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Abdlaty R, Abbass MA, Awadallah AM. Toward near real-time precise supervision of radiofrequency ablation for liver fibrosis using hyperspectral imaging. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 336:125994. [PMID: 40086137 DOI: 10.1016/j.saa.2025.125994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 02/17/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND AND AIMS Chronic liver diseases pose a significant global health concern, ranking as the 11th leading cause of death worldwide. It often progresses to organ fibrosis and severe complications such as portal hypertension and cirrhosis. Liver transplantation is the most effective treatment for such diseases, however, the persistent shortage of donors highlights the need for alternatives. Radiofrequency ablation (RFA) is a promising alternative since it is a minimally invasive procedure. RFA uses heat to destroy abnormal tissues. Its benefits include reduced recovery time compared to surgery, precise targeting of affected areas, and long-lasting symptom relief in many cases. However, RFA has challenges, such as potential risks of nerve damage, infection, or incomplete ablation, requiring repeat treatments. Although significant progress in RFA techniques, effective monitoring remains challenging due to the limited ability to accurately characterize the dynamic thermal diffusion and complex tissue responses. METHODS To address this challenge, hyperspectral imaging (HSI) shows promise in monitoring tissue necrosis post-ablation. Our study evaluated HSI's efficacy in monitoring RFA on ex vivo human fibrotic liver tissue samples. RESULTS Statistical analysis revealed correlations between spectral patterns and tissue conditions, which helped identify the optimal spectral bands of 543 nm and 579 nm for accurately distinguishing different tissue states. Analyzing the hemoglobin absorption profile indicated significant reductions in absorption of the green light band, showing approximately 40 % reduction in fibrotic tissue and around 20 % reduction in ablated tissue when compared to normal liver tissue. Additionally, a threshold was established for predicting the ablated area of liver samples, ensuring a condition of 90 % specificity. CONCLUSIONS Consequently, HSI proved to be a valuable tool for monitoring ablation and a step for improving treatment outcomes for liver fibrosis.
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Affiliation(s)
- Ramy Abdlaty
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt.
| | - Mohamed A Abbass
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt
| | - Ahmed M Awadallah
- Department of Biomedical Engineering, Military Technical College, Cairo, Egypt
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Hu Y, Kuang M, Song H, Tan Y, Zhou F, Pei G, Jiao L. Astragaloside IV prevents liver fibrosis by blocking glycolysis-mediated macrophage M1 polarization. Eur J Pharmacol 2025; 995:177353. [PMID: 39971227 DOI: 10.1016/j.ejphar.2025.177353] [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: 12/02/2024] [Revised: 01/22/2025] [Accepted: 02/05/2025] [Indexed: 02/21/2025]
Abstract
Hepatic fibrosis is a late-stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the disease. Hepatic macrophages are a remarkably heterogeneous population of immune cells that play multiple functions in homeostasis and are central to liver fibrosis. Glycolysis-mediated macrophage metabolic reprogramming leads to an increase in the proportion of M1 macrophages and the release of pro-inflammatory cytokines. The present study aimed to investigate the therapeutic effect and mechanism of Astragaloside IV (AS-IV) against carbon tetrachloride (CCl4)-induced liver fibrosis. The study found that AS-IV is an effective agent for reducing the production of inflammatory factors in CCl4-induced liver fibrosis. It was also found that AS-IV blocks macrophage M1 polarization and relieves liver fibrosis. Mechanistically, AS-IV reduces the methylation level of the FoxO1 promoter region and then upregulates its expression. FoxO1 can inhibit the expression of key enzymes in the glycolysis pathway and block glycolysis-mediated macrophage M1 polarization. Our findings indicate that AS-IV is an attractive option for treating liver fibrosis.
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Affiliation(s)
- Yutong Hu
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Ming Kuang
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Hao Song
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Yang Tan
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Feng Zhou
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Gang Pei
- Hunan University of Chinese Medicine, Changsha, 410000, China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410000, China; Key Laboratory of Modern Research of TCM, Education Department of Hunan Province, Changsha, 410000, China.
| | - Luojia Jiao
- Hunan University of Chinese Medicine, Changsha, 410000, China.
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Jian PA, Yang TN, Wang YX, Ma XY, Huang NN, Ren YF, Yuan SH, Li JL, Wang CC, Li XN. Lycopene, a natural plant extract, alleviates atrazine-induced ferroptosis in hepatocytes by activating cytochrome P450 oxidoreductase. Int J Biol Macromol 2025; 308:142311. [PMID: 40139611 DOI: 10.1016/j.ijbiomac.2025.142311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 03/16/2025] [Accepted: 03/18/2025] [Indexed: 03/29/2025]
Abstract
Atrazine (ATZ) and diaminochlorotriazine (DACT) accumulation poses liver health risks in animals and humans. Lycopene (LYC), a carotenoid found in red plants and fruits, exhibits potent antioxidant effects. This study explores the interaction between LYC and ATZ in mouse hepatocyte ferroptosis and the potential regulatory role of Cytochrome P450 oxidoreductase (CYPOR) in this process. Male mice were exposed to ATZ (50 mg/kg or 200 mg/kg) and/or LYC (5 mg/kg) by gavage for 21 days. In vitro experiments, a mouse hepatocyte cell line (AML12) was exposed to DACT (200 μM) and/or LYC (2 μM) for 12 h with or without small interfering RNA treatment. We found that both ATZ and DACT promoted CYPOR expression and caused liver injury. ATZ/DACT promotes Fe2+ accumulation and lipid peroxidation, ultimately leading to Ferroptosis in mouse hepatocytes. However, LYC alleviated ATZ/DACT-induced Ferroptosis by inhibiting CYPOR. The CYPOR knockdown resulted in the blockage of ATZ/DACT-induced ferroptosis, while the alleviation of ferroptosis by LYC was further enhanced. Thus, CYPOR can regulate ferroptosis in mouse hepatocytes and is a novel target for the treatment of hepatocyte ferroptosis-related diseases. Lycopene can be used as a functional dietary supplement to scavenge ferroptosis and reduce chronic liver disease.
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Affiliation(s)
- Ping-An Jian
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Tian-Ning Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Yu-Xiang Wang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Xiang-Yu Ma
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Ning-Ning Huang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Yi-Fei Ren
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Shi-Hao Yuan
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China
| | - Jin-Long Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China
| | - Chi-Chiu Wang
- Department of Obstetrics & Gynaecology, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, The Chinese University of Hong Kong-Sichuan University Joint Laboratory for Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong.
| | - Xue-Nan Li
- College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Department of Obstetrics & Gynaecology, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, The Chinese University of Hong Kong-Sichuan University Joint Laboratory for Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China.
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Liu J, Bai Y, Yao W, Sun P, Zhou B, Liu X, Liang B, Zheng C. Using intra-voxel incoherent motion MRI to dynamically evaluate the attenuating effects of donafenib combined with carvedilol in a thioacetamide-induced hepatic fibrosis rat model. MAGMA (NEW YORK, N.Y.) 2025:10.1007/s10334-025-01241-7. [PMID: 40095171 DOI: 10.1007/s10334-025-01241-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 02/07/2025] [Accepted: 02/24/2025] [Indexed: 03/19/2025]
Abstract
OBJECTIVE This study aimed to dynamically evaluate the attenuating effects of donafenib combined with carvedilol using intra-voxel incoherent motion (IVIM) MRI at different time points of disease course in a thioacetamide (TAA)-induced hepatic fibrosis rat model. METHODS In this study, 40 male Sprague-Dawley rats received TAA for 6 weeks to induce liver fibrosis and were divided into four groups randomly (N = 10). From week 3 to week 6 of modeling, each group of rats received daily gavage of vehicle, carvedilol (CARV), donafenib (DON), and donafenib plus carvedilol (DON + CARV), respectively. IVIM MRI was used to assess the degree of liver fibrosis in the above groups at 0, 2, 4, and 6 weeks after modeling. Liver fibrosis was classified according to the METAVIR scoring system (F0-F4). IVIM parameters were calculated using a biexponential fitting model, and a least-squares fitting approach was applied for parameter estimation. RESULTS The mean pathological collagen areas and the expression of α-SMA and collagen I in the CARV, DON, and DON + CARV groups were significantly less than that in the vehicle group (P < 0.001). IVIM-derived parameters (D, D*, and f) and ADC values were negatively correlated with the fibrosis levels (D: r2 = 0.594, P < 0.001; D*: r2 = 0.556, P < 0.001; f: r2 = 0.737, P < 0.001; ADC: r2 = 0.694, P < 0.001). At 4 and 6 weeks after modeling, the mean IVIM parameters and ADC values of the DON + CARV group were significantly higher than those of the vehicle group. CONCLUSION IVIM MRI is a noninvasive and valuable dynamic monitoring tool for liver fibrosis, and it was useful to monitor the dynamic inhibition process of donafenib and carvedilol on liver fibrosis in a TAA-induced rat model.
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Affiliation(s)
- Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Yaowei Bai
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Wei Yao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Peng Sun
- MSC Clinical & Technical Solutions, Philips Healthcare, Wuhan, China
| | - Binqian Zhou
- Department of Ultrasound, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China
| | - Xiaoming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
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Yi Y, Li L, Chen Y, Luo Y. Interaction between age and blood urea nitrogen to creatinine ratio on mortality in patients with severe cirrhosis: a retrospective cohort study from the MIMIC database. Front Endocrinol (Lausanne) 2025; 16:1544223. [PMID: 40110543 PMCID: PMC11919653 DOI: 10.3389/fendo.2025.1544223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/14/2025] [Indexed: 03/22/2025] Open
Abstract
Background Cirrhosis is a leading cause of global disease burden, with high mortality, particularly in critically ill patients. The blood urea nitrogen to creatinine ratio (BCR) is a straightforward biochemical indicator of renal excretory function and is linked to negative outcomes across different conditions. However, the relationship between BCR and mortality in critically ill patients with cirrhosis is unclear, The purpose of this study is to explore this question. Methods A retrospective cohort study was performed utilizing the MIMIC-IV database. We divided BCR into quartiles and evaluated 180-day and 365-day mortality as the primary outcomes. Kaplan-Meier survival analysis and multivariate Cox regression modeling were used to assess the link between BCR and mortality. Linear relationships were further determined using restricted cubic spline (RCS) curves, and finally, subgroup analyses were also performed. Results In our study of 2,816 critically ill cirrhotic patients, elevated BCR was significantly linked to higher mortality at both 180 and 365 days. The top BCR quartile showed a 45% higher risk of 180-day mortality (HR=1.45, 95% CI: 1.21-1.73) and a 38% higher risk of 365-day mortality (HR=1.38, 95% CI: 1.17-1.63) relative to the bottom quartile. RCS analysis demonstrated a notable linear correlation between BCR and mortality risk. Subgroup analyses indicated a stronger association between BCR and mortality among older patients. Conclusion In critically ill cirrhotic patients, elevated BCR values are strongly linked to increased mortality risk. Our research highlights BCR's potential as a prognostic marker for cirrhosis, especially in elderly patients.
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Affiliation(s)
- Yu Yi
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Lin Li
- Department of Oncology, Zibo Municipal Hospital, Zibo, China
| | - Yinghua Chen
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yawen Luo
- Department of Infectious Diseases, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
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Khetsuriani N, Tursunova D, Kasimova R, Sharapov S, Stewart B, Matyakubov M, Latipov R, Mosina L, Yusupaliyev B, Musabaev E. Prevalence of chronic hepatitis B virus infection among children in Uzbekistan: Impact of vaccination. Vaccine 2025; 48:126743. [PMID: 39862544 DOI: 10.1016/j.vaccine.2025.126743] [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: 10/02/2024] [Revised: 12/08/2024] [Accepted: 01/12/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Uzbekistan, a highly endemic country for hepatitis B virus (HBV), introduced infant vaccination with hepatitis B vaccine (HepB) in 2001. Since 2002, it had ≥90 % reported immunization coverage for ≥3 doses of HepB (HepB3) and the birth dose (HepB-BD). However, the impact of HepB vaccination and the progress towards achieving the regional hepatitis B control and global viral hepatitis B elimination goals had not been assessed. METHODS To determine current HBsAg prevalence among children in Uzbekistan, in 2022, we conducted a nationwide serosurvey among schoolchildren (grades 1-3) using a stratified, multi-stage cluster design. Participants' basic demographics and HepB immunization information were obtained. Blood specimens were tested for HBsAg using a WHO-prequalified rapid test (Bioline HBsAg WB, Abbott Diagnostics). Samples with positive and indeterminate results were tested for HBsAg by ELISA (Murex HBsAg Version3, Diasorine). Weighted proportions and adjusted 95 % confidence intervals (CI) were calculated. RESULTS Of 4119 children enrolled in 148 schools, blood was collected from 3753 (91.1 %) and immunization data were available for 3833 (93.3 %). National HBsAg prevalence was 0.20 % (adjusted 95 % CI, 0.09 %-0.38 %). Among children with available immunization data, 97.7 % (97.2 %-98.1 %) received ≥3 HepB doses and 94.9 % (94.1 %-95.5 %) received HepB-BD, including timely HepB-BD in 93.7 % (92.9 %-94.5 %). CONCLUSIONS The survey demonstrated that Uzbekistan has met the <0.5 % European regional HBsAg seroprevalence target and has made substantial progress towards meeting the <0.1 % HBsAg seroprevalence target for the elimination of HBV mother to-child transmission (MTCT). Based on these findings and ≥ 90 % HepB-BD and HepB3 coverage, in 2023, Uzbekistan was validated as having achieved the regional hepatitis B control goal. To achieve the elimination of MTCT of HBV, additional interventions, including improving antenatal screening for HBsAg, providing antiviral treatment of eligible HBsAg-positive pregnant women and hepatitis B immunoglobulin to infants born to HBsAg-positive mothers, should be considered.
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Affiliation(s)
| | - Dilorom Tursunova
- Service for Sanitary-Epidemiological Welfare and Public Health, Ministry of Health, Tashkent, Uzbekistan
| | - Rano Kasimova
- Institute of Virology, Tashkent, Uzbekistan; Central Asian University, Tashkent, Uzbekistan
| | | | - Brock Stewart
- Centers for Disease Control and Prevention, Atlanta, USA
| | - Mansurbek Matyakubov
- Institute of Virology, Tashkent, Uzbekistan; Republican Specialized Scientific and Practical Medical Center of Epidemiology, Microbiology, Infectious and Parasitic Diseases, Tashkent, Uzbekistan
| | - Renat Latipov
- World Health Organization Uzbekistan Country Office, Tashkent, Uzbekistan
| | - Liudmila Mosina
- World Health Organization Regional Office for Europe, Copenhagen, Denmark
| | - Bakhodir Yusupaliyev
- Service for Sanitary-Epidemiological Welfare and Public Health, Ministry of Health, Tashkent, Uzbekistan
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Hamada O, Tsutsumi T, Tsunemitsu A, Sasaki N, Kunisawa S, Fushimi K, Imanaka Y. Association of cirrhosis severity with outcomes after hip fracture repairs: A propensity-score matched analysis using a large inpatient database. J Orthop Sci 2025:S0949-2658(25)00038-7. [PMID: 39979173 DOI: 10.1016/j.jos.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/22/2025] [Accepted: 01/28/2025] [Indexed: 02/22/2025]
Abstract
BACKGROUND Advanced cirrhosis is associated with increased mortality in certain surgeries, but the impact of cirrhosis severity on outcomes in patients with hip fractures remains unclear. METHODS In a large nationwide administrative database of hospitalized patients, we compared postoperative outcomes in patients with hip fractures across different Child-Pugh classes of cirrhosis in Japan. Using the Japanese Diagnosis Procedure Combination Database, we identified 833,648 eligible patients diagnosed with hip fractures and underwent surgery between July 2010 and March 2021. Three sets of 1:1 propensity-score matching were performed for four groups: non-cirrhosis cases and Child-Pugh classes A, B, and C. We compared in-hospital mortality, length of stay, hospitalization fees, readmission, and complications in non-cirrhosis cases vs. Child-Pugh class A, Child-Pugh class A vs. B, and Child-Pugh class B vs. C. RESULTS Propensity-score matching created 1065 pairs for non-cirrhosis vs. Child-Pugh class A, 1012 for Child-Pugh class A vs. B, and 489 for Child-Pugh class B vs. C. In-hospital mortality did not differ between non-cirrhosis cases and those with Child-Pugh class A. However, in-hospital mortality was significantly higher in patients with Child-Pugh class B than in those with class A (1.5 % vs. 5.9 %; RD 4.45 %; 95 % CI: 2.79%-6.10 %), and higher in patients with Child-Pugh class C compared with class B (6.3 % vs. 28.4 %; RD 22.09 %; 95 % CI: 17.54%-26.63 %). Patients in more severe Child-Pugh classes had longer hospital stays, higher hospitalization fees, and higher complication rates. CONCLUSION Patients with hip fractures and cirrhosis who are at high risk of poor postoperative outcomes could be identified. This study highlights the significantly higher in-hospital mortality observed in patients with Child-Pugh class C cirrhosis undergoing hip fracture surgery compared to those with class B. These findings underscore the need for careful risk-benefit discussions, considering the severity of cirrhosis, surgical risks, and care goals for each patient.
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Affiliation(s)
- Osamu Hamada
- Department of General Internal Medicine, Takatsuki General Hospital, Osaka, Japan; Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiko Tsutsumi
- Department of General Internal Medicine, Takatsuki General Hospital, Osaka, Japan; Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ayako Tsunemitsu
- Department of General Internal Medicine, Takatsuki General Hospital, Osaka, Japan; Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Noriko Sasaki
- Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Susumu Kunisawa
- Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | - Yuichi Imanaka
- Department of Healthcare Economics and Quality Management, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Health Security System, Centre for Health Security, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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Jiang K, Bao J, Lou Z, Liu F, Xu K, Kwan HY. An Integration of RNA Sequencing and Network Pharmacology Approaches Predicts the Molecular Mechanisms of the Huo-Xue-Shen Formula in the Treatment of Liver Fibrosis. Pharmaceuticals (Basel) 2025; 18:227. [PMID: 40006040 PMCID: PMC11859937 DOI: 10.3390/ph18020227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/17/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Liver fibrosis is a prevalent, chronic inflammatory condition characterized by the excessive accumulation of extracellular matrix components and, primarily, collagen in the liver. Huo-xue-shen (HXS) has proven effective for the treatment of liver fibrosis. However, the mechanism is yet to be deciphered. Methods: Network pharmacology, machine learning algorithms and RNA-seq were used to predict the immune-treated targets and mechanisms associated with HXS in liver fibrosis. Molecular docking was employed to screen for effective agents based on the drug-compound-hub gene network in HXS, aiming to identify the most critical bioactive compound in HXS for the treatment of liver fibrosis. Results: A total of 100 immune-treated targets (ITTs) of HXS were found to significantly regulate the PI3K-Akt signaling pathway and the MAPK signaling pathway. Among these, CDKN1A, NR1I3, and TUBB1, which can concurrently interact with quercetin, were associated with the prognosis of liver fibrosis, indicating that HXS may inhibit or reverse HSC activation primarily by suppressing neutrophil extracellular trap formation, stimulating oxidative phosphorylation and promoting thyroid hormone synthesis in the regulation of the liver microenvironment. Conclusions: Our study suggests that HXS may delay the progression of liver fibrosis by targeting multiple pathways, as shown by the network pharmacology and transcriptome profiling used to examine the liver immune environment. Quercetin, its key ingredient, likely plays an important role by mediating the CDKN1A, NR1I3, and TUBB1 signaling pathways. Overall, our findings provide a new perspective on the potential biological mechanisms of this traditional Chinese medicine formula.
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Affiliation(s)
- Keying Jiang
- Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;
| | - Jianfeng Bao
- Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou 310020, China; (J.B.); (Z.L.); (F.L.)
| | - Zhonghan Lou
- Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou 310020, China; (J.B.); (Z.L.); (F.L.)
| | - Fei Liu
- Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou 310020, China; (J.B.); (Z.L.); (F.L.)
| | - Keyang Xu
- Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;
- State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
| | - Hiu Yee Kwan
- Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;
- Institute of Systems Medicine and Health Sciences, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
- Institute of Research and Continuing Education, Hong Kong Baptist University, Shenzhen 518000, China
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Lyu W, Cao Z, Ye Y, Xing L. [Interpretation of the Guidelines for Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Liver Cirrhosis]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2025; 56:5-9. [PMID: 40109466 PMCID: PMC11914030 DOI: 10.12182/20250160201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Indexed: 03/22/2025]
Abstract
Liver cirrhosis is the terminal stage of various acute and chronic liver diseases and ranks 11th among the most common causes of death worldwide. In recent years, with the progress of clinical research, there has been increasing support from evidence-based medicine for the treatment of liver cirrhosis with integrated traditional Chinese and Western medicine. In 2023, the Chinese Association of Integrative Medicine, the China Association of Chinese Medicine, and the Chinese Medical Association jointly released the first evidence-based guideline in this field, the Guidelines for Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Liver Cirrhosis. By combining the latest research at home and abroad, this article provides a detailed interpretation of the highlights in the guideline, including traditional Chinese medicine etiology and pathogenesis, diagnostic progress, disease and syndrome combination, stage-based diagnostic mode, and treatment strategies of integrated traditional Chinese and Western medicine. The aim is to enhance understanding of this guideline among health workers and promote the improvement of the diagnosis and treatment of liver cirrhosis with integrated traditional Chinese and Western medicine.
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Affiliation(s)
- Wenliang Lyu
- ( 100053) Department of Hepatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zhengmin Cao
- ( 100053) Department of Hepatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yong'an Ye
- ( 100053) Department of Hepatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Lianjun Xing
- ( 100053) Department of Hepatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Zan Q, Fan L, Lu W, Zhang Y, Huang Y, Yu X, Han Y, Zhang R, Dong C, Shuang S. Early Diagnosis of Liver Injury and Real-Time Evaluation of Photothermal Therapy Efficacy with a Viscosity-Responsive NIR-II Smart Molecule. Adv Healthc Mater 2025; 14:e2402614. [PMID: 39440592 DOI: 10.1002/adhm.202402614] [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: 07/16/2024] [Revised: 10/14/2024] [Indexed: 10/25/2024]
Abstract
The early diagnosis of liver injury and in situ real-time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near-infrared window (NIR-II) molecule (BITX-OH) is rationally designed for diagnosis and therapy by vinyl-bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX-OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167-fold) in NIR-II fluorescence at 962 nm. With the assistance of BITX-OH and NIR-II fluorescence imaging, early diagnosis and therapeutic evaluation of non-alcoholic fatty liver (NAFL), as well as in-site real-time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX-OH displays excellent photothermal conversion efficiency when exposed to an 808 nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR-II fluorescence for the real-time evaluation of photothermal therapy (PTT). This viscosity-based "self-monitoring" strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over- or under-treatment, thus enabling personalized precision therapy.
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Affiliation(s)
- Qi Zan
- School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China
| | - Li Fan
- School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China
| | - Wenjing Lu
- School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China
| | - Yuewei Zhang
- School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin, 132022, China
| | - Yunong Huang
- School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin, 132022, China
| | - Xue Yu
- School of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin, 132022, China
| | - Yahong Han
- Shanxi Medical University, Taiyuan, 030032, China
| | - Ruiping Zhang
- Shanxi Provincial People's Hospital, Taiyuan, 030001, China
| | - Chuan Dong
- School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China
| | - Shaomin Shuang
- School of Chemistry and Chemical Engineering, Institute of Environmental Science, Shanxi University, Taiyuan, 030006, China
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11
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Ford JS, Debes JD. Hepatitis B virus. TREATMENT AND MANAGEMENT OF TROPICAL LIVER DISEASE 2025:8-16. [DOI: 10.1016/b978-0-323-87031-3.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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12
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Sadri M, Shafaghat Z, Roozbehani M, Hoseinzadeh A, Mohammadi F, Arab FL, Minaeian S, Fard SR, Faraji F. Effects of Probiotics on Liver Diseases: Current In Vitro and In Vivo Studies. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10431-z. [PMID: 39739162 DOI: 10.1007/s12602-024-10431-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/02/2025]
Abstract
Various types of liver or hepatic diseases cause the death of about 2 million people worldwide every year, of which 1 million die from the complications of cirrhosis and another million from hepatocellular carcinoma and viral hepatitis. Currently, the second most common solid organ transplant is the liver, and the current rate represents less than 10% of global transplant requests. Hence, finding new approaches to treat and prevent liver diseases is essential. In liver diseases, the interaction between the liver, gut, and immune system is crucial, and probiotics positively affect the human microbiota. Probiotics are a non-toxic and biosafe alternative to synthetic chemical compounds. Health promotion by lowering cholesterol levels, stimulating host immunity, the natural gut microbiota, and other functions are some of the activities of probiotics, and their metabolites, including bacteriocins, can exert antimicrobial effects against a broad range of pathogenic bacteria. The present review discusses the available data on the results of preclinical and clinical studies on the effects of probiotic administration on different types of liver diseases.
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Affiliation(s)
- Maryam Sadri
- Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Shafaghat
- Department of Immunology, Iran University of Medical Sciences, Tehran, Iran
| | - Mona Roozbehani
- Vaccine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akram Hoseinzadeh
- Cancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Mohammadi
- Department of Immunology, School of Medicine, Mashhad University of Medicine Sciences, Mashhad, Iran
| | - Fahimeh Lavi Arab
- Department of Immunology, School of Medicine, Mashhad University of Medicine Sciences, Mashhad, Iran
| | - Sara Minaeian
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran
| | - Soheil Rahmani Fard
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran
| | - Fatemeh Faraji
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medicine Sciences, Tehran, Iran.
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13
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Wang Y, Wang M, Liu C, Hao M, Wang W, Li Y, Shi J, Jia X, Zhang X, Dang S. Global burden of liver cirrhosis 1990-2019 and 20 years forecast: results from the global burden of disease study 2019. Ann Med 2024; 56:2328521. [PMID: 38727511 PMCID: PMC11089929 DOI: 10.1080/07853890.2024.2328521] [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: 03/27/2023] [Revised: 02/01/2024] [Accepted: 03/04/2024] [Indexed: 05/15/2024] Open
Abstract
BACKGROUND Cirrhosis is a disease that imposes a heavy burden worldwide, but its incidence varies widely by region. Therefore, we analysed data on the incidence and mortality of cirrhosis in 204 countries and territories from 1990-2019 and projected the disease development from 2019-2039. METHODS Data on the incidence and mortality of liver cirrhosis from 1990 to 2019 were acquired from the public Global Burden of Disease (GBD) study. In addition, the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) of the age-standardized rate (ASR) of cirrhosis in different regions were calculated. The estimates of risk factor exposure were summarized, and the proportion of causes and risk factors of liver cirrhosis and their relationship with the human development index (HDI) and socio-demographic index (SDI) were analysed. Trends in the incidence of cirrhosis in 2019-2039 were predicted using Nordpred and BAPC models. RESULTS Globally, the ASR of cirrhosis incidence decreased by 0.05% per year from 25.7/100,000 in 1990 to 25.3/100,000 in 2019. The mortality risk associated with cirrhosis is notably lower in females than in males (13 per 100,000 vs 25 per 100,000). The leading cause of cirrhosis shifted from hepatitis B to C. Globally, alcohol use increased by 14%. In line, alcohol use contributed to 49.3% of disability-adjusted life years (DALYs) and 48.4% of global deaths from liver cirrhosis. Countries with a low ASR in 1990 experienced a faster increase in cirrhosis, whereas in 2019, the opposite was observed. In countries with high SDI, the ASR of cirrhosis is generally lower. Finally, projections indicate that the number and incidence of cirrhosis will persistently rise from 2019-2039. CONCLUSIONS Cirrhosis poses an increasing health burden. Given the changing etiology, there is an imperative to strengthen the prevention of hepatitis C and alcohol consumption, to achieve early reduce the incidence of cirrhosis.
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Affiliation(s)
- Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Muqi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chenrui Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Miao Hao
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yaping Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Juanjuan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xin Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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14
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Wang J, Niu D, Li X, Zhao Y, Ye E, Huang J, Yue S, Hou X, Wu J. Effects of 24-hour urine-output trajectories on the risk of acute kidney injury in critically ill patients with cirrhosis: a retrospective cohort analysis. Ren Fail 2024; 46:2298900. [PMID: 38178568 PMCID: PMC10773636 DOI: 10.1080/0886022x.2023.2298900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 12/20/2023] [Indexed: 01/06/2024] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling. MATERIALS AND METHODS This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects. RESULTS The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1-5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87-3.51), 1.86 (1.34-2.59), and 1.83 1.29-2.59). CONCLUSIONS The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses.
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Affiliation(s)
- Jia Wang
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Dongdong Niu
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Xiaolin Li
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yumei Zhao
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Enlin Ye
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Jiasheng Huang
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Suru Yue
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Xuefei Hou
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Jiayuan Wu
- Clinical Research Service Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- Guangdong Engineering Research Center of Collaborative Innovation of Clinical Medical Big Data Cloud Service in Western Guangdong Medical Union, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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15
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Forte E, Sanders JM, Pla I, Kanchustambham VL, Hollas MAR, Huang CF, Sanchez A, Peterson KN, Melani RD, Huang A, Polineni P, Doll JM, Dietch Z, Kelleher NL, Ladner DP. Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression. Mol Cell Proteomics 2024; 23:100876. [PMID: 39521382 DOI: 10.1016/j.mcpro.2024.100876] [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: 06/18/2024] [Revised: 10/16/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
Cirrhosis, advanced liver disease, affects 2 to 5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery top-down proteomics to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
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Affiliation(s)
- Eleonora Forte
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Jes M Sanders
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Indira Pla
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | | | - Michael A R Hollas
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | - Che-Fan Huang
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | - Aniel Sanchez
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | - Katrina N Peterson
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | - Rafael D Melani
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA
| | - Alexander Huang
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Praneet Polineni
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Julianna M Doll
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Zachary Dietch
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Neil L Kelleher
- Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA; Department of Chemistry, Northwestern University, Evanston, Illinois, USA; Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
| | - Daniela P Ladner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
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Jo Y, Lim E, Park J, Kang K, Shin MY, Choi JW, Kim S, Lee J. Epigenetic dysregulation of H19/IGF2 in hepatic cells exposed to toxic metal mixtures in vitro. Sci Rep 2024; 14:29413. [PMID: 39592715 PMCID: PMC11599747 DOI: 10.1038/s41598-024-80142-6] [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: 06/28/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024] Open
Abstract
Exposure to mixtures of toxic metals is known to cause adverse health effects through epigenetic alterations. Here we aimed to examine the unexplored area of aberrant DNA methylation in the H19/IGF2 domain following combined toxic metal exposure. An in vitro epigenotoxicity assay using the human normal liver epithelial cell line THLE-3 was conducted. When THLE-3 cells were exposed to specific concentrations of either organic arsenic or MeHgCl, an increase in the H19 lncRNA levels and a marked reduction in the IGF2 mRNA levels were observed. In contrast, combined exposures coupled with CdCl2 resulted in the transcriptional repression of H19 and transcriptional activation of IGF2. It should be noted that the correlation between the dysregulated expression of H19/IGF2 and the hypermethylated CpG sites within the H19 differentially methylated region (DMR) was statistically significant. Furthermore, we performed transcriptomic analysis of the hepatocytes exposed to toxic metal combinations indicating enrichment of pro-inflammatory and anti-proliferative pathways compared to the unexposed cells. Our results suggest that hazardous metal mixtures may trigger epigenetic aberrations at the H19/IGF2 locus. We propose that altered CpG methylation in the H19 DMR could be a candidate biomarker for hepatic epigenotoxicity, in part, due to environmental exposure.
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Affiliation(s)
- Yehoon Jo
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Eugene Lim
- Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Jihye Park
- Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, Republic of Korea
| | - Keunsoo Kang
- Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, Republic of Korea
| | - Mi-Yeon Shin
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
- Office of Dental Education, School of Dentistry, Seoul National University, Seoul, Republic of Korea
| | - Jeong Weon Choi
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
- Department of Environmental Science, Baylor University, Waco, TX, USA
| | - Sungkyoon Kim
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
- Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
| | - Jaehyouk Lee
- Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
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Zhu S, Chen X, Sun L, Li X, Chen Y, Li L, Suo X, Xu C, Ji M, Wang J, Wang H, Zhang L, Meng X, Huang C, Li J. N6-Methyladenosine modification of circDcbld2 in Kupffer cells promotes hepatic fibrosis via targeting miR-144-3p/Et-1 axis. Acta Pharm Sin B 2024. [DOI: 10.1016/j.apsb.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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18
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Ren W, Zheng J, Yang S, Zhong J, Liu X, Liu X, Feng J, Wei T, Yang Y, Tie C, Hong C, Feng B, Huang R. The relationship between imaging-based body composition abnormalities and long-term mortality in patients with liver cirrhosis. Eur J Radiol 2024; 180:111707. [PMID: 39197272 DOI: 10.1016/j.ejrad.2024.111707] [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: 02/22/2024] [Accepted: 08/23/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND Emerging evidence on cirrhosis suggests a close correlation between abnormality in body composition characteristics and poor prognosis. This study aimed to evaluate the impact of dynamic changes in body composition on the prognostic outcomes in patients with cirrhosis. METHODS This retrospective analysis included 158 patients diagnosed as cirrhosis from January 2018 to August 2023. Skeletal muscle mass, muscle quality, visceral and subcutaneous adiposity were evaluated using computed tomography (CT) imaging at the third lumbar vertebra level. Competing risk model was performed four different body composition status (i.e., normal, only sarcopenia, only myosteatosis, and combined status) for liver-related mortality. We also explored the relationship between the dynamic change in body composition and long-term prognosis by applying Gray's test. RESULTS Of the 158 cirrhotic patients (mean [SD] age, 57.1 [12.6] years), sarcopenia was present in 85 (60.1 %) patients, while 22 (13.9 %) patients had sarcopenic obesity and 68 (43.0 %) had myosteatosis. Patients solely diagnosed with sarcopenia exhibited a higher mortality rate compared to those with normal body composition (Gray's test, P=0.006), while patients solely diagnosed with myosteatosis or with a combination of sarcopenia and myosteatosis did not reach statistical significance (Gray's test, P=0.076; P=0.140). Multivariable analysis also revealed that VSR (HR=1.10 [1.01∼1.20]; P=0.028), sarcopenia (HR=2.73 [1.20∼6.22], P=0.017) and myosteatosis (HR=2.39 [1.10∼5.18], P=0.028) were significant independent predictors of liver-related deaths. Otherwise, patients exhibiting aggravating body composition during follow-up period were associated with a significantly higher mortality risk compared to those with normal or remission body composition status (HR=7.63 [1.12∼51.14]; P=0.036). CONCLUSION Progressive alterations in body composition status appears to be associated with liver-related mortality in individuals with liver cirrhosis. Focusing on the management of skeletal muscle, along with visceral and subcutaneous adiposity, may contribute to improving the prognosis of cirrhotic patients.
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Affiliation(s)
- Wenhui Ren
- Department of Clinical Epidemiology, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing 100044, China
| | - Jiarui Zheng
- Peking University Hepatology Institute, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China
| | - Shuo Yang
- Department of Radiology, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing 100044, China
| | - Juan Zhong
- School of Information, Renmin University of China, No. 59 Zhongguancun Avenue, Beijing, 100871, China
| | - Xin Liu
- Department of Gastroenterology, Huaihe Hospital of Henan University, No.115 Ximen Avenue, Kaifeng 475000, China
| | - Xinyue Liu
- Department of Nephrology, Peking University People's Hospital, Beijing 10044, China
| | - Jiajun Feng
- Department of Marketing, School of Business, Renmin University of China, No. 59 Zhongguancun Avenue, Beijing, 100871, China
| | - Tingyang Wei
- School of Basic Medical Sciences, Peking University Health Science Center, No.38 Xueyuan Avenue, Beijing, 10038, China
| | - Yuteng Yang
- School of Basic Medical Sciences, Peking University Health Science Center, No.38 Xueyuan Avenue, Beijing, 10038, China
| | - Changjie Tie
- School of Basic Medical Sciences, Peking University Health Science Center, No.38 Xueyuan Avenue, Beijing, 10038, China
| | - Chengwu Hong
- School of Basic Medical Sciences, Peking University Health Science Center, No.38 Xueyuan Avenue, Beijing, 10038, China
| | - Bo Feng
- Peking University Hepatology Institute, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China
| | - Rui Huang
- Peking University Hepatology Institute, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, China.
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Sarkari M, Chaudhary S, Gautam BK. Assessment of the Fibrosis Score and the Child-Turcotte-Pugh (CTP) Score in Patients With Chronic Liver Disease in India. Cureus 2024; 16:e74728. [PMID: 39734958 PMCID: PMC11682605 DOI: 10.7759/cureus.74728] [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] [Accepted: 11/29/2024] [Indexed: 12/31/2024] Open
Abstract
OBJECTIVE This study aimed to evaluate the severity of liver fibrosis in chronic liver disease patients using aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), FibroScan, and the Child-Turcotte-Pugh (CTP) score. It emphasized assessing fibrosis progression toward cirrhosis (F4 stage) and exploring the correlation between non-invasive markers and the CTP score for liver function and prognosis. METHODOLOGY This observational cross-sectional study was conducted over one calendar year in the Department of Medicine at Baba Raghav Das (BRD) Medical College, Gorakhpur, India. A total of 200 patients with chronic liver disease were selected. Fibrosis scores were calculated using FibroScan, APRI, and FIB-4, while the modified CTP score was determined for each participant. Pearson's correlation was used to assess relationships between variables, while logistic regression evaluated the association of non-invasive methods (APRI, FIB-4, FibroScan) with severe fibrosis (F4). Odds ratios (ORs), sensitivity, specificity, and AUC were calculated, and ROC curves visualized their discriminative ability. Statistical significance was defined as p < 0.05. RESULTS The study revealed a predominance of advanced fibrosis (F4) in males (82.5%) and patients with ethanol-induced liver disease (84.6%). FIB-4 had the strongest predictive value for advanced fibrosis with an OR of 3.8 (95% CI: 3.0-4.5) and AUC of 0.743, followed by APRI with an OR of 2.5 (95% CI: 1.9-3.1) and AUC of 0.757. CTP showed the highest sensitivity (95.45%) but a lower AUC (0.697), indicating its clinical value in correlating fibrosis severity with liver dysfunction. Hemoglobin, platelets, and INR showed no significant correlation with fibrosis, while total bilirubin was elevated in advanced CTP classes. A moderate positive correlation (r = 0.481, p < 0.001) was observed between fibrosis scores and CTP, linking fibrosis severity with liver dysfunction. These findings emphasize FIB-4's superior predictive accuracy, while APRI and CTP remain valuable complementary tools for liver disease prognosis. CONCLUSION In conclusion, FIB-4 is the most accurate for staging advanced fibrosis, while APRI excels in initial screening due to its higher sensitivity. FibroScan effectively assesses direct fibrosis, and the CTP score adds prognostic value, making these methods complementary for managing chronic liver diseases.
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Affiliation(s)
- Madhavi Sarkari
- Department of Medicine, Baba Raghav Das Medical College, Gorakhpur, Gorakhpur, IND
| | - Smita Chaudhary
- Department of Medicine, Baba Raghav Das Medical College, Gorakhpur, Gorakhpur, IND
| | - Bechan Kumar Gautam
- Department of Medicine, Baba Raghav Das Medical College, Gorakhpur, Gorakhpur, IND
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20
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Nakhostin-Ansari A, Menbari Oskouie I, Aghajani R, Khadembashiri MM, Ahmadi M, Gandomkar A, Malekzadeh F, Poustchi H, Fattahi MR, Anushiravani A, Malekzadeh R. Prevalence and Correlates of Probable Nonalcoholic Steatohepatitis (NASH) in Pars Cohort Study. ARCHIVES OF IRANIAN MEDICINE 2024; 27:598-605. [PMID: 39534993 PMCID: PMC11558611 DOI: 10.34172/aim.30020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 10/12/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Studies on the prevalence of nonalcoholic steatohepatitis (NASH) and the factors associated with its high prevalence among Iranian people are limited. This study evaluated the prevalence of NASH and its associated factors among Iranian adults using Pars Cohort Study (PCS) data. METHODS This cross-sectional study was conducted based on PCS, which includes 40-75-year-old adults from the Valashahr area. NASH was defined as alanine aminotransferase (ALT) higher than 40 U/L without evidence of hepatitis B or C infections. The prevalence of NASH and its associations with basic and demographic characteristics, socioeconomic characteristics, medical history, gastrointestinal symptoms, and laboratory tests were evaluated. RESULTS Overall, 8734 patients, including 3917 men (44.8%), were enrolled in this study. The mean age of participants was 52.62 years (SD=9.68), and 605 individuals had NASH (6.9%). In the regression analysis, in contrast to female gender (OR=0.31, 95% CI=0.249‒0.386, P<0.001) and age (OR=0.951, 95% CI=0.941‒0.962, P<0.001), history of heart disease (OR=1.499, 95% CI=1.146‒1.962, P=0.003), history of diabetes (OR=1.523, 95% CI=1.162‒1.995, P=0.002), hypertension (OR=1.241, 95% CI=1.023‒1.506, P=0.029), being overweight or obese (OR=2.192, 95% CI=1.755‒2.737, P<0.001), being in the richest or second richest wealth index quantiles (OR=1.315, 95% CI=1.107‒1.156, P=0.002), and increased waist circumference (OR=1.409, 95% CI=1.107‒1.793, P<0.005) were independently associated with a higher risk of having NASH. CONCLUSION In this study, we determined the prevalence of NASH and found male gender, younger age, history of heart disease, history of diabetes, hypertension, socioeconomic status, and obesity as possible factors associated with a higher risk of NASH among Iranians.
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Affiliation(s)
- Amin Nakhostin-Ansari
- Neuromusculoskeletal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Iman Menbari Oskouie
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Aghajani
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Ahmadi
- Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdollah Gandomkar
- Non-Communicable Disease Research Center, Shiraz University of medical Sciences, Shiraz, Iran
| | - Fatemeh Malekzadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran
| | - Mohammad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Anushiravani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran
| | - Reza Malekzadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Teheran, Iran
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21
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Pham YTH, Huang DQ, Zhang Z, Ng CH, Tan DJH, Nguyen HC, Nguyen TC, Behari J, Yuan JM, Luu HN. Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease. Eur J Cancer Prev 2024; 33:512-524. [PMID: 38568179 PMCID: PMC11416569 DOI: 10.1097/cej.0000000000000885] [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] [Indexed: 06/12/2024]
Abstract
BACKGROUND Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. METHODS We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. RESULTS Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. CONCLUSION Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.
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Affiliation(s)
- Yen Thi-Hai Pham
- University of Pittsburgh Medical Center Hillman Cancer Center
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Daniel Q. Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Zhongjie Zhang
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Darren Jun Hao Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore
| | - Hiep C. Nguyen
- Kanazawa University Graduate School of Medicine, Kanazawa, Japan
| | - Tin C. Nguyen
- Department of Computer Science and Software Engineering, Auburn University, Auburn, Alabama
| | - Jaideep Behari
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jian-Min Yuan
- University of Pittsburgh Medical Center Hillman Cancer Center
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Hung N. Luu
- University of Pittsburgh Medical Center Hillman Cancer Center
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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22
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Al Ta'ani O, Aleyadeh W, Al-Ajlouni Y, Alnimer L, Ismail A, Natour B, Njei B. The burden of cirrhosis and other chronic liver disease in the middle east and North Africa (MENA) region over three decades. BMC Public Health 2024; 24:2979. [PMID: 39468483 PMCID: PMC11514855 DOI: 10.1186/s12889-024-20445-5] [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: 04/11/2024] [Accepted: 10/17/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Cirrhosis comprises a significant health challenge in the Middle East and North African (MENA) region impacting healthcare systems and communities. This study sought to investigate trends in the burden of cirrhosis and other chronic liver disease, different etiologies, deaths, and the disability burden utilizing data from the Global Burden of Disease (GBD) database. METHODS Analyzing epidemiological trends from 1990 to 2021 across 21 MENA countries, this research utilized data on age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized disability-adjusted life years (DALYs) to evaluate the burden of cirrhosis and other chronic liver disease. The study also examined national variations and sociodemographic relationships. RESULTS The study identified a 114.9% increase in cirrhosis and other chronic liver disease incidence within the MENA region between 1990 and 2021, with 7,344,030 incident cases reported in 2021. The ASIR showed a steeper rise in females (9.6%) compared to males (7.0%). Etiology-specific analysis revealed an increase in the ASIR for MASLD related cirrhosis and other chronic liver disease by 22.2%, while those due to alcohol as well as hepatitis B and C decreased by 28.1%, 59.3%, and 30%, respectively. Despite the rising incidence, overall age-standardized death rates across all etiologies decreased by 54.3%, with DALYs showing a 51.4% decrease during the same period. Country-specific trends varied significantly, with Oman recording the highest annual ASIR increase (0.64%), and Qatar observing the most substantial annual reduction in age-standardized death rates (-2.88%). CONCLUSION The study highlights evolving trends in cirrhosis and other chronic liver disease within the MENA region, emphasizing the necessity for comprehensive, etiology, and gender-specific interventions. Despite an increasing incidence, the observed improvements in mortality rates and age-standardized disability burden indicate progress in public health efforts to mitigate cirrhosis's impact. These findings point to the complex nature of cirrhosis outcomes and the urgent need for tailored strategies to manage its increasing burden effectively.
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Affiliation(s)
| | - Wesam Aleyadeh
- Cleveland Clinic Akron General, Akron, OH, USA
- Toronto Centre for Liver Disease, Toronto, ON, Canada
| | | | - Lynna Alnimer
- Providence Hospital, College of Human Medicine, Michigan State University, Southfield, MI, USA
| | - Abdellatif Ismail
- University of Maryland Medical Center Midtown Campus, Baltimore, MD, USA
| | - Bashar Natour
- John H. Stroger Hospital of Cook County, Chicago, IL, USA
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23
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Dejanović B, Barak O, Čolović P, Janjić N, Savić Ž, Gvozdanović N, Ružić M. Hospital Mortality in Acute Decompensation of Alcoholic Liver Cirrhosis: Can Novel Survival Markers Outperform Traditional Ones? J Clin Med 2024; 13:6208. [PMID: 39458158 PMCID: PMC11508931 DOI: 10.3390/jcm13206208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 10/13/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
Background: There is a strong correlation between systemic inflammation intensity and clinical presentation, disease progression, and survival during liver cirrhosis decompensation. This study aimed to evaluate the prognostic performance of blood-based biomarkers as meta-inflammation markers, including NLR, PLR, LMR, INPR, MPR, ALBI, FIB4, and APRI, in predicting hospital mortality in patients with acute decompensation of alcohol-related liver cirrhosis. Methods: Data from 411 patients with their first onset of acute decompensation were analyzed, forming two groups: deceased and survived during hospitalization. Generalized partial least squares regression analysis was applied to explore the effects of surrogate indicators on mortality rates, using mortality rate as the dependent variable. Root Mean Square Error, Akaike's, and Bayesian information criteria determined that four components accounted for most of the variance. Results: Variables with significant negative contributions to the outcome prediction (ranked by standardized regression coefficients) were encephalopathy grade, total bilirubin, Child-Turcotte-Pugh score, MELD, NLR, MPV, FIB4, INR, PLR, and ALT. Coefficient sizes ranged from -0.63 to -0.09, with p-values from 0 to 0.018. Conclusions: NLR, PLR, and FIB4 significantly contribute to hospital mortality prediction in patients with acute decompensation of alcohol-related liver cirrhosis. Conversely, some variables used to predict liver disease severity, including INPR, APRI, LMR, and ALBI score, did not significantly contribute to hospital mortality prediction in this patient population.
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Affiliation(s)
- Božidar Dejanović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia
| | - Otto Barak
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
| | - Petar Čolović
- Department of Psychology, Faculty of Philosophy, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Nebojša Janjić
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia
| | - Željka Savić
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia
| | - Nikola Gvozdanović
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia
| | - Maja Ružić
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; (O.B.); (N.J.); (Ž.S.); (N.G.); (M.R.)
- Clinic of Infectious Disease, University Clinical Center of Vojvodina, 21000 Novi Sad, Serbia
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24
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Faisal N, Lix LM, Walld R, Singer A, Kosowan L, Singh H, Renner E, Mahar A. Trends in the incidence and prevalence of cirrhosis in Manitoba, Canada: A population-based study (2010-2019). Ann Hepatol 2024; 30:101581. [PMID: 39389266 DOI: 10.1016/j.aohep.2024.101581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 06/28/2024] [Accepted: 08/22/2024] [Indexed: 10/12/2024]
Abstract
INTRODUCTION AND OBJECTIVES The burden of chronic liver disease and cirrhosis continues to increase in North America. We sought to estimate the incidence and prevalence of cirrhosis in Manitoba, Canada over time and assess changes in trends between 2010-2019. MATERIAL AND METHODS We performed a population-based study using Manitoba administrative health care data, and two validated case-finding algorithms. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations, adjusting for age and sex. Changes in estimates were tested using linear trend regression models. RESULTS Two algorithms estimated the number of prevalent cirrhosis to be 16,140 and 29,943 respectively. The age- and sex-adjusted incidence rates increased over the study (from 149 to 264 cases per 100,000 population in 2010, to 177 to 388 cases per 100,000 population in 2019). Cirrhosis incidence increased annually by 2-6 %, with the largest increase (6-8 % 95 % CI 7-9 %, p <0.0001) in those aged 18-44 years. Irrespective of the algorithm used, females consistently exhibited higher cirrhosis incidence and prevalence compared to males over time (P <0.0001). Prevalence demonstrated an upward trend among all age groups over time for both algorithms (P < 0.0001). CONCLUSIONS This population-based study highlights concerning temporal trends in cirrhosis, characterized by rising annual incidence and prevalence estimates, particularly among young adults and females. These findings underscore the urgent need for comprehensive strategies that encompass prevention, early detection, and the delivery of high-quality healthcare and public health initiatives to effectively tackle this escalating health burden.
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Affiliation(s)
- Nabiha Faisal
- Department of Internal Medicine, University of Manitoba, GC430-820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada; Department of Community Health Sciences, University of Manitoba, Room S113 - 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R3E 0W3 Canada.
| | - Lisa M Lix
- Department of Community Health Sciences, University of Manitoba, Room S113 - 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R3E 0W3 Canada; Manitoba Centre of Health Policy, University of Manitoba, Room 408-727 McDermot Ave., Winnipeg, MB R3E 3P5, Canada
| | - Randy Walld
- Manitoba Centre of Health Policy, University of Manitoba, Room 408-727 McDermot Ave., Winnipeg, MB R3E 3P5, Canada
| | - Alexander Singer
- Department of Family Medicine, University of Manitoba Canada, S100, 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R33 0W2, Canada
| | - Leanne Kosowan
- Department of Family Medicine, University of Manitoba Canada, S100, 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R33 0W2, Canada
| | - Harminder Singh
- Department of Internal Medicine, University of Manitoba, GC430-820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada; Department of Community Health Sciences, University of Manitoba, Room S113 - 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R3E 0W3 Canada
| | - Eberhard Renner
- Department of Internal Medicine, University of Manitoba, GC430-820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada
| | - Alyson Mahar
- Department of Community Health Sciences, University of Manitoba, Room S113 - 750 Bannatyne Avenue, University of Manitoba (Bannatyne campus), Winnipeg, MB R3E 0W3 Canada; School of Nursing, Queen's University, 92 Barrie Street Kingston, Ontario K7L 3N6, Canada
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25
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Liu Y, Meng F, Ma J, Zhang W, Yu J, Zhou Y, Zuo W, Yan Z, Pan C, Luo J. Unveiling the impact of cirrhotic cardiomyopathy on portal hemodynamics and survival after transjugular intrahepatic portosystemic shunt: a prospective study. Abdom Radiol (NY) 2024; 49:3507-3516. [PMID: 38900326 DOI: 10.1007/s00261-024-04446-x] [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: 04/07/2024] [Revised: 05/31/2024] [Accepted: 06/07/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND AND AIMS The placement of Transjugular intrahepatic portosystemic shunt (TIPS) results in a sudden increase in central circulating blood volume, which requires proper regulation of the cardiovascular system. We aimed to investigate the impact of TIPS on cirrhotic cardiomyopathy (CCM). METHOD A consecutive case series of patients with cirrhosis who underwent TIPS were evaluated by echocardiography and pressure measurements before, immediately after TIPS and 2-4 days later (delayed). Furthermore, all patients underwent a one-year follow-up. RESULTS In this study, 107 patients were enrolled, 38 (35.5%) with CCM. Echocardiography revealed an increase in postoperative left ventricular filling pressure accompanied by an elevation in left ventricular ejection fraction (LVEF). However, patients in the CCM group exhibited lower LVEF and mean arterial pressure (MAP) compared to the non-CCM group. Post-TIPS, CCM patients showed increased right atrium pressure (RAP) that normalized within 2-4 days, whereas non-CCM patients had lower RAP than baseline. Compared to patient without CCM, CCM patients revealed lower immediate (16.7 ± 4.4 vs. 18.9 ± 4.8, p = 0.022) and delayed 15.9 ± 3.7 vs. 17.7 ± 5.3, p = 0.044) portal vein pressures (PVP) and portal pressure gradients (PPG) (7.7 ± 3.4 vs. 9.2 ± 3.6, p = 0.032 and 10.1 ± 3.1 vs. 12.3 ± 4.9, p = 0.013). The 1-year mortality rates were 13.2% for CCM patients and 4.3% for non-CCM patients (log-rank test, p = 0.093), with MELD score, and preoperative RAP significantly associated with the mortality. CONCLUSION Cirrhotic patients with CCM exhibit lower PVP and PPG immediately after TIPS and 2-4 days later, without significantly impacting one-year survival outcomes.
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Affiliation(s)
- Yaozu Liu
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fangmin Meng
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingqin Ma
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen Zhang
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiaze Yu
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongjie Zhou
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wuxu Zuo
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiping Yan
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
- Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China
| | - Cuizhen Pan
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China.
- Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Jianjun Luo
- Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China.
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, NO. 180 Fenglin Road, 200032, China.
- National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
- Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China.
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26
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Willmann R, Almeida M, Stoppa E, Barbisan LF, Miranda JRA, Soares G. Evaluation and imaging of biodistribution of magnetic nanoparticles in a model of hepatic cirrhosis via alternating current biosusceptometry. Biomed Phys Eng Express 2024; 10:065024. [PMID: 39260388 DOI: 10.1088/2057-1976/ad795b] [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: 03/25/2024] [Accepted: 09/11/2024] [Indexed: 09/13/2024]
Abstract
In recent years, magnetic nanoparticles (MNPs) have exhibited theragnostic characteristics which confer a wide range of applications in the biomedical field. Consequently, through Alternating Current Biosusceptometry (ACB), magnetic nanoparticles can be used as tracers, allowing the study of healthy and cirrhotic livers and providing the ability to differentiate them through the reconstruction of quantitative images. The ACB system consists of a developing biomagnetic technique that has the ability to magnetize and measure the magnetic susceptibility of a material such as MNPs, thereby offering quantitative information about biological systems with magnetic tracers.
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Affiliation(s)
- Raffael Willmann
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
| | - Michael Almeida
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
| | - Erick Stoppa
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
| | - Luis F Barbisan
- Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
| | - Jose R A Miranda
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
| | - Guilherme Soares
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University-UNESP, Botucatu, 18618-689, SP, Brazil
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27
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Njifon AM, Modiyinji AF, Monamele CG, Mbouyap PR, Ngono L, Tagnouokam-Ngoupo PA, Lissock SF, Zekeng MR, Assam JPA, Njouom R. A decade-long retrospective study of hepatitis C virus genetic diversity in Cameroon, 2013-2023: presence of a high proportion of unsubtypable and putative recombinant HCV strains. Arch Virol 2024; 169:197. [PMID: 39256207 DOI: 10.1007/s00705-024-06124-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 07/22/2024] [Indexed: 09/12/2024]
Abstract
While treatment options for hepatitis C virus (HCV) infection have expanded considerably over the past decade thanks to the development of pan-genotypic therapies, genotype testing remains a prerequisite for treatment in sub-Saharan African countries, including Cameroon, where multiple HCV genotypes and subtypes exist. The main objective of this study was to describe the trend in the distribution of HCV genotypes and subtypes from 2013 to 2023 in the Cameroonian population. Viral loads were determined using the Abbott real-time assay, and genotyping/subtyping was based on nested and semi-nested reverse transcription polymerase chain reaction (RT-PCR) amplification of the regions encoding the core and non-structural protein 5B (NS5B) regions, respectively, followed by sequencing and phylogenetic analysis. A total of 512 patients with NS5B and core sequencing results were included in our study. Genotyping revealed a predominance of both genotype 4 (38.48%) and genotype 1 (37.11%), followed by genotype 2, detected in 22.46% of patients. Interestingly, 10 samples (1.95%) had discordant genotypes in both regions, suggesting the presence of putative recombinant forms of HCV. Twelve different subtypes were detected during the study period, with a predominance of subtypes 4f (18.95%) and 1e (16.02%). Furthermore, phylogenetic analysis failed to assign a subtype to a relatively high proportion of sequences (38.67%) for the two genomic regions, and their classification was limited to genotype assignment. The frequency distribution of HCV genotypes did not show any statistical difference according to year or sex. These results confirm the genetic diversity of HCV in Cameroon and the potential for the generation of recombinant strains.
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Affiliation(s)
- Aristide Mounchili Njifon
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
- Department of Microbiology, Faculty of Sciences, University of Yaounde I, P.O. Box 337, Yaoundé, Cameroon
| | - Abdou Fatawou Modiyinji
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Chavely Gwladys Monamele
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Pretty Rose Mbouyap
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Laure Ngono
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | | | - Simon Frederic Lissock
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Martin Ridole Zekeng
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon
| | - Jean Paul Assam Assam
- Department of Microbiology, Faculty of Sciences, University of Yaounde I, P.O. Box 337, Yaoundé, Cameroon
| | - Richard Njouom
- Department of Virology, Centre Pasteur of Cameroon, 451 Rue 2005, P.O. Box 1274, Yaoundé, Cameroon.
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Makokha GN, Bao H, Hayes CN, Abuduwaili M, Songok E, Hijikata M, Chayama K. The Prevalence and Genotype Distribution of Hepatitis C Virus in Kenya: A Systematic Review and Meta-Analysis. J Epidemiol Glob Health 2024; 14:677-689. [PMID: 39254917 PMCID: PMC11442939 DOI: 10.1007/s44197-024-00299-1] [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: 04/23/2024] [Accepted: 09/04/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Hepatitis C (HCV) is a virus that causes chronic liver disease, end-stage cirrhosis, and liver cancer, yet most infected individuals remain undiagnosed or untreated. Kenya is a country located in Sub-Saharan Africa (SSA) where the prevalence of HCV remains high but with uncertain disease burden due to little population-based evidence of the epidemic. We aimed to highlight the HCV disease burden in Kenya with a summary of the available data. METHODS The study was performed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We searched publications reporting HCV prevalence and genotypes in Kenya between January 2000 to December 2022. The effect size, i.e., the HCV prevalence, was defined as the proportion of samples testing positive for HCV antibody. Study quality was assessed by the Joanna Briggs Institute (JBI) critical appraisal checklist. Due to high study heterogeneity, the studies were categorized into low-, intermediate-, and high-risk for HCV infection. The pooled estimate prevalence per category was determined by the random effects model. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023401892). RESULTS A total of 29 studies with a sample size of 90,668 met our inclusion criteria, a third of which were from the capital city Nairobi (34.5%). Half of the studies included HIV-infected individuals (31%) or injection drug users (20.7%). HCV genotype 1 was the most common, with genotype 4 only slightly less common, and together they accounted for 94% of cases. The pooled prevalence for the low-, intermediate- and high-risk groups were 2.0%, 3.4%, and 15.5%, respectively. Over 80% of the studies had a score of > 6 on the JBI scale, indicating a low risk of bias in terms of study design, conduct and analysis. CONCLUSION Our findings demonstrate that there is a higher prevalence of HCV in key populations such as HIV-infected individuals and drug users than in the general population in Kenya. We found that HCV genotypes 1 and 4 were the most common genotypes. More data from the general population is required in order to establish baseline data on the prevalence and genotypes of HCV in Kenya.
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Affiliation(s)
- Grace Naswa Makokha
- Hiroshima Institute of Life Sciences, 7-21 Nishi Asahi-machi, Minami-ku, Hiroshima City, Hiroshima, 734-0002, Japan.
| | - Huarui Bao
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Higashihiroshima, Japan
| | - C Nelson Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Higashihiroshima, Japan
| | - Maidina Abuduwaili
- Hiroshima Institute of Life Sciences, 7-21 Nishi Asahi-machi, Minami-ku, Hiroshima City, Hiroshima, 734-0002, Japan
| | - Elijah Songok
- Graduate School of Health Sciences, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Makoto Hijikata
- Hiroshima Institute of Life Sciences, 7-21 Nishi Asahi-machi, Minami-ku, Hiroshima City, Hiroshima, 734-0002, Japan
| | - Kazuaki Chayama
- Hiroshima Institute of Life Sciences, 7-21 Nishi Asahi-machi, Minami-ku, Hiroshima City, Hiroshima, 734-0002, Japan
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Favre-Bulle T, Moradpour D, Marques-Vidal P, Vaucher J. Trends in the burden of hospitalised patients with cirrhosis in Switzerland: a cross-sectional study of cirrhosis-related hospitalisations between 1998 and 2020. BMJ Open 2024; 14:e081822. [PMID: 39181561 PMCID: PMC11344505 DOI: 10.1136/bmjopen-2023-081822] [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: 11/07/2023] [Accepted: 08/05/2024] [Indexed: 08/27/2024] Open
Abstract
OBJECTIVE Liver cirrhosis is an increasing cause of morbidity and mortality worldwide with a heavy load on healthcare systems. We analysed the trends in hospitalisations for cirrhosis in Switzerland. DESIGN Cross-sectional study. SETTING Large nationwide inpatient database, years between 1998 and 2020. PARTICIPANTS Hospitalisations for cirrhosis of adult patients were selected. MAIN OUTCOMES AND MEASURES Hospitalisations with either a primary diagnosis of cirrhosis or a cirrhosis-related primary diagnosis with a mandatory presence of cirrhosis as a secondary diagnosis were considered following the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. Trends in demographic and clinical characteristics, in-hospital mortality and length of stay were analysed. Causes and costs of cirrhosis-related hospitalisations were available from 2012 onwards. RESULTS Cirrhosis-related hospitalisations increased from 1631 in 1998 to 4052 in 2020. Of the patients, 68.7% were men. Alcohol-related liver disease was the leading cause, increasing from 44.1% (95% CI, 42.4% to 45.9%) in 2012 to 47.9% (95% CI, 46.4% to 49.5%) in 2020. Assessed by exclusion of other coded causes, non-alcoholic fatty liver disease was the second cause at 42.7% (95% CI, 41.2% to 44.3%) in 2020. Hepatitis C virus-related cirrhosis decreased from 12.3% (95% CI, 11.2% to 13.5%) in 2012 to 3.2% (95% CI, 2.7% to 3.8%) in 2020. Median length of stay decreased from 11 to 8 days. Hospitalisations with an intensive care unit stay increased from 9.8% (95% CI, 8.4% to 11.4%) to 15.6% (95% CI, 14.5% to 16.8%). In-hospital mortality decreased from 12.1% (95% CI, 10.5% to 13.8%) to 9.7% (95% CI, 8.8% to 10.7%). Total costs increased from 54.4 million US$ (51.4 million €) in 2012 to 92.6 million US$ (87.5 million €) in 2020. CONCLUSIONS Cirrhosis-related hospitalisations and related costs increased in Switzerland from 1998 to 2020 but in-hospital mortality decreased. Alcohol-related liver disease and non-alcoholic fatty liver disease were the most prevalent and preventable aetiologies of cirrhosis-related hospitalisations.
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Affiliation(s)
- Timothee Favre-Bulle
- Service of Internal Medicine, Etablissements Hospitaliers du Nord Vaudois, Yverdon-les-Bains, Switzerland
- Department of Medicine, University of Lausanne Faculty of Biology and Medicine, Lausanne, Switzerland
| | - Darius Moradpour
- Department of Medicine, Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
| | | | - Julien Vaucher
- Department of Medicine, University of Lausanne, Lausanne, Switzerland
- Department of Medicine and Specialties, University of Fribourg, Fribourg, Switzerland
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Qin D, Han C, Gao Y, Li H, Zhu L. Lactucin reverses liver fibrosis by inhibiting TGF-β1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism. Sci Rep 2024; 14:19323. [PMID: 39164375 PMCID: PMC11336071 DOI: 10.1038/s41598-024-70253-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 08/14/2024] [Indexed: 08/22/2024] Open
Abstract
TGF-β1 activation of hepatic stellate cells (HSCs), transcriptional activator 3 (Stat3) activation and short chain fatty acids (SCFAs), metabolite of intestinal bacteria, is closely associated with hepatic fibrosis. Previous studies have shown that Lactucin has significant anti-inflammatory and hepatoprotective effects; however, the mechanism of Lactucin's role in liver fibrosis associated with SCFAs remains unknown. This study was intended to investigate whether effect of Lactucin on liver fibrosis was mediated by TGF-β1/Stat3 and SCFAs. We found that Lactucin induced apoptosis in HSC-T6 cells, and inhibition of nuclear translocation of Stat3 and p-Stat3. And Smad3 and TGF-β1 protein expression was significantly inhibited, while TLR4 and Smad7 protein expression was significantly enhanced. For in vivo experiments, we demonstrated that Lactucin alleviated liver fibrosis in mice, as evidenced by a reduction in inflammatory factors, collagen deposition, liver injury and fibrosis-related factors expression, especially the expression of Smad3 and TGF-β1 proteins was significantly suppressed and Smad7 protein expression was significantly increased in the liver. In addition, the levels of acetic acid, butyric acid and valeric acid in the intestine of Lactucin-treated mice were significantly higher than those in the intestine of liver fibrosis mice. In conclusion, based on the results of in vivo and in vitro experiments, preventive mechanism of Lactucin against liver fibrosis in mice may be to improve the enterohepatic circulation by regulating the metabolites of intestinal microorganisms, acetic acid and butyric acid, and to further regulate the Stat3 and TGF-β1 signaling pathway through the "gut-liver axis" to combat liver fibrosis.
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Affiliation(s)
- Dongmei Qin
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China.
| | - Chang Han
- Department of Pharmacy, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Yuefeng Gao
- College of Applied Engineering, Henan University of Science and Technology, Sanmenxia, People's Republic of China
| | - Hong Li
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China
| | - Liping Zhu
- Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China
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Yang J, Chen J, Li Q, Xu RA, Chen X. Effects of three flavonoids on the metabolism of lenvatinib. Front Pharmacol 2024; 15:1438259. [PMID: 39228528 PMCID: PMC11368737 DOI: 10.3389/fphar.2024.1438259] [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: 05/25/2024] [Accepted: 07/26/2024] [Indexed: 09/05/2024] Open
Abstract
Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib. Enzyme reaction system was established and optimized in vitro, and in vivo experiments were conducted in Sprague-Dawley (SD) rats, where the analytes were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We found that among three flavonoids, luteolin and myricetin had strong inhibitory effects on lenvatinib metabolism, with half-maximal inhibitory concentration (IC50) values of 11.36 ± 0.46 µM and 11.21 ± 0.81 µM in rat liver microsomes (RLM), respectively, and 6.89 ± 0.43 µM and 12.32 ± 1.21 µM in human liver microsomes (HLM), respectively. In Sprague-Dawley rats, the combined administration of lenvatinib and luteolin obviously expanded the exposure to lenvatinib; however, co-administered with myricetin did not have any changes, which may be due to the poor bioavailability of myricetin in vivo. Furthermore, the inhibitory type of luteolin on lenvatinib showed an un-competitive in RLM and a mixed in HLM. Collectively, flavonoids with liver protection, especially luteolin, may inhibit lenvatinib metabolism in vitro and in vivo.
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Affiliation(s)
- Jinzhao Yang
- Wenzhou People’s Hospital, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jie Chen
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qingqing Li
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ren-ai Xu
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaohai Chen
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Adiri WN, Basil B, Onyia CP, Asogwa P, Ugwuanyi OJ, Obienu O, Ijoma UN, Nwokediuko SC. Association between serum vitamin D status and severity of liver cirrhosis: implications for therapeutic targeting in Nigerian patients. BMC Gastroenterol 2024; 24:259. [PMID: 39135191 PMCID: PMC11318153 DOI: 10.1186/s12876-024-03353-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 08/06/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Liver cirrhosis is a chronic and progressive liver disease with significant global health implications. Recent evidence suggests an association between serum vitamin D levels and the severity of liver cirrhosis, potentially serving as a therapeutic target. This study aimed to investigate the relationship between serum vitamin D status and the severity of liver cirrhosis in a population of Nigerian patients. METHODS This analytical, cross-sectional study involved 201 participants, including 103 with liver cirrhosis and 98 age- and sex-matched controls. Serum vitamin D was measured using ELISA, with deficiency defined as < 20 ng/ml. Cirrhosis severity was assessed using Child-Pugh and MELD scores. Spearman's correlation was used to assess the relationship between vitamin D and severity of liver cirrhosis while ordinal regression analysis assessed its performance as an indicator of the disease severity. RESULT Among cirrhotic patients, 36.9% were deficient, 31.1% insufficient, and 32.0% had sufficient vitamin D levels. Serum vitamin D showed strong negative correlations with Child-Pugh and MELD scores (r = -0.696, p < 0.001; r = -0.734, p < 0.001, respectively). Ordinal regression showed that higher vitamin D levels were associated with lower severity scores (Child-Pugh: OR = 0.856, 95% CI: 0.815-0.900, p < 0.001; MELD: OR = 0.875, 95% CI: 0.837-0.915, p < 0.001). CONCLUSION Lower serum vitamin D levels correlated with increased liver cirrhosis severity, suggesting its potential as both a prognostic marker and therapeutic target. Further studies should investigate the efficacy of vitamin D supplementation in improving cirrhosis outcomes.
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Affiliation(s)
- Winnifred Njideka Adiri
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
| | - Bruno Basil
- Department of Chemical Pathology, Benue State University, Makurdi, Nigeria.
| | - Chinwe Philomena Onyia
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
| | - Promise Asogwa
- Department of Medicine, Enugu State University Teaching Hospital, Parklane, Enugu, Nigeria
| | - Oluchi Joy Ugwuanyi
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
| | - Olive Obienu
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
| | - Uchenna Nkemdilim Ijoma
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
- Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria
| | - Slyvester Chuks Nwokediuko
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital, Ituku-Ozalla, Nigeria
- Department of Medicine, College of Medicine, University of Nigeria, Ituku-Ozalla Campus, Enugu, Nigeria
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Lionis C, Papadakis S, Anastasaki M, Aligizakis E, Anastasiou F, Francque S, Gergianaki I, Mendive JM, Marketou M, Muris J, Manolakopoulos S, Papatheodoridis G, Samonakis D, Symvoulakis E, Tsiligianni I. Practice Recommendations for the Management of MASLD in Primary Care: Consensus Results. Diseases 2024; 12:180. [PMID: 39195179 DOI: 10.3390/diseases12080180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European research consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis, and linkage to specialty care for European PC settings. Based on the lessons from this project, the latest research evidence, and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral, and management of MASLD in PC. METHODS The Rand/UCLA modified Delphi panel method, with two rounds, was used to reach consensus on practice recommendations. The international panel consisted of experts from six countries, representing family medicine, gastroenterology, hepatology, cardiology, and public health. Initially, fifteen statements were drafted based on a synthesis of evidence from the literature and earlier findings from our consortium. Prior to the consensus meeting, the statements were rated by the experts in the first round. Then, in a hybrid meeting, the experts discussed findings from round one, adjusted the statements, and reassessed the updated recommendations in a second round. RESULTS In round one, there was already a high level of consensus on 10 out of 15 statements. After round 2, there were fourteen statements with a high degree of agreement (>90%). One statement was not endorsed. The approved recommendations addressed the following practice areas: risk screening and diagnosis, management of MASLD-lifestyle interventions, pharmacological treatment of MASLD/MASH, pharmacological treatment for co-morbidity, integrated care, surgical management, and other referrals to specialists. CONCLUSIONS The final set of 14 recommendations focuses on increasing comprehensive care for MASLD in PC. The recommendations provide practical evidence-based guidance tailored to PC practitioners. We expect that these recommendations will contribute to the ongoing discussion on systematic approaches to tackling MASLD and supporting European PC providers by integrating the latest evidence into practice.
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Affiliation(s)
- Christos Lionis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Sophia Papadakis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Marilena Anastasaki
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | | | - Foteini Anastasiou
- 4th Local Health Team-Municipality Practice and Academic Unit of Heraklion, Crete, 71303 Heraklion, Greece
| | - Sven Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, 2650 Edegem, Belgium
| | - Irini Gergianaki
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Juan Manuel Mendive
- La Mina Primary Health Care Centre, IDIAP Jordi Gol, 08003 Barcelona, Spain
- European Society for Primary Care Gastroenterology, London E1 6HU, UK
| | - Maria Marketou
- Clinic of Cardiology, University Hospital of Heraklion, Crete, 70013 Heraklion, Greece
| | - Jean Muris
- Department of Family Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, 6229 Maastricht, The Netherlands
| | - Spilios Manolakopoulos
- Department of Gastroenterology, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Georgios Papatheodoridis
- Gastroenterology Department, Medical School, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 11527 Athens, Greece
| | - Dimitrios Samonakis
- Clinic of Gastroenterology & Hepatology, University Hospital of Heraklion, 70013 Heraklion, Greece
| | - Emmanouil Symvoulakis
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Ioanna Tsiligianni
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, 71003 Heraklion, Greece
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Zheng W, Pang K, Min Y, Wu D. Prospect and Challenges of Volatile Organic Compound Breath Testing in Non-Cancer Gastrointestinal Disorders. Biomedicines 2024; 12:1815. [PMID: 39200279 PMCID: PMC11351786 DOI: 10.3390/biomedicines12081815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 07/16/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett's esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.
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Affiliation(s)
- Weiyang Zheng
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
| | - Ke Pang
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (K.P.); (Y.M.)
| | - Yiyang Min
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100006, China; (K.P.); (Y.M.)
| | - Dong Wu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;
- Clinical Epidemiology Unit, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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Li R, Li H, Ye X, Qin J. Metabolic Dysfunction-associated Steatotic Liver Disease is Becoming the Leading Driver of the Burden of Cirrhosis in China: Results From the Global Burden of Disease Study 2019. J Clin Gastroenterol 2024:00004836-990000000-00335. [PMID: 39102453 DOI: 10.1097/mcg.0000000000002055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 07/07/2024] [Indexed: 08/07/2024]
Abstract
OBJECTIVE Cirrhosis and other chronic liver diseases (generally referred to as cirrhosis in this article) are major causes of morbidity and mortality in China. The disease pattern of cirrhosis caused by different etiologies has been changing due to economic development and changes in lifestyle. METHODS Prevalence, incidence, disability-adjusted life-years, and mortality data were retrieved from the Global Burden of Disease study, 2019. Estimated annual percentage change was used to quantify the trends in the age-standardized prevalence rate and prevalence number of cirrhosis from 1990 to 2019. We presented the results for five causes of cirrhosis, and for different age and sex groups. RESULTS Nationwide, we found that the prevalence number of liver cirrhosis increased steadily (from 3025.3×105 to 4279.8×105) from 1990 to 2019. Notably, the age-standardized prevalence rate of cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) increased throughout the study period, and MASLD has exceeded the hepatitis B virus and become the leading cause of liver cirrhosis since 1992. The highest prevalence number of MASLD occurred in the young population aged between 15 to 49 years. CONCLUSION The prevalence of liver cirrhosis caused by hepatitis B virus decreased, whereas the prevalence of liver cirrhosis caused by MASLD increased. MASLD has become the leading cause of liver cirrhosis in China. The prevalence of liver cirrhosis increased most significantly in the young age group compared with the other age group. Preventive strategies targeting MASLD would be necessary to reduce the disease burden of cirrhosis in China, especially in the young aged generation.
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Affiliation(s)
- Rui Li
- Comprehensive Medical Department
- Department of Geriatrics, Zhongnan Hospital, Wuhan University
| | - Hang Li
- Comprehensive Medical Department
- Department of Geriatrics, Zhongnan Hospital, Wuhan University
| | - Xujun Ye
- Department of Geriatrics, Zhongnan Hospital, Wuhan University
- School of Nursing, Wuhan University, Wuhan, Hubei, China
| | - Juanjuan Qin
- Department of Geriatrics, Zhongnan Hospital, Wuhan University
- School of Nursing, Wuhan University, Wuhan, Hubei, China
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36
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Oppong B, Amponsah GM, Gyabaah S, Nicholas MK, Boateng S, Ameyaw PA, Asamoah DO, Nkum BC. Upper Gastrointestinal Endoscopic Findings and Their Clinical Correlates in Patients With Liver Cirrhosis in Northern Ghana. Cureus 2024; 16:e67725. [PMID: 39318930 PMCID: PMC11421874 DOI: 10.7759/cureus.67725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2024] [Indexed: 09/26/2024] Open
Abstract
Background and study aim Liver cirrhosis causes portal hypertension that leads to dysfunction of the gastrointestinal tract, which may result in complications including upper gastrointestinal (UGI) bleeding. This study sought to determine the prevalence and the clinical correlates of these UGI abnormalities in patients with liver cirrhosis receiving care at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Patients and methods One hundred and forty-five participants with liver cirrhosis were consecutively sampled and clinically evaluated for symptoms and signs of liver cirrhosis and then underwent esophagogastroduodenoscopy (EGD). Results The mean age of the respondents was 46.50 ± 12.14 years, with the majority being males (106, 73.10%) and in Child-Pugh class C (111, 76.55%). Fatigue (128, 88.28%) and ascites (127, 87.59%) were the most common symptoms and signs, respectively. Fatigue, itch, and ascites were significantly correlated with the severity of liver cirrhosis, with an adjusted odd ratio (AOR) (confidence interval (CI)) of 3.56 (1.11-11.47), p-value of 0.03, 4.35 (1.34-14.18), p-value of 0.02 and 22.50 (4.88-103.77), p-value < 0.01, respectively. Esophageal varices were the most common UGI endoscopic findings, occurring in 102 (70.34%) patients, and correlated with the severity of liver cirrhosis, AOR (CI) of 5.19 (1.70-15.87), p-value of 0.01. Other common findings included gastritis in 71 (48.97%), portal hypertensive gastropathy in 67 (46.2%), duodenitis in 49 (33.79%), and peptic ulcer in 46 (31.72%). Conclusions Fatigue, ascites, and esophageal varices were the most common symptoms, signs, and EGD findings, respectively. Fatigue, itch, ascites, esophageal varices, duodenitis, and gastric antral vascular ectasia correlate with the severity of liver cirrhosis.
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Affiliation(s)
- Bright Oppong
- Internal Medicine/Gastroenterolgy, Komfo Anokye Teaching Hospital, Kumasi, GHA
- Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, GHA
| | - Gordon M Amponsah
- Internal Medicine/Cardiology, Komfo Anokye Teaching Hospital, Kumasi, GHA
- Physiology, Kwame Nkrumah University of Science and Technology, Kumasi, GHA
| | - Solomon Gyabaah
- Internal Medicine, Komfo Anokye Teaching Hospital, Kumasi, GHA
| | | | - Sarpong Boateng
- Internal Medicine, Bridgeport Hospital/Yale New Haven Health, Bridgeport, USA
| | - Prince A Ameyaw
- Internal Medicine, Bridgeport Hospital/Yale New Haven Health, Bridgeport, USA
| | | | - Bernard C Nkum
- Internal Medicine/Cardiology, Kwame Nkrumah University of Science and Technology, Kumasi, GHA
- Medicine, Komfo Anokye Teaching Hospital, Kumasi, GHA
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Feng X, Huang N, Wu Y, Gao F, Chen X, Zhang C, Zhang B, Sun T. Alcoholic Liver Disease in China: A Disease Influenced by Complex Social Factors That Should Not Be Neglected. J Clin Transl Hepatol 2024; 12:677-684. [PMID: 38993514 PMCID: PMC11233974 DOI: 10.14218/jcth.2024.00034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/06/2024] [Indexed: 07/13/2024] Open
Abstract
Alcoholic liver disease (ALD) encompasses liver damage caused by chronic, excessive alcohol consumption. It manifests initially as marked hepatocellular steatosis and can progress to steatohepatitis, liver fibrosis, and cirrhosis. With China's rapid economic growth, coupled with a complex social background and the influence of a deleterious wine culture, the number of patients with ALD in China has increased significantly; the disease has become a social and health problem that cannot be ignored. In this review, we briefly described the social factors affecting ALD in China and elaborated on differences between alcoholic and other liver diseases in terms of complications (e.g., cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma, addiction, and other extrahepatic diseases). We also emphasized that ALD was more dangerous and difficult to treat than other liver diseases due to its complications, and that precise and effective treatment measures were lacking. In addition, we considered new ideas and treatment methods that may be generated in the future.
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Affiliation(s)
- Xiaofeng Feng
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Nafei Huang
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yuqin Wu
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Fei Gao
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xiaomei Chen
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chenyi Zhang
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Bing Zhang
- Hangzhou First People's Hospital, Hangzhou, Zhejiang, China
| | - Tao Sun
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Wei H, Zhao T, Liu X, Ding Q, Yang J, Bi X, Cheng Z, Ding C, Liu W. Mechanism of Action of Dihydroquercetin in the Prevention and Therapy of Experimental Liver Injury. Molecules 2024; 29:3537. [PMID: 39124941 PMCID: PMC11314611 DOI: 10.3390/molecules29153537] [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: 06/27/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.
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Affiliation(s)
- Hewei Wei
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
| | - Ting Zhao
- School of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China; (T.Z.); (X.L.)
| | - Xinglong Liu
- School of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China; (T.Z.); (X.L.)
| | - Qiteng Ding
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
- School of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China; (T.Z.); (X.L.)
| | - Junran Yang
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
| | - Xiaoyu Bi
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
| | - Zhiqiang Cheng
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
| | - Chuanbo Ding
- College of Traditional Chinese Medicine, Jilin Agricultural University, Changchun 130118, China; (H.W.); (Q.D.); (J.Y.); (X.B.); (Z.C.)
- College of Traditional Chinese Medicine, Jilin Agriculture Science and Technology College, Jilin 132101, China
| | - Wencong Liu
- School of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543002, China; (T.Z.); (X.L.)
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Ng QX, Lim YL, Xin X, Ong C, Ng WK, Thumboo J, Tan HK. What is said about #donateliver or #liverdonor? Reflexive thematic analysis of Twitter (X) posts from 2012 to 2022. BMC Public Health 2024; 24:1904. [PMID: 39014341 PMCID: PMC11250948 DOI: 10.1186/s12889-024-19381-1] [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: 01/18/2024] [Accepted: 07/05/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND There is sustained interest in understanding the perspectives of liver transplant recipients and living donors, with several qualitative studies shedding light on this emotionally charged subject. However, these studies have relied primarily on traditional semi-structured interviews, which, while valuable, come with inherent limitations. Consequently, there remains a gap in our comprehension of the broader public discourse surrounding living liver donation. This study aims to bridge this gap by delving into public conversations related to living liver donation through a qualitative analysis of Twitter (now X) posts, offering a fresh perspective on this critical issue. METHODS To compile a comprehensive dataset, we extracted original tweets containing the hashtags "#donateliver" OR "#liverdonor", all posted in English from January 1, 2012, to December 31, 2022. We then selected tweets from individual users whose Twitter (X) accounts featured authentic human names, ensuring the credibility of our data. Employing Braun and Clarke's reflexive thematic analysis approach, the study investigators read and analysed the included tweets, identifying two main themes and six subthemes. The Health Policy Triangle framework was applied to understand the roles of different stakeholders involved in the discourse and suggest areas for policy improvement. RESULTS A total of 361 unique tweets from individual users were analysed. The major theme that emerged was the persistent shortage of liver donors, underscoring the desperation faced by individuals in need of life-saving liver transplants and the urgency of addressing the organ shortage problem. The second theme delved into the experiences of liver donors post-surgery, shedding light on a variety of aspects related to the transplantation process, including the visibility of surgical scars, and the significance of returning to physical activity and exercise post-surgery. CONCLUSION The multifaceted experiences of individuals involved in the transplantation process, both recipients and donors, should be further studied in our efforts to improve the critical shortage of liver donors.
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Affiliation(s)
- Qin Xiang Ng
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
- Health Services Research Unit, Singapore General Hospital, Singapore, Singapore.
- SingHealth Duke-NUS Global Health Institute, Singapore, Singapore.
| | - Yu Liang Lim
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Xiaohui Xin
- Health Services Research Unit, Singapore General Hospital, Singapore, Singapore
| | - Clarence Ong
- Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
| | - Wee Khoon Ng
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Julian Thumboo
- Health Services Research Unit, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Medicine Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Hiang Khoon Tan
- Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
- SingHealth Duke-NUS Global Health Institute, Singapore, Singapore
- Duke Global Health Institute, Duke University, Durham, USA
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Paukner M, Ladner DP, Zhao L. Dynamic risk prediction of survival in liver cirrhosis: A comparison of landmarking approaches. PLoS One 2024; 19:e0306328. [PMID: 38968260 PMCID: PMC11226049 DOI: 10.1371/journal.pone.0306328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 06/14/2024] [Indexed: 07/07/2024] Open
Abstract
Electronic health records (EHR) data provides the researcher and physician with the opportunity to improve risk prediction by employing newer, more sophisticated modeling techniques. Rather than treating the impact of predictor variables on health trajectories as static, we explore the use of time-dependent variables in dynamically modeling time-to-event data through the use of landmarking (LM) data sets. We compare several different dynamic models presented in the literature that utilize LM data sets as the basis of their approach. These techniques include using pseudo-means, pseudo-survival probabilities, and the traditional Cox model. The models are primarily compared with their static counterparts using appropriate measures of model discrimination and calibration based on what summary measure is employed for the response variable.
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Affiliation(s)
- Mitchell Paukner
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Research (NUTORC), Comprehensive Transplant Center (CTC), Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Lihui Zhao
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
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Cuciureanu D, Filip PV, Pop CS, Diaconu SL. A short history of sarcopenia and frailty and their impact on advanced chronic liver disease. J Med Life 2024; 17:660-664. [PMID: 39440333 PMCID: PMC11493170 DOI: 10.25122/jml-2024-0304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 06/26/2024] [Indexed: 10/25/2024] Open
Abstract
Sarcopenia, first introduced as a concept by I. Rosenberg in 1989, has since been extensively studied, particularly in its correlation with chronic diseases. In recent years, sarcopenia has been increasingly associated with advanced chronic liver disease, leading to a lower quality of life and poor outcomes for these patients. Studies have shown that sarcopenia has a prevalence of 33% in individuals with advanced chronic liver disease, impacting not only the patient's health but also contributing to increased healthcare costs. The prevalence of frailty in patients with advanced chronic liver disease is 27%. Given the high prevalence of sarcopenia and frailty in this population, early diagnosis and treatment are crucial to improving patient quality of life outcomes and reducing the strain on healthcare systems globally.
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Affiliation(s)
- Denisa Cuciureanu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Petruta-Violeta Filip
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II and Gastroenterology, Emergency University Hospital of Bucharest, Romania
| | - Corina-Silvia Pop
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II and Gastroenterology, Emergency University Hospital of Bucharest, Romania
| | - Sorina-Laura Diaconu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II and Gastroenterology, Emergency University Hospital of Bucharest, Romania
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Deep A, Kumari S, Malakar S, Swaroop S, Rungta S. Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India. Cureus 2024; 16:e64550. [PMID: 39144860 PMCID: PMC11322852 DOI: 10.7759/cureus.64550] [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] [Accepted: 07/15/2024] [Indexed: 08/16/2024] Open
Abstract
Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes.
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Affiliation(s)
- Amar Deep
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
| | - Shweta Kumari
- Biochemistry, King George's Medical University, Lucknow, IND
| | - Sayan Malakar
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
| | | | - Sumit Rungta
- Medical Gastroenterology, King George's Medical University, Lucknow, IND
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Saxena D, Yadav M, Kumar T, Sharma S, Beniwal P, Malhotra V, Agarwal D, Nijhawan S. Acute Kidney Injury in Chronic Liver Disease in Northwest India: Still a Battle to Conquer. Indian J Nephrol 2024; 34:317-322. [PMID: 39156834 PMCID: PMC11328058 DOI: 10.25259/ijn_286_23] [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: 07/04/2023] [Accepted: 10/19/2023] [Indexed: 08/20/2024] Open
Abstract
Background Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis. Materials and Methods This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded. Results A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45). Conclusion Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management.
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Affiliation(s)
- Disha Saxena
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Manoj Yadav
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Tarun Kumar
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sanjeev Sharma
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Pankaj Beniwal
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Vinay Malhotra
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Dhananjai Agarwal
- Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sandeep Nijhawan
- Department of Gastroenterology, SMS Medical College and Hospital, Jaipur, Rajasthan, India
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Waseem A, Jamal A, Qadir A, Amitabh V. Serum Prolactin as a Marker of the Severity of Liver Cirrhosis in a Tertiary Hospital in India: A Cross-Sectional Study. Niger J Clin Pract 2024; 27:844-849. [PMID: 39082909 DOI: 10.4103/njcp.njcp_880_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 06/12/2024] [Indexed: 08/15/2024]
Abstract
BACKGROUND In India, cirrhosis is becoming a growing concern, leading to an unmet need for new non-invasive markers to assess the severity of liver disease. Serum prolactin is one such marker. AIM To determine the association between serum prolactin, the severity of liver cirrhosis, and its complications such as ascites, hepatic encephalopathy, and esophageal varices. METHODS This cross-sectional study involved 117 patients with liver cirrhosis. They were evaluated for some complications such as ascites, esophageal varices, and hepatic encephalopathy, as well as for severity by using the Child-Turcotte-Pugh (CTP) score. Serum prolactin levels were measured, and their relationship with both the severity and complications of liver cirrhosis was determined. A P value of < 0.05 was considered significant. RESULTS The mean age of the patients was 48.3 ± 12.08 years, and the majority (80.3%) were males. Seventy-one percent of the patients had elevated serum prolactin levels (>19.40 ng/mL). Elevated serum prolactin was found in approximately 95.0% and 86.8% of patients with hepatic encephalopathy and ascites, respectively. The median serum prolactin levels were significantly associated with esophageal varices grades (P = 0.043) and hepatic encephalopathy (P < 0.001). The sensitivity and specificity of serum prolactin for predicting severe CTP scores were 81.6% and 91.2%, respectively, with a diagnostic accuracy of 87.2%. On multivariate regression analysis, ascites (AOR = 3.8, 95%CI = 1.29-10.98, P = 0.015), hepatic encephalopathy (AOR = 6.1, 95%CI = 0.68-53.78, P = 0.012), CTP class B (AOR = 5.9, 95%CI = 1.39-24.68, P = 0.016), and CTP class C (AOR = 13.4, 95%CI = 2.25-82.21, P = 0.004) were significantly associated with elevated serum prolactin levels. CONCLUSION There was a significant association between serum prolactin levels and CTP classes, esophageal varices, ascites, and hepatic encephalopathy in patients with liver cirrhosis.
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Affiliation(s)
- A Waseem
- Department of Medicine, Hamdard Institute of Medical Sciences and Research, New Delhi, India
| | - A Jamal
- Department of Medicine, Hamdard Institute of Medical Sciences and Research, New Delhi, India
| | - A Qadir
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - V Amitabh
- Department of Medicine, Hamdard Institute of Medical Sciences and Research, New Delhi, India
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Forte E, Sanders JM, Pla I, Kanchustambham VL, Hollas MAR, Huang CF, Sanchez A, Peterson KN, Melani RD, Huang A, Polineni P, Doll JM, Dietch Z, Kelleher NL, Ladner DP. Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.19.599662. [PMID: 38948836 PMCID: PMC11212939 DOI: 10.1101/2024.06.19.599662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
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Affiliation(s)
- Eleonora Forte
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Jes M. Sanders
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Indira Pla
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | | | - Michael A. R. Hollas
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | - Che-Fan Huang
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | - Aniel Sanchez
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | - Katrina N. Peterson
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | - Rafael D. Melani
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
| | - Alexander Huang
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Praneet Polineni
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Julianna M. Doll
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Zachary Dietch
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
| | - Neil L. Kelleher
- Proteomics Center of Excellence, Northwestern University, Evanston, IL, 60208, USA
- Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA
- Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
| | - Daniela P. Ladner
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA
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Nguyen BT, Nguyen VH, Le M, Henry L, Cheung R, Nguyen MH. Impact of Income-to-Poverty Ratio on Long-Term Mortality of Persons with Chronic Liver Disease in the USA, 1999-2018. Dig Dis 2024; 42:473-485. [PMID: 38885622 PMCID: PMC11457980 DOI: 10.1159/000539858] [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: 02/08/2024] [Accepted: 06/10/2024] [Indexed: 06/20/2024]
Abstract
INTRODUCTION Chronic liver disease (CLD) is associated with increased morbidity and mortality. Understanding health disparities can inform appropriate interventions. We aimed to study mortality outcomes of those with CLD by the income level (income-to-poverty ratio <5 as lower income and ≥5 as higher income). METHODS In this retrospective cohort study, we analyzed data of adults from the National Health and Nutrition Examination Survey, 1999-2018. CLD included viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). RESULTS We analyzed 59,204 adults: 47,224 without CLD and 11,980 with CLD. The CLD group was older, more likely male, racial/ethnic minority groups or foreign-born, and had lower educational and income levels (p < 0.001). Most (80.02%) CLD participants did not have college degrees and had lower income (79.18%). Among CLD participants, similar differences were observed between lower and higher income groups. Lower income participants with CLD had significantly higher 10-year cumulative mortality compared to higher income CLD participants (15.26 vs. 8.00%, p < 0.001), with consistent findings in viral hepatitis and NAFLD subgroups (p < 0.001) but not ALD (p = 0.71). Adjusting for age, sex, race, birthplace, lower income CLD participants were 2.01 (hazard ratio [HR]: 2.01; 95% CI: 1.79-2.26) times more likely to die overall and in viral hepatitis (HR: 2.05; 95% CI: 1.31-3.24) and NAFLD subgroups (HR: 2.32; 95% CI: 1.69-3.18) but not ALD (HR: 1.17; 95% CI: 0.55-2.51). CONCLUSION Lower income, foreign-born, and racial/ethnic minority groups were disproportionately represented among those with CLD, with lower income and CLD individuals having double the mortality risk compared to their higher income counterparts. Interventions should be culturally appropriate and address socioeconomic barriers.
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Affiliation(s)
- Brian Thanh Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Brown University, Providence, RI, USA
| | - Vy Hoang Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Harvard Medical School, Boston, MA, USA
| | - Michael Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Larner College of Medicine at the University of Vermont, Burlington, VT, USA
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Palo Alto Veterans Affairs Medical Center, Palo Alto, CA, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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Cloutier M, Variya B, Akbari SA, Rexhepi F, Ilangumaran S, Ramanathan S. Profibrogenic role of IL-15 through IL-15 receptor alpha-mediated trans-presentation in the carbon tetrachloride-induced liver fibrosis model. Front Immunol 2024; 15:1404891. [PMID: 38919611 PMCID: PMC11196400 DOI: 10.3389/fimmu.2024.1404891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 05/22/2024] [Indexed: 06/27/2024] Open
Abstract
Background Inflammatory cytokines play key pathogenic roles in liver fibrosis. IL-15 is a proinflammatory cytokine produced by myeloid cells. IL-15 promotes pathogenesis of several chronic inflammatory diseases. However, increased liver fibrosis has been reported in mice lacking IL-15 receptor alpha chain (IL-15Rα), suggesting an anti-fibrogenic role for IL-15. As myeloid cells are key players in liver fibrosis and IL-15 signaling can occur independently of IL-15Rα, we investigated the requirement of IL-15 and IL-15Rα in liver fibrosis. Methods We induced liver fibrosis in Il15-/- , Il15ra-/- and wildtype C57BL/6 mice by the administration of carbon tetrachloride (CCl4). Liver fibrosis was evaluated by Sirius red and Mason's trichrome staining and α-smooth muscle acting immunostaining of myofibroblasts. Gene expression of collagens, matrix modifying enzymes, cytokines and chemokines was quantified by RT-qPCR. The phenotype and the numbers of intrahepatic lymphoid and myeloid cell subsets were evaluated by flow cytometry. Results Both Il15-/- and Il15ra-/- mice developed markedly reduced liver fibrosis compared to wildtype control mice, as revealed by reduced collagen deposition and myofibroblast content. Il15ra-/- mice showed further reduction in collagen deposition compared to Il15-/- mice. However, Col1a1 and Col1a3 genes were similarly induced in the fibrotic livers of wildtype, Il15-/- and Il15ra-/- mice, although notable variations were observed in the expression of matrix remodeling enzymes and chemokines. As expected, Il15-/- and Il15ra-/- mice showed markedly reduced numbers of NK cells compared to wildtype mice. They also showed markedly less staining of CD45+ immune cells and CD68+ macrophages, and significantly reduced inflammatory cell infiltration into the liver, with fewer pro-inflammatory and anti-inflammatory monocyte subsets compared to wildtype mice. Conclusion Our findings indicate that IL-15 exerts its profibrogenic role in the liver by promoting macrophage activation and that this requires trans-presentation of IL-15 by IL-15Rα.
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Mazhnaya A, Geurts B, Brigida K, Bakieva S, Sadirova S, Witzigmann A, Musabaev E, Brandl M, Weishaar H, Dudareva S, Bcheraoui CE. Barriers and facilitators to viral hepatitis testing in Uzbekistan: scoping qualitative study among key stakeholders, healthcare workers, and the general population. BMC Public Health 2024; 24:1482. [PMID: 38831285 PMCID: PMC11145832 DOI: 10.1186/s12889-024-18953-5] [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: 12/07/2023] [Accepted: 05/24/2024] [Indexed: 06/05/2024] Open
Abstract
INTRODUCTION In the World Health Organization European Region, an estimated 14 million people live with a chronic hepatitis B virus infection (HBV), and 12 million are affected by a hepatitis C virus infection (HCV). Uzbekistan bears a major burden of HBV and has one of the highest HCV prevalence in the region. Following a presidential decree in May 2022, significant funds were allocated to the viral hepatitis (VH) elimination program in Uzbekistan. The program expands VH testing to reach 500,000 people annually during 2022-2025 as part of the VH elimination strategy that includes the provision of free testing and affordable treatment. Exploring the existing barriers and facilitators to VH testing is pivotal for informing these interventions. METHODS This study uses a cross-sectional qualitative design to identify and explore the barriers and facilitators to VH testing among the general population in Uzbekistan. We collected data during October-November 2022 through semi-structured interviews with 12 key informants (KIs) and 7 focus group discussions with two target populations: the general population and healthcare workers (HCW) in Tashkent, Uzbekistan. RESULTS Following the capability-opportunity-motivation-behavior model (COM-B model) as a framework for the analysis, we identified major capability barriers to VH testing primarily linked to low health literacy and limited knowledge about VH types, symptoms, transmission, testing and treatment. Physical opportunity barriers included the time and financial costs associated with testing, diagnostics, and treatment. Sociocultural opportunity barriers involved anticipated negative reactions and stigmatization, particularly affecting women. Motivational barriers included a reluctance to be tested when asymptomatic and a general fear of receiving positive test results. The involvement of healthcare workers in promoting VH awareness and motivating the general population emerged as a facilitator. CONCLUSIONS A multi-pronged approach is recommended to achieve VH testing goals among the general population, focusing on raising awareness and health literacy and creating an enabling environment that ensures easy accessibility and minimizing VH testing-associated costs.
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Affiliation(s)
- Alyona Mazhnaya
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany.
- National University of Kyiv-Mohyla Academy, Kyiv, Ukraine.
| | - Brogan Geurts
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
| | | | | | | | - Annika Witzigmann
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
| | | | - Michael Brandl
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Heide Weishaar
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
| | - Sandra Dudareva
- Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany
| | - Charbel El Bcheraoui
- Centre for International Health Protection, Robert Koch Institute, Berlin, Germany
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Jha AA, Singh A, Nair S, Manrai M, Jha AA, Thareja S, Rao PP, Sood AK, Sharma PK, Shukla R. Demography of brain stem death and factors leading to successful consent for organ donation. Med J Armed Forces India 2024. [DOI: 10.1016/j.mjafi.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2024] Open
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50
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Shan S, Zhao X, Wood-Trageser MA, Hu D, Liu L, Qi B, Jian J, Wang P, Lv W, Hu C. Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis. J Pathol 2024; 263:178-189. [PMID: 38551075 DOI: 10.1002/path.6273] [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: 08/08/2023] [Revised: 01/05/2024] [Accepted: 02/13/2024] [Indexed: 05/12/2024]
Abstract
The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Shan Shan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, PR China
| | - Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Disease, Beijing, PR China
| | | | - Doudou Hu
- The Second Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, PR China
| | - Liwei Liu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
| | - Beining Qi
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
| | - Jianbo Jian
- Department of Radiation Oncology, Tianjin Medical University General Hospital, Tianjin, PR China
| | - Ping Wang
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China
| | - Wenjuan Lv
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
| | - Chunhong Hu
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, PR China
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