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Simancas-Racines D, Annunziata G, Verde L, Fascì-Spurio F, Reytor-González C, Muscogiuri G, Frias-Toral E, Barrea L. Nutritional Strategies for Battling Obesity-Linked Liver Disease: the Role of Medical Nutritional Therapy in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Management. Curr Obes Rep 2025; 14:7. [PMID: 39797961 PMCID: PMC11724794 DOI: 10.1007/s13679-024-00597-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/03/2024] [Indexed: 01/13/2025]
Abstract
PURPOSE OF REVIEW This narrative review explores the role of Medical Nutritional Therapy (MNT) in managing Metabolic-Associated Steatotic Liver Disease (MASLD), previously known as nonalcoholic fatty liver disease. It aims to examine the effectiveness of specific nutritional strategies in preventing and treating this obesity-linked liver disease. RECENT FINDINGS Emerging evidence underscores the benefits of the Mediterranean diet, low-carbohydrate diets, and intermittent fasting in reducing liver fat, improving insulin sensitivity, and mitigating inflammation. Supplementing with vitamin E, omega-3 fatty acids, and silymarin can potentially reduce liver fibrosis and promote liver health. MNT is a key intervention for MASLD management, emphasizing dietary patterns, caloric restriction, and nutraceutical supplementation. Integrating these strategies with lifestyle modifications, including regular physical activity, offers a comprehensive approach to improving metabolic and liver outcomes in patients with MASLD. Further research is needed to refine and personalize these therapeutic interventions.
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Affiliation(s)
- Daniel Simancas-Racines
- Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC), Quito, 170527, Ecuador.
| | - Giuseppe Annunziata
- Facoltà di Scienze Umane, della Formazione e dello Sport, Università Telematica Pegaso, Via Porzio, Centro Direzionale, Isola F2, Naples, 80143, Italy
| | - Ludovica Verde
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | | | - Claudia Reytor-González
- Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC), Quito, 170527, Ecuador
| | - Giovanna Muscogiuri
- Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, 80131, Naples, Italy
| | - Evelyn Frias-Toral
- Universidad Espíritu Santo, Escuela de Medicina, Samborondón, 0901952, Ecuador.
| | - Luigi Barrea
- Dipartimento Psicologia e Scienze della Salute, Università Telematica Pegaso, Centro Direzionale Isola F2, Via Porzio, Naples, 80143, Italy
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El-Kassas M, Barakat EMF, Shousha HI, Kohla M, Said M, Moustafa EF, Tawheed A, Shamkh MAA, Nabeel MM, Elkhateeb E, Dabees H, Abdelmalek MO, Sayed H, Abdallah NM, Elbaz T, Rewisha E, Nassief A, Riad AR, Sweedy AT, Askar SR, Abdelmaksoud AH, Gaber Y, Eysa B, Shaker M, Hashem MB, Kaddah M, Radwan H, Hassan MS, Lithy R, AbouElmaaty ME, Abo-Elazm OM, Abdelaziz AO. Characteristics and survival of patients with viral versus nonviral associated hepatocellular carcinoma: a multicenter cohort study. Eur J Gastroenterol Hepatol 2025; 37:83-93. [PMID: 39621880 DOI: 10.1097/meg.0000000000002870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
BACKGROUND Viral hepatitis B and C are the leading causes of hepatocellular carcinoma (HCC). With obesity, metabolic-related disorders are increasingly associated with a higher incidence of nonviral HCC. This study aimed to investigate the characteristics, tumor features, treatment outcomes, and survival of patients with viral versus nonviral HCC. METHODS This multicenter cohort study was conducted at six tertiary care centers. Patients were recruited between February 2007 and June 2022 and follow-up was recorded until death or the study end (July 2023). The patients were divided into viral-related and nonviral HCC groups. We studied baseline patient characteristics, tumor characteristics, treatment, and overall survival (OS). RESULTS This study included 2233 patients, 1913 patients with viral and 320 patients with nonviral HCC. Patients with nonviral HCC presented with more advanced Barcelona Clinic Liver Cancer (BCLC) stages (BCLC stage C or D were present in 26.3% and 53.8% of patients with viral and nonviral HCC, respectively) that affected the median OS (19.167 vs. 13.830 months, P-value <0.001 for viral and nonviral HCC, respectively). The OS did not differ between patients with viral and nonviral HCC treated with resection, percutaneous ablation, trans-arterial chemoembolization, or Sorafinib. The independent factors affecting the survival of nonviral HCC were albumin-bilirubin score (hazard ratio = 2.323, 95% confidence interval (CI): 1.696-3.181, P-value <0.001), tumor size (hazard ratio = 1.085, 95% CI: 1.019-1.156, P-value 0.011), and alpha-fetoprotein (hazard ratio = 1.000, 95% CI: 1.000-1.000, P-value 0.042). CONCLUSION Patients with nonviral HCC had higher BMI, worse performance status, BCLC stage, and tumor response than those with viral HCC.
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Affiliation(s)
| | - Eman M F Barakat
- Hepatoma Group, Tropical Medicine Department, Ain Shams University
| | - Hend Ibrahim Shousha
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
| | - Mohamed Kohla
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia
| | - Mohamed Said
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
- Internal Medicine Department, National Medical Institute of Damnhour, Damnhour
| | - Ehab Fawzy Moustafa
- Department of Tropical Medicine and Gastroenterology, Assiut University, Assiut
| | | | | | | | - Eman Elkhateeb
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia
| | - Hossam Dabees
- Internal Medicine Department, National Medical Institute of Damnhour, Damnhour
| | | | - Hamdy Sayed
- Endemic Medicine Department, Helwan University
| | | | - Tamer Elbaz
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
- Internal Medicine Department, Newgiza University, School of Medicine, Giza
| | - Eman Rewisha
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia
| | - Anwar Nassief
- Internal Medicine Department, National Medical Institute of Damnhour, Damnhour
| | - Ahmed Radwan Riad
- Department of Tropical Medicine and Gastroenterology, Assiut University, Assiut
| | | | | | | | - Yasmine Gaber
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
| | - Basem Eysa
- Hepato-Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute
| | - Mohamed Shaker
- Diagnostic and Interventional Radiology Department, Ain Shams University
| | | | - Mona Kaddah
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
| | - Hend Radwan
- Internal Medicine Department, Medicine and Clinical Studies Research Institute, National Research Center
| | | | - Rania Lithy
- Endemic Medicine and Hepato-Gastroenterology Department, Cairo University, Cairo
| | | | - Omnia M Abo-Elazm
- Department of Biostatistics and Cancer Epidemiology, National Cancer Institute, Cairo, Egypt
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Inukai Y, Ito T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Honda T, Shimizu T, Hattori M, Takeyama T, Ando Y, Nishikawa T, Morita K, Toyoda H, Ishigami M, Kawashima H. Type 2 Diabetes and Hypertension as Risk Factors for Advanced Fibrosis in Biopsy Proven Metabolic Dysfunction-Associated Steatotic Liver Disease. J Dig Dis 2024; 25:685-693. [PMID: 39805320 DOI: 10.1111/1751-2980.13325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 12/04/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025]
Abstract
OBJECTIVES To identify the diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) related to liver fibrosis and to characterize patients with cryptogenic steatotic liver disease (SLD) (non-MASLD) among those previously diagnosed with nonalcoholic fatty liver disease (NAFLD). METHODS This multicenter retrospective study included 511 patients diagnosed with NAFLD via liver biopsy, and the prevalence of MASLD was assessed based on the diagnostic criteria. Patients were divided into those who met the MASLD criteria and those who did not, and the characteristics of advanced fibrosis and associated cardiometabolic factors were evaluated. RESULTS Of the 475 patients with NAFLD, 458 (96.4%) met the criteria for MASLD, showing a high overlap between classical NAFLD and MASLD populations. Severe fibrosis was observed, regardless of the number of cardiometabolic factors. Hypertension and diabetes mellitus significantly contributed to advanced fibrosis (≥ F3), with odds ratio of 1.92 and 2.00 (95% confidence interval of 1.17-3.16 and 1.22-3.28, respectively; both p < 0.01) on multivariate analysis. The other seventeen (3.6%) patients did not meet the diagnostic criteria for MASLD. Among them, seven had significant fibrosis and a high fibrosis-4 index. CONCLUSIONS Diabetes mellitus and hypertension are key metabolic factors associated with advanced fibrosis. Some cases, classified as cryptogenic SLD, also exhibit significant fibrosis. Consequently, identifying high-risk patients, including those undergoing noninvasive tests for fibrosis, is crucial.
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Affiliation(s)
- Yosuke Inukai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinya Yokoyama
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norihiro Imai
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tatsuji Shimizu
- Department of Gastroenterology, Japan Community Health Care Organization Kani Tono Hospital, Kani, Japan
| | - Masashi Hattori
- Department of Gastroenterology, Yamashita Hospital, Ichinomiya, Japan
| | - Tomoaki Takeyama
- Department of Gastroenterology, Nishichita General Hospital, Tokai, Japan
| | - Yusuke Ando
- Department of Gastroenterology, Handa City Hospital, Handa, Japan
| | | | - Kiyoshi Morita
- Department of Gastroenterology, Toyota Kosei Hospital, Toyota, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Rehman WU, Ahmad E, Nadeem A, Ahmed S, Shah IA. Cryptogenic cirrhosis: Decoding diagnostic challenges through radiological insights. Radiol Case Rep 2024; 19:2735-2740. [PMID: 38680743 PMCID: PMC11047172 DOI: 10.1016/j.radcr.2024.03.069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 03/17/2024] [Accepted: 03/25/2024] [Indexed: 05/01/2024] Open
Abstract
This case report delves into the intricate diagnostic journey of a 42-year-old male presenting with jaundice, abdominal distension, and ascites, where medical imaging, including CT scans and ultrasound, played a central role. Noteworthy radiological findings, such as irregular nodular margins and caudate lobe hypertrophy, illuminated the distinctive pathophysiology of cryptogenic cirrhosis. The study underscores the pivotal role of medical imaging in elucidating complex liver pathologies, emphasizing the relevance of radiological approaches in diagnosing cryptogenic cirrhosis and guiding comprehensive management strategies.
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Affiliation(s)
- Wajeeh Ur Rehman
- Saidu Medical College, Khyber Medical University, Swat, Pakistan
| | - Eeman Ahmad
- Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan
| | - Arsalan Nadeem
- Department of Medicine, Allama Iqbal Medical College, Lahore, Punjab, Pakistan
| | - Shahzaib Ahmed
- Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan
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Vitale E, Rizzo A, Santa K, Jirillo E. Associations between "Cancer Risk", "Inflammation" and "Metabolic Syndrome": A Scoping Review. BIOLOGY 2024; 13:352. [PMID: 38785834 PMCID: PMC11117847 DOI: 10.3390/biology13050352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/08/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and pro-inflammatory conditions which more probably can lead to cardiovascular diseases progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting the association between cancer risk, inflammation, and metabolic syndrome. METHODS A search strategy was performed, mixing keywords and MeSH terms, such as "Cancer Risk", "Inflammation", "Metabolic Syndrome", "Oncogenesis", and "Oxidative Stress", and matching them through Boolean operators. A total of 20 manuscripts were screened for the present study. Among the selected papers, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general. CONCLUSIONS Cancer and its related progression may also depend also on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer.
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Affiliation(s)
- Elsa Vitale
- Scientific Directorate, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Alessandro Rizzo
- Medical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy;
| | - Kazuki Santa
- Faculty of Medical Science, Juntendo University, 6-8-1 Hinode, Urayasu 279-0013, Chiba, Japan;
| | - Emilio Jirillo
- Scuola di Medicina, University of Bari, 70121 Bari, Italy;
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Candolo ACR, Cançado GGL, Zitelli PM, Mazo DFDC, Oliveira CPM, Cunha-Silva M, Greca RD, Araújo RC, Alustau ASPT, Couto CA, Nardelli MJ, de Lima RGR, Farias AQ, Carrilho FJ, Pessôa MG. Lysosomal Acid Lipase Deficiency in the Etiological Investigation of Cryptogenic Liver Disease in Adults: A Multicenter Brazilian Study. GASTROENTEROLOGY INSIGHTS 2023; 14:564-574. [DOI: 10.3390/gastroent14040040] [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: 02/11/2025] Open
Abstract
Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m2. The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival.
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Affiliation(s)
- Aline Coelho Rocha Candolo
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Guilherme Grossi Lopes Cançado
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte 30130-100, Brazil
| | - Patricia Momoyo Zitelli
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Daniel Ferraz de Campos Mazo
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-894, Brazil
| | - Claudia Pinto Marques Oliveira
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Marlone Cunha-Silva
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-894, Brazil
| | - Raquel Dias Greca
- Division of Gastroenterology (Gastrocentro), School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-894, Brazil
| | - Roberta Chaves Araújo
- Gastroenterology Division, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Ribeirão Preto 14049-900, Brazil
| | | | - Claudia Alves Couto
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte 30130-100, Brazil
| | - Mateus Jorge Nardelli
- Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Federal University of Minas Gerais (UFMG), Belo Horizonte 30130-100, Brazil
| | - Roque Gabriel Rezende de Lima
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Alberto Queiroz Farias
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Flair José Carrilho
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
| | - Mário Guimarães Pessôa
- Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, University of São Paulo School of Medicine (HCFMUSP), São Paulo 05403-900, Brazil
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Yang JH, Byeon EH, Kang D, Hong SG, Yang J, Kim DR, Yun SP, Park SW, Kim HJ, Huh JW, Kim SY, Kim YW, Lee DK. Fermented Soybean Paste Attenuates Biogenic Amine-Induced Liver Damage in Obese Mice. Cells 2023; 12:cells12050822. [PMID: 36899958 PMCID: PMC10000487 DOI: 10.3390/cells12050822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/28/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Biogenic amines are cellular components produced by the decarboxylation of amino acids; however, excessive biogenic amine production causes adverse health problems. The relationship between hepatic damage and biogenic amine levels in nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, mice were fed a high-fat diet (HFD) for 10 weeks to induce obesity, presenting early-stage of NAFLD. We administered histamine (20 mg/kg) + tyramine (100 mg/kg) via oral gavage for 6 days to mice with HFD-induced early-stage NAFLD. The results showed that combined histamine and tyramine administration increased cleaved PARP-1 and IL-1β in the liver, as well as MAO-A, total MAO, CRP, and AST/ALT levels. In contrast, the survival rate decreased in HFD-induced NAFLD mice. Treatment with manufactured or traditional fermented soybean paste decreased biogenically elevated hepatic cleaved PARP-1 and IL-1β expression and blood plasma MAO-A, CRP, and AST/ALT levels in HFD-induced NAFLD mice. Additionally, the biogenic amine-induced reduction in survival rate was alleviated by fermented soybean paste in HFD-induced NAFLD mice. These results show that biogenic amine-induced liver damage can be exacerbated by obesity and may adversely affect life conservation. However, fermented soybean paste can reduce biogenic amine-induced liver damage in NAFLD mice. These results suggest a beneficial effect of fermented soybean paste on biogenic amine-induced liver damage and provide a new research perspective on the relationship between biogenic amines and obesity.
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Affiliation(s)
- Ju-Hwan Yang
- Department of Physiology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Eun-Hye Byeon
- Department of Physiology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Dawon Kang
- Department of Physiology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Seong-Geun Hong
- Department of Physiology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Jinsung Yang
- Department of Biochemistry and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Deok-Ryong Kim
- Department of Biochemistry and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Seung-Pil Yun
- Department of Pharmacology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Sang-Won Park
- Department of Pharmacology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Hyun-Joon Kim
- Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
| | - Jae-Won Huh
- National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea
| | - So-Yong Kim
- Fermented and Processed Food Science Division, National Institute of Agricultural Sciences, Wanju-Gun 55365, Republic of Korea
| | - Young-Wan Kim
- Department of Food Science and Biotechnology, Korea University, Sejong 30019, Republic of Korea
| | - Dong-Kun Lee
- Department of Physiology and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University Medical School, Jinju 52727, Republic of Korea
- Correspondence:
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8
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Han Y, Byun J, Zhu C, Sun R, Roh JY, Cordell HJ, Lee HS, Shaw VR, Kang SW, Razjouyan J, Cooley MA, Hassan MM, Siminovitch KA, Folseraas T, Ellinghaus D, Bergquist A, Rushbrook SM, Franke A, Karlsen TH, Lazaridis KN, McGlynn KA, Roberts LR, Amos CI. Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis. Nat Commun 2023; 14:1069. [PMID: 36828809 PMCID: PMC9958016 DOI: 10.1038/s41467-023-36678-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 02/10/2023] [Indexed: 02/26/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.
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Affiliation(s)
- Younghun Han
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Jinyoung Byun
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Catherine Zhu
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
| | - Ryan Sun
- Department of Biostatistics, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
| | - Julia Y Roh
- Department of Pharmacy, Ochsner Health, New Orleans, LA, USA
| | - Heather J Cordell
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Hyun-Sung Lee
- David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Vikram R Shaw
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
| | - Sung Wook Kang
- David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - Javad Razjouyan
- VA HSR&D, Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA
- Big Data Scientist Training Enhancement Program (BD-STEP), VA Office of Research and Development, Washington, DC, USA
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- VA Quality Scholars Coordinating Center, IQuESt, Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Matthew A Cooley
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA
| | - Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Katherine A Siminovitch
- Departments of Medicine, Immunology and Medical Sciences, University of Toronto, Toronto, Ontario, Canada
- Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute, Toronto, Ontario, Canada
| | - Trine Folseraas
- Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - David Ellinghaus
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Annika Bergquist
- Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Simon M Rushbrook
- Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich, United Kingdom
- Norwich Medical School, University of East Anglia, Norfolk, United Kingdom
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Tom H Karlsen
- Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
| | - Konstantinos N Lazaridis
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Lewis R Roberts
- Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
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9
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Han SK, Baik SK, Kim MY. Non-alcoholic fatty liver disease: Definition and subtypes. Clin Mol Hepatol 2023; 29:S5-S16. [PMID: 36577427 PMCID: PMC10029964 DOI: 10.3350/cmh.2022.0424] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/21/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regenerative Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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10
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Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023; 29:51-64. [PMID: 35903020 PMCID: PMC9845683 DOI: 10.3350/cmh.2022.0095] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/03/2022] [Indexed: 02/02/2023] Open
Abstract
The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.
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Affiliation(s)
- Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan,Corresponding author : Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel: +81-3-3815-5411, Fax: +81-3-3814-0021, E-mail:
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11
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Bortz JH. Metabolic-Associated Fatty Liver Disease: Opportunistic Screening at CT Colonography. CT COLONOGRAPHY FOR RADIOGRAPHERS 2023:277-290. [DOI: 10.1007/978-3-031-30866-6_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Ismaiel A, Portincasa P, Dumitrascu DL. Natural History of Nonalcoholic Fatty Liver Disease. ESSENTIALS OF NON-ALCOHOLIC FATTY LIVER DISEASE 2023:19-43. [DOI: 10.1007/978-3-031-33548-8_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Zhou P, Tan Y, Hao Z, Xu W, Zhou X, Yu J. Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1144838. [PMID: 36936142 PMCID: PMC10014961 DOI: 10.3389/fendo.2023.1144838] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 02/14/2023] [Indexed: 03/05/2023] Open
Abstract
OBJECTIVE Clinical trials have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2i) are closely associated with hepatic fibrosis and steatosis by FibroScan. This paper aimed at evaluating the effects of SGLT2i on hepatic fibrosis and steatosis, which are presented as liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). METHODS PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, and Wanfang Database were searched for randomized clinical trials from database establishment to 30 November 2022 with no language restrictions. The risk of bias was evaluated by Collaboration Handbook. Software Stata 17 and Review Manager (version 5.3) were used for meta-analysis. RESULTS A total of eight articles including 686 patients were included. Compared with the control group, our results showed that SGLT2i could lower levels of LSM [MD = -0.82, 95%CI (-1.38, -0.25), p = 0.005] and CAP [MD = -12.80, 95%CI (-20.57, -5.03), p = 0.001]. Further subgroup analyses indicated that SGLT2i presented more advantages on longer treatment duration and more serious steatosis in decreasing LSM. For CAP, SGLT2i exhibited a clear advantage in subgroup analyses of longer treatment duration, younger people, dapagliflozin, worse fibrosis, and steatosis. CONCLUSION SGLT2i could reduce LSM and CAP in contrast to other antihyperglycemic drugs. However, the included studies are not definitive, and well-designed, more multi-centered, blinded randomized clinical trials are warranted to definitively establish reliable evidence.
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Affiliation(s)
- Peipei Zhou
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ying Tan
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenning Hao
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weilong Xu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiqiao Zhou
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- *Correspondence: Jiangyi Yu, ; Xiqiao Zhou,
| | - Jiangyi Yu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
- *Correspondence: Jiangyi Yu, ; Xiqiao Zhou,
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14
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Choi WT, Gill RM. Pathologic features and differential diagnosis of chronic hepatitis. DIAGNOSTIC HISTOPATHOLOGY 2023; 29:12-22. [DOI: 10.1016/j.mpdhp.2022.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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15
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Fukushima M, Miyaaki H, Sasaki R, Haraguchi M, Miuma S, Hara T, Soyama A, Hidaka M, Eguchi S, Nakao K. Most Cases of Cryptogenic Cirrhosis May be Nonobese Nonalcoholic Steatohepatitis-Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study. Intern Med 2022; 62:1415-1423. [PMID: 36171128 DOI: 10.2169/internalmedicine.0514-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aim The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of NASH in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; P=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, P=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; P=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; P=0.04). Conclusions Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.
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Affiliation(s)
- Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
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Shigematsu Y, Kanda H, Amori G, Takahashi Y, Takazawa Y, Inamura K. Nonalcoholic non-virus-related hepatocellular carcinoma arising from nonsteatotic liver: Clinical and pathological features. Medicine (Baltimore) 2022; 101:e28746. [PMID: 35119029 PMCID: PMC8812618 DOI: 10.1097/md.0000000000028746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 01/07/2022] [Indexed: 01/04/2023] Open
Abstract
Nonalcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is considered to occur in steatotic livers; however, emerging evidence indicates that a subset of NANV-HCC occurs in nonsteatotic livers. Currently, little information is available regarding this subset. This study sought to provide the clinical and pathological features of NANV-HCC in nonsteatotic livers.We retrospectively investigated the clinicopathological features of 101 consecutive patients with NANV-HCC treated with a curative-intent hepatectomy. A background liver with <5% steatosis by area was regarded as a nonsteatotic liver. Survivals of patient subgroups were estimated using the Kaplan-Meier method, and log-rank tests were conducted to assess the survival difference. Multivariate analysis was performed with the Cox proportional hazards method.Overall, 34 of 101 patients with NANV-HCC were found to have a nonsteatotic liver. Vascular invasion of the tumor was more frequently observed in patients with a nonsteatotic liver than in those with a steatotic liver (P = .03). The extent of lobular inflammation and fibrosis did not differ between patients with and without steatosis in the liver. NANV-HCC with a nonsteatotic liver was independently associated with a shorter disease-free survival (DFS) (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.21-3.80; P = .009) and a shorter overall survival (OS) (HR 2.79; 95% CI 1.27-6.16; P = .01) than NANV-HCC with a steatotic liver.The absence of steatosis in the liver is independently associated with shorter DFS and OS in patients with NANV-HCC. Our findings indicate that nonsteatotic liver can be a surrogate phenotype of aggressive NANV-HCC.
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Affiliation(s)
- Yasuyuki Shigematsu
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Hiroaki Kanda
- Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina, Kita-adachi-gun, Saitama, Japan
| | - Gulanbar Amori
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Yutaka Takazawa
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon Minato, Tokyo, Japan
| | - Kentaro Inamura
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
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17
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Bharath Kumar C, Goel A, Jaleel R, David D, Zachariah U, Ramachandran J, Eapen CE. Prevalence of Risk Factors for Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Patients With Cryptogenic Cirrhosis. J Clin Exp Hepatol 2022; 12:492-502. [PMID: 35535099 PMCID: PMC9077180 DOI: 10.1016/j.jceh.2021.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 05/22/2021] [Indexed: 12/12/2022] Open
Abstract
Aim of the study To study the prevalence of risk factors for nonalcoholic fatty liver disease (NAFLD) in middle-aged (40-59 years) and elderly patients (≥60 years) with cryptogenic cirrhosis as compared to those with hepatitis B or C virus (HBV or HCV) related cirrhosis. Methods and materials Between August 2013 and December 2014, cases (cryptogenic cirrhosis) and controls (HBV/HCV cirrhosis) above 40 years of age were prospectively recruited and assessed for the cause and prevalence of risk factors for NAFLD. Results One hundred eighteen cases (male-74%; age 55 (40-74) years; median (range); Child's class A:B:C-46:38:16) and 59 controls (male-80%; age 55.5 (40-69) years; Child's class A:B:C-56:30:14) were enrolled. Obesity (53% v/s 39%, P-0.081), diabetes mellitus (DM) (52% v/s 27%; P-0.002), family history of DM (30% v/s 13%; P-0.016), family history of Obesity (21% v/s 3.5%; P-0.002) and metabolic syndrome (65% v/s 44%; P-0.01) were more among cases than controls. Lifetime weight as obese was also longer in cases than in controls (5.9 ± 6.2 years v/s 3.2 ± 5.1 years, P-0.002). On subgroup analysis, in elderly age group, DM (55% v/s 17%, P-0.006), family history of DM (40% v/s 11%, P-0.025), metabolic syndrome (76% v/s 44%, P-0.017) and family history of obesity (19% v/s 0, P-0.047) were more common in cases as compared to controls, where as in the middle-age group, family history of obesity was the only significant factor (22% v/s 5%, P-0.025). Lifetime weight as obese was longer in cases than controls in both middle and elderly age groups. Conclusion Among middle-aged and elderly patients with cirrhosis, there was a higher prevalence of risk factors for NAFLD in those with cryptogenic cirrhosis, compared to those with HBV or HCV cirrhosis.
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Affiliation(s)
| | - Ashish Goel
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Rajeeb Jaleel
- Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Deepu David
- Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India,Address for correspondence: Department of Gastroenterology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India. Tel.: +91 4162282148.
| | - Uday Zachariah
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Jeyamani Ramachandran
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
| | - Chundamannil E. Eapen
- Department of Hepatology, Division of GI Sciences, CMC Hospital, Vellore, Tamil Nadu, India
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Tomonari T, Sato Y, Tanaka H, Mitsuhashi T, Hirao A, Tanaka T, Taniguchi T, Okamoto K, Sogabe M, Miyamoto H, Muguruma N, Takayama T. Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma. JGH Open 2021; 5:1275-1283. [PMID: 34816013 PMCID: PMC8593789 DOI: 10.1002/jgh3.12663] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 08/31/2021] [Accepted: 09/19/2021] [Indexed: 12/30/2022]
Abstract
AIM To investigate the therapeutic effect of lenvatinib (LEN) in liver disease etiology, especially nonviral hepatocellular carcinoma (HCC). METHODS AND RESULTS Sixty-seven patients with unresectable advanced HCC (u-HCC) treated with LEN and consisting of 26 hepatitis C virus (HCV), 19 hepatitis B virus (HBV), 11 alcohol, and 11 nonalcoholic steatohepatitis (NASH) cases were retrospectively recruited. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for survival. The objective response rate in the nonviral (alcohol and NASH) group was higher than that in the viral group (59.1% [13/22] vs. 46.7% [21/45]). Progression-free survival was significantly longer in the nonviral group than in the viral group (13.7 vs. 6.6 months; hazard ratio [HR] 0.324; 95% confidence interval [CI] 0.174-0.602; P < 0.01). Similarly, median overall survival (OS) was significantly longer in the nonviral group than in the viral group (not evaluable vs. 15.9 months; HR = 0.277; 95% CI = 0.116-0.662; P < 0.01). Multivariate analysis revealed that portal vein invasion (HR = 5.327, P = 0.0025), treatment line (HR = 0.455, P = 0.023), and etiology (HR = 0.180, P = 0.00055) were significant independent factors associated with OS in u-HCC patients treated with LEN. CONCLUSION Our results suggest that LEN is more effective against nonviral u-HCC than against viral u-HCC.
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Affiliation(s)
- Tetsu Tomonari
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Hironori Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Takeshi Mitsuhashi
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Akihiro Hirao
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Takahiro Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Tatsuya Taniguchi
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Masahiro Sogabe
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
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Islam SMT, Won J, Khan M, Chavin KD, Singh I. Peroxisomal footprint in the pathogenesis of nonalcoholic steatohepatitis. Ann Hepatol 2021; 19:466-471. [PMID: 31870746 DOI: 10.1016/j.aohep.2019.11.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 11/08/2019] [Accepted: 11/20/2019] [Indexed: 02/08/2023]
Abstract
Nonalcoholic steatohepatitis (NASH) is a form of fatty liver disease where benign hepatic steatosis leads to chronic inflammation in the steatotic liver of a patient without any history of alcohol abuse. Mechanisms underlying the progression of hepatic steatosis to NASH have long been investigated. This review outlines the potential role of peroxisomal dysfunctions in exacerbating the disease in NASH. Loss of peroxisomes as well as impaired peroxisomal functions have been demonstrated to occur in inflammatory conditions including NASH. Because peroxisomes and mitochondria co-operatively perform many metabolic functions including O2 and lipid metabolisms, a compromised peroxisomal biogenesis and function can potentially contribute to defective lipid and reactive oxygen species metabolism which in turn can lead the progression of disease in NASH. Impaired peroxisomal biogenesis and function may be due to the decreased expression of peroxisomal proliferator-activated receptor-α (PPAR-α), the major transcription factor of peroxisomal biogenesis. Recent studies indicate that the reduced expression of PPAR-α in NASH is correlated with the activation of the toll-like receptor-4 pathway (TLR-4). Further investigations are required to establish the mechanistic connection between the TLR-4 pathway and PPAR-α-dependent impaired biogenesis/function of peroxisomes in NASH.
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Affiliation(s)
- S M Touhidul Islam
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Jeseong Won
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Mushfiquddin Khan
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA
| | - Kenneth D Chavin
- Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Inderjit Singh
- Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
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20
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Son IW, Kim S, Hong SB, Lee NK, Jeong MR, Han SY, Woo HY. Puncture needle with a hard plastic sheath and plastic wings minimizes repuncture attempts in ultrasound-guided paracentesis. Yeungnam Univ J Med 2021; 39:18-23. [PMID: 34247458 PMCID: PMC8895958 DOI: 10.12701/yujm.2021.01109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 06/16/2021] [Indexed: 11/09/2022] Open
Abstract
Background This study was performed to evaluate periprocedural factors, complications, and repuncture rate of the newly developed puncture needle and compare it with the routinely used puncture needle for ultrasound (US)-guided paracentesis. Methods We retrospectively identified 137 patients who underwent US-guided paracentesis between July 2018 and March 2019. Among them, 82 patients underwent US-guided paracentesis with a newly developed puncture needle. The other 55 patients underwent US-guided paracentesis with a routinely used puncture needle. The periprocedural factors, complications, and repuncture rate were compared between the two groups using the Mann-Whitney U test and Fisher exact test. The repuncture-associated factors were assessed using logistic regression analysis. Results There were no major or minor complications in either group. The rate of repuncture was significantly lower in the group using the newly developed puncture needle compared with the group using the routinely used puncture needle (p=0.01). The duration of the procedure was significantly shorter with the newly developed puncture needle compared with the routinely used puncture needle (p=0.01). In univariate analysis, the thickness of the abdominal wall (p=0.04) and the use of the newly developed puncture needle (p=0.01) were significantly associated with the rate of repuncture. In multivariate analysis, only the use of the newly developed puncture needle was significantly associated with the rate of repuncture. Conclusion Using this novel puncture needle with a hard plastic sheath and plastic wings, the rate of repuncture and the duration of the procedure were decreased without complications of US-guided paracentesis.
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Affiliation(s)
- Il Wan Son
- Department of Radiology, Dongnam Institution of Radiological & Medical Sciences, Busan, Korea
| | - Suk Kim
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Seung Baek Hong
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Nam Kyung Lee
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Mi Ri Jeong
- Department of Radiology, Busan Medical Center, Busan, Korea
| | - Sung Yong Han
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Hyun Young Woo
- Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
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21
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Finotti M, Romano M, Auricchio P, Scopelliti M, Brizzolari M, Grossi U, Piccino M, Benvenuti S, Morana G, Cillo U, Zanus G. Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives. J Pers Med 2021; 11:499. [PMID: 34199535 PMCID: PMC8229090 DOI: 10.3390/jpm11060499] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.
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Affiliation(s)
- Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Pasquale Auricchio
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Ugo Grossi
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Marco Piccino
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
| | - Stefano Benvenuti
- Gastroenterology Unit (IV), Cà Foncello Regional Hospital, 31100 Treviso, Italy;
| | - Giovanni Morana
- Division of Radiology, Treviso Regional Hospital, 31100 Treviso, Italy;
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, DISCOG, University of Padua, 35121 Padua, Italy; (P.A.); (U.C.)
| | - Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, DISCOG, University of Padua, 31100 Padua, Italy; (M.R.); (M.S.); (M.B.); (U.G.); (M.P.); (G.Z.)
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22
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Bhat M, Usmani SE, Azhie A, Woo M. Metabolic Consequences of Solid Organ Transplantation. Endocr Rev 2021; 42:171-197. [PMID: 33247713 DOI: 10.1210/endrev/bnaa030] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/- donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.
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Affiliation(s)
- Mamatha Bhat
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Shirine E Usmani
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
| | - Amirhossein Azhie
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Minna Woo
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
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23
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Chehrehgosha H, Sohrabi MR, Ismail-Beigi F, Malek M, Reza Babaei M, Zamani F, Ajdarkosh H, Khoonsari M, Fallah AE, Khamseh ME. Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Diabetes Ther 2021; 12:843-861. [PMID: 33586120 PMCID: PMC7882235 DOI: 10.1007/s13300-021-01011-3] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 01/23/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). METHODS In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. RESULTS A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: - 29.6 dB/m (- 39.5 to - 19.6) versus - 16.4 dB/m (- 25.0 to - 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: - 0.77 kPa (- 1.45, - 0.09), p = 0.02, versus 0.01 kPa (95% CI - 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. CONCLUSION Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. TRIAL REGISTRATION Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.
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Affiliation(s)
- Haleh Chehrehgosha
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Masoud Reza Sohrabi
- Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Faramarz Ismail-Beigi
- Department of Medicine, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA
| | - Mojtaba Malek
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mohammad Reza Babaei
- Department of Interventional Radiology, Firouzgar Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Farhad Zamani
- Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Hossein Ajdarkosh
- Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mahmood Khoonsari
- Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Afshin Eshghi Fallah
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran
| | - Mohammad E Khamseh
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran.
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24
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Investigating the Relationship Between Insulin Resistance and Fatty Liver in a Random Population of Tehran. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.102972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: Insulin resistance can be a predictor of adverse fatty liver disease and health problems. Objectives: The present study aimed to investigate the effect of insulin resistance on fatty liver disease. Methods: This study used the data of 2,160 individuals registered in a cross-sectional study who were randomly selected from among clients of a nutrition clinic in Tehran from April to December 2019. Insulin resistance and beta-cell activity were calculated by the homeostasis model assessment formula. The study outcome was defined as having fatty liver disease. The odds ratio (95% CI) was calculated using logistic regression models. Results: The mean age was 35 (± 9) in healthy subjects and 49 (± 8) in fatty liver disease patients (age range: 16 to 42 years). Nearly 34.5% of the individuals had fatty liver disease. According to the adjusted results of the logistic regression model, the risk of NAFLD was 1.05 (P < 0.001) for one unit increase in fasting insulin and 1.01 (P < 0.001) for one unit increase in 2-h insulin, which indicated the statistically significant relationship of NAFLD with fasting insulin and 2-h insulin. Also, the risk of NAFLD was 1.01 P < 0.001) for one unit increase in FPG, which was statistically significant. Moreover, the adjusted risk of NAFLD was 1.00 (P < 0.001) for one unit increase in 2-h glucose, which was not statistically significant. Finally, the adjusted risk of NAFLD was 1.29 (P < 0.001) for one unit increase in HOMA-IR, which was statistically significant. Conclusions: The findings of the present study demonstrated that insulin resistance could increase the risk of fatty liver disease. Also, each one-unit increase in fasting blood sugar, fasting insulin, and 2-h insulin increased the risk of fatty liver disease. Therefore, the results of this study may be useful for health policymakers to design suitable preventive and therapeutic interventions for those with NAFLD to prevent and control this disease.
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25
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Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence. Cells 2020; 9:cells9112458. [PMID: 33187255 PMCID: PMC7698018 DOI: 10.3390/cells9112458] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/28/2020] [Accepted: 11/07/2020] [Indexed: 12/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined clinicopathologically by the accumulation of lipids in >5% of hepatocytes and the exclusion of secondary causes of fat accumulation. NAFLD encompasses a wide spectrum of liver damage, extending from simple steatosis or non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH)—the latter is characterized by inflammation and hepatocyte ballooning degeneration, in addition to the steatosis, with or without fibrosis. NAFLD is now the most common cause of chronic liver disease in Western countries and affects around one quarter of the general population. It is a multisystem disorder, which is associated with an increased risk of type 2 diabetes mellitus as well as liver- and cardiovascular-related mortality. Although earlier studies had suggested that NAFL is benign (i.e., non-progressive), cumulative evidence challenges this dogma, and recent data suggest that nearly 25% of those with NAFL may develop fibrosis. Importantly, NAFLD patients are more susceptible to the toxic effects of alcohol, drugs, and other insults to the liver. This is likely due to the functional impairment of steatotic hepatocytes, which is virtually undetectable by current clinical tests. This review provides an overview of the current evidence on the clinical significance of NAFL and discusses the molecular basis for NAFL development and progression.
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26
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Gitto S, Falcini M, Marra F. Metabolic Disorders After Liver Transplantation. Metab Syndr Relat Disord 2020; 19:65-69. [PMID: 33104408 DOI: 10.1089/met.2020.0068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Early after surgery, liver transplant (LT) recipients often develop weight gain due to an increase of caloric intake and fat mass (without recovery of muscle frame). This modification of body composition together with a negative metabolic impact of immunosuppressive drugs leads to a high prevalence of all the main metabolic disorders. Indeed, as expected, transplanted patients show a higher cardiovascular risk in comparison with general population. Notably, seeing the increase of mean age of transplanted population, metabolic disorders represent the true challenge for the transplant community. Considering the lack of evidences or clear indications about prevention, early diagnosis and treatment of metabolic disorders after LT, it would be mandatory to develop targeted further studies on this matter.
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Affiliation(s)
- Stefano Gitto
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Margherita Falcini
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
| | - Fabio Marra
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, University Hospital Careggi, University of Florence, Florence, Italy
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27
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Castelló B, Aguilera V, Blázquez MT, Rubín Á, García M, Vinaixa C, Benlloch S, SanJuan F, Montalva E, López R, Berenguer M. Post-transplantation outcome in non-alcoholic steatohepatitis cirrhosis: Comparison with alcoholic cirrhosis. Ann Hepatol 2020; 18:855-861. [PMID: 31543468 DOI: 10.1016/j.aohep.2019.06.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 05/26/2019] [Accepted: 01/29/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Non-alcoholic steatohepatitis (NASH) indication of liver transplant (LT) has increased recently, whereas alcoholic cirrhosis remains a major indication for LT. To characterize NASH-related cases and to compare the post-transplant outcome of these two conditions represents our major objective. MATERIAL AND METHODS Patients undergoing LT for NASH between 1997 and 2016 were retrieved. Those transplanted between 1997 and 2006 were compared to an "age and LT date" matched group of patients transplanted for alcoholic cirrhosis (ratio 1:2). Baseline features and medium-term outcome measures were compared. RESULTS Of 1986 LT performed between 1997 and 2016, 40 (2%) were labeled as NASH-related indications. NASH-related cases increased initially (from 0.8% in 1997-2001 to 2.7% in 2002-2006) but remained stable in subsequent years (2.3%). Hepatocellular carcinoma (HCC) prevalence was greater in NASH-vs alcohol-related cirrhosis (40% vs 3%, p=0.001). The incidence of overweight, obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia, renal insufficiency and cardiovascular (CV) disease was similar in both groups at 5 years post-LT. Five-year survival was higher in NASH but without reaching statistical significance (83% vs 72%, p=0.21). The main cause of mortality in NASH-LT patients was HCC recurrence. CONCLUSION Most previously considered cryptogenic cases are actually NASH-cirrhosis. While the incidence of this indication is increasing in many countries, it has remained relatively stable in our Unit, the largest LT center in Spain. HCC is common in these patients and represents a main cause of post-transplant mortality. Metabolic complications, CV-related disease and 5-yr survival do not differ in patients transplanted for NASH vs alcohol.
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Affiliation(s)
- Beatriz Castelló
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain
| | - Victoria Aguilera
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
| | - M Teresa Blázquez
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain
| | - Ángel Rubín
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - María García
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Carmen Vinaixa
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Salvador Benlloch
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Fernando SanJuan
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain
| | - Eva Montalva
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Rafael López
- Liver Transplantation Surgical Unit, La Fe University Hospital, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Valencia, Spain; Networked Biomedical Research Center oh Hepatic and Digestive Diseases, CIBERehd, Spain; Faculty of Medicine, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria La Fe, Valencia, Spain
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28
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Vorobioff JD, Contreras F, Tanno F, Hernández L, Bessone F, Colombato L, Adi J, Fassio E, Felgueres M, Fernández G, Gaite L, Gibelli D, Darrichon HG, Lafage M, Lombardo D, López S, Mateo A, Mendizábal M, Pecoraro J, Ruf A, Ruiz P, Severini J, Stieben T, Sixto M, Zárate F, Barraza SDLB, Sierra ID, Pacheco VR, Roblero JP, Rojas JO, González PR, Rodríguez DSM, Sierralta A, Manchego AU, Valdes E, Yaquich P, Wolff R, Valdivia FB, Gallegos RC, Galloso R, Marcelo JS, Montes P, Tenorio L, Veramendi I, Alava E, Armijos X, Benalcazar G, Carrera E, Pazmiño GF, Díaz EM, Garassini M, Marrero RP, Infante M, Suárez DP, Gutiérrez JC, Reyes CMV, Serrano YM, Hernández RH, Martínez OM, González TP, Andara MT, Hernández MS, Gerona S, García I, Tijera FDL, López EP, Torres K, Garzón M. A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management. Ann Hepatol 2020; 19:396-403. [PMID: 32418749 DOI: 10.1016/j.aohep.2020.03.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/19/2020] [Accepted: 03/25/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION & OBJECTIVES Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.
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Affiliation(s)
- Julio D Vorobioff
- Gastroenterology Department & Liver Unit, Hospital Provincial del Centenario, Rosario, Argentina.
| | - Fernando Contreras
- Gastroenterology Department, Hospital Luis E. Aybar, Santo Domingo, Dominican Republic
| | - Federico Tanno
- Gastroenterology Department & Liver Unit, Hospital Provincial del Centenario, Rosario, Argentina
| | - Lucía Hernández
- Facultad de Ciencias Económicas y Estadística, Universidad de Rosario, Argentina
| | - Fernando Bessone
- Gastroenterology Department & Liver Unit, Hospital Provincial del Centenario, Rosario, Argentina
| | - Luis Colombato
- Gastroenterology Department, & Liver Unit, Hospital Británico, CABA, Argentina
| | - José Adi
- Gastroenterology Department, Hospital Lagomaggiore, Mendoza, Argentina
| | - Eduardo Fassio
- Gastroenterology Department & Liver Unit, Hospital Alejandro Posadas, El Palomar, Argentina
| | | | | | - Luis Gaite
- Gastroenterology Department, Hospital Cullen, Santa Fe, Argentina
| | - Diana Gibelli
- Gastroenterology Department, Hospital San Roque, Córdoba, Argentina
| | | | - Matías Lafage
- Gastroenterology Department, Instituto Lanari, CABA, Argentina
| | - Daniel Lombardo
- Gastroenterology Department, Hospital Angel Padilla, Tucumán, Argentina
| | - Susana López
- Gastroenterology Department, Hospital Juan Garraham, CABA, Argentina
| | - Alejandro Mateo
- Gastroenterology Department, Hospital Eva Perón, Granadero Baigorria, Argentina
| | | | | | - Andrés Ruf
- Liver Unit, Hospital Privado, Rosario, Argentina
| | - Pablo Ruiz
- Internal Medicine Department, Hospital Regional, Río Gallegos, Argentina
| | - Javier Severini
- Internal Medicine Department, Hospital Alberdi, Rosario, Argentina
| | - Teodoro Stieben
- Gastroenterology Department, Hospital San Martín, Paraná, Argentina
| | - Marcela Sixto
- Gastroenterology Department, Hospital Jaime Ferré, Rafaela, Argentina
| | - Fabián Zárate
- Gastroenterology Department, Hospital Córdoba, Córdoba, Argentina
| | | | | | | | - Juan P Roblero
- Gastroenterology Department, Hospital San Borja Arriaran, Santiago, Chile
| | - Juan O Rojas
- Gastroenterology Department, Hospital Dr. Sotero del Río, Santiago, Chile
| | | | | | | | - Alvaro Urzúa Manchego
- Gastroenterology & Liver Unit, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Eliana Valdes
- Gastroenterology Department, Hospital Regional de Talca, Talca, Chile
| | - Pamela Yaquich
- Gastroenterology Department, Hospital San Juan de Dios, Santiago, Chile
| | - Rodrigo Wolff
- Gastroenterology Department & Liver Unit, Hospital Clínico, Universidad Católica de Chile, Santiago, Chile
| | | | | | - Rocío Galloso
- Gastroenterology Department, Hospital San José, Callao, Peru
| | - Julio S Marcelo
- Gastroenterology Department, Hospital Villa El Salvador, Lima, Peru
| | - Pedro Montes
- Gastroenterology Department, Hospital Nacional Daniel A. Carrión, Callao, Peru
| | - Laura Tenorio
- Gastroenterology Department & Liver Unit, Hospital Edgardo Rebagliati, Lima, Peru
| | - Isabel Veramendi
- Gastroenterology Department, Hospital Hipólito Unanue, Lima, Peru
| | - Elizabeth Alava
- Department of Internal Medicine, Hospital Verdi Ceballos, Portoviejo, Ecuador
| | - Ximena Armijos
- Gastroenterology Department & Liver Unit, Hospital Andrade Marín, Quito, Ecuador
| | - Gonzalo Benalcazar
- Gastroenterology Department & Liver Unit, Hospital Luis Vernaza, Guayaquil, Ecuador
| | - Enrique Carrera
- Gastroenterology Department, Hospital Eugenio Espejo, Quito, Ecuador
| | - Galo F Pazmiño
- Gastroenterology Department, Hospital de Especialidades FFAA, Quito, Ecuador
| | | | - Miguel Garassini
- Gastroenterology Department, Centro Médico La Trinidad, Caracas, Venezuela
| | - Rosalía P Marrero
- Gastroenterology Department, Hospital Pérez Carreño, Caracas, Venezuela
| | - Mirta Infante
- Sociedad Cubana de Gastroenterología, La Habana, Cuba
| | - Dayron Páez Suárez
- Gastroenterology Department, Hospital Hermanos Ameijeiras, La Habana, Cuba
| | | | | | | | | | | | | | - María T Andara
- Instituto Hondureño de la Seguridad Social, Tegucigalpa, Honduras
| | | | - Solange Gerona
- Liver Unit, Hospital de Fuerzas Armadas, Montevideo, Uruguay
| | - Iván García
- Gastroenterology Department, Hospital Rooselvet, Guatemala, Guatemala
| | - Fátima de la Tijera
- Gastroenterology Department & Liver Unit, Hospital General de Mexico Dr. E. Liceaga, Ciudad de Mexico, Mexico
| | | | | | - Martín Garzón
- Gastroenterology Department, Hospital de la Samaritana, Bogotá, Colombia
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Reha JL, Lee S, Hofmann LJ. Prevalence and Predictors of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery: A Department of Defense Experience. Am Surg 2020. [DOI: 10.1177/000313481408000624] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Nonalcoholic steatohepatitis (NASH) is a silent liver disease that can lead to inflammation and subsequent scaring. If left untreated, cirrhosis may ensue. Morbidly obese patients are at an increased risk of NASH. We report the prevalence and predictors of NASH in patients undergoing morbid obesity surgery. A retrospective review was conducted on morbidly obese patients undergoing weight reduction surgery from September 2005 through December 2008. A liver biopsy was performed at the time of surgery. Patients who had a history of hepatitis infection or previous alcohol dependency were excluded. Prevalence of NASH was studied. Predictors of NASH among clinical and biochemical variables were analyzed using multivariate regression analysis. One hundred thirteen patients were analyzed (84% female; mean age, 42.6 ± 11.4 years; mean body mass index, 45.1 ± 5.7 kg/m2). Sixty-one patients had systemic hypertension (54%) and 35 patients had diabetes (31%). The prevalence of NASH in this study population was 35 per cent (40 of 113). An additional 59 patients (52%) had simple steatosis without NASH. Only 14 patients had normal liver histology. On multivariate analysis, only elevated aspartate aminotransferase (AST) (greater than 41 IU/L) was the independent predictor for NASH (odds ratio, 5.85; confidence interval, 1.06 to 32.41). Patient age, body mass index, hypertension, diabetes, hypercholesterolemia, and abnormal alanine aminotransferase did not predict NASH. NASH is a common finding in obese population. Abnormal AST was the only predictive factor for NASH.
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Affiliation(s)
| | - Sukhyung Lee
- The University of Texas MD Anderson Cancer Center, Houston, Texas; and
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Fraisse T, Savey L, Hentgen V, Rossi-Semerano L, Koné-Paut I, Grateau G, Georgin-Lavialle S, Ducharme-Bénard S. Non-amyloid liver involvement in familial Mediterranean fever: A systematic literature review. Liver Int 2020; 40:1269-1277. [PMID: 32196885 DOI: 10.1111/liv.14445] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 03/09/2020] [Accepted: 03/11/2020] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Familial Mediterranean fever (FMF), the most frequent autoinflammatory disease, is caused by mutations in the MEFV gene. It is characterized by recurrent febrile attacks of polyserositis. Liver abnormalities may develop during its course, but they remain poorly defined. OBJECTIVE To describe liver involvement in FMF patients. METHODS A systematic search was conducted through PubMed/Medline and Embase from 1946 to January 2020. All articles describing children and adults with FMF and liver involvement were included. Patients with amyloidosis were excluded. The selected full-text articles were independently reviewed by three investigators. RESULTS Forty-three articles were identified, of which 20 articles with a total of 99 patients were included: 74 adults, 23 children and two patients of unknown age. Ten patients had cryptogenic cirrhosis, 48 had nonalcoholic fatty liver disease (NAFLD), four had Budd-Chiari syndrome (BCS), 12 had isolated hyperbilirubinaemia and 25 had elevated liver enzymes. CONCLUSION Despite a low prevalence of metabolic risk factors, FMF may be associated with NAFLD and cryptogenic cirrhosis as a consequence of chronic or recurrent inflammation. FMF patients should be regularly screened for liver injury. The latter may be prevented and treated by daily colchicine intake. The evidence was insufficient to establish an association with BCS, hyperbilirubinaemia or autoimmune hepatitis.
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Affiliation(s)
- Thibault Fraisse
- Service de médecine interne, Hôpital Tenon, APHP, Université Sorbonne, Paris, France
| | - Léa Savey
- Service de médecine interne, Hôpital Tenon, APHP, Université Sorbonne, Paris, France
| | | | - Linda Rossi-Semerano
- Service de rhumatologie-pédiatrie, Hôpital Bicêtre, APHP, Université Paris-Sud, Paris, France
| | - Isabelle Koné-Paut
- Service de rhumatologie-pédiatrie, Hôpital Bicêtre, APHP, Université Paris-Sud, Paris, France
| | - Gilles Grateau
- Service de médecine interne, Hôpital Tenon, APHP, Université Sorbonne, Paris, France
| | | | - Stéphanie Ducharme-Bénard
- Service de médecine interne, Hôpital Tenon, APHP, Université Sorbonne, Paris, France
- Service de médecine interne, Hôpital du Sacré-Cœur de Montréal, Université de Montréal, Montréal, Québec, Canada
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Positive Hepatitis B Core Antibody Is Associated With Cirrhosis and Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease. Am J Gastroenterol 2020; 115:867-875. [PMID: 32149781 DOI: 10.14309/ajg.0000000000000588] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD). METHODS This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. RESULTS In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity. DISCUSSION Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.
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Clinical Features and Outcomes of Repeated Endoscopic Therapy for Esophagogastric Variceal Hemorrhage in Cirrhotic Patients: Ten-Year Real-World Analysis. Gastroenterol Res Pract 2020; 2020:5747563. [PMID: 32508912 PMCID: PMC7245665 DOI: 10.1155/2020/5747563] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 03/11/2020] [Accepted: 04/20/2020] [Indexed: 12/11/2022] Open
Abstract
Objective This study is aimed at evaluating the survival of cirrhotic patients with different etiologies after endoscopic therapy for acute variceal bleeding and the effect of repeated endotherapy on patients' prognosis. Methods We retrospectively evaluated the clinical features and outcomes between cirrhotic patients with chronic HBV or HCV infections and other etiologies. The 3-year and 5-year survival rates and rehemorrhage rate in one year between the viral and nonviral cirrhosis patients were compared by Kaplan-Meier curves and log-rank test. Cox analysis was used to identify the impact factors that affect the long-term survival of patients with cirrhosis and variceal bleeding after endotherapy. Results Out of 2665 patients with liver cirrhosis and variceal hemorrhage selected from our medical center between September 2008 and December 2017, a total of 1342 patients were included for analysis. The median follow-up duration was 32.9 months (range 0.16-111.4 months), the 3- and 5-year cumulative survival rates were 75.3% and 52.8%, respectively. The median survival time was significantly longer in viral cirrhosis patients (47.1 months [95% CI: 24.9-69.1]) compared with nonviral cirrhosis patients (37.0 months [95% CI: 25.0-56.0], p = 0.001). The 3-year and 5-year survival rates of the viral group were higher than the nonviral group. The rehemorrhage rate at one year was higher in nonviral patients than in viral patients (p < 0.001). Conclusion Repeated endotherapy combined with effective antiviral therapy is helpful for long-term survival of cirrhotic population with variceal hemorrhage and HBV or HCV infection.
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Lang S, Martin A, Kasper P, Schramm C, Kütting F, Goeser T, Steffen HM, Demir M. Hepatocellular carcinoma surveillance with liver imaging is not associated with improved survival. Scand J Gastroenterol 2020; 55:222-227. [PMID: 31990240 DOI: 10.1080/00365521.2020.1718747] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany.Material and methods: We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis (n = 111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance (n = 290).Results: Median follow-up in the surveillance group was 76 months (range 4-310 months). Patients in the surveillance group had smaller median tumor sizes (3.5 cm vs. 4.5 cm; p < .001), fulfilled more often Milan criteria (64% vs. 42%; p < .001) and received more often liver transplantation (27% vs. 9%, p < .001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14 months in the surveillance group vs. 12 months in the non-surveillance group, p = .375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62-1.04, p = .09).Conclusions: HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.
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Affiliation(s)
- Sonja Lang
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Department of Medicine, University of California San Diego, San Diego, La Jolla, CA, USA
| | - Anna Martin
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Philipp Kasper
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Christoph Schramm
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Fabian Kütting
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Tobias Goeser
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Hans-Michael Steffen
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Münevver Demir
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
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Umetsu S, Mizukami H, Saito T, Uchida C, Igawa A, Kudo K, Itabashi C, Osonoi S, Danyang G, Sasaki T, Yagihashi S, Hakamada K. Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation. Sci Rep 2020; 10:1156. [PMID: 31980687 PMCID: PMC6981134 DOI: 10.1038/s41598-020-57883-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 01/03/2020] [Indexed: 12/13/2022] Open
Abstract
A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.
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Affiliation(s)
- Satoko Umetsu
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.,Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
| | - Takeshi Saito
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.,Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Chiaki Uchida
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.,Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Akiko Igawa
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.,Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kazuhiro Kudo
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Chieko Itabashi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Sho Osonoi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Guo Danyang
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Takanori Sasaki
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Soroku Yagihashi
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Acharya SK, Bopanna S. Hepatocellular Carcinoma Screening and Nonalcoholic Fatty Liver Disease: How is it Different? J Clin Exp Hepatol 2020; 10:518-524. [PMID: 33029058 PMCID: PMC7527837 DOI: 10.1016/j.jceh.2020.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 04/05/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are major contributors to the burden of liver disease today. Effective therapeutic strategies for prevention of progression of NASH to cirrhosis are still elusive. As with other diseases causing cirrhosis, NASH also increases risk of hepatocellular carcinoma (HCC). NAFLD without cirrhosis also, has been shown to be a risk factor for HCC but pathogenesis of HCC in these patients, is not clear. Several risk factors for HCC in patients with NAFLD-/NASH-related cirrhosis have been identified. Surveillance strategies for HCC in NASH-related cirrhosis is similar to other patients with cirrhosis. No guidelines are currently available for surveillance in patients with NAFLD exclusively, owing to considerable gaps in knowledge. Prevention of NAFLD and lifestyle changes addressing the risk factors for HCC remain the backbone of managing patients with NAFLD- and NAFLD-related complications such as HCC.
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Affiliation(s)
- Subrat K. Acharya
- KIIT University, Chandrasekhar Pur, Bhubaneswar, 751024, Odisha, India,Address for correspondence: Subrat Kumar Acharya, Pro Chancellor, KIIT University, Chandrasekhar pur, Bhubaneswar, 751024, Odisha, India.
| | - Sawan Bopanna
- Department of Gastroenterology, Fortis Flt. Lt. Rajan Dhall Hospital, Aruna Asaf Ali Marg, Pocket 1, Sector B, Vasant Kunj, New Delhi, 110070, India
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Scott C, Stokes R, Cha KM, Clouston A, Eslam M, Metwally M, Swarbrick MM, George J, Gunton JE. Myeloid cell deletion of Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) induces non-alcoholic steatohepatitis. PLoS One 2019; 14:e0225332. [PMID: 31800592 PMCID: PMC6892561 DOI: 10.1371/journal.pone.0225332] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 11/01/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIM Non-alcoholic steatohepatitis (NASH) is predicted to become the most common cause of cirrhosis and liver failure. Risk factors include obesity, insulin resistance and diabetes. Macrophages and other myeloid cells play crucial roles in initiating and driving inflammation. Aryl hydrocarbon Receptor Nuclear Translocator (ARNT) is a transcription factor which binds to a range of partners to mediate responses to environmental signals, including the diet. In people with diabetes it is decreased in liver. We hypothesised that myeloid cell ARNT activity may contribute to the development of liver pathology. METHODS Floxed-ARNT mice were bred with LysM-Cre mice to generate mice with reduced ARNT in myeloid cells. Animals were fed a high fat diet (HFD) and liver pathology was assessed. Histology, mRNA, fat accumulation and metabolism were studied. RESULTS Animals with reduced myeloid ARNT developed steatohepatitis on a HFD, with additional alterations of metabolism and fat deposition. Steatohepatitis was accompanied by hepatic macrophage infiltration and expression of both M1 and M2 markers. Expression of mRNAs for Cxcl1, Mcp-1, Tnf-α and Tgf-β1 were increased. Human livers from controls and people with NASH were tested; ARNT mRNA was decreased by 80% (p = 0.0004). CONCLUSIONS Decreased myeloid ARNT may play a role in the conversion from non-alcoholic fatty liver to steatohepatitis. Increasing ARNT may be a therapeutic strategy to reduce NASH.
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Affiliation(s)
- Christopher Scott
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
| | - Rebecca Stokes
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
| | - Kuan Minn Cha
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Andrew Clouston
- Envoi Specialist Pathologists, Brisbane, Queensland, Australia
| | - Mohammed Eslam
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Mayda Metwally
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Michael M. Swarbrick
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Jacob George
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
| | - Jenny E. Gunton
- Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
- St. Vincent’s Clinical School, University of NSW, Sydney, NSW, Australia
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Møhlenberg M, Terczynska-Dyla E, Thomsen KL, George J, Eslam M, Grønbæk H, Hartmann R. The role of IFN in the development of NAFLD and NASH. Cytokine 2019; 124:154519. [PMID: 30139548 DOI: 10.1016/j.cyto.2018.08.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 08/10/2018] [Accepted: 08/11/2018] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and its progressive inflammatory form non-alcoholic steatohepatitis (NASH) are major health challenges due to a significant increase in their incidence and prevalence. While NAFLD is largely benign, the chronic liver inflammation in NASH patients may cause progression to liver cirrhosis and hepatocellular carcinoma. There is an urgent need for a better understanding of the factors, which drive the progression from NAFLD to NASH and how to use this information both to improve diagnostic and to develop new treatment strategies. Increasing evidence points to interferons (IFNs) as key players in NAFLD and particular in the progression to NASH. IFNs crucial role in disease development is supported by both genetic evidence and animal studies. In this review, we describe the involvement of both type I and type III IFNs in the development and progression of NAFLD and NASH.
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Affiliation(s)
- Michelle Møhlenberg
- Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
| | - Ewa Terczynska-Dyla
- Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
| | - Karen Louise Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Mohammed Eslam
- Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney and Westmead Hospital, Westmead, Australia
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Rune Hartmann
- Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
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Kim SK, Kim KI, Kim SR. [Overview of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Management]. YAKUGAKU ZASSHI 2019; 139:1147-1153. [PMID: 31474630 DOI: 10.1248/yakushi.19-00011-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The number of patients with chronic liver diseases is expected to decline due to progress in antivirus therapy, including direct-acting antivirals for hepatitis C and nucleot(s)ide analogues for hepatitis B. On the other hand, the number of patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) in the setting of metabolic syndrome has been increasing worldwide. Hepatocellular carcinoma (HCC) arises in the setting of chronic hepatic inflammation and liver cirrhosis associated with NAFLD/NASH. However, the detailed clinical features of NAFLD/NASH and NAFLD/NASH-derived HCC prevalence have not yet been fully elucidated as there are two major problems in diagnosing definitive NAFLD/NASH: it is difficult to evaluate past alcoholic consumption history precisely and to obtain certain pathologic findings from all patients with fatty liver. Although previous studies clarified some of the genetic and pathophysiological aspects of NAFLD/NASH, basic knowledge of NAFLD/NASH mechanisms remains insufficient and the methods for predicting the risk of tumorigenesis and effective therapy for NAFLD/NASH are not well defined. The treatment of NAFLD/NASH comprises changes in lifestyle including eating habits and exercise leading to weight loss, and drug intake such as vitamin E. A number of new drugs for NAFLD/NASH patients have been under trial. Additional larger-scale studies are required to elucidate fully the clinical and basic landscape of NAFLD-HCC. This paper gives an overview of NAFLD/NASH management based on the most recent findings.
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Affiliation(s)
- Soo Ki Kim
- Department of Gastroenterology, Kobe Asahi Hospital
| | - Ke Ih Kim
- Department of Pharmacy, Kobe Asahi Hospital
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Muhie OA. Causes and Clinical Profiles of Ascites at University of Gondar Hospital, Northwest Ethiopia: Institution-Based Cross-Sectional Study. Can J Gastroenterol Hepatol 2019; 2019:5958032. [PMID: 31360695 PMCID: PMC6644216 DOI: 10.1155/2019/5958032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 07/01/2019] [Indexed: 11/17/2022] Open
Abstract
Background Ascites is a common clinical condition encountered by physicians in day-to-day practice. It is caused by various underlying diseases. Knowing the etiologies is vital because further investigations and definitive treatment largely rely on the specific disease entity considered. Objective The aim of this study was to determine the epidemiology of causes of ascites and complications among patients with ascites from the medical department at the University of Gondar Hospital. Methods Data on sociodemography, major symptoms, and signs, risk factors, past medical illnesses, and results of important investigations were collected using pretested questionnaires among all patients with ascites in the University of Gondar Hospital in a sample size of 52. Data were collected by well-trained physicians and analyzed by using SPSS 16. Results were depicted descriptively with measures of central tendency, dispersion, and using tables and graphs. Results A total of 52 patients were included in this study from November 1, 2018 to March 30, 2019. Thirty (57.7%) of them were males and the majority (77%) of the participants were fifty years old or younger. The mean age was 43.8 (± 14). The majority (86.5%) of the participants were from a rural area. Thirty-eight (73%) patients take alcohol occasionally while 11(21.2%) patients take alcohol frequently or massively. Eight (15.4%) patients reported a history of multiple sexual partners. Herbal medicine use was reported by 28 patients (53.8%). Only 5 (9.6%) patients were overweight. Chronic liver disease (CLD) was the major cause of ascites in this study in 24 (46.2%) patients. The other main causes of ascites were heart failure from various causes (19.2%), tuberculosis and hepatosplenic schistosomiasis contributing to 11.5% each and chronic kidney disease (5.8%). Five (20.8%) CLD patients had spontaneous bacterial peritonitis as a complication. Five (20.8%) and 4 (16.7%) CLD patients had hepatocellular carcinoma and hepatic encephalopathy as complications, respectively. Nine (17.3%) patients had variceal bleeding; six of the patients were diagnosed to have CLD while the remaining patients were having hepatosplenic schistosomiasis. Conclusion In conclusion, liver cirrhosis is the major cause of ascites in Gondar, Ethiopia, while chronic viral hepatitis infections (hepatitis B (HBV) and C (HCV) viruses) are the main causes of liver cirrhosis. The other major causes included heart failure, tuberculosis, and hepatosplenic schistosomiasis. It is wise to consider and give priority to these diseases whenever one is evaluating a patient with ascites.
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Affiliation(s)
- Oumer Abdu Muhie
- Department of Internal Medicine, CMHS, University of Gondar, P.O. Box 196, Ethiopia
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Berhane S, Fox R, García-Fiñana M, Cucchetti A, Johnson P. Using prognostic and predictive clinical features to make personalised survival prediction in advanced hepatocellular carcinoma patients undergoing sorafenib treatment. Br J Cancer 2019; 121:117-124. [PMID: 31182766 PMCID: PMC6738086 DOI: 10.1038/s41416-019-0488-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 05/01/2019] [Accepted: 05/10/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Sorafenib is the current standard of care for patients with advanced hepatocellular carcinoma (aHCC) and has been shown to improve survival by about 3 months compared to placebo. However, survival varies widely from under three months to over two years. The aim of this study was to build a statistical model that allows personalised survival prediction following sorafenib treatment. METHODS We had access to 1130 patients undergoing sorafenib treatment for aHCC as part of the control arm for two phase III randomised clinical trials (RCTs). A multivariable model was built that predicts survival based on baseline clinical features. The statistical approach permits both group-level risk stratification and individual-level survival prediction at any given time point. The model was calibrated, and its discrimination assessed through Harrell's c-index and Royston-Sauerbrei's R2D. RESULTS The variables influencing overall survival were vascular invasion, age, ECOG score, AFP, albumin, creatinine, AST, extra-hepatic spread and aetiology. The model-predicted survival very similar to that observed. The Harrell's c-indices for training and validation sets were 0.72 and 0.70, respectively indicating good prediction. CONCLUSIONS Our model ('PROSASH') predicts patient survival using baseline clinical features. However, it will require further validation in a routine clinical practice setting.
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Affiliation(s)
- Sarah Berhane
- Department of Biostatistics, University of Liverpool, Liverpool, UK
| | - Richard Fox
- Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, UK
| | | | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Philip Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
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Interpretation of core biopsy of liver mass lesions: A comparison study between cytopathologist and gastrointestinal pathologist. Ann Diagn Pathol 2019; 40:152-160. [DOI: 10.1016/j.anndiagpath.2019.05.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 05/02/2019] [Accepted: 05/02/2019] [Indexed: 12/21/2022]
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Cekdemir D. Correlation of Liver Enzyme Levels and Insulin Resistance in Patients with Non-Alcoholic Steatosis. ANKARA MEDICAL JOURNAL 2019. [DOI: 10.17098/amj.542200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019; 92:82-97. [PMID: 30502373 DOI: 10.1016/j.metabol.2018.11.014] [Citation(s) in RCA: 784] [Impact Index Per Article: 130.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 11/24/2018] [Accepted: 11/24/2018] [Indexed: 02/06/2023]
Abstract
The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis (SS), but also with advanced disease, i.e., nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. As a consequence, apart from increasing all-cause mortality, obesity seems to increase liver-specific mortality in NAFLD patients. Given the lack of approved pharmacological interventions for NAFLD, targeting obesity is a rational option for its management. As the first step, lifestyle modification (diet and exercise) is recommended, although it is difficult to achieve and sustain. When the first step fails, adding pharmacotherapy is recommended. Several anti-obesity medications have been investigated in NAFLD (e.g., orlistat, glucagon-like peptide-1 analogs), other anti-obesity medications have not been investigated (e.g., lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion), whereas some medications with weight-lowering efficacy have not been approved for obesity (e.g., sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands). If the combination of lifestyle modification and pharmacotherapy also fails, then bariatric surgery should be considered in selected morbidly obese individuals. This review summarizes best evidence linking obesity with NAFLD and presents related therapeutic options.
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Affiliation(s)
- Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Jannis Kountouras
- Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
| | - Christos S Mantzoros
- Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA, USA
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Comparison of Hepatocellular Carcinoma in Patients with Cryptogenic Versus Hepatitis B Etiology: A Study of 1079 Cases Over 3 Decades. Dig Dis Sci 2019; 64:585-590. [PMID: 30327962 DOI: 10.1007/s10620-018-5331-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 10/09/2018] [Indexed: 01/11/2023]
Abstract
BACKGROUND Traditionally in Asia, hepatitis B (HBV) accounts for the majority of hepatocellular carcinoma (HCC), but increasingly, non-viral or nonalcoholic steatohepatitis (NASH) etiology may play a more prominent role with current socioeconomic changes. There remains a paucity in data comparing NASH-HCC to HBV-related HCC. In this study, we explored the differences in clinical characteristics between HBV- and cryptogenic-related HCC. METHODS Patients with HCC seen in the Department of Gastroenterology and Hepatology, Singapore General Hospital were enrolled in an ongoing database since 1980. Patients with HCC attributed to HBV or cryptogenic etiology were identified. Comparison of clinical characteristics was performed between the two groups. RESULTS There were 916 HBV-HCC patients and 163 cryptogenic HCC patients, accounting for 70.9% and 12.6% of the total HCC cases (1292 patients), respectively. Out of the total cohort enrolled from 1980 to 2005, the ratio of cryptogenic to HBV patients was 1:6.7, while from 2006 to the current year, the ratio of cryptogenic to HBV patients has increased significantly to 1:3.9. Relative to patients with HBV, cryptogenic HCC patients were older (67.6 vs. 59.4 years old; p < 0.001), had lower proportion of male patients (69.9% vs. 83.8%; p < 0.001), and had higher incidence of smoking (32.2% vs. 25.8%; p = 0.008). HBV group had higher alanine transaminase (60.9 ± 85.7 U/L vs. 48.0 ± 52.1 U/L; p = 0.003), hemoglobin (12.7 ± 2.28 g/dL vs. 12.0 ± 2.46 g/dL, p < 0.001), albumin (32.9 ± 6.8 g/L vs. 31.3 ± 7.7 g/L; p = 0.007), and prothrombin time (13.2 ± 2.95 s vs. 12.7 ± 2.01 s, p = 0.023), as compared to the cryptogenic group. Cryptogenic HCC patients presented more frequently with unifocal HCC (55.2% vs. 46.5%; p = 0.002). There was no difference in the proportions of patients receiving surgical resection in both groups (23.5% in HBV group vs. 17.9% in cryptogenic group; p = 0.202). Cox regression analysis revealed no survival difference between cryptogenic-related HCC and HBV-related HCC (p = 0.367). CONCLUSION Temporal trends suggest that HCC attributed to HBV is on the decline, while cryptogenic- or NASH-related HCC is an emerging clinical entity. A paradigm shift in approach to screening, surveillance, and management of HCC may be required in view of the changing landscape of HCC epidemiology into an increasing non-viral etiology.
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Lin TY, Yeh ML, Huang CF, Huang CI, Dai CY, Hsieh MH, Chen SC, Huang JF, Yu ML, Chuang WL. Disease progression of nonalcoholic steatohepatitis in Taiwanese patients: a longitudinal study of paired liver biopsies. Eur J Gastroenterol Hepatol 2019; 31:224-229. [PMID: 30308578 DOI: 10.1097/meg.0000000000001285] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Nonalcoholic steatohepatitis (NASH) might progress to fibrosis, cirrhosis, and hepatocellular carcinoma. However, the natural history of NASH has not been fully clarified. This study aimed to investigate the disease progression in NASH patients receiving paired liver biopsies. We also aimed to examine the factors associated with NASH progression. PATIENTS AND METHODS Ten NASH patients who had received liver biopsies during June 2001 and February 2010 were consecutively enrolled. The histopathological changes were examined retrospectively, including nonalcoholic fatty liver disease activity score (NAS) and fibrosis stage. The associated clinical profiles were also analyzed. RESULTS The median duration between paired biopsies was 20.5 months (range: 12-106 months). According to NAS and fibrosis stage, disease progression, stable disease, and disease regression were observed in seven patients, two patients, and one patient, respectively. Six (60%) patients had increased NAS on second biopsy, and two were lean NASH patients. The only patient with an improvement in NAS had achieved body weight reduction (13.3%) between paired biopsies. None of the 10 patients experienced an improvement in fibrosis. Five (50%) patients showed progression of fibrosis on second biopsy and the annual fibrosis progression rate was 0.32/year. Two of the five patients who showed progression of fibrosis were of the nonobese phenotype, whereas three patients were nondiabetic. CONCLUSION NASH is a progressive disease in Taiwanese patients. The disease progression should be further clarified in lean and nondiabetic NASH patients.
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Affiliation(s)
- Ta-Ya Lin
- Department of Internal Medicine, Hepatobiliary Division
| | - Ming-Lun Yeh
- Department of Internal Medicine, Hepatobiliary Division
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Department of Internal Medicine, Hepatobiliary Division
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Hepatobiliary Division
| | - Chia-Yen Dai
- Department of Internal Medicine, Hepatobiliary Division
- Graduate Institute of Clinical Medicine
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Department of Internal Medicine, Hepatobiliary Division
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Department of Internal Medicine, Hepatobiliary Division
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Department of Internal Medicine, Hepatobiliary Division
- Graduate Institute of Clinical Medicine
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Department of Internal Medicine, Hepatobiliary Division
- Graduate Institute of Clinical Medicine
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Department of Internal Medicine, Hepatobiliary Division
- Graduate Institute of Clinical Medicine
- College of Medicine, Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo M, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia M, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera J, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera M, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio J, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez J, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila J, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco J. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo MS, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia MA, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera JA, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera MF, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio JA, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez JL, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila JF, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco JA. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:69-99. [PMID: 30711302 DOI: 10.1016/j.rgmx.2018.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.
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Affiliation(s)
- R Bernal-Reyes
- Sociedad Española de Beneficencia, Pachuca, Hidalgo, México.
| | - G Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, México
| | | | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Chávez-Tapia
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - C Aguilar-Salinas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de enfermedades hepáticas, Hospital Ángeles Lómas, Ciudad de México, México
| | | | | | - M Castillo-Barradas
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico La Raza IMSS, Ciudad de México, México
| | - J A Chávez-Barrera
- Servicio de Gastroenterología Pediátrica, Hospital General, Centro Médico La Raza, IMSS, Ciudad de México, México
| | - L Cisneros-Garza
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - J Flores-Calderón
- Servicio de Gastroenterología, Hospital de Pediatría, Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - D García-Compeán
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - Y Gutiérrez-Grobe
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | | | | | | | - J Lizardi-Cervera
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J A López-Cossio
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - S Martínez-Vázquez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - E Márquez-Guillén
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Méndez-Sánchez
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - R Moreno-Alcantar
- Servicio de Gastroenterología, Hospital de Especialidades Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - J L Poo-Ramírez
- Centro de Innovación y Educación Ejecutiva, Tec de Monterrey, Ciudad de México, México
| | | | - H Rodríguez-Hernández
- Unidad de Investigación Biomédica AMCCI, Hospital de Especialidades, Durango, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, México
| | - M Stoopen-Rometti
- Centro de Diagnóstico CT-Scanner Lomas Altas, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - G Torres-Villalobos
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - M Uribe-Esquivel
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
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Current Models of Fatty Liver Disease; New Insights, Therapeutic Targets and Interventions. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1134:33-58. [PMID: 30919331 DOI: 10.1007/978-3-030-12668-1_3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to steatosis with inflammation and fibrosis. NAFLD is currently the most prevalent chronic liver disease worldwide, with a global prevalence of 25%, and is soon projected to be the leading cause for liver transplantation in the US. Alarmingly, few effective pharmacotherapeutic approaches are currently available to block or attenuate development and progression of NAFLD. Preclinical models are critical for unraveling the complex and multi-factorial etiology of NAFLD and for testing potential therapeutics. Here we review preclinical models that have been instrumental in highlighting molecular and cellular mechanisms underlying the pathogenesis of NAFLD and in facilitating early proof-of-concept investigations into novel intervention strategies.
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Thuluvath PJ, Kantsevoy S, Thuluvath AJ, Savva Y. Reply to: "NASH-related and cryptogenic cirrhosis similarities extend beyond cirrhosis": Cryptogenic cirrhosis should not be equated with NASH cirrhosis based on UNOS data mining and Bayesian 'doctrine of chances'. J Hepatol 2018; 69:973-975. [PMID: 29983203 DOI: 10.1016/j.jhep.2018.06.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 06/19/2018] [Indexed: 12/04/2022]
Affiliation(s)
- Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, United States; Departments of Surgery & Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.
| | - Sergey Kantsevoy
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, United States; Departments of Surgery & Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Avesh J Thuluvath
- Johns Hopkins University School of Medicine, Baltimore, United States
| | - Yulia Savva
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, United States
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Koch LK, Yeh MM. Nonalcoholic fatty liver disease (NAFLD): Diagnosis, pitfalls, and staging. Ann Diagn Pathol 2018; 37:83-90. [PMID: 30312882 DOI: 10.1016/j.anndiagpath.2018.09.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 09/25/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with obesity, diabetes and the metabolic syndrome, not only in the Western societies, but also in most regions of the world in the 21st century. The spectrum of its histopathology ranges from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma (HCC). Benign and malignant liver tumors have also been more frequently reported with the increasing prevalence of obesity and diabetes. This review addresses the pathology of NAFLD and NASH, and their diagnostic features, diagnostic pitfalls, grading and staging, and clinical correlation.
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Affiliation(s)
- Lisa K Koch
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America
| | - Matthew M Yeh
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States of America.
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