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Yang Y, He X, Tan S, Qu X, Huang W, Cai J, You J, Fu X, He Y, Yang H. The association between immunoinflammatory biomarkers NLR, PLR, LMR and nonalcoholic fatty liver disease: a systematic review and meta-analysis. Clin Exp Med 2025; 25:39. [PMID: 39812894 PMCID: PMC11735594 DOI: 10.1007/s10238-024-01539-1] [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: 11/05/2024] [Accepted: 12/13/2024] [Indexed: 01/16/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder closely linked to metabolic syndrome. Identifying novel, easily measurable biomarkers could significantly enhance the diagnosis and management of NAFLD in clinical settings. Recent studies suggest that immunoinflammatory biomarkers-specifically, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-may offer diagnostic value for NAFLD. However, the effectiveness of these biomarkers has not been comprehensively assessed in this patient population. This systematic review and meta-analysis aimed to evaluate the association between these immunoinflammatory biomarkers and NAFLD. As of August 8, 2024, databases including PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were systematically searched to compare NLR, PLR, and LMR levels in NAFLD patients and healthy controls. Study quality was assessed using the Newcastle-Ottawa Scale, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated (PROSPERO registry number: CRD42024580812). A total of 20 studies were included in the meta-analysis. Results indicated that NAFLD patients had significantly higher NLR levels (SMD = 0.43; 95% CI 0.28-0.58; p < 0.001) and lower PLR levels (SMD = - 0.29; 95% CI - 0.41 to - 0.17; p < 0.001) compared to controls. However, no significant difference in LMR was observed between NAFLD patients and controls(SMD = 0.08; 95% CI - 0.00 to 0.17; p = 0.051). These findings suggest that NLR and PLR may hold promise as diagnostic markers for NAFLD, while LMR appears to have limited diagnostic utility. Further research is warranted to explore the potential role of these biomarkers in tracking disease progression.
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Affiliation(s)
- Yunyi Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Xiaoli He
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Shufa Tan
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Xiaoxiao Qu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Weijin Huang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Jiayuan Cai
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Jiawen You
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Xinyi Fu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China
| | - Yanming He
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China.
| | - Hongjie Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai, 200437, China.
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Yang Y, Ding R, Li T, Li R, Song Y, Yuan Y, Bai X, Hu Y. Elevated neutrophil-percentage-to-albumin ratio predicts increased all-cause and cardiovascular mortality in hypertensive patients: Evidence from NHANES 1999-2018. Maturitas 2025; 192:108169. [PMID: 39662204 DOI: 10.1016/j.maturitas.2024.108169] [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: 08/08/2024] [Revised: 12/02/2024] [Accepted: 12/04/2024] [Indexed: 12/13/2024]
Abstract
BACKGROUND This study investigates the association between the neutrophil-percentage-to-albumin ratio (NPAR) and all-cause mortality in patients with hypertension, and its relationship with cardiovascular mortality. METHODS This study examined data from 18,469 adults with hypertension in the National Health and Nutrition Examination Survey (1999-2018) and the mortality data from the National Death Index. The link between NPAR and mortality risk was visualized using restricted cubic splines. The optimal NPAR cut-off value for the prediction of survival outcomes was identified via maximally selected rank statistics. We employed weighted multivariate Cox regression and subgroup analyses to evaluate the relationship between NPAR and risk of all-cause and cardiovascular mortality. We assessed NPAR's predictive accuracy for survival outcomes using time-related receiver operating characteristic analysis. RESULTS During a median follow-up of 105 months, 31.8 % of 18,469 participants died, with 8.9 % from cardiovascular causes. Restricted cubic splines analysis showed a positive link between NPAR and both all-cause and cardiovascular mortality. Cox models indicated that higher NPAR (>1602.08) significantly raised risks of all-cause (HR 1.80, 95 % CI 1.54-2.12, p < 0.0001) and cardiovascular mortality (HR 1.54, 95 % CI 1.24-1.91, p < 0.0001). The stability of results was confirmed through stratified and interaction analyses. The area under the curve for 3-, 5-, and 10-year survival were 0.67, 0.65, and 0.63 for all-cause mortality and 0.61, 0.62, and 0.63 for cardiovascular mortality. CONCLUSIONS Elevated NPAR independently raises the risk of all-cause and cardiovascular mortality in hypertensive patients, indicating its potential in the clinic as a practical tool for predicting long-term mortality risks and influencing treatment strategies.
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Affiliation(s)
- Yan Yang
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Renzhong Ding
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - TingTing Li
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Ruihao Li
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Yi Song
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Ye Yuan
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Xue Bai
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China
| | - Yijie Hu
- Department of Cardiovascular Surgery, Daping Hospital, Amy Medical University, Chongqing 400042, China.
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Dong K, Zheng Y, Wang Y, Guo Q. Predictive role of neutrophil percentage-to-albumin ratio, neutrophil-to-lymphocyte ratio, and systemic immune-inflammation index for mortality in patients with MASLD. Sci Rep 2024; 14:30403. [PMID: 39638820 PMCID: PMC11621551 DOI: 10.1038/s41598-024-80801-8] [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: 09/19/2024] [Accepted: 11/21/2024] [Indexed: 12/07/2024] Open
Abstract
There are no studies discussing the significance of neutrophil-to-lymphocyte ratio (NLR), neutrophil-percentage-to-albumin ratio (NPAR), and systemic immune-inflammation index (SII) in predicting poor prognosis in patients with metabolic dysfunction associated steatotic liver disease (MASLD); this study aimed to investigate the relationship between these three inflammatory markers and all-cause mortality and cardiovascular disease (CVD) mortality in patients with MASLD. Survival data for 3970 participants were obtained from National Death Index (NDI) records associated with the National Health and Nutrition Examination Survey (NHANES) dataset, the associations of NPAR, NLR, and SII with all-cause and CVD mortality were analyzed using multivariate COX regression modeling, restricted cubic spline (RCS) was used to explore nonlinear relationships and to determine the inflection point, regrouping was done according to the nonlinear inflection point, using multivariate COX regression modeling, subgroup analysis, and the Kaplan-Meier survival curves to evaluate differences in risk of death between the two groups. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to assess the predictive efficacy of NPAR, NLR, and SII on survival outcomes. Multivariate COX regression and RCS analyses revealed a positive linear correlation between NLR and all-cause and CVD mortality, whereas a nonlinear relationship was found between NPAR and SII and all-cause and CVD mortality. Further reclassified into two groups according to the inflection point, multivariate COX regression analyses showed a significant difference in the risk of death between the two NPAR groups (HR 1.37, 95% CI = (1.01, 1.86) for all-cause mortality and HR 2.03, 95% CI = (1.24, 3.32) for CVD mortality ) and no difference in the risk of death between the two SII groups (HR 1.11, 95% CI = (0.87, 1.42) for all-cause mortality and HR 1.35, 95% CI = (0.86, 2.12) for CVD mortality), and Kaplan-Meier survival curves showed that both all-cause and CVD mortality rates were higher in patients with MASLD above the NPAR inflection point (log-rank P < 0.05). Subgroup analyses showed that the associations between high levels of NPAR and all-cause mortality were generally consistent across populations (P interaction > 0.05). Also, COPD subgroups had a significant effect on the correlation between high levels of NPAR and CVD mortality (P interaction < 0.05). Time-dependent ROC show the predictive value of NPAR, NLR, and SII for all-cause and CVD mortality in MASLD patients. The correlation between NPAR and mortality was nonlinear, and NLR was linearly and positively correlated with mortality, Measuring NPAR and NLR may be useful in assessing risk and predicting prognosis in populations of patients with MASLD.
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Affiliation(s)
- Kaixuan Dong
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, China
- Department of Gastroenterology, Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
- Department of Gastroenterology, Gansu Province Clinical Research Center for Digestive Diseases, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
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Yang X, Zhuo S, Zhuang H, Fang T. Interaction between the systemic immune-inflammation index and trouble sleeping in nonalcoholic fatty liver disease: a cross-sectional study of the NHANES 2005-2018 data. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:175. [PMID: 39478637 PMCID: PMC11526651 DOI: 10.1186/s41043-024-00670-9] [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: 05/08/2024] [Accepted: 10/16/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND The systemic immune-inflammation index (SII) and trouble sleeping are independent risk factors for nonalcoholic fatty liver disease (NAFLD). Nevertheless, studies investigating the combined effects of the SII and troubled sleeping on NAFLD are lacking. In this study, we investigated the independent relationships and interactions between trouble sleeping and the SII among patients with NAFLD. METHODS Data from seven survey cycles of the National Health and Nutrition Examination Survey (NHANES) (2005-2018) were analyzed. The SII was obtained by counting platelets, neutrophils, and lymphocytes. NAFLD was diagnosed using the US fatty liver index. Trouble sleeping was diagnosed using a sleep disorder questionnaire. The correlation between trouble sleeping and the SII in NAFLD was investigated using multiple regression analysis, subgroup stratification, interaction tests, and restricted cubic spline, and the presence or absence of additive or multiplicative interactions was determined. Additionally, mediation analyses were performed to explore the role of the SII in mediating the effects of trouble sleeping on NAFLD. RESULTS The survey included 10 963 participants. Multivariate logistic regression revealed that SII (OR: 1.21, 95% CI 1.08-1.35) and trouble sleeping (OR: 1.24, 95% CI 1.05-1.47) were positively correlated with NAFLD. For NAFLD, an additive but not multiplicative interaction was noted between the SII and trouble sleeping. The SII partially mediated the association between trouble sleeping and NAFLD, accounting for approximately 3.11% of the total effect (95% CI 0.01-0.05). CONCLUSION The SII and trouble sleeping were independently correlated with NAFLD risk. Furthermore, a combined effect may exist between SII and trouble sleeping, which increases the risk of NAFLD.
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Affiliation(s)
- Xinxia Yang
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China
| | - Shitu Zhuo
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China
| | - Huie Zhuang
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China
| | - Taiyong Fang
- The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
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Shen HC, Wang CH, Yang CW, Lin YH, Yeh HY, Perng DW, Yang YY, Hou MC. Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis. Medicine (Baltimore) 2024; 103:e38530. [PMID: 38941417 PMCID: PMC11466115 DOI: 10.1097/md.0000000000038530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 05/17/2024] [Indexed: 06/30/2024] Open
Abstract
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
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Affiliation(s)
- Hsiao-Chin Shen
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Chest, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Hsiang Wang
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Wen Yang
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsuan Lin
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Hsiao-Yun Yeh
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Diahn-Warng Perng
- Department of Chest, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ying-Ying Yang
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan
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Li L, Yu J, Zhou Z. Association between platelet indices and non-alcoholic fatty liver disease: a systematic review and meta-analysis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:264-273. [PMID: 36263810 DOI: 10.17235/reed.2022.9142/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
BACKGROUND Platelet indices have the potential for the evaluation of the activity of non-alcoholic fatty liver disease (NAFLD), but their associations are under hard debate. This meta-analysis aims to assess whether platelet count (PC), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with NAFLD and its progression. METHODS A literature search was conducted using electronic databases to find publications up to July 2022, where the relationship between PC, MPV, PDW and NAFLD was evaluated. Random-effects models were applied to pool effect estimates that were presented as standardized mean differences (SMD) with 95% confidence interval (CI). RESULTS Nineteen studies involving 3592 NAFLD patients and 1194 healthy individuals were included. The pooled results showed that NAFLD patients had a lower PC (SMD=-0.66, 95% CI =-1.22 to -0.09, P=0.023) but a higher MPV (SMD=0.89, 95% CI=0.26-1.51, P=0.005) and PDW (SMD=0.55, 95% CI=0.11-0.99, P=0.014) compared to healthy controls. Patients with non-alcoholic steatohepatitis (NASH) exhibited a lower PC (SMD=-0.86, 95% CI=-1.20 to -0.52, P<0.001) and a higher MPV (SMD=0.71, 95% CI=0.40-1.02, P<0.001) than non-NASH individuals. A meta-regression analysis demonstrated that MPV was significantly positively correlated with aspartate aminotransferase (P=0.008), the total cholesterol (P=0.003), triglyceride (P=0.006) and low-density lipoprotein cholesterol (P=0.007), but was significantly negatively correlated with high-density lipoprotein cholesterol (P=0.010). CONCLUSION This meta-analysis revealed that NAFLD patients presented a reduced PC but an increased MPV and PDW, and the changes might be associated with NAFLD severity. A higher MPV is associated with lipid metabolic disorders in NAFLD.
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Affiliation(s)
- Li Li
- Clinical Laboratory, Binhai County People's Hospital
| | - Jianxiu Yu
- Clinical Laboratory, Binhai County People's Hospital
| | - Zhongwei Zhou
- Clinical Laboratory, Yancheng Third People's Hospital, China
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Duran-Bertran J, Rusu EC, Barrientos-Riosalido A, Bertran L, Mahmoudian R, Aguilar C, Riesco D, Martínez S, Ugarte Chicote J, Sabench F, Richart C, Auguet T. Platelet-associated biomarkers in nonalcoholic steatohepatitis: Insights from a female cohort with obesity. Eur J Clin Invest 2024; 54:e14123. [PMID: 37929908 DOI: 10.1111/eci.14123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/20/2023] [Accepted: 10/21/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND There is a lack of noninvasive diagnostic methods for nonalcoholic steatohepatitis (NASH), the severe condition of metabolic dysfunction-associated steatotic liver disease (MASLD). Platelet activation, evaluated through certain related parameters, is associated with liver disease and inflammation, but previous results are inconclusive. AIM To investigate the potential utility of platelet-related indices as noninvasive diagnostic markers for the detection and prediction of MASLD, focusing on NASH. RESULTS We found that mean platelet volume (MPV), plateletcrit (PCT) and platelet distribution width (PDW) were increased in the severe and morbidly obese (SMO) group compared to the normal weight (NW) group. We found decreased levels of MPV in steatosis and NASH patients. MPV and PCT values were decreased in the presence of mild liver inflammation. Platelet count (PLA) and PCT values were lower in the presence of ballooning. We obtained an area under the ROC curve of 0.84 using MPV and three other variables to predict MASLD. CONCLUSIONS Some platelet-related indices vary depending on liver condition. Here, we reported decreased MPV in MASLD presence. Moreover, we presented for the first time a predictive model using MPV, ALT levels and the presence of diabetes mellitus and metabolic syndrome to predict MASLD in obese women. Also, MPV is closely related to early liver inflammation in NASH, and PLA and PCT are related to hepatic ballooning. These indices could be widely used for the early detection of NASH since they are usually determined in routine laboratory tests.
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Affiliation(s)
- Joan Duran-Bertran
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei Medicina Interna, Departament de Medicina i Cirurgia, Hospital Universitari de Tarragona Joan XXIII, URV, Tarragona, Spain
| | - Elena Cristina Rusu
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Andrea Barrientos-Riosalido
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Laia Bertran
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Razieh Mahmoudian
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Carmen Aguilar
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - David Riesco
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei Medicina Interna, Departament de Medicina i Cirurgia, Hospital Universitari de Tarragona Joan XXIII, URV, Tarragona, Spain
| | - Salomé Martínez
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei Anatomia Patològica, Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
| | - Javier Ugarte Chicote
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei Anatomia Patològica, Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain
| | - Fàtima Sabench
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei de Cirurgia, Departament de Medicina i Cirurgia, Hospital Sant Joan de Reus, URV, IISPV, Reus, Spain
| | - Cristóbal Richart
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Teresa Auguet
- Grup de Recerca GEMMAIR (AGAUR) - Medicina Aplicada (URV), Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
- Servei Medicina Interna, Departament de Medicina i Cirurgia, Hospital Universitari de Tarragona Joan XXIII, URV, Tarragona, Spain
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Săsăran MO, Muntean C, Lupu A, Lupu VV. Neutrophils: tissue and circulating signatures of pediatric non-alcoholic fatty liver disease. Front Cell Dev Biol 2024; 11:1336033. [PMID: 38239291 PMCID: PMC10794720 DOI: 10.3389/fcell.2023.1336033] [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: 11/09/2023] [Accepted: 12/18/2023] [Indexed: 01/22/2024] Open
Abstract
The recent rise in non-alcoholic fatty liver disease (NAFLD) among children and adolescents led to a thorough investigation of the peculiarities of the cellular infiltrate which characterize the disease at young ages. This review aims to highlight the key involvement of neutrophils in the pathogenesis of pediatric NAFLD and the potential biomarker role of neutrophil-to-lymphocyte ratio (NLR) in the same pediatric disorder. Neutrophils, which are first responders to inflammation, constitute an abundant component of an infiltrate which is particularly disposed within the portal area of children with NAFLD. The involvement of neutrophils in triggering liver fibrosis has been related amongst others to reactive oxygen species (ROS) production, to the stimulation of hepatic stellate cells, and to their synthesis of neutrophil elastase. As immune imbalance characterizes NAFLD, potentially emerging non-invasive biomarkers such as NLR have been proposed for the detection and prognosis of NAFLD. In adults, several studies asserted the role of NLR in the prediction of advancing liver fibrosis and mortality in subjects with NAFLD. In children, data is scarce with contradicting findings, as some studies failed to identify significant shifting in NLR values in children with NAFLD when compared with obese controls without liver impairment. However, NLR seems to significantly increase in children with obesity and different degrees of NAFLD when compared to healthy counterparts and their changes seem to be reversible with weight loss. Still, paucity of pediatric studies calls for future research addressing the role of NLR in predicting NAFLD development and progression in children with obesity.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics 3, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania
| | - Carmen Muntean
- Department of Pediatrics 1, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Romania
| | - Ancuța Lupu
- Department of Pediatrics, University of Medicine and Pharmacy Gr. T. Popa Iași, Iași, Romania
| | - Vasile Valeriu Lupu
- Department of Pediatrics, University of Medicine and Pharmacy Gr. T. Popa Iași, Iași, Romania
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Malladi N, Alam MJ, Maulik SK, Banerjee SK. The role of platelets in non-alcoholic fatty liver disease: From pathophysiology to therapeutics. Prostaglandins Other Lipid Mediat 2023; 169:106766. [PMID: 37479133 DOI: 10.1016/j.prostaglandins.2023.106766] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/29/2023] [Accepted: 07/17/2023] [Indexed: 07/23/2023]
Abstract
Platelets are one of the key mediators in thrombosis as well as in the progression of many diseases. An increase in platelet activation and a decrease in platelet count is associated with a plethora of liver diseases. In non-alcoholic fatty liver disease (NAFLD), platelets are highly activated and participate in the disease progression by enhancing the pro-thrombotic and pro-inflammatory state. Some altered platelet parameters such as mean platelet volume, plateletcrits, and platelet distribution width, aspartate transaminase to platelet ratio index, liver stiffness to platelet ratio and red cell distribution width to platelet ratio were found to be associated with NAFLD disease. Further, platelet contributes to the progression of cardiovascular complications in NAFLD is gaining the researcher's attention. An elevated mean platelet volume is known to enhance the risk of stroke, atherosclerosis, thrombosis, and myocardial infarction in NAFLD. Evidence also suggested that modulation in platelet function using aspirin, ticlopidine, and cilostazol help in controlling the NAFLD progression. Future research should focus on antiplatelet therapy as a treatment strategy that can control platelet activation in NAFLD as well as its cardiovascular risk. In the present review, we have detailed the role of platelets in NAFLD and its cardiovascular complications. We further aimed to highlight the growing need for antiplatelet therapy in NAFLD.
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Affiliation(s)
- Navya Malladi
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati 781101, Assam, India
| | - Md Jahangir Alam
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati 781101, Assam, India; Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India
| | - Subir K Maulik
- Indian Council of Medical Research, Ministry of Health, New Delhi 110029, India
| | - Sanjay K Banerjee
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Guwahati 781101, Assam, India.
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10
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Zhu H, Zheng M, He H, Lei H, Tai W, Yang J. High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study. BMC Gastroenterol 2023; 23:400. [PMID: 37978445 PMCID: PMC10657125 DOI: 10.1186/s12876-023-03031-8] [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: 09/10/2023] [Accepted: 11/05/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by inflammation of the interlobular bile ducts. Ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to 40% of patients with PBC have an incomplete response to UDCA. Neutrophil-to-lymphocyte (NLR) has been used to predict prognosis in various liver diseases. There is limited evidence on the treatment response to UDCA in PBC patients. Our study aimed to evaluate the relationship between NRL and the response to UDCA treatment in PBC patients. METHODS A total of 257 primary biliary cholangitis (PBC) patients treated with UDCA (13-15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on alkaline phosphatase levels ≤1.67 times the upper limit of the normal value after 12 months of UDCA treatment. Multivariable logistic regression analysis was performed to investigate the association between NLR at baseline and the response to 12 months of UDCA treatment after adjusting for important confounding variables. The stability of the results was evaluated by unadjusted and adjusted models. RESULTS The results of multiple regression analysis showed that NLR at baseline was positively associated with the nonresponse to UDCA treatment after adjustments for potential confounders (age, sex, BMI, hypertension, arterial plaque, thyroid disease, jaundice, albumin, globulin, total bile acid, ALP, GGT, LDLC, total cholesterol, hemoglobin, and APTT) (OR = 1.370, 95% CI 1.066-1.761). These results reveal that NLR is an independent risk factor for UDCA treatment nonresponse. CONCLUSIONS Our results suggest that PBC patients with a high NLR had a worse response to UDCA therapy.
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Affiliation(s)
- Huiling Zhu
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Mengyao Zheng
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Haiyu He
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hongtao Lei
- School of Public Health Kunming Medical University, Kunming, China
| | - Wenlin Tai
- Clinical Lab, Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jinhui Yang
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University, Kunming, China.
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11
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Noormohammadi M, Ghorbani Z, Shahinfar H, Shidfar F. Is there any hepatic impact associated with rice bran arabinoxylan compound supplementation? A systematic review and dose-response meta-analysis of randomized controlled trials. Clin Nutr ESPEN 2023; 57:665-675. [PMID: 37739721 DOI: 10.1016/j.clnesp.2023.08.023] [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: 05/25/2023] [Revised: 08/01/2023] [Accepted: 08/19/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND & AIMS Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). METHODS In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied. RESULTS Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value = 0.001, I2 (%) = 29.9; P heterogeneity = 0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170). CONCLUSIONS In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results. REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYZES CRD42022361002, registration time: 29/09/2022.
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Affiliation(s)
- Morvarid Noormohammadi
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran; Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Zeinab Ghorbani
- Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Department of Clinical Nutrition, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| | - Hossein Shahinfar
- Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran; Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Farzad Shidfar
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
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12
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Vachliotis ID, Polyzos SA. The Role of Tumor Necrosis Factor-Alpha in the Pathogenesis and Treatment of Nonalcoholic Fatty Liver Disease. Curr Obes Rep 2023; 12:191-206. [PMID: 37407724 PMCID: PMC10482776 DOI: 10.1007/s13679-023-00519-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/20/2023] [Indexed: 07/07/2023]
Abstract
PURPOSE OF REVIEW To summarize experimental and clinical evidence on the association between tumor necrosis factor-α (TNF-α) and nonalcoholic fatty liver disease (NAFLD) and discuss potential treatment considerations. RECENT FINDINGS Experimental evidence suggests that TNF-α is a cytokine with a critical role in the pathogenesis of NAFLD. Although, the production of TNF-α may be an early event during the course of nonalcoholic fatty liver (NAFL), TNF-α may play a more substantial role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and NAFLD-associated fibrosis. Moreover, TNF-α may potentiate hepatic insulin resistance, thus interconnecting inflammatory with metabolic signals and possibly contributing to the development of NAFLD-related comorbidities, including cardiovascular disease, hepatocellular carcinoma, and extra-hepatic malignancies. In clinical terms, TNF-α is probably associated with the severity of NAFLD; circulating TNF-α gradually increases from controls to patients with NAFL, and then, to patients with NASH. Given this potential association, various therapeutic interventions (obeticholic acid, peroxisome proliferator-activated receptors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, probiotics, synbiotics, rifaximin, vitamin E, pentoxifylline, ursodeoxycholic acid, fibroblast growth factor-21, n-3 polyunsaturated fatty acids, statins, angiotensin receptor blockers) have been evaluated for their effect on TNF-α and NAFLD. Interestingly, anti-TNF biologics have shown favorable metabolic and hepatic effects, which may open a possible therapeutic window for the management of advanced NAFLD. The potential key pathogenic role of TNF-α in NAFLD warrants further investigation and may have important diagnostic and therapeutic implications.
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Affiliation(s)
- Ilias D. Vachliotis
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Second Department of Internal Medicine, 424 General Military Hospital, Thessaloniki, Greece
| | - Stergios A. Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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13
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Liu CF, Chien LW. Predictive Role of Neutrophil-Percentage-to-Albumin Ratio (NPAR) in Nonalcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Nondiabetic US Adults: Evidence from NHANES 2017-2018. Nutrients 2023; 15:nu15081892. [PMID: 37111111 PMCID: PMC10141547 DOI: 10.3390/nu15081892] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/31/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent globally and includes chronic liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). The neutrophil-to-albumin ratio (NPAR) is a cost-effective, readily available biomarker of inflammation used to assess cancer and cardiovascular disease prognosis, and it may be of predictive value in NAFLD. This study was to evaluate the associations between the NPAR, the neutrophil-to-lymphocyte ratio (NLR), and the presence of NAFLD or advanced liver fibrosis, and to assess the predictive value of the NPAR in NAFLD in a nationally representative database. This population-based, cross-sectional, retrospective study analyzed the secondary data of adults with NAFLD or advanced liver fibrosis extracted from the National Health and Nutrition Examination Survey (NHANES) database 2017-2018. NHANES participants with complete information of vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) were enrolled. A logistic regression analysis was used to determine the associations between the variables in the participants with and without NAFLD or advanced liver fibrosis. The mean values of the lymphocyte counts, neutrophil counts, NPAR, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), total cholesterol, triglycerides, and HbA1c were significantly higher in the participants with NAFLD than in those without NAFLD or advanced liver fibrosis. The mean blood albumin levels of the subjects without NAFLD or advancing fibrosis were considerably greater than those of the individuals with these conditions. The mean values of the NLR, NPAR, AST, ALT, triglycerides, lymphocyte count, neutrophil count, and HbA1c were significantly higher in patients with advanced fibrosis than in those without advanced fibrosis. A multivariate analysis showed that per unit increases in both the NLR and NPAR were significantly associated with an increased risk of developing NAFLD, while neither the NLR nor NPAR was significantly associated with higher odds of advanced fibrosis. In conclusion, the novel biomarker NPAR demonstrates a good association with NAFLD, along with participants' clinical characteristics, in a nationwide population. The NPAR may serve as a biomarker for NAFLD and help clinicians refine the diagnosis and treatment of chronic liver disease.
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Affiliation(s)
- Chi-Feng Liu
- School of Nursing, National Taipei University of Nursing and Health Science, Taipei 112, Taiwan
| | - Li-Wei Chien
- Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 112, Taiwan
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 112, Taiwan
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14
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Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2023; 24:ijms24032313. [PMID: 36768637 PMCID: PMC9916753 DOI: 10.3390/ijms24032313] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/18/2023] [Accepted: 01/21/2023] [Indexed: 01/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation. Along with the high associated economic burden, the high mortality rate among NAFLD patients raises interest, not only in the search for novel therapeutic approaches, but also in early diagnosis and prevention to reduce the incidence of NAFLD-related complications. In this line, an exhaustive characterization of the immune status of patients with NAFLD is mandatory. Herein, we attempted to gather and compare the current and relevant scientific evidence on this matter, mainly on human reports. We addressed the current knowledge related to circulating cellular and soluble mediators, particularly platelets, different leukocyte subsets and relevant inflammatory soluble mediators.
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15
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Lack of Faecalibacterium prausnitzii and Bifidobacterium is associated with a higher risk of metabolic associated fatty liver disease in young-onset type 2 diabetes. Int J Diabetes Dev Ctries 2023. [DOI: 10.1007/s13410-022-01161-5] [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] [Indexed: 01/24/2023] Open
Abstract
Abstract
Background
The incidence of comorbidity between type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) is high, and patients tend to be younger. When people develop metabolic diseases such as T2DM and MAFLD, the original homeostasis of the gut microbiota in the body is disrupted, and gut flora drift occurs. This study investigated the relationship between the number of gut flora and MAFLD in young-onset T2DM.
Methods
This retrospective study analyzed 44 adolescent T2DM patients who were divided into a non-MAFLD group and a MAFLD group. Anthropometric measurements, clinical and biochemical markers, inflammatory markers, thyroid function assessments, and stool specimens were collected. Real-time PCR was performed to quantify several important gut flora constituents at the genus level. Student’s t-test and the chi-square test were applied for group comparisons, and binary regression models were used to explore the relationship between gut flora and MAFLD in young-onset T2DM.
Results
Among the 44 subjects, 26 (59.1%) were diagnosed with MAFLD, and 18 (40.9%) were not. Compared with the non-MAFLD group, body mass index (BMI), abdominal circumference, and levels of blood uric acid and thyroid stimulating hormone (TSH) in the MAFLD group were significantly increased, and age level and high-density lipoprotein cholesterol (HDL-C) were significantly decreased (p < 0.05). Compared with the non-MAFLD group, the abundance of Faecalibacterium prausnitzii and Bifidobacterium in the MAFLD group was significantly reduced, and the abundance of Enterococcus and Lactobacillus was significantly increased (p < 0.05). In the multivariate regression analysis, Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM, after excluding confounding factors.
Conclusion
In young-onset T2DM, there was a difference in gut flora between patients with MAFLD and those without MAFLD. Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM.
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16
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Li P, Liu L, Niu B, Mi Y, Liu Y, Feng J, Zhang P, Wu X, Chu W. Clinical value of thyroid related hormones combined with neutrophil to lymphocyte ratio in patients with nonalcoholic fatty liver disease. Medicine (Baltimore) 2022; 101:e31978. [PMID: 36595785 PMCID: PMC9794251 DOI: 10.1097/md.0000000000031978] [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] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND In sufferers with nonalcoholic fatty liver disease (NAFLD), the differences of thyroid associated hormones and neutrophil to lymphocyte ratio (NLR) in different liver pathological groups have been compared. METHODS Patients with NAFLD diagnosed by liver biopsy in our hospital from July 2012 to February 2019 were selected. All subjects were divided into nonalcoholic steatohepatitis (NASH) team and non-NASH group, no/mild fibrosis group (F0-1) and significant fibrosis group (F2-4). The differences of thyroid related hormones and NLR in these groups were in contrast, respectively. For the TSH, we conducted further evaluation based on gender. RESULTS The TSH and NLR in NASH patients were significantly higher than non-NASH patients, but there was no considerable difference in free triiodothyronine (FT3) and free thyroxine (FT4) between the 2 groups. In the gender-based subgroup analysis, the variations of TSH between the 2 groups were nonetheless statistically significant (P < .05). The TSH and NLR in the significant fibrosis group were higher than these in the non/mild liver fibrosis group, and the differences were statistically significant (P < .05), but there was no large difference in FT3 and FT4 between the 2 groups (P > .05). In addition, in the gender-based subgroup analysis and further multivariable analysis, the variations of TSH between the 2 groups were still statistically significant (P < .05). CONCLUSIONS In this study, we found that serum thyroid stimulating hormone (TSH) and neutrophil to lymphocyte ratio (NLR) were closely associated to the severity of NAFLD, suggesting that this simple available laboratory index may additionally be incorporated into the future noninvasive diagnostic scoring model to predict the incidence of NASH and the degree of fibrosis.
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Affiliation(s)
- Ping Li
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- * Correspondence: Ping Li, Department of Hepatology, Tianjin Second People’s Hospital, Tianjin 300000, China (e-mail: )
| | - Liang Liu
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China
- First Hospital Affiliated to Nanchang University, Nanchang, China
| | - Bin Niu
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- School of Graduates, Tianjin Medical University, Tianjin, China
| | - YuQiang Mi
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
| | - YongGang Liu
- Clinical School of the Second People’s Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
| | - Jing Feng
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- School of Graduates, Tianjin Medical University, Tianjin, China
| | - Peng Zhang
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- School of Graduates, Tianjin Medical University, Tianjin, China
| | - Xue Wu
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- School of Graduates, Tianjin Medical University, Tianjin, China
| | - WeiKe Chu
- Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, China
- School of Graduates, Tianjin Medical University, Tianjin, China
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Muacevic A, Adler JR. The Accuracy of Neutrophil-to-Lymphocyte Ratio and Abdominal Computed Tomography to Predict the Severity of Acute Cholecystitis. Cureus 2022; 14:e32243. [PMID: 36620833 PMCID: PMC9813872 DOI: 10.7759/cureus.32243] [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: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
Background In this study, we evaluated neutrophil-to-lymphocyte ratio (NLR) values and abdominal computed tomography (CT) scans in preoperative patients of acute cholecystitis (AC) and their significance in differentiating between severe and non-severe conditions. This study will help further in-depth investigation on both of these diagnostic modalities and timely assess severe AC to avoid the worst prognosis. Methodology This single-center, cross-sectional study was conducted at Government Villupuram Medical College from July 2021 to January 2022. We enrolled patients aged >18 years diagnosed with AC. The demographic variables and clinical features of the enrolled patients were collected. All enrolled patients were divided into two categories (severe or non-severe AC) based on the pathological and clinical findings. The data were collected and entered in SPSS Statistics version 26 (IBM Corp., Armonk, NY, USA). The variation between the severe and non-severe AC groups was compared using Student's t-test to analyze continuous variables. The chi-square test was used to evaluate the association between the categorical variables. A p-value of <0.05 was considered significant. Results Among patients with severe AC, 29 (72.5%) were female, 29 (72.5%) were aged >50 years, 34 (85%) were alcoholics, and 26 (65%) were smokers. In patients with severe AC, the mean for NLR was 18.6500 ± 2.32655. On CT scans, 29 (72.5%) patients showed gallbladder distension, 31 (77.5%) showed increased pericholecystic fat stranding, and 18 (45%) showed pericholecystic fluid collection. CT scan findings and NLR values were significantly associated. Conclusions Gallbladder distension, increased pericholecystic fat stranding, and pericholecystic fluid collection on abdominal CT scan along with raised NLR are significant findings associated with assessing the severity of AC. Therefore, both testing modalities (CT scan and NLR) should be utilized together in hospitals to achieve better outcomes for AC and avoid complications.
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18
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Shavakhi M, Nourigheimasi S, Dioso E, Goutnik M, Lucke-Wold B, Khanzadeh S, Heidari F. Prognostic Role of Neutrophil to Lymphocyte Ratio in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Can J Gastroenterol Hepatol 2022; 2022:1554079. [PMID: 37601979 PMCID: PMC10432763 DOI: 10.1155/2022/1554079] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 08/22/2023] Open
Abstract
Introduction Nonalcoholic steatohepatitis (NASH) and liver fibrosis are the most common complications of nonalcoholic fatty liver disease (NAFLD). In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the association of neutrophil to lymphocyte ratio (NLR) with NASH and fibrosis in patients with NAFLD. Methods PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment. Results Thirteen studies were included in our study. The pooled results showed that NAFLD patients with significant NASH had elevated levels of NLR compared to those with nonsignificant or without NASH (SMD = 0.97, 95% CI = 0.59-1.39, p < 0.001). The pooled sensitivity and specificity of NLR were 78.16% (95% CI = 73.70%-82.04%), and 76.93% (95% CI = 70.22%-82.50%), respectively. In addition, NAFLD patients with significant liver fibrosis had elevated levels of NLR compared to those with nonsignificant or without fibrosis (SMD = 1.59, 95% CI = 0.76-2.43, p < 0.001). The pooled sensitivity and specificity of NLR were 82.62% (95% CI = 70.235%-90.55%) and 81.22% (95% CI = 75.62%-85.78%), respectively. Conclusion Our findings support NLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of NASH and fibrosis among patients with NAFLD.
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Affiliation(s)
- Mitra Shavakhi
- Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Iran
| | | | - Emma Dioso
- Department of Neurosurgery, University of Utah, Salt Lake City, USA
| | - Michael Goutnik
- Department of Neurosurgery, University of Florida, Gainesville, USA
| | | | - Shokoufeh Khanzadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fariba Heidari
- Department of Community and Family Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Liu Y, Zhong Z, Li Z, Li X, Zhang S, Sun J, Zhai J, Liu X, Liu M. Association Between NLR and NAFLD in Adults Exposed to Famine in Early Life. Risk Manag Healthc Policy 2022; 15:1561-1568. [PMID: 36039148 PMCID: PMC9419726 DOI: 10.2147/rmhp.s368369] [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: 04/01/2022] [Accepted: 08/04/2022] [Indexed: 11/23/2022] Open
Abstract
Aim Exposure to famine in early life has been shown to increase the prevalence of non-alcoholic fatty liver disease (NAFLD). Neutrophil-to-lymphocyte ratio (NLR) is a risk factor for developing NAFLD. However, it is not clear that the association between NLR and NAFLD in individuals who were exposed to famine in early life. Methods To match for age, we selected two group populations from Xuzhou city, China, on two different occasions, 2013 and 2017. The group recruited in 2013 included participants who were born during a period of great famine in China. Participants in the another group recruited in 2017 were born between 1965 and 1968. Clinical characteristics of individuals as well as serology indexes were examined for all participants. Ultrasonography to diagnose NAFLD was performed by trained doctors. A total of 10,574 participants were included in the final analysis. Results Individuals born during the famine period have a higher NAFLD prevalence than those who had not been exposed to famine and these findings were similar for both sexes (male: 57.6% vs 48.9%, female: 47.6% vs 40.3%). The prevalence of NAFLD according to NLR quartiles in those exposed to famine was 49.5%, 52.7%, 52.9% and 55.5% for Q1, Q2, Q3 and Q4 NLR, respectively, and was higher than that in non-exposed to famine group. After adjusting for age, BMI, and other metabolic variables, the association between NLR and NAFLD disappeared in the non-famine group. The non-linear relationship between NLR and NAFLD was found in those who had been exposed to famine. Conclusion Individuals who were exposed to famine in early life have a higher prevalence of NAFLD than those who were not exposed. Compared with lower NLR levels, elevated NLR is a risk factor for developing NAFLD. However, there is a non-linear relationship between NLR and the risk of developing NAFLD.
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Affiliation(s)
- Ying Liu
- Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Zhifang Zhong
- Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Zhihong Li
- Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Xin Li
- Department of Obstetrical and Gynecological, Xuzhou Central hospital, Xuzhou, People's Republic of China
| | - Shengkun Zhang
- Department of Obstetrical and Gynecological, Xuzhou Central hospital, Xuzhou, People's Republic of China
| | - Jie Sun
- Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Jingfang Zhai
- Prenatal Diagnosis Center, Xuzhou Central Hospital, Xuzhou, People's Republic of China
| | - Xuekui Liu
- Department of Endocrinology, Xuzhou Central hospital, Xuzhou, People's Republic of China
| | - Min Liu
- Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, People's Republic of China
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20
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Sonaglioni A, Cerini F, Cerrone A, Argiento L, Nicolosi GL, Rigamonti E, Lombardo M, Rumi MG, Viganò M. Liver stiffness measurement identifies subclinical myocardial dysfunction in non-advanced non-alcoholic fatty liver disease patients without overt heart disease. Intern Emerg Med 2022; 17:1425-1438. [PMID: 35302179 DOI: 10.1007/s11739-022-02966-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 02/26/2022] [Indexed: 12/14/2022]
Abstract
Patients with non-advanced non-alcoholic fatty liver disease (NAFLD) have an increased cardiovascular risk. The present study was designed to evaluate the relationship between liver stiffness measurement (LSM) by transient elastography (TE) and myocardial deformation indices of all cardiac chambers in NAFLD patients without overt heart disease. All consecutive NAFLD patients diagnosed with LSM < 12.5 kPa on TE between September 2021 and December 2021 entered the study. All participants underwent blood tests, TE and two-dimensional (2D) transthoracic echocardiography (TTE) implemented with speckle-tracking echocardiography (STE) analysis of left ventricular (LV) global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), right ventricular (RV) GLS, left atrial (LA) total global strain (TGSA) and right atrial (RA) TGSA. Main independent predictors of impaired LV-GLS (defined as absolute value less negative than - 20%) were evaluated. A total of 92 NAFLD patients (54.0 ± 11.1 years, 50% males) were prospectively analyzed. Mean LSM was 6.2 ± 2.4 kPa. Fibroscan results revealed that 76.1% of patients had F0-F1, 5.4% F2 and 18.5% F3 liver fibrosis. Despite normal biventricular systolic function on 2D-TTE, LV-GLS, LV-GCS and LV-GRS, RV-GLS, LA-TGSA and RA-TGSA were reduced in 64.1%, 38.0%, 38.0%, 31.5%, 39.1% and 41.3% of patients, respectively. Body mass index (BMI) (OR 1.76, 95% CI 1.18-2.64), neutrophil-to-lymphocyte ratio (NLR) (OR 4.93, 95% CI 1.15-31.8) and LSM (OR 9.26, 95% CI 2.24-38.3) were independently associated to impaired LV-GLS. BMI ≥ 29.3 kg/m2, NLR ≥ 1.8 and LSM ≥ 5.5 kPa were the best cut-off values for detecting outcome. LSM ≥ 5.5 kPa identifies NAFLD patients with subclinical myocardial dysfunction.
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Affiliation(s)
- Andrea Sonaglioni
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy.
| | - Federica Cerini
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Antonio Cerrone
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Lorenzo Argiento
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | | | - Elisabetta Rigamonti
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Michele Lombardo
- Division of Cardiology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Maria Grazia Rumi
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- University of Milan, Milan, Italy
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21
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Duan Y, Pan X, Luo J, Xiao X, Li J, Bestman PL, Luo M. Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease. Front Immunol 2022; 13:880298. [PMID: 35603224 PMCID: PMC9122097 DOI: 10.3389/fimmu.2022.880298] [Citation(s) in RCA: 153] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/11/2022] [Indexed: 01/30/2023] Open
Abstract
Background Inflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive. Objective This study aimed to evaluate the association between inflammatory cytokines and NAFLD. Methods PubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out. Results The search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-β (TGF-β) with NAFLD. Our results also showed that CRP, IL-1β, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Conclusions Our results indicated that increased CRP, IL‐1β, IL-6, TNF‐α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.
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Affiliation(s)
- Yamei Duan
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiongfeng Pan
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Jiayou Luo
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Xiang Xiao
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Jingya Li
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Prince L. Bestman
- Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China
| | - Miyang Luo
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- *Correspondence: Miyang Luo,
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22
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Tang J, Chen C, Zhou M, Wang J, Feng Z, Wang M. NLR contributed to the diagnosis and detection of nonalcoholic fatty liver disease: A meta - analysis. Clin Res Hepatol Gastroenterol 2022; 46:101847. [PMID: 34920140 DOI: 10.1016/j.clinre.2021.101847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/02/2021] [Accepted: 12/09/2021] [Indexed: 02/04/2023]
Affiliation(s)
- Jiake Tang
- Hangzhou Institute of Cardiovascular Diseases, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China; Hangzhou Normal University, Hangzhou, 311121, China
| | - Chen Chen
- Hangzhou Institute of Cardiovascular Diseases, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China; Hangzhou Normal University, Hangzhou, 311121, China
| | - Mengyun Zhou
- Department of Molecular & Cellular Physiology, Shinshu University School of Medicine,3900803, Japan
| | - Jianjun Wang
- Hangzhou Institute of Cardiovascular Diseases, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China
| | - Zhanhui Feng
- Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
| | - Mingwei Wang
- Hangzhou Institute of Cardiovascular Diseases, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China.
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23
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Lesmana CRA, Kencana Y, Rinaldi I, Kurniawan J, Hasan I, Sanityoso Sulaiman A, Gani RA. Diagnostic Value of Neutrophil to Lymphocyte Ratio in Non-Alcoholic Fatty Liver Disease Evaluated Using Transient Elastography (TE) with Controlled Attenuated Parameter (CAP). Diabetes Metab Syndr Obes 2022; 15:15-22. [PMID: 35023936 PMCID: PMC8743379 DOI: 10.2147/dmso.s330526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/30/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease with excessive fat accumulation in the liver. Transient elastography (TE) with controlled attenuation parameter (CAP) is a device and method to examine the degree of fibrosis and steatosis. However, this device is not widely available across Indonesia. Neutrophil and lymphocyte ratio (NLR) is a simple marker for inflammation, which has a potency to predict disease outcome. This study aims to know the diagnostic value of NLR as the indicator of steatosis and fibrosis severity. METHODS This was a cross-sectional study with consecutive sample collection. We used secondary data from medical records, starting from 2016 to 2018. A descriptive and data analysis, including correlation test, multivariate linear regression, t-test, receiver operating curve (ROC) and area under the curve (AUC) were done to find out the outcome of the study. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) Version 20.0 (SPSS Inc, Chicago, Illinois). A P value <0.05 was considered as statistically significant. RESULTS Out of 106 subjects, 62.3% patients were women with the mean of age 57.29 years old and 77.4% had metabolic syndrome. Most patients had moderate to severe steatosis degree (66%) with the mean of TE mean 6.14 (2.8-18.2) kPa. There was a positive correlation between CAP and TE compared with NLR with r = 0.648 (p < 0.001) and r = 0.621 (p < 0.001), respectively. The use of RNL to assess moderate-severe steatosis has a cutoff point of 1.775 with sensitivity, specificity, PPV and NPV, respectively, at 81.5%, 80.6%, 89.1%, and 69.1%; cutoff point 2.150 to assess significant fibrosis with sensitivity, specificity, PPV and NPV of 92.3%, 87.5%, 70.6%, and 97.2%, respectively. CONCLUSION NLR has a positive and significant correlation with the degree of steatosis and fibrosis with high sensitivity and specificity as evaluated by TE/CAP.
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Affiliation(s)
- Cosmas Rinaldi Adithya Lesmana
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
- Digestive Disease & GI Oncology Center, Medistra Hospital, Jakarta, Indonesia
- Correspondence: Cosmas Rinaldi Adithya Lesmana Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jalan Diponegoro No. 71, Jakarta, Indonesia Email
| | - Yoppi Kencana
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Ikhwan Rinaldi
- Department of Internal Medicine, Haematology and Oncology Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Juferdy Kurniawan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Irsan Hasan
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Andri Sanityoso Sulaiman
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Rino Alvani Gani
- Department of Internal Medicine, Hepatobiliary Division, Dr. Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
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24
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Potoupni V, Georgiadou M, Chatzigriva E, Polychronidou G, Markou E, Zapantis Gakis C, Filimidou I, Karagianni M, Anastasilakis D, Evripidou K, Ftergioti A, Togkaridou M, Tsaftaridis N, Apostolopoulos A, Polyzos SA. Circulating tumor necrosis factor-α levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis. J Gastroenterol Hepatol 2021; 36:3002-3014. [PMID: 34289181 DOI: 10.1111/jgh.15631] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/22/2021] [Accepted: 07/17/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM To synthesize data on circulating tumor necrosis factor (TNF)-α levels between patients with histologically confirmed non-alcoholic fatty liver disease (NAFLD) (simple steatosis or non-alcoholic fatty liver [NAFL] and/or non-alcoholic steatohepatitis [NASH]) and controls. METHODS We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty-six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients). RESULTS Higher circulating TNF-α levels were observed in NAFLD patients than controls (standardized mean difference [SMD] 0.84; 95% confidence interval [95% CI] 0.59-1.09), NAFL patients than controls (SMD 0.56; 95% CI 0.27-0.85), NASH patients than controls (SMD 0.93; 95% CI 0.64-1.22), and NASH than NAFL patients (SMD 0.31; 95% CI 0.16-0.46). There were only minimal changes in the comparisons between groups after excluding studies with morbidly obese populations (n = 11), or pediatric/adolescent populations (n = 6), or other than enzyme-linked immunosorbent assay method of TNF-α measurement (n = 8). There was high heterogeneity among studies in all comparisons, which was not essentially affected after sensitivity analyses. The meta-regression analysis revealed that the male ratio was positively associated with TNF-α SMD in the comparison between patients with NASH and NAFL (beta = 0.809; 95% CI 0.052-1.566) and accounted for 36% (P = 0.037) of the heterogeneity in this pair of comparison. TNF-α SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. CONCLUSIONS Circulating TNF-α levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF-α were also associated with the severity of NAFLD.
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Affiliation(s)
- Victoria Potoupni
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Georgiadou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eftychia Chatzigriva
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgia Polychronidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Erietta Markou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christos Zapantis Gakis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ioanna Filimidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Myriam Karagianni
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Anastasilakis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kleo Evripidou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Argyro Ftergioti
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Marianthi Togkaridou
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nikolaos Tsaftaridis
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Apostolos Apostolopoulos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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25
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Predictive markers of nonalcoholic fatty liver disease in lean patients. A multinomial regression model and a 2k factorial analysis. Eur J Gastroenterol Hepatol 2021; 33:1316-1321. [PMID: 32868653 DOI: 10.1097/meg.0000000000001845] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance; however, there is a group of non-obese patients with NAFLD that need to be characterized. Our aim was to evaluate the factors associated with NAFLD in non-obese subjects in a third-level hospital. METHODS A comparative cross-sectional study was performed. Participants were divided into four groups: non-obese without NAFLD (group 1), non-obese with NAFLD (group 2), obese without NAFLD (group 3), and obese with NAFLD (group 4). We evaluated the effect of clinical and biochemical characteristics with the disease by groups using a multinomial regression model and a 2K factorial analysis. RESULTS We included 278 participants. Low platelet-lymphocyte ratio (PLR) as a novel parameter associated with NAFLD in non-obese subjects. Age, uric acid, alanine transaminase (ALT), high-density lipoprotein (HDL)-cholesterol, and neutrophil-lymphocyte ratio (NLR) were other related parameters (akaike information criterion = 557). NLR had the larger OR in groups with NAFLD (lean with NAFLD 7.12, obese with NAFLD 13.02). The 2k factorial design found inverse effect on PLR by NAFLD (effect -21.89, P < 0.001), which was higher than BMI (effect -1.33, P < 0.045). CONCLUSION Our study found that PLR is a novel parameter with inverse correlation with NAFLD in non-obese patients. Other related parameters are age, hyperuricemia, elevation of ALT and NLR, and low HDL-cholesterol.
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26
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Kosekli MA, Kurtkulagii O, Kahveci G, Duman TT, Tel BMA, Bilgin S, Demirkol ME, Aktas G. The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study. ACTA ACUST UNITED AC 2021; 67:549-554. [PMID: 34495059 DOI: 10.1590/1806-9282.20201005] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 12/24/2020] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Non-alcoholic fatty liver disease, which is characterized by lipid being deposited into hepatocytes, affects nearly one in three adults globally. Inflammatory markers were suggested to be related with hepatic steatosis. Uric acid to HDL cholesterol ratio is proposed as a novel inflammatory and metabolic marker. We aimed to compare Uric acid to HDL cholesterol ratio levels of patients with Non-alcoholic fatty liver disease to those of healthy controls and find out potential correlations between Uric acid to HDL cholesterol ratio and other inflammatory and metabolic markers of Non-alcoholic fatty liver disease. METHODS Patients with a diagnosis of Non-alcoholic fatty liver disease who were on clinical follow-up in our institution were enrolled in the study as the Non-alcoholic fatty liver disease group, while healthy volunteers were enrolled as the control group. The Uric acid to HDL cholesterol ratio of the groups was compared and potential correlations were studied between Uric acid to HDL cholesterol ratio and fasting blood glucose, transaminases, serum lipids (triglyceride, LDL-cholesterol), weight, and body mass index. RESULTS The Uric acid to HDL cholesterol ratio of the Non-alcoholic fatty liver disease (13±5%) group was significantly higher compared to the Uric acid to HDL cholesterol ratio of the control (10±4%) group (p<0.001). Uric acid to HDL cholesterol ratio was significantly and positively correlated with fasting blood glucose, transaminases, triglyceride, body weight, waist circumference, hip circumference, and body mass index. A ROC analysis revealed that a Uric acid to HDL cholesterol ratio level greater than 9.6% has 73% sensitivity and 51% specificity in determining Non-alcoholic fatty liver disease. CONCLUSION Due to the inexpensive and easy-to-assess nature of Uric acid to HDL cholesterol ratio, we suggest that elevated Uric acid to HDL cholesterol ratio levels be considered a useful tool in diagnosing hepatic steatosis.
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Affiliation(s)
- Mehmet Ali Kosekli
- Abant Izzet Baysal University Hospital, Department of Internal Medicine and Gastroenterology - Bolu, Turkey
| | - Ozge Kurtkulagii
- Abant Izzet Baysal University Hospital, Department of Internal Medicine - Bolu, Turkey
| | - Gizem Kahveci
- Abant Izzet Baysal University Hospital, Department of Internal Medicine - Bolu, Turkey
| | | | | | - Satilmis Bilgin
- Abant Izzet Baysal University Hospital, Department of Internal Medicine - Bolu, Turkey
| | | | - Gulali Aktas
- Abant Izzet Baysal University Hospital, Department of Internal Medicine - Bolu, Turkey
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27
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Tuzer C, Sertbas Y, Duman E, Komoglu S, Kan O, Ay S, Yigit A, Sertbas M, Okuroglu N, Ozen B, Dalbeler A, Ozdemir A. The role of mean platelet volume in nonalcoholic fatty liver disease without cardiovascular comorbidities, obesity and diabetes mellitus. Eur J Gastroenterol Hepatol 2021; 33:1222-1228. [PMID: 34397640 DOI: 10.1097/meg.0000000000002189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND While the relation of mean platelet volume (MPV) with inflammatory diseases is obvious, its role in nonalcoholic fatty liver disease (NAFLD) without cardiovascular comorbidities, obesity and diabetes mellitus is not clear. METHODS A total of 249 patients (nonobese, nondiabetic and not having cardiac diseases) who underwent an abdominal ultrasonography assessment were enrolled. They were divided according to the absence (group 1) or presence (group 2) of hepatic steatosis. The patients with steatosis were further divided according to the severity of steatosis as group 2a (grade 1), 2b (grade 2) and 2c (grade 3). The demographic and laboratory features were compared between groups. RESULTS Hepatic steatosis was absent in 120 patients and detected in 129 patients (grade 1, 2, 3 hepatic steatosis in 75, 49 and 5 patients, respectively). BMI, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and serum AST, ALT, triglyceride levels were significantly higher in group 2 than in group 1 (P < 0.001, P < 0.001, P < 0.001, P = 0.005, P < 0.001, respectively). BMI, serum AST and triglyceride levels were significant factors for NAFLD (P < 0.001, P = 0.018, P = 0.001). MPV was neither different between groups (P > 0.05) nor a predictor factor for NAFLD (P > 0.05). CONCLUSION MPV is a useless parameter to detect NAFLD without cardiovascular comorbidities, obesity and diabetes mellitus.
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Affiliation(s)
- Can Tuzer
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Yasar Sertbas
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Emrah Duman
- Department of Radiology, Istanbul Medeniyet University, Istanbul, Turkey
| | - Sabiha Komoglu
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Omer Kan
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Seval Ay
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Abdurrahman Yigit
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Meltem Sertbas
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Nalan Okuroglu
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Birgul Ozen
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Aysegul Dalbeler
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
| | - Ali Ozdemir
- Department of Internal Medicine, Fatih Sultan Mehmet Education and Research Hospital
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Seen TK, Sayed M, Bilal M, Reyes JV, Bhandari P, Lourdusamy V, Al-khazraji A, Syed U, Sattar Y, Bansal R. Clinical indicators for progression of nonalcoholic steatohepatitis to cirrhosis. World J Gastroenterol 2021; 27:3238-3248. [PMID: 34163108 PMCID: PMC8218360 DOI: 10.3748/wjg.v27.i23.3238] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 12/06/2020] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation, known as nonalcoholic steatohepatitis. Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma (HCC). Fatty liver disease prevalence has increased at alarming rates alongside obesity, diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide. Given this rise in prevalence, it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis. Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease. This article discusses the utility of current non-invasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available. Additionally, we summarize available treatment options including targeted medical therapy through four different pathways, surgical or endoscopic intervention.
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Affiliation(s)
- Tasur Kumar Seen
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Muntazir Sayed
- Division of Internal Medicine, R.C.S.M. Government College, Mahrashta 416013, India
| | - Muhammad Bilal
- Division of Gastroenterology, Hepatology and Endoscopy, Pakistan Institute of Medical Sciences, Islamabad 45710, Pakistan
| | - Jonathan Vincent Reyes
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Priyanka Bhandari
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Vennis Lourdusamy
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Ahmed Al-khazraji
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Umer Syed
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Yasar Sattar
- Division of Internal Medicine, Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, Elmhurst, NY 11375, United States
| | - Raghav Bansal
- Division of Gastroenterology, Icahn School of Medicine, Elmhurst Hospital, Elmhurst, NY 11375, United States
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Chua DW, Koh YX, Syn NL, Chuan TY, Yao TJ, Lee SY, Goh BKP, Cheow PC, Chung AY, Chan CY. Repeat hepatectomy versus radiofrequency ablation in management of recurrent hepatocellular carcinoma: an average treatment effect analysis. Ann Surg Oncol 2021; 28:7731-7740. [PMID: 33969464 DOI: 10.1245/s10434-021-09948-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 03/19/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with high rates of recurrence post-resection. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) are the mainstays for managing recurrent HCC following initial curative resection. This retrospective study aims to determine the average treatment effect of RH and RFA in patients with recurrent HCC. PATIENTS AND METHODS From 2000 to 2016, a total of 219 consecutive patients with recurrent HCC who underwent either RH or RFA were included in the study. The analysis was performed using inverse probability of treatment weighting (IPTW), and propensity score-matched (PSM) methods. RESULTS The minor and major post-operative morbidity after propensity score-matched analysis for the RH group was 30.0% and 6.0%, respectively, and 19.2% and 0.0% (p = 0.1006), respectively, for the RFA group. After propensity score matching, the median OS for RH and RFA was 85.5 (IQR, 33.5-not reached) and 53.3 months (IQR, 27.5-not reached) (p = 0.8474), respectively. There was no significant difference in 90-day mortality between both groups (p = 0.1287). RH showed improved long-term overall survival over RFA at the third [71.3% versus 65.7% (p = 0.0432)], fifth [59.9% versus 45.4% (p = 0.0271)] and tenth [35.4% versus 32.2% (p = 0.0132)] year follow-up, respectively. Median time to recurrence was 11.1 (IQR, 5.0-33.2) and 28.0 months (IQR, 9.1-not reached) (p = 0.0225) for the RFA and RH group, respectively. CONCLUSIONS RH confers a late survival benefit compared with RFA for patients with recurrent HCC despite a higher morbidity rate.
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Affiliation(s)
- Darren W Chua
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore. .,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore. .,NUS Yong Loo Lin School of Medicine, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.
| | - Nicholas L Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore
| | - Tan Yu Chuan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore
| | - Teo Jin Yao
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
| | - Ser-Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
| | - Alexander Y Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore.,Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
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Chen S, Guo H, Xie M, Zhou C, Zheng M. Neutrophil: An emerging player in the occurrence and progression of metabolic associated fatty liver disease. Int Immunopharmacol 2021; 97:107609. [PMID: 33887577 DOI: 10.1016/j.intimp.2021.107609] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/01/2021] [Accepted: 03/20/2021] [Indexed: 12/12/2022]
Abstract
Metabolic-associated fatty liver disease (MAFLD) is a common type of chronic liver disease characterized by excessive lipid accumulation in hepatocytes, but the pathogenesis is still unclear. Neutrophils, the most abundant immune cells in the human body, defend against pathogens and regulate the inflammatory response. Recent studies have indicated that excessive liver infiltration of neutrophils is a significant histological hallmark of MAFLD, and neutrophils and their derived granule proteins participate in different stages of MAFLD, including hepatic steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. Hence, in this review, we summarize the role of neutrophils in the occurrence and progression of MAFLD and provide a perspective for the clinical application of neutrophils in MAFLD diagnosis and treatment.
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Affiliation(s)
- Shiwei Chen
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Huiting Guo
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Mingjie Xie
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Cheng Zhou
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China.
| | - Min Zheng
- The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China.
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Lambrecht J, Tacke F. Controversies and Opportunities in the Use of Inflammatory Markers for Diagnosis or Risk Prediction in Fatty Liver Disease. Front Immunol 2021; 11:634409. [PMID: 33633748 PMCID: PMC7900147 DOI: 10.3389/fimmu.2020.634409] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 12/29/2020] [Indexed: 12/12/2022] Open
Abstract
In the Western society, non-alcoholic fatty liver disease (NAFLD), characterized by the excessive accumulation of fat in the liver, represents the most common cause of chronic liver disease. If left untreated, approximately 15%-20% of patients with NAFLD will progress to non-alcoholic steatohepatitis (NASH), in which lobular inflammation, hepatocyte ballooning and fibrogenesis further contribute to a distorted liver architecture and function. NASH initiation has significant effects on liver-related mortality, as even the presence of early stage fibrosis increases the chances of adverse patient outcome. Therefore, adequate diagnostic tools for NASH are needed, to ensure that relevant therapeutic actions can be taken as soon as necessary. To date, the diagnostic gold standard remains the invasive liver biopsy, which is associated with several drawbacks such as high financial costs, procedural risks, and inter/intra-observer variability in histology analysis. As liver inflammation is a major hallmark of disease progression, inflammation-related circulating markers may represent an interesting source of non-invasive biomarkers for NAFLD/NASH. Examples for such markers include cytokines, chemokines or shed receptors from immune cells, circulating exosomes related to inflammation, and changing proportions of peripheral blood mononuclear cell (PBMC) subtypes. This review aims at documenting and critically discussing the utility of such novel inflammatory markers for NAFLD/NASH-diagnosis, patient stratification and risk prediction.
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Affiliation(s)
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany
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AKAR M. Is mean platelet volume better than other long-used non-invasive parameters in assessing severe fibrosis in patients with chronic hepatitis B? JOURNAL OF HEALTH SCIENCES AND MEDICINE 2021. [DOI: 10.32322/jhsm.840794] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
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Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
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Cai J, Zhang XJ, Ji YX, Zhang P, She ZG, Li H. Nonalcoholic Fatty Liver Disease Pandemic Fuels the Upsurge in Cardiovascular Diseases. Circ Res 2020; 126:679-704. [PMID: 32105577 DOI: 10.1161/circresaha.119.316337] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cardiovascular diseases (CVDs) remain a leading cause of death worldwide. Among the major risk factors for CVD, obesity and diabetes mellitus have received considerable attention in terms of public policy and awareness. However, the emerging prevalence of nonalcoholic fatty liver disease (NAFLD), as the most common liver and metabolic disease and a cause of CVD, has been largely overlooked. Currently, the number of individuals with NAFLD is greater than the total number of individuals with diabetes mellitus and obesity. Epidemiological studies have established a strong correlation between NAFLD and an increased risk of CVD and CVD-associated events. Although debate continues over the causal relationship between NAFLD and CVD, many mechanistic and longitudinal studies have indicated that NAFLD is one of the major driving forces for CVD and should be recognized as an independent risk factor for CVD apart from other metabolic disorders. In this review, we summarize the clinical evidence that supports NAFLD as a risk factor for CVD epidemics and discuss major mechanistic insights regarding the acceleration of CVD in the setting of NAFLD. Finally, we address the potential treatments for NAFLD and their potential impact on CVD.
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Affiliation(s)
- Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J.C.).,Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Xiao-Jing Zhang
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.).,Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.).,Medical Science Research Center, Zhongnan Hospital of Wuhan University, China (X.-J.Z.)
| | - Yan-Xiao Ji
- Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Peng Zhang
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.).,Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Zhi-Gang She
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.).,Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.)
| | - Hongliang Li
- From the Department of Cardiology, Renmin Hospital of Wuhan University, China (X.-J.Z., P.Z., Z.-G.S., H.L.).,Institute of Model Animal of Wuhan University, China (J.C., X.-J.Z., Y.-X.J., P.Z., Z.-G.S., H.L.).,Basic Medical School, Wuhan University, China (H.L.)
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35
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Shiha G, Mousa N. Noninvasive Biomarkers for Liver Fibrosis. LIVER DISEASES 2020:427-441. [DOI: 10.1007/978-3-030-24432-3_36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
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Neutrophil-to-lymphocyte ratio is independently associated with inflammatory activity and fibrosis grade in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2019; 31:1110-1115. [PMID: 30888972 DOI: 10.1097/meg.0000000000001393] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a lack of noninvasive methods for the diagnosis of NASH. The aim of the present study was to determine the role of neutrophil-to-lymphocyte ratio (NLR) in predicting histological severity in NAFLD. PATIENTS AND METHODS We performed a single-center retrospective study in EMMS Nazareth Hospital from July 2014 to May 2017. Liver biopsies were evaluated using the steatosis, activity, and fibrosis scoring system, which includes three components: (i) steatosis (0-3), (ii) activity grade (0-4), and (iii) fibrosis (0-4). Patients were divided into two groups. The first group was considered to have NAFLD when fibrosis grade was 0-1 and inflammatory activity was 0-1, whereas the second group included patients with fibrosis grade of 2-4 and inflammatory activity grade of 2-3, considered to have NASH. RESULTS Ninety-one (91) patients with biopsy-proven fatty liver were included. The average age was 42.13 ± 11.5 (18-74) years. Fifty-seven (62.6%) patients were male. Univariate analysis revealed several factors to be associated with advanced fibrosis and inflammatory activity, including NLR, C-reactive protein, and HOMA-IR, which correlated with fibrosis [odds ratio (OR): 1.405, 95% confidence interval (CI): 1.21-1.63, P < 0.0001; OR: 1.329, 95% CI: 1.05-1.68, P = 0.016; and OR: 1.922, 95% CI: 1.18-3.11, P = 0.007, respectively], and NLR, triglycerides, and HOMA-IR, which correlated with hepatocyte inflammation (OR: 1.210, 95% CI: 1.08-1.35, P = 0.0009; OR: 0.984, 95% CI: 0.97-0.99, P = 0.01; and OR: 2.069, 95% CI: 1.28-3.34, P = 0.003, respectively). On multivariate logistic regression analysis, NLR remains independently associated with advanced fibrosis grade and inflammatory activity (OR: 0.734, 95% CI: 0.631-0.854, P < 0.0001, area under the curve: 0.8622 and OR: 0.836, 95% CI: 0.74-0.95, P = 0.006, area under the curve: 0.7845, respectively). Our second major finding was defining an NLR cut-off point that was associated with inflammatory activity and fibrosis grade using receiver operating characteristic analysis based on the Youden index (J), which is defined by the maximal sensitivity and specificity. CONCLUSION NLR showed significant independent correlation with advanced inflammation and fibrosis in patients with NAFLD. This simple available laboratory tool may be incorporated into future diagnostic scores.
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Koh YX, Tan HJ, Liew YX, Syn N, Teo JY, Lee SY, Goh BKP, Goh GBB, Chan CY. Liver Resection for Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma. J Am Coll Surg 2019; 229:467-478.e1. [PMID: 31398386 DOI: 10.1016/j.jamcollsurg.2019.07.012] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 07/23/2019] [Accepted: 07/23/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is on the rise worldwide, but data on long-term outcomes after curative operations are limited. The primary aim of this study was to characterize the perioperative and long-term outcomes after liver resection. The secondary aim was to investigate the influence of the histologic severity of nonalcoholic steatohepatitis and its impact on perioperative outcomes and long-term survival. METHODS A total of 996 patients who underwent liver resection for HCC in our institution were analyzed. Patients were categorized into subgroups of NAFLD vs non-NAFLD HCC based on histologic evidence of hepatic steatosis. Comparisons of patients' demographic, clinical, and surgical characteristics; postoperative complications; and survival outcomes were performed. RESULTS Eight hundred and forty-four patients had non-NAFLD HCC and 152 patients had NAFLD HCC. Comorbidities were significantly more common in the NAFLD group (p < 0.0001). In the non-NAFLD group, larger median tumor size, higher liver cirrhosis, and lower median neutrophil to lymphocyte ratio were observed (p < 0.0001). The NAFLD group had a greater amount of intraoperative blood loss, more postoperative complications, and longer length of stay. Five-year overall survival was significantly better in the NAFLD group (p = 0.0355). Significant factors that contribute to poorer survival outcomes include age, congestive cardiac failure, Child-Pugh's class B, cirrhosis, tumor size, multinodularity, and R1 resection. For NAFLD group, patients with abnormal parenchyma showed poorer survival and 5-year overall survival rates (64.8% vs 75.6%; p = 0.2291). CONCLUSIONS Nonalcoholic fatty liver disease-related HCC is associated with greater surgical morbidity and post-hepatectomy liver failure. Despite this, long-term survival outcomes are favorable compared with non-NAFLD etiologies.
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Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore.
| | - Hiang Jin Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Yi Xin Liew
- Department of Pharmacy, Singapore General Hospital, Singapore
| | - Nicholas Syn
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Ser Yee Lee
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - George B B Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-National University of Singapore Medical School, Singapore
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Abdel-Razik A, Mousa N, Abdel-Aziz M, Elsherbiny W, Zakaria S, Shabana W, Abed S, Elhelaly R, Elzehery R, Eldars W, El-Bendary M. Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt. Eur J Gastroenterol Hepatol 2019; 31:1017-1024. [PMID: 30694910 DOI: 10.1097/meg.0000000000001364] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP. PATIENTS AND METHODS Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants. RESULTS The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135). CONCLUSION The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Waleed Eldars
- Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Abeles RD, Mullish BH, Forlano R, Kimhofer T, Adler M, Tzallas A, Giannakeas N, Yee M, Mayet J, Goldin RD, Thursz MR, Manousou P. Derivation and validation of a cardiovascular risk score for prediction of major acute cardiovascular events in non-alcoholic fatty liver disease; the importance of an elevated mean platelet volume. Aliment Pharmacol Ther 2019; 49:1077-1085. [PMID: 30836450 PMCID: PMC6519040 DOI: 10.1111/apt.15192] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 10/24/2018] [Accepted: 01/23/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Atherosclerotic cardiovascular disease is a key cause of morbidity in non-alcoholic fatty liver disease (NAFLD) but appropriate means to predict major acute cardiovascular events (MACE) are lacking. AIM To design a bespoke cardiovascular risk score in NAFLD. METHODS A retrospective derivation (2008-2016, 356 patients) and a prospective validation (2016- 2017, 111 patients) NAFLD cohort study was performed. Clinical and biochemical data were recorded at enrolment and mean platelet volume (MPV), Qrisk2 and Framingham scores were recorded one year prior to MACE (Cardiovascular death, acute coronary syndrome, stroke and transient ischaemic attack). RESULTS The derivation and validation cohorts were well-matched, with MACE prevalence 12.6% and 12%, respectively. On univariate analysis, age, diabetes, advanced fibrosis, collagen proportionate area >5%, MPV and liver stiffness were associated with MACE. After multivariate analysis, age, diabetes and MPV remained independently predictive of MACE. The "NAFLD CV-risk score" was generated using binary logistic regression: 0.06*(Age) + 0.963*(MPV) + 0.26*(DM1 ) - 16.44; 1 Diabetes mellitus: 1: present; 2: absent. (AUROC 0.84). A cut-off of -3.98 gave a sensitivity 97%, specificity 27%, PPV 16%, and NPV 99%. An MPV alone of >10.05 gave a sensitivity 97%, specificity 59%, PPV 24% and NPV 97% (AUROC 0.83). Validation cohort AUROCs were comparable at 0.77 (NAFLD CV-risk) and 0.72 (MPV). In the full cohort, the NAFLD CV-risk score and MPV outperformed both Qrisk2 and Framingham scores. CONCLUSIONS The NAFLD CV risk score and MPV accurately predict 1-year risk of MACE, thereby allowing better identification of patients that require optimisation of their cardiovascular risk profile.
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Affiliation(s)
- Robin D. Abeles
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
| | - Benjamin H. Mullish
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
| | - Roberta Forlano
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
| | - Torben Kimhofer
- Department of Surgery and CancerCentre for Computational and System Medicine, Imperial College LondonLondonUK
| | - Maciej Adler
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
| | - Alexandros Tzallas
- Department of Computer Engineering, School of Applied TechnologyTechnological Educational Institute of EpirusArtaGreece
| | - Nikolaos Giannakeas
- Department of Computer Engineering, School of Applied TechnologyTechnological Educational Institute of EpirusArtaGreece
| | - Michael Yee
- Department of EndocrinologySt Mary’s Hospital, Imperial College Healthcare NHS TrustLondonUK
| | - Jamil Mayet
- National Heart and Lung Institute, Hammersmith Hospital, Imperial College LondonLondonUK
| | - Robert D. Goldin
- Department of Cellular PathologySt Mary’s Hospital, Imperial College Healthcare NHS TrustLondonUK
| | - Mark R. Thursz
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
| | - Pinelopi Manousou
- Liver Unit/ Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and CancerSt Mary’s Hospital Campus, Imperial College LondonLondonUK
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Associations between CT-determined visceral fat burden, hepatic steatosis, circulating white blood cell counts and neutrophil-to-lymphocyte ratio. PLoS One 2018; 13:e0207284. [PMID: 30458019 PMCID: PMC6245737 DOI: 10.1371/journal.pone.0207284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 10/29/2018] [Indexed: 02/08/2023] Open
Abstract
Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p<0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p<0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p<0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p<0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC<0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity.
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Kosmalski M, Mokros Ł, Kuna P, Witusik A, Pietras T. Changes in the immune system - the key to diagnostics and therapy of patients with non-alcoholic fatty liver disease. Cent Eur J Immunol 2018; 43:231-239. [PMID: 30135638 PMCID: PMC6102613 DOI: 10.5114/ceji.2018.77395] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 06/12/2017] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common pathologies of that organ. The development of the disease involves a variety of mechanisms, including insulin resistance, oxidative stress, endoplasmic reticulum stress, endotoxins from the intestinal flora and genetic predispositions. Additionally, clinical data suggest that the presence of NAFLD is associated with excessive activation of the immune system. For practical purposes, attention should be paid to the moment when the subjects predisposed to NAFLD develop inflammatory infiltration and signs of fibrosis in the liver (non-alcoholic steatohepatitis - NASH). Their presence is an important risk factor for hepatic cirrhosis, hepatic failure, and hepatocellular carcinoma, as well as for the occurrence of cardiovascular events. Regardless of the diagnostic methods used, including laboratory tests and imaging, liver biopsy remains the gold standard to identify and differentiate patients with NAFLD and NASH. The search for other, safer, cheaper and more readily available diagnostic tests is still being continued. Attention has been drawn to the usefulness of markers of immune status of the organism, not only for the diagnosis of NASH, but also for the identification of NAFLD patients at risk of disease progression. Despite the effectiveness of medication, no recommendations have been established for pharmacotherapy of NAFLD. Data indicate the primary need for non-pharmacological interventions to reduce body weight. However, there is evidence of the applicability of certain drugs and dietary supplements, which, by their effect on the immune system, inhibit its excessive activity, thus preventing the progression of NAFLD to NASH.
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Affiliation(s)
- Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, Poland
| | - Łukasz Mokros
- Department of Clinical Pharmacology, Medical University of Lodz, Poland
| | - Piotr Kuna
- Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Poland
| | - Andrzej Witusik
- Department of Psychology, Piotrków Trybunalski Branch, Jan Kochanowski University in Kielce, Poland
| | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Lodz, Poland
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Verhaegh P, Bavalia R, Winkens B, Masclee A, Jonkers D, Koek G. Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018; 16:837-861. [PMID: 28838784 DOI: 10.1016/j.cgh.2017.08.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 08/15/2017] [Accepted: 08/16/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. METHODS We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sensp) and specificity (specp) values were determined using the Meta-Analysis Package for R (metafor). RESULTS In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sensp, 63.5% and specp, 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and specp, 75.7%) within inflammatory markers, CK18-M30 (sensp, 68.4% and specp, 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sensp, 69.0% and specp, 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sensp and 95.3% specp) and the GlycoNASH test (67.1% sensp and 63.8% specp). CONCLUSION In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis.
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Affiliation(s)
- Pauline Verhaegh
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Roisin Bavalia
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistic, School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the Netherlands
| | - Ad Masclee
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Daisy Jonkers
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Ger Koek
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Centre, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.
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The Effect of a Hydrolyzed Polysaccharide Dietary Supplement on Biomarkers in Adults with Nonalcoholic Fatty Liver Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:1751583. [PMID: 29853945 PMCID: PMC5960521 DOI: 10.1155/2018/1751583] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 04/12/2018] [Indexed: 02/07/2023]
Abstract
The primary objective of the study was to evaluate the effect of a hydrolyzed polysaccharide, Rice Bran Arabinoxylan Compound (RBAC), on biomarkers in adults with nonalcoholic fatty liver disease (NAFLD). A 90-day randomized double-blind placebo-controlled trial examined the effect of RBAC on complete blood count, liver enzymes, lipids, oxidative stress markers, cytokines, and growth factors. Twenty-three adults with NAFLD were enrolled and randomly assigned to one of the two study conditions (n = 12 RBAC and n = 11 placebo) and consumed 1 gram/day of either compound for 90 days. Subjects were assessed at baseline and 45 and 90 days. No adverse effects were reported. Alkaline phosphatase significantly decreased (−3.1%; SD = 19.9; F[1,19] = 5.1, p = 0.03) in the RBAC group compared to placebo. Percent monocytes (17.9%; SD = 18.3; F[1,19] = 5.9, p = 0.02) and percent eosinophils (30.6%; SD = 30.5; F[1,19] = 12.3, p < 0.01) increased in the RBAC group. IFN-γ (156%; SD = 131.8; F[1,19] = 4.2, p = 0.06) and IL-18 (29.1%; SD = 64; F[1,19] = 5.3, p = 0.03) increased in the RBAC group compared to placebo. Other improvements were noted for platelets, neutrophils, neutrophil-lymphocyte ratio, γ-glutamyl transferase, and 4-hydroxynonenal. RBAC had beneficial effects on several biomarkers that add to the known immunomodulatory activities of RBAC, which may be promising for people with NAFLD.
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Peng Y, Li Y, He Y, Wei Q, Xie Q, Zhang L, Xia Y, Zhou X, Zhang L, Feng X, Chen K, Chen S, Chen W, Long Q, Chai J. The role of neutrophil to lymphocyte ratio for the assessment of liver fibrosis and cirrhosis: a systematic review. Expert Rev Gastroenterol Hepatol 2018; 12:503-513. [PMID: 29629626 DOI: 10.1080/17474124.2018.1463158] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Neutrophil to lymphocyte ratio (NLR) is widely used to assess inflammatory diseases. We performed a systematic review to explore the prognostic role of NLR for the assessment of liver fibrosis and cirrhosis. Areas covered: We searched the PubMed and EMBASE databases for the eligible papers which explored the association between NLR and liver fibrosis/cirrhosis or investigated the prognostic value of NLR in cirrhotic patients. Expert commentary: In accordance with assessment of liver fibrosis stage, we classified papers into four subgroups by etiology. For the patients with nonalcoholic fatty liver disease (NAFLD) there was a significant association between NLR and fibrosis stage and nonalcoholic fatty liver disease activity score (NAS), while NLR had a negative correlation with fibrosis stage for the patients with chronic hepatitis B (CHB). As for the patients with and chronic hepatitis C (CHC), NLR might not be significantly associated with fibrosis stage. Moreover, NLR seemed to be significantly useful for predicting outcomes in cirrhotic patients. Hence, NLR might be associated with liver fibrosis stage, especially in patients with NAFLD. Furthermore, NLR might be a useful biomarker for evaluating the prognosis in cirrhotic patients.
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Affiliation(s)
- Ying Peng
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Yan Li
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Yonghong He
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Qinglin Wei
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Qiaoling Xie
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Liangjun Zhang
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Yiju Xia
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Xueqian Zhou
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Lu Zhang
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Xinchan Feng
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Kun Chen
- b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Sheng Chen
- c Department of Pediatrics, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Wensheng Chen
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Qinglin Long
- b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
| | - Jin Chai
- a Cholestatic Liver Diseases Center, Southwest Hospital , Third Military Medical University , Chongqing , China.,b Department of Gastroenterology, Southwest Hospital , Third Military Medical University , Chongqing , China
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Micić D, Stanković S, Lalić N, Đukić V, Polovina S. Prognostic Value of Preoperative Neutrophil-to-lymphocyte Ratio for Prediction of Severe Cholecystitis. J Med Biochem 2018; 37:121-127. [PMID: 30581347 PMCID: PMC6294096 DOI: 10.1515/jomb-2017-0063] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 12/26/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with cholecystitis has not been established. The aim of this study was to investigate preoperative NLR in patients with cholecystitis and to identify a relevant NLR value that discriminates between simple and severe cholecystitis. METHODS This study included 136 patients who under went laparoscopic cholecystectomy due to cholecystitis. The Receiver Operating Characteristic (ROC) analysis was performed to identify the most useful NLR cut-off value in relation to the severity of cholecystitis. The patients were di vided into two groups according to the cut-off NLR value: high NLR group (≥4.18, n=23) and low NLR group (<4.18, n=113). Severe cholecystitis was defined as a state which includes inflammation, empyema, gangrene, perforation of gallbladder, adhesions or difficulty in dissecting Calot's triangle. RESULTS In the high NLR group, severe cholecystitis (p<0.0001) and higher C-reactive protein level (CRP) and white blood cells count (WBC) (p<0.0001) were significantly more frequent. There was no difference in homeostatic model assessment-insulin resistance index (HOMA-IR) between both groups before the operation (p<0.634). The incidence of severe cholecystitis was 16.9%. The NLR of 4.18 could predict severe cholecystitis with 78.3% sensitivity and 74.3% specificity. Spearman's correlation revealed significant association between the preoperative NLR and HOMA-IR on day 1, (r=0.254, p=0.030) and between preoperative NLR and CRP on day 1 (ρ=0.355; p<0.0001). CONCLUSIONS NLR ≥4.18 was significantly associated with severe cholecystitis. The preoperative NLR in patients under going cholecystectomy due to cholecystitis could be a useful surrogate marker of severe cholecystitis.
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Affiliation(s)
- Dušan Micić
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Emergency Surgery, Emergency Center, Clinical Center of Serbia, Belgrade, Serbia
| | - Sanja Stanković
- Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia
| | - Nebojša Lalić
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
| | - Vladimir Đukić
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Emergency Surgery, Emergency Center, Clinical Center of Serbia, Belgrade, Serbia
| | - Snežana Polovina
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Belgrade, Serbia
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Acar T, Adıbelli ZH. The effect of neutrophil / lymphocyte ratio on abdominal fat distribution, fatty liver and liver volume. KONURALP TIP DERGISI 2017. [DOI: 10.18521/ktd.298292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Abstract
OBJECTIVES Cholesteatoma is a chronic inflammatory clinical disorder, and it may cause hearing loss and various complications due to its destructive nature. Mean platelet volume (MPV) is a prothrombotic and proinflammatory marker. The aim of this study is to investigate predictive values of MPV, neutrophil-to-lymphocyte ratio, erythrocyte distribution width, and platelet lymphocyte ratio in cholesteatomatous or noncholesteatomatous pediatric chronic otitis media. METHODS In this study, the authors retrospectively analyzed 24 patients with cholesteatomatous chronic otitis media, 9 patients with noncholesteatomatous chronic otitis media, and 36 age- and sex-matched healthy controls. Cholesteatomatous and noncholesteatomatous chronic otitis media groups were compared with each other, and with controls for WBC, MPV, erythrocyte distribution width, neutrophil-to-lymphocyte ratio, and platelet lymphocyte ratio. RESULTS Mean platelet volume was significantly lower in patients with cholesteatoma (8.17 ± 1.22 fL) compared with the control group (10.42 ± 0.87 fL) (P <0.001). Region of conversion curve analysis showed that the cutoff level of 9.5 fL for MPV was an independent predictor for cholesteatoma with a high sensitivity (86%) and specificity (84%). Cholesteatomatous and noncholesteatomous chronic otitis media patients were similar for other parameters studied. CONCLUSION Mean platelet volume may be used as a fast-to-obtain, reliable, and inexpensive marker with a high predictive level to indicate cholesteatoma in children.
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Paquissi FC. Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets. Front Immunol 2016; 7:490. [PMID: 27891128 PMCID: PMC5104753 DOI: 10.3389/fimmu.2016.00490] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 10/25/2016] [Indexed: 12/21/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.
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Predictors of steatohepatitis in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2016; 28:606-7. [PMID: 27010475 DOI: 10.1097/meg.0000000000000575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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