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Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations

Published online by Cambridge University Press:  22 March 2013

S. Zelber-Sagi ,
S. Toker ,
G. Armon ,
S. Melamed ,
S. Berliner ,
I. Shapira ,
Z. Halpern ,
E. Santo  and
O. Shibolet
S. Zelber-Sagi
Affiliation:
Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel School of Public Health, University of Haifa, Haifa, Israel
S. Toker
Affiliation:
Department of Organizational Behavior, Faculty of Management, Tel Aviv University, Tel Aviv, Israel
G. Armon
Affiliation:
Department of Psychology, Faculty of Social Science, University of Haifa, Haifa, Israel
S. Melamed
Affiliation:
The Academic College of Tel Aviv-Yaffo, Tel Aviv, Israel The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
S. Berliner
Affiliation:
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Internal Medicine Department E, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
I. Shapira
Affiliation:
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Internal Medicine Department E, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
Z. Halpern
Affiliation:
Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
E. Santo
Affiliation:
Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
O. Shibolet*
Affiliation:
Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
*
*Address for correspondence: O. Shibolet, M.D., Liver Unit, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. (Email: orensh@tasmc.health.gov.il)
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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression.

Method

The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score.

Results

The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40–2.92] and major (OR 3.132, 95% CI 1.81–5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001).

Conclusions

Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.

Keywords

Alanine aminotransferasedepressionnon-alcoholic fatty liver diseaseprospective cohort studies
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 12 , December 2013 , pp. 2603 - 2613
Copyright
Copyright © Cambridge University Press 2013 

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References

Andersen, LB, Harro, M, Sardinha, LB, Froberg, K, Ekelund, U, Brage, S, Anderssen, SA (2006). Physical activity and clustered cardiovascular risk in children: a cross-sectional study (The European Youth Heart Study). Lancet 368, 299–304.CrossRefGoogle ScholarPubMed
Anderson, RJ, Freedland, KE, Clouse, RE, Lustman, PJ (2001). The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24, 1069–1078.CrossRefGoogle ScholarPubMed
Andre, F (2000). Hepatitis B epidemiology in Asia, the Middle East and Africa. Vaccine 18 (Suppl. 1), S20–S22.CrossRefGoogle ScholarPubMed
Anisman, H, Merali, Z, Hayley, S (2008). Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Progress in Neurobiology 85, 1–74.CrossRefGoogle ScholarPubMed
Armstrong, MJ, Houlihan, DD, Bentham, L, Shaw, JC, Cramb, R, Olliff, S, Gill, PS, Neuberger, JM, Lilford, RJ, Newsome, PN (2012). Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. Journal of Hepatology 56, 234–240.CrossRefGoogle Scholar
Ayalon, L, Goldfracht, M, Bech, P (2010). ‘Do you think you suffer from depression?’ Reevaluating the use of a single item question for the screening of depression in older primary care patients. International Journal of Geriatric Psychiatry 25, 497–502.CrossRefGoogle Scholar
Bar-Shany, S, Green, MS, Slepon, R, Shinar, E (1995). Ethnic differences in the prevalence of anti-hepatitis C antibodies and hepatitis B surface antigen in Israeli blood donors by age, sex, country of birth and origin. Journal of Viral Hepatitis 2, 139–144.CrossRefGoogle ScholarPubMed
Basaranoglu, M, Kayacetin, S, Yilmaz, N, Kayacetin, E, Tarcin, O, Sonsuz, A (2010). Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease. World Journal of Gastroenterology 16, 2223–2226.CrossRefGoogle ScholarPubMed
Baumeister, SE, Volzke, H, Marschall, P, John, U, Schmidt, CO, Flessa, S, Alte, D (2008). Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology 134, 85–94.CrossRefGoogle Scholar
Bedogni, G, Miglioli, L, Masutti, F, Tiribelli, C, Marchesini, G, Bellentani, S (2005). Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42, 44–52.CrossRefGoogle ScholarPubMed
Bellentani, S, Saccoccio, G, Masutti, F, Croce, LS, Brandi, G, Sasso, F, Cristanini, G, Tiribelli, C (2000). Prevalence of and risk factors for hepatic steatosis in Northern Italy. Annals of Internal Medicine 132, 112–117.CrossRefGoogle ScholarPubMed
Brown, ES, Varghese, FP, McEwen, BS (2004). Association of depression with medical illness: does cortisol play a role? Biological Psychiatry 55, 1–9.CrossRefGoogle ScholarPubMed
Browning, JD, Szczepaniak, LS, Dobbins, R, Nuremberg, P, Horton, JD, Cohen, JC, Grundy, SM, Hobbs, HH (2004). Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395.CrossRefGoogle Scholar
Bugianesi, E, Moscatiello, S, Ciaravella, MF, Marchesini, G (2010). Insulin resistance in nonalcoholic fatty liver disease. Current Pharmaceutical Design 16, 1941–1951.CrossRefGoogle ScholarPubMed
Chen, PH, Chen, JD, Lin, YC (2009). A better parameter in predicting insulin resistance: obesity plus elevated alanine aminotransferase. World Journal of Gastroenterology 15, 5598–5603.CrossRefGoogle ScholarPubMed
Clark, JM, Diehl, AM (2003). Defining nonalcoholic fatty liver disease: implications for epidemiologic studies. Gastroenterology 124, 248–250.CrossRefGoogle ScholarPubMed
Cowen, PJ (2010). Editorial: not fade away: the HPA axis and depression. Psychological Medicine 40, 1–4.CrossRefGoogle Scholar
Dan, AA, Kallman, JB, Wheeler, A, Younoszai, Z, Collantes, R, Bondini, S, Gerber, L, Younossi, ZM (2007). Health-related quality of life in patients with non-alcoholic fatty liver disease. Alimentary Pharmacology and Therapeutics 26, 815–820.CrossRefGoogle ScholarPubMed
Dantzer, R, O'Connor, JC, Freund, GG, Johnson, RW, Kelley, KW (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience 9, 46–56.CrossRefGoogle ScholarPubMed
Dantzer, R, O'Connor, JC, Lawson, MA, Kelley, KW (2011). Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology 36, 426–436.CrossRefGoogle ScholarPubMed
David, K, Kowdley, KV, Unalp, A, Kanwal, F, Brunt, EM, Schwimmer, JB (2009). Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network. Hepatology 49, 1904–1912.CrossRefGoogle ScholarPubMed
DeSalvo, KB, Bloser, N, Reynolds, K, He, J, Muntner, P (2006). Mortality prediction with a single general self-rated health question. A meta-analysis. Journal of General Internal Medicine 21, 267–275.CrossRefGoogle ScholarPubMed
Elwing, JE, Lustman, PJ, Wang, HL, Clouse, RE (2006). Depression, anxiety, and nonalcoholic steatohepatitis. Psychosomatic Medicine 68, 563–569.CrossRefGoogle ScholarPubMed
Fracanzani, AL, Valenti, L, Bugianesi, E, Andreoletti, M, Colli, A, Vanni, E, Bertelli, C, Fatta, E, Bignamini, D, Marchesini, G, Fargion, S (2008). Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 48, 792–798.CrossRefGoogle Scholar
Fracanzani, AL, Valenti, L, Bugianesi, E, Vanni, E, Grieco, A, Miele, L, Consonni, D, Fatta, E, Lombardi, R, Marchesini, G, Fargion, S (2011). Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity. Journal of Hepatology 54, 1244–1249.CrossRefGoogle ScholarPubMed
French, JRP, Caplan, RD, Harrison, RV (1982). The Mechanisms of Job Stress and Strain. John Wiley and Sons: Chichester.Google Scholar
Fujii, H, Kawada, N (2012). Inflammation and fibrogenesis in steatohepatitis. Journal of Gastroenterology 47, 215–225.CrossRefGoogle ScholarPubMed
Green, RM, Flamm, S (2002). AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 123, 1367–1384.CrossRefGoogle ScholarPubMed
Gutteling, JJ, de Man, RA, van der Plas, SM, Schalm, SW, Busschbach, JJ, Darlington, AS (2006). Determinants of quality of life in chronic liver patients. Alimentary Pharmacology and Therapeutics 23, 1629–1635.CrossRefGoogle ScholarPubMed
Herrera-Marquez, R, Hernandez-Rodriguez, J, Medina-Serrano, J, Boyzo-Montes de Oca, A, Manjarrez-Gutierrez, G (2011). Association of metabolic syndrome with reduced central serotonergic activity. Metabolic Brain Disease 26, 29–35.CrossRefGoogle ScholarPubMed
Hobfoll, SE, Canetti, D, Hall, BJ, Brom, D, Palmieri, PA, Johnson, RJ, Pat-Horenczyk, R, Galea, S (2011). Are community studies of psychological trauma's impact accurate? A study among Jews and Palestinians. Psychological Assessment 23, 599–605.CrossRefGoogle ScholarPubMed
Hobfoll, SE, Canetti-Nisim, D, Johnson, RJ (2006). Exposure to terrorism, stress-related mental health symptoms, and defensive coping among Jews and Arabs in Israel. Journal of Consulting and Clinical Psychology 74, 207–218.CrossRefGoogle ScholarPubMed
Insel, TR, Charney, DS (2003). Research on major depression: strategies and priorities. Journal of the American Medical Association 289, 3167–3168.CrossRefGoogle ScholarPubMed
Kariv, R, Leshno, M, Beth-Or, A, Strul, H, Blendis, L, Kokia, E, Noff, D, Zelber-Sagie, S, Sheinberg, B, Oren, R, Halpern, Z (2006). Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study. Liver International 26, 445–450.CrossRefGoogle Scholar
Kashyap, SR, Diab, DL, Baker, AR, Yerian, L, Bajaj, H, Gray-McGuire, C, Schauer, PR, Gupta, M, Feldstein, AE, Hazen, SL, Stein, CM (2009). Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring) 17, 1696–1701.CrossRefGoogle ScholarPubMed
Kerkar, N, D'Urso, C, Van Nostrand, K, Kochin, I, Gault, A, Suchy, F, Miloh, T, Arnon, R, Chu, J, Annunziato, R (2013). Psychosocial outcomes for children with nonalcoholic fatty liver disease over time and compared to obese controls. Journal of Pediatric Gastroenterology and Nutrition 56, 77–82.CrossRefGoogle ScholarPubMed
Kroenke, K, Spitzer, RL, Williams, JBW, Löwe, B (2010). The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. General Hospital Psychiatry 32, 345–359.CrossRefGoogle ScholarPubMed
Kroenke, K, Strine, TW, Spitzer, RL, Williams, JB, Berry, JT, Mokdad, AH (2009). The PHQ-8 as a measure of current depression in the general population. Journal of Affective Disorders 114, 163–173.CrossRefGoogle ScholarPubMed
Lee, CK, Jonas, MM (2007). High prevalence of psychiatric and attention-deficit/hyperactivity disorders in children with NAFLD at children's hospital Boston 1995–2005: a retrospective study. Gastroenterology 132, A738–A739.Google Scholar
Lett, HS, Blumenthal, JA, Babyak, MA, Sherwood, A, Strauman, T, Robins, C, Newman, MF (2004). Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosomatic Medicine 66, 305–315.Google ScholarPubMed
Lotrich, FE, El-Gabalawy, H, Guenther, LC, Ware, CF (2011). The role of inflammation in the pathophysiology of depression: different treatments and their effects. Journal of Rheumatology Supplement 88, 48–54.CrossRefGoogle Scholar
Marchesini, G, Brizi, M, Bianchi, G, Tomassetti, S, Bugianesi, E, Lenzi, M, McCullough, AJ, Natale, S, Forlani, G, Melchionda, N (2001). Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50, 1844–1850.CrossRefGoogle ScholarPubMed
Milaneschi, Y, Corsi, AM, Penninx, BW, Bandinelli, S, Guralnik, JM, Ferrucci, L (2009). Interleukin-1 receptor antagonist and incident depressive symptoms over 6 years in older persons: the InCHIANTI study. Biological Psychiatry 65, 973–978.CrossRefGoogle ScholarPubMed
Miller, AH (2009). Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behavior and Immunity 23, 149–158.CrossRefGoogle Scholar
Miller, GE, Freedland, KE, Carney, RM, Stetler, CA, Banks, WA (2003). Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behavior and Immunity 17, 276–285.CrossRefGoogle ScholarPubMed
Moussavi, S, Chatterji, S, Verdes, E, Tandon, A, Patel, V, Ustun, B (2007). Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370, 851–858.CrossRefGoogle ScholarPubMed
Muldoon, MF, Mackey, RH, Korytkowski, MT, Flory, JD, Pollock, BG, Manuck, SB (2006). The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers. Journal of Clinical Endocrinology and Metabolism 91, 718–721.CrossRefGoogle ScholarPubMed
Newton, JL, Jones, DE, Henderson, E, Kane, L, Wilton, K, Burt, AD, Day, CP (2008). Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 57, 807–813.CrossRefGoogle ScholarPubMed
Nguyen, QM, Srinivasan, SR, Xu, JH, Chen, W, Hassig, S, Rice, J, Berenson, GS (2011). Elevated liver function enzymes are related to the development of prediabetes and type 2 diabetes in younger adults: the Bogalusa Heart Study. Diabetes Care 34, 2603–2607.CrossRefGoogle Scholar
Omagari, K, Takamura, R, Matsutake, S, Ichimura, M, Kato, S, Morikawa, S, Nagaoka, S, Osabe, M (2011). Serum alanine aminotransferase concentration as a predictive factor for the development or regression of fatty liver. Journal of Clinical Biochemisty and Nutrition 49, 200–206.CrossRefGoogle ScholarPubMed
Pearson, S, Schmidt, M, Patton, G, Dwyer, T, Blizzard, L, Otahal, P, Venn, A (2010). Depression and insulin resistance: cross-sectional associations in young adults. Diabetes Care 33, 1128–1133.CrossRefGoogle ScholarPubMed
Prati, D, Taioli, E, Zanella, A, Della Torre, E, Butelli, S, Del Vecchio, E, Vianello, L, Zanuso, F, Mozzi, F, Milani, S, Conte, D, Colombo, M, Sirchia, G (2002). Updated definitions of healthy ranges for serum alanine aminotransferase levels. Annals of Internal Medicine 137, 1–10.CrossRefGoogle ScholarPubMed
Pratt, DS, Kaplan, MM (2000). Evaluation of abnormal liver-enzyme results in asymptomatic patients. New England Journal of Medicine 342, 1266–1271.CrossRefGoogle ScholarPubMed
Pressler, SJ, Subramanian, U, Perkins, SM, Gradus-Pizlo, I, Kareken, D, Kim, J, Ding, Y, Sauvé, MJ, Sloan, R (2011). Measuring depressive symptoms in heart failure: validity and reliability of the Patient Health Questionnaire-8. American Journal of Critical Care 20, 146–152.CrossRefGoogle ScholarPubMed
Raison, CL, Capuron, L, Miller, AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 24–31.CrossRefGoogle ScholarPubMed
Richards, D (2011). Prevalence and clinical course of depression: a review. Clinical Psychology Review 31, 1117–1125.CrossRefGoogle ScholarPubMed
Richardson, CR, Kriska, AM, Lantz, PM, Hayward, RA (2004). Physical activity and mortality across cardiovascular disease risk groups. Medicine and Science in Sports and Exercise 36, 1923–1929.CrossRefGoogle ScholarPubMed
Sayuk, GS, El-Dirani, S, Elwing, JE, Lustman, P, Lisker-Melman, M, Crippin, JS, Clouse, RE (2007). Severity of depression symptoms and transaminase levels are related in non-alcoholic steatohepatitis (NASH) and chronic hepatitis C. Gastroenterology 132, A-813.Google Scholar
Schillinger, M, Exner, M, Amighi, J, Mlekusch, W, Sabeti, S, Rumpold, H, Wagner, O, Minar, E (2003). Joint effects of C-reactive protein and glycated hemoglobin in predicting future cardiovascular events of patients with advanced atherosclerosis. Circulation 108, 2323–2328.CrossRefGoogle ScholarPubMed
Sermoneta-Gertel, S, Donchin, M, Adler, R, Baras, M, Perlstein, T, Manny, N, Shouval, D, Galun, E (2001). Hepatitis C virus infection in employees of a large university hospital in Israel. Infection Control and Hospital Epidemiology 22, 754–761.CrossRefGoogle ScholarPubMed
Shirom, A (1989). Burnout in work organizations. In International Review of Industrial and Organizational Psychology (ed. Cooper, C. L. and Robertson, I.), pp. 25–48. Wiley: New York.Google Scholar
Shirom, A (2003). Job-related burnout. In Handbook of Occupational Health Psychology (ed. Quick, J. C. and Tetrick, L. E.), pp. 245–265. American Psychological Association: Washington, DC.CrossRefGoogle Scholar
Silva, N, Atlantis, E, Ismail, K (2011). A review of the association between depression and insulin resistance: pitfalls of secondary analyses or a promising new approach to prevention of type 2 diabetes? Current Psychiatry Reports 14, 8–14.CrossRefGoogle Scholar
Simon, GE, Goldberg, DP, Von Korff, M, Ustun, TB (2002). Understanding cross-national differences in depression prevalence. Psychological Medicine 32, 585–594.CrossRefGoogle ScholarPubMed
Soldatos, CR, Dikeos, DG, Paparrigopoulos, TJ (2000). Athens Insomnia Scale: validation of an instrument based on ICD-10 criteria. Journal of Psychosomatic Research 48, 555–560.CrossRefGoogle ScholarPubMed
Stanca, CM, Bach, N, Krause, C, Tandon, N, Freni, MA, Gutierrez, JA, Bodian, C, Lopez, J, Berk, PD, Bodenheimer, HC Jr, Branch, AD, Odin, JA (2005). Evaluation of fatigue in U.S. patients with primary biliary cirrhosis. American Journal of Gastroenterology 100, 1104–1109.CrossRefGoogle ScholarPubMed
Suzuki, A, Binks, M, Wachholtz, A, Diehl, AM (2007). Relationship of psychological issues and sleep disturbance to liver function in obese patients at a residential weight loss program. Gastroenterology 132, A-811.Google Scholar
Swain, MG (2006). Fatigue in liver disease: pathophysiology and clinical management. Canadian Journal of Gastroenterology 20, 181–188.CrossRefGoogle ScholarPubMed
Taylor, VH, Macqueen, GM (2010). The role of adipokines in understanding the associations between obesity and depression. Journal of Obesity 2010, 748048.CrossRefGoogle ScholarPubMed
Tilg, H (2010). The role of cytokines in non-alcoholic fatty liver disease. Digestive Diseases 28, 179–185.CrossRefGoogle ScholarPubMed
Timonen, M, Laakso, M, Jokelainen, J, Rajala, U, Meyer-Rochow, VB, Keinanen-Kiukaanniemi, S (2005). Insulin resistance and depression: cross sectional study. British Medical Journal 330, 17–18.CrossRefGoogle ScholarPubMed
Toker, S, Biron, M (2012). Job burnout and depression: unraveling their temporal relationship and considering the role of physical activity. Journal of Applied Psychology 97, 699–710.CrossRefGoogle ScholarPubMed
Toker, S, Shirom, A, Melamed, S (2008). Depression and the metabolic syndrome: gender-dependent associations. Depression and Anxiety 25, 661–669.CrossRefGoogle ScholarPubMed
Weinstein, AA, Kallman Price, J, Stepanova, M, Poms, LW, Fang, Y, Moon, J, Nader, F, Younossi, ZM (2011). Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C. Psychosomatics 52, 127–132.CrossRefGoogle ScholarPubMed
Wong, VW, Wong, GL, Choi, PC, Chan, AW, Li, MK, Chan, HY, Chim, AM, Yu, J, Sung, JJ, Chan, HL (2010). Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 59, 969–974.CrossRefGoogle ScholarPubMed
Younossi, ZM, Boparai, N, Price, LL, Kiwi, ML, McCormick, M, Guyatt, G (2001). Health-related quality of life in chronic liver disease: the impact of type and severity of disease. American Journal of Gastroenterology 96, 2199–2205.CrossRefGoogle ScholarPubMed
Zelber-Sagi, S, Nitzan-Kaluski, D, Halpern, Z, Oren, R (2006). Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver International 26, 856–863.CrossRefGoogle Scholar
Zelber-Sagi, S, Ratziu, V, Oren, R (2011). Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World Journal of Gastroenterology 17, 3377–3389.CrossRefGoogle ScholarPubMed