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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Cheng HH, Ho MW, Chi CY, Kao JT. Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024; 57:840-853. [PMID: 39216998 DOI: 10.1016/j.jmii.2024.08.005] [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: 02/07/2024] [Revised: 07/15/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND/PURPOSE There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. METHODS From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. RESULTS Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). CONCLUSION For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.
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Affiliation(s)
- Ming-Han Hsieh
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ting-Hui Hsieh
- Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chi Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsing-Hung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Yu Chi
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Goh MJ, Park HC, Kim N, Bae BK, Choi MS, Rhu J, Lee MW, Jeong WK, Kim M, Kim K, Yu JI. Modified Albumin-Bilirubin Grade After Curative Treatment: Predicting the Risk of Late Intrahepatic Recurrence of Hepatocellular Carcinoma. J Korean Med Sci 2024; 39:e251. [PMID: 39355950 PMCID: PMC11444816 DOI: 10.3346/jkms.2024.39.e251] [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] [Received: 05/22/2024] [Accepted: 07/18/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND We aimed to identify the prognostic factors for late intrahepatic recurrence (IHR), defined as recurrence more than two years after curative treatment of newly diagnosed hepatocellular carcinoma (HCC). METHODS This retrospective cohort study included patients with newly diagnosed, previously untreated, very early, or early HCC treated with initial curative treatment and followed up without recurrence for more than two years, excluding early IHR defined as recurrence within two years in single center. Late IHR-free survival (IHRFS) was defined as the time interval from initial curative treatment to the first IHR or death without IHR, whichever occurred first. RESULTS Among all the enrolled 2,304 patients, 1,427 (61.9%) underwent curative intent hepatectomy and the remaining 877 (38.1%) underwent local ablative therapy (LAT). During the follow-up after curative treatment (median, 82.6 months; range, 24.1 to 195.7), late IHR was detected in 816 (35.4%) patients. In the multivariable analysis, age, male sex, cirrhotic liver at diagnosis, type of initial treatment, and modified albumin-bilirubin (mALBI) grade were significant prognostic baseline factors. Furthermore, mALBI grade at three (2a vs. 1, P = 0.02, hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.04-1.70; 2b/3 vs. 1, P = 0.03; HR, 1.42; 95% CI, 1.03-1.94) and six months (2b/3 vs. 1; P = 0.006; HR, 1.61; 95% CI, 1.13-2.30) after initial curative treatment was also a significant prognostic factor for late IHR. CONCLUSION After curative treatment for newly diagnosed early HCC, the mALBI grade at three and six months after initial curative treatment, as well as at baseline, was one of the most crucial prognostic factors for late IHR.
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Affiliation(s)
- Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nalee Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Bong Kyung Bae
- Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min Woo Lee
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Kyoung Jeong
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Minji Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Sinclair S, Shearen S, Ghobrial Y, Trad G, Abdul Basit S, Shih D, Ryan JK. Review of the Effects of Antiviral Therapy on Hepatitis B/C-Related Mortality and the Regression of Fibrosis. Viruses 2024; 16:1531. [PMID: 39459866 PMCID: PMC11512229 DOI: 10.3390/v16101531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/19/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis.
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Affiliation(s)
| | | | | | | | | | | | - John K. Ryan
- Comprehensive Digestive Institute of Nevada, Las Vegas, NV 89148, USA (S.A.B.); (D.S.)
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Huang JY, Peng JY, Long HY, Zhong X, Xie YH, Yao L, Xie XY, Lin MX. Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered. World J Hepatol 2024; 16:1018-1028. [PMID: 39086533 PMCID: PMC11287610 DOI: 10.4254/wjh.v16.i7.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 05/27/2024] [Accepted: 06/27/2024] [Indexed: 07/26/2024] Open
Abstract
BACKGROUND Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.
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Affiliation(s)
- Jia-Yao Huang
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Jian-Yun Peng
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Hai-Yi Long
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Xian Zhong
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Yu-Hua Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Lu Yao
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Man-Xia Lin
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
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Mondelli MU, Ottolini S, Oliviero B, Mantovani S, Cerino A, Mele D, Varchetta S. Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity. Int J Mol Sci 2023; 25:268. [PMID: 38203436 PMCID: PMC10779088 DOI: 10.3390/ijms25010268] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatitis C virus (HCV) has spread worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of the host's immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct-acting antivirals (DAA) has created hope for the progressive elimination of chronic HCV infections; however, this approach requires a monumental global effort. HCV elicits a prompt innate immune response in the host, characterized by a robust production of interferon-α (IFN-α), although interference in IFN-α signaling by HCV proteins may curb this effect. The late appearance of largely ineffective neutralizing antibodies and the progressive exhaustion of T cells, particularly CD8 T cells, result in the inability to eradicate the virus in most infected patients. Moreover, an HCV cure resulting from DAA treatment does not completely restore the normal immunologic homeostasis. Here, we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.
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Affiliation(s)
- Mario U. Mondelli
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Sabrina Ottolini
- Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Barbara Oliviero
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Stefania Mantovani
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Antonella Cerino
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Dalila Mele
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
| | - Stefania Varchetta
- Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (B.O.); (S.M.); (A.C.); (D.M.); (S.V.)
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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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Yoon JH, Kim SE, Cho SH, Kim GA, Park Y, Park JW, Kang SH, Lee YS, Kim JH. Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1436. [PMID: 37629725 PMCID: PMC10456703 DOI: 10.3390/medicina59081436] [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: 06/11/2023] [Revised: 08/01/2023] [Accepted: 08/06/2023] [Indexed: 08/27/2023]
Abstract
Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.
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Affiliation(s)
- Jae-Hyun Yoon
- Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea; (J.-H.Y.); (S.-H.C.)
| | - Sung-Eun Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Su-Hyeon Cho
- Department of Internal Medicine, School of Medicine, Chonnam National University Hospital, Gwangju 61469, Republic of Korea; (J.-H.Y.); (S.-H.C.)
| | - Gi-Ae Kim
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (G.-A.K.); (Y.P.)
| | - Yewan Park
- Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (G.-A.K.); (Y.P.)
| | - Ji-Won Park
- Department of Internal Medicine, College of Medicine, Hallym University, Anyang 14068, Republic of Korea; (S.-E.K.); (J.-W.P.)
| | - Seong-Hee Kang
- Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul 01757, Republic of Korea;
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University Medical Center, Seoul 08308, Republic of Korea;
| | - Jeong-Han Kim
- Department of Internal Medicine, School of Medicine, Konkuk University, Seoul 05030, Republic of Korea
- Research Institute of Medical Science, School of Medicine, Konkuk University, Seoul 05030, Republic of Korea
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Niu B, Zang W, Zhou H, Mi Y, Lu C, Li P. Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment. BMC Gastroenterol 2023; 23:102. [PMID: 37013471 PMCID: PMC10069046 DOI: 10.1186/s12876-023-02732-4] [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: 09/16/2022] [Accepted: 03/20/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.
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Affiliation(s)
- Bin Niu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Wenqian Zang
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Hui Zhou
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Chengzhen Lu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China.
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Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol 2023; 29:1243-1260. [PMID: 36925456 PMCID: PMC10011963 DOI: 10.3748/wjg.v29.i8.1243] [Citation(s) in RCA: 87] [Impact Index Per Article: 43.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 01/06/2023] [Accepted: 01/30/2023] [Indexed: 02/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ernesto Claar
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Domenico Cozzolino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli,” Naples 80138, Italy
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GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives. Int J Mol Sci 2023; 24:ijms24021703. [PMID: 36675217 PMCID: PMC9865319 DOI: 10.3390/ijms24021703] [Citation(s) in RCA: 97] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.
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Salmi A, di Filippo L, Ferrari C, Frara S, Giustina A. Ultrasound and FibroScan ® Controlled Attenuation Parameter in patients with MAFLD: head to head comparison in assessing liver steatosis. Endocrine 2022; 78:262-269. [PMID: 35980569 DOI: 10.1007/s12020-022-03157-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/27/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Controlled attenuation parameter (CAP) has been suggested as a new non-invasive measurement performed during transient elastography (TE) to assess liver steatosis. The aim of this study was to evaluate CAP values head to head with ultrasound (US) as reference standard. METHODS A consecutive cohort of patients attending abdominal US in an outpatient liver unit was included in this study with simultaneous CAP determination using the FibroScan® M probe and fibrosis scored by TE. Patients were subdivided in four groups on the basis of risk factors for Metabolically Associated Fatty Liver Disease (MAFLD). RESULTS Four hundred thirty-five patients were included in the analysis: 221 (51%) were male; 117 (26.9%) were in control group, 144 (33.1%) in group 2 with inactive HCV or HBV infection and at low-risk for MAFLD, 134 (30.8%) in group 3 at high-risk of MAFLD, 40 (9.2%) in group 4 at high-risk of MAFLD and concomitant inactive HCV or HBV infection. Liver steatosis detected with US evaluation was observed in the 41% of the entire cohort; in particular in the 3.4%, 20.1%, 83.6% and 87.4% of the group 1, 2, 3 and 4, respectively (p < 0.001). In patients at high-risk factor for MAFLD (group 3 and 4), CAP median levels were found statistically different among the severity-grading groups for US steatosis (S0 [n.27], ≥S1 [n.59], ≥S2 + S3 [n.89]), observing higher CAP levels in patients with a higher steatosis grade (≥S2 + S3 327.5 [±40.6] vs ≥S1 277.7 [±45.6] vs S0 245.1 [±47.4]; p < 0.001 for the whole cohort analysis) (p < 0.001 between ≥S2 + S3 and ≥S1) (p < 0.001 between ≥S2 + S3 and S0) (p = 0.004 between ≥S1 and S0). ROC analysis showed that the global performance of the CAP median level ≥ 258 to predict liver steatosis (S0 vs S1-3), was excellent with an Area Under the Curve (AUC) value of 0.87 [CI 95% 0. 835-0.904] with an 84% of sensitivity and a 78% of specificity, and a positive predictive value (PPV) of 73% and negative predictive value (NPV) of 88%. A TE-kPa median value <8.0 was detected in the 100%, 84%, 83.6% and 60% of patients in group 1, 2, 3 and 4, respectively. A TE-kPa median value >13.0 was detected in the 0%, 4.2%, 5.2% and 17.5% of patients in group 1, 2, 3 and 4, respectively. CONCLUSIONS CAP values are strongly associated with the standard US criteria for different degree of steatosis. Integrating TE up to 5% of patients may be identified at risk for advanced fibrosis.
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Affiliation(s)
- Andrea Salmi
- Hepato-Gastroenterology Outpatient Unit, Ospedale San Camillo, Brescia, Italy.
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy.
| | - Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Clarissa Ferrari
- Statistic Unit, IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Stefano Frara
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
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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: 05/14/2022] [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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13
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Genomic Relevance of FGFR2 on the Prognosis of HCV-Induced Hepatocellular Carcinoma Patients. J Clin Med 2022; 11:jcm11113093. [PMID: 35683481 PMCID: PMC9181427 DOI: 10.3390/jcm11113093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 12/24/2022] Open
Abstract
The Fibroblast Growth Factor Receptors (FGFRs) are known to regulate cancer metabolism in different tumor types, including hepatocellular carcinoma (HCC). Several risk factors are associated with HCC, of which viral infections (Hepatitis B and C) and cirrhosis are prominent. In Pakistan as well as in highly developed countries like the United States, hepatitis C virus HCV infections are most commonly reported in HCC. Here, we aimed to investigate the clinical relevance of FGFR receptors in HCC and their role in HCV-positive HCC cases. 264 HCC samples along with their clinical information and 96 normal liver samples were collected. qPCR was done to estimate the expression of FGFR1, FGFR2, FGFR3 and FGFR4. Three independent HCV-induced HCC cohorts (containing 293 HCC samples) were used for validation. According to in vitro results, FGFR1 was upregulated in HCV+ HCC patients. However, in all three independent cohorts of HCC, significant a down-regulation of FGFR1 was observed. FGFR2 overexpression was observed in the in vitro cohort as well as in three independent HCC cohorts. Interestingly, a strong correlation of FGFR2 expression was observed between cirrhosis and HCV in all four HCC cohorts. Our study suggested that FGFR2 expression can be used to classify HCC patients based on HCV infection. This FGFR2-based classification may lead to new therapeutic strategies against HCV-positive HCC subtypes.
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Su PY, Chen YY, Lai JH, Chen HM, Yao CT, Liu IL, Zeng YH, Huang SP, Hsu YC, Wu SS, Siao FY, Yen HH. Real-World Experience of Chronic Hepatitis C-Related Compensated Liver Cirrhosis Treated with Glecaprevir/Pibrentasvir: A Multicenter Retrospective Study. J Clin Med 2021; 10:jcm10225236. [PMID: 34830518 PMCID: PMC8619604 DOI: 10.3390/jcm10225236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen that has been approved for the treatment of chronic hepatitis C. The present study aimed to evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis in a real-world setting. Methods: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from five hospitals in the Changhua Christian Care System, who underwent treatment between August 2018 and October 2020. The primary endpoint was a sustained virological response observed 12 weeks after completion of the treatment. Results: Ninety patients, including 70 patients who received the 12-week therapy and 20 patients who received the 8-week therapy, were enrolled. The mean age of the patients was 65 years, and 57.8% of the patients were males. Sixteen (17.8%) patients had end-stage renal disease, and 15 (16.7%) had co-existing hepatoma. The hepatitis C virus genotypes 1 (40%) and 2 (35.6%) were most common. The common side effects included anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%), and malaise (7.8%). Laboratory adverse grade ≥3 events included anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%). The overall sustained virological response rates were 94.4% and 97.7% in the intention-to-treat and per-protocol analyses, respectively. Conclusions: the glecaprevir/pibrentasvir treatment regimen was highly effective and well tolerated among patients with compensated cirrhosis in the real-world setting.
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Affiliation(s)
- Pei-Yuan Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yang-Yuan Chen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua 500, Taiwan
- Department of Hospitality, MingDao University, Changhua 500, Taiwan
| | - Jun-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua 500, Taiwan;
| | - Hung-Ming Chen
- Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin 648, Taiwan;
| | - Chih-Ta Yao
- Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua 500, Taiwan;
| | - I-Ling Liu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Ya-Huei Zeng
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Siou-Ping Huang
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Yu-Chun Hsu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Shun-Sheng Wu
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
| | - Fu-Yuan Siao
- Department of Emergency Medicine, Changhua Christian Hospital, Changhua 500, Taiwan;
- Department of Kinesiology, Health and Leisure, Chienkuo Technology University, Changhua 500, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; (P.-Y.S.); (Y.-Y.C.); (I.-L.L.); (Y.-H.Z.); (S.-P.H.); (Y.-C.H.); (S.-S.W.)
- Artificial Intelligence Development Center, Changhua Christian Hospital, Changhua 500, Taiwan
- General Education Center, Chienkuo Technology University, Changhua 500, Taiwan
- Department of Electrical Engineering, Chung Yuan University, Taoyuan 320, Taiwan
- College of Medicine, National Chung Hsing University, Taichung 400, Taiwan
- Correspondence: ; Tel.: +886-4-723-8595-5501
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