairo University, from November 2013 to February 2018. Group I (60 patients) who received DAAs after HCC ablation and group II (273 patients) who were DAAs-untreated. We studied factors that could play a role in HCC recurrence. RESULTS The sustained virological response rate was 88.3% among DAA-treated patients. HCC recurrence rate was 45% in the post-DAA group vs. 19% in the non-DAAs group; P < 0.001. Mean survival was significantly higher in the post-DAA group (34.23 ± 16.16 vs. 23.92 ± 13.99 months respectively; P value <0.001). There was a significant correlation between HCC recurrence rate and age, male gender, mean size of tumors and time interval between complete HCC ablation and occurrence of HCC recurrence. CONCLUSION Our study reports high rate of HCC recurrence post-DAA therapy in patients treated with transarterial chemoembolization but not in those treated with curative measures. DAA therapy after curative treatment for HCC led to significantly earlier HCC recurrence, which correlated with specific clinic-pathologic features in our prospective single-institution study. However, future independent prospective randomized studies are warranted to evaluate this correlation which may lead to a change in the current standard-of-care approach to patients with hepatitis C virus-related HCC.
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Affiliation(s)
- Rania M Lithy
- Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Tamer Elbaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Ahmed H Abdelmaksoud
- Diagnostic and Interventional Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed M Nabil
- Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Noha Rashed
- Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Dalia Omran
- Endemic Medicine Department, Faculty of Medicine, Cairo University
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | - Hend I Shousha
- Endemic Medicine Department, Faculty of Medicine, Cairo University
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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Salum GM, el Meguid MA, Abelhafez TH, Medhat E, Abdel Aziz AO, Dawood R. Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation. J Genet Eng Biotechnol 2021; 19:174. [PMID: 34757522 PMCID: PMC8581076 DOI: 10.1186/s43141-021-00266-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Accepted: 10/05/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Orthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. RESULTS Seven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02-1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5-1407.8]. CONCLUSIONS Accordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.
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Affiliation(s)
- Ghada M. Salum
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Mai Abd el Meguid
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Tawfeek H. Abelhafez
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
| | - Eman Medhat
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf O. Abdel Aziz
- Department of Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Reham Dawood
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Dokki, P.O. 12622, Giza, Egypt
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Isaac A, Mohamed SM, Ahmed OA, Hassan AGM, Rasmy HS. Amphiregulin as a novel diagnostic and prognostic biomarker of hepatocellular carcinoma before and after locoregional treatment. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.1186/s43162-021-00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is a highly prevalent tumor worldwide. Amphiregulin is a ligand of the epidermal growth factor receptor. Its elevation is linked to different inflammatory and neoplastic conditions. Therefore, amphiregulin may represent a potential diagnostic target in HCC, which has sparked interest as a potential predictor of diagnosis and progression of HCC. The current work was set out to evaluate amphiregulin as a possible diagnostic and prognostic biomarker for HCC on top of cirrhosis. Thirty adult patients with liver cirrhosis and HCC (HCC group) were randomly selected as candidates for locoregional therapies, either radiofrequency ablation or transarterial chemoembolization. A separate group of thirty liver cirrhosis patients served as controls (cirrhosis group). All patients underwent standard laboratory tests and abdominal ultrasounds. Alpha-fetoprotein and amphiregulin were measured twice at baseline and 1 month after the intervention.
Results
Baseline serum amphiregulin was significantly higher in the HCC group than in the cirrhosis group (23.2 ± 11.5 vs. 11.1 ± 7.1), with a p value < 0.001. Patients with multiple and larger focal lesions had greater levels of amphiregulin, with p values of 0.015 and 0.002, respectively. At 1 month following locoregional treatment, the amphiregulin level considerably declined compared with its baseline levels (from 23.2 ± 11.5 to 19.4 ± 10.9), with a p value of 0.012, while AFP showed an insignificant reduction. At follow-up, the level of serum amphiregulin was statistically significantly greater in recurrence cases than in remission cases (30.8 ± 14.1 vs. 17.2 ± 8.8), with a p value of 0.008, and the same was observed for AFP level.
At a cutoff ≥ 17 pg/mL, amphiregulin was a valuable marker in HCC detection with a sensitivity and specificity of 63.3% and 86.7%, respectively, while it has 60% sensitivity and 96% specificity in detecting possible tumor recurrence at a cutoff ≥ 29.7 pg/ml.
Conclusions
Amphiregulin may be a good diagnostic marker for HCC and a prognostic marker after locoregional therapies because its follow-up levels are useful in predicting possible tumor recurrence.
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Elbahrawy A, Ibrahim MK, Eliwa A, Alboraie M, Madian A, Aly HH. Current situation of viral hepatitis in Egypt. Microbiol Immunol 2021; 65:352-372. [PMID: 33990999 DOI: 10.1111/1348-0421.12916] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/02/2021] [Accepted: 05/11/2021] [Indexed: 12/12/2022]
Abstract
An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.
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Affiliation(s)
- Ashraf Elbahrawy
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Marwa K Ibrahim
- Department of Microbial Biotechnology, Division of Genetic Engineering and Biotechnology Research, National Research Centre, Giza, Egypt
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Ahmed Eliwa
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Ali Madian
- Department of Internal Medicine, Al-Azhar University, Assiut, Egypt
| | - Hussein Hassan Aly
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
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Kilany S, Ata L, Gomaa A, Sabry A, Nada A, Tharwa ES, Badra G, Abogabal A, Elwaraky M, Moaz E, Ezzat S, Elsharawy A, Waked I. Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis. J Hepatocell Carcinoma 2021; 8:925-935. [PMID: 34408991 PMCID: PMC8367200 DOI: 10.2147/jhc.s295330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 05/06/2021] [Indexed: 01/03/2023] Open
Abstract
Background and Aim Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). Methods Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. Results The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. Conclusion Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.
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Affiliation(s)
- Shimaa Kilany
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Lmyaa Ata
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Asmaa Gomaa
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Aliaa Sabry
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Ali Nada
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - El-Sayed Tharwa
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Gamal Badra
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Ashraf Abogabal
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Mohamed Elwaraky
- Radiology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Enas Moaz
- Epidemiology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Sameera Ezzat
- Epidemiology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Ahmed Elsharawy
- Clinical Pathology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Imam Waked
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt
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Montasser IF, Ibrahim AA, Farid HM, Al Balakosy AM. De novo hepatocellular carcinoma in cirrhotic hepatitis C virus: Are directly acting antivirals beneficial? Clin Res Hepatol Gastroenterol 2021; 45:101517. [PMID: 32900667 DOI: 10.1016/j.clinre.2020.07.022] [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: 05/19/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Behavior of HCC that developed after DAAs therapy for HCV infection is still debated. In this study we aim to compare characteristics and pattern of de novo HCC in cirrhotic HCV patients who were treated and untreated with DAAs. PATIENTS AND METHODS This study included 160 cirrhotic HCV patients presented with de novo HCC during the period of December 2017 to December 2018. Patients were divided into two groups, group A included 80 patients who received DAAs and group B included 80 patients who were not exposed to DAAs. The characteristics of HCC in both groups were compared using BCLC Staging System. RESULTS The size of the largest lesion was 47mm±26 in group A and 41mm±27 in group B with statistically significant difference between both groups (p=0.03). No other significant differences existed regarding number, site, or total tumor size and most of the lesions were solid in both groups. Portal vein thrombosis and extrahepatic spread detected in 16 and 11 patients in group A, while in group B the number was 17 and 9 patients respectively (p=0.83 and 0.06). No significant differences between groups in type of intervention done, BCLC staging (p=0.4), or survival. CONCLUSION Although CHCV patients treated with DAAs had larger de novo HCC lesions than untreated patients, there was no difference in BCLC staging or in aggressive behavior between both groups.
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Affiliation(s)
- Iman F Montasser
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Amany A Ibrahim
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Hoda M Farid
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
| | - Amira M Al Balakosy
- Department of Tropical Medicine, Faculty of Medicine - Ain Shams University, Cairo, Egypt.
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30
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Sahakyan Y, Lee-Kim V, Bremner KE, Bielecki JM, Krahn MD. Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta-analysis. J Viral Hepat 2021; 28:739-754. [PMID: 33556225 DOI: 10.1111/jvh.13482] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/23/2021] [Indexed: 02/06/2023]
Abstract
The long-term effects of direct-acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta-analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non-DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random-effects meta-analyses with inverse variance weighting, with sensitivity analyses and meta-regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI = 0.44; 0.38-0.52), decompensation (HR; CI = 0.54; 0.38- 0.76) and HCC occurrence (HR; CI = 0.72; 0.61- 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI = 0.72; 0.44-1.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI = 0.33; 0.23-0.46), decompensation (HR; CI = 0.11; 0.05-0.24), HCC occurrence (HR; CI = 0.31; 0.27-0.37) and HCC recurrence (HR; CI = 0.32; 0.20-0.51). Meta-regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow-up. In conclusion, our findings show protective effects of DAA treatment and DAA-related SVR on CHC progression and mortality.
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Affiliation(s)
- Yeva Sahakyan
- Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Victoria Lee-Kim
- Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,School of Medicine, Queens University, Kingston, ON, Canada
| | - Karen E Bremner
- Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Joanna M Bielecki
- Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Murray D Krahn
- Toronto Health Economics and Technology Assessment (THETA) Collaborative, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Institute of Health Policy, Management and Evaluation (IHPME), University of Toronto, Toronto, ON, Canada.,Department of Medicine, University of Toronto and University Health Network, Toronto, ON, Canada.,Institute for Clinical Evaluative Sciences (ICES), Toronto, ON, Canada
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31
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Frazzoni L, Sikandar U, Metelli F, Sadalla S, Mazzella G, Bazzoli F, Fuccio L, Azzaroli F. Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:1694. [PMID: 33920785 PMCID: PMC8071154 DOI: 10.3390/jcm10081694] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 03/08/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. AIM To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). METHODS A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. RESULTS Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26-34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17-28%) to US studies (34%, CI, 30-38%), to Egyptian studies (37%, CI, 27-47%), and to Asian studies (33%, CI, 27-40%). Sixty-eight percent (CI, 45-91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51-0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49-0.94). CONCLUSIONS The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.
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Affiliation(s)
- Leonardo Frazzoni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (L.F.); (F.B.); (L.F.)
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Usama Sikandar
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Flavio Metelli
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Sinan Sadalla
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Giuseppe Mazzella
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Franco Bazzoli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (L.F.); (F.B.); (L.F.)
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Lorenzo Fuccio
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (L.F.); (F.B.); (L.F.)
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
| | - Francesco Azzaroli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (L.F.); (F.B.); (L.F.)
- Department of Medical and Surgical Sciences, Gastroenterology Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; (U.S.); (F.M.); (S.S.); (G.M.)
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Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients. Cancers (Basel) 2021; 13:cancers13071729. [PMID: 33917345 PMCID: PMC8038691 DOI: 10.3390/cancers13071729] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 03/29/2021] [Accepted: 03/29/2021] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) recurrence is the major obstacle concerning patients’ survival. Tertiary prevention by antiviral therapies could reduce HCC recurrence rate in both chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients. In chronic hepatitis B (CHB) patients, nucleos(t)ide analogues (Nuc) provide a more effective HCC tertiary prevention effect than an interferon (IFN)-based regimen. In chronic hepatitis C (CHC) patients, the tertiary prevention effect by direct acting antiviral agents (DAAs) was reported non-inferior to that by IFN-based therapy. Chronic hepatitis C patients left untreated had the worst survival benefit as well as shorted recurrence-free interval than those treated by either type of antiviral regimen. Although the risk of HCC recurrence could only be decreased but not diminished by antiviral therapies due to host and microenvironmental factors beyond virus infection, antiviral therapy helps to preserve and improve liver function which makes multi-modality anticancer treatment feasible to improve survival. Abstract Hepatocellular carcinoma (HCC) ranks as a leading cause of common cancer and cancer-related death. The major etiology of HCC is due to chronic hepatitis virus including HBV and HCV infections. Scheduled HCC surveillance in high risk populations improves the early detection rate and the feasibility of curative treatment. However, high HCC recurrence rate still accounts for the poor prognosis of HCC patients. In this article, we critically review the pathogenesis of viral hepatitis-related hepatocellular carcinoma and the evidence of tertiary prevention efficacy by current available antiviral treatment, and discuss the knowledge gap in viral hepatitis-related HCC tertiary prevention.
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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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Mangoud NOM, Ali SA, El Kassas M, Soror SH. Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals. IUBMB Life 2021; 73:474-482. [PMID: 33347699 DOI: 10.1002/iub.2444] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/19/2020] [Accepted: 12/20/2020] [Indexed: 02/02/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer death in Egypt. There is still a risk for HCC development even after eradicating hepatitis C virus (HCV) by direct-acting antivirals (DAAs). Chitinase-3-like-protein-1 (CHI3L1), a biomarker for predicting many diseases, plays an essential role in inflammation, angiogenesis, and antiapoptosis. Tolloid-like protein 1 (TLL1) may be involved in hepatic fibrogenesis and carcinogenesis. This study aimed to determine the role and combined effect of CHI3L1 (rs880633), TLL1 (rs1503298), and an intergenic (rs597533) polymorphisms on the risk of developing HCC in Egyptian patients after achieving sustained virological response (SVR) by DAAs. Blood samples were collected from 68 HCC patients, 77 non-HCC subjects, and 80 healthy controls. The DNA was extracted and analyzed for rs880633, rs1503298, and rs597533 using Genotyping TaqMan™ assay. The result of the present study showed a significant difference in genotypes and alleles frequencies in both (rs880633) and (rs597533) in HCC group as compared to healthy control and also as compared to the non-HCC group. However, regarding to (rs1503298) genotypes and alleles between the HCC and non-HCC groups, there were no significant differences. Combined polymorphism in more than one gene simultaneously showed a higher risk to HCC after SVR than an individual locus. Both allelic and genotypic variations of the CHI3L1 gene (rs880633) and an intergenic (rs597533) seemed to be significant predictors confirming a great risk for HCC susceptibility in Egyptian patients achieved SVR. Patients with a polymorphism in more than one gene showed an increased risk to HCC after SVR rather than individual locus.
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Affiliation(s)
- Nadia O M Mangoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Sahar A Ali
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Helwan, Egypt
| | - Sameh H Soror
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, Egypt
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Absence of impact of direct acting antivirals for hepatitis C virus on recurrent hepatocellular carcinoma tumor growth in the AFEF/ANRS CO22 Hepather cohort. Clin Res Hepatol Gastroenterol 2021; 45:101459. [PMID: 32595103 DOI: 10.1016/j.clinre.2020.04.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/08/2020] [Accepted: 04/23/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although it has now been excluded that direct-acting antivirals (DAA) are associated with a significant risk of hepatocellular carcinoma (HCC) in HCV-infected patients, a possible effect of DAA on tumor growth is still a subject of debate. We performed a blind comparison of the kinetics of HCC recurrence in patients after HCV treatment with or without DAA to evaluate the potential aggressiveness of HCC after DAA treatment. BASIC PROCEDURES Thirty-nine HCV-infected patients from the AFEF/ANRS CO22 Hepather cohort who experienced HCC recurrence after so-called curative treatment were evaluated. Contrast-enhanced CT and/or MR images were read blindly 6 months before HCC recurrence and during the follow-up period. Seventeen patients who received DAA (DAA+) before HCC recurrence were compared to the 22 who did not receive (DAA-), according to the LiRads and mRECIST criteria. MAIN FINDINGS There were 28 men and 11 women, median age 62 years old, 37 (95%) with cirrhosis. DAA+ patients had a lower median MELD score (8±2 vs. 10±4, P=0.0286) than DAA- patients. The median time to HCC recurrence (time from the date of curative treatment to the diagnosis of recurrence) was not different (20 vs. 18 months) (P=0.73) between the two groups. There was no difference between the 2 groups in the overall survival and/or transplantation-free survival (P=0.71) and for the mRECIST time to progression (P=0.25). CONCLUSION This blinded analysis of HCC recurrence after HCC treatment does not support any negative impact of DAA therapy on the severity or progression of recurrent HCC.
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Salum GM, Dawood RM, Abd el-Meguid M, Ibrahim NE, Abdel Aziz AO, El Awady MK. Correlation between IL28B/TLR4 genetic variants and HCC development with/without DAAs treatment in chronic HCV patients. Genes Dis 2020; 7:392-400. [PMID: 32884993 PMCID: PMC7452484 DOI: 10.1016/j.gendis.2019.05.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 05/13/2019] [Accepted: 05/20/2019] [Indexed: 02/07/2023] Open
Abstract
In Egypt, Sofosbuvir (SOF) in combination with Dataclasvir (DCV) is the broadly used DAAs with excellent therapeutic profile. This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings; HCC development post SOF/DCV treatment, progression to HCC in naïve patients and SOF/DCV therapy outcome. A total of 493 blood samples were collected (controls (n = 70); HCV patients treated with SOF/DCV (n = 252) of whom 65 patients developed HCC, 187 patients didn't develop HCC (125 responders, 62 relapsers); naïve HCV patients (n = 171) had early (n = 48), late liver fibrosis (n = 21) and HCC (n = 102)). Both SNPs were genotyped using a TaqMan 5' allelic discrimination assay. At IL28B rs12979860 SNP, the C allele was significantly correlating with the response rate more than T allele (OR 1.9, 95% CI 1.29-2.9, p = 0.004), while at TLR4 rs4986791 SNP, no association was found (OR 6.5, 95% 0.57-75.28, p = 0.09). Both SNPs couldn't detect the probability for HCC emergence after treatment. In naïve patients, the protective alleles were detected in their lowest frequency in HCC patients (p = 0.1, for rs12979860 and, p = 0.001 for rs4986791). SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype, with the best rates in those lacking the T allele.
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Key Words
- DAAs
- DAAs, Direct acting antiviral agents
- DCV
- DCV, Dataclasvir
- HCC
- HCC, Hepatocellular carcinoma
- HCV
- HCV, hepatitis C virus
- IFNλ, Type III IFNs
- IL28B
- ISGs, interferon-stimulated genes
- JAK/STAT, Janus kinase/signal transducers and activators of transcription
- PAMPs/DAMPs, pathogen/damage associated molecular patterns
- SNP, single nucleotide polymorphism
- SOF
- SOF, Sofosbuvir
- SVR, sustained virological response
- TLR4
- TLRs, toll like receptors
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Affiliation(s)
- Ghada M. Salum
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St.(former El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Reham M. Dawood
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St.(former El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Mai Abd el-Meguid
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St.(former El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Noha E. Ibrahim
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St.(former El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
| | - Ashraf O. Abdel Aziz
- Department of Tropical Medicine, Faculty of Medicine, Cairo University, Giza, P.O. 12622, Egypt
| | - Mostafa K. El Awady
- Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, 33 EL Bohouth St.(former El Tahrir St.), Dokki, Giza, P.O. 12622, Egypt
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Musa NI, Mohamed IE, Abohalima AS. Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma recurrence. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-00035-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
The impact of direct-acting antivirals (DAAs) remains a debate, whether they accelerate the recurrence rate of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative therapy. We evaluated the impact of direct-acting antiviral therapy on the rate of recurrence of HCV-related hepatocellular carcinoma following intervention in Egyptian patients.
Results
The results of the study represented an HCC recurrence rate of 38% in patients who received direct-acting antiviral therapy after HCC intervention versus 62% in those who did not receive antiviral therapy. In group I, according to the Barcelona Clinic of Liver Cancer (BCLC) staging, a higher recurrence rate was observed (57.9%) among patients who were classified as BCLC stage B.
Conclusions
HCC patients who did not receive direct-acting antiviral therapy after HCC intervention had a greater risk of HCC recurrence. DAAs did not increase the risk of HCC recurrence following HCC treatment; however, it did not abolish it. Close monitoring of patients after antiviral therapy is recommended.
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Esmat G, Elbaz T, Elsharkawy A, Abdullah M, El Kassas M. Emerging from the screening of 57 million citizens and treating 4 million patients: future strategies to eliminate hepatitis C from Egypt. Expert Rev Anti Infect Ther 2020; 18:637-642. [PMID: 32302245 DOI: 10.1080/14787210.2020.1758065] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 04/16/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Egypt succeeded in establishing a successful model of care for hepatitis C virus (HCV) management in the country with the highest worldwide disease prevalence. The Egyptian ministry of health announced an optimistic goal of near disease elimination. More steps are still required to achieve such a goal. AREAS COVERED This review covers the efforts made in treatment and prevention of HCV by the Egyptian National Committee for the Control of Viral Hepatitis (NCCVH) with emphasis on the extensive screening program that was able to screen more than 57 million citizens, and future strategies implemented to ensure eradicating the virus from the country. EXPERT OPINION Despite the great efforts and the proven success in controlling the HCV epidemic in Egypt, some facets of the Egyptian program still need to be upgraded to reach the HCV elimination goal. A significant workload with follow up programs for those who were successfully treated, and treatment failure cases are existing. More enhancement for the currently performed prevention and control measure is missing. Also, we strongly recommend conducting a recent nationwide survey to document the actual infection rates of HCV after all these efforts.
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Affiliation(s)
- Gamal Esmat
- Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Giza, Egypt
| | - Tamer Elbaz
- Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Giza, Egypt
| | - Aisha Elsharkawy
- Endemic Hepatogastroenterology, Faculty of Medicine, Cairo University , Giza, Egypt
| | | | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University , Cairo, Egypt
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Khalid J, Umar M, Ur-Rehman T, Ali M, Khan GM. Tumor aggression among hepatitis-C related hepatocellular carcinoma patients: an observational study regarding the impact of anti-HCV therapy. Infect Agent Cancer 2020; 15:35. [PMID: 32508980 PMCID: PMC7251734 DOI: 10.1186/s13027-020-00300-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 05/04/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, however development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated. In this study we aim to analyze association between anti-HCV therapy and tumor pattern of HCV related HCC patients. METHODS Hepatocellular Carcinoma (HCC) patients with seropositivity for hepatitis C virus (HCV) antibodies, registered at three tertiary care hospitals of Rawalpindi and Islamabad, Pakistan during August 2017 to July 2018 were enrolled. Selected patients were then segregated in two groups on the basis of their HCV treatment history i.e., "TN" (HCV Treatment Naïve i.e. having no history/medical record for treatment prior to HCC diagnosis) and "TH" (Treated for HCV infection). Aggressiveness index (AgI) scoring system was applied to determine the tumor pattern. Univariate and multivariate analysis was carried out to analyze the independent effect of anti-HCV therapy on tumor pattern. RESULTS Out of 234 consecutive HCC patients, 171 HCV-related HCC patients were enrolled in final analysis and labeled as "TN" (n = 120) and "TH" (n = 51). Tumor pattern was found to be significantly aggressive (P = 0.02) in the treated cohort with an adjusted odds of 2.47 for aggressive and 6.92 for highly aggressive tumor. Neutrophil to lymphocyte ratio (NLR) was strongly associated with highly aggressive tumor pattern (P = 0.012). Patients in TN group were found to be marginally older than those in the TH group (59.5 vs. 55 years) where mean age of the patients treated with direct acting anti-viral agents was found to be visibly lower than mean age of patients who received interferon based treatment (53.5 vs. 57 years) with significant masculine predominance (62.1 vs. 37.9%, P = 0.049). CONCLUSION We observed raised neutrophil to lymphocyte ratio and prominence of younger age with aggressive tumor biology in HCV treated HCC patients. These observations highlight the need for a longitudinal prospective study on HCV positive subjects treated with antivirals, irrespective of treatment response.
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Affiliation(s)
- Javeria Khalid
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320 Pakistan
- Clinical Pharmacist at Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Mohammad Umar
- Center for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi Medical University, Rawalpindiand, 46300 Pakistan
| | - Tofeeq Ur-Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320 Pakistan
| | - Mashhood Ali
- Gasteroenterology Department, Pakistan Institute of Medical Sciences (PIMS) Hospital, Islamabad, 44000 Pakistan
| | - Gul Majid Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320 Pakistan
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Negro F. Natural History of Hepatic and Extrahepatic Hepatitis C Virus Diseases and Impact of Interferon-Free HCV Therapy. Cold Spring Harb Perspect Med 2020; 10:cshperspect.a036921. [PMID: 31636094 DOI: 10.1101/cshperspect.a036921] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The hepatitis C virus (HCV) infects 71.1 million persons and causes 400,000 deaths annually worldwide. HCV mostly infects the liver, causing acute and chronic necroinflammatory damage, which may progress toward cirrhosis and hepatocellular carcinoma. In addition, HCV has been associated with several extrahepatic manifestations. The advent of safe and effective direct-acting antivirals (DAAs) has made the dream of eliminating this public health scourge feasible in the medium term. Prospective studies using DAA-based regimens have shown the benefit of HCV clearance in terms of both liver- and non-liver-related mortality.
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Affiliation(s)
- Francesco Negro
- Divisions of Clinical Pathology and of Gastroenterology and Hepatology, University Hospital, 1211 Genève 4, Switzerland
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Ozeki I, Nakajima T, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y. Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc. J Clin Biochem Nutr 2020; 66:245-252. [PMID: 32523252 DOI: 10.3164/jcbn.19-98] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 12/04/2019] [Indexed: 12/20/2022] Open
Abstract
The recently approved direct-acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV-infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow-up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 µg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline-zinc <60 µg/dl (HR 6.283), EOT-serum zinc <63 µg/dl (HR 6.011), baseline-AFP ≥6.0 ng/dl (HR 8.163), and EOT-M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.
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Affiliation(s)
- Itaru Ozeki
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Masakatsu Yamaguchi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
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Joko K, Mashiba T, Ochi H, Yano R, Sato K, Okujima Y, Aono M, Azemoto N, Takechi S, Yokota T, Jinoka R, Moriyama Y, Nishiyama M. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepatogastroenterol 2020; 9:78-83. [PMID: 32117695 PMCID: PMC7047307 DOI: 10.5005/jp-journals-10018-1305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background A possible interaction of hepatitis viruses at cellular and molecular levels has been suggested. Eradication of hepatitis C virus (HCV) has been reported to induce activation of hepatitis B virus (HBV)-related liver diseases. Materials and methods The present study examined association of HBV markers with recurrence of hepatocellular carcinoma (HCC) in patients with resolved HCV infection by direct-acting antiviral (DAA) therapy. In a patient pool of 378 patients with sustained virologic response (SVR) by DAA, the antibody to the hepatitis B surface antigen (anti-HBs), the antibody to the hepatitis B core antigen (anti-HBc), and HBV-DNA levels were estimated before and at the end of DAA therapy. These patients were HBsAg negative. Eighty-nine patients had a history of curative treatment of HCC by resection or radiofrequency ablation. A Cox proportional hazards model was used to identify risk factors for HCC recurrence, including the change ratio of the antibody against HBV proteins. Results Although 188 patients had resolved HBV infection, no patient showed HBV reactivation, but anti-HBs and anti-HBc levels decreased significantly. No significant difference in the HCC recurrence rate was evident between patients with and without resolved HBV infection. Changes of immune responses to HBV proteins did not affect HCC recurrence after DAA therapy for HCV infection in this cohort. Conclusion The mechanisms underlying diverse roles of DAA-induced SVR of HCV on HBV kinetics need to be resolved in future. How to cite this article Joko K, Mashiba T, Ochi H, et al. Relation of Reduction of Antibodies against Hepatitis B Virus to Hepatocellular Carcinoma Recurrence in the Patients with Resolved Hepatitis B Virus Infection Following Direct-acting Antiviral Therapy for Hepatitis C Virus Infection. Euroasian J Hepato-Gastroenterol 2019;9(2):78–83.
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Affiliation(s)
- Kouji Joko
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan; Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Toshie Mashiba
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Hironori Ochi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryo Yano
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Kaori Sato
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yusuke Okujima
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Michiko Aono
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Nobuaki Azemoto
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Shunji Takechi
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Tomoyuki Yokota
- Department of Hepatology, Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Ryosuke Jinoka
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Yasunori Moriyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Masataka Nishiyama
- Department of Medical Laboratory, Matsuyama Red Cross Hospital, Ehime, Japan
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Szereday L, Meggyes M, Berki T, Miseta A, Farkas N, Gervain J, Par A, Par G. Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C. Clin Exp Med 2020; 20:219-230. [PMID: 32108916 PMCID: PMC7181552 DOI: 10.1007/s10238-020-00618-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 02/18/2020] [Indexed: 12/13/2022]
Abstract
Chronic hepatitis C (CHC) infection is associated with increased TIM-3, PD-1 immune checkpoint receptors expression that inhibits adaptive T cells and increases NK cell cytotoxicity against T helper cells, both resulting T cell exhaustion. Elimination of the virus with direct-acting antivirals (DAAs) may modify host immune response via altering these immune checkpoint receptors’ expression. We conducted a prospective study to analyze changes in TIM-3, PD-1 and their ligands galectin-9, PD-L1 expression by peripheral blood T cell subpopulations, NK cell subpopulations, and monocytes by multicolor flow cytometry in 14 CHC patients successfully treated with 12 weeks of dasabuvir, ombitasvir, and paritaprevir/ritonavir plus ribavirin. Blood samples were collected before, at the end of treatment, and 12 and 24 weeks later. Sustained virological response (SVR) was associated with increased percentage of peripheral blood CD3+ T and CD8+ cytotoxic T lymphocytes and decreased percentage of NKbright cells. After DAA treatment, decreased TIM-3 expression by CD4+ T cells, by NKbright, and by NKT cells was found. Expression of immune checkpoint molecules’ ligand PD-L1 by NK cells and by regulatory T cells and galectin-9 by NK cells and monocytes also decreased significantly at SVR. Our data suggest that DAA treatment not only inhibits viral replication but may alter host adaptive and innate immune responses. A decrease in immune checkpoint molecules and their ligands expression both on adaptive and on innate immune cells may contribute to the recovery of exhausted adaptive immune responses and to sustained virological response.
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Affiliation(s)
- Laszlo Szereday
- Department of Medical Microbiology and Immunology, University of Pecs, Medical School, 12 Szigeti Street, Pecs, 7624, Hungary. .,Janos Szentagothai Research Centre, Pecs, Hungary.
| | - Matyas Meggyes
- Department of Medical Microbiology and Immunology, University of Pecs, Medical School, 12 Szigeti Street, Pecs, 7624, Hungary.,Janos Szentagothai Research Centre, Pecs, Hungary
| | - Timea Berki
- Department of Biotechnology and Immunology, University of Pecs, Medical School, Pecs, Hungary
| | - Attila Miseta
- Department of Laboratory Medicine, University of Pecs, Medical School, Pecs, Hungary
| | - Nelli Farkas
- Institute for Translational Medicine, University of Pecs, Medical School, Pecs, Hungary
| | - Judit Gervain
- County Hospital Fejér, Szent György Hospital, Szekesfehervar, Hungary
| | - Alajos Par
- Division of Gastroenterology, First Department of Medicine, University of Pecs, Medical School, Pecs, Hungary
| | - Gabriella Par
- Institute for Translational Medicine, University of Pecs, Medical School, Pecs, Hungary.,Division of Gastroenterology, First Department of Medicine, University of Pecs, Medical School, Pecs, Hungary
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Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst 2020; 32:5. [PMID: 32372179 DOI: 10.1186/s43046-020-0016-x] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/02/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is a universal problem and its epidemiological data showed variation from place to place. Hepatocellular carcinoma (HCC) is the sixth and fourth common cancer in worldwide and Egypt, respectively. Egypt ranks the third and 15th most populous country in Africa and worldwide, respectively. The aim of this review is to compare the status of HCC in Egypt to that in the worldwide from different issues; risk factors, screening and surveillance, diagnosis and treatment, prevention, as well as research strategy. MAIN BODY The risk factors for HCC in Egypt are of great importance to be reported. The risk factor for HCC are either environmental- or host/genetic-related risk factors. In the last years, there is a tangible improvement of both screening and surveillance strategies of HCC in Egypt. The unprecedented national screening campaign launched by the end of 2018 is a mirror image of this improvement. While the improvement of the HCC prevention requires the governmental health administration to implement health policies. Although the diagnosis of Egyptian HCC patients follows the international guidelines but HCC treatment options are limited in terms of cost. In addition, there are limited Egyptian reports about HCC survival and relapse. Both basic and clinical HCC research in Egypt are still limited compared to worldwide. SHORT CONCLUSION Deep analysis and understanding of factors affecting HCC burden variation worldwide help in customization of efforts exerted to face HCC in different countries especially large country like Egypt. Overall, the presence of a research strategy to fight HCC in Egyptian patients will help in the optimum allocation of available resources to reduce the numbers of HCC cases and deaths and to improve the quality of life.
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Affiliation(s)
- Wafaa M Rashed
- Department of Research, Children's Cancer Hospital-57357, Cairo, Egypt.
| | | | - Mohamed O Mahmoud
- Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Sameera Ezzat
- Department of Epidemiology and Prevention Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
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He S, Lockart I, Alavi M, Danta M, Hajarizadeh B, Dore GJ. Systematic review with meta-analysis: effectiveness of direct-acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma. Aliment Pharmacol Ther 2020; 51:34-52. [PMID: 31808566 DOI: 10.1111/apt.15598] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 07/25/2019] [Accepted: 11/06/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision-making. AIM To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC. METHODS Bibliographic databases and conference abstracts were searched. Meta-analysis was conducted to pool sustained virologic response (SVR) estimates. RESULTS Fifty-six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1-90.4). Twenty-seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0-91.4) and 92.4% (95% CI 91.1-93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43-0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3-92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3-99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1-95.6). CONCLUSION Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.
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Affiliation(s)
- Sichan He
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Ian Lockart
- St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.,St Vincent's Hospital, Sydney, NSW, Australia
| | - Maryam Alavi
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia
| | - Mark Danta
- St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.,St Vincent's Hospital, Sydney, NSW, Australia
| | | | - Gregory J Dore
- The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.,St Vincent's Hospital, Sydney, NSW, Australia
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Teng W, Jeng WJ, Yang HI, Chen WT, Hsieh YC, Huang CH, Lin CC, Lin CY, Lin SM, Sheen IS. Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma. Cancers (Basel) 2019; 12:23. [PMID: 31861706 PMCID: PMC7016942 DOI: 10.3390/cancers12010023] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/16/2019] [Accepted: 12/17/2019] [Indexed: 01/27/2023] Open
Abstract
The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm (p < 0.001), but diminished in the DAA arm (p = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 104 person-years, log-rank p = 0.042) and III (5259 vs. 3278 per 104 person-years, log-rank p = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.
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Affiliation(s)
- Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Hwai-I Yang
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
- Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
| | - Wei-Ting Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Yi-Chung Hsieh
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Chien-Hao Huang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 333, Taiwan; (W.T.); (W.-T.C.); (Y.-C.H.); (C.-H.H.); (C.-C.L.); (S.-M.L.); (I.-S.S.)
- College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan
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El Kassas M, Tawheed A, Eltabbakh M, Kaseb A. Hepatitis C Antiviral Therapy In Patients With Successfully Treated Hepatocellular Carcinoma: Dancing With Wolves. J Hepatocell Carcinoma 2019; 6:183-191. [PMID: 31819865 PMCID: PMC6879003 DOI: 10.2147/jhc.s206668] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 10/21/2019] [Indexed: 12/16/2022] Open
Abstract
Hepatitis C virus (HCV) infection is known to be one of the leading causes of hepatocellular carcinoma (HCC) all over the world. Previously, multiple studies have confirmed a decreased rate of HCC occurrence or recurrence in the cases of hepatitis C associated cirrhosis after treatment with interferon, in comparison to the untreated cases, even in the absence of clearance of HCV. Treatment programs with direct-acting antivirals (DAAs) as a new method for HCV treatment and cure in 2014, with higher safety and efficacy, were considered as an important step in the treatment of patients with history of HCC, improving their overall prognosis. Recently, reports coming from various European centers claimed that the risk of HCC increased following DAAs therapy, especially in cases with previous HCC. Moreover, other studies revealed that the recurrence of HCC after DAAs treatment was more aggressive. Even though others were not able to conclude the same results, the role of DAA therapy in recurrence of HCC in patients with previous HCC after sustained virological response (SVR) achievement remains questionable. This review explored the existing literature and discussed opinions on the possibility of increasing recurrence of HCC following DAA therapy, possible mechanisms, predictors of HCC recurrence post DAAs, and whether those patients should be treated or not.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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Direct-acting antivirals for patients with chronic hepatitis C and hepatocellular carcinoma in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2019; 54:385-395. [PMID: 31771822 DOI: 10.1016/j.jmii.2019.09.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 09/16/2019] [Accepted: 09/17/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND/PURPOSE The treatment of chronic hepatitis C (CHC) has evolved from interferon (IFN)-based therapy to direct acting antivirals (DAAs). The effect of antiviral treatment on outcome of hepatocellular carcinoma (HCC) patients with CHC has not been well analyzed in Taiwan. METHODS From April 2015 to May 2018, 199 HCC patients with CHC undergoing DAAs treatment, including 127 having prospectively longitudinal observation, were enrolled. Among them, 107 BCLC 0/A patients achieving curative treatment of HCC were further compared with a historical cohort of 42 HCC patients experienced pegylated interferon (Peg-IFN) plus ribavirin for CHC after curative treatment. RESULTS The sustained virological response (SVR) rates were 95.0% in BCLC stage 0/A (114/120), 97.1% in BCLC B (68/70), and 77.8% in BCLC C (7/9). The median recurrence-free survivals (RFS) between the DAA and IFN arms were of no difference by counting either from antiviral treatment (29.3 mo vs 39.2 mo, p = 0.764) or from curative treatment (65.8 mo vs 44.0 mo, p = 0.130), respectively. Achievement of SVR was the key independent factor associated with RFS and overall survival. The pattern of recurrence was also similar between the DAA and IFN arms. For intermediate stage HCC patients, the median time to tumor progression was 9.2 months from the initiation of DAA therapy, and 90% of patients maintained in BCLC B till 12 months after the DAA treatment. CONCLUSIONS The SVR is high within BCLC B HCV-HCC patients by DAAs treatment. The risk of HCC recurrence and progression is not increased by DAAs.
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Ji F, Yeo YH, Wei MT, Ogawa E, Enomoto M, Lee DH, Iio E, Lubel J, Wang W, Wei B, Ide T, Preda CM, Conti F, Minami T, Bielen R, Sezaki H, Barone M, Kolly P, Chu PS, Virlogeux V, Eurich D, Henry L, Bass MB, Kanai T, Dang S, Li Z, Dufour JF, Zoulim F, Andreone P, Cheung RC, Tanaka Y, Furusyo N, Toyoda H, Tamori A, Nguyen MH. Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis. J Hepatol 2019; 71:473-485. [PMID: 31096005 DOI: 10.1016/j.jhep.2019.04.017] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 03/31/2019] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
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Affiliation(s)
- Fanpu Ji
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Mike Tzuhen Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Eiichi Ogawa
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Dong Hyun Lee
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology, Department of Internal Medicine, Good Gang-An Hospital, Busan, Republic of Korea
| | - Etsuko Iio
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - John Lubel
- Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Wenjun Wang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Carmen Monica Preda
- University of Medicine and Pharmacy "Carol Davila", Department of Gastroenterology and Hepatology, Clinical Institute Fundeni, Bucharest, Romania
| | - Fabio Conti
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan
| | - Rob Bielen
- Faculty of Medicine and Life Sciences, Hasselt University, Belgium
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Michele Barone
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, Azienda Universitario-Ospedaliera Policlinico, University of Bari, Bari, Italy
| | - Philippe Kolly
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Po-Sung Chu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Victor Virlogeux
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France
| | - Dennis Eurich
- Department of Surgery Campus Charité Mitte / Campus Virchow-Klinikum, Berlin, Germany
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Michelle B Bass
- Lane Medical Library & Knowledge Management Center, Stanford University, Palo Alto, CA, USA
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shuangsuo Dang
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Zongfang Li
- National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Jean-François Dufour
- Department of Clinical Research, University of Bern, Bern, Switzerland; University Clinic of Visceral Surgery and Medicine, Inselspital Bern, Bern, Switzerland
| | - Fabien Zoulim
- Department of Hepatology, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France; Cancer Research Center of Lyon (CRCL-INSERM U1052), Lyon University, Lyon, France
| | - Pietro Andreone
- Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Yasuhito Tanaka
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akihiro Tamori
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
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Darweesh SK, Elsaeed K, Omar H, El Raziky M, Elakel W, Elserafy M, Ismail SA, Gomaa AA, Mehrez M, El Kassas M, Abdullah M, Shaker MK, Esmat G, El Shazly Y, Doss W, Waked I. High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study. Expert Rev Gastroenterol Hepatol 2019; 13:907-914. [PMID: 31173527 DOI: 10.1080/17474124.2019.1629287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 06/05/2019] [Indexed: 01/26/2023]
Abstract
Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.
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Affiliation(s)
- Samar K Darweesh
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Kadry Elsaeed
- General Medicine, Hepatology and Gastroenterology Department, Faculty of Medicine, Ain Shams University , Cairo , Egypt
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Maissa El Raziky
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Wafaa Elakel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Magdy Elserafy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | | | - Ahmed A Gomaa
- Tropical Medicine Department, El- Fayoum University , Cairo , Egypt
| | - Mai Mehrez
- Hepatology-Internal Medicine Department, National Hepatology, and Tropical Medicine Research Institute , Cairo , Egypt
| | - Mahamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University , Cairo , Egypt
| | - Mohamed Abdullah
- Medical Research Division, National Research Center , Cairo , Egypt
| | | | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Yehia El Shazly
- General Medicine, Hepatology and Gastroenterology Department, Faculty of Medicine, Ain Shams University , Cairo , Egypt
| | - Wahid Doss
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University , Cairo , Egypt
| | - Imam Waked
- Hepatology Department, National Liver Institute, Menoufiya University , Shebeen EL Kom , Egypt
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