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Mekuria AN, Nedi T, Gong YY, Abula T, Engidawork E. Liver Cirrhosis of Unknown Etiology and Its Predictors in Eastern Ethiopia. Risk Manag Healthc Policy 2024; 17:225-232. [PMID: 38282786 PMCID: PMC10812135 DOI: 10.2147/rmhp.s425954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 01/18/2024] [Indexed: 01/30/2024] Open
Abstract
Background The global burden of liver cirrhosis is increasing, with 2.1 million incident cases and nearly 1.5 million deaths in 2019. Despite the enormous progress in our understanding of the etiology of liver cirrhosis, significant cases of the disease have been reported in Eastern Ethiopia due to unidentified causes. Hence, this study aimed to identify predictors of liver cirrhosis of unknown etiology in Eastern Ethiopia. Methods A score of 7 out of 11 possible points on the ultrasound-based cirrhosis scale was used as a diagnostic criterion to include 127 liver cirrhosis patients. The study participants' demographic, dietary, lifestyle, and clinical data were gathered using a structured questionnaire and standardized reporting forms. The associations between the outcome (known and unknown etiology) and independent variables were modeled using binary logistic regression analysis. Results The etiology of liver cirrhosis was known in only 23% of patients and attributed to hepatitis B virus (21%), hepatitis C virus (0.8%), and alcohol abuse (0.8%). Sorghum consumption as a staple food (adjusted odds ratio (AOR) =3.8; 95% CI: 1.2, 12.5), splenomegaly (AOR = 4.0; 95% CI: 1.1, 14.4), and a family history of liver disease (AOR = 0.24; 95% CI: 0.06, 0.91) were significantly associated with liver cirrhosis of unknown etiology. Conclusion Sorghum consumption was found to be the determinant factor of liver cirrhosis of unknown etiology, suggesting it as a possible source of exposure to aflatoxin B1.
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Affiliation(s)
- Abraham Nigussie Mekuria
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Teshome Nedi
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yun Yun Gong
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Teferra Abula
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Ephrem Engidawork
- Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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2
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Elbaset MA, Mohamed BMSA, Moustafa PE, Mansour DF, Afifi SM, Esatbeyoglu T, Abdelrahman SSM, Fayed HM. Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:5514248. [PMID: 37649466 PMCID: PMC10465256 DOI: 10.1155/2023/5514248] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 07/16/2023] [Accepted: 07/21/2023] [Indexed: 09/01/2023]
Abstract
Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.
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Affiliation(s)
- Marawan A. Elbaset
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, P.O. Box 12622, Cairo, Egypt
| | - Bassim M. S. A. Mohamed
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, P.O. Box 12622, Cairo, Egypt
| | - Passant E. Moustafa
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, P.O. Box 12622, Cairo, Egypt
| | - Dina F. Mansour
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, P.O. Box 12622, Cairo, Egypt
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Galala University, Attaka, Suez, Egypt
| | - Sherif M. Afifi
- Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Tuba Esatbeyoglu
- Department of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, Hannover 30167, Germany
| | - Sahar S. M. Abdelrahman
- Department of Pathology, College of Veterinary Medicine, Cairo University, P.O. Box 12211, Cairo, Egypt
| | - Hany M. Fayed
- Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, P.O. Box 12622, Cairo, Egypt
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Khandait H, Jaiswal V, Hanif M, Shrestha AB, Iturburu A, Shah M, Ishak A, Garimella V, Ang SP, Mathew M. Percutaneous Coronary Intervention Outcomes in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis 2023; 10:jcdd10030092. [PMID: 36975856 PMCID: PMC10059068 DOI: 10.3390/jcdd10030092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/01/2023] [Accepted: 02/14/2023] [Indexed: 02/24/2023] Open
Abstract
There is a paucity of data and minimal literature on outcomes of percutaneous coronary intervention (PCI) among liver cirrhosis patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the clinical outcomes among liver cirrhosis patients post-PCI. We conducted a comprehensive literature search in the PubMed, Embase, Cochrane, and Scopus databases for relevant studies. Effect sizes were pooled using the DerSimonian and Laird random-effects model as an odds ratio (OR) with 95% confidence intervals (CI). A total of 3 studies met the inclusion criteria, providing data from 10,705,976 patients. A total of 28,100 patients were in the PCI + Cirrhosis group and 10,677,876 patients were in the PCI-only group. The mean age of patients with PCI + Cirrhosis and PCI alone was 63.45 and 64.35 years. The most common comorbidity was hypertension among the PCI + Cirrhosis group compared with PCI alone (68.15% vs. 73.6%). Cirrhosis patients post-PCI were had higher rates of in-hospital mortality (OR, 4.78 (95%CI: 3.39–6.75), p < 0.001), GI bleeding (OR, 1.91 (95%CI:1.83–1.99), p < 0.001, I2 = 0%), stroke (OR, 2.48 (95%CI:1.68–3.66), p < 0.001), AKI (OR, 3.66 (95%CI: 2.33–6.02), p < 0.001), and vascular complications (OR, 1.50 (95%CI: 1.13–1.98), p < 0.001) compared with the PCI group without cirrhosis. Patients with cirrhosis are at a high risk for mortality and adverse outcomes post-PCI procedure compared to the PCI-only group of patients.
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Affiliation(s)
| | - Vikash Jaiswal
- Department of Research, JCCR Cardiology Research, Varanasi 221005, India
- Correspondence:
| | - Muhammad Hanif
- Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA
| | | | - Alisson Iturburu
- Department of Medicine, Universidad de Guayaquil, Guayas 090514, Ecuador
| | - Maitri Shah
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, FL 33143, USA
| | - Angela Ishak
- Department of Research and Academic Affairs, Larkin Community Hospital, South Miami, FL 33143, USA
| | - Vamsi Garimella
- Department of Internal Medicine, University of Miami (Holy Cross), Miami, FL 33136, USA
| | - Song Peng Ang
- Division of Internal Medicine, Rutgers Health/Community Medical Center, Toms River, NJ 08755, USA
| | - Midhun Mathew
- Trinitas Regional Medical Center/RWJ Barnabas Health, Elizabeth, NJ 07202, USA
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4
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Huang J, Lucero-Prisno DE, Zhang L, Xu W, Wong SH, Ng SC, Wong MCS. Updated epidemiology of gastrointestinal cancers in East Asia. Nat Rev Gastroenterol Hepatol 2023; 20:271-287. [PMID: 36631716 DOI: 10.1038/s41575-022-00726-3] [Citation(s) in RCA: 112] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/29/2022] [Indexed: 01/13/2023]
Abstract
Globally, gastrointestinal cancers represent more than one-fourth of all cancer incidence and one-third of cancer-related mortality. Although there has been much progress in screening colorectal cancer, the prognosis of other gastrointestinal cancers tends to be poor. The highest burden of gastrointestinal cancers, including stomach, liver, oesophageal and gallbladder cancers, was observed in regions in East Asia. The increasing burden of gastrointestinal cancers in East Asian regions is related to population growth, ageing and the westernization of lifestyle habits in this region. Furthermore, the rising incidence of young-onset colorectal cancer is an emerging trend in East Asia. This Review provides a comprehensive and updated summary of the epidemiology of gastrointestinal cancers in East Asia, with emphasis on comparing their epidemiology in East Asia with that in Western regions, and highlights the major risk factors and implications for prevention. Overall, to optimally reduce the disease burden incurred by gastrointestinal cancers in East Asian regions, a concerted effort will be needed to modify unhealthy lifestyles, promote vaccination against the hepatitis virus, control Helicobacter pylori, liver fluke and hepatitis virus infections, increase the uptake rate of colorectal cancer screening, enhance detection of early cancers and their precursors, and improve cancer survivorship through an organized rehabilitation programme.
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Affiliation(s)
- Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.,Centre for Health Education and Health Promotion, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Don Eliseo Lucero-Prisno
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK
| | - Lin Zhang
- Centre of Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia.,Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.,School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wanghong Xu
- School of Public Health, Fudan University, Shanghai, China
| | - Sunny H Wong
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong SAR, China.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Siew C Ng
- Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory for Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong SAR, China.,Center for Gut Microbiota Research, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Martin C S Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. .,Centre for Health Education and Health Promotion, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China. .,School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. .,Department of Global Health, School of Public Health, Peking University, Beijing, China.
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Human stem cells for decompensated cirrhosis in adults. Cochrane Database Syst Rev 2022; 2022:CD015173. [PMCID: PMC9531721 DOI: 10.1002/14651858.cd015173] [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: 01/04/2025]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of stem cell treatment in adults with decompensated cirrhosis, regardless of ethnicity, sex, types of stem cells, route of stem cell injection, and administered dose.
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Ristic-Medic D, Bajerska J, Vucic V. Crosstalk between dietary patterns, obesity and nonalcoholic fatty liver disease. World J Gastroenterol 2022; 28:3314-3333. [PMID: 36158263 PMCID: PMC9346467 DOI: 10.3748/wjg.v28.i27.3314] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 05/03/2022] [Accepted: 06/18/2022] [Indexed: 02/06/2023] Open
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising worldwide, paralleling the epidemic of obesity. The liver is a key organ for the metabolism of proteins, fats and carbohydrates. Various types of fats and carbohydrates in isocaloric diets differently influence fat accumulation in the liver parenchyma. Therefore, nutrition can manage hepatic and cardiometabolic complications of NAFLD. Even moderately reduced caloric intake, which leads to a weight loss of 5%-10% of initial body weight, is effective in improving liver steatosis and surrogate markers of liver disease status. Among dietary patterns, the Mediterranean diet mostly prevents the onset of NAFLD. Furthermore, this diet is also the most recommended for the treatment of NAFLD patients. However, clinical trials based on the dietary interventions in NAFLD patients are sparse. Since there are only a few studies examining dietary interventions in clinically advanced stages of NAFLD, such as active and fibrotic steatohepatitis, the optimal diet for patients in these stages of the disease must still be determined. In this narrative review, we aimed to critically summarize the associations between different dietary patterns, obesity and prevention/risk for NAFLD, to describe specific dietary interventions' impacts on liver steatosis in adults with NAFLD and to provide an updated overview of dietary recommendations that clinicians potentially need to apply in their daily practice.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic Serbia, Belgrade PO Box 102, Serbia
| | - Joanna Bajerska
- Department of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań 60-624, Poland
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic Serbia, Belgrade PO Box 102, Serbia
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7
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Alleviation of liver cirrhosis and associated portal-hypertension by Astragalus species in relation to their UPLC-MS/MS metabolic profiles: a mechanistic study. Sci Rep 2022; 12:11884. [PMID: 35831335 PMCID: PMC9279505 DOI: 10.1038/s41598-022-15958-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/01/2022] [Indexed: 11/08/2022] Open
Abstract
Liver cirrhosis is a late-stage liver disease characterized by excessive fibrous deposition triggering portal-hypertension (PH); the prime restrainer for cirrhosis-related complications. Remedies that can dually oppose hepatic fibrosis and lower PH, may prevent progression into decompensated-cirrhosis. Different Astragalus-species members have shown antifibrotic and diuretic actions with possible subsequent PH reduction. However, A.spinosus and A.trigonus were poorly tested for eliciting these actions. Herein, A.spinosus and A.trigonus roots and aerial parts extracts were subjected to comprehensive metabolic-fingerprinting using UHPLC-MS/MS resulting in 56 identified phytoconstituents, followed by chemometric untargeted analysis that revealed variable metabolic profiles exemplified by different species and organ types. Consequently, tested extracts were in-vivo evaluated for potential antifibrotic/anticirrhotic activity by assessing specific markers. The mechanistic prospective to induce diuresis was investigated by analyzing plasma aldosterone and renal-transporters gene-expression. Serum apelin and dimethylarginine-dimethylaminohydrolase-1 were measured to indicate the overall effect on PH. All extracts amended cirrhosis and PH to varying extents and induced diuresis via different mechanisms. Further, An OPLS model was built to generate a comprehensive metabolic-profiling of A.spinosus and A.trigonus secondary-metabolites providing a chemical-based evidence for their efficacious consistency. In conclusion, A.spinosus and A.trigonus organs comprised myriad pharmacologically-active constituents that act synergistically to ameliorate cirrhosis and associated PH.
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Lee HL, Lee J, Cha JH, Cho S, Sung PS, Hur W, Yoon SK, Bae SH. Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells. Korean J Intern Med 2022; 37:53-62. [PMID: 32872742 PMCID: PMC8747913 DOI: 10.3904/kjim.2020.197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/20/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Patients with liver cirrhosis (LC) have low levels of branched-chain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). METHODS LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real-time quantitative polymerase chain reaction and Western blotting. RESULTS The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively. CONCLUSION BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.
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Affiliation(s)
- Hae Lim Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jungmin Lee
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Hoon Cha
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Sungwoo Cho
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Wonhee Hur
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Korea
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Lee SW, Kim SM, Hur W, Kang BY, Lee HL, Nam H, Yoo SH, Sung PS, Kwon JH, Jang JW, Kim SJ, Yoon SK. Tenofovir disoproxil fumarate directly ameliorates liver fibrosis by inducing hepatic stellate cell apoptosis via downregulation of PI3K/Akt/mTOR signaling pathway. PLoS One 2021; 16:e0261067. [PMID: 34879114 PMCID: PMC8654182 DOI: 10.1371/journal.pone.0261067] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 11/23/2021] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Antifibrotic agent for the treatment of liver fibrosis has not been developed so far. Long term treatment of chronic hepatitis B patients with antiviral drugs tenofovir disoproxil fumarate (TDF) and entecavir (ETV) results in the regression of liver fibrosis, but the underlying mechanism has not been clarified. Therefore, we aimed to investigate the direct impact of TDF and ETV on liver fibrosis. METHODS Activated hepatic stellate cell (HSC) cell lines were used to evaluate the effects of TDF and ETV. After treatment with each antiviral agent, cell viability, morphology, apoptotic features, autophagy and antifibrosis signalling pathways were examined. Then, collagen deposition, fibrosis markers and activated HSCs were measured in liver tissues of the liver fibrosis model mice. RESULTS After TDF treatment, the viabilities of LX2 and HSC-T6 cells were decreased, and the cells exhibited apoptotic features, but ETV did not induce these effects. Cleavage of PARP and Caspase-3 and the inhibition of the antiapoptotic gene Bcl-xl indicated activated HSC apoptosis following TDF treatment. TDF simultaneously increased autophagy, which also regulated apoptosis through crosstalk. TDF inactivated the PI3K/Akt/mTOR signalling pathway, which was associated with the activation of both apoptosis and autophagy. In the liver fibrosis mouse model, the fibrotic area and activated HSC markers were decreased by TDF but not ETV treatment. Additionally, apoptotic cells were concentrated in the periportal fibrotic area after TDF treatment, which indicated the specific antifibrotic effect of TDF. CONCLUSIONS TDF directly ameliorates liver fibrosis by downregulating the PI3K/Akt/mTOR signalling pathway, which results in the apoptosis of activated HSCs. The antifibrotic effects of TDF indicate that it may be a therapeutic agent for the treatment of liver fibrosis.
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Affiliation(s)
- Sung Won Lee
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Min Kim
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
| | - Wonhee Hur
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Yoon Kang
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hae Lim Lee
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Heechul Nam
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sun Hong Yoo
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Pil Soo Sung
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Hyun Kwon
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seong-Jun Kim
- Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
| | - Seung Kew Yoon
- Department of Biomedicine & Health Sciences, The Catholic University Liver Research Centre, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, Republic of Korea
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Alboraie M, Khairy M, Elsharkawy A, Asem N, El Kassas M, Elgendy AA, Nagdy H, Shady Z, Eliwa A, El-Ansary AR, Ibrahem M, Allam MA, Elsherif A, Elghamry F, Hassan F, Hassany M, Esmat G, On behalf of the Egyptian Liver Fibrosis Study Group. Role of liver biopsy versus non-invasive biomarkers for diagnosis of significant fibrosis and cirrhosis: a web-based survey. EGYPTIAN LIVER JOURNAL 2021; 11:94. [DOI: 10.1186/s43066-021-00166-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 12/12/2021] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Liver biopsy is the standard reference for staging hepatic fibrosis. Non-invasive methods for assessment of hepatic fibrosis and cirrhosis are becoming increasingly popular.
Objective
We aimed at exploring the change in practice regarding the use of liver biopsy and non-invasive methods for staging hepatic fibrosis and cirrhosis among hepatologists.
Methods
We performed a survey-based study that recruited hepatologists from various Egyptian institutions. Physicians were deemed eligible if they had a degree in internal medicine with hepatology as a subspecialty. We utilized an online-based survey that assessed the acceptability and reliability of liver biopsy, serum biomarkers, and radiological tools for evaluating liver fibrosis and cirrhosis.
Results
A total of 573 responses were retrieved (response rate = 80.3%). Out of them, 58% were having more than 15 years of experience as a hepatologist.
Liver biopsy is still considered the gold standard for assessment of hepatic fibrosis and cirrhosis by 61% of participants. Liver biopsy was accepted by 44% of their patients. 84% reported the need for a more practical alternative to liver biopsy to assess disease progression or response to treatment. 78.34% of participants know serum biomarkers, 84.08% reported that they were acceptable by their patients, 37.79% thought they are reliable. 95.4% were familiar with radiological methods of non-invasive assessment of hepatic fibrosis, 89.1% reported that radiological methods were acceptable by their patients, 62% think that they are reliable and 78% reported they were applicable in clinical practice. Sixty-five percent think that combining non-invasive methods is better than using a single method. Forty percent of participants thought that radiological methods are easier to use for assessment of hepatic fibrosis followed by a combination of non-invasive methods, serum biomarkers, and liver biopsy respectively.
Conclusion
In conclusion, liver biopsy is still considered the most reliable method for evaluation and staging of liver cirrhosis by hepatologists in Egyptian institutions, despite the modest acceptance by the patients. Nonetheless, non-invasive methods are gaining acceptance by Egyptian physicians and patients, and most of them consider these methods as reliable and applicable tools for predicting the course of liver cirrhosis.
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Roe JD, Garcia LA, Klimentidis YC, Coletta DK. Association of PNPLA3 I148M with Liver Disease Biomarkers in Latinos. Hum Hered 2021; 86:21-27. [PMID: 34749354 DOI: 10.1159/000520734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/03/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help to estimate liver damage, including AST-to-ALT ratio, AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and nonalcoholic fatty liver disease (NAFLD) fibrosis score. The aims of the present study were to (1) perform an association analysis of the patatin-like phospholipase domain containing 3 (PNPLA3) I148M (rs738409) variant with ALT, AST, and various liver fibrosis indices, and (2) determine whether there are gender-related differences in these associations. METHODS We obtained demographic, anthropometric, and metabolic phenotypes from Latino adult participants (n = 503, 64% female, 36.4 ± 0.5 years) from the Arizona Insulin Resistance (AIR) registry. SNP genotyping of I148M was performed using the TaqMan allelic discrimination assay. We used linear regression for the association analyses of the genotypes with ALT, AST, and the various liver fibrosis indices. We included genotype, age, body mass index, and alcohol status in the linear regression model. RESULTS The variant I148M was in Hardy-Weinberg equilibrium, with genotype distribution: non-risk CC 118, heterozygous CG 246, and risk GG 139. The G allele was significantly associated with increased ALT and AST levels (p = 7.8 × 10-7 and p = 9.7 × 10-6, respectively). Moreover, we showed that the G allele was significantly associated with higher APRI (p = 3.7 × 10-7) and FIB-4 score (p = 4.1 × 10-3). When we analyzed the data by gender, we observed similar significant trends for ALT, AST, and APRI (all, p < 0.01). In females, the G allele was significantly associated with increased FIB-4 score (p = 6.9 × 10-3), which was not observed in the males (p > 0.05). There was no association of the I148M variant with AST/ALT ratio nor NAFLD risk score, whether analyzed in all adults or by gender. DISCUSSION/CONCLUSION Our findings provide additional evidence of an association of PNPLA3 I148M with several liver disease biomarkers in male and female Latinos residing in the Southwest of the United States.
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Affiliation(s)
- Jonathan D Roe
- Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona, USA
| | - Luis A Garcia
- Department of Medicine, Division of Endocrinology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Center for Disparities in Diabetes Obesity, and Metabolism, University of Arizona, Tucson, Arizona, USA
| | - Yann C Klimentidis
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, USA
| | - Dawn K Coletta
- Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Department of Medicine, Division of Endocrinology, College of Medicine, University of Arizona, Tucson, Arizona, USA.,Center for Disparities in Diabetes Obesity, and Metabolism, University of Arizona, Tucson, Arizona, USA
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12
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Trends in the Economic Burden of Chronic Liver Diseases and Cirrhosis in the United States: 1996-2016. Am J Gastroenterol 2021; 116:2060-2067. [PMID: 33998785 DOI: 10.14309/ajg.0000000000001292] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/29/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The management of chronic liver diseases (CLDs) and cirrhosis is associated with substantial healthcare costs. We aimed to estimate trends in national healthcare spending for patients with CLDs or cirrhosis between 1996 and 2016 in the United States. METHODS National-level healthcare expenditure data developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project and prevalence of CLDs and cirrhosis derived from the Global Burden of Diseases Study were used to estimate temporal trends in inflation-adjusted US healthcare spending, stratified by setting of care (ambulatory, inpatient, emergency department, and nursing care). Joinpoint regression was used to evaluate temporal trends, expressed as annual percent change (APC) with 95% confidence intervals (CIs). Drivers of change in spending for ambulatory and inpatient services were also evaluated. RESULTS Total expenditures in 2016 were $32.5 billion (95% CI, $27.0-$40.4 billion). Over 65% of spending was for inpatient or emergency department care. From 1996 to 2016, there was a 4.3%/year (95% CI, 2.8%-5.8%) increase in overall healthcare spending for patients with CLDs or cirrhosis, driven by a 17.8%/year (95% CI, 14.5%-21.6%) increase in price and intensity of hospital-based services. Total healthcare spending per patient with CLDs or cirrhosis began decreasing after 2008 (APC -1.7% [95% CI, -2.1% to -1.2%]), primarily because of reductions in ambulatory care spending (APC -9.1% [95% CI, -10.7% to -7.5%] after 2011). DISCUSSION Healthcare expenditures for CLDs or cirrhosis are substantial in the United States, driven disproportionately by acute care in-hospital spending.
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13
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Huang J, Lok V, Ngai CH, Chu C, Patel HK, Thoguluva Chandraseka V, Zhang L, Chen P, Wang S, Lao XQ, Tse LA, Xu W, Zheng ZJ, Wong MC. Disease Burden, Risk Factors, and Recent Trends of Liver Cancer: A Global Country-Level Analysis. Liver Cancer 2021; 10:330-345. [PMID: 34414121 PMCID: PMC8339459 DOI: 10.1159/000515304] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 02/06/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND This study aimed to evaluate the updated disease burden, risk factors, and temporal trends of liver cancer based on age, sex, and country. METHODS We estimated the incidence of liver cancer and its attribution to hepatitis B virus (HBV) and hepatitis C virus (HCV) in 2018 based on the Global Cancer Observatory and World Health Organization (WHO) Cancer Causes database. We extracted the prevalence of risk factors from the WHO Global Health Observatory to examine the associations by weighted linear regression. The trend analysis used data from the Cancer Incidence in Five Continents and the WHO mortality database from 48 countries. Temporal patterns of incidence and mortality were calculated using average annual percent change (AAPC) by joinpoint regression analysis. RESULTS The global incidence of liver cancer was (age-standardized rate [ASR]) 9.3 per 100,000 population in 2018, and there was an evident disparity in the incidence related to HBV (ASR 0.2-41.2) and HCV (ASR 0.4-43.5). A higher HCV/HBV-related incidence ratio was associated with a higher level of alcohol consumption (β 0.49), overweight (β 0.51), obesity (β 0.64), elevated cholesterol (β 0.70), gross domestic product (β 0.20), and Human Development Index (HDI; β 0.45). An increasing trend in incidence was identified in many countries, especially for male individuals, population aged ≥50 years, and countries with a higher HCV/HBV-related liver cancer incidence ratio. Countries with the most drastic increase in male incidence were reported in India (AAPC 7.70), Ireland (AAPC 5.60), Sweden (AAPC 5.72), the UK (AAPC 5.59), and Norway (AAPC 4.87). CONCLUSION We observed an overall increasing trend of liver cancer, especially among male subjects, older individuals, and countries with a higher prevalence of HCV-related liver cancer. More efforts are needed in enhancing lifestyle modifications and accessibility of antiviral treatment for these populations. Future studies should investigate the reasons behind these epidemiological changes.
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Affiliation(s)
- Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Veeleah Lok
- Department of Global Public Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Chun Ho Ngai
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Cedric Chu
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Harsh K. Patel
- Department of Internal Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
| | | | - Lin Zhang
- Centre of Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia,Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia,School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ping Chen
- Department of Gastroenterology, Ruijing Hospital North, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Shanjuan Wang
- Department of Gastroenterology, Jiading District Hospital, Shanghai, China
| | - Xiang-Qian Lao
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China,School of Public Health, Zhengzhou University, Zhengzhou, China
| | - Lap Ah Tse
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Wanghong Xu
- School of Public Health, Fudan University, Shanghai, China
| | - Zhi-Jie Zheng
- Department of Global Health, School of Public Health, Peking University, Beijing, China,*Zhi-Jie Zheng,
| | - Martin C.S. Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China,School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,Department of Global Health, School of Public Health, Peking University, Beijing, China,**Martin C.S. Wong,
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14
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Alvarez CS, Hernández E, Escobar K, Villagrán CI, Kroker-Lobos MF, Rivera-Andrade A, Smith JW, Egner PA, Lazo M, Freedman ND, Guallar E, Dean M, Graubard BI, Groopman JD, Ramírez-Zea M, McGlynn KA. Aflatoxin B 1 exposure and liver cirrhosis in Guatemala: a case-control study. BMJ Open Gastroenterol 2021; 7:bmjgast-2020-000380. [PMID: 32641287 PMCID: PMC7342465 DOI: 10.1136/bmjgast-2020-000380] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 04/21/2020] [Accepted: 04/24/2020] [Indexed: 02/07/2023] Open
Abstract
Objective In Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B1 (AFB1) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB1 increases the risk of cirrhosis in the absence of viral infection, however, is not clear. Design Cirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB1 in crude and adjusted models. A sex-stratified analysis was also conducted. Results The median AFB1 level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression analyses, higher levels of AFB1 was associated with cirrhosis (quintile 5 vs quintile 1, OR: 11.55; 95% CI 4.05 to 32.89). No attenuation was observed with adjustment by sex, ethnicity, hepatitis B virus status, and heavy alcohol consumption. A significantly increasing trend in association was observed in both models (p trend <0.01). Additionally, the cirrhosis–AFB1 association was more prominent among men. Conclusions The current study found a significant positive association between AFB1 exposure and cirrhosis. Mitigation of AFB1 exposure and a better understanding of additional risk factors may be important to reduce the burden of cirrhosis in Guatemala.
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Affiliation(s)
- Christian S Alvarez
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - Elisa Hernández
- Centro de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Universidad de San Carlos de Guatemala, Guatemala, Guatemala
| | - Kira Escobar
- Centro de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Universidad de San Carlos de Guatemala, Guatemala, Guatemala
| | - Carmen I Villagrán
- Centro de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Universidad de San Carlos de Guatemala, Guatemala, Guatemala
| | - María F Kroker-Lobos
- INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala, Guatemala
| | - Alvaro Rivera-Andrade
- INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala, Guatemala
| | - Joshua W Smith
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Patricia A Egner
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Mariana Lazo
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.,Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - Eliseo Guallar
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Michael Dean
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - Barry I Graubard
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
| | - John D Groopman
- Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.,Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Manuel Ramírez-Zea
- INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala, Guatemala
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
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15
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Jo HH, Min C, Kyoung DS, Park MA, Kim SG, Kim YS, Chang Y, Jeong SW, Jang JY, Lee SH, Kim HS, Jun BG, Kim YD, Cheon GJ, Yoo JJ. Adverse outcomes after surgeries in patients with liver cirrhosis among Korean population: A population-based study. PLoS One 2021; 16:e0253165. [PMID: 34125860 PMCID: PMC8202950 DOI: 10.1371/journal.pone.0253165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 05/30/2021] [Indexed: 11/30/2022] Open
Abstract
Background Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. Methods and findings We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56–1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36). Conclusion The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment.
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Affiliation(s)
- Hyun Ho Jo
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Changwook Min
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | | | - Min-Ae Park
- Data Science Team, Hanmi Pharm. Co., Ltd., Seoul, Korea
| | - Sang Gyune Kim
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Young Seok Kim
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Young Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Jae Young Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Seoul, Korea
| | - Sae Hwan Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Cheonan, Korea
| | - Hong Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine, Cheonan, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Seoul, Korea
| | - Young Don Kim
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Seoul, Korea
| | - Gab Jin Cheon
- Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Seoul, Korea
| | - Jeong-Ju Yoo
- Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea
- * E-mail:
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16
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Design and evaluation of bioenhanced oral tablets of Dunaliella salina microalgae for treatment of liver fibrosis. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101845] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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17
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Jang WY, Chung WJ, Jang BK, Hwang JS, Lee HJ, Hwang MJ, Kweon YO, Tak WY, Park SY, Lee SH, Lee CH, Kim BS, Kim SH, Suh JI, Park JG. Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea. J Korean Med Sci 2020; 35:e233. [PMID: 32715667 PMCID: PMC7384901 DOI: 10.3346/jkms.2020.35.e233] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 05/28/2020] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. METHODS We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. RESULTS A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. CONCLUSION In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.
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Affiliation(s)
- Won Young Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Heon Ju Lee
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Moon Joo Hwang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Su Hyun Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Chang Hyeong Lee
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Byung Seok Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Si Hye Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Jeong Ill Suh
- Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, Korea
| | - Jun Gi Park
- Department of Internal Medicine, Dongguk University College of Medicine, Gyeongju, Korea
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18
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Akbulut S, Gunes G, Saritas H, Aslan B, Karipkiz Y, Demyati K, Gungor S, Yilmaz S. Differences in parents of pediatric liver transplantation and chronic liver disease patients. World J Clin Cases 2020; 8:2162-2172. [PMID: 32548146 PMCID: PMC7281060 DOI: 10.12998/wjcc.v8.i11.2162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/18/2020] [Accepted: 05/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND With advancements in the treatment of chronic liver disease (CLD), including liver transplantation (LT), quality of life and satisfaction after LT have become an important issue for pediatric patients and their parents. More evidence-based information is needed to describe and assess the impact of pediatric CLD on parents and the satisfaction of parents with treatment to better understand their needs. AIM To assess the satisfaction of parents of pediatric LT patients and that of parents of pediatric CLD patients. METHODS During this survey, data were collected from parents of pediatric patients who underwent LT between January 2010 and April 2017 (LT group; n = 91) and parents of pediatric patients with chronic liver disease (CLD group; n = 94). Group comparisons were made based on the pediatric health-related quality of life (PedsQL) health care parent satisfaction scale, impact on family scale (IFS) and demographic characteristics. The PedsQL was administered to parents during a phone interview and the results were used to assess the health care-related satisfaction of parents. The IFS was used to assess the impact of the child's CLD status on the family. Demographic variables such as education level (elementary vs middle vs high vs university), monthly income (low vs middle vs high), and place of residence (village vs town vs city) were compared between CLD and LT parent groups. Finally, PedsQL and IFS results were also analyzed according to demographic variables. RESULTS A total of 185 parents aged 19 to 65 years were included. There were statistically significant differences between the LT and CLD groups in terms of career (P < 0.001), monthly income (P = 0.016), and education level (P = 0.041). According to the PedsQL results, family inclusion, communication, technical skills, emotional needs, and overall satisfaction were significantly different between the groups; the LT group had consistently higher scores (P < 0.001). Additionally, scores for the IFS parameters of financial impact, familial-social impact, personal strain, and total impact were consistently higher for the LT group (P < 0.001). There were statistically significant relationships between education level, monthly income, and place of residence according to the IFS results but not the PedsQL results. There were inverse relationships between the difficulties that parents experience because of their child's health and education levels, monthly income, and place of residence. However, no relationship was found between education level, monthly income, or place of residence and satisfaction with health care services provided in the hospital according to the PedsQL results. CONCLUSION Parents of children who underwent LT were very satisfied with the health care services provided to their children. However, they had more difficulties than parents of children with CLD.
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Affiliation(s)
- Sami Akbulut
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
- Department of Public Health, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Gulsen Gunes
- Department of Public Health, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Hasan Saritas
- Department of Surgical Nursing, Inonu University Faculty of Nursing's, Malatya 44280, Turkey
| | - Bahar Aslan
- Department of Surgical Nursing, Inonu University Faculty of Nursing's, Malatya 44280, Turkey
| | - Yunus Karipkiz
- Department of Nursing Care Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Khaled Demyati
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
- Department of Surgery, An-Najah National University Hospital, An-Najah National University, Nablus 11941, Palestin
| | - Sukru Gungor
- Department of Pediatric Gastroenterology, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Sezai Yilmaz
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
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Dwivedi DK, Jena G, Kumar V. Dimethyl fumarate protects thioacetamide-induced liver damage in rats: Studies on Nrf2, NLRP3, and NF-κB. J Biochem Mol Toxicol 2020; 34:e22476. [PMID: 32060995 DOI: 10.1002/jbt.22476] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/17/2019] [Accepted: 02/06/2020] [Indexed: 12/30/2022]
Abstract
The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)-induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA-induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA-induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains-containing protein 3; NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain; ASC, caspase-1, nuclear factor-kappa B; NF-κB, interleukin-6), fibrogenic makers (α-smooth muscle actin; ɑ-SMA, transforming growth factor; TGF-β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid-derived 2)-like factor 2; Nrf2, superoxide dismutase-1; SOD-1, catalase). The present findings concluded that DMF protects against TAA-induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.
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Affiliation(s)
- Durgesh K Dwivedi
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India
| | - Gopabandhu Jena
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India
| | - Vinod Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India
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20
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Fortea JI, Puerto M, Fernández-Mena C, Asensio I, Arriba M, Almagro J, Bañares J, Ripoll C, Bañares R, Vaquero J. Sevoflurane versus ketamine+diazepam anesthesia for assessing systemic and hepatic hemodynamics in rats with non-cirrhotic portal hypertension. PLoS One 2020; 15:e0233778. [PMID: 32469999 PMCID: PMC7259621 DOI: 10.1371/journal.pone.0233778] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 05/12/2020] [Indexed: 11/30/2022] Open
Abstract
The selection of the anesthetic regime is a crucial component in many experimental animal studies. In rodent models of liver disease, the combination of ketamine and diazepam (KD), generally by the intramuscular (i.m.) route, has traditionally been the anesthesia of choice for the evaluation of systemic and hepatic hemodynamics but it presents several problems. Here, we compared the performance of inhalational sevoflurane (Sevo) against the KD combination as the anesthesia used for hemodynamic studies involving the measurement of portal pressure in normal rats (Ctrl) and rats with non-cirrhotic portal hypertension induced by partial portal vein ligation (PPVL). Compared with Ctrl rats, rats with PPVL presented characteristic alterations that were not influenced by the anesthetic regime, which included liver atrophy, splenomegaly, increased plasma fibrinogen, decreased alkaline phosphatase and glycemia, and frequent ascites. The use of the KD combination presented several disadvantages compared with the inhalational anesthesia with sevoflurane, including considerable mortality, a higher need of dose adjustments to maintain an optimal depth of anesthesia, increases of heart rate, and alteration of blood biochemical parameters such as the concentration of aspartate aminotransferase, lactate, and lactic dehydrogenase. Rats anesthetized with sevoflurane, on the other hand, presented lower respiratory rates. Importantly, the anesthetic regime did not influence the measurement of portal pressure either in Ctrl or PPVL rats, with the increase of portal pressure being similar in Sevo- and KD- anesthetized groups of PPVL rats compared with their respective control groups. Overall, our results suggest that anesthesia with sevoflurane is preferable to the combination of KD for performing systemic and hepatic hemodynamic studies in rats with non-cirrhotic portal hypertension.
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Affiliation(s)
- José Ignacio Fortea
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Servicio de Digestivo, Hospital Universitario Marqués de Valdecilla, Santander, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Marta Puerto
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Carolina Fernández-Mena
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Iris Asensio
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - María Arriba
- Servicio de Bioquímica Clínica del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Jorge Almagro
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Juan Bañares
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Cristina Ripoll
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Innere Medizin I, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany
| | - Rafael Bañares
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Facultad de Medicina, Universidad Complutense, Madrid, Spain
| | - Javier Vaquero
- HepatoGastro Lab, Servicio de Ap. Digestivo del HGU Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- * E-mail:
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Lim SL, Johal J, Ong KW, Han CY, Chan YH, Lee YM, Loo WM. Lifestyle Intervention Enabled by Mobile Technology on Weight Loss in Patients With Nonalcoholic Fatty Liver Disease: Randomized Controlled Trial. JMIR Mhealth Uhealth 2020; 8:e14802. [PMID: 32281943 PMCID: PMC7186867 DOI: 10.2196/14802] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/09/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023] Open
Abstract
Background The prevalence of nonalcoholic fatty liver disease (NAFLD) reaches up to 30% in the Asian adult population, with a higher prevalence in obese patients. Weight reduction is typically recommended for patients at high risk or diagnosed with NAFLD, but is a challenge to achieve. Objective We aimed to evaluate the effect of a lifestyle intervention with a mobile app on weight loss in NAFLD patients. Methods This prospective randomized controlled trial included 108 adults with NAFLD confirmed by steatosis on ultrasound and a body mass index ≥23 kg/m2 who were recruited from a fatty liver outpatient clinic. The patients were randomly allocated to either a control group (n=53) receiving standard care, consisting of dietary and lifestyle advice by a trained nurse, or an intervention group (n=55) utilizing the Nutritionist Buddy (nBuddy) mobile app in addition to receiving dietary and lifestyle advice by a dietitian. Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST), waist circumference, and blood pressure were measured at baseline, and then at 3 and 6 months. Intention-to-treat and per-protocol analyses were used for statistical comparisons. Results The intervention group had a 5-fold higher likelihood (relative risk 5.2, P=.003, 95% CI 1.8-15.4) of achieving ≥5% weight loss compared to the control group at 6 months. The intervention group also showed greater reductions in weight (mean 3.2, SD 4.1 kg vs mean 0.5, SD 2.9 kg; P<.001), waist circumference (mean 2.9, SD 5.0 cm vs mean –0.7, SD 4.4 cm; P<.001), systolic blood pressure (mean 12.4, SD 14.8 mmHg vs mean 2.4, SD 12.4 mmHg; P=.003), diastolic blood pressure (mean 6.8, SD 8.9 mmHg vs mean –0.9, SD 10.0 mmHg; P=.001), ALT (mean 33.5, SD 40.4 IU/L vs mean 11.5, SD 35.2 IU/L; P=.004), and AST (mean 17.4, SD 27.5 U/L vs mean 7.4, SD 17.6 IU/L, P=.03) at 6 months. Conclusions Lifestyle intervention enabled by a mobile app can be effective in improving anthropometric indices and liver enzymes in patients with NAFLD. This treatment modality has the potential to be extended to a larger population scale. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12617001001381;
https://tinyurl.com/w9xnfmp
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Affiliation(s)
- Su Lin Lim
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Jolyn Johal
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Kai Wen Ong
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Chad Yixian Han
- Dietetics Department, National University Hospital, National University Health System, Singapore, Singapore
| | - Yiong Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yin Mei Lee
- Department of Medicine, Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
| | - Wai Mun Loo
- Department of Medicine, Gastroenterology and Hepatology, National University Hospital, National University Health System, Singapore, Singapore
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Vadhariya A, Chen H, Serna O, Zamil H, Abughosh SM. A retrospective study of drug utilization and hospital readmissions among Medicare patients with hepatic encephalopathy. Medicine (Baltimore) 2020; 99:e19603. [PMID: 32311928 PMCID: PMC7220267 DOI: 10.1097/md.0000000000019603] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 01/22/2020] [Accepted: 02/19/2020] [Indexed: 12/20/2022] Open
Abstract
Hepatic encephalopathy (HE) is a complication occurring in patients with cirrhosis and is associated with neuropsychiatric and motor abnormalities. Symptomatic HE episodes almost always require hospitalization and the frequent recurrence of episodes is associated with poor prognosis and increased medical costs. The utilization of existing therapies for management of HE and adherence to them has yet to be evaluated using real-world claims data.The aim of this study was to evaluate HE drug regimens and adherence and their association with hospital readmissions in Medicare Advantage plan patients.This was a retrospective cohort study of patients discharged from a HE-related hospitalization or emergency room visit. Based on subsequent enrollment in the plan they were categorized into cohorts of 1 month, 3, and 6 months follow-up, and medication regimen was evaluated within the first month. The drugs evaluated included lactulose, rifaximin, and neomycin. Multivariable logistic regression was conducted to evaluate the association of drug regimen and medication adherence measured as proportion of days covered with HE readmissions.There were 347 patients hospitalized for HE with 184 patients having 30-day enrollment and either a drug refill or an outpatient visit in this duration. Medications were not refilled by 67 (36.4%) patients. Various drug regimens had different adherence with mean (standard deviation) proportion of days covered ranging from 0.56 (0.29) to 0.82 (0.16) at 3 months and 0.48 (0.3) to 0.77 (0.15) at 6 months. The results of logistic regression at 3 and 6 months did not show a significant association of medication use or medication adherence with hospital readmissions.Despite availability of therapy, medication utilization was alarmingly low after discharge of patients from HE-related hospitalization. Medication adherence was also low, which may affect the rate of recurrence and costs associated with readmissions. Efforts are needed in both care coordination of these patients to ensure they are prescribed appropriate medications and to enhance adherence to them.
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Affiliation(s)
| | - Hua Chen
- Department of Pharmaceutical Health Outcomes and Policy, University of Houston College of Pharmacy, Houston, TX
| | | | - Hani Zamil
- McGovern Medical School at the University of Texas Health Science Center, Houston, TX
| | - Susan M. Abughosh
- Department of Pharmaceutical Health Outcomes and Policy, University of Houston College of Pharmacy, Houston, TX
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23
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Ye L, Yu Y, Zhao Y. Icariin-induced miR-875-5p attenuates epithelial-mesenchymal transition by targeting hedgehog signaling in liver fibrosis. J Gastroenterol Hepatol 2020; 35:482-491. [PMID: 31617598 DOI: 10.1111/jgh.14875] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 09/18/2019] [Accepted: 09/23/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatic fibrosis is the final endpoint for most chronic liver diseases and remains a significant public health problem worldwide. Icariin, a naturally occurring flavonol glucoside, has been reported to exhibit protective effects on liver injury and alleviate liver fibrosis. However, the underlying detail molecular mechanism is not fully revealed. METHODS Mouse primary hepatic stellate cells (HSCs) and carbon tetrachloride (CCL4 )-induced liver fibrosis model in mice were used as in vitro and in vivo models in this study. The expression levels of miR-875-5p were detected by quantitative reverse transcription-PCR. The validation of the direct target of miR-875-5p was through dual-luciferase reporter assay and western blotting assay. The cell proliferation and cell mobility were determined using MTT assay and Transwell migration assay, respectively. RESULTS We found that icariin inhibited epithelial-mesenchymal transition and collagen protein section of HSCs. Icariin exerted hepatoprotective effects on mice model of CCL4 -induced liver fibrosis. Our further results revealed that miR-875-5p was downregulated in human cirrhosis tissues and activated murine HSCs. Icariin induced miR-875-5p upregulation and subsequently decreased glioma-associated oncogene homolog 1 (GLI1) expression through direct binding to the three prime untranslated region of GLI1 mRNA. CONCLUSION Our study highlighted the potential therapeutic application of icariin for liver fibrosis management.
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Affiliation(s)
- Lei Ye
- First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Zhejiang, China
| | - Yaping Yu
- First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Zhejiang, China
| | - Yanping Zhao
- First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Zhejiang, China
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24
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Maraolo AE, Scotto R, Zappulo E, Pinchera B, Schiano Moriello N, Nappa S, Buonomo AR, Gentile I. Novel strategies for the management of bacterial and fungal infections in patients with liver cirrhosis: focus on new antimicrobials. Expert Rev Anti Infect Ther 2020; 18:191-202. [PMID: 32011191 DOI: 10.1080/14787210.2020.1725473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Liver cirrhosis is a frequent condition caused by different etiologies. Bacterial and fungal infections are common complications, representing an independent prognostic stage in patients with cirrhosis, dramatically worsening their clinical outcomes.Areas covered: The present review article addresses manifold points and to this purpose an inductive literature search of MEDLINE database through PubMed was performed. First, it provides an overview on the mechanisms underlying immune disfunctions in patients with cirrhosis, who are prone to develop infections being at higher risk than the general population. Second, commonest types of bacterial and fungal infections in patients with advanced liver disease are described, focusing on their deleterious impact as decompensating events. Third, the rise of multidrug-resistant (MDR) bacteria and fungi as causative agents of infection in cirrhotic subjects is illustrated. Eventually, the most promising novel therapeutic options against MDR pathogens and fungi are reviewed.Expert opinion: The management of bacterial and fungal infections in patients with cirrhosis is difficult, due to the frequent co-existence of renal impairment, low platelet count and other conditions that limit the antimicrobial choice. New antibacterial and antifungal compounds may overcome this issue by providing a better tolerability profile, along with equal or superior efficacy compared with older drugs.
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Affiliation(s)
- Alberto E Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Nicola Schiano Moriello
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Salatore Nappa
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
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Therapeutic Effect of Tanshinone IIA on Liver Fibrosis and the Possible Mechanism: A Preclinical Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:7514046. [PMID: 31915451 PMCID: PMC6930756 DOI: 10.1155/2019/7514046] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/27/2019] [Accepted: 11/11/2019] [Indexed: 12/14/2022]
Abstract
Background Liver fibrosis is a serious human health problem, and there is a need for specific antifibrosis drugs in the clinic. Tanshinone IIA has recently been reported to have a role in the treatment of liver fibrosis. However, the evidence supporting its antifibrotic effect is not sufficient, and the underlying mechanism is not clear. We thus performed this meta-analysis of animal research to assess the therapeutic effect of tanshinone IIA on liver fibrosis and analyzed the possible associated mechanism to provide a reference for further clinical drug preparation and clinical research. Methods We collect related articles from the databases PubMed, Web of Science, Embase, Wanfang, VIP, and CNKI. The quality of the included studies was evaluated according to the SYRCLE risk of bias tool for animal studies. Data were analyzed using RavMan 5.3 and Stata 12.0 software. Results A total of 404 articles were retrieved from the databases. After screening, 11 articles were included in the analysis. The included studies' methodological quality was generally low, and an obvious publication bias was found. The results showed that tanshinone IIA significantly improved liver function in experimental animals and reduced the level of liver fibrosis by reducing inflammation and inhibiting immunity, antiapoptotic processes, and HSC activation. Conclusion Tanshinone IIA can effectively improve liver fibrosis and liver function in animal models and is worthy of future higher quality animal studies and clinical drug trials.
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Alqahtani F, Balla S, AlHajji M, Chaudhary F, Albeiruti R, Kawsara A, Alkhouli M. Temporal trends in the utilization and outcomes of percutaneous coronary interventions in patients with liver cirrhosis. Catheter Cardiovasc Interv 2019; 96:802-810. [PMID: 31713989 DOI: 10.1002/ccd.28593] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 10/21/2019] [Accepted: 10/27/2019] [Indexed: 01/27/2023]
Abstract
OBJECTIVES We sought to assess the national trends in the utilization and outcomes of percutaneous coronary interventions (PCI) in patients with cirrhosis. BACKGROUND Contemporary data on PCI in patients with liver cirrhosis are limited. METHODS The National-Inpatient-Sample was used to identify patients who underwent PCI between 2003 and 2016. We examined the annual PCI rate, and compared the in-hospital morbidity, mortality, resource utilization, and cost following PCI in patients with and without cirrhosis. RESULTS A total of 8,860,178 PCI hospitalizations were identified, of those, 20,339 (0.2%) were performed in patients with cirrhosis. Annual PCI rates decreased overtime in patients without liver cirrhosis but increased in those with cirrhosis (Ptrend < .001). Patients with cirrhosis had a characteristic clinical, demographic, and socioeconomic profile compared with those without cirrhosis. The use of bare-metal stents decreased from 69.1 to 11.4% in the noncirrhosis group, and from 81.9 to 21.3% in the cirrhosis group. Compared with propensity-matched patients without cirrhosis, PCI in cirrhotic patients was associated with higher in-hospital mortality across all indications (STEMI 19.1 vs. 11.5%, p = .002; NSTEMI 8.7 vs. 5.6%, p = .002; and UA/SIHD 7.7 vs. 4.3%, p < .001). Cirrhotic patients also had significantly higher rates of acute kidney injury, but similar rates of vascular complications and stroke. Additionally, cirrhotic patients had longer hospitalizations, were less likely to be discharged home, and accrued higher cost across all PCI indications. CONCLUSIONS Patients with cirrhosis who are deemed "suitable PCI candidates" in current practice remain at high-risk for worse short-term morbidity and mortality, and higher cost of care.
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Affiliation(s)
- Fahad Alqahtani
- Division of Cardiology, West Virginia University, Morgantown, West Virginia
| | - Sudarashan Balla
- Division of Cardiology, West Virginia University, Morgantown, West Virginia
| | - Mohamed AlHajji
- Division of Cardiology, West Virginia University, Morgantown, West Virginia
| | - Fahad Chaudhary
- Department of Medicine, West Virginia University, Morgantown, West Virginia
| | - Ridwaan Albeiruti
- Department of Medicine, West Virginia University, Morgantown, West Virginia
| | - Akram Kawsara
- Division of Cardiology, West Virginia University, Morgantown, West Virginia
| | - Mohamad Alkhouli
- Division of Cardiology, West Virginia University, Morgantown, West Virginia
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Grindheim JM, Nicetto D, Donahue G, Zaret KS. Polycomb Repressive Complex 2 Proteins EZH1 and EZH2 Regulate Timing of Postnatal Hepatocyte Maturation and Fibrosis by Repressing Genes With Euchromatic Promoters in Mice. Gastroenterology 2019; 156:1834-1848. [PMID: 30689973 PMCID: PMC6599454 DOI: 10.1053/j.gastro.2019.01.041] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 01/02/2019] [Accepted: 01/16/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Little is known about mechanisms that underlie postnatal hepatocyte maturation and fibrosis at the chromatin level. We investigated the transcription of genes involved in maturation and fibrosis in postnatal hepatocytes of mice, focusing on the chromatin compaction the roles of the Polycomb repressive complex 2 histone methyltransferases EZH1 and EZH2. METHODS Hepatocytes were isolated from mixed background C57BL/6J-C3H mice, as well as mice with liver-specific disruption of Ezh1 and/or Ezh2, at postnatal day 14 and 2 months after birth. Liver tissues were collected and analyzed by RNA sequencing, H3K27me3 chromatin immunoprecipitation sequencing, and sonication-resistant heterochromatin sequencing (a method to map heterochromatin and euchromatin). Liver damage was characterized by histologic analysis. RESULTS We found more than 3000 genes differentially expressed in hepatocytes during liver maturation from postnatal day 14 to month 2 after birth. Disruption of Ezh1 and Ezh2 in livers caused perinatal hepatocytes to differentiate prematurely and to express genes at postnatal day 14 that would normally be induced by month 2 and differentiate prematurely. Loss of Ezh1 and Ezh2 also resulted in liver fibrosis. Genes with H3K27me3-postive and H3K4me3-positive euchromatic promoters were prematurely induced in hepatocytes with loss of Ezh1 and Ezh2-these genes included those that regulate hepatocyte maturation, fibrosis, and genes not specifically associated with the liver lineage. CONCLUSIONS The Polycomb repressive complex 2 proteins EZH1 and EZH2 regulate genes that control hepatocyte maturation and fibrogenesis and genes not specifically associated with the liver lineage by acting at euchromatic promoter regions. EZH1 and EZH2 thereby promote liver homeostasis and prevent liver damage. Strategies to manipulate Polycomb proteins might be used to improve hepatocyte derivation protocols or developed for treatment of patients with liver fibrosis.
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Affiliation(s)
- Jessica Mae Grindheim
- Institute for Regenerative Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Penn Epigenetics Institute, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Dept. Cell and Developmental Biology, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Dept. of Cancer Biology, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA
| | - Dario Nicetto
- Institute for Regenerative Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Penn Epigenetics Institute, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Dept. Cell and Developmental Biology, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA
| | - Greg Donahue
- Institute for Regenerative Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Penn Epigenetics Institute, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Dept. Cell and Developmental Biology, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA.,Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Blvd, Bldg. 421, Philadelphia, PA 19104-5157, USA
| | - Kenneth S Zaret
- Institute for Regenerative Medicine, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, Pennsylvania; Penn Epigenetics Institute, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, Pennsylvania; Department of Cell and Developmental Biology, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, Philadelphia, Pennsylvania.
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