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Lu K, Sui J, Yu W, Chen Y, Hou Z, Li P, Sun Y. An analysis of the burden of liver cirrhosis: Differences between the global, China, the United States and India. Liver Int 2024; 44:3183-3203. [PMID: 39287155 DOI: 10.1111/liv.16087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 07/15/2024] [Accepted: 08/19/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND Cirrhosis continues to be the most common cause of chronic liver disease-related deaths globally, which puts significant strain on global health. This report aims to investigate the patterns of cirrhosis in China, the United States, India and worldwide from 1990 to 2019 through an epidemiological analysis of the disease utilizing data from the Global Burden of Disease Study (GBD) 2019 database. METHODS Download the GBD database's statistics on liver cirrhosis deaths and Disability-Adjusted Life Years for the years 1990-2019 worldwide as well as for China, the United States and India. Utilize techniques like age-period-cohort interaction, decomposition analysis, study of health inequities, Joinpoint model and Bayesian Average Annual Percentage Change model to process the data. RESULTS The main age group affected by cirrhosis disease, according to the results, is 50-69 years old. According to the Joinpoint model, there has been a negative worldwide Average Annual Percent Change (AAPC) in the burden of cirrhosis between 1990 and 2019. Only the USA's AAPC is positive out of the three nations that were evaluated (albeit its 95% confidence interval spans 0). These are China, India and the United States. Forecasting models indicate that the prevalence of cirrhosis will keep rising in the absence of government action. According to decomposition analysis, the main factors contributing to the rising burden of cirrhosis are population ageing and size, whereas changes in the disease's epidemiology slow the disease's growth. Research on health disparities indicates that, between 1990 and 2019, there was a downward trend in health disparities between various locations. CONCLUSION Health organizations across different areas should take aggressive measures to address the worrisome prevalence of cirrhosis.
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Affiliation(s)
- Keqiang Lu
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
| | - Juanjuan Sui
- Department of Infectious Disease, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, P.R. China
| | - Wenhui Yu
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, P.R. China
| | - Yan Chen
- Department of Nursing, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, P.R. China
| | - Zhiyong Hou
- China Academy of Chinese Medical Sciences, Institute of Basic Research in Clinical Medicine, Beijing, P.R. China
| | - Pengyan Li
- Department of Infectious Disease, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, P.R. China
| | - Yuli Sun
- Department of Hepatobiliary Internal Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P.R. China
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Suzuki T, Matsuura K, Nagura Y, Ito K, Ogawa S, Kawamura H, Fujiwara K, Nagaoka K, Iio E, Watanabe T, Kataoka H, Tanaka Y. MicroRNA-223-3p levels in serum-derived extracellular vesicles predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents. J Gastroenterol 2024; 59:719-731. [PMID: 38739200 DOI: 10.1007/s00535-024-02115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/02/2024] [Indexed: 05/14/2024]
Abstract
BACKGROUND We retrospectively investigated microRNA (miRNA) levels in serum-derived extracellular vesicles (EVs) as predictive indicators for regression of liver fibrosis, after achievement of a sustained virological response (SVR) by direct-acting antiviral (DAA) therapy for chronic hepatitis C (CHC). METHODS The study subjects were recruited from a historical cohort of 108 CHC patients whose pretreatment serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels were ≥ 2.0 cut-off index (COI). We classified patients with M2BPGi levels < 1.76 and ≥ 1.76 COI at 2 years after the end of treatment (EOT) into the regression and non-regression groups, respectively. Eleven of the patients were assigned to the discovery set, and we comprehensively investigated the miRNAs contained in serum-derived EVs at 24 weeks after the EOT (EOT24W), using RNA sequencing. The remaining 97 patients were assigned to the validation set, and reproducibility was verified by quantitative real-time PCR. RESULTS Through analysis of the discovery and validation sets, we identified miR-223-3p and miR-1290 as candidate predictors. Subsequently, we analyzed various clinical data, including these candidate miRNAs. Multivariate analyses revealed that the levels of miR-223-3p at EOT24W were significantly associated with regression of M2BPGi-based liver fibrosis (Odds ratio: 1.380; P = 0.024). Consistent results were obtained, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis (pretreatment M2BPGi levels ≥ 3.3 COI). CONCLUSIONS The miR-223-3p level in serum-derived EVs at EOT24W is a feasible predictor of regression of M2BPGi-based liver fibrosis after achievement of an SVR by DAA therapy.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan.
| | - Yoshihito Nagura
- Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Kyoko Ito
- Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Katsuya Nagaoka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho, Nagoya, Aichi, 467-8601, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Suzuki T, Matsuura K, Nagura Y, Kawamura H, Fujiwara K, Ogawa S, Nagaoka K, Iio E, Watanabe T, Kataoka H, Tanaka Y. Serum Angiopoietin-2 Levels Predict the Development of Hepatocellular Carcinoma following Hepatitis C Virus Eradication Using Direct-Acting Antiviral Agents. Oncology 2024; 102:611-620. [PMID: 38211572 DOI: 10.1159/000536154] [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: 12/08/2023] [Accepted: 12/31/2023] [Indexed: 01/13/2024]
Abstract
INTRODUCTION Our previous studies showed that serum angiopoietin-2 (Ang-2) and C-X-C motif chemokine ligand 10 (CXCL10) levels predicted improvement in liver fibrosis following sustained virological response (SVR) of hepatitis C virus (HCV) obtained with administration of with direct-acting antiviral agents (DAAs). These levels were evaluated retrospectively as predictive indicators of hepatocellular carcinoma (HCC) development following SVR. METHODS We enrolled individuals from a historical cohort of 89 chronic HCV patients without history of HCC at baseline and with SVR following DAA therapy and had baseline serum levels of Mac-2 binding protein glycosylation isomer ≥2.0 cut-off index (C.O.I.). RESULTS Multivariate analyses revealed that only the Ang-2 level at 24 weeks following the end of treatment (EOT24W) was significantly related to HCC development (hazard ratio 2.27; p = 0.003). This result was reproduced in individuals without history of HCC and with advanced liver fibrosis (M2BPGi level ≥3.3 C.O.I. at baseline). Time-dependent receiver operating characteristic curve analyses for the future risk of developing HCC within 5 years of follow-up (5y-HCC) showed the best cut-off Ang-2 level at the EOT24W was 2,780 pg/mL, and significantly stratified the cumulative incidence of HCC (≥2,780 vs. < 2,780 pg/mL, 5y-HCC: 45.5 vs. 8.2%, p < 0.001). CONCLUSIONS At the EOT24W, serum Ang-2 level predicts the likelihood of developing HCC following SVR to DAA therapy.
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Affiliation(s)
- Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kentaro Matsuura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshihito Nagura
- Department of Gastroenterology, Kasugai Municipal Hospital, Kasugai, Japan
| | - Hayato Kawamura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shintaro Ogawa
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsuya Nagaoka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takehisa Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Chuaypen N, Siripongsakun S, Hiranrat P, Tanpowpong N, Avihingsanon A, Tangkijvanich P. Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants. PLoS One 2022; 17:e0269641. [PMID: 35696400 PMCID: PMC9191717 DOI: 10.1371/journal.pone.0269641] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/22/2022] [Indexed: 12/05/2022] Open
Abstract
Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.
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Affiliation(s)
- Natthaya Chuaypen
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Surachate Siripongsakun
- Sonographer School, Faculty of Health Science Technology, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pantajaree Hiranrat
- Sonographer School, Faculty of Health Science Technology, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Anchalee Avihingsanon
- The HIV Netherlands Australia Thailand Research Collaboration (HIV NAT), Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- * E-mail:
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Nakano M, Yatsuhashi H, Bekki S, Takami Y, Tanaka Y, Yoshimaru Y, Honda K, Komorizono Y, Harada M, Shibata M, Sakisaka S, Shakado S, Nagata K, Yoshizumi T, Itoh S, Sohda T, Oeda S, Nakao K, Sasaki R, Yamashita T, Ido A, Mawatari S, Nakamuta M, Aratake Y, Matsumoto S, Maeshiro T, Goto T, Torimura T. Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019. Sci Rep 2022; 12:1517. [PMID: 35087153 PMCID: PMC8795252 DOI: 10.1038/s41598-022-05444-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/12/2022] [Indexed: 12/26/2022] Open
Abstract
We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996-2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60-69 years, 70-79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.
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Affiliation(s)
- Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hiroshi Yatsuhashi
- Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura, Nagasaki, 856-8562, Japan.
| | - Shigemune Bekki
- Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 2-1001-1 Kubara, Omura, Nagasaki, 856-8562, Japan
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoko Yoshimaru
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Koichi Honda
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu, Japan
| | | | - Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Satoshi Shakado
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Kenji Nagata
- Division of Gastroenterology and Hematology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tetsuro Sohda
- Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Satoshi Oeda
- Liver Center, Saga University Hospital, Saga, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
| | - Tsutomu Yamashita
- Department of Gastroenterology, National Hospital Organization Oita Medical Center, Oita, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yoshifusa Aratake
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Shuichi Matsumoto
- Department of Gastroenterology, Fukuoka Tokushukai Hospital, Kasuga, Japan
| | - Tatsuji Maeshiro
- First Department of Internal Medicine, University of the Ryukyus Hospital, Nakagami, Japan
| | - Takashi Goto
- Department of Gastroenterology, Nagasaki Rosai Hospital, Sasebo, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Luna-Cuadros MA, Chen HW, Hanif H, Ali MJ, Khan MM, Lau DTY. Risk of hepatocellular carcinoma after hepatitis C virus cure. World J Gastroenterol 2022; 28:96-107. [PMID: 35125821 PMCID: PMC8793019 DOI: 10.3748/wjg.v28.i1.96] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/12/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a significant cause of hepatocellular carcinoma (HCC). The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95% cure rate. Successful treatment of chronic hepatitis C greatly reduces the risk of HCC. A proportion of patients, especially those with pre-existing cirrhosis, remain at risk for HCC despite sustained virologic response (SVR). Diabetes mellitus, hepatic steatosis, alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure. Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis. More recently, various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR. These models still need to be validated and standardized prior to applying to routine clinical care.
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Affiliation(s)
- Maria Alejandra Luna-Cuadros
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Hao-Wei Chen
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Hira Hanif
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Mukarram Jamat Ali
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Muzammil Muhammad Khan
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Daryl Tan-Yeung Lau
- Liver Center, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
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Lin CY, Chien RN, Sheen IS. The 2020 Nobel Prize in Medicine for the Discovery of Hepatitis C Virus: An epic saga of the fight against a troublesome virus. Biomed J 2021; 44:567-569. [PMID: 34245922 PMCID: PMC8640543 DOI: 10.1016/j.bj.2021.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/22/2021] [Accepted: 07/01/2021] [Indexed: 01/12/2023] Open
Abstract
Chronic hepatitis C, which is caused by the hepatitis C virus, represents a substantial health threat to humans and causes approximately 700,000 deaths each year worldwide. However, 30 years after the discovery of this virus in 1989, nearly perfect antiviral drugs that can clear up to 95% of this virus have been developed due to numerous biomedical research studies and cooperation among members of the hepatitis C community. Because of these advances, the WHO announced a goal to eliminate the hepatitis C virus globally by 2030. Reviewing prior advances in detail, it is clear that all these achievements are based on initial seminal research conducted by the three 2020 Nobel laureates in medicine, namely, Harvey J. Alter, Michael Houghton and Charles M. Rice. In this short essay, we describe the seminal studies conducted by these authors. At the same time, the impacts of the contributions of these researchers on subsequent developments in research and in the treatment of chronic hepatitis C are honored.
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Affiliation(s)
- Chun-Yen Lin
- College of Medicine, Chang Gung University, Taipei, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Taipei, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - I-Shyan Sheen
- College of Medicine, Chang Gung University, Taipei, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
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Chu JYK, Ou JHJ. Autophagy in HCV Replication and Protein Trafficking. Int J Mol Sci 2021; 22:ijms22031089. [PMID: 33499186 PMCID: PMC7865906 DOI: 10.3390/ijms22031089] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 01/19/2021] [Accepted: 01/21/2021] [Indexed: 12/11/2022] Open
Abstract
Autophagy is a catabolic process that is important for maintaining cellular homeostasis. It is also known to possess other functions including protein trafficking and anti-microbial activities. Hepatitis C virus (HCV) is known to co-opt cellular autophagy pathway to promote its own replication. HCV regulates autophagy through multiple mechanisms to control intracellular protein and membrane trafficking to enhance its replication and suppress host innate immune response. In this review, we discuss the current knowledge on the interplay between HCV and autophagy and the crosstalk between HCV-induced autophagy and host innate immune responses.
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