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Woo J, Choi Y. Biomarkers in Detection of Hepatitis C Virus Infection. Pathogens 2024; 13:331. [PMID: 38668286 PMCID: PMC11054098 DOI: 10.3390/pathogens13040331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 04/10/2024] [Accepted: 04/12/2024] [Indexed: 04/29/2024] Open
Abstract
The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).
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Affiliation(s)
| | - Youkyung Choi
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329-4018, USA;
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Li Z, Zhang N, Dong Z, Wang X, Zhou J, Gao J, Yang Y, Li J, Guan F, Zhou Y, Tan Z. Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma. Cell Commun Signal 2024; 22:200. [PMID: 38561745 PMCID: PMC10983713 DOI: 10.1186/s12964-024-01569-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 03/12/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. METHODS An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. RESULTS Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. CONCLUSIONS The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.
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Affiliation(s)
- Zhuo Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China
| | - Na Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China
| | - Zewen Dong
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China
| | - Xin Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China
| | - Jian Zhou
- Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China
| | - Juan Gao
- Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, P.R. China
| | - Yunyun Yang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China
| | - Jing Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China
| | - Feng Guan
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China
| | - Yue Zhou
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, P.R. China.
| | - Zengqi Tan
- Institute of Hematology, Provincial Key Laboratory of Biotechnology, School of Medicine, Northwest University, Xi'an, Shaanxi, 710069, P.R. China.
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Yang K, Pan Y, Liu L, Sun B, Shi W. Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59050923. [PMID: 37241155 DOI: 10.3390/medicina59050923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/03/2023] [Accepted: 04/03/2023] [Indexed: 05/28/2023]
Abstract
Background and Objectives: Non-invasive methods for evaluating liver fibrosis have been a crucial focus of clinical research. The aim of the current study is to assess the accuracy of serum alpha-fetoprotein (AFP) in determining the stage of liver fibrosis in patients with chronic hepatitis B (CHB) who are positive for HBeAg. Materials and Methods: The current study included a total of 276 HBeAg-positive CHB patients who underwent liver biopsy. The levels of serum AFP were measured in these patients using electrochemiluminescence immunoassays. The correlations between serum AFP levels and other laboratory parameters were analyzed using Spearman's correlation analysis. Binary logistic regression analysis was performed to determine the independent associations between serum AFP levels and liver fibrosis. The diagnostic performance of serum AFP and other non-invasive markers was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 59 (21.4%) patients were found to have elevated levels of serum AFP (>7 ng/mL). These patients displayed a significantly higher proportion of both advanced fibrosis and cirrhosis compared to those with normal serum AFP levels (0-7 ng/mL). The level of serum AFP was positively associated with levels of serum globulin (GLB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL), as well as the AST-to-platelet ratio (APRI), fibrosis-4 (FIB-4), and Scheuer's classification, and negatively correlated with platelet (PLT) counts. Furthermore, serum AFP was found to be independently associated with significant fibrosis, advanced fibrosis, and cirrhosis. The results of the ROC analysis showed that serum AFP was an effective predictor of significant fibrosis, advanced fibrosis, and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% CI: 0.721-0.821), 0.889 (95% CI: 0.847-0.923), and 0.925 (95% CI: 0.887-0.953), respectively. These values are higher than those of the APRI and FIB-4. Conclusions: Serum AFP could serve as a valuable supplemental biomarker for determining the severity of liver fibrosis in HBeAg-positive patients with chronic hepatitis B.
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Affiliation(s)
- Kai Yang
- Department of Medical Technology, Anhui Medical College, Hefei 230601, China
| | - Ying Pan
- Department of Medical Technology, Anhui Medical College, Hefei 230601, China
| | - Liwei Liu
- Department of Medical Technology, Anhui Medical College, Hefei 230601, China
| | - Beibei Sun
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Wei Shi
- Department of Medical Technology, Anhui Medical College, Hefei 230601, China
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Short Half-Life of Des-γ-Carboxy Prothrombin Is a Superior Factor for Early Prediction of Outcomes of Hepatocellular Carcinoma Treated with Radiofrequency Ablation. Diagnostics (Basel) 2023; 13:diagnostics13040696. [PMID: 36832184 PMCID: PMC9955975 DOI: 10.3390/diagnostics13040696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. MATERIALS AND METHODS 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. RESULTS Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). CONCLUSIONS Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA.
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Shirai K, Hikita H, Sakamori R, Doi A, Tahata Y, Sakane S, Kamada Y, Murai K, Nishio A, Yamada R, Kodama T, Nozaki Y, Kakita N, Ishida H, Nakanishi F, Morishita N, Imanaka K, Sakakibara M, Tatsumi T, Miyoshi E, Takehara T. Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis. PLoS One 2022; 17:e0279416. [PMID: 36542633 PMCID: PMC9770342 DOI: 10.1371/journal.pone.0279416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Patients with advanced fibrosis are at risk for developing hepatocellular carcinoma (HCC) even after hepatitis C virus (HCV) elimination. We previously reported that serum fucosylated haptoglobin (Fuc-Hp) levels increase as the disease progresses from chronic hepatitis to cirrhosis and then HCC. However, it remains unclear whether serum Fuc-Hp levels can stratify the risk of HCC occurrence after a sustained virological response (SVR) is achieved with direct-acting antivirals (DAAs) in patients with advanced liver fibrosis. METHODS Among 3,550 patients with chronic hepatitis C treated with DAAs at Osaka University Hospital and related hospitals, the stored sera of 140 patients who were diagnosed with F3 or F4 by liver biopsy before DAA treatment, achieved SVR, and had no history of HCC were available at both baseline and the end of treatment (EOT). We measured the Fuc-Hp levels in these samples. RESULTS The median serum levels of Fuc-Hp at EOT were significantly lower than those at baseline. During the 54.4-month follow-up period, 16 of 140 patients developed HCC. Multivariate Cox proportional hazards analysis revealed that high Fuc-Hp at EOT, high body mass index (BMI), and low albumin at EOT were independent risk factors for HCC occurrence. Patients with all three factors-high Fuc-Hp, high BMI, and low albumin-had a higher incidence of HCC than patients without these factors. CONCLUSIONS High serum Fuc-Hp levels at EOT were an independent risk factor for HCC occurrence after SVR. Combined with BMI and albumin, Fuc-Hp can stratify the risk of HCC occurrence among those with advanced fibrosis.
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Affiliation(s)
- Kumiko Shirai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryotaro Sakamori
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
- National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Akira Doi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Sadatsugu Sakane
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoshihiro Kamada
- Division of Health Sciences, Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Kazuhiro Murai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Akira Nishio
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoko Yamada
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takahiro Kodama
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | | | | | | | - Fumihiko Nakanishi
- National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan
| | | | | | | | - Tomohide Tatsumi
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Eiji Miyoshi
- Division of Health Sciences, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
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Liu S, Sun L, Yao L, Zhu H, Diao Y, Wang M, Xing H, Lau WY, Guan M, Pawlik TM, Shen F, Xu M, Tong X, Yang T. Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. J Clin Med 2022; 11:5075. [PMID: 36079006 PMCID: PMC9456633 DOI: 10.3390/jcm11175075] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/18/2022] [Accepted: 08/26/2022] [Indexed: 11/25/2022] Open
Abstract
Background and Aim: Alpha-fetoprotein (AFP), a lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), is a protein that is induced by vitamin K deficiency or antagonist-II (PIVKA-II) that has been clinically used as a serum biomarker for early detection and diagnosis of hepatocellular carcinoma (HCC). Diagnostic performance of each serum biomarker alone, or their combinations for the detection of hepatitis C virus (HCV)-associated HCC were compared. Methods: Serum AFP, AFP-L3, and PIVKA-II levels were evaluated in patients with HCV-associated HCC, and those with chronic HCV infection without HCC (HCV-controls). The areas under the curve (AUC), sensitivity, and specificity were compared to identify the diagnostic performance of each serum HCC biomarker alone or in combination. Results: Overall, 172 HCV controls and 105 patients with HCV-associated HCC were enrolled. The AFP, AFP-L3, and PIVKA-II levels were significantly increased among patients with HCV-associated HCC when compared with HCV patients without HCC (p < 0.001). When these biomarkers were analyzed individually, PIVKA-II revealed the best predictive performance (AUC: PIVKA-II 0.90 vs. AFP 0.80 vs. AFP-L3 0.69, p < 0.001). In evaluating the combinations of any two biomarkers, the best predictive performance was found in PIVKA-II + AFP (0.93 vs. AFP + AFP-L3 0.78, p = 0.001; and PIVKA-II + AFP-L3 0.89, p < 0.001), which had no difference compared to the predictive performance of the combination of all three serum biomarkers (AFP + AFP-L3 + PIVKA-II 0.93, p = 0.277). Similar results were identified in the subgroups of patients with HCV-induced cirrhosis, and among patients with early-stage HCC defined by BCLC and TNM staging. Conclusions: The addition of the PIVKA-II test to routine AFP test maybe provide a more suitable biomarker approach to detect HCV-induced HCC in patients with HCV infection undergoing HCC surveillance.
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Affiliation(s)
- Siyu Liu
- Department of Laboratory Medicine, Lishui Municipal Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
| | - Liyang Sun
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Lanqing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hong Zhu
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Yongkang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Mingda Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China
| | - Mingcheng Guan
- Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
| | - Min Xu
- Department of Interventional Radiology, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui 323050, China
| | - Xiangmin Tong
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
- Department of Laboratory, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323050, China
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’ s Hospital (People’ s Hospital of Hangzhou Medical College), No. 158, Shangtang Road, Hangzhou 310014, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
- Cancer Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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Qian X, Liu Y, Wu F, Zhang S, Gong J, Nan Y, Hu B, Chen J, Zhao J, Chen X, Pan W, Dang S, Lu F. The Performance of Serum Alpha-Fetoprotein for Detecting Early-Stage Hepatocellular Carcinoma Is Influenced by Antiviral Therapy and Serum Aspartate Aminotransferase: A Study in a Large Cohort of Hepatitis B Virus-Infected Patients. Viruses 2022; 14:1669. [PMID: 36016291 PMCID: PMC9416230 DOI: 10.3390/v14081669] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/25/2022] [Accepted: 07/14/2022] [Indexed: 11/17/2022] Open
Abstract
Background and aims: Factors associated with abnormally elevated alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-infected patients remain to be studied. We aimed to identify factors associated with elevated serum AFP in patients with non-hepatocellular carcinoma (HCC) and early-stage HCC and their influences on the performance of AFP for detecting early-stage HCC. Methods: This multicenter, retrospective study was conducted in 4401 patients with chronic HBV infection, including 3680 patients with non-HCC and 721 patients with early-stage HCC. Factors associated with elevated AFP were analyzed. Diagnostic performance of AFP for early-stage HCC were compared among groups through area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: When analyzed by multivariate logistic regression, antiviral therapy was negatively associated with elevated AFP, while hepatitis B e antigen (HBeAg) and aspartate aminotransferase (AST) > 1× upper limit of normal (ULN) were positively associated with elevated AFP both in patients with non-HCC and early-stage HCC (all p < 0.05). The AUCs of AFP for detecting early-stage HCC in patients with antiviral therapy, HBV DNA (−), alanine aminotransferase (ALT) ≤ 1× ULN, and AST ≤ 1× ULN were significantly higher compared to those in non-antiviral therapy, HBV DNA (+), ALT > 1× ULN, and AST > 1× ULN groups, respectively. When categorizing patients into AST ≤ 1× ULN and > 1× ULN, AFP achieved the highest AUCs in patients with AST ≤ 1× ULN regardless of antiviral treatment (AUCs = 0.813 and 0.806, respectively). Furthermore, there were considerable differences in the cut-off values of AFP in detecting early-stage HCC in different subgroups when applying similar sensitivity and specificity. Conclusions: Antiviral therapy and serum AST might be used to help judge and select the specific cut-off values of serum AFP for HCC surveillance in different at-risk populations.
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Affiliation(s)
- Xiangjun Qian
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
- Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
| | - Yanna Liu
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
| | - Fengping Wu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;
| | - Siyu Zhang
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China; (S.Z.); (Y.N.)
| | - Jiao Gong
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; (J.G.); (B.H.)
| | - Yuemin Nan
- Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China; (S.Z.); (Y.N.)
| | - Bo Hu
- Department of Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; (J.G.); (B.H.)
| | - Junhui Chen
- Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen 518035, China;
| | - Jingmin Zhao
- Department of Pathology and Hepatology, The 5th Medical Centre, Chinese PLA General Hospital, Beijing 100039, China;
| | - Xiangmei Chen
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
| | - Weidong Pan
- Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;
| | - Fengmin Lu
- Department of Microbiology, Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; (X.Q.); (Y.L.); (X.C.)
- Precision Medicine Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
- Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People’s Hospital, Beijing 100044, China
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El Kassas M, Eltabbakh M, Elbadry M, Tawheed A, Elbaz T. Establishing a research production line in real-life settings: the case of Hepatitis C management in a viral hepatitis specialized Egyptian center. Curr Med Res Opin 2022; 38:553-563. [PMID: 35118916 DOI: 10.1080/03007995.2022.2038489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/23/2022] [Accepted: 02/02/2022] [Indexed: 11/03/2022]
Abstract
Efforts toward eradicating the Hepatitis C virus (HCV) have advanced rapidly, due to the development of direct-acting antivirals (DAAs), especially with the appearance of pan-genotypic combinations. Real-world studies, in particular, have verified the efficacy and safety of DAA combinations documented in registration trials. This review documents the results of using DAA combinations in real-life settings in everyday clinical practice in Egypt, the country with the highest prevalence of HCV. The significant number of treated patients in Egypt, which exceeded four million allowed tremendous data about the results of HCV management in real-life settings for different treatment regimens and disease conditions. DAA combinations have resulted in high sustained virologic response rates (SVR12) and few adverse reactions in real-life settings. SVR12 rates ranged from 90% to 100%, depending on the combination of drugs used, the HCV genotype, and the stage of liver disease. Most adverse reactions reported in real-world settings were mild and resulted in treatment discontinuation in only a minority of cases. Data from real-life studies covered most aspects of HCV management that were lacking after initial approval studies. More research is needed to tailor treatment and produce generic HCV combinations to overcome the residual limitations of the currently available DAAs.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Elbadry
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Tamer Elbaz
- Endemic Medicine and Hepatogastroenterology, Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Serum TERT C228T is an important predictor of non-viral liver cancer with fatty liver disease. Hepatol Int 2022; 16:412-422. [PMID: 35306637 PMCID: PMC9013341 DOI: 10.1007/s12072-022-10313-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 12/05/2021] [Indexed: 11/05/2022]
Abstract
Background Molecular therapies and precision medicine are expected to be developed for liver cancer based on the diagnosis of DNA somatic alterations. However, it remains unclear whether TERT promoter mutation (TERT C228T) in serum cfDNA is useful for the diagnosis of liver cancer with non-viral fatty liver disease (FLD). Methods This retrospective cohort study examined 258 Japanese patients who had a confirmed diagnosis of primary liver cancer. We investigated the factors associated with TERT C228T and abnormal levels of liver cancer-specific tumor markers (AFP and PIVKAII) in serum samples. Results Multivariate analysis identified the etiology of FLD, vascular invasion, and non-cirrhosis as determinants of TERT C228T-positive liver cancer. Rates of positive TERT C228T in FLD were significantly higher than those of HBV and HCV. Conversely, rates of abnormal AFP in FLD were significantly lower than those of HBV and HCV. Viral suppression of HBV/HCV and alcohol intake did not affect TERT C228T, but AFP was significantly reduced by viral suppression. The rates of positive TERT C228T were significantly lower in HCV patients with viral clearance than those of FLD patients. Conclusion Our results highlight the importance of serum TERT C228T for the detection of non-viral FLD-related liver cancer. TERT C228T is a tumor marker that might not be influenced by inflammation. Supplementary Information The online version contains supplementary material available at 10.1007/s12072-022-10313-y.
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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Chuang PH, Kao JT. Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study. Ther Adv Chronic Dis 2022; 13:20406223211067631. [PMID: 35070254 PMCID: PMC8771741 DOI: 10.1177/20406223211067631] [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: 06/03/2021] [Accepted: 12/01/2021] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored. METHODS This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63-7.54). RESULTS In patients with baseline METAVIR fibrosis stages (F) <4 (able to undergo fibrosis progression; n = 77), cases achieving sustained virological response (SVR) (n = 52) had a significantly lower rate of fibrosis progression than non-SVR cases (n = 25) (3.8% versus 24.0%, p = 0.012). Among the entire cohort (n = 85), the rate of activity response [METAVIR activity grades (A) decreasing or maintaining at A0] in SVR cases (n = 59) was significantly higher than that in non-SVR cases (n = 26) (94.9% versus 65.4%, p = 0.001). For SVR cases among the entire cohort, independent predictors of fibrosis clearance included baseline F <2 [odds ratio (OR) = 7.877, p = 0.042] and aspartate transaminase (AST) levels declining by >70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively. CONCLUSIONS Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.
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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
- Faculty of Medicine, Wroclaw Medical University, Wroclaw, Dolnoslaskie, Poland
| | - Ting-Hui Hsieh
- Interdisciplinary Program for Undergraduates, 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
| | - Po-Heng Chuang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
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Abd Eldaim MA, Barakat ER, Alkafafy M, Elaziz SAA. Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:57997-58006. [PMID: 34100211 DOI: 10.1007/s11356-021-14722-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 05/31/2021] [Indexed: 06/12/2023]
Abstract
This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.
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Affiliation(s)
- Mabrouk Attia Abd Eldaim
- Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Sheben El-Koom, 32512, Egypt.
| | - Eman Ragab Barakat
- Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, 32897, Egypt
| | - Mohamed Alkafafy
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
| | - Samy Ahmed Abd Elaziz
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
- Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
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Khalil A, Elsheashaey A, Abdelsameea E, Obada M, Mohamed Bayomy FF, El-Said H. Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00142-3] [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
Bile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50).
Results
The progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638).
Conclusion
The level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.
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Huynh T, Hu KQ. Excellent Safety and Sustained Virologic Response to Direct-Acting Antivirals Treatment in HCV-Infected Geriatric Patients: A Real-World Data. Dig Dis Sci 2021; 66:1327-1334. [PMID: 32405981 DOI: 10.1007/s10620-020-06286-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2019] [Accepted: 04/17/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) are current standard of HCV treatment (Rx). However, data remain lacking on real-world safety, patterns of biochemical, virologic responses, and sustained virologic response (SVR12) rate in geriatric patients. AIMS The present study assessed clinical presentation, safety, SVR12 rate, dynamic changes in HCV RNA, ALT, and AFP in geriatric patients (age ≥ 65 year old, G1) versus non-geriatric patients (G2) with chronic hepatitis C and received DAA treatment. METHODS This was a single-center, retrospective study on 183 patients with DAA Rx and 12-week post-Rx follow-up. RESULTS There were no significant differences in patterns of biochemical and virologic responses between the two groups. Undetectable HCV RNA rates were 67.2% versus 75.7% (p = 0.22) and 77.3% versus 84.3% (p = 0.24) at Rx week 2 and Rx week 4, respectively. The SVR12 rate was comparable in 2 groups, 94.1% (G1) versus 95.7% (G2, p = 0.64). ALT normalization rates were 91.2% versus 91.3% (p = 0.98), 92.6% versus 93.9% (p = 0.74), and 97.1% versus 97.4% (p = 0.89) at Rx week 2, post-Rx week12, and post-Rx week 24, respectively. AFP normalization was lower in G1 with 89.7% versus 95.7% (p = 0.12), 77.9% versus 87.8% (p = 0.08), and 79.4% versus 92.2% (p = 0.01), at Rx week 2, and post-Rx week 12, and post-Rx week 24, respectively. Both groups showed similar side effects profile including fatigue 11.8% versus 12.2% (p = 0.93) and headache 11.8% versus 13.9% (p = 0.68). CONCLUSION Based on our real-world data, geriatric patients had excellent and comparable treatment outcomes with non-geriatric patients in safety and SVR12 rates to different DAA regimens.
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Affiliation(s)
- Tung Huynh
- Department of Pharmacy, University of California Irvine Medical Center, Orange, CA, USA
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, 101 The City Drive, Building 56, Ste. 801, Orange, CA, 92868, USA.
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Association of α-fetoprotein levels with liver stiffness measurement in outpatients with chronic hepatitis B. Biosci Rep 2021; 41:227182. [PMID: 33289529 PMCID: PMC7789808 DOI: 10.1042/bsr20203048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/25/2020] [Accepted: 12/07/2020] [Indexed: 02/05/2023] Open
Abstract
The association between α-fetoprotein (AFP) levels with the assessment of liver stiffness (LS) in chronic hepatitis B (CHB) patients were explored. A total of 283 outpatients with CHB were enrolled. Patient age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AFP, platelet (PLT), total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), albumin (ALB), globulin, and albumin/globulin (A/G) levels were associated with LS values in the univariate model (P<0.05). Significant associations between AFP and PLT levels with LS values were observed when both variables were included in the multivariate analysis models. Receiver operation characteristic (ROC) analysis indicated that the combination of AFP and PLT levels could enhance the predictive performance of liver fibrosis (area under the curve (AUC) = 0.819, P<0.001) and that PLT levels (PLT < 100 × 109/l) combined with high AFP levels (AFP > 8 ng/ml) significantly increased the prediction of liver fibrosis (OR = 11.216). More importantly, LS values associated with higher AFP levels (AFP > 8 ng/ml), independently of higher ALT or AST values, were significantly higher than those of low AFP level groups. In conclusion, in Chinese outpatients with CHB, AFP outperformed ALT and/or AST levels in terms of their association with LS. AFP and PLT levels were independently associated with LS, and their combined assessment could enhance the diagnostic and predictive performance of liver fibrosis among CHB patients.
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Qian X, Liu S, Long H, Zhang S, Yan X, Yao M, Zhou J, Gong J, Wang J, Wen X, Zhou T, Zhai X, Xu Q, Zhang T, Chen X, Hu G, Wang J, Gao Z, Nan Y, Chen J, Hu B, Zhao J, Lu F. Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy. J Viral Hepat 2021; 28:20-29. [PMID: 32852885 PMCID: PMC7756791 DOI: 10.1111/jvh.13388] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 07/03/2020] [Accepted: 07/30/2020] [Indexed: 12/15/2022]
Abstract
This study was designed to explore if antiviral treatment influences the performance of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) among the high-risk chronic HBV-infected patients. A total of 5936 patients who had evidence of chronic HBV infection were enrolled from four independent centres in this retrospective study, including 1721 chronic hepatitis B (CHB), 2286 liver cirrhosis (LC), 798 HCC within Milan criteria and 1131 HCC beyond Milan criteria patients. Stratified by whether they received treatment or not, the patients were further divided into antiviral and non-antiviral groups. Then, the performance of AFP for discriminating HCC was evaluated. Patients receiving antivirals had significantly lower median levels of AFP compared with the non-antiviral patients (P < .001), and there were significantly less patients with abnormal AFP levels in antiviral groups (P < .001). Antiviral therapy improved the AUROCs of AFP for discriminating HCC within Milan criteria. When setting the cut-off values at 20 ng/mL and 100 ng/mL as surveillance and confirmatory tests respectively for HCC among patients receiving antiviral treatment, AFP exhibited a significantly higher sensitivity than those of 200 ng/mL and 400 ng/mL, which are currently recommended by some guidelines, without compromising specificity. Further analysis in antiviral patients revealed that serum AFP had better performance for discriminating HCC within Milan criteria in ALT ≤ 1ULN patients than that in ALT > 1ULN patients. In conclusion, in the era of antiviral therapy, serum AFP's surveillance performance was substantially improved for HCC within Milan criteria among the high-risk population of CHB and LC patients.
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Affiliation(s)
- Xiangjun Qian
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Shuhong Liu
- Department of Pathology and HepatologyThe 5th Medical CentreChinese PLA General HospitalBeijingChina
| | - Huiling Long
- Department of Infectious DiseasesThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Siyu Zhang
- Department of Traditional and Western Medical HepatologyThe Third Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Xiaotong Yan
- Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
| | - Mingjie Yao
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Jiyuan Zhou
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Jiao Gong
- Department of Laboratory MedicineThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jianwen Wang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Xiajie Wen
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Tao Zhou
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Xiangwei Zhai
- Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
| | - Qiang Xu
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Ting Zhang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Xiangmei Chen
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Guoxin Hu
- Department of Infectious DiseasesPeking University Shenzhen HospitalShenzhenChina
| | - Jie Wang
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina
| | - Zhiliang Gao
- Department of Infectious DiseasesThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Yuemin Nan
- Department of Traditional and Western Medical HepatologyThe Third Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Junhui Chen
- Intervention and Cell Therapy CenterPeking University Shenzhen HospitalShenzhenChina
| | - Bo Hu
- Department of Laboratory MedicineThird Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina
| | - Jingmin Zhao
- Department of Pathology and HepatologyThe 5th Medical CentreChinese PLA General HospitalBeijingChina
| | - Fengmin Lu
- Department of Microbiology & Infectious Disease CenterSchool of Basic Medical SciencesPeking University Health Science CenterBeijingChina,Department of Epidemiology and BiostatisticsCollege of Public HealthZhengzhou UniversityZhengzhouChina
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Influence of Alanine Transaminase Levels on Alpha-Fetoprotein for Predicting Hepatocellular Carcinoma in Patients with Hepatitis B Infection. BIOMED RESEARCH INTERNATIONAL 2020; 2020:2043715. [PMID: 33490235 PMCID: PMC7787738 DOI: 10.1155/2020/2043715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 11/24/2020] [Accepted: 11/30/2020] [Indexed: 01/22/2023]
Abstract
Purpose To investigate the influence of alanine transaminase (ALT) on the accuracy of alpha-fetoprotein (AFP) for detecting hepatocellular carcinoma (HCC). Methods This retrospective study recruited 799 patients with HCC, cirrhosis, and chronic hepatitis due to hepatitis B infection and healthy adults between July 2017 and January 2019. Comparisons of the area under the receiver operating characteristic curves (AUCs) for detecting HCC in different ALT levels were calculated. Results Serum ALT and gamma-glutamyl transferase levels were significantly associated with elevated AFP in patients without HCC. The AUC of AFP was higher in patients with ALT ≤ 2 upper limit of normal (ULN) than in patients with ALT > 2 ULN (0.806 vs. 0.611, P < 0.001). Nevertheless, there were no significant differences in the AUCs of AFP/(ALT × aspartate aminotransferase (AST)) in patients with ALT ≤ 2 ULN and with ALT > 2 ULN (0.745 vs. 0.769, P = 0.68). AFP/(ALT × AST) was better than AFP in patients with ALT > 2 ULN for detecting HCC (P < 0.001). Conclusions Higher ALT levels might impair the accuracy of AFP for diagnosing HCC. AFP tests showed better accuracy in patients with ALT ≤ 2 ULN whereas the AFP/(ALT × AST) ratio was recommended in patients with elevated ALT levels.
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Tamai H, Shingaki N, Ida Y, Shimizu R, Maeshima S, Okamura J, Kawashima A, Nakao T, Hara T, Matsutani H, Nishikawa I, Higashi K. Sofosbuvir plus ribavirin is tolerable and effective even in elderly patients 75-years-old and over. World J Hepatol 2020; 12:672-684. [PMID: 33033572 PMCID: PMC7522558 DOI: 10.4254/wjh.v12.i9.672] [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: 04/10/2020] [Revised: 07/12/2020] [Accepted: 07/26/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although clinical use of sofosbuvir plus ribavirin has been approved for patients infected with genotype 2 hepatitis C virus, patients ≥ 75-years-old have not been included in previous clinical trials.
AIM To evaluate the real-world safety and efficacy of sofosbuvir plus ribavirin for elderly patients (≥ 75-years-old) compared to nonelderly patients, we conducted a post-marketing prospective cohort study.
METHODS We treated 265 patients with genotype 2 hepatitis C virus using standard approved doses of sofosbuvir (400 mg/d) plus ribavirin adjusted by body weight, administered orally for 12 wk.
RESULTS Sustained virological response rates for the overall cohort, patients < 65-years-old, ≥ 65-years-old but < 75-years-old, and ≥ 75-years-old were 97% (258/265), 98% (93/95), 97% (84/87), and 98% (81/83), respectively (P = 0.842). Logistic regression analyses identified history of hepatocellular carcinoma treatment and alpha-fetoprotein as factors significantly associated with sustained virological response. Alpha-fetoprotein was the only independent factor identified. Sustained virological response rate was significantly lower for patients with hepatocellular carcinoma treatment (91%) than for patients without history of hepatocellular carcinoma treatment (98%, P = 0.004). One patient (0.4%) discontinued treatment due to drug-induced pneumonia. Dose reduction or interruption of ribavirin was required for 12.1% (32/265) of patients because of anemia, including 7.7% (14/182) of patients < 75-years-old and 21.7% (18/83) of patients ≥ 75-years-old (P = 0.002).
CONCLUSION Although ribavirin dose reduction or interruption was required with advanced age, sofosbuvir plus ribavirin appears tolerable and highly effective even in patients ≥ 75-years-old.
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Affiliation(s)
- Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Naoki Shingaki
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Yoshiyuki Ida
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Ryo Shimizu
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Shuya Maeshima
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama 6418509, Japan
| | - Junpei Okamura
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Akira Kawashima
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Taisei Nakao
- Department of Internal Medicine, Naga Municipal Hospital, Wakayama 6496414, Japan
| | - Takeshi Hara
- Department of Gastroenterology, Wakayama Rosai Hospital, Wakayama 6408505, Japan
| | - Hiroyoshi Matsutani
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
| | - Izumi Nishikawa
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
| | - Katsuhiko Higashi
- First Department of Internal Medicine, Hidaka General Hospital, Wakayama 6440002, Japan
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Ozeki I, Nakajima T, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y. Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc. J Clin Biochem Nutr 2020; 66:245-252. [PMID: 32523252 DOI: 10.3164/jcbn.19-98] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 12/04/2019] [Indexed: 12/20/2022] Open
Abstract
The recently approved direct-acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV-infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow-up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 µg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline-zinc <60 µg/dl (HR 6.283), EOT-serum zinc <63 µg/dl (HR 6.011), baseline-AFP ≥6.0 ng/dl (HR 8.163), and EOT-M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.
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Affiliation(s)
- Itaru Ozeki
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Masakatsu Yamaguchi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
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Negahdary M. Aptamers in nanostructure-based electrochemical biosensors for cardiac biomarkers and cancer biomarkers: A review. Biosens Bioelectron 2020; 152:112018. [PMID: 32056737 DOI: 10.1016/j.bios.2020.112018] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 12/16/2019] [Accepted: 01/09/2020] [Indexed: 01/01/2023]
Abstract
Heart disease (especially myocardial infarction (MI)) and cancer are major causes of death. Recently, aptasensors with the applying of different nanostructures have been able to provide new windows for the early and inexpensive detection of these deadly diseases. Early, inexpensive, and accurate diagnosis by portable devices, especially aptasensors can increase the likelihood of survival as well as significantly reduce the cost of treatment. In this review, recent studies based on the designed aptasensors for the diagnosis of these diseases were collected, ordered, and reviewed. The biomarkers for the diagnosis of each disease were discussed separately. The primary constituent elements of these aptasensors including, analyte, aptamer sequence, type of nanostructure, diagnostic technique, analyte detection range, and limit of detection (LOD), were evaluated and compared.
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Affiliation(s)
- Masoud Negahdary
- Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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20
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Association of Common Variants in HNF1A Gene with Serum AFP Level in Healthy Chinese Individuals and HCC Patients. DISEASE MARKERS 2020; 2019:6273497. [PMID: 31915469 PMCID: PMC6935455 DOI: 10.1155/2019/6273497] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 08/24/2019] [Accepted: 09/26/2019] [Indexed: 02/08/2023]
Abstract
Although alpha-fetoprotein (AFP) is a widely used tumor marker in hepatocellular carcinoma (HCC), 40% of newly diagnosed patients do not have an elevated AFP level. Research has revealed that mutations in the HNF1A binding site of the AFP gene promoter cause significantly elevated serum AFP levels in patients with hereditary persistence of AFP. This study investigated the relationship between HNF1A genetic variants and serum AFP levels. We examined the association between the HNF1A-rs1169288 (A/C), rs2464196 (G/A), and rs1169310 (C/T) polymorphisms and AFP levels in a healthy Chinese population (n = 1010) and HCC patients (n = 185). Single nucleotide polymorphisms were genotyped by the amplification refractory mutation system combined with TaqMan probe in real-time PCR. The serum AFP concentrations were measured using the Architect i2000 immunochemistry analyzer. In healthy individuals, serum AFP levels were significantly lower with the rs2464196-AA and rs1169310-TT genotypes. Similar significant differences were observed in HCC patients. Moreover, in HCC patients, the distribution frequencies of rs2464196-AA+AG and rs1169310-TT+TC among those with AFP ≤ 20 ng/ml or ≤400 ng/ml were significantly lower than those in patients with AFP > 20 ng/ml or >400 ng/ml. Among all subjects, those carrying the HNF1A-rs2464196-A or rs1169310-T allele tended to have low levels of AFP. However, the HNF1A-rs1169288 polymorphism showed no significant association with the serum AFP level. These findings provide new insight into the genetic determinants of serum AFP level and can aid the differential diagnosis of HCC patients with low serum AFP.
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21
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Manuc D, Preda CM, Sandra I, Baicus C, Cerban R, Constantinescu I, Olteanu AO, Ciora CA, Manuc T, Chiriac DE, Chifulescu AE, Diculescu M, Tieranu C, Negreanu L, Oprea-Calin G, Manuc M. Signification of Serum Alpha-Fetoprotein Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma. J Med Life 2020; 13:68-74. [PMID: 32341704 PMCID: PMC7175429 DOI: 10.25122/jml-2019-0076] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 12/24/2020] [Indexed: 02/06/2023] Open
Abstract
AFP (alpha-fetoprotein) levels are increased during the development of HCC (hepatocellular carcinoma); nonetheless, it can also be produced by non-tumoral hepatocytes in conditions of high cell turnover. Our study aims to provide additional data regarding the causes of elevated AFP in patients with liver cirrhosis due to hepatitis C virus (HCV) infection. We conducted an observational prospective cohort study that included 2068 patients with compensated cirrhosis and chronic hepatitis C genotype 1b infection. The two main inclusion criteria were the presence of advanced liver fibrosis - Metavir stage F4 - diagnosed by FibroMax testing, Fibroscan or liver biopsy, and the presence of detectable HCV RNA in the serum. Plasmatic AFP levels were determined through the electrochemiluminescence method, with a standard value ranging from 0 to 7 ng/ml. All data were obtained from the Romanian National Health Agency. The average AFP serum levels in patients with compensated cirrhosis without HCC were 9.4 ng/ml (range 0.5 ÷ 406 ng/ml); 30.1% of patients had significantly increased levels of AFP (>15 ng/ml). High values of serum AFP in patients with compensated liver cirrhosis without HCC was correlated with more advanced age (p<0.001), severe necroinflammatory activity detected by FibroMax (p<0.001), severe NASH (p<0.001), severe steatosis (p<0.001), low platelets (p<0.001), increased values of AST and ALT (p<0.001).
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Affiliation(s)
- Daniela Manuc
- Public Health Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Carmen Monica Preda
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Irina Sandra
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Cristian Baicus
- Internal Medicine Department, Colentina Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Razvan Cerban
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Ileana Constantinescu
- Immunogenetics Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Andrei Ovidiu Olteanu
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Cosmin Alexandru Ciora
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Teodora Manuc
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Daniela Elena Chiriac
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Andreea Elena Chifulescu
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Mircea Diculescu
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Cristian Tieranu
- Gastroenterology and Hepatology Department, Elias Emergency Hospital, Bucharest, Romania
| | - Lucian Negreanu
- Gastroenterology and Hepatology Department, Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Gabriela Oprea-Calin
- Gastroenterology and Hepatology Department, Emergency University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Mircea Manuc
- Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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22
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Hu CC, Weng CH, Hua MC, Chang PH, Lin CL, Chen YT, Chien CH, Lin ST, Chien RN. New Scoring Method to Predict Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C After Pegylated Interferon and Ribavirin Therapy. J Interferon Cytokine Res 2019; 40:82-91. [PMID: 31800346 DOI: 10.1089/jir.2019.0103] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Antiviral therapy for chronic hepatitis C (CHC) infection using pegylated interferon and ribavirin (PR) therapy can reduce the risk of hepatocellular carcinoma (HCC). Our study developed a new scoring method for predicting HCC risk after PR therapy. Between 2002 and 2016, 743 PR-treated patients with CHC were enrolled. Significant predictors for HCC were identified using multiple Cox regression analysis in study cohort: treatment age ≥60 years (hazard ratio [HR]: 2.04, 95% confidence interval [CI] = 1.3-3.7), pretreatment bilirubin ≥1.1 mg/dL (HR: 1.99, 95% CI = 1.08-3.67), α-fetoprotein ≥7.9 ng/mL (HR: 2.44, 95% CI = 1.16-5.32), no sustained virological response (SVR; HR: 1.91, 95% CI = 1.05-3.45), and baseline cirrhosis (HR: 4.45, 95% CI = 2.07-9.73). These predictors form the new HCC prediction scoring method with an area under the receiver operating characteristic curve of 0.884, sensitivity of 86.2%, and specificity of 74%. In patients with CHC and SVR, the cumulative incidence of HCC at 5 and 10 years was 16.7% and 30.4%, respectively, in patients with high risk scores and 1.2% and 4.2%, respectively, in patients with low risk scores (P < 0.001). Patients with SVR and high risk scores after viral eradication should remain under an intensive surveillance program for HCC. [Figure: see text].
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Affiliation(s)
- Ching-Chih Hu
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Hao Weng
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Nephrology and Poison Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Man-Chin Hua
- Department of Pediatrics, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Pei-Hung Chang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yen-Ting Chen
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Cheng-Hung Chien
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Shu-Ting Lin
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- Department of Hepatogastroenterology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Hepatogastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
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23
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Huynh T, Hu KQ. Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma. Front Med 2019; 13:658-666. [PMID: 31655955 DOI: 10.1007/s11684-019-0707-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/25/2019] [Indexed: 12/14/2022]
Abstract
Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12-213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (> 5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP > 5.5 was associated with the presence of cirrhosis (P =0.001), coexisting non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child-Pugh score < 6 (P = 0.015), and baseline AFP < 10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child-Pugh score < 6, and baseline AFP < 10.
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Affiliation(s)
- Tung Huynh
- Department of Pharmacy, University of California, Irvine, School of Medicine, Orange, CA, 92868, USA
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, CA, 92868, USA.
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24
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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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25
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Heiat M, Negahdary M. Sensitive diagnosis of alpha-fetoprotein by a label free nanoaptasensor designed by modified Au electrode with spindle-shaped gold nanostructure. Microchem J 2019. [DOI: 10.1016/j.microc.2019.05.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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26
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Elevated α-Fetoprotein in the Absence of Carcinoma Caused by Relapse of Hepatitis C Viral Infection after Liver Transplantation. ACG Case Rep J 2019; 5:e103. [PMID: 30643846 PMCID: PMC6317834 DOI: 10.14309/crj.2018.103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 11/07/2018] [Indexed: 01/31/2023] Open
Abstract
We report a rare case of marked elevation of α-fetoprotein in the absence of hepatocellular carcinoma caused by a relapse of hepatitis C virus (HCV) infection. A 58-year-old man underwent liver transplantation to treat hepatocellular carcinoma caused by HCV-related liver cirrhosis. The HCV was of genotype 2a, and the ribonucleic acid titer was >8.0 log IU/mL. Direct-acting antiviral drugs were prescribed for 12 weeks; however, the HCV infection relapsed after treatment had ended, and α-fetoprotein levels increased to 8,981 ng/mL. Imaging did not reveal any malignancies. The patient initiated interferon therapy, at which time AFP levels decreased, and the HCV was successfully cleared.
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27
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Spadaccini M, Lleo A, Ceriani R, Covini G, Rimassa L, Torzilli G, Di Tommaso L, Aghemo A. Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era. Hepatobiliary Pancreat Dis Int 2018; 17:570-574. [PMID: 30420319 DOI: 10.1016/j.hbpd.2018.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 10/24/2018] [Indexed: 02/06/2023]
Affiliation(s)
- Marco Spadaccini
- Internal Medicine and Liver Unit, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Ana Lleo
- Internal Medicine and Liver Unit, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Roberto Ceriani
- Internal Medicine and Liver Unit, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Giovanni Covini
- Internal Medicine and Liver Unit, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Pathology Unit, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessio Aghemo
- Internal Medicine and Liver Unit, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
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28
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Masetti C, Lionetti R, Lupo M, Siciliano M, Giannelli V, Ponziani FR, Teti E, Dell'Unto C, Francioso S, Brega A, Montalbano M, Visco-Comandini U, Taibi C, Galati G, Vespasiani Gentilucci U, Picardi A, Andreoni M, Pompili M, Pellicelli AM, D'Offizi G, Gasbarrini A, De Santis A, Angelico M. Lack of reduction in serum alpha-fetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with hepatitis C virus-related cirrhosis. J Viral Hepat 2018; 25:1493-1500. [PMID: 30112854 DOI: 10.1111/jvh.12982] [Citation(s) in RCA: 3] [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: 04/09/2018] [Revised: 06/07/2018] [Accepted: 06/23/2018] [Indexed: 12/22/2022]
Abstract
Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct-acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow-up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan-Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end-stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment.
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Affiliation(s)
- Chiara Masetti
- Liver and Transplant Unit, Tor Vergata University Hospital, Rome, Italy
| | - Raffaella Lionetti
- Infectious Diseases-Hepatology, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | - Marinella Lupo
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
| | | | - Valerio Giannelli
- Liver Disease Unit, Department of Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | | | - Elisabetta Teti
- Department of Infectious Disease, Tor Vergata University Hospital, Rome, Italy
| | - Chiara Dell'Unto
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
| | - Simona Francioso
- Liver and Transplant Unit, Tor Vergata University Hospital, Rome, Italy
| | - Arianna Brega
- Liver and Transplant Unit, Tor Vergata University Hospital, Rome, Italy
| | - Marzia Montalbano
- Infectious Diseases-Hepatology, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | - Ubaldo Visco-Comandini
- Infectious Diseases-Hepatology, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | - Chiara Taibi
- Infectious Diseases-Hepatology, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | - Giovanni Galati
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
| | | | - Antonio Picardi
- Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy
| | - Massimo Andreoni
- Department of Infectious Disease, Tor Vergata University Hospital, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine, Gastroenterology and Hepatology, A. Gemelli Hospital, Rome, Italy
| | - Adriano M Pellicelli
- Liver Disease Unit, Department of Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Gianpiero D'Offizi
- Infectious Diseases-Hepatology, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | | | - Adriano De Santis
- Department of Clinical Medicine, Gastroenterology Unit, Sapienza University of Rome, Rome, Italy
| | - Mario Angelico
- Liver and Transplant Unit, Tor Vergata University Hospital, Rome, Italy
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29
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Canale M, Ulivi P, Foschi FG, Scarpi E, De Matteis S, Donati G, Ercolani G, Scartozzi M, Faloppi L, Passardi A, Tamburini E, Valgiusti M, Marisi G, Frassineti GL, Casadei Gardini A. Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma. Crit Rev Oncol Hematol 2018; 129:44-53. [PMID: 30097237 DOI: 10.1016/j.critrevonc.2018.06.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 06/08/2018] [Accepted: 06/19/2018] [Indexed: 02/08/2023] Open
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30
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Malik A, Arooj M, Butt TT, Zahid S, Zahid F, Jafar TH, Waquar S, Gan SH, Ahmad S, Mirza MU. In silico and in vivo characterization of cabralealactone, solasodin and salvadorin in a rat model: potential anti-inflammatory agents. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:1431-1443. [PMID: 29872266 PMCID: PMC5973396 DOI: 10.2147/dddt.s154169] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Background The present study investigates the hepato- and DNA-protective effects of standardized extracts of Cleome brachycarpa (cabralealactone), Solanum incanum (solasodin), and Salvadora oleioides (salvadorin) in rats. Materials and methods Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied. Results Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents. Conclusion Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects.
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Affiliation(s)
- Arif Malik
- Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan
| | - Mahwish Arooj
- University College of Medicine and Dentistry (UCMD), University of Lahore, Lahore, Pakistan
| | | | - Sara Zahid
- Faculty of Pharmacy, University of Lahore, Lahore, Pakistan
| | - Fatima Zahid
- Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan
| | - Tassadaq Hussain Jafar
- Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan
| | - Sulayman Waquar
- Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan
| | - Siew Hua Gan
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| | - Sarfraz Ahmad
- Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore, Lahore, Pakistan
| | - Muhammad Usman Mirza
- Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, Medicinal Chemistry, University of Leuven, Leuven, Belgium
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Gamil M, Alboraie M, El-Sayed M, Elsharkawy A, Asem N, Elbaz T, Mohey M, Abbas B, Mehrez M, Esmat G. Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients. J Med Virol 2018; 90:1080-1086. [PMID: 29315641 DOI: 10.1002/jmv.25026] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 12/09/2017] [Accepted: 12/10/2017] [Indexed: 12/25/2022]
Abstract
Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis.
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Affiliation(s)
- Mohamed Gamil
- National Hepatology and Tropical Medicine Research institute, Cairo, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo, Egypt
| | - Mohammad El-Sayed
- Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt
| | - Aisha Elsharkawy
- Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt
| | - Noha Asem
- Department of Public Health and Community Medicine, Cairo University, Cairo, Egypt
| | - Tamer Elbaz
- Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt
| | - Mohammad Mohey
- Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt
| | | | - Mai Mehrez
- National Hepatology and Tropical Medicine Research institute, Cairo, Egypt
| | - Gamal Esmat
- Department of Endemic Medicine and Hepatology, Cairo University, Cairo, Egypt
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32
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Xia P, He H, Kristine MS, Guan W, Gao J, Wang Z, Hu J, Han L, Li J, Han W, Yu Y. Therapeutic effects of recombinant human S100A6 and soluble receptor for advanced glycation end products(sRAGE) on CCl 4-induced liver fibrosis in mice. Eur J Pharmacol 2018; 833:86-93. [PMID: 29800549 DOI: 10.1016/j.ejphar.2018.05.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 05/08/2018] [Accepted: 05/18/2018] [Indexed: 01/08/2023]
Abstract
Hepatic fibrosis is a pathological process in which extracellular matrix excessively aggregates in an injured liver. Research on hepatic fibrosis is expanding, however, much information in this process is still unclear. Here, we examined the gene expression changes within the process of liver fibrosis, providing the first evidence that secreted S100A6 is a critical contributor. We discovered that expression of the S100 family is highly correlated with CCl4-induced liver fibrosis and post self-recovery in mice. Recombinant human S100A6 (rhS100A6) introduced to CCl4-induced mice was found to enhance liver fibrosis through the promotion of activated hepatic stellate cell (HSC) proliferation. More importantly, we showed that rhS100A6 can induce cell cycle transition from S to G2 stage and significantly elevate the level of ERK phosphorylation in the MARK pathway. In contrast to rhS100A6, recombinant human and soluble receptor for advanced glycation end products (sRAGE), a natural antagonist of the S100/RAGE pathway, was found to have a preventative effect on liver fibrosis in CCl4-induced mice. In conclusion, our study supports that S100A6 could be a novel therapeutic in liver fibrosis and its receptor antagonist, sRAGE, proofed to be effective for the treatment of liver fibrosis.
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Affiliation(s)
- Peng Xia
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China; Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, PBS 323, 205 E. Spokane Falls Blvd., P.O. Box 1495, Spokane, WA 99210-1495, USA
| | - Honglin He
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Modrak Samantha Kristine
- Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, PBS 323, 205 E. Spokane Falls Blvd., P.O. Box 1495, Spokane, WA 99210-1495, USA
| | - Wen Guan
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Jin Gao
- Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Zhen Wang
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Jianjun Hu
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China
| | - Lei Han
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Jinjing Li
- Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China
| | - Wei Han
- Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
| | - Yan Yu
- Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
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Hu CC, Weng CH, Chang LC, Lin CL, Chen YT, Hu CF, Hua MC, Chen LW, Chien RN. Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy. Ther Clin Risk Manag 2018; 14:783-791. [PMID: 29750037 PMCID: PMC5933468 DOI: 10.2147/tcrm.s158424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Purpose Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9–12.6 years). Results The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390–4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420–4.871, P=0.002), pretreatment platelet counts <146.5 × 103/μL (HR: 2.751, 95% CI: 1.373–5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277–4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283–7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). Conclusion The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.
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Affiliation(s)
- Ching-Chih Hu
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Cheng-Hao Weng
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Liang-Che Chang
- Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Yen-Ting Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Fang Hu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Man-Chin Hua
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Li-Wei Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan
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Qin J, Yang L, Sheng X, Sa Z, Huang T, Li Q, Gao K, Chen Q, Ma J, Shen H. Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo. Oncol Lett 2018; 15:6137-6146. [PMID: 29731843 PMCID: PMC5920962 DOI: 10.3892/ol.2018.8168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Accepted: 10/12/2017] [Indexed: 12/29/2022] Open
Abstract
In vitro and in vivo studies have demonstrated that brucine is able to inhibit the proliferation of liver cancer cells and growth of animal tumors, and may be a promising anticancer drug. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, and similar therapeutic and toxic doses limit its clinical application in the treatment of malignant tumors. In our previous study, brucine immuno-nanoparticles were successfully prepared and added to the culture medium of liver cancer SMMC-7721 cells, and the results indicated that the brucine immuno-nanoparticles were able to target the cell membrane of liver cancer SMMC-7721 cells and significantly inhibit the proliferation, adhesion, invasion and metastasis of SMMC-7721 cells. The aim of the present study was to investigate the antitumor effect of brucine immuno-nanoparticles in vivo by establishing an in situ transplanted liver cancer in nude mice. The results indicated that in vivo application of the brucine immuno-nanoparticles resulted in temporary liver and kidney damage, and significantly reduced the α-fetoprotein (AFP) secretion of tumor cells (Bru-NP-MAb vs. the other groups; P<0.05). The brucine concentration of tumor tissues in the brucine immuno-nanoparticles group was significantly increased compared with that of the brucine nanoparticles group (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). The brucine immuno-nanoparticles were able to inhibit tumor growth and cluster of differentiation 34 expression and angiogenesis of tumor tissues, and induce the apoptosis of tumor cells (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). In conclusion, as a novel type of targeted drug, brucine nanoparticles combined with anti-AFP monoclonal antibodies was more effective compared with brucine nanoparticles or brucine alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis in vivo. Therefore, the brucine immuno-nanoparticle is a promising targeted drug for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Jianmin Qin
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China.,Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Lin Yang
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Xia Sheng
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Zhongqiu Sa
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China.,Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Tao Huang
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Qi Li
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Kepan Gao
- National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, P.R. China
| | - Qinghua Chen
- National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, P.R. China
| | - Jingwei Ma
- Department of Physical Chemistry, Shanghai Normal University, Shanghai 200234, P.R. China
| | - Hebai Shen
- Department of Physical Chemistry, Shanghai Normal University, Shanghai 200234, P.R. China
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Tsukamoto M, Nitta H, Imai K, Higashi T, Nakagawa S, Okabe H, Arima K, Kaida T, Taki K, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H. Clinical significance of half-lives of tumor markers α-fetoprotein and des-γ-carboxy prothrombin after hepatectomy for hepatocellular carcinoma. Hepatol Res 2018; 48:E183-E193. [PMID: 28796412 DOI: 10.1111/hepr.12942] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 08/01/2017] [Accepted: 08/04/2017] [Indexed: 12/13/2022]
Abstract
AIM The prognostic significance of the half-lives (HLs) of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients. METHODS This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post-hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis. RESULTS Three-year recurrence-free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five-year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07). CONCLUSION Post-hepatectomy HLs of AFP and DCP are predictors of long-term outcome in patients with HCC.
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Affiliation(s)
- Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kota Arima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunobu Taki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Toru Beppu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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Elevated a-Fetoprotein in the Absence of Carcinoma Caused by Relapse of Hepatitis C Viral Infection after Liver Transplantation. ACG Case Rep J 2018. [DOI: 10.14309/02075970-201805120-00019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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37
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Elevated a-Fetoprotein in the Absence of Carcinoma Caused by Relapse of Hepatitis C Viral Infection after Liver Transplantation. ACG Case Rep J 2018. [DOI: 10.14309/02075970-201805000-00103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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38
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Precision diagnosis and treatment of liver cancer in China. Cancer Lett 2018; 412:283-288. [DOI: 10.1016/j.canlet.2017.10.008] [Citation(s) in RCA: 220] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 10/09/2017] [Accepted: 10/09/2017] [Indexed: 02/06/2023]
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Lee MH, Huang CF, Lai HC, Lin CY, Dai CY, Liu CJ, Wang JH, Huang JF, Su WP, Yang HC, Kee KM, Yeh ML, Chuang PH, Hsu SJ, Huang CI, Kao JT, Chen CC, Chen SH, Jeng WJ, Yang HI, Yuan Y, Lu SN, Sheen IS, Liu CH, Peng CY, Kao JH, Yu ML, Chuang WL, Chen CJ. Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients. Sci Rep 2017; 7:3718. [PMID: 28623331 PMCID: PMC5473811 DOI: 10.1038/s41598-017-02313-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 04/10/2017] [Indexed: 12/23/2022] Open
Abstract
This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004-2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22-0.63) for those without cirrhosis and 0.54 (0.31-0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Shih-Jer Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jung-Ta Kao
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Juei Jeng
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
- School of Traditional Chinese Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol Myers-Squibb, Princeton, NJ, USA
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan
- College of Medicine, Chang Guang University, Kweishan, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan
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Zayed RA, Omran D, Mokhtar DA, Zakaria Z, Ezzat S, Soliman MA, Mobarak L, El-Sweesy H, Emam G. Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients. Am J Trop Med Hyg 2017; 96:720-726. [PMID: 28093541 DOI: 10.4269/ajtmh.16-0644] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls. Genotyping of TLR-3 (_7 C/A [rs3775296]), TLR-3 (c.1377C/T [rs3775290]) and TLR-9 (1237T/C [rs5743836]) were done by polymerase chain reaction restriction fragment length polymorphism technique. Frequency of polymorphic genotypes in TLR-3 (_7 C/A), TLR-3 (c.1377C/T) and TLR-9 (1237T/C) were not significantly different between studied HCV-positive patients and controls with P values 0.121, 0.112, and 0.683, respectively. TLR-3 c.1377 T-allele was associated with advanced stage of hepatic fibrosis (P = 0.003).
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Affiliation(s)
- Rania A Zayed
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dalia Omran
- Department of Endemic Medicine and Hepato-gastroentrology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Doha A Mokhtar
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Zinab Zakaria
- Department of Endemic Medicine and Hepato-gastroentrology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Sameera Ezzat
- Community Medicine Department, National Liver Institute, Menofia University, Menofia, Egypt
| | - Mohamed A Soliman
- Specialized Liver Unit, Kasr Alainy Hospital, Cairo University, Cairo, Egypt
| | - Lamiaa Mobarak
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Hossam El-Sweesy
- Tropical Medicine Department, Cairo Fatemic Hospital, Ministry of Health, Cairo, Egypt
| | - Ghada Emam
- Clinical Pathology Department, National Institute of Neuromotor System, Cairo, Egypt
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Ko YS, Bae JH, Sinn DH, Gwak GY, Kang W, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. The Clinical Significance of Serum Alpha-fetoprotein in Diagnosing Hepatocellular Carcinoma in a Health Screening Population. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 69:232-238. [DOI: 10.4166/kjg.2017.69.4.232] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Young Sun Ko
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joo Hwan Bae
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wonseok Kang
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein. Int J Mol Sci 2016; 17:ijms17122143. [PMID: 27999409 PMCID: PMC5187943 DOI: 10.3390/ijms17122143] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 11/30/2016] [Accepted: 12/14/2016] [Indexed: 01/06/2023] Open
Abstract
We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA+-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA+-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA+-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA+-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA+-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA+-M2BP level is a useful predictor for HCC development after achieving SVR.
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Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B. PLoS One 2016; 11:e0168189. [PMID: 27997559 PMCID: PMC5172583 DOI: 10.1371/journal.pone.0168189] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 11/29/2016] [Indexed: 12/21/2022] Open
Abstract
Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance.
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Sanda M, Benicky J, Wu J, Wang Y, Makambi K, Ahn J, Smith CI, Zhao P, Zhang L, Goldman R. Increased sialylation of site specific O-glycoforms of hemopexin in liver disease. Clin Proteomics 2016; 13:24. [PMID: 27688741 PMCID: PMC5034550 DOI: 10.1186/s12014-016-9125-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Accepted: 09/16/2016] [Indexed: 02/07/2023] Open
Abstract
Background Non-invasive monitoring of liver disease remains an important health issue. Liver secreted glycoproteins reflect pathophysiological states of the organ and represent a rational target for serologic monitoring. In this study, we describe sialylated O-glycoforms of liver-secreted hemopexin (HPX) and quantify them as a ratio of disialylated to monosialylated form (S-HPX). Methods We measured S-HPX in serum of participants of the HALT-C trial using a LC–MS/MS-MRM assay. Results Repeated measurements of S-HPX in the samples of 23 disease-free controls, collected at four different time points, show that the ratio remains stable in the healthy controls but increases with the progression of liver disease. The results of measurement of S-HPX in serum of participants of the HALT-C trial show that it increased significantly (Kruskal–Wallis test, p < 0.01) in liver disease as the stage of fibrosis progressed in liver biopsies. We observed a 1.7-fold increase in fibrosis defined as Ishak score 3–4 (24.9 + 14.2, n = 22) and 4.7-fold increase in cirrhosis defined as Ishak score 5–6 (68.6 + 38.5; n = 24) compared to disease-free controls (14.7 + 6.7, n = 23). S-HPX is correlated with AFP, bilirubin, INR, ALT, and AST while inversely correlated with platelet count and albumin. In an independent verification set of samples, S-HPX separated the Ishak 5–6 (n = 15) from the Ishak 3–4 (n = 15) participants with AuROC 0.84; at the same time, the Ishak 3–4 group was separated from disease-free controls (n = 15) with AuROC 0.82. Conclusion S-HPX, a measure of sialylated O-glycoforms of hemopexin, progressively increases in fibrotic and cirrhotic patient of HCV etiology and can be quantified by an LC–MS/MS-MRM assay in unfractionated serum of patients. Quantification of sialylated O-glycoforms of this liver secreted glycoprotein represents a novel measure of the stage of liver disease that could have a role in monitoring the progression of liver pathology. Electronic supplementary material The online version of this article (doi:10.1186/s12014-016-9125-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Miloslav Sanda
- Department of Oncology, Georgetown University, PS Room GD11, 3800 Reservoir Rd NW, Washington, DC 20057 USA
| | - Julius Benicky
- Department of Oncology, Georgetown University, NRB Room E207, 3970 Reservoir Rd NW, Washington, DC 20057 USA
| | - Jing Wu
- Department of Oncology, Georgetown University, NRB Room E207, 3970 Reservoir Rd NW, Washington, DC 20057 USA
| | - Yiwen Wang
- Department of Oncology, Georgetown University, NRB Room E207, 3970 Reservoir Rd NW, Washington, DC 20057 USA
| | - Kepher Makambi
- Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Building D Suite 180 Room 185, 4000 Reservoir Rd NW, Washington, DC 20057 USA
| | - Jaeil Ahn
- Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Basic Science Building D Room 255, 3900 Reservoir Rd NW, Washington, DC 20057 USA
| | - Coleman I Smith
- MedStar Georgetown University Transplant Institute, 2-PHC, 3800 Reservoir Rd NW, Washington, DC 20057 USA
| | - Peng Zhao
- Complex Carbohydrate Research Center, University of Georgia, Athens, GA USA
| | - Lihua Zhang
- Department of Oncology, Georgetown University, PS Room GD11, 3800 Reservoir Rd NW, Washington, DC 20057 USA
| | - Radoslav Goldman
- Department of Oncology, Georgetown University, NRB Room E207, 3970 Reservoir Rd NW, Washington, DC 20057 USA
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A Chemiluminescent Protein Microarray Method for Determining the Seroglycoid Fucosylation Index. Sci Rep 2016; 6:31132. [PMID: 27528397 PMCID: PMC4985809 DOI: 10.1038/srep31132] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 07/13/2016] [Indexed: 12/21/2022] Open
Abstract
The Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) is widely used to screen for hepatocellular carcinoma (HCC) in Japan and China. We developed a chemiluminescent protein microarray for determining the AFP-L3/AFP index (the ratio of AFP-L3 to total AFP, AFP-L3%) by fixing AFP-specific antibodies and Lens culinaris lectin on aldehyde-coated glass slides. Serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA) to validate the microarray. AFP-L3 was detected using Hotgen Biotech glycosyl capture spin column pretreatment technology and ELISA. When the AFP cut-off value was set to 20 ng/ml, the protein microarray displayed 89.74% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 87.17% sensitivity and 100% specificity. When the AFP-L3% cut-off value was set to 0.1, the protein microarray displayed 56.41% sensitivity and 100% specificity for HCC diagnosis, and the ELISA displayed 53.84% sensitivity and 100% specificity. The ROC curve for the HCC diagnosis showed that the AFP area under the ROC curve (AUC = 0.996; 95% CI: 0.986-1.005) was much higher than that of AFP-L3 (AUC = 0.857; 95% CI: 0.769-0.94) and AFP-L3% (AUC = 0.827; CI: 0.730-0.924). The microarray assay used in this study is a highly sensitive, accurate, and efficient assay for the determination of the AFP-L3%.
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Jin J, Niu X, Zou L, Li L, Li S, Han J, Zhang P, Song J, Xiao F. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis. Cancer Lett 2016; 378:33-7. [PMID: 27160647 DOI: 10.1016/j.canlet.2016.04.033] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 04/20/2016] [Accepted: 04/21/2016] [Indexed: 01/28/2023]
Abstract
Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis.
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Affiliation(s)
- Junhua Jin
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing, China
| | - Xiaojuan Niu
- Department of Surgery, Beijing Hospital, Beijing, China
| | - Lihui Zou
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing, China
| | - Lin Li
- Department of Oncology, Beijing Hospital, Beijing, China
| | - Shugang Li
- Xuzhou Central Hospital, Affiliated Hospital of Medical College of Southeast University, Nanjing, China
| | - Jingli Han
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing, China
| | - Peiying Zhang
- Xuzhou Central Hospital, Affiliated Hospital of Medical College of Southeast University, Nanjing, China
| | - Jinghai Song
- Department of Surgery, Beijing Hospital, Beijing, China.
| | - Fei Xiao
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing, China.
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Lee S, Rhim H, Kim YS, Kang TW, Song KD. Post-ablation des-gamma-carboxy prothrombin level predicts prognosis in hepatitis B-related hepatocellular carcinoma. Liver Int 2016; 36:580-7. [PMID: 26503910 DOI: 10.1111/liv.12991] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 10/13/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS We investigated whether pre- or post-ablation serum alpha-foetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels can predict prognosis in patients with curative radiofrequency ablation (RFA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS We retrospectively analysed 412 patients with HBV-related single HCC treated with percutaneous RFA between January 2004 and December 2013. AFP and DCP levels were measured before (pre-ablation) and 1 month after treatment (post-ablation). We assessed predictive factors for overall and recurrence-free survival. RESULTS On univariate analysis, Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, platelet count, tumour size, Barcelona Clinic Liver Cancer (BCLC) stage, and pre- and post-ablation DCP were significant for overall survival; and age, Child-Pugh score, MELD score, platelet count, tumour size, Cancer of the Liver Italian Program (CLIP) score, BCLC stage, and pre- and post-ablation AFP and DCP were significant for recurrence-free survival. Multivariate analysis revealed significant differences in overall survival by MELD score and tumour size and in recurrence-free survival by BCLC stage. Among the tumour markers, post-ablation DCP was an independent prognostic factor for overall and recurrence-free survival [hazard ratio (HR), 3.438; 95% confidence interval (CI), 1.331-8.877; P = 0.011 and HR, 4.934; 95% CI, 2.761-8.816; P < 0.001 respectively]. Post-ablation AFP was associated with recurrence-free survival (HR, 1.995; 95% CI, 1.476-2.697; P < 0.001) but not overall survival. CONCLUSIONS In patients with HBV-related HCC, post-ablation serum DCP is a useful biomarker for predicting survival and recurrence after curative RFA.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyunchul Rhim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-sun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyoung Doo Song
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abdel-Razik A, Mousa N, Abdel-Aziz M, Elhelaly R, Elzehery R, Zalata K, Elkashef W, Fouda O, Awad M, Hafez M, Eldars W. Elevated serum α-fetoprotein levels in patients with chronic hepatitis C virus genotype 4: not the end of the story. Eur J Gastroenterol Hepatol 2016; 28:313-322. [PMID: 26618566 DOI: 10.1097/meg.0000000000000534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Elevated serum α-fetoprotein (AFP) is not uncommonly seen among patients with chronic hepatitis C. This study aimed to identify clinical characteristics, histological characteristics, and biochemical markers associated with increased serum AFP levels in hepatitis C virus genotype 4-infected patients with no evidence of hepatocellular carcinoma and to determine the effect of lifestyle modification on these parameters. METHODS The study included 447 chronic hepatitis C patients with no evidence of hepatocellular carcinoma and 100 healthy controls. They underwent liver biopsies, homeostasis model assessment-insulin resistance (HOMA-IR), measurement of serum insulin, leptin, adiponectin, tumor necrosis factor-α, and interleukin-6 levels by an enzyme-linked immunosorbent assay, and assessment of AFP levels. Eighty patients with HOMA-IR greater than 3 received prospective longitudinal lifestyle intervention. RESULTS In a multivariate analysis, platelet count less than 140×10/cm, a mean platelet volume of at least 9.5 fl, a neutrophil-lymphocyte ratio (NLR) of at least 2, an aspartate transaminase level of at least 55 IU/l, a γ-glutamyl transpeptidase level of at least 40 IU/l, an albumin level of up to 3.8 g/dl, HOMA-IR greater than 3, a leptin level of at least 10 pg/ml, an iron level of at least 165 μg/dl, a ferritin level of at level 175 ng/ml, and hepatic fibrosis F3-F4 were found to be independently associated with elevated AFP levels. The lifestyle intervention significantly improved BMI, platelet indices, NLR, γ-glutamyl transpeptidase, leptin, leptin/adiponectin ratio, tumor necrosis factor-α, interleukin-6, HOMA-IR, and AFP levels. CONCLUSION Elevated insulin resistance, leptin, serum iron, ferritin, mean platelet volume, NLR, and advanced fibrosis, as well as decreased platelet count and serum albumin, are independently associated with an elevated AFP level. Lifestyle modification can improve (reduce) insulin resistance, leptin, leptin/adiponectin ratio, platelet count and their indices, NLR, and AFP level.
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Affiliation(s)
- Ahmed Abdel-Razik
- Departments of aTropical Medicine, Faculty of Medicine bClinical Pathology cPathology dInternal Medicine eMedical Microbiology and Immunology, Mansoura University, Mansoura fDepartment of Internal Medicine, Aswan University, Aswan, Egypt
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Khedr MA, Sira AM, Saber MA, Raia GY. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response? Int J Hepatol 2015; 2015:617623. [PMID: 26640716 PMCID: PMC4657070 DOI: 10.1155/2015/617623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/23/2015] [Accepted: 10/25/2015] [Indexed: 02/06/2023] Open
Abstract
Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.
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Affiliation(s)
- Mohamed Ahmed Khedr
- Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Ahmad Mohamed Sira
- Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Magdy Anwar Saber
- Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
| | - Gamal Yousef Raia
- Department of Clinical Pathology, National Liver Institute, Menofiya University, Shebin El-koom, Menofiya 32511, Egypt
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Tong MJ, Huynh TT, Siripongsakun S, Chang PW, Tong LT, Ha YP, Mena EA, Weissman MF. Predicting clinical outcomes in patients with HBsAg-positive chronic hepatitis. Hepatol Int 2015. [PMID: 26219830 DOI: 10.1007/s12072-015-9651-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS The progression of HBsAg-positive chronic hepatitis is insidious and unpredictable. Identification of factors leading to either a benign or more serious clinical outcome may assist in decision making for antiviral therapy. METHODS From 1989 to 1998, 130 untreated patients with chronic hepatitis were enrolled in a prospective study and followed every 3-6 months with liver and virologic tests, platelet counts and alpha-fetoprotein (AFP) measurements. RESULTS During a mean follow-up of 107 ± 86 months, 16 (12.3 %) chronic hepatitis patients progressed to cirrhosis (annual rate 1.4 %), and 23 (17.7 %) reverted to being inactive carriers (annual rate 2.1 %). Compared to baseline values, chronic hepatitis patients who progressed to cirrhosis exhibited declines in mean platelet counts (225.7-195.2 mm(3), p = 0.008-0.04) during the first 4 years of follow-up, while those who reverted to being inactive carriers had substantial reductions in mean levels of AST (83.5-27.2 u/l, p < 0.001-0.002) and ALT (100.2-29.2 u/l, p < 0.001-0.007). In addition, during spontaneous alanine aminotransferase (ALT) flares, patients progressing to cirrhosis had concomitant elevations of AFP levels, while patients who became inactive carriers maintained normal AFP values during ALT flares (13.45 vs. 4.65 ng/ml, p = 0.001). These AFP differences during episodes of ALT flares were similarly observed when analyzed in two separate cohorts of cirrhosis and inactive carrier patients. CONCLUSION Patients with chronic hepatitis who progressed to cirrhosis exhibited declines in platelet counts and had AFP elevations during ALT flares. To prevent progression, serial measurements of these parameters during the chronic hepatitis stage will assist in identifying patients requiring antiviral therapy.
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Affiliation(s)
- Myron John Tong
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA.
- Division of Digestive Diseases, The Pfleger Liver Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
| | - Thatcher Thi Huynh
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
| | - Surachate Siripongsakun
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA.
- Division of Digestive Diseases, The Pfleger Liver Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
- Chulabhorn Hospital, Bangkok, Thailand.
| | - Patrick Weijen Chang
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
| | - Lori Terese Tong
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
| | - Yen Phi Ha
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
| | - Edward Alphonso Mena
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
| | - Matthew Frank Weissman
- Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA
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