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Abdel Alem S, Abdellatif Z, Mohamed R, Elsharkawy A, Fouad R, Esmat G, Cordie A. Changes in liver stiffness and non-invasive markers in chronic hepatitis C virus patients with and without HIV co-infection following interferon-free antiviral treatment. Arab J Gastroenterol 2025:S1687-1979(25)00020-6. [PMID: 40335375 DOI: 10.1016/j.ajg.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 12/13/2024] [Accepted: 02/08/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND AND STUDY AIMS HIV alone can induce liver fibrosis whereas co-infection with HCV presents a significant challenge in hastening the development of chronic liver disorders such a liver fibrosis, cirrhosis, and hepatic malignancy. Information on the influence of HIV on liver stiffness (LS) after treatment with direct-acting antiviral (DAAs) agents is scarce. The aim of this study was to assess the changes in LS using transient elastography (TE) and fibrosis scores (Fibrosis-4 [FIB-4] and AST-to-platelet ratio index [APRI]) before the initiation of treatment and six months after the end of treatment (EOT) with DAAs in HCV/HIV co-infected patients compared with HCV mono-infected patients. PATIENTS AND METHODS All consecutive chronic HCV patients treated with DAAs during 2016-2020 were retrospectively recruited. TE was performed at baseline and SVR24. Fibrosis scores such as FIB-4 and APRI were calculated in parallel. Improvement of liver fibrosis was defined as any changes in the fibrosis category at baseline to a lower fibrosis category at SVR24. RESULTS Of 288 HCV-infected patients, 217 (75.3 %) were HCV mono-infected and 71 (24.7 %) were HCV/HIV co-infected. A significant decrease in TE values was noted at SVR24 compared with baseline (10.3 kPa vs. 7.9 kPa, respectively; P= <0.0001 in HCV mono-infection; 5.9 kPa vs. 5.3 kPa, respectively; P= <0.0001 in HCV/HIV co-infection). Moreover, the proportion of HCV mono-infected patients who had stable, improvement, and worsening in fibrosis stage at follow-up was 50.2 %, 43.3 %, and 6.5 %, respectively while it was 54.9 %, 32.4 %, and 12.7 %, respectively in HCV/HIV co-infection. In multivariable analysis, the higher fibrosis category was the only factor that influenced the improvement of liver fibrosis at follow-up, whereas HIV co-infection wasn't confirmed. CONCLUSION patients with HCV mono-infection and HCV/HIV co-infection experienced a rapid and significant improvement in LS and fibrosis indices. This improvement was more pronounced in those with high fibrosis grades at baseline.
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Affiliation(s)
- Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rahma Mohamed
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Dos Santos DM, Penteado JO, Nader MM, Basso RP, da Silva NMO, Quiche LCP, Borges MP, Gehres LFS, Hoffmann T, Rodrigues LF, da Silva Júnior FMR. Analysis of noninvasive methods in chronic hepatitis/human immunodeficiency virus mono- and co-infected patients with advanced fibrosis. Eur J Gastroenterol Hepatol 2025; 37:638-643. [PMID: 39976004 DOI: 10.1097/meg.0000000000002936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
OBJECTIVES The aim of this study was to evaluate the degree of advanced fibrosis (F3/F4) using noninvasive methods [elastography, Fibrosis-4 (FIB4), and aspartate aminotransferase to platelet ratio index (APRI)] before and after treatment with new direct-acting antiviral agents (DAAs) in patients with hepatitis C virus (HCV), both in cases of co-infection (HCV/HIV) and single infection (HCV). METHODS This is a longitudinal study involving patients with HCV who are co-infected with HIV, who initiated HCV treatment between a positive anti-HCV test for more than 6 months and detectable HCV RNA. The control group consisted of patients with HCV infection without HIV co-infection, who received treatment during the same period as the co-infected patients. RESULTS A total of 75 co-infected and 87 mono-infected HCV patients were eligible. Before treatment, elastography and FIB4 methods showed a strong agreement (0.73), while after treatment, the agreement was moderate (0.58). Between elastography and APRI, a strong agreement was observed before treatment (0.66) and fair/weak agreement after treatment (0.30). Both FIB4 and APRI showed perfect agreement at both time points with values above 0.9 (0.97 for pretreatment and 0.92 for posttreatment). The use of DAAs was associated with high rates of sustained virological response and reduction in fibrosis degrees in the posttreatment period, as assessed through biomarkers and hepatic elastography. CONCLUSION The utilization of biomarkers in clinical practice for assessing hepatic fibrosis is an essential tool. Thus, for an accurate evaluation of hepatic fibrosis, particularly after HCV treatment, the use of elastography, rather than biomarkers alone, is more appropriate.
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Affiliation(s)
| | - Júlia Oliveira Penteado
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
| | - Maiba Mikhael Nader
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Rossana Patrícia Basso
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | | | | | | | | | - Tchurle Hoffmann
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
| | - Leandro Farias Rodrigues
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
| | - Flavio Manoel Rodrigues da Silva Júnior
- Faculdade de Medicina, Universidade Federal do Rio Grande - FURG
- Laboratório de Testes Farmacológicos e Toxicológicos - LEFT, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande
- Centro de Aplicação e Monitorização de Medicamentos Injetáveis, Hospital Universitário Dr. Miguel Riet Corrêa Junior, Rio Grande, Rio Grande do Sul, Brazil
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Cerban R, Iacob S, Ester C, Ghioca M, Chitul M, Iacob R, Gheorghe L. Liver Elastography Methods for Diagnosis of De Novo and Recurrent Hepatocellular Carcinoma. Diagnostics (Basel) 2025; 15:1087. [PMID: 40361905 PMCID: PMC12072106 DOI: 10.3390/diagnostics15091087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 05/15/2025] Open
Abstract
Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress.
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Affiliation(s)
- Razvan Cerban
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Speranta Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Carmen Ester
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Mihaela Ghioca
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Mirela Chitul
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
| | - Razvan Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Liana Gheorghe
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (R.C.); (C.E.); (M.C.); (R.I.); (L.G.)
- Center for Digestive Diseases and Liver Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania;
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Fouad R, El-Akel W, ElMakhzangy H, Lithy RM, Sherif M, Fateen M, Hassany M, Abdel-Razek W, Doss W. Effect of sofosbuvir and daclatasvir treatment on the blood indices in patients with chronic hepatitis C virus. Arab J Gastroenterol 2025; 26:78-83. [PMID: 39875290 DOI: 10.1016/j.ajg.2024.11.004] [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: 05/10/2023] [Revised: 11/09/2024] [Accepted: 11/30/2024] [Indexed: 01/30/2025]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) infection is a significant problem in Egypt, as it is associated with various hematological disorders, both benign and malignant. In Egypt, direct-acting antivirals (DAAs) serve as the principal therapy for HCV to achieve a sustained virological response (SVR). This study investigated the effects of sofosbuvir (SOF) and daclatasvir (DCV) on HCV patients with benign blood index abnormalities and examined the correlation between these abnormalities and SVR. PATIENTS AND METHODS Data were obtained from 59,069 enrolled patients who were treatment-naïve and met the eligibility criteria for therapy as per the standards of Egypt's National Committee for Control of Viral Hepatitis (NCCVH). The patients adhered to the SOF and DCV therapy protocol. RESULTS The predominant hematological abnormality was thrombocytopenia, followed by leukopenia and anemia. Non-SVR was significantly correlated with the existence of one or more baseline cytopenias. The primary predictors of treatment failure were male gender, elevated Fib-4 score, and baseline thrombocytopenia. Despite the low incidence of cytopenia among patients after therapy, non-SVR was seen in instances of anemia. CONCLUSION Hematological problems often occur in HCV patients both before and after SOF and DCV treatment. Treatment failure was associated with the presence of one or more baseline cytopenias, as well as the development of anemia during treatment. Nonetheless, SOF and DCV are still safe to be used in the presence of cytopenia.
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Affiliation(s)
- Rabab Fouad
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wafaa El-Akel
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham ElMakhzangy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rania M Lithy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Mirella Sherif
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Fateen
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Hassany
- Department of Tropical Diseases, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Wael Abdel-Razek
- Hepatology and Gastroenterology Department, National Liver Institute, Menofia University, Shebeen El-Kom, Menofia, Egypt
| | - Wahid Doss
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Hassan AM, Orabi HH, Abdel-Gawad M, Mohamed O, Sawy SS, Abdelmeguid MM, Bashir MA, Abdelrazzak E, Ead K, Haridy MA. Changes in Vascular Endothelial Growth Factor and Development of Hepatocellular Carcinoma in Direct-Acting Antiviral Drugs (DAAs)-Treated Hepatitis C Virus (HCV) Patients. Cureus 2024; 16:e75982. [PMID: 39830567 PMCID: PMC11742266 DOI: 10.7759/cureus.75982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/22/2025] Open
Abstract
Background There is ongoing debate regarding the impact of direct-acting antiviral drugs (DAAs) on the occurrence of de novo hepatocellular carcinoma (HCC). Vascular endothelial growth factor (VEGF) plays a crucial role in the development and angiogenesis of HCC. Aim This study aims to evaluate dynamic changes in vascular endothelial growth factor (VEGF) levels at different point times during and after treatment of HCV to evaluate the risk of de novo HCC in DAAs-treated HCV patients. Methods This prospective cohort study was conducted on 60 HCV-infected patients; 30 patients had early fibrosis (F1-F2) and 30 patients had advanced fibrosis (F3-F4). HCV-RNA, aspartate aminotransferase (AST) to platelet ratio index (APRI), and fibrosis-4 index scores, liver function tests, serum VEGF, alpha-fetoprotein (AFP), and abdominal ultrasound were done at baseline, 4 weeks after starting treatment, at the end of treatment, and 12 weeks after treatment. Results VEGF was significantly decreased after completion of treatment (78.94± 10.03) compared to its baseline level (103.17 ± 33.89 pg/ml). Conclusion No de-novo hepatic focal lesion was detected during and up to 12 weeks after completion of treatment. The treatment of HCV by DAAs was associated with a significant decrease in VEGF and AFP levels and an improvement in liver enzymes and fibrosis scores.
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Affiliation(s)
- Amro M Hassan
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Heba H Orabi
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Muhammad Abdel-Gawad
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Omran Mohamed
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Safwat S Sawy
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | | | - Mohamed A Bashir
- Department of Clinical Pathology, Al-Azhar University, Assiut, EGY
| | - Emad Abdelrazzak
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Khalid Ead
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
| | - Mustafa A Haridy
- Department of Hepatology, Gastroenterology, and Infectious Diseases, Al-Azhar University, Assiut, EGY
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Xu S, Qiu L, Xu L, Liu Y, Zhang J. Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. Infect Agent Cancer 2024; 19:17. [PMID: 38664813 PMCID: PMC11046761 DOI: 10.1186/s13027-024-00578-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 04/11/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. METHOD Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. RESULTS During the median follow-up period of 61.00 (57.00-66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02-1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10-5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86-1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01-1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram's 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80-0.88), 0.83 (95% CI 0.79-0.87), and 0.81 (95% CI 0.77-0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). CONCLUSIONS Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
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Affiliation(s)
- Shanshan Xu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Lixia Qiu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Liang Xu
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People's Republic of China
| | - Yali Liu
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China
| | - Jing Zhang
- The Third Unit, Department of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People's Republic of China.
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Yasmeen S, Khan A, Anwar F, Akhtar MF, Yasmeen S, Shah SA. An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:95660-95672. [PMID: 37556059 DOI: 10.1007/s11356-023-29134-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 07/30/2023] [Indexed: 08/10/2023]
Abstract
Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.
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Affiliation(s)
- Sadaf Yasmeen
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Aslam Khan
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan.
| | - Fareeha Anwar
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Muhammad Furqan Akhtar
- Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, 13 KM Raiwind Road, Lahore, Pakistan
| | - Sidra Yasmeen
- Department of Pharmaceutics, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan
| | - Shafeeq Ali Shah
- Faculty of Pharmacy, Superior University, Raiwind Road, Lahore, Pakistan
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Rinaldi L, Giorgione C, Mormone A, Esposito F, Rinaldi M, Berretta M, Marfella R, Romano C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023; 15:1730. [PMID: 37632072 PMCID: PMC10459581 DOI: 10.3390/v15081730] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Andrea Mormone
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Francesca Esposito
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Michele Rinaldi
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, 80131 Naples, Italy;
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
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Rasmy HS, Elmalatawy MAE, ElKarmoty KZ, Abdelwarth EY, Isaac A. Serum retinol-binding protein 4 as a predictor of fibrosis regression and response to direct-acting antiviral drugs in chronic hepatitis C virus patients. EGYPTIAN LIVER JOURNAL 2023. [DOI: 10.1186/s43066-023-00251-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023] Open
Abstract
Abstract
Background
Hepatitis C virus is the underlying cause of chronic hepatitis which frequently progresses to cirrhosis and hepatocellular carcinoma. In addition, HCV is thought to cause steatosis, dyslipidemia, insulin resistance, diabetes, obesity, and cardiovascular events. The aim of this study is to evaluate the role of serum RBP-4 in the prediction of fibrosis regression and the response of treatment among chronic HCV patients receiving direct-acting antiviral agents.
Methods
This study included 40 chronic HCV Egyptian patients, divided into two groups: Naive cases, 20 chronic HCV patients before starting first line of treatment; Relapser cases, 20 chronic HCV patients who were non-responders before starting second line treatment; and 10 healthy subjects as control. Laboratory investigations including complete blood count, full hepatic profile, fibroscan assessment, and retinol-binding protein-4 level at baseline and re-assessed 12 weeks after the end of treatment [sustained virological response SVR12]. Student T test, analysis of variance, chi-square, Tukey’s test, and Pearson correlation coefficient tests were used for statistical analysis.
Results
Baseline retinol-binding protein-4 level was significantly higher in the naïve case group than in the relapser and control groups with a P value of P value of < 0.001. All the naïve patients had 100% SVR12, only 90% of the relapser group achieved SVR12. A significant reduction in retinol-binding protein-4 and fibrosis staging and measurements by fibroscan among all studied patients were noted after receiving direct acting antivirals (P value < 0.001). Retinol-binding protein-4 levels before and after treatment were significantly lower among F4 patients in comparison to those of F1–F3 patients (P value 0.002, 0.009, respectively). The best cutoff value of retinol-binding protein-4 in the prediction of liver cirrhosis (F4) was ≤ 46 pg/ml with sensitivity of 100% and specificity of 66.67%.
Conclusion
Serum retinol-binding protein-4 was found to be higher in chronic HCV infection with a significant reduction after successful eradication. Its level is much lower in cirrhotic patients [F4]. As a result, retinol-binding protein-4 may have a promising role in assessing direct acting antivirals response, as well as a prognostic value in predicting liver cirrhosis.
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Rodprasert N, Hongboontry T, Cherdchoochart C, Chaiteerakij R. Association between Liver Stiffness and Liver-Related Events in HCV-Infected Patients after Successful Treatment with Direct-Acting Antivirals. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59030602. [PMID: 36984603 PMCID: PMC10053469 DOI: 10.3390/medicina59030602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/11/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023]
Abstract
Background and Objectives: Direct-acting antivirals (DAAs) are highly effective for the treatment of chronic hepatitis C virus (HCV) infection, but the risk of liver-related events and hepatocellular carcinoma (HCC) remains after successful therapy. We aimed to evaluate post-treatment changes in liver stiffness (LS) and identify a cut-off LS value for predicting such events in chronic HCV-infected patients receiving DAA. Materials and Methods: A total of 185 patients who had achieved sustained virologic response (SVR) after DAA therapy were included. Baseline characteristics and laboratory results were retrospectively abstracted. LS was measured by transient elastography at baseline, 12, 24, 48, and 96 weeks after SVR. FIB-4 index was assessed at baseline and 48 weeks after SVR. Development of liver-related events (hepatocellular carcinoma (HCC), portal-hypertension-related decompensation, listing for transplantation, and mortality) after SVR were identified. The association between liver fibrosis and the occurrence of liver-related events was analyzed using Cox regression analysis. Results: Significant differences in LS values were observed between baseline and 24, 48, 72, and 96 weeks after SVR. FIB-4 index at 48 weeks after SVR was significantly lower than the FIB-4 index at baseline. During the 41.6-month follow-up time, the incidence rates of all liver-related events and HCC were 2.36 and 1.17 per 100 person-years, respectively. Age, LS ≥8 kPa, and FIB-4 ≥1.35 at 48 weeks post-SVR were significantly associated with the occurrence of any liver-related events. By multivariate analysis, LS ≥8 kPa at 48 weeks post-SVR remained significantly associated with any liver-related events, with an adjusted hazard ratio (95%CI) of 5.04 (1.01-25.26), p = 0.049. Conclusions: Despite a significant reduction in LS after SVR, patients with LS ≥8 kPa at 48 weeks after SVR should be regularly monitored for liver-related complications, particularly HCC development.
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Affiliation(s)
- Napas Rodprasert
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Tinn Hongboontry
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | | | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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11
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Yu JH, Lee HA, Kim SU. Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future. Clin Mol Hepatol 2023; 29:S136-S149. [PMID: 36503205 PMCID: PMC10029967 DOI: 10.3350/cmh.2022.0436] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the "gold standard" method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.
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Affiliation(s)
- Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital and School of Medicine, Incheon, Korea
| | - Han Ah Lee
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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12
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Ramadan MS, Boccia F, Moretto SM, De Gregorio F, Gagliardi M, Iossa D, Durante-Mangoni E, Zampino R. Cardiovascular Risk in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals. J Clin Med 2022; 11:5781. [PMID: 36233646 PMCID: PMC9572655 DOI: 10.3390/jcm11195781] [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: 08/31/2022] [Revised: 09/23/2022] [Accepted: 09/26/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Chronic hepatitis C (CHC) is associated with hepatic and extrahepatic complications, including cardiovascular disease (CVD). The effects of sustained virological response (SVR) and liver fibrosis on CVD risk are not well established. Aims: We aim to assess the dynamics of Fibrosis-4 (FIB-4) and Atherosclerotic Cardiovascular Disease 2013 (ASCVD) scores up to three years after direct acting antivirals (DAA) treatment and explore the time-dependent association between the two scores. Methods: We included consecutive CHC patients treated with DAA and followed up with them for three years. Outcomes were changes from baseline (before DAA) in ASCVD and FIB-4 scores, measured at the end of treatment, 12-, 24-, and 36-months follow-up. Results: In total, 91 patients with CHC were finally included (median age: 66 years (IQR = 58−72 years); 43% females). Median follow-up was 2 years (1−3 years) and all patients reached SVR. The ASCVD score did not significantly change from baseline (Mean = 17.2%, 95% CI 14.1, 20.3), but the FIB-4 score significantly decreased at any time-point by an average of 0.8 (95% CI 0.78, 0.82, p < 0.001). Elevated FIB-4 scores at one (β = 1.16, p < 0.001) and three years (β = 2.52, p < 0.001) were associated with an increased ASCVD score. Clinically, two participants- with non-decreasing FIB-4 scores after treatment- had acute coronary syndrome at the end of treatment and one year follow-up, respectively. Conclusions: In our study, we found that FIB-4 and ASCVD scores exhibited a positive correlation irrespective of time-point after treatment. Larger studies are essential to further investigate the utility of FIB-4 scores in cardiovascular risk assessment.
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Affiliation(s)
- Mohammad Said Ramadan
- Department of Precision Medicine, University of Campania ‘L. Vanvitelli’ Napoli, 80138 Naples, Italy
| | - Filomena Boccia
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Simona Maria Moretto
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Fabrizio De Gregorio
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Massimo Gagliardi
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
| | - Domenico Iossa
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania ‘L. Vanvitelli’ Napoli, 80138 Naples, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
| | - Rosa Zampino
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘L. Vanvitelli’, 81031 Naples, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Piazzale E. Ruggieri, 80131 Naples, Italy
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13
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Elsharkawy A, Samir R, El-Kassas M. Fibrosis regression following hepatitis C antiviral therapy. World J Hepatol 2022; 14:1120-1130. [PMID: 35978676 PMCID: PMC9258254 DOI: 10.4254/wjh.v14.i6.1120] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/16/2022] [Accepted: 05/12/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Reham Samir
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11566, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt.
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14
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Mezina A, Krishnan A, Woreta TA, Rubenstein KB, Watson E, Chen PH, Rodriguez-Watson C. Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis C patients. World J Clin Cases 2022; 10:5566-5576. [PMID: 35979107 PMCID: PMC9258363 DOI: 10.12998/wjcc.v10.i17.5566] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 12/16/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases. Fibrosis progression varies markedly in patients with hepatitis C virus (HCV). Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV. AIM To investigate changes in liver stiffness measured by transient elastography (TE) in a large, racially diverse cohort of United States patients with chronic hepatitis C (CHC). METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral (DAA) therapy and untreated patients. Patients had ≥ 2 TE measurements and no prior DAA exposure. We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment, controlling for age, sex, race, diabetes, smoking status, human immunodeficiency virus status, baseline alanine aminotransferase, and baseline liver stiffness. Separate regression models analyzed the change in liver stiffness as measured by kPa, stratified by cirrhosis status. RESULTS Of 813 patients, 419 (52%) initiated DAA treatment. Baseline liver stiffness was 12 kPa in 127 (16%). Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients, respectively. There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment (0.016 kPa/month; CI: -0.051, 0.084) or in the untreated group (0.001 kPa/mo; CI: -0.090, 0.092), controlling for covariates. A higher baseline kPa score was independently associated with decreased liver stiffness. CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.
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Affiliation(s)
- Anya Mezina
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Kevin B Rubenstein
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Eric Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21231, United States
| | - Carla Rodriguez-Watson
- Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville 20852, United States
- Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, United States
- Innovation in Medical Evidence Development and Surveillance (IMEDS) Program, Reagan-Udall Foundation for the FDA, Washington, 20036, United States
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15
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Kimura K, Kanto T, Shimoda S, Harada K, Kimura M, Nishikawa K, Imamura J, Ogawa E, Saio M, Ikura Y, Okusaka T, Inoue K, Ishikawa T, Ieiri I, Kishimoto J, Todaka K, Kamisawa T. Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus-induced liver cirrhosis: An investigator-initiated, open-label, non-randomised, multicentre, phase 1/2a study. EBioMedicine 2022; 80:104069. [PMID: 35605429 PMCID: PMC9126795 DOI: 10.1016/j.ebiom.2022.104069] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/15/2022] [Accepted: 05/06/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND We conducted an exploratory study to assess the safety tolerability, and anti-fibrotic effects of PRI-724, a CBP/β-catenin inhibitor, in patients with hepatitis C virus (HCV)- and hepatitis B virus (HBV)-induced cirrhosis. METHODS This multicentre, open-label, non-randomised, non-placebo-controlled phase 1/2a trial was conducted at three hospitals in Japan. Between July 27, 2018, and July 13, 2021, we enrolled patients with HCV- and HBV-induced cirrhosis classified as Child-Pugh (CP) class A or B. In phase 1, 15 patients received intravenous infusions of PRI-724 at escalating doses of 140, 280, and 380 mg/m2/4 h twice weekly for 12 weeks. In phase 2a, 12 patients received the recommended PRI-724 dose. The primary endpoints of phases 1 and 2a were the frequency and severity of adverse events and efficacy in treating cirrhosis based on liver biopsy. This study was registered at ClinicalTrials.gov (no. NCT03620474). FINDINGS Three patients from phase 1 who received the recommended PRI-724 dose were evaluated to obtain efficacy and safety data in phase 2a. Serious adverse events occurred in three patients, one of which was possibly related to PRI-724. The most common adverse events were diarrhoea and nausea. PRI-724 did not decrease hepatic fibrosis with any statistical significance, either by ordinal scoring or measurement of collagen proportionate area at 12 weeks; however, we observed statistically significant improvements in liver stiffness, Model for End-stage Liver Disease score, and serum albumin level. INTERPRETATION Intravenous administration of 280 mg/m2/4 h PRI-724 over 12 weeks was preliminarily assessed to be well tolerated; however, further evaluation of anti-fibrotic effects in patients with cirrhosis is warranted. FUNDING AMED, Ohara Pharmaceutical.
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Affiliation(s)
- Kiminori Kimura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
| | - Tatsuya Kanto
- The Research Center for Hepatitis and Immunology, Gastroenterology Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan
| | - Shinji Shimoda
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Masamichi Kimura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Koji Nishikawa
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Jun Imamura
- Department of Hepatology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masanao Saio
- Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Gunma, Japan
| | - Yoshihiro Ikura
- Department of Pathology, Takatsuki General Hospital, Osaka, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuaki Inoue
- Department of Gastroenterology, International University of Health and Welfare, Narita Hospital, Chiba, Japan
| | - Tetsuya Ishikawa
- Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Ichiro Ieiri
- Department of Clinical Pharmacokinetics, Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
| | - Junji Kishimoto
- Department of Clinical Research Promotion, Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan
| | - Koji Todaka
- Department of Clinical Research Promotion, Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan
| | - Terumi Kamisawa
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
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16
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Isaac A, El Sakaty TM, Hussein SH, Rasmy HS. Angiopoietin-2 as a predictor of fibrosis regression in chronic hepatitis C virus patients after direct-acting antiviral drugs. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2021. [DOI: 10.1186/s43162-021-00086-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level.
Results
Statistically significantly higher levels of baseline Ang-2 were detected with the progression of fibrosis stages with a p-value of <0.001. The best cutoff value of baseline Ang-2 in discrimination of liver cirrhosis (F4) from F0-F3 was > 630 pg/ml with 85.71% sensitivity and 84.85% specificity. A statistically significant decline of Ang-2 (from 464.3±237.2 pg/ml to 401.3±277.1 pg/ml) was noted after the achievement of SVR12 with a p-value < 0.001. Regression of liver fibrosis in this study is defined as a decrease of more than or equal to one stage in liver fibrosis. Lower baseline fibrosis stages and other non-invasive scoring systems (FIB-4 and APRI scores) were associated with regression of fibrosis following successful DAAs treatment. However, higher baseline Ang-2 levels were significantly associated with non-regression of fibrosis, and at a cutoff of >680 pg/ml, it might predict non-regression of fibrosis after successful eradication of HCV with DAAs with 93.33% sensitivity and 70% specificity.
Conclusions
Angiopoietin-2 can be a useful predictor of fibrosis regression in chronic HCV patients receiving direct-acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced fibrosis stages may predict non-regression of liver fibrosis.
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17
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Changes in serum interferon-γ-inducible protein-10 levels and liver stiffness among chronic hepatitis C Egyptian patients in response to directly acting antiviral agents. Eur J Gastroenterol Hepatol 2021; 33:e335-e340. [PMID: 33470694 DOI: 10.1097/meg.0000000000002059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Interferon-γ inducible protein-10 (IP-10) is chemokine biomarker of liver inflammation, elevated in patients with chronic hepatitis C infection. AIMS Investigating if changes in serum IP-10 levels in response to directly acting antiviral agents (DAAs) treatment for chronic HCV patients are paralleled by changes in liver stiffness measurements (LSM), and assessing role of using serum IP-10 as a noninvasive accurate method to predict changes in hepatic necro-inflammation and fibrosis. MATERIAL AND METHODS A prospective observational study included 92 Egyptian chronic HCV patients, who received treatment with sofosbuvir with daclatasvir regimen. Patients were classified into two groups; group I (53 patients) with non to mild significant liver fibrosis (F0-F1), and group II (39 patients) with significant to advanced liver fibrosis (F2-F4). Fibroscan and serum IP-10 were assessed pretreatment and 3 months after end of treatment. RESULTS All patients achieved SVR. Both IP-10 and LSM showed significant decline after treatment in both groups. No significant correlation was found between changes in LSM and IP-10. IP-10 detected liver cirrhosis at cut off level of 17.8 pg/ml, with 75% sensitivity and 73.86% specificity, with area under the curve = 0.66, however, IP-10 had no statistical significance in detecting advanced fibrosis. CONCLUSION IP-10 might be of significance as a noninvasive predictor of liver cirrhosis. IP-10 significant decline post-DAAs treatment in chronic HCV genotype IV infected patients reflects significant improvement in fibrosis stage and hepatic necro-inflammation in response to treatment. No significant correlation was detected in the changes of both IP-10 and LSM.
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18
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Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals. Eur J Gastroenterol Hepatol 2021; 33:e746-e752. [PMID: 34231522 DOI: 10.1097/meg.0000000000002240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens. METHODS a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed. RESULTS Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time. CONCLUSION This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.
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19
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Cerrito L, Ainora ME, Nicoletti A, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals. World J Hepatol 2021; 13:1663-1676. [PMID: 34904036 PMCID: PMC8637667 DOI: 10.4254/wjh.v13.i11.1663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/08/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.
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Affiliation(s)
- Lucia Cerrito
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Alberto Nicoletti
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Matteo Garcovich
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Laura Riccardi
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maurizio Pompili
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Assunta Zocco
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168,
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20
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Garbuzenko DV. [The role of antiviral therapy in the management of patients with liver cirrhosis associated with chronic HBV and HCV infection]. Vopr Virusol 2021; 66:331-339. [PMID: 34738448 DOI: 10.36233/0507-4088-70] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 11/04/2021] [Indexed: 12/12/2022]
Abstract
The formation of the liver cirrhosis (LC) is an unfavorable event of the natural history of chronic liver diseases being accompanied by complications that often cause a fatal outcome. The study of the effectiveness of drugs that affect various etiopathogenetic mechanisms of this condition is an urgent problem of modern hepatology.The aim of the review was to show the role of antiviral therapy (AVT) in the management of patients with LC associated with chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection.PubMed database, Google Scholar search engine, Cochrane Systematic Reviews, eLIBRARY.RU electronic scientific library, as well as the reference lists of articles were used to search for scientific articles. The relevant objectives of the review of the publications were identified for the period since 2000 up to 2021 by the search queries as following: «liver cirrhosis», «liver fibrosis», «chronic HBV infection», «chronic HCV infection», «portal hypertension», «treatment». The inclusion criteria were restricted to the management of patients with LC associated with chronic HBV and HCV infection.Current guidelines recommend indefinite treatment of patients with HBV-associated LC with nucleos(t)ide analogues regardless of serum HBV DNA levels, while the modern concept of using direct-acting antiviral drug combinations has become the standard treatment for HCV-associated cirrhosis. Studies have shown the ability of AVT to inhibit and reverse fibrotic processes in LC associated with chronic HBV and HCV infection. It has also been reported that HBV/HCV eradication prior to orthotopic liver transplantation improves long-term overall survival.This, in turn, can reduce the severity of portal hypertension and decrease the risk of associated complications, as well as normalize liver function. Thus, ensuring the availability of drugs for those in need of AVT will not only help prevent the development of LC, but also improve the quality of life and increase its expectancy of patients suffering from this disease.
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Affiliation(s)
- D V Garbuzenko
- FSBEI HE «South Ural State Medical University» of the Ministry of the Health of Russia
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21
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Long-Term Impact of Hepatitis C Virus Eradication on Liver Stiffness in Egyptian Patients. Can J Gastroenterol Hepatol 2021; 2021:4961919. [PMID: 34589447 PMCID: PMC8476245 DOI: 10.1155/2021/4961919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/25/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
METHODS Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. RESULTS The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa (p < 0.0001) at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa (p < 0.0001). The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. CONCLUSIONS There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0-F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3-F4) take a longer time to regress to lower fibrosis stages.
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22
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Evaluation of long-term changes of aspartate—platelet ratio index, FIB4, and liver stiffness in chronic hepatitis C patients successfully treated by direct-acting antivirals. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00141-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
A large number of chronic hepatitis C patients had been successfully treated by directly acting antivirals; therefore, strategies for the long-term follow-up of these patients have to be planned based on the post-treatment fibrosis stage—the main determinant of prognosis. In this study, we aim to evaluate changes in aspartate-platelet ratio index, FIB4, and liver stiffness in chronic hepatitis C patients who achieved SVR and ended treatment more than 1 year by DAAs.
Results
One hundred chronic hepatitis C patients who achieved SVR were enrolled at a median of 16 months after the end of treatment by DAAs. According to the baseline liver stiffness, 63 and 37 patients belonged to early (F0, F1, and F2) and advanced (F3 and F4) fibrosis stages, respectively. Both groups showed a decline of the degree of liver stiffness at follow-up compared to the baseline that was statistically significant in the early fibrosis group (5.9±1.5 vs 5.4±2.2 Kpcal, p=0.04), while measurements in the advanced group were (18±8.8 vs 15.9 ± 7.8 Kpcal, p=0.07). Also, serum biomarkers of fibrosis improved in both groups, where the recorded APRI and FIB4 before and after treatment were 0.42±0.3 vs 0.24±0.1, p<0.01 and 1±0.6 vs 0.93 ±0.5, p=0.1 in the early group and 0.85 ±0.5 vs 0.4±0.2, p <0.001 and 2.9±2.3 vs 1.8±1.4, p<0.02) in the advanced group, respectively. Changes in APRI and FIB4 correlated with changes in AST and ALT, but liver stiffness changes were not affected by changes in liver enzymes.
Conclusion
Although long-term improvement of APRI, FIB4, and liver stiffness scores could be achieved in chronic HCV patients after SVR by DAAS. High measurements of liver stiffness before treatment likely persist. We recommend transient elastography as a reliable tool for fibrosis assessment post-treatment.
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Zakaria S, El-Sisi AE. Daclatasvir and Sofosbuvir Mitigate Hepatic Fibrosis Through Downregulation of TNF-α / NF-κB Signaling Pathway. Curr Mol Pharmacol 2021; 13:318-327. [PMID: 31951178 DOI: 10.2174/1874467213666200116114919] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 12/02/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatic fibrosis is the major issue in chronic liver diseases such as chronic hepatitis C virus (HCV). The newly approved direct acting antiviral (DAA) agents such as Sofosbuvir (SOF) and daclatasvir (DAC) have been found to be associated with decreased fibrotic markers in HCV patients. AIM This study tried to explore whether the reported antifibrotic effect of these drugs is antiviral dependent or drug induced. METHOD Hepatic fibrosis was induced by (0.5ml/kg) CCl4 IP twice a week for six weeks. SOF (20 mg/kg/d) and DAC (30 mg/kg/d) were added in the last four weeks of treatments. Liver functions, fibrotic markers such as Hyaluronic acid and metalloproteinase-9 were detected using immunoassay. The expression of TNF-α/NF-κB signaling pathway as well as Bcl-2 were done using immunoassay. RESULTS SOF and DAC exerted a potent antifibrotic effect evidenced by their activity against hyaluronic acid HA and metalloproteinase MMP-9 significantly (P≤0.001). This effect was further proved histopathologically where liver tissues from rats treated by drugs showed marked inhibition of collagen precipitation as well as inhibition of HSCs activation. This antifibrotic action was associated with decreased expression of TNF-α /NF-κB signaling pathway and induction of Bcl-2. CONCLUSION SOF/ DAC antifibrotic effect is independent of its antiviral activity. The molecular events associated with this effect were the downregulation of TNF-α / NF-κB signaling pathway and induction of Bcl-2.
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Affiliation(s)
- Sherin Zakaria
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kaferelsheikh University, Kaferelsheikh, Egypt
| | - Alaa E El-Sisi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
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Risk Factors for Liver Decompensation and HCC in HCV-Cirrhotic Patients after DAAs: A Multicenter Prospective Study. Cancers (Basel) 2021; 13:cancers13153810. [PMID: 34359711 PMCID: PMC8345116 DOI: 10.3390/cancers13153810] [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] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/09/2021] [Accepted: 07/25/2021] [Indexed: 01/06/2023] Open
Abstract
Simple Summary The present study explored the predictors of the development of liver-related events in HCV cirrhotic subjects achieving SVR following antiviral therapy with direct-acting antiviral agents (DAAs) during a follow-up of 24 months after SVR confirmation. Patients had a liver stiffness measurement (LSM) of ≥14 kPa at baseline. We found that baseline liver stiffness ≥ 20 kPa and HCV genotype different from 1 were both independent predictors of liver decompensation, while only LSM ≥ 20 kPa was an independent predictor of HCC. Abstract Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p < 0.03). The incidence rate x 100 p/y was 1.6 for HCC, 1.7 for any liver decompensation, and 0.5 for hepatic death. Baseline liver stiffness (LSM) ≥ 20 kPa (HR 4.0; 95% CI 1.1–14.1) and genotype different from 1 (HR 7.5; 95% CI 2.1–27.3) were both independent predictors of liver decompensation. Baseline LSM > 20 KPa (HR 7.2; 95% CI 1.9–26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR.
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Cordie A, Elsharkawy A, Abdel Alem S, Meshaal S, El Akel W, Abdellatif Z, Kamal W, Al Askalany M, Kamel S, Abdel Aziz H, Kandeel A, Esmat G. Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection. Trans R Soc Trop Med Hyg 2021; 114:232-240. [PMID: 31925434 DOI: 10.1093/trstmh/trz120] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/19/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. METHODS A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. RESULTS SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (<F2) and those with significant fibrosis (≥F2) (p=0.9 and p=0.3, respectively). AEs occurred in 45 (90%) patients. The most frequent AEs were fatigue, headache and nausea. No treatment-related serious AEs or deaths were reported. HIV control was not compromised. LSM, fibrosis 4 score and aspartate aminotransferase-to-platelet ratio index showed a significant decrease at SVR12 when compared with baseline (p=0.0004, p=0.0003 and p<0.0001, respectively). Logistic regression analysis showed no association between baseline variables and SVR12 while significant fibrosis (≥F2) was the only baseline variable that was significantly associated with improvement of LSM at SVR12. CONCLUSION SOF/DCV achieved a high SVR12 and was well-tolerated in HIV/HCV-GT 4-coinfected patients.
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Affiliation(s)
- Ahmed Cordie
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Safa Meshaal
- Clinical pathology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Zeinab Abdellatif
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Walid Kamal
- Preventive sector, Ministry of Health and Population, Cairo 11516, Egypt
| | - Mahmoud Al Askalany
- Imbaba Fever Hospital, Ministry of Health and Population, Cairo 12651, Egypt
| | - Sherif Kamel
- Imbaba Fever Hospital, Ministry of Health and Population, Cairo 12651, Egypt
| | - Hossam Abdel Aziz
- Department of Hepatology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt
| | - Amr Kandeel
- Preventive sector, Ministry of Health and Population, Cairo 11516, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
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Sadeghi A, Amiri R, Akbarpour E, Mirminachi B, Sharifi AH, Merat S. Changes in liver fibrosis in patients with chronic hepatitis C after successful direct-acting antiviral therapy. Int J Clin Pract 2021; 75:e14145. [PMID: 33709413 DOI: 10.1111/ijcp.14145] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/09/2021] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION AND OBJECTIVES After successful treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV-infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017. MATERIAL AND METHODS In this observational cohort, all HCV-infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre- and post-treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline. RESULTS A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q1 -Q3 ) liver stiffness (LS) value at baseline was 26.3 kPa (18.1-38 kPa), which significantly decreased to 20.9 kPa (12-29.7 kPa) [z = -8.45, P-value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = -2.3, P-value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study. CONCLUSION Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Amiri
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Akbarpour
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Mirminachi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir-Houshang Sharifi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Merat
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Jayaswal ANA, Levick C, Collier J, Tunnicliffe EM, Kelly MD, Neubauer S, Barnes E, Pavlides M. Liver cT 1 decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus. Abdom Radiol (NY) 2021; 46:1947-1957. [PMID: 33247768 PMCID: PMC8131342 DOI: 10.1007/s00261-020-02860-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 11/04/2020] [Accepted: 11/07/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Direct-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs. METHODS In this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT1 (fibroinflammation), liver fat and T2* (LIC). RESULTS All patients achieved a sustained virological response. Liver cT1 showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed. CONCLUSION Liver cT1 decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT1 suggests a reduction in inflammation rather than regression of fibrosis.
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Affiliation(s)
- Arjun N A Jayaswal
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
| | - Christina Levick
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Jane Collier
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Elizabeth M Tunnicliffe
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Oxford NIHR Biomedical Research Centre, Oxford, UK
| | | | - Stefan Neubauer
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Oxford NIHR Biomedical Research Centre, Oxford, UK
| | - Eleanor Barnes
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK
- Oxford NIHR Biomedical Research Centre, Oxford, UK
- Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK
| | - Michael Pavlides
- Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
- Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
- Oxford NIHR Biomedical Research Centre, Oxford, UK.
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Itakura J, Kurosaki M, Setoyama H, Simakami T, Oza N, Korenaga M, Tanaka M, Torimura T, Sakamoto N, Enomoto N, Ueno Y, Kawada N, Kaneko S, Nishiguchi S, Chayama K, Tanaka J, Izumi N, Kanto T. Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis. J Gastroenterol 2021; 56:470-478. [PMID: 33791882 DOI: 10.1007/s00535-021-01782-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/18/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.
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Affiliation(s)
- Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroko Setoyama
- Department of Gastroenterology and Hepatology, Kumamoto Rosai Hospital, Yatsushiro, Japan
| | - Tetsuro Simakami
- Department of Gastroenterology, Saga Medical Center Kouseikan, Saga, Japan
| | - Noriko Oza
- Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
| | - Masaaki Korenaga
- Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan
| | - Motohiko Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Saga Medical Center Kouseikan, Saga, Japan
| | - Shuhei Nishiguchi
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tatsuya Kanto
- Department of Liver Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, Tokyo, 272-8516, Japan.
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Mohamed IELK, EL-Saeed KM, Al-Sadik MH, Anwar CA. Safety and efficacy of directly acting antivirals (sofosbuvir and daclatasvir) in treatment of chronic HCV in HIV-HCV co-infected Egyptian patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00089-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Cure of chronic hepatitis C (HCV) in HIV/HCV co-infected patients is a priority due to their increased risk of complications. Daclatasvir and sofosbuvir treatment regimens with or without ribavirin are considered an important chance for better HCV treatment in patients with HIV/HCV co-infection. This study aimed at the assessment of safety and efficacy of sofosbuvir-daclatasvir treatment regimens in HIV/HCV co-infected Egyptian patients.
Results
Thirty HIV/HCV co-infected adult patients were included. All patients completed the study duration without major problems or drug interactions, HCV PCR was negative for all patients at the end of treatment, yet 12 weeks after ending treatment, only one patient (3.33%) had HCV relapse.
Liver enzymes showed a significant decrease by the end of treatment and 12 weeks after end of treatment in comparison with their values before treatment (P-value = 0.0001). CD4 counts as well showed significant increase. There was non-significant change in serum albumin, total bilirubin, alfa fetoprotein, complete blood count (CBC), coagulation profile, random blood sugar, or serum creatinine. Ultrasonographic findings did not show significant difference.
Conclusion
Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a good safety profile. Moreover, the treated patients showed a significant increase in CD4 lymphocytic count.
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Soliman Z, El Kassas M, Elsharkawy A, Elbadry M, Hamada Y, ElHusseiny R, M El-Nahaas S, Fouad R, Esmat G, Abdel Alem S. Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome. Platelets 2021; 32:383-390. [PMID: 32250721 DOI: 10.1080/09537104.2020.1742313] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/21/2020] [Indexed: 12/11/2022]
Abstract
Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84-127) × 103/mm3 vs. 120 (87-153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn't reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.
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Affiliation(s)
- Zeinab Soliman
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Elbadry
- Tropical Medicine and Gastroenterology Department, Aswan University, Aswan, Egypt
| | - Yasser Hamada
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ramy ElHusseiny
- Internal Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Saeed M El-Nahaas
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of research development, Badr University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Fahmy DM, Shokeir M, El Zeiny SM, Jonas MM, Abdallah A. Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection. J Pediatr 2021; 231:110-116. [PMID: 33347957 DOI: 10.1016/j.jpeds.2020.12.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/22/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 β-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.
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Affiliation(s)
- Doaa M Fahmy
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA.
| | - Mohamed Shokeir
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Sherine M El Zeiny
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Ahmed Abdallah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Bert F, Stahmeyer JT, Parpalea AL, Rossol S. Non-Invasive Reliable Methods to Objectify the Positive Influence of Hepatitis C Virus Treatment on Liver Stiffness. Gastroenterology Res 2021; 14:31-40. [PMID: 33737997 PMCID: PMC7935613 DOI: 10.14740/gr1347] [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: 11/30/2020] [Accepted: 01/22/2021] [Indexed: 11/11/2022] Open
Abstract
Background Chronic active hepatitis C virus (HCV) infection is a major public health problem and causes liver fibrosis (LF) up to liver cirrhosis (LC). LF can be estimated by non-invasive, easy handling methods. With implementation of new HCV therapies, elimination rates of HCV are near 100%, resulting in less clinical complications and costs. The aim of our study was to evaluate the positive influence of HCV treatment on liver stiffness by non-invasive assessments of LF. Methods Sixty-two patients with HCV were treated with antiviral drug regimes. Serological fibrosis scores and ultrasound elastography (acoustic radiation force impulse and shear wave elasticity imaging (ARFI-SWEI)) were used for LF assessment on day 0 and 6 months after therapy. Results Antiviral treatment was successful in all cases. ARFI-SWEI measurements showed an improvement of all LF stages. Results of serological markers and scores were heterogeneous. Significant positive effects of treatment were seen for aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores, only. Further Pearson's coefficient showed moderate till very high correlations for ARFI-SWEI and FIB-4/APRI scores. Conclusion Today HCV therapy is able to cure HCV. Positive influences are improvement of LF stages. ARFI-SWEI, APRI and FIB-4 score are useful, easy handling tools to verify positive influence of HCV treatment on LF alone or in combination.
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Affiliation(s)
- Florian Bert
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/Main, Germany
| | - Jona Theodor Stahmeyer
- Institute for Epidemiology, Social Medicine and Health Systems Research, Medical School, Hannover, Germany
| | | | - Siegbert Rossol
- Department of Internal Medicine, Krankenhaus Nordwest, Frankfurt/Main, Germany
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PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy. J Cyst Fibros 2021; 20:205-212. [PMID: 33619012 DOI: 10.1016/j.jcf.2021.02.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/25/2021] [Accepted: 02/06/2021] [Indexed: 12/12/2022]
Abstract
Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.
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Laursen TL, Villesen IF, Leeming DJ, Karsdal MA, Sølund C, Tarp B, Kristensen LH, Holmboe CH, Leutscher P, Laursen AL, Gudmann NS, Grønbaek H. Altered balance between collagen formation and degradation after successful direct-acting antiviral therapy of chronic hepatitis C. J Viral Hepat 2021; 28:236-244. [PMID: 33058390 DOI: 10.1111/jvh.13416] [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: 05/14/2020] [Revised: 08/30/2020] [Accepted: 09/20/2020] [Indexed: 12/26/2022]
Abstract
The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers' dynamics with DAA therapy in CHC patients. Plasma PRO-C3, PRO-C4, C3M and C4M were assessed before, during and up till one year after 12-24 weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n = 14) or cirrhosis (n = 63). Liver stiffness was evaluated using transient elastography. PRO-C3, C3M and C4M levels decreased significantly (P < .00001) while PRO-C4 was unchanged (P = .20) during the study period. There was a steep decrease in the PRO-C3/C3M ratio during DAA therapy and follow-up (P < .02). The PRO-C4/C4M ratio was unchanged (P > .27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had >20% higher levels of C3M, PRO-C4 and C4M at all time points (P < .05). The collagen markers correlated with liver stiffness at baseline and follow-up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.
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Affiliation(s)
- Tea Lund Laursen
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | - Christina Sølund
- Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark
| | - Britta Tarp
- Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark
| | | | | | - Peter Leutscher
- Centre for Clinical Research, North Denmark Regional Hospital & Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Alex Lund Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | | | - Henning Grønbaek
- Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Fraquelli M, Fanetti I, Costantino A. Elastography After Treatment and During Follow-Up. ELASTOGRAPHY OF THE LIVER AND BEYOND 2021:119-141. [DOI: 10.1007/978-3-030-74132-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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36
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Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2020.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Taouli B, Alves FC. Imaging biomarkers of diffuse liver disease: current status. Abdom Radiol (NY) 2020; 45:3381-3385. [PMID: 32583139 DOI: 10.1007/s00261-020-02619-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/09/2020] [Accepted: 06/13/2020] [Indexed: 12/15/2022]
Abstract
We are happy to introduce this special issue of Abdominal Radiology on "diffuse liver disease". We have invited imaging experts to discuss various topics pertaining to diffuse liver disease, covering a vast array of imaging techniques including ultrasound (US), CT, MRI and new molecular imaging agents. Below, we briefly discussed the current status, limitations, and future directions of imaging biomarkers of diffuse liver disease.
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Affiliation(s)
- Bachir Taouli
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine At Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA.
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine At Mount Sinai, New York, NY, USA.
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Lombardo SD, Lombardo S. Some stability results for a model of Hepatitis C including alanine aminotransferase and immune system. INT J BIOMATH 2020. [DOI: 10.1142/s1793524520500801] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
In clinical practice, many cirrhosis scores based on alanine aminotransferase (ALT) levels exist. Although the most recent direct acting antivirals (DAAs) reduce fibrosis and ALT levels, the Hepatitis C virus (HCV) is not always removed. In this paper, we study a mathematical model of the HCV virus, which takes into account the role of the immune system, to investigate the ALT behavior during therapy. We find five equilibrium points and analyze their stability. A sufficient condition for global asymptotical stability of the infection-free equilibrium is obtained and local asymptotical stability conditions are given for the immune-free infection and cytotoxic T lymphocytes (CTL) response equilibria. The stability of the infection equilibrium with the full immune response is numerically performed.
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Affiliation(s)
- Salvo Danilo Lombardo
- CeMM Research Center for Molecular Medicine of the Austrian, Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, A-1090 Vienna, Austria
| | - Sebastiano Lombardo
- Department of Mathematics and Computer Science, University of Catania (Ret.), 95125, Catania, Italy
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Laursen TL, Sandahl TD, Kazankov K, George J, Grønbæk H. Liver-related effects of chronic hepatitis C antiviral treatment. World J Gastroenterol 2020; 26:2931-2947. [PMID: 32587440 PMCID: PMC7304101 DOI: 10.3748/wjg.v26.i22.2931] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/26/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
More than five years ago, the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral (DAA) drugs. They proved highly efficient in curing patients with chronic hepatitis C (CHC), including patients with cirrhosis. The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis, but the exact cause of the expected benefit was unclear. Further, little was known about how the underlying liver disease would be affected during and after viral clearance. In this review, we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects, such as macrophage activation, and the time-dependent effects of therapy, with specific emphasis on inflammation, structural liver changes, and liver function, as these factors are all related to morbidity and mortality in CHC patients. It seems clear that antiviral therapy, especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis. There seems to be a time-dependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions. These improvements lead to favorable effects on liver function, followed by an improvement in cognitive dysfunction and portal hypertension. Overall, the data provide knowledge on the several beneficial effects of DAA therapy on liver-related parameters in CHC patients suggesting short- and long-term improvements in the underlying disease with the promise of an improved long-term prognosis.
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Affiliation(s)
- Tea L Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Thomas D Sandahl
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Sydney NSW 2145, Australia
- University of Sydney, Sydney NSW 2145, Australia
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Saleh SA, Salama MM, Alhusseini MM, Mohamed GA. M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals. World J Gastroenterol 2020; 26:2864-2876. [PMID: 32550761 PMCID: PMC7284180 DOI: 10.3748/wjg.v26.i21.2864] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.
AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.
METHODS From December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.
RESULTS All patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).
CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.
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Affiliation(s)
- Shereen A Saleh
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Mohamed M Salama
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Marwan M Alhusseini
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Ghada A Mohamed
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
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Shousha HI, Fouad R, Elbaz TM, Sabry D, Mahmoud Nabeel M, Hosni Abdelmaksoud A, Mahmoud Elsharkawy A, Soliman ZA, Habib G, Abdelaziz AO. Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers. Arab J Gastroenterol 2020; 21:95-101. [PMID: 32439234 DOI: 10.1016/j.ajg.2020.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 03/23/2020] [Accepted: 04/05/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival. PATIENTS AND METHODS This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates. RESULTS TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation. CONCLUSION Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.
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Affiliation(s)
- Hend Ibrahim Shousha
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Rabab Fouad
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tamer Mahmoud Elbaz
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dina Sabry
- Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Mahmoud Nabeel
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Hosni Abdelmaksoud
- Diagnostic and Interventional Radiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aisha Mahmoud Elsharkawy
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Zeinab Abdellatif Soliman
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ghada Habib
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf Omar Abdelaziz
- Endemic Medicine and Hepato-gastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Kohla MAS, Fayoumi AE, Akl M, Abdelkareem M, Elsakhawy M, Waheed S, Abozeid M. Early fibrosis regression by shear wave elastography after successful direct-acting anti-HCV therapy. Clin Exp Med 2020; 20:143-148. [PMID: 31792631 DOI: 10.1007/s10238-019-00597-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 11/27/2019] [Indexed: 12/17/2022]
Abstract
Shear wave elastography (SWE) is a noninvasive ultrasound-based marker of hepatic fibrosis not requiring a special device. Successful direct-acting anti-HCV therapy was associated with hepatic fibrosis regression assessed by transient elastography (FibroScan). Data on the utility of SWE in these patients and how early fibrosis can regress after treatment are still lacking. To assess liver fibrosis by SWE before and after direct-acting antiviral treatment of chronic hepatitis C (CHC), we enrolled 165 CHC genotype 4 Egyptian patients treated with different Sofosbuvir-based regimens. Patients' laboratory characteristics, fibrosis biomarkers, namely Fibrosis-4 (FIB-4) index and AST/platelet ratio index (APRI) and liver stiffness measurements (LSM) by SWE were evaluated at baseline, end of treatment (EOT at week 12), week 24 and week 36. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as FIB-4 and APRI indices decreased significantly at EOT, week 24 and week 36 in comparison to baseline (P value < 0.001). Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to week 24 and week 36 with a P value < 0.001. The mean LSM showed improvement at EOT (7.01 ± 3.59 kpa), week 24 (6.18 ± 3.39 kpa) and week 36 (5.74 ± 3.21 kpa) in comparison to baseline (8.49 ± 0.83 kpa) (P value < 0.001). There is early liver fibrosis regression at EOT and throughout the time after successful treatment with direct-acting antiviral agents (DAAs). SWE is a feasible, easily applicable noninvasive relatively inexpensive assessment method of liver fibrosis.
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Affiliation(s)
- Mohamed Ahmed Samy Kohla
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt.
| | - Ahmed El Fayoumi
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mohamed Akl
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mervat Abdelkareem
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mahmoud Elsakhawy
- Department of Diagnostic and Interventional Radiology and Medical Imaging, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Sally Waheed
- Department of Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mai Abozeid
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
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Liver stiffness in chronic hepatitis C virus infection. ACTA ACUST UNITED AC 2020; 57:85-98. [PMID: 30447147 DOI: 10.2478/rjim-2018-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The severity of liver fibrosis can be assessed noninvasively today by liver stiffness measurements. Vibration-controlled transient elastography, shear wave elastography or magnetic resonance elastography are techniques increasingly used for this purpose. METHODS This article presents the recent advances in the use of new techniques for liver fibrosis assessment in chronic hepatitis C: the correlation between liver stiffness values and liver fibrosis estimated by liver biopsies, the prognosis role of liver stiffness values, their usefulness in monitoring the treatment response, in assessing the severity of portal hypertension and in estimating the presence of esophageal varices. Scientific articles from January 2017 to January 2018 were searched in PubMed and PubMed Central databases, using the terms "liver stiffness" and "hepatitis C". RESULTS The median liver stiffness values measured with different techniques are not identical, so that FibroScan thresholds cannot be used on any other elastographic machine. The higher the liver's stiffness measurement, the higher the liver-related events in patients with chronic hepatitis C. A liver stiffness measurement over 17 kPa could be an independent predictor for the presence of esophageal varices as well as a spleen with a longitudinal span ≥ 15 cm for patients with a value of liver stiffness < 17 kPa. A progressive and persistent decrease in liver stiffness is dependent on sustained virological response achievement. The lack of liver stiffness decrease has been associated with relapsers and a low value of liver stiffness at baseline. CONCLUSION Liver stiffness provides clues about the severity and evolution of liver disease.
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Ishizu Y, Ishigami M, Hayashi K, Honda T, Kuzuya T, Ito T, Fujishiro M. Rapid increase of platelet counts during antiviral therapy in patients with hepatitis C virus infection. Hepatol Res 2020; 50:47-56. [PMID: 31496023 DOI: 10.1111/hepr.13426] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 08/20/2019] [Accepted: 08/29/2019] [Indexed: 12/27/2022]
Abstract
AIM The cause of thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is multifactorial: hypersplenism, decreased thrombopoietin levels, and myelosuppression induced by HCV. Platelet counts increase after eradication of HCV; however, this mechanism is not fully understood. Therefore, the aim of this study was to determine the influence of these three factors on platelet counts. METHODS We retrospectively analyzed data from 109 HCV-infected patients with platelet counts ≤150 × 103 /μL who achieved viral eradication using interferon-free anti-HCV therapy. Changes in hematological parameters, thrombopoietin levels, HCV titers, and spleen volumes, and the correlations among them were evaluated. RESULTS HCV RNA levels significantly decreased at 4 weeks after initiating antiviral therapy. Platelet counts rapidly increased at 4 weeks from baseline (120 ± 35 vs. 106 ± 28 × 103 /μL, P < 0.001), and remained at a plateau until 48 weeks after initiating antiviral therapy. Neutrophil counts showed the same pattern. Spleen volume was evaluated in 32 patients and, among them, it decreased in 21 patients, but remained unchanged in seven and increased in four. In addition to patients with decreased spleen volume, patients with unchanged spleen volume showed marginally increased platelet counts. Thrombopoietin levels did not correlate with platelet counts. CONCLUSIONS Platelet counts increased at 4 weeks after starting anti-HCV treatment. Our results suggest that this rapid change was possibly caused by improvement of hypersplenism and HCV-induced myelosuppression resulting from anti-HCV therapy.
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Affiliation(s)
- Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Meijo Hospital, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Soliman H, Ziada D, Salama M, Hamisa M, Badawi R, Hawash N, Selim A, Abd-Elsalam S. Predictors for Fibrosis Regression in Chronic HCV Patients after the Treatment with DAAS: Results of a Real-world Cohort Study. Endocr Metab Immune Disord Drug Targets 2020; 20:104-111. [PMID: 31448717 DOI: 10.2174/1871530319666190826150344] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 05/31/2019] [Accepted: 07/01/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens. METHODS This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients. RESULTS Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one year of interferon containing and interferon free DAAs regimens respectively. Using multiple regression analysis; it was found that BMI, degrees of hepatic stiffness and steatosis were related to regression of hepatic fibrosis after therapy. CONCLUSION DAAs with or without interferon resulted in a significant reduction of liver fibrosis. BMI, steatosis and liver stiffness were independent factors for fibrosis regression in chronic HCV patients treated with DAAs. Further studies are needed to explore the mechanism by which steatosis affects HCV related fibrosis regression after treatment with DAAs.
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Affiliation(s)
- Hanan Soliman
- Department of Tropical Medicine, Tanta University, Tanta, Egypt
| | - Dina Ziada
- Department of Tropical Medicine, Tanta University, Tanta, Egypt
| | - Marwa Salama
- Department of Tropical Medicine, Tanta University, Tanta, Egypt
| | - Manal Hamisa
- Department of Radiology, Tanta University, Tanta, Egypt
| | - Rehab Badawi
- Department of Tropical Medicine, Tanta University, Tanta, Egypt
| | - Nehad Hawash
- Department of Tropical Medicine, Tanta University, Tanta, Egypt
| | - Amal Selim
- Department of Internal Medicine, Tanta University, Tanta, Egypt
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Zhang X, Wong GLH, Wong VWS. Application of transient elastography in nonalcoholic fatty liver disease. Clin Mol Hepatol 2019; 26:128-141. [PMID: 31696690 PMCID: PMC7160347 DOI: 10.3350/cmh.2019.0001n] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend non-invasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.
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Affiliation(s)
- Xinrong Zhang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.,State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Rinaldi L, Guarino M, Perrella A, Pafundi PC, Valente G, Fontanella L, Nevola R, Guerrera B, Iuliano N, Imparato M, Trabucco A, Sasso FC, Morisco F, Ascione A, Piai G, Adinolfi LE. Role of Liver Stiffness Measurement in Predicting HCC Occurrence in Direct-Acting Antivirals Setting: A Real-Life Experience. Dig Dis Sci 2019; 64:3013-3019. [PMID: 30937719 DOI: 10.1007/s10620-019-05604-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 03/26/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE The aim of this study was to evaluate the relationship between the liver stiffness measurement and the risk of developing hepatocellular carcinoma (HCC) in HCV cirrhotic patients undergoing new direct-acting antivirals. METHODS From April 2015 to April 2017, all consecutive HCV cirrhotic patients treated by direct-acting antivirals were enrolled. A liver stiffness measurement was computed at baseline, and an ultrasound evaluation was provided for all patients at baseline and every 6 months until 1 year after the stopping of the antiviral therapy. The diagnosis of HCC was performed according to international guidelines by imaging technique workup. RESULTS Two hundred and fifty-eight HCV patients with a diagnosis of cirrhosis were identified. The median liver stiffness was 25.5 kPa. Thirty-five patients developed HCC. Patients were divided into three groups, based on their liver stiffness: < 20 kPa (n = 72), between 20 and 30 kPa (n = 92) and > 30 kPa (n = 94). Compared to the < 20 kPa and 20-30 kPa groups, the > 30 kPa group showed a statistically significant increased risk of HCC (p = 0.019; HR 0.329; 95% CI 0.131-0.830). A ROC curve analysis to assess the overall predictive performance of liver stiffness measurement on the HCC risk was performed. The results allow us to identify a cutoff value of liver stiffness measurement equal to 27.8 kPa, which guarantees the highest sensitivity and specificity (respectively, 72% and 65%). CONCLUSIONS The data underline that the baseline liver stiffness measurement and ultrasound surveillance is a valuable tool for assessing the risk of HCC in cirrhotic patients undergoing the direct-acting antivirals treatment.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy.
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Alessandro Perrella
- VII Department of Infectious Diseases and Immunology, Ospedali dei Colli P. O. D. Cotugno, Naples, Italy
| | - Pia Clara Pafundi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Giovanna Valente
- Department of Medical Sciences, A.O.R.N. S. Anna and S. Sebastiano, Caserta, Italy
| | - Luca Fontanella
- Department of Internal Medicine, Centre for Liver Disease, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Barbara Guerrera
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Natalina Iuliano
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Michele Imparato
- Department of Internal Medicine, Centre for Liver Disease, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy
| | - Alessio Trabucco
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Antonio Ascione
- Department of Internal Medicine, Centre for Liver Disease, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy
| | - Guido Piai
- Department of Medical Sciences, A.O.R.N. S. Anna and S. Sebastiano, Caserta, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Miraglia, 80138, Naples, Italy
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Abdel Alem S, Elsharkawy A, El Akel W, Abdelaziz AO, Salama RM, El-Sayed MH, El Kassas M, Anees M, Shedeed M, Abdelsalam F, Ziada DH, El Shazly Y, El-Serafy M, Waked I, Esmat G, Doss W. Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients. Expert Rev Gastroenterol Hepatol 2019; 13:1009-1016. [PMID: 31418303 DOI: 10.1080/17474124.2019.1653183] [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: 01/11/2019] [Accepted: 08/05/2019] [Indexed: 12/18/2022]
Abstract
Objectives: To assess the role of baseline liver stiffness (LS) by Transient elastography (TE) and FIB-4 in the prediction of virological response to sofosbuvir - based regimens in chronic HCV patients.Methods: A retrospective, multicenter study including 7256 chronic HCV patients who received different sofosbuvir-based regimens. Baseline demographic and laboratory data were recorded. TE was performed with FIB-4 calculation at baseline.Results: Sustained virological response at week 12 post-treatment (SVR12) was 91.4%. Pretreatment TE values and FIB-4 were significantly lower among sustained responders (17.8 ± 11.5 kPa, 2.66 ± 1.98, respectively) versus relapsers (24.5 ± 13.9 kPa, 4.02 ± 3.3, respectively). Best cutoff levels for LS by TE and FIB-4 score for prediction of failure to treatment response were 16.7 kPa and 2.4, respectively. Among different treatment protocol, patients with FIB-4 > 2.4, TE values >16.7 kPa are more prone to treatment failure except when using SOF/SIM treatment regimens.Conclusion: Baseline LS by TE and FIB-4 score may be useful for predicting treatment outcome in the new era of DAAs and could be integrated into pretreatment assessment of chronic HCV patients for better optimization of patient management.
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Affiliation(s)
- Shereen Abdel Alem
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aisha Elsharkawy
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ashraf O Abdelaziz
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rabab Maamoun Salama
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan university, Cairo, Egypt
| | - Mahmoud Anees
- Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mahmoud Shedeed
- Department of infectious and Endemic Diseases, Faculty of medicine, Suez Canal University, Ismailia, Egypt
| | - Fatma Abdelsalam
- Department of hepatology, gastroenterology and infectious diseases, Banha University, Banh, Egypt
| | - Dina H Ziada
- Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Yehia El Shazly
- Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Magdy El-Serafy
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Hepatology, National Liver Institute, Menoufyia University, Menoufyia, Egypt
| | - Gamal Esmat
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wahid Doss
- Endemic Medicine and Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Fouad R, Elsharkawy A, Abdel Alem S, El Kassas M, Alboraie M, Sweedy A, Afify S, Abdellatif Z, Khairy M, Esmat G. Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals. Eur J Gastroenterol Hepatol 2019; 31:1129-1134. [PMID: 30896550 DOI: 10.1097/meg.0000000000001400] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND α-Fetoprotein (AFP) is used widely as a serological marker for hepatocellular carcinoma. However, the AFP value is elevated in chronic hepatitis C virus (HCV) patients without hepatocellular carcinoma. Yet, data on the impact of direct-acting antiviral agents (DAAs) therapy on AFP levels after viral eradication are still lacking. AIM The aim of this study was to elucidate the changes in the serum AFP level in chronic hepatitis C patients treated with DAA-based therapy and their relation to response and liver fibrosis parameters. PATIENTS AND METHODS A total of 456 chronic HCV patients who received different DAAs-based treatment regimens were enrolled. Laboratory data including serum AFP, transient elastography values, and fibrosis scores were recorded at baseline and sustained virological response at 24 weeks after treatment (SVR24). The outcome was the changes in the AFP level from baseline to SVR24 and its relation to changes in liver fibrosis parameters at SVR24 using Spearman's rank correlation test. RESULTS Overall, 96.9% of enrolled patients were responders. A statistically significant improvement in serum transaminases, albumin, transient elastography values, and fibrosis scores at SVR24 was reported. The AFP level was significantly decreased from a median (interquartile range) of 6 (3.2-10.8) ng/ml before DAAs to 4 (2.3-6) ng/ml at SVR24 (P < 0.0001). Only 22.6% of patients showed an increase in the AFP level after treatment. On multivariate analysis, the only independent baseline variable associated with an increase in the AFP level after treatment was baseline AFP (odds ratio: 0.95, 95% confidence interval: 0.91-0.99, P = 0.02). There is a significant correlation between changes in AFP and liver fibrosis parameters at SVR24. CONCLUSION DAAs-based regimens are a highly efficient antiviral therapy for chronic hepatitis C patients that resulted in improvements in the serum AFP level.
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Affiliation(s)
- Rabab Fouad
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Aisha Elsharkawy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Shereen Abdel Alem
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Mohamed El Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University
| | | | | | - Shimaa Afify
- Department of Tropical Medicine, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Zeinab Abdellatif
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Marwa Khairy
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
| | - Gamal Esmat
- Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University
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50
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Kwon JH, Yoo SH, Nam SW, Kim HY, Kim CW, You CR, Choi SW, Cho SH, Han JY, Song DS, Chang UI, Yang JM, Lee SW, Lee HL, Han NI, Kim SH, Song MJ, Sung PS, Jang JW, Bae SH, Choi JY, Yoon SK. Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea. J Med Virol 2019; 91:1104-1111. [PMID: 30695109 DOI: 10.1002/jmv.25412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/17/2019] [Accepted: 01/23/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.
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Affiliation(s)
- Jung Hyun Kwon
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sun Hong Yoo
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soon Woo Nam
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chang Wook Kim
- Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chan Ran You
- Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sang Wook Choi
- Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Se Hyun Cho
- Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon-Yeol Han
- Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Do Seon Song
- Department of Internal Medicine, St.Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - U Im Chang
- Department of Internal Medicine, St.Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St.Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Won Lee
- Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hae Lim Lee
- Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Nam Ik Han
- Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seok-Hwan Kim
- Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Myeong Jun Song
- Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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