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Abdelmoneim RS, Sedki F, Bakosh MF. Changes in the presentation and characteristics OF HCV related hepatocellular carcinoma in the era of direct acting antiviral therapy: A retrospective study. Clin Res Hepatol Gastroenterol 2025; 49:102567. [PMID: 40043794 DOI: 10.1016/j.clinre.2025.102567] [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: 12/14/2024] [Revised: 02/19/2025] [Accepted: 03/02/2025] [Indexed: 03/10/2025]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth common malignancy worldwide. In Egypt, the main cause of HCC is hepatitis C virus (HCV)-related cirrhosis. After the successful mass treatment program of HCV in 2018 with direct-acting antivirals (DAAs) therapy, a large percentage of patients have been treated and effectively achieved sustained virological response (SVR). Recently, some studies claimed that HCCs that developed after treatment with DAAs have more aggressive behavior. Purpose of the study is to detect the possible change of HCC pattern before and after DAAs era and its effect on overall survival (OS). METHODS 428 naïve HCC patients were divided into 2 groups: Group I HCC patients not treated with DAAs and Group II HCC patients treated with DAAs. Then we compared demographic, clinical, radiological, and laboratory characteristics between both groups. RESULTS Group II had improved liver function tests, including serum bilirubin, albumin, and international normalized ratio, than Group I (p < 0.001, p < 0.001, p < 0.001, respectively). They had a lower level of liver aminotransferases. Group II showed a larger infiltrative pattern of HCC, with a high incidence of portal vein thrombosis (p = 0.003, p < 0.001, p = 0.048, respectively). Group II received more curative or palliative treatment options, while 55 % of Group I received the best supportive care. There was no significant difference in 1-year and 2-years OS between both group, except that group II patients had better 2-year OS in subgroup BCLC stage C. CONCLUSION The tumor pattern has changed into a more aggressive phenotype after DAAs. DAAs have succeeded in preserving the liver condition. However, they did not demonstrate any protective effect on the OS of the patients. There is a strong need for strict screening program for early detection of HCC in the early stages, that are eligible for curative options, after HCV treatment of DAAs.
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Affiliation(s)
- Randa Salah Abdelmoneim
- Hepato-pancreatico-biliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt.
| | - Fathalla Sedki
- Hepato-pancreatico-biliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt.
| | - Mohamed Fathy Bakosh
- Hepato-pancreatico-biliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, 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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Elbahrawy A, Atalla H, Mahmoud AA, Eliwa A, Alsawak A, Alboraie M, Madian A, Alashker A, Mostafa S, Alwassief A, Aly HH. Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents. FRONTIERS IN VIROLOGY 2023; 3. [DOI: 10.3389/fviro.2023.1227317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
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El-Kassas M, Sayed H, Omran D, Eldahrouty AH, Elbaz T, Kamal E. Prospective Comparison of Hepatocellular Carcinoma Behavior and Survival of Patients who Did or Did not Receive HCV Direct-Acting Antivirals. Asian Pac J Cancer Prev 2023; 24:597-605. [PMID: 36853310 PMCID: PMC10162632 DOI: 10.31557/apjcp.2023.24.2.597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 02/09/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND & AIMS The safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs) have been established in several real-world trials; however, some reports have claimed an association between DAAs and hepatocellular carcinoma (HCC) occurrence or aggressive behavior. We aimed to prospectively examine differences in de-novo HCC tumor behavior and overall survival (OS) in DAAs-treated versus HCV-untreated patients as measured by BCLC progression during a two-year follow-up period. METHODS This multicenter cohort study recruited 523 patients with de-novo HCV-related HCC. After exclusion criteria were applied, 353 patients were placed into; Group 1, including 236 patients without a history of DAAs therapy, and Group 2 including 117 patients with de-novo HCC developed after receiving DAAs. Patients were then stratified in each group according to BCLC staging (Liver, 2018). All patients received standard of care management and were followed until death or a maximum of 2 years. RESULTS No statistically significant differences were observed between the two groups regarding tumor characteristics (number and size of lesions) and criteria for aggressiveness upon presentation. Among all BCLC stages, DAAs treated patients showed significantly lower baseline Fib4 values than DAA untreated patients in BCLC-0 stage (4.1 vs 7.7, p 0.019). No statistically significant differences were evident in HCC progression in the different BCLC stages at 12 and 24 months follow up periods (p 0.0718 and 0.279 respectively). Significantly better survival was recorded in Group 1 compared to Group 2 patients for BCLC stages C and D (p = 0.003 and 0.01, respectively). CONCLUSION HCC may develop at an earlier stage of liver disease after DAAs therapy. No defensive role was found for DAAs treatment in delaying HCC progression that occurs after viral eradication.
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Affiliation(s)
- Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
| | - Hamdy Sayed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
| | - Dalia Omran
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Ali Hussein Eldahrouty
- Gastroenterology, Hepatology, and Endemic Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt.
| | - Tamer Elbaz
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Enas Kamal
- Gastroenterology, Hepatology, and Endemic Medicine Department, Faculty of Medicine, Minia University, Minia, Egypt.
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Sweed D, Sweed E, Moaz I, Mosbeh A, Fayed Y, Elhamed SMA, Sweed E, Macshut M, Abdelsattar S, Kilany S, Saied SA, Badr R, Abdallah MS, Ehsan N. The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt. World J Surg Oncol 2022; 20:298. [PMID: 36117166 PMCID: PMC9484175 DOI: 10.1186/s12957-022-02764-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/06/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).
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Affiliation(s)
- Dina Sweed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Enas Sweed
- Radiology Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Inas Moaz
- Epidemiology, and Preventive Medicine Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Asmaa Mosbeh
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Yahya Fayed
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara Mohamed Abd Elhamed
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Eman Sweed
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud Macshut
- Hepatopancreatobiliary Surgery Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Abdelsattar
- Clinical Biochemistry and Molecular Diagnostics Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Shimaa Kilany
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Sara A. Saied
- Clinical Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Reda Badr
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
| | - Mahmoud S. Abdallah
- Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia Egypt
| | - Nermine Ehsan
- Pathology Department, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia Egypt
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The diagnostic utility of microRNA 222-3p, microRNA 21-5p, and microRNA 122-5p for HCV-related hepatocellular carcinoma and its relation to direct-acting antiviral therapy. Arab J Gastroenterol 2022; 23:108-114. [DOI: 10.1016/j.ajg.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/22/2022] [Accepted: 04/11/2022] [Indexed: 11/21/2022]
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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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8
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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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Baglieri J, Zhang C, Liang S, Liu X, Nishio T, Rosenthal SB, Dhar D, Su H, Cong M, Jia J, Hosseini M, Karin M, Kisseleva T, Brenner DA. Nondegradable Collagen Increases Liver Fibrosis but Not Hepatocellular Carcinoma in Mice. THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:1564-1579. [PMID: 34119473 PMCID: PMC8406794 DOI: 10.1016/j.ajpath.2021.05.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022]
Abstract
Although hepatocellular cancer (HCC) usually occurs in the setting of liver fibrosis, the causal relationship between liver fibrosis and HCC is unclear. in vivo and in vitro models of HCC involving Colr/r mice (that produce a collagenase-resistant type I collagen) or wild-type (WT) mice were used to assess the relationship between type I collagen, liver fibrosis, and experimental HCC. HCC was either chemically induced in WT and Colr/r mice or Hepa 1-6 cells were engrafted into WT and Colr/r livers. The effect of hepatic stellate cells (HSCs) from WT and Colr/r mice on the growth of Hepa 1-6 cells was studied by using multicellular tumor spheroids and xenografts. Collagen type I deposition and fibrosis were increased in Colr/r mice, but they developed fewer and smaller tumors. Hepa 1-6 cells had reduced tumor growth in the livers of Colr/r mice. Although Colr/r HSCs exhibited a more activated phenotype, Hepa 1-6 growth and malignancy were suppressed in multicellular tumor spheroids and in xenografts containing Colr/r HSCs. Treatment with vitronectin, which mimics the presence of degraded collagen fragments, converted the Colr/r phenotype into a WT phenotype. Although Colr/r mice have increased liver fibrosis, they exhibited decreased HCC in several models. Thus, increased liver type I collagen does not produce increased experimental HCC.
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Affiliation(s)
- Jacopo Baglieri
- Department of Medicine, University of California San Diego, San Diego, California; Department of Surgery, University of California San Diego, San Diego, California
| | - Cuili Zhang
- Department of Medicine, University of California San Diego, San Diego, California
| | - Shuang Liang
- Department of Medicine, University of California San Diego, San Diego, California
| | - Xiao Liu
- Department of Medicine, University of California San Diego, San Diego, California
| | - Takahiro Nishio
- Department of Medicine, University of California San Diego, San Diego, California
| | - Sara B Rosenthal
- Center for Computational Biology and Bioinformatics, University of California San Diego, San Diego, California
| | - Debanjan Dhar
- Department of Medicine, University of California San Diego, San Diego, California
| | - Hua Su
- Department of Pharmacology, University of California San Diego, San Diego, California
| | - Min Cong
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, China
| | - Mojgan Hosseini
- Department of Pathology, University of California San Diego, San Diego, California
| | - Michael Karin
- Department of Pharmacology, University of California San Diego, San Diego, California
| | - Tatiana Kisseleva
- Department of Surgery, University of California San Diego, San Diego, California
| | - David A Brenner
- Department of Medicine, University of California San Diego, San Diego, California.
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Muzica CM, Stanciu C, Cijevschi-Prelipcean C, Girleanu I, Huiban L, Petrea OC, Singeap AM, Cojocariu C, Cuciureanu T, Sfarti C, Zenovia S, Chriac S, Stefanescu G, Ciortescu I, Lupașcu-Ursulescu C, Miftode E, Trifan A. Long-term Risk of Hepatocellular Carcinoma Following Direct-Acting Antiviral Therapy in Compensated Liver Cirrhosis Induced by Hepatitis C Virus Infection. HEPATITIS MONTHLY 2021; 21. [DOI: 10.5812/hepatmon.115910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of hepatocelullar carcinoma (HCC) following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11 ± 3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%) had a single tumor, 12 patients (52.2%) were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3 ± 93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP ≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL).
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11
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Brozzetti S, Tancredi M, Bini S, De Lucia C, Antimi J, D’Alterio C, De Sanctis GM, Furlan C, Malpassuti VC, Lucatelli P, Di Martino M, Bezzi M, Ciardi A, Pascale RM. HCC in the Era of Direct-Acting Antiviral Agents (DAAs): Surgical and Other Curative or Palliative Strategies in the Elderly. Cancers (Basel) 2021; 13:3025. [PMID: 34204186 PMCID: PMC8235445 DOI: 10.3390/cancers13123025] [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: 04/29/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver malignancies, and elderlies have the highest incidence rates. Direct-acting antiviral agents (DAAs) have shown satisfying results in terms of HCV sustained viral response (SVR). However, data regarding HCC risk post-DAA-SVR is still conflicting. This study aims to consider HCC onset in moderate underlying liver disease. We conducted a retrospective study on 227 chronically infected patients (cHCV), treated with DAAs. Patients were divided into three groups: "de novo occurrent HCC", "recurrent HCC", and "without HCC". Fifty-six patients aged <65 years (yDAA) were studied separately. HCC patients aged ≥65 years (DAA-HCC) were compared to a historical group of 100 elderly HCC patients, treated with peginterferon (Peg-IFN) ± ribavirin antiviral agents, non-SVR (hHCC). The HCC prevalence in DAA patients was 32.75%: "de novo occurrent'' 18.13% and "recurrent'' 14.62%, despite 42.85% of them having no fibrosis to mild or moderate fibrosis (F0-F1-F2). yDAA showed 5.36% "de novo occurrent" HCC. Curative procedure rates were compared between DAA-HCC and hHCC at the first and at recurrent presentation (22 (39.29%) vs. 72 (72%); 17 (30.36%) vs. 70 (70%), respectively (p < 0.001)). No significant difference was found in 3-year OS (p = 0.6). However, in cause-specific mortality analysis, HCC-related death was higher in the DAA-treated group, whereas cirrhosis-related death was more common in the historical group (p = 0.0288), considering together the two causes of death. A more accurate patient stratification according to multifactorial and new diagnostic investigations identifying HCC risk might allow an improvement in management and access to curative therapies.
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Affiliation(s)
- Stefania Brozzetti
- Department of Surgery “Pietro Valdoni”, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (S.B.); (M.T.); (C.D.L.); (J.A.); (C.D.)
| | - Marsia Tancredi
- Department of Surgery “Pietro Valdoni”, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (S.B.); (M.T.); (C.D.L.); (J.A.); (C.D.)
| | - Simone Bini
- Department of Translational and Precision Medicine, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy
| | - Chiara De Lucia
- Department of Surgery “Pietro Valdoni”, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (S.B.); (M.T.); (C.D.L.); (J.A.); (C.D.)
| | - Jessica Antimi
- Department of Surgery “Pietro Valdoni”, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (S.B.); (M.T.); (C.D.L.); (J.A.); (C.D.)
| | - Chiara D’Alterio
- Department of Surgery “Pietro Valdoni”, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (S.B.); (M.T.); (C.D.L.); (J.A.); (C.D.)
| | - Giuseppe Maria De Sanctis
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (G.M.D.S.); (C.F.)
| | - Caterina Furlan
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (G.M.D.S.); (C.F.)
| | | | - Pierleone Lucatelli
- Department of Radiological Sciences Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (P.L.); (M.D.M.); (M.B.)
| | - Michele Di Martino
- Department of Radiological Sciences Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (P.L.); (M.D.M.); (M.B.)
| | - Mario Bezzi
- Department of Radiological Sciences Policlinico Umberto I, University of Rome La Sapienza, 00161 Rome, Italy; (P.L.); (M.D.M.); (M.B.)
| | - Antonio Ciardi
- Department of Radiological, Oncological, Pathological Sciences, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy;
| | - Rosa Maria Pascale
- Department of Medical, Surgery and Experimental Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy;
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12
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Fatima T, Mumtaz H, Khan MH, Rasool S, Tayyeb M, Haider MZ, Hussain ST, Shahzad A, Ali S, Hussain T. Patterns of Hepatocellular Carcinoma After Direct Antiviral Agents and Pegylated-Interferon Therapy. Cureus 2020; 12:e11565. [PMID: 33364092 PMCID: PMC7749863 DOI: 10.7759/cureus.11565] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Introduction: The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). Methods: A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. Results: The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. Conclusion: Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.
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Affiliation(s)
- Tehreem Fatima
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology (CIBNP), Fairfield, USA
| | - Hassan Mumtaz
- Urology, Guys & St. Thomas Hospital, London, GBR.,General Medicine, Surrey Docks Health Center, London, GBR.,Surgery, Kahutta Research Laboratory (KRL) Hospital, Islamabad, PAK
| | | | - Saad Rasool
- Internal Medicine, Holy Family Hospital, Rawalpindi, PAK
| | - Muhammad Tayyeb
- Internal Medicine, Mayo Hospital, Lahore, PAK.,Internal Medicine, King Edward Medical University, Lahore, PAK
| | - Mobeen Z Haider
- Internal Medicine, King Edward Medical University, Lahore, PAK
| | - Syed T Hussain
- Internal Medicine, Holy Family Hospital, Rawalpindi, PAK
| | | | - Sundas Ali
- Internal Medicine, Holy Family Hospital/Rawalpindi Medical University, Rawalpindi, PAK
| | - Tanveer Hussain
- Gastroenterology and Hepatology, Holy Family Hospital, Rawalpindi, PAK
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