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Al-Busafi SA, Al Balushi AS, Al Shuaili HH, Mahmood DA, Al Alawi AM. Prevalence of Non-Alcoholic Fatty Liver Disease and Its Impact on Fibrosis Risk in Inactive Chronic Hepatitis B Patients: Insights from a Cross-Sectional Study. J Clin Med 2024; 13:4738. [PMID: 39200880 PMCID: PMC11355821 DOI: 10.3390/jcm13164738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are significant causes of chronic liver disease, potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, the coexistence of CHB and NAFLD is increasingly common, although the relationship between NAFLD and inactive CHB infection remains poorly understood. Objectives: This study aimed to investigate the prevalence of NAFLD among patients with inactive CHB, identify risk factors for NAFLD, and determine predictors of significant fibrosis in these patients. Methods: This single-center cross-sectional study targeted patients with inactive CHB at Sultan Qaboos University Hospital from January 2010 to November 2021. Results: A total of 425 patients with inactive CHB were identified, of which 53.1% were male and 62.6% were aged 40-60 years. The prevalence of NAFLD was 47.8%. Various independent factors were associated with NAFLD, including type 2 diabetes mellitus, elevated low-density lipoprotein levels, high hemoglobin levels, low platelet counts, and normal alpha-fetoprotein levels. Significant associations were noted between NAFLD and significant fibrosis, with 10.5% of CHB patients with NAFLD exhibiting significant fibrosis compared to 1.4% of those without NAFLD. Other significant parameters included male gender, increased age, high alanine transaminase levels, elevated hemoglobin, and decreased platelet levels. Conclusions: The high prevalence of NAFLD in patients with inactive CHB and its associations with increased fibrosis and cirrhosis risk underscore the need for comprehensive management strategies for these patients.
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Affiliation(s)
- Said A. Al-Busafi
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Amna S. Al Balushi
- Internal Medicine Program, Oman Medical Specialty Board, Muscat 130, Oman
| | | | | | - Abdullah M. Al Alawi
- Internal Medicine Program, Oman Medical Specialty Board, Muscat 130, Oman
- Department of Medicine, Sultan Qaboos University Hospital, Muscat 123, Oman
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2
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O'Neill C, O'Connell C. Idiopathic erythrocytosis: A diagnostic and management challenge with emerging areas for exploration. Br J Haematol 2024; 204:774-783. [PMID: 38262687 DOI: 10.1111/bjh.19287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 12/18/2023] [Accepted: 12/22/2023] [Indexed: 01/25/2024]
Abstract
Despite published algorithms for approaching the work-up of erythrocytosis, a significant proportion of patients are left with uncertainty as to its aetiology and prognosis. The term 'idiopathic erythrocytosis' (IE) is applied when known primary and secondary aetiologies have been ruled out. However, the assignment of secondary aetiologies is not always straightforward or evidence based, which can lead to misdiagnosis and heterogeneity in cohort studies. Furthermore, new studies have identified germline or somatic mutations that may affect prognosis. Epidemiological and cohort data are inconsistent as to whether IE increases the risk for complications such as arterial and venous thromboembolism, clonal transformation or comorbid conditions. Randomized trials assessing the role of phlebotomy for long-term management of IE have not been performed, so treatment remains a vexing problem for clinicians. Standardization of terminology and testing strategies, including comprehensive genetic screening in clinical research, are key to refining our understanding of IE.
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Affiliation(s)
- Caitlin O'Neill
- Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Casey O'Connell
- Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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3
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Ding Q, Zhou Y, Zhang S, Liang M. Association between hemoglobin levels and non-alcoholic fatty liver disease in patients with young-onset type 2 diabetes mellitus. Endocr J 2020; 67:1139-1146. [PMID: 32684526 DOI: 10.1507/endocrj.ej20-0071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
This retrospective study aimed to investigate the relationship between hemoglobin (Hb) levels and non-alcoholic fatty liver disease (NAFLD) in patients with young-onset type 2 diabetes mellitus (T2DM). Data were collected for 296 patients with young-onset T2DM admitted to the first Affiliated Hospital of Guangxi Medical University from May 2017 to January 2020. Subjects were divided into NAFLD (n = 186) and non-NAFLD groups (n = 110). Patients with NAFLD had significantly higher Hb levels (p = 0.001). According to logistic regression analysis, Hb levels were significantly correlated with NAFLD after adjusting for confounding factors [odds ratio (OR) = 1.024, 95% confidence interval = 1.003-1.046, p = 0.028]. Subjects were also grouped according to Hb quartiles. After adjusting for sex and body mass index (BMI), the OR (95%CI) for NAFLD significantly increased with increasing Hb levels (p for trend = 0.009). Patients were also divided into lean (BMI <25 kg/m2, n = 139) and overweight/obese groups (BMI ≥25 kg/m2, n = 157), with adjusted ORs (95%CI) for the highest quartiles of 1.797 (0.559-5.776) and 6.009 (1.328-27.181), respectively. Further quartile classification of Hb according to sex showed adjusted OR (95%CI) for the highest compared with the lowest quartile of 2.796 (1.148-6.814) for males and 2.945 (0.482-17.997) for females. In conclusion, high Hb levels were associated with the presence of NAFLD in patients with young-onset T2DM, especially in males and overweight/obese patients.
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Affiliation(s)
- Qinpei Ding
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yubo Zhou
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shu Zhang
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Min Liang
- Department of Endocrinology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
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Association between Hemoglobin Levels and Colorectal Polyps in Asymptomatic Chinese Adults. Gastroenterol Res Pract 2020; 2020:3808163. [PMID: 32411196 PMCID: PMC7201817 DOI: 10.1155/2020/3808163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 01/01/2020] [Accepted: 01/11/2020] [Indexed: 12/24/2022] Open
Abstract
Methods A cross-sectional analysis was performed among 1633 asymptomatic adults who underwent colonoscopy examinations during routine health check-ups at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2015 and 2018. Results A total of 449 (27.50%) participants were diagnosed with colorectal polyps, and those with colorectal polyps had significantly higher hemoglobin levels than did those without colorectal polyps. Hemoglobin levels were positively associated with the prevalence of colorectal polyps, with rates of 16.43%, 26.20%, 32.17%, and 35.87% among participants with hemoglobin levels in the first, second, third, and fourth quartiles, respectively (P for trend < 0.001). Stepwise multiple regression analysis showed that elevated hemoglobin levels independently increased the risk of colorectal polyps (odd ratio = 1.017; 95% confidence interval: 1.008–1.026). Conclusion Elevated hemoglobin levels were significantly and independently associated with the prevalence and risk of colorectal polyps in asymptomatic adults.
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Li H, Guo M, An Z, Meng J, Jiang J, Song J, Wu W. Prevalence and Risk Factors of Metabolic Associated Fatty Liver Disease in Xinxiang, China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17061818. [PMID: 32168920 PMCID: PMC7143027 DOI: 10.3390/ijerph17061818] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/06/2020] [Accepted: 03/08/2020] [Indexed: 12/14/2022]
Abstract
Metabolic associated fatty liver disease (MAFLD) is recognized as the liver disease component of metabolic syndrome, which is mainly related to insulin resistance and genetic susceptibility. It is the most prevalent chronic liver disease worldwide. With rapid lifestyle transitions, its prevalence worldwide is increasing, and tremendous challenges in controlling this pandemic are arising. The objective of this study was to investigate the prevalence and risk factors of MAFLD in rural areas of Xinxiang, Henan in 2017. We conducted a cross-sectional analysis of rural inhabitants aged 20–79 years in Xinxiang, Henan in 2017, using cluster random sampling (N = 9140). Physical examinations were conducted at local clinics from April to June 2017. After overnight fasting, all participants underwent physical examinations, blood routine tests, biochemical examinations, and liver ultrasound and completed questionnaires. We investigated the crude and age-adjusted MAFLD prevalence and analyzed the characteristics of those with, and without, MAFLD, using logistic regression. Approximately 2868 (31.38%) participants were diagnosed with MAFLD. The overall age-adjusted MAFLD prevalence was 29.85% (men: 35.36%; women: 26.49%). The MAFLD prevalence increased with age, and peaked at the 50–59-year age group, and then began to decline. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were independently and positively correlated with MAFLD; In contrary, active physical activity and high-density lipoprotein cholesterol were negatively correlated with MAFLD. In summary, the MAFLD prevalence in the study population was 29.85%. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were risk factors for MAFLD.
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Affiliation(s)
- Hongbin Li
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
| | - Meihao Guo
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
| | - Zhen An
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
| | - Jun Meng
- School of Management, Xinxiang Medical University, Xinxiang 453003, Henan, China;
| | - Jing Jiang
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
| | - Jie Song
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
| | - Weidong Wu
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, Henan, China; (H.L.); (M.G.); (Z.A.); (J.J.); (J.S.)
- Correspondence:
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Kang NL, Zhang JM, Liu YR, Lin S, Dong J, Jiang JJ, Zhu YY, Zeng DW. Novel predictive models using serum ceruloplasmin levels for hepatic steatosis in patients with chronic hepatitis B infection. Clin Res Hepatol Gastroenterol 2020; 44:57-65. [PMID: 31076363 DOI: 10.1016/j.clinre.2019.04.001] [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] [Received: 12/12/2018] [Revised: 03/15/2019] [Accepted: 03/19/2019] [Indexed: 02/07/2023]
Abstract
AIMS To evaluate the significance of serum ceruloplasmin (CP) to diagnosis hepatic steatosis (HS) in Chronic hepatitis B (CHB) patients. METHODS A total of 360 CHB patients with HS (n = 136) or without HS (n = 224) were included. Relationships between CP and HS degrees were analyzed by Spearman rank correlation. HS-predictive models including CP were constructed using multivariate logistic regression analysis and compared to other HS predicting indexes. RESULTS Serum CP were significantly higher in CHB patients with HS than in patients without HS (P < 0.001) and were positively correlated with HS degree (r = 0.487, P < 0.001). The area under the receiver-operating characteristic curves (AUCs) of using CP to predict HS (S ≥ 1), moderate and severe steatosis (S ≥ 2) and severe steatosis (S = 3) were 0.758, 0.794 and 0.883, respectively. Multivariate analysis showed that CP, age, high density lipoprotein (HDL) and hemoglobin were independent predictors of HS, and CP, body mass index and HDL were independent predictors of moderate and severe HS. Two novel indexes for predicting HS of CHB patients were generated. The AUC of HSCHB-1 (for S ≥ 1) and HSCHB-2 (for S ≥ 2) were 0.881 and 0.916 in the training group, and 0.865 and 0.841 in the validation group, respectively. HSCHB-1 was superior to HS index (P < 0.001), fatty liver disease index (P = 0.0043) and steatosis index of patients with hepatitis B virus infection (P = 0.0029) in predicting HS in CHB patients. CONCLUSIONS HS of CHB patients was positively associated with serum CP. HSCHB-1 and HSCHB-2 with inclusion of CP are two novel models for predicting HS in CHB patients.
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Affiliation(s)
- Na-Ling Kang
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Jie-Min Zhang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Yu-Rui Liu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Su Lin
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Jing Dong
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Jia-Ji Jiang
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Yue-Yong Zhu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China
| | - Da-Wu Zeng
- Liver Center, The First Affiliated Hospital, Fujian Medical University, No. 20, Chazhong road, 350005 Taijiang, Fuzhou, Fujian, PR China.
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Shen Y, Chen L, Yang W, Wang Z. Exploration of serum sensitive biomarkers of fatty liver in dairy cows. Sci Rep 2018; 8:13574. [PMID: 30206404 PMCID: PMC6133919 DOI: 10.1038/s41598-018-31845-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 08/10/2018] [Indexed: 12/24/2022] Open
Abstract
Serum proteins are sensitive with diseases in dairy cows, and some of them could be used as biomarkers for fatty liver. This study aimed to explore serum biomarkers for fatty liver in dairy cows. A total of 28 early lactating dairy cows were chosen from a commercial dairy herds, liver samples were collected for determining concentration of triacylglycerol (TAG), and serum samples were collected for measuring fibroblast growth factor-21 (FGF-21), adiponectin, Lipoprotein-associated phospholipase A2 (LP-PLA2), and hemoglobin (Hb). Dairy cows were divided into fatty liver (liver TAG > 5%, wet weight) and control group (liver TAG < 5%, wet weight). Concentration of FGF-21 was greater in fatty liver cows, while the concentration of LP-PLA2 and Hb was less. The concentration of FGF-21 and total Hb had strong correlation with the liver TAG as well as good prediction power (kappa value = 0.79 and 0.58, respectively). These results suggested that the serum concentration of FGF-21 and total Hb could be potentially used as fatty liver biomarkers in lactating dairy cows.
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Affiliation(s)
- Yizhao Shen
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, 271018, P.R. China.,Agriculture and Agri-Food Canada, Lethbridge Research Centre, Alberta, T1J 4B1, Canada
| | - Lianmin Chen
- Department of Paediatrics & Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands
| | - Wenzhu Yang
- Agriculture and Agri-Food Canada, Lethbridge Research Centre, Alberta, T1J 4B1, Canada
| | - Zhonghua Wang
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, 271018, P.R. China.
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Juárez-Hernández E, C Chávez-Tapia N, C Brizuela-Alcántara D, Uribe M, H Ramos-Ostos M, Nuño-Lámbarri N. Association Between Serum Hemoglobin Levels and Non Alcoholic Fatty Liver Disease in a Mexican Population. Ann Hepatol 2018; 17:577-584. [PMID: 29893698 DOI: 10.5604/01.3001.0012.0920] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers. This study aimed to determine the association of serum Hb levels in patients with steatosis and fibrosis as a noninvasive marker. MATERIAL AND METHODS A 1,186 patient cross-sectional study nested in a randomized clinical trial (NCT01874249) was conducted. Patients were diagnosed by ultrasound for hepatic steatosis and fibroscan for fibrosis; blood test and anthropometric measurements were also assessed. RESULTS Serum Hb increased proportionally related to the steatosis level, being significantly higher in patients with severe steatosis than in patients with moderate and mild steatosis. CONCLUSION Patients with non-alcoholic fatty liver disease showed elevated levels of circulating Hb, evidence that suggests that Hb exerts a protective role, as it may act as an antioxidant and may counteract the adverse effects of this disease.
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Affiliation(s)
| | - Norberto C Chávez-Tapia
- Translational Research Unit, Medica Sur Clinic & Foundation. Mexico City, Mexico. Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation. Mexico City, Mexico
| | | | - Misael Uribe
- Obesity and Digestive Diseases Unit, Medica Sur Clinic & Foundation. Mexico City, Mexico
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Elevated Hemoglobin Level Is Associated With Advanced Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr 2017; 65:150-155. [PMID: 28737569 DOI: 10.1097/mpg.0000000000001614] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Hemoglobin (Hb) and red blood cell distribution width (RDW) have been reported to be a risk marker of metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). No study exists on pediatric populations. We aimed to determine the association between hematological parameters, and the severity of disease in children with biopsy-proven NAFLD. METHODS A total of 117 children (85 boys, mean age 12 years) with ultrasound evidence of NAFLD undergoing liver biopsy for diagnosis of nonalcoholic steatohepatitis (NASH), were prospectively enrolled between January 2011 and May 2013 in the setting of a tertiary care center. Children were screened for routine hematological and metabolic parameters, and causes of liver steatosis other than nonalcoholic were excluded, before liver biopsy was performed. RESULTS A total of 41 NAFLD (boys 29, mean age 11.2 years) and 76 NASH (boys 56, mean age 12.8 years) children were studied. Alanine transaminase levels were significantly higher in NASH group compared with NAFLD group (P = 0.05), and homeostatic model assessment of insulin resistance and triglycerides levels (P = 0.03 and 0.02, respectively). Regarding hematological components: red cell count, Hb, hematocrit, and RDW values were all significantly higher in NASH group compared with NAFLD group (P < 0.05 for each parameter). CONCLUSIONS Children with NASH were more likely to have high levels of RDW compared to those with steatosis only. Moreover, NASH was associated with higher red cell count, Hb, and hematocrit. If confirmed in future follow-up studies, hematological parameters may be introduced in algorithms for NASH risk prediction.
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Caira S, Iannelli A, Sciarrillo R, Picariello G, Renzone G, Scaloni A, Addeo P. Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity. J Enzyme Inhib Med Chem 2017; 32:672-682. [PMID: 28274171 PMCID: PMC6009959 DOI: 10.1080/14756366.2017.1292262] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.
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Affiliation(s)
- Simonetta Caira
- a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy
| | - Antonio Iannelli
- b Département de Chirurgie Digestive , Centre Hospitalier Universitarie de Nice , Nice , France
| | - Rosaria Sciarrillo
- c Dipartimento di Scienze e Tecnologie , Università degli Studi del Sannio , Benevento , Italy
| | | | - Giovanni Renzone
- a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy
| | - Andrea Scaloni
- a Proteomics and Mass Spectrometry Laboratory , ISPAAM, National Research Council , Naples , Italy
| | - Pietro Addeo
- e Service de Chirurgie Hépatique, Pancréatique, Biliaire et Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre , Université de Strasbourg, Hôpitaux Universitaires de Strasbourg , Strasbourg , France
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Diagnostic accuracy and clinical utility of a new noninvasive index for hepatic steatosis in patients with hepatitis B virus infection. Sci Rep 2016; 6:32875. [PMID: 27597515 PMCID: PMC5011766 DOI: 10.1038/srep32875] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 08/16/2016] [Indexed: 12/11/2022] Open
Abstract
The aim of the present study was to construct a cost-effective noninvasive diagnostic index for prediction of hepatic steatosis in patients with hepatitis B virus(HBV) infection. From January 2011 to January 2015, a total of 364 consecutive subjects who underwent liver biopsies were enrolled. The Receiver-operating characteristic(ROC) curves and Obuchowski measure were constructed to evaluate the diagnostic accuracy of the new index. The AUROCs of steatosis index of patients with HBV infection (SIHBV) in predicting of steatosis were 0.929 (95% confidence interval:0.889–0.970, P < 0.05) in the model group and 0.855 (0.794–0.917, P < 0.05) in the validation group respectively. Comparisons of AUROCs demonstrated that SIHBV was significantly superior to Korean Score, fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product(LAP), and fatty liver disease (FLD) index for prediction of hepatic steatosis in model group and validation group(all P < 0.01). Especially for patients with hepatic steatosis percentage of 5.0–9.9% and 10.0–19.9%, SIHBV had a sensitivity of 63.6% and 79.2%, whereas it were 29.1% and 45.8% for Ultrasonography (all P < 0.05). In conclusion, as a cost-effective, simple, noninvasive, and readily available method, SIHBV may act as a massive screening tool before further examinations such as MRI, CT, transient elastography, or liver biopsy, especially for developing countries.
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12
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Zhang ZQ, Wang GS, Kang KF, Wu GB, Wang P. Nomogram for hepatic steatosis: A simple and economical diagnostic tool for massive screening. Dig Liver Dis 2016; 48:914-20. [PMID: 27246795 DOI: 10.1016/j.dld.2016.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 03/18/2016] [Accepted: 05/03/2016] [Indexed: 12/11/2022]
Abstract
AIM To establish a simple economical diagnostic tool for prediction of hepatic steatosis in patients with hepatitis B virus (HBV) infection. METHODS From January 2006 to January 2015,a total of 1325 consecutive subjects who underwent liver biopsy were enrolled. According to the results of multivariate logistic regression analysis, a new nomogram was conducted. Then discrimination and calibration were conducted to assess the clinical diagnostic value of nomogram. RESULTS The nomogram consisted of age, triglyceride (TG), low-density lipoprotein (LDL), uric acid (UA), haemoglobin (HGB). For prediction of hepatic steatosis, the AUROC of nomogram was 0.792 (95%CI: 0.758-0.826). With cut off value of 0.11, 699 (52.8%) of 1325 patients could be free from liver biopsy with a correct rate of 95.3% for diagnosis of hepatic steatosis. CONCLUSION The nomogram for hepatic steatosis has a better clinical diagnostic value for prediction of hepatic steatosis in patients with HBV infection. From the perspective of cost-effectiveness and clinical practice, it is worth considering the use of the nomogram as a mass screening tool before further liver biopsy or imaging examinations.
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Affiliation(s)
- Zhi-Qiao Zhang
- Department of Infectious Diseases, The Shunde First People's Hospital, Shunde, Guangdong, China
| | - Gong-Sui Wang
- Department of Infectious Diseases, The Shunde First People's Hospital, Shunde, Guangdong, China
| | - Kai-Fu Kang
- Department of Pathology, The Shunde First People's Hospital, Shunde, Guangdong, China
| | - Guo-Biao Wu
- Department of Pathology, The Shunde First People's Hospital, Shunde, Guangdong, China
| | - Peng Wang
- Department of Infectious Diseases, The Shunde First People's Hospital, Shunde, Guangdong, China.
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13
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Nonalcoholic fatty liver disease-related cardiovascular risk: Is there an association with blood hemoglobin levels? Eur J Gastroenterol Hepatol 2015; 27:1126-9. [PMID: 26193051 DOI: 10.1097/meg.0000000000000434] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is emerging evidence on the relationship between NAFLD and increased cardiovascular risk. NAFLD is strongly associated with metabolic syndrome, but several other entities play a role in the pathogenesis of NAFLD more than metabolic syndrome. Currently, studies suggest that elevated hemoglobin levels are associated not only with the existence of nonalcoholic steatohepatitis but also with the severity of hepatic fibrosis. In this review, we aimed to discuss the potential role of high hemoglobin levels in the pathogenesis of NAFLD and NAFLD-associated cardiovascular risk.
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Akyuz U, Yesil A, Yilmaz Y. Characterization of lean patients with nonalcoholic fatty liver disease: potential role of high hemoglobin levels. Scand J Gastroenterol 2015; 50:341-6. [PMID: 25540973 DOI: 10.3109/00365521.2014.983160] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Overweight and obesity are major risk factors for the development of nonalcoholic fatty liver disease (NAFLD). However, a minority of NAFLD patients have a body mass index (BMI) <25 kg/m(2) (lean NAFLD). We sought to investigate whether significant differences exist between lean NAFLD and more common forms of NAFLD associated with overweight/obesity. PATIENTS AND METHODS A total of 483 consecutive patients with biopsy-proven NAFLD were enrolled. Lean NAFLD was defined as having a BMI <25 kg/m(2). We identified 37 patients with lean NAFLD (7.6%). RESULTS Compared with NAFLD patients with overweight/obesity, lean NAFLD patients were younger, had lower blood pressure values, higher levels of hemoglobin, a lower prevalence of the metabolic syndrome, and less severe hepatic fibrosis. In NAFLD patients with overweight/obesity, diabetes was the only independent predictor of nonalcoholic steatohepatitis (NASH). In lean NAFLD, the only variable independently associated with NASH was hemoglobin. Alanine aminotransferase and diabetes were independent predictors of fibrosis ≥2 in NAFLD patients with overweight/obesity, whereas hemoglobin was the only independent predictor of fibrosis ≥2 in lean NAFLD. CONCLUSION In summary, lean NAFLD patients are younger and show less severe hepatic fibrosis. However, such subjects have higher hemoglobin levels, which seem to predict the histological severity.
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Affiliation(s)
- Umit Akyuz
- Department of Gastroenterology, Medical Faculty, Yeditepe University , Istanbul , Turkey
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Lim JW, Dillon J, Miller M. Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis. World J Gastroenterol 2014; 20:8325-8340. [PMID: 25024592 PMCID: PMC4093687 DOI: 10.3748/wjg.v20.i26.8325] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 01/14/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.
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Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: the Zhejiang Zhenhai Study. Am J Gastroenterol 2013; 108:1299-304. [PMID: 23567356 DOI: 10.1038/ajg.2013.104] [Citation(s) in RCA: 123] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2012] [Accepted: 03/04/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The precise prevalence and risk factors for the development of nonalcoholic fatty liver disease (NAFLD) in nonobese adults remains unclear. The objective of this study was to investigate the prevalence of NAFLD and risk factors for its development in a nonobese Chinese population. METHODS We firstly investigated the prevalence and factors associated with the presence of NAFLD in nonobese (body mass index (BMI) <25 kg/m(2)) Chinese subjects via a cross-sectional study, and then analyzed the risk factors for the development of NAFLD via a subsequent prospective 5-year follow-up of the same population. RESULTS A total of 6,905 nonobese subjects were enrolled in the cross-sectional study. Baseline evaluation revealed that the prevalence of NAFLD was 7.27%. A total of 5,562 subjects who were free of NAFLD at baseline completed the follow-up study, and 494 (8.88%) had developed NAFLD during the 5-year follow-up. Further analyses revealed that age, gender, BMI, waist circumference, triglyceride, high-density lipoprotein (HDL) cholesterol, serum uric acid, hemoglobin, and platelet count were independently associated with the presence and development of NAFLD. CONCLUSIONS NAFLD is prevalent in the nonobese Chinese population, and a substantial proportion of subjects developed NAFLD over the 5-year follow-up period. Special attention should be paid to the factors associated with the presence and development of NAFLD in nonobese subjects, to improve prevention and management of NAFLD.
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Tarantino G, Finelli C. What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome? World J Gastroenterol 2013; 19:3375-3384. [PMID: 23801829 PMCID: PMC3683675 DOI: 10.3748/wjg.v19.i22.3375] [Citation(s) in RCA: 134] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2012] [Accepted: 01/24/2013] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently not a component of the diagnostic criteria for metabolic syndrome (MetS); however, the development of NAFLD has some common mechanisms with the development of MetS, as they share the pathophysiologic basis of insulin resistance. It is also recognized that NAFLD is the hepatic manifestation of MetS. To define MetS, the presence of at least three of the proposed criteria is required, and sometimes it is sufficient to have only one laboratory value, modified by diet or drugs, for the classification of MetS. Ultrasonographically-detected NAFLD (US-NAFLD) is more stable, only changing during the middle- to long-term. Although controversies over MetS continue, and considering that abdominal ultrasonography for diagnosing NAFLD has high specificity and guidelines to modify the natural course of NAFLD by diet composition or lifestyle have not yet been established, why should we not introduce US-NAFLD as a new criterion to define MetS?
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Beaton MD, Chakrabarti S, Levstik M, Speechley M, Marotta P, Adams P. Phase II clinical trial of phlebotomy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2013; 37:720-9. [PMID: 23441892 DOI: 10.1111/apt.12255] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Revised: 12/07/2012] [Accepted: 01/29/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Elevated iron indices are described in non-alcoholic fatty liver disease and iron reduction has been suggested as a potential therapy. AIM To determine whether phlebotomy is an effective therapy for non-alcoholic fatty liver disease. METHODS Patients with biopsy proven non-alcoholic fatty liver disease underwent baseline evaluation to determine severity of metabolic and liver disease. A Phase II trial of phlebotomy was carried out to achieve near-iron depletion (serum ferritin ≤50 μg/L or haemoglobin 100 g/L). Repeat liver biopsy, anthropometric and biochemical measurements were performed 6 months following the end of treatment. Primary outcome was improvement in liver histology, assessed using the non-alcoholic fatty liver disease activity score. RESULTS Thirty-one patients completed follow-up. Iron reduction resulted in a significant improvement in the non-alcoholic fatty liver disease activity score (-0.74 ± 1.83, P = 0.019). Reductions in individual histological features of lobular inflammation (-0.29 ± 1.07, P = 0.182), steatosis (-0.26 ± 0.82, P = 0.134), hepatocyte ballooning (-0.19 ± 0.70, P = 0.213) did not achieve significance nor did the score for fibrosis (-0.32 ± 0.94, P = 0.099). CONCLUSIONS This prospective Phase II study of phlebotomy with paired liver biopsies evaluating phlebotomy therapy in non-alcoholic fatty liver disease patients suggests that iron reduction may improve liver histology. However, the effect size of phlebotomy raises questions of whether treatment could have sufficient clinical significance to justify a definitive Phase III trial. This trial has been registered with the US National Institute of Health (clinicaltrials.gov, Identifier NCT 00641524).
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Affiliation(s)
- M D Beaton
- Division of Gastroenterology, University of Western Ontario, University Hospital, London, ON, Canada.
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Yilmaz Y. Is nonalcoholic fatty liver disease the hepatic expression of the metabolic syndrome? World J Hepatol 2012; 4:332-4. [PMID: 23355910 PMCID: PMC3554796 DOI: 10.4254/wjh.v4.i12.332] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Revised: 10/06/2012] [Accepted: 11/14/2012] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is generally considered as the hepatic manifestation of the metabolic syndrome (MS). Although there is no doubt that NAFLD is tightly linked to the MS, the diagnosis of NAFLD encompasses a broad range of histological entities and as a composite phenotype may be hindering attempts to understand the mechanistic basis of these variants. The awareness that NAFLD is not solely and invariably associated with the MS is a useful means to help direct future studies. We should be aware that mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. Further studies with special focus on hemoglobin as a risk factor for the development of NAFLD in the absence of MS should be performed.
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Affiliation(s)
- Yusuf Yilmaz
- Yusuf Yilmaz, Department of Gastroenterology, School of Medicine, Marmara University, 34840 Istanbul, Turkey
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Serum proteomics for biomarker discovery in nonalcoholic fatty liver disease. Clin Chim Acta 2012; 413:1190-3. [PMID: 22546610 DOI: 10.1016/j.cca.2012.04.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2012] [Revised: 04/14/2012] [Accepted: 04/17/2012] [Indexed: 02/08/2023]
Abstract
Proteomic platforms have gained increasing attention in the clinical spectrum of nonalcoholic fatty liver disease (NAFLD). This approach allows for the unbiased discovery of circulating biochemical markers, i.e., it is not limited to known molecules of presumed importance. This manuscript provides an overview of proteomic serum biomarker discovery in NAFLD. Hemoglobin is currently the most widely replicated proteomic circulating biomarker of NAFLD; it was identified as a biomarker of fatty liver in two distinct proteomic studies and subsequently validated using distinct analytical methods by independent research groups in large replication cohorts. Given the increasing availability of numerous serum samples and the refinement of the technological platforms available to scrutinize the blood proteome, large collaborative studies between academia and industry are warmly encouraged to identify novel, unbiased circulating biomarkers of NAFLD.
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Yilmaz Y, Senates E, Ayyildiz T, Colak Y, Tuncer I, Ovunc AOK, Dolar E, Kalayci C. Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome. Eur J Clin Invest 2012; 42:411-8. [PMID: 21913918 DOI: 10.1111/j.1365-2362.2011.02597.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MS). However, not all patients with the MS will develop NAFLD and not all patients with NAFLD have the MS. We sought to investigate the differences between patients with biopsy-proven NAFLD with and without the MS. METHODS A total of 357 consecutive patients with biopsy-proven NAFLD were analysed. Of them, 216 patients had nonalcoholic steatohepatitis (NASH) and 96 a fibrosis score ≥ 2. The MS was defined as ≥ 3 of the ATP III criteria. RESULTS A total of 214 patients with NAFLD met the criteria for the MS, while the remaining 143 did not. In NAFLD patients with the MS, homeostasis model of insulin resistance (P = 0·03; OR, 1·06; 95% CI, 1·023-1·25 per unit increase) and diabetes (P = 0·01; OR, 1·2; 95% CI, 1·1-2·4) were independent predictors of NASH. In NAFLD patients without the MS, the only variable independently associated with NASH was haemoglobin (P = 0·007; OR, 1·9; 95% CI, 1·4-3·6 per 50 g/L increase). Alanine aminotransferase (P = 0·03; OR, 1·04; 95% CI, 1·006-1·11 per 10 U/L increase) was an independent predictor of fibrosis ≥ 2 in NAFLD patients with the MS, while haemoglobin (P = 0·02; OR, 1·4; 95% CI, 1·2-1·9 per 50 g/L increase) was the only variable significantly associated with fibrosis ≥ 2 in NAFLD patients without the MS. CONCLUSIONS Increased haemoglobin in NAFLD subjects without MS should be considered in the selection of cases for histological assessment.
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Affiliation(s)
- Yusuf Yilmaz
- Department of Gastroenterology, Marmara University, School of Medicine, Pendik, Istanbul, Turkey.
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Yu C, Xu C, Xu L, Yu J, Miao M, Li Y. Serum proteomic analysis revealed diagnostic value of hemoglobin for nonalcoholic fatty liver disease. J Hepatol 2012; 56:241-7. [PMID: 21756851 DOI: 10.1016/j.jhep.2011.05.027] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2010] [Revised: 05/08/2011] [Accepted: 05/11/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The two linked studies presented herein aimed to identify and verify new biomarkers for NAFLD. METHODS First, 70 serum samples were analyzed using proteomics approaches to identify potential biomarkers for NAFLD. Second, a total of 6944 initial NAFLD-free subjects were followed up for 3 years to evaluate the predictive value of hemoglobin for NAFLD. RESULTS In the first study, 20 differentially expressed protein peaks (11 up-regulated and nine down-regulated) were observed in NAFLD patients upon comparison to the controls. With the aid of bioinformatic tools, we established a biomarker pattern for NAFLD with a sensitivity of 89% and a specificity of 83%. Further analysis suggested a protein peak to be hemoglobin subunit alpha. In the second study, prospective analysis showed that subjects with higher baseline hemoglobin levels were associated with higher incidence of NAFLD. Cox proportional hazards regression analyses showed that the age, gender, and body mass index adjusted hazard ratio (95% CI) for subjects with baseline hemoglobin level in quintile 2, 3, 4, and 5 vs. quintile 1 was 1.36 (1.02-1.81), 1.66 (1.23-2.25), 1.76 (1.28-2.41), and 1.83 (1.33-2.53), respectively. CONCLUSIONS Our study showed that serum hemoglobin may have significant predictive value for NAFLD.
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Affiliation(s)
- Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
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Liu W, Baker SS, Baker RD, Nowak NJ, Zhu L. Upregulation of hemoglobin expression by oxidative stress in hepatocytes and its implication in nonalcoholic steatohepatitis. PLoS One 2011; 6:e24363. [PMID: 21931690 PMCID: PMC3171444 DOI: 10.1371/journal.pone.0024363] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Accepted: 08/08/2011] [Indexed: 12/11/2022] Open
Abstract
Recent studies revealed that hemoglobin is expressed in some non-erythrocytes and it suppresses oxidative stress when overexpressed. Oxidative stress plays a critical role in the pathogenesis of non-alcoholic steatohepatitis (NASH). This study was designed to investigate whether hemoglobin is expressed in hepatocytes and how it is related to oxidative stress in NASH patients. Analysis of microarray gene expression data revealed a significant increase in the expression of hemoglobin alpha (HBA1) and beta (HBB) in liver biopsies from NASH patients. Increased hemoglobin expression in NASH was validated by quantitative real time PCR. However, the expression of hematopoietic transcriptional factors and erythrocyte specific marker genes were not increased, indicating that increased hemoglobin expression in NASH was not from erythropoiesis, but could result from increased expression in hepatocytes. Immunofluorescence staining demonstrated positive HBA1 and HBB expression in the hepatocytes of NASH livers. Hemoglobin expression was also observed in human hepatocellular carcinoma HepG2 cell line. Furthermore, treatment with hydrogen peroxide, a known oxidative stress inducer, increased HBA1 and HBB expression in HepG2 and HEK293 cells. Importantly, hemoglobin overexpression suppressed oxidative stress in HepG2 cells. We concluded that hemoglobin is expressed by hepatocytes and oxidative stress upregulates its expression. Suppression of oxidative stress by hemoglobin could be a mechanism to protect hepatocytes from oxidative damage in NASH.
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Affiliation(s)
- Wensheng Liu
- Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, United States of America
| | - Susan S. Baker
- Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, United States of America
| | - Robert D. Baker
- Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, United States of America
| | - Norma J. Nowak
- Department of Biochemistry and the New York State Center of Excellence in Bioinformatics and Life Sciences, The State University of New York at Buffalo, Buffalo, New York, United States of America
- Microarray and Genomics Facility, Roswell Park Cancer Institute, Buffalo, New York, United States of America
| | - Lixin Zhu
- Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, United States of America
- * E-mail:
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