De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation

Clinics in Liver Disease

Volumn 21, Issue 2, 2017, Pages 321-335

  Kappus, Matthew ^a   Abdelmalek, Manal ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Cryptogenic cirrhosis; Hyperlipidemia; Hypertension; Insulin resistance; Metabolic syndrome; Nonalcoholic fatty liver disease; Obesity

Indexed keywords

CALCINEURIN INHIBITOR; CORTICOSTEROID; CYCLOSPORIN; CYCLOSPORIN A; GLUCOCORTICOID; IMMUNOSUPPRESSIVE AGENT; MYCOPHENOLATE MOFETIL; RAPAMYCIN; TACROLIMUS;

AGE; COMORBIDITY; DE NOVO NONALCOHOLIC FATTY LIVER; ETHNICITY; GENDER; GENETICS; GRAFT RECIPIENT; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LIFESTYLE MODIFICATION; LIVER GRAFT REJECTION; LIVER TRANSPLANTATION; METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; NONHUMAN; ORGAN DONOR; PHYSICAL ACTIVITY; RECURRENT DISEASE; REVIEW; RISK FACTOR; WEIGHT GAIN; GLOBAL HEALTH; INCIDENCE; POSTOPERATIVE COMPLICATION;

GLOBAL HEALTH; HUMANS; INCIDENCE; LIVER TRANSPLANTATION; NON-ALCOHOLIC FATTY LIVER DISEASE; POSTOPERATIVE COMPLICATIONS; RECURRENCE; RISK FACTORS;

EID: 85011060358     PISSN: 10893261     EISSN: 15578224     Source Type: Journal    
DOI: 10.1016/j.cld.2016.12.006     Document Type: Review

References (110)

1. 1 Torres, D.M., Williams, C.D., Harrison, S.A., Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 10:8 (2012), 837–858.
2. 2 Ong, J.P., Younossi, Z.M., Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 11:1 (2007), 1–16 vii.
3. 3 Ratziu, V., Goodman, Z., Sanyal, A., Current efforts and trends in the treatment of NASH. J Hepatol 62:1 Suppl (2015), S65–S75.
4. 4 Vernon, G., Baranova, A., Younossi, Z.M., Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:3 (2011), 274–285.
5. 5 Mittal, S., El-Serag, H.B., Sada, Y.H., et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 14:1 (2016), 124–131.e1.
6. 6 Schuppan, D., Schattenberg, J.M., Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol 28:Suppl 1 (2013), 68–76.
7. 7 White, D.L., Kanwal, F., El-Serag, H.B., Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol 10:12 (2012), 1342–1359.e2.
8. 8 Younossi, Z.M., Stepanova, M., Rafiq, N., et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 53:6 (2011), 1874–1882.
9. 9 Angulo, P., Kleiner, D.E., Dam-Larsen, S., et al. Liver fibrosis, but No other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149:2 (2015), 389–397.e10.
10. 10 Angulo, P., Keach, J.C., Batts, K.P., et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30:6 (1999), 1356–1362.
11. 11 Ong, J.P., Elariny, H., Collantes, R., et al. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes Surg 15:3 (2005), 310–315.
12. 12 Charlton, M., Evolving aspects of liver transplantation for nonalcoholic steatohepatitis. Curr Opin Organ Transplant 18:3 (2013), 251–258.
13. 13 Friman, S., Recurrence of disease after liver transplantation. Transplant Proc 45:3 (2013), 1178–1181.
14. 14 Ong, J., Younossi, Z.M., Reddy, V., et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl 7:9 (2001), 797–801.
15. 15 Malik, S.M., Devera, M.E., Fontes, P., et al. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl 15:12 (2009), 1843–1851.
16. 16 Marsman, W.A., Wiesner, R.H., Rodriguez, L., et al. Use of fatty donor liver is associated with diminished early patient and graft survival. Transplantation 62:9 (1996), 1246–1251.
17. 17 Hines, C.D., Frydrychowicz, A., Hamilton, G., et al. T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:4 (2011), 873–881.
18. 18 Kosmalski, M., Kasznicki, J., Drzewoski, J., Relationship between ultrasound features of nonalcoholic fatty liver disease and cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. Pol Arch Med Wewn 123:9 (2013), 436–442.
19. 19 Wong, T.C., Fung, J.Y., Chok, K.S., et al. Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors. Liver Transpl 22:2 (2016), 226–236.
20. 20 Tanaka, T., Sugawara, Y., Tamura, S., et al. Living donor liver transplantation for non-alcoholic steatohepatitis: a single center experience. Hepatol Res 44:10 (2014), E3–E10.
21. 21 Aduen, J.F., Sujay, B., Dickson, R.C., et al. Outcomes after liver transplant in patients aged 70 years or older compared with those younger than 60 years. Mayo Clin Proc 84:11 (2009), 973–978.
22. 22 Shimada, M., Hashimoto, E., Kaneda, H., et al. Nonalcoholic steatohepatitis: risk factors for liver fibrosis. Hepatol Res 24:4 (2002), 429–438.
23. 23 Kemmer, N., Neff, G.W., Franco, E., et al. Nonalcoholic fatty liver disease epidemic and its implications for liver transplantation. Transplantation 96:10 (2013), 860–862.
24. 24 Collins, B.H., Pirsch, J.D., Becker, Y.T., et al. Long-term results of liver transplantation in older patients 60 years of age and older. Transplantation 70:5 (2000), 780–783.
25. 25 Emre, S., Mor, E., Schwartz, M.E., et al. Liver transplantation in patients beyond age 60. Transplant Proc 25:1 Pt 2 (1993), 1075–1076.
26. 26 Ford, E.S., Giles, W.H., Dietz, W.H., Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:3 (2002), 356–359.
27. 27 Hildrum, B., Mykletun, A., Hole, T., et al. Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education program: the Norwegian HUNT 2 study. BMC Public Health, 7, 2007, 220.
28. 28 Ravaglia, G., Forti, P., Maioli, F., et al. Metabolic syndrome: prevalence and prediction of mortality in elderly individuals. Diabetes Care 29:11 (2006), 2471–2476.
29. 29 Saad, M.A., Cardoso, G.P., Martins Wde, A., et al. Prevalence of metabolic syndrome in elderly and agreement among four diagnostic criteria. Arq Bras Cardiol 102:3 (2014), 263–269.
30. 30 Chatterjee, A., Basu, A., Chowdhury, A., et al. Comparative analyses of genetic risk prediction methods reveal extreme diversity of genetic predisposition to nonalcoholic fatty liver disease (NAFLD) among ethnic populations of India. J Genet 94:1 (2015), 105–113.
31. 31 Weston, S.R., Leyden, W., Murphy, R., et al. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 41:2 (2005), 372–379.
32. 32 Graham, R.C., Burke, A., Stettler, N., Ethnic and sex differences in the association between metabolic syndrome and suspected nonalcoholic fatty liver disease in a nationally representative sample of US adolescents. J Pediatr Gastroenterol Nutr 49:4 (2009), 442–449.
33. 33 Browning, J.D., Szczepaniak, L.S., Dobbins, R., et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40:6 (2004), 1387–1395.
34. 34 Giday, S.A., Ashiny, Z., Naab, T., et al. Frequency of nonalcoholic fatty liver disease and degree of hepatic steatosis in African-American patients. J Natl Med Assoc 98:10 (2006), 1613–1615.
35. 35 Solga, S.F., Clark, J.M., Alkhuraishi, A.R., et al. Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients. Surg Obes Relat Dis 1:1 (2005), 6–11.
36. 36 WHO Expert Consultation, Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:9403 (2004), 157–163.
37. 37 Deurenberg, P., Yap, M., van Staveren, W.A., Body mass index and percent body fat: a meta-analysis among different ethnic groups. Int J Obes Relat Metab Disord 22:12 (1998), 1164–1171.
38. 38 Okosun, I.S., Dever, G.E., Abdominal obesity and ethnic differences in diabetes awareness, treatment, and glycemic control. Obes Res 10:12 (2002), 1241–1250.
39. 39 Ruhl, C.E., Everhart, J.E., Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 124:1 (2003), 71–79.
40. 40 Younossi, Z.M., Stepanova, M., Negro, F., et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 91:6 (2012), 319–327.
41. 41 Neuschwander-Tetri, B.A., Clark, J.M., Bass, N.M., et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 52:3 (2010), 913–924.
42. 42 Rodriguez-Castro, K.I., De Martin, E., Gambato, M., et al. Female gender in the setting of liver transplantation. World J Transplant 4:4 (2014), 229–242.
43. 43 Suzuki, A., Abdelmalek, M.F., Unalp-Arida, A., et al. Regional anthropometric measures and hepatic fibrosis in patients with nonalcoholic Fatty liver disease. Clin Gastroenterol Hepatol 8:12 (2010), 1062–1069.
44. 44 Yang, J.D., Abdelmalek, M.F., Pang, H., et al. Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology 59:4 (2014), 1406–1414.
45. 45 Yang, J.D., Abdelmalek, M.F., Guy, C.D., et al. Patient sex, reproductive status, and synthetic hormone use associate with histologic severity of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 15:1 (2016), 127–131.e2.
46. 46 Guerrero, R., Vega, G.L., Grundy, S.M., et al. Ethnic differences in hepatic steatosis: an insulin resistance paradox?. Hepatology 49:3 (2009), 791–801.
47. 47 Schwimmer, J.B., Celedon, M.A., Lavine, J.E., et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology 136:5 (2009), 1585–1592.
48. 48 Dongiovanni, P., Donati, B., Fares, R., et al. PNPLA3 I148M polymorphism and progressive liver disease. World J Gastroenterol 19:41 (2013), 6969–6978.
49. 49 Romeo, S., Kozlitina, J., Xing, C., et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:12 (2008), 1461–1465.
50. 50 Zelber-Sagi, S., Salomone, F., Yeshua, H., et al. Non-high-density lipoprotein cholesterol independently predicts new onset of non-alcoholic fatty liver disease. Liver Int 34:6 (2014), e128–e135.
51. 51 Mohamed, J., Nazratun Nafizah, A.H., Zariyantey, A.H., et al. Mechanisms of diabetes-induced liver damage: the role of oxidative stress and inflammation. Sultan Qaboos Univ Med J 16:2 (2016), e132–e141.
52. 52 Dongiovanni, P., Valenti, L., Rametta, R., et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease. Gut 59:2 (2010), 267–273.
53. 53 Valenti, L., Rametta, R., Dongiovanni, P., et al. The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease. PLoS One, 7(11), 2012, e48804.
54. 54 Finkenstedt, A., Auer, C., Glodny, B., et al. Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clin Gastroenterol Hepatol 11:12 (2013), 1667–1672.
55. 55 Liu, Z.T., Chen, T.C., Lu, X.X., et al. PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients. World J Gastroenterol 21:34 (2015), 10054–10056.
56. 56 Leone, L., Ippoliti, P.F., Antonicelli, R., et al. Treatment and liver transplantation for cholesterol ester storage disease. J Pediatr 127:3 (1995), 509–510.
57. 57 Jankowska, I., Socha, P., Pawlowska, J., et al. Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy. Pediatr Transplant 11:7 (2007), 796–798.
58. 58 Molloy, R.M., Komorowski, R., Varma, R.R., Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation. Liver Transpl Surg 3:2 (1997), 177–178.
59. 59 Hamilton, J., Jones, I., Srivastava, R., et al. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta 413:15–16 (2012), 1207–1210.
60. 60 Valayannopoulos, V., Malinova, V., Honzik, T., et al. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol 61:5 (2014), 1135–1142.
61. 61 Kim, W.R., Smith, J.M., Skeans, M.A., et al. OPTN/SRTR 2012 annual data report: liver. Am J Transplant 14:Suppl 1 (2014), 69–96.
62. 62 Leonard, J., Heimbach, J.K., Malinchoc, M., et al. The impact of obesity on long-term outcomes in liver transplant recipients-results of the NIDDK liver transplant database. Am J Transplant 8:3 (2008), 667–672.
63. 63 Palmer, M., Schaffner, F., Thung, S.N., Excessive weight gain after liver transplantation. Transplantation 51:4 (1991), 797–800.
64. 64 Richards, J., Gunson, B., Johnson, J., et al. Weight gain and obesity after liver transplantation. Transpl Int 18:4 (2005), 461–466.
65. 65 Wawrzynowicz-Syczewska, M., Karpinska, E., Jurczyk, K., et al. Risk factors and dynamics of weight gain in patients after liver transplantation. Ann Transplant 14:3 (2009), 45–50.
66. 66 Everhart, J.E., Lombardero, M., Lake, J.R., et al. Weight change and obesity after liver transplantation: incidence and risk factors. Liver Transpl Surg 4:4 (1998), 285–296.
67. 67 Rezende Anastacio, L., Garcia Ferreira, L., Costa Liboredo, J., et al. Overweight, obesity and weight gain up to three years after liver transplantation. Nutr Hosp 27:4 (2012), 1351–1356.
68. 68 Aberg, F., Jula, A., Hockerstedt, K., et al. Cardiovascular risk profile of patients with acute liver failure after liver transplantation when compared with the general population. Transplantation 89:1 (2010), 61–68.
69. 69 Dolgos, S., Hartmann, A., Jenssen, T., et al. Determinants of short-term changes in body composition following renal transplantation. Scand J Urol Nephrol 43:1 (2009), 76–83.
70. 70 van den Ham, E.C., Kooman, J.P., Christiaans, M.H., et al. Weight changes after renal transplantation: a comparison between patients on 5-mg maintenance steroid therapy and those on steroid-free immunosuppressive therapy. Transpl Int 16:5 (2003), 300–306.
71. 71 Beckmann, S., Ivanovic, N., Drent, G., et al. Weight gain, overweight and obesity in solid organ transplantation–a study protocol for a systematic literature review. Syst Rev, 4, 2015, 2.
72. 72 Subichin, M., Clanton, J., Makuszewski, M., et al. Liver disease in the morbidly obese: a review of 1000 consecutive patients undergoing weight loss surgery. Surg Obes Relat Dis 11:1 (2015), 137–141.
73. 73 Prashanth, M., Ganesh, H.K., Vima, M.V., et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India 57 (2009), 205–210.
74. 74 Wong, R.J., Aguilar, M., Cheung, R., et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 148:3 (2015), 547–555.
75. 75 Pagadala, M., Dasarathy, S., Eghtesad, B., et al. Posttransplant metabolic syndrome: an epidemic waiting to happen. Liver Transpl 15:12 (2009), 1662–1670.
76. 76 Sprinzl, M.F., Weinmann, A., Lohse, N., et al. Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation. Transpl Int 26:1 (2013), 67–74.
77. 77 Laryea, M., Watt, K.D., Molinari, M., et al. Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events. Liver Transpl 13:8 (2007), 1109–1114.
78. 78 Pfitzmann, R., Nussler, N.C., Hippler-Benscheidt, M., et al. Long-term results after liver transplantation. Transpl Int 21:3 (2008), 234–246.
79. 79 Gisbert, C., Prieto, M., Berenguer, M., et al. Hyperlipidemia in liver transplant recipients: prevalence and risk factors. Liver Transpl Surg 3:4 (1997), 416–422.
80. 80 Neal, D.A., Tom, B.D., Luan, J., et al. Is there disparity between risk and incidence of cardiovascular disease after liver transplant?. Transplantation 77:1 (2004), 93–99.
81. 81 Watt, K.D., Charlton, M.R., Metabolic syndrome and liver transplantation: a review and guide to management. J Hepatol 53:1 (2010), 199–206.
82. 82 Dumortier, J., Giostra, E., Belbouab, S., et al. Non-alcoholic fatty liver disease in liver transplant recipients: another story of “seed and soil.”. Am J Gastroenterol 105:3 (2010), 613–620.
83. 83 Rockall, A.G., Sohaib, S.A., Evans, D., et al. Hepatic steatosis in Cushing's syndrome: a radiological assessment using computed tomography. Eur J Endocrinol 149:6 (2003), 543–548.
84. 84 Mueller, K.M., Kornfeld, J.W., Friedbichler, K., et al. Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice. Hepatology 54:4 (2011), 1398–1409.
85. 85 Dolinsky, V.W., Douglas, D.N., Lehner, R., et al. Regulation of the enzymes of hepatic microsomal triacylglycerol lipolysis and re-esterification by the glucocorticoid dexamethasone. Biochem J 378:Pt 3 (2004), 967–974.
86. 86 Wang, J.C., Gray, N.E., Kuo, T., et al. Regulation of triglyceride metabolism by glucocorticoid receptor. Cell Biosci, 2(1), 2012, 19.
87. 87 Waki, K., UNOS Liver Registry: ten year survivals. Clin Transplant, 2006, 29–39.
88. 88 Hong, J.C., Kahan, B.D., Immunosuppressive agents in organ transplantation: past, present, and future. Semin Nephrol 20:2 (2000), 108–125.
89. 89 Tarantino, G., Palmiero, G., Polichetti, G., et al. Long-term assessment of plasma lipids in transplant recipients treated with tacrolimus in relation to fatty liver. Int J Immunopathol Pharmacol 23:4 (2010), 1303–1308.
90. 90 Gueguen, Y., Ferrari, L., Souidi, M., et al. Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase. Basic Clin Pharmacol Toxicol 100:6 (2007), 392–397.
91. 91 Derfler, K., Hayde, M., Heinz, G., et al. Decreased postheparin lipolytic activity in renal transplant recipients with cyclosporin A. Kidney Int 40:4 (1991), 720–727.
92. 92 Orlando, G., Baiocchi, L., Cardillo, A., et al. Switch to 1.5 grams MMF monotherapy for CNI-related toxicity in liver transplantation is safe and improves renal function, dyslipidemia, and hypertension. Liver Transpl 13:1 (2007), 46–54.
93. 93 Bakar, F., Keven, K., Dogru, B., et al. Low-density lipoprotein oxidizability and the alteration of its fatty acid content in renal transplant recipients treated with cyclosporine/tacrolimus. Transplant Proc 41:5 (2009), 1630–1633.
94. 94 Sandrini, S., Aslam, N., Tardanico, R., et al. Tacrolimus versus cyclosporine for early steroid withdrawal after renal transplantation. J Nephrol 25:1 (2012), 43–49.
95. 95 Neff, G.W., Montalbano, M., Tzakis, A.G., Ten years of sirolimus therapy in orthotopic liver transplant recipients. Transplant Proc 35:3 Suppl (2003), 209S–216S.
96. 96 Zimmermann, A., Zobeley, C., Weber, M.M., et al. Changes in lipid and carbohydrate metabolism under mTOR- and calcineurin-based immunosuppressive regimen in adult patients after liver transplantation. Eur J Intern Med 29 (2016), 104–109.
97. 97 Fuhrmann, A., Lopes, P., Sereno, J., et al. Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model. Biochem Pharmacol 88:2 (2014), 216–228.
98. 98 Wong, V.W., Chan, R.S., Wong, G.L., et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol 59:3 (2013), 536–542.
99. 99 Marchesini, G., Petta, S., Dalle Grave, R., Diet, weight loss, and liver health in nonalcoholic fatty liver disease: pathophysiology, evidence, and practice. Hepatology 63:6 (2016), 2032–2043.
100. 100 Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149:2 (2015), 367–378.e5 [quiz: e14–5].
101. 101 Abdelmalek, M.F., Suzuki, A., Guy, C., et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51:6 (2010), 1961–1971.
102. 102 Hejlova, I., Honsova, E., Sticova, E., et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl 22:5 (2016), 644–655.
103. 103 Liu, Y., Dai, M., Bi, Y., et al. Active smoking, passive smoking, and risk of nonalcoholic fatty liver disease (NAFLD): a population-based study in China. J Epidemiol 23:2 (2013), 115–121.
104. 104 Pulixi, E.A., Tobaldini, E., Battezzati, P.M., et al. Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease. PLoS One, 9(4), 2014, e96349.
105. 105 Gitto, S., Vitale, G., Villa, E., et al. Treatment of nonalcoholic steatohepatitis in adults: present and future. Gastroenterol Res Pract, 2015, 2015, 732870.
106. 106 Aguilar-Olivos, N.E., Almeda-Valdes, P., Aguilar-Salinas, C.A., et al. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome. Metabolism 65:8 (2016), 1196–1207.
107. 107 Bower, G., Toma, T., Harling, L., et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg 25:12 (2015), 2280–2289.
108. 108 Sanyal, A.J., Chalasani, N., Kowdley, K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362:18 (2010), 1675–1685.
109. 109 Armstrong, M.J., Gaunt, P., Aithal, G.P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387:10019 (2016), 679–690.
110. 110 Kargiotis, K., Athyros, V.G., Giouleme, O., et al. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol 21:25 (2015), 7860–7868.