Liver transplantation for nonalcoholic fatty liver disease: New challenges and new opportunities

World Journal of Gastroenterology

Volumn 20, Issue 18, 2014, Pages 5320-5330

  Shaker, Mina ^a   Tabbaa, Adam ^a   Albeldawi, Mazen ^a   Alkhouri, Naim ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

Liver cirrhosis; Liver transplantation; Metabolic syndrome; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADIPONUTRIN; ALANINE AMINOTRANSFERASE; ALPHA TOCOPHEROL; ANGIOTENSIN RECEPTOR ANTAGONIST; ASPARTATE AMINOTRANSFERASE; CALCINEURIN INHIBITOR; CYCLOSPORIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FARNESOID X RECEPTOR; GLUCOCORTICOID; INTERLEUKIN 28B; JANUS KINASE; METFORMIN; OBETICHOLIC ACID; PATATIN LIKE PHOSPHOLIPASE DOMAIN CONTAINING PROTEIN 3; PENTOXIFYLLINE; PEPTIDES AND PROTEINS; PREDNISONE; RAPAMYCIN; SIMTUZUMAB; STAT PROTEIN; STEROID; TACROLIMUS; TRANSFORMING GROWTH FACTOR 1; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

BARIATRIC SURGERY; CARDIOVASCULAR RISK; DIETARY INTAKE; DISEASE ASSOCIATION; DISEASE COURSE; DNA POLYMORPHISM; FOLLOW UP; HISTOLOGY; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INCIDENCE; KIDNEY INJURY; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER TRANSPLANTATION; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; NONHUMAN; PREVALENCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT DISEASE; REVIEW; RISK FACTOR; STEATOSIS; SURVIVAL RATE; ADVERSE EFFECTS; GENETIC PREDISPOSITION; GENETICS; GRAFT SURVIVAL; NON-ALCOHOLIC FATTY LIVER DISEASE; PHENOTYPE; POSTOPERATIVE COMPLICATIONS; TIME; TREATMENT OUTCOME;

GENETIC PREDISPOSITION TO DISEASE; GRAFT SURVIVAL; HUMANS; LIVER TRANSPLANTATION; NON-ALCOHOLIC FATTY LIVER DISEASE; PHENOTYPE; POSTOPERATIVE COMPLICATIONS; RECURRENCE; RISK FACTORS; TIME FACTORS; TREATMENT OUTCOME;

EID: 84900453365     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i18.5320     Document Type: Review

References (101)

1. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011; 9: 524-530. e1; quiz e60 [PMID: 21440669 DOI: 10.1016/j.cgh.2011.03.020]
2. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-1395 [PMID: 15565570 DOI: 10.1002/hep.20466]
3. Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol 2004; 40: 578-584 [PMID: 15030972 DOI: 10.1016/j.jhep.2004.02.013]
4. Desai HG. Cryptogenic cirrhosis: a vanishing entity. J Assoc Physicians India 2009; 57: 751-754, 759 [PMID: 20329442]
5. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med 1997; 126: 137-145 [PMID: 9005748]
6. Dureja P, Mellinger J, Agni R, Chang F, Avey G, Lucey M, Said A. NAFLD recurrence in liver transplant recipients. Transplantation 2011; 91: 684-689 [PMID: 21248661 DOI: 10.1097/ TP.0b013e31820b6b84]
7. Seo S, Maganti K, Khehra M, Ramsamooj R, Tsodikov A, Bowlus C, McVicar J, Zern M, Torok N. De novo nonalcoholic fatty liver disease after liver transplantation. Liver Transpl 2007; 13: 844-847 [PMID: 17029282 DOI: 10.1002/lt.20932]
8. Lim LG, Cheng CL, Wee A, Lim SG, Lee YM, Sutedja DS, Da Costa M, Prabhakaran K, Wai CT. Prevalence and clinical associations of posttransplant fatty liver disease. Liver Int 2007; 27: 76-80 [PMID: 17241384 DOI: 10.1111/j.1478-3231.2006.01396.x]
9. Brandman D, Pingitore A, Lai JC, Roberts JP, Ferrell L, Bass NM, Terrault NA. Hepatic steatosis at 1 year is an additional predictor of subsequent fibrosis severity in liver transplant recipients with recurrent hepatitis C virus. Liver Transpl 2011; 17: 1380-1386 [PMID: 21770018 DOI: 10.1002/lt.22389]
10. Dumortier J, Giostra E, Belbouab S, Morard I, Guillaud O, Spahr L, Boillot O, Rubbia-Brandt L, Scoazec JY, Hadengue A. Non-alcoholic fatty liver disease in liver transplant recipients: another story of "seed and soil". Am J Gastroenterol 2010; 105: 613-620 [PMID: 20040915 DOI: 10.1038/ ajg.2009.717]
11. Watt KD, Dierkhising RA, Fan C, Krishnan A, Tillmann HL, Goldstein DB, Heimbach J, Charlton M. Recipient but not Donor PNPLA3 and IL28B Genotype are Important Determinants of Posttransplant Diabetes and Obesity. Hepatology 2013; 56: 193A
12. Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant 2009; 9: 782-793 [PMID: 19344467 DOI: 10.1111/ j.1600-6143.2009.02590.x]
13. Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 2011; 141: 1249-1253 [PMID: 21726509 DOI: 10.1053/j.gastro.2011.06.061]
14. Houlihan DD, Armstrong MJ, Davidov Y, Hodson J, Nightingale P, Rowe IA, Paris S, Gunson BK, Bramhall SB, Mutimer DJ, Neuberger JM, Newsome PN. Renal function in patients undergoing transplantation for nonalcoholic steatohepatitis cirrhosis: time to reconsider immunosuppression regimens? Liver Transpl 2011; 17: 1292-1298 [PMID: 21761549 DOI: 10.1002/lt.22382]
15. Laish I, Braun M, Mor E, Sulkes J, Harif Y, Ben Ari Z. Metabolic syndrome in liver transplant recipients: prevalence, risk factors, and association with cardiovascular events. Liver Transpl 2011; 17: 15-22 [PMID: 21254340 DOI: 10.1002/ lt.22198]
16. Watt KD, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. Am J Transplant 2010; 10: 1420-1427 [PMID: 20486907 DOI: 10.1111/j.1600-6143.2010.03126.x]
17. Stegall MD, Everson G, Schroter G, Bilir B, Karrer F, Kam I. Metabolic complications after liver transplantation. Diabetes, hypercholesterolemia, hypertension, and obesity. Transplantation 1995; 60: 1057-1060 [PMID: 7491685]
18. Bianchi G, Marchesini G, Marzocchi R, Pinna AD, Zoli M. Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression. Liver Transpl 2008; 14: 1648-1654 [PMID: 18975273 DOI: 10.1002/lt.21588]
19. Everhart JE, Lombardero M, Lake JR, Wiesner RH, Zetterman RK, Hoofnagle JH. Weight change and obesity after liver transplantation: incidence and risk factors. Liver Transpl Surg 1998; 4: 285-296 [PMID: 9649642]
20. Finkenstedt A, Auer C, Glodny B, Posch U, Steitzer H, Lanzer G, Pratschke J, Biebl M, Steurer M, Graziadei I, Vogel W, Zoller H. Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clin Gastroenterol Hepatol 2013; 11: 1667-1672 [PMID: 23872669 DOI: 10.1016/j.cgh.2013.06.025]
21. Bhagat V, Mindikoglu AL, Nudo CG, Schiff ER, Tzakis A, Regev A. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl 2009; 15: 1814-1820 [PMID: 19938128 DOI: 10.1002/lt.21927]
22. Contos MJ, Cales W, Sterling RK, Luketic VA, Shiffman ML, Mills AS, Fisher RA, Ham J, Sanyal AJ. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl 2001; 7: 363-373 [PMID: 11303298 DOI: 10.1053/jlts.2001.23011]
23. Maor-Kendler Y, Batts KP, Burgart LJ, Wiesner RH, Krom RA, Rosen CB, Charlton MR. Comparative allograft histology after liver transplantation for cryptogenic cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases. Transplantation 2000; 70: 292-297 [PMID: 10933151]
24. Molloy RM, Komorowski R, Varma RR. Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation. Liver Transpl Surg 1997; 3: 177-178 [PMID: 9346733]
25. Kim WR, Poterucha JJ, Porayko MK, Dickson ER, Steers JL, Wiesner RH. Recurrence of nonalcoholic steatohepatitis following liver transplantation. Transplantation 1996; 62: 1802-1805 [PMID: 8990367]
26. Burke GW, Cirocco R, Hensley G, Ranjan D, Reddy R, Jeffers L, Schiff E, Miller J. Liver transplantation for cirrhosis following jejuno-ileal bypass--regional cytokine differences associated with pathological changes in the transplant liver. Transplantation 1992; 54: 374-377 [PMID: 1496549]
27. Poordad F, Gish R, Wakil A, Garcia-Kennedy R, Martin P, Yao FY. De novo non-alcoholic fatty liver disease following orthotopic liver transplantation. Am J Transplant 2003; 3: 1413-1417 [PMID: 14525603]
28. Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003; 37: 1286-1292 [PMID: 12774006 DOI: 10.1053/ jhep.2003.50229]
29. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, Mullen KD, Cooper JN, Sheridan MJ. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745-750 [PMID: 12198701]
30. Das SK, Balakrishnan V. Role of cytokines in the pathogenesis of non-alcoholic Fatty liver disease. Indian J Clin Biochem 2011; 26: 202-209 [PMID: 22468051 DOI: 10.1007/ s12291-011-0121-7]
31. Carazo A, León J, Casado J, Gila A, Delgado S, Martín A, Sanjuan L, Caballero T, Muñoz JA, Quiles R, Ruiz-Extremera A, Alcázar LM, Salmerón J. Hepatic expression of adiponectin receptors increases with non-alcoholic fatty liver disease progression in morbid obesity in correlation with glutathione peroxidase 1. Obes Surg 2011; 21: 492-500 [PMID: 21240660 DOI: 10.1007/s11695-010-0353-2]
32. Kaser S, Moschen A, Cayon A, Kaser A, Crespo J, Pons-Romero F, Ebenbichler CF, Patsch JR, Tilg H. Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut 2005; 54: 117-121 [PMID: 15591515 DOI: 10.1136/gut.2003.037010]
33. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011; 140: 124-131 [PMID: 20858492 DOI: 10.1053/j.gastro.2010.09.038]
34. Charlton M. Evolving aspects of liver transplantation for nonalcoholic steatohepatitis. Curr Opin Organ Transplant 2013; 18: 251-258 [PMID: 23652610 DOI: 10.1097/MOT.0b013e3283615d30]
35. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362 [PMID: 10573511 DOI: 10.1002/hep.510300604]
36. Peng XE, Wu YL, Lin SW, Lu QQ, Hu ZJ, Lin X. Genetic variants in PNPLA3 and risk of non-alcoholic fatty liver disease in a Han Chinese population. PLoS One 2012; 7: e50256 [PMID: 23226254 DOI: 10.1371/journal.pone.0050256]
37. Petta S, Grimaudo S, Cammà C, Cabibi D, Di Marco V, Licata G, Pipitone RM, Craxì A. IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease. J Hepatol 2012; 56: 1356-1362 [PMID: 22314430 DOI: 10.1016/j.jhep.2012.01.007]
38. Valenti L, Alisi A, Nobili V. I148M PNPLA3 variant and progressive liver disease: A new paradigm in hepatology. Hepatology 2012; Epub 2012 Feb 6 [PMID: 22307816 DOI: 10.1002/hep.25634]
39. Watt KD, Dierkhising R, Fan C, Heimbach JK, Tillman H, Goldstein D, Thompson A, Krishnan A, Charlton MR. Investigation of PNPLA3 and IL28B genotypes on diabetes and obesity after liver transplantation: insight into mechanisms of disease. Am J Transplant 2013; 13: 2450-2457 [PMID: 23859071 DOI: 10.1111/ajt.12355]
40. Garcia RF, Morales E, Garcia CE, Saksena S, Hübscher SG, Elias E. Recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver transplantation. Arq Gastroenterol 2001; 38: 247-253 [PMID: 12068535]
41. Zahmatkeshan MBG, Eshraghian A, Nikeghbalian S, Bahador A, Salahi H, Malek-Hosseini SA. De novo Fatty Liver Due to Vascular Complications After Liver Transplantation. Transplantation Proceedings. Elsevier Inc 2011; 43: 615-617 [PMID: 21440778 DOI: 10.1016/j.transproceed.2011.01.023]
42. Pruthi J, Medkiff KA, Esrason KT, Donovan JA, Yoshida EM, Erb SR, Steinbrecher UP, Fong TL. Analysis of causes of death in liver transplant recipients who survived more than 3 years. Liver Transpl 2001; 7: 811-815 [PMID: 11552217 DOI: 10.1053/jlts.2001.27084]
43. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-1465 [PMID: 18820647 DOI: 10.1038/ng.257]
44. He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 2010; 285: 6706-6715 [PMID: 20034933 DOI: 10.1074/jbc.M109.064501]
45. Kienesberger PC, Oberer M, Lass A, Zechner R. Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions. J Lipid Res 2009; 50 Suppl: S63-S68 [PMID: 19029121 DOI: 10.1194/jlr.R800082-JLR200]
46. Baulande S, Lasnier F, Lucas M, Pairault J. Adiponutrin, a transmembrane protein corresponding to a novel dietaryand obesity-linked mRNA specifically expressed in the adipose lineage. J Biol Chem 2001; 276: 33336-33344 [PMID: 11431482 DOI: 10.1074/jbc.M105193200]
47. Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006; 55: 148-157 [PMID: 16380488]
48. Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883-1894 [PMID: 21381068 DOI: 10.1002/hep.24283]
49. Rotman Y, Koh C, Zmuda JM, Kleiner DE, Liang TJ. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 2010; 52: 894-903 [PMID: 20684021 DOI: 10.1002/hep.23759]
50. Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet 2008; 83: 520-528 [PMID: 18940312 DOI: 10.1016/j.ajhg.2008.09.012]
51. Romeo S, Sentinelli F, Dash S, Yeo GS, Savage DB, Leonetti F, Capoccia D, Incani M, Maglio C, Iacovino M, O'Rahilly S, Baroni MG. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. Int J Obes (Lond) 2010; 34: 190-194 [PMID: 19844213 DOI: 10.1038/ijo.2009.216]
52. Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010; 139: 120-129. e18 [PMID: 20399780 DOI: 10.1053/j.gastro.2010.04.013]
53. Persico M, Capasso M, Persico E, Svelto M, Russo R, Spano D, Crocè L, La Mura V, Moschella F, Masutti F, Torella R, Tiribelli C, Iolascon A. Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus-related chronic hepatitis: Insulin resistance and response to antiviral therapy. Hepatology 2007; 46: 1009-1015 [PMID: 17668875 DOI: 10.1002/hep.21782]
54. Clark PJ, Thompson AJ, Zhu Q, Vock DM, Zhu M, Patel K, Harrison SA, Naggie S, Ge D, Tillmann HL, Urban TJ, Shianna K, Fellay J, Goodman Z, Noviello S, Pedicone LD, Afdhal N, Sulkowski M, Albrecht JK, Goldstein DB, McHutchison JG, Muir AJ. The association of genetic variants with hepatic steatosis in patients with genotype 1 chronic hepatitis C infection. Dig Dis Sci 2012; 57: 2213-2221 [PMID: 22543885 DOI: 10.1007/s10620-012-2171-y]
55. Veldt BJ, Duarte-Rojo A, Thompson AJ, Watt KD, Heimbach JK, Tillmann HL, Goldstein DD, McHutchison JG, Charlton MR. Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C. Am J Transplant 2012; 12: 737-744 [PMID: 22300408 DOI: 10.1111/ j.1600-6143.2011.03843.x]
56. Patil DT, Yerian LM. Evolution of nonalcoholic fatty liver disease recurrence after liver transplantation. Liver Transpl 2012; 18: 1147-1153 [PMID: 22740341 DOI: 10.1002/lt.23499]
57. Charlton M, Kasparova P, Weston S, Lindor K, Maor-Kendler Y, Wiesner RH, Rosen CB, Batts KP. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 2001; 7: 608-614 [PMID: 11460228 DOI: 10.1053/ jlts.2001.25453]
58. Ayata G, Gordon FD, Lewis WD, Pomfret E, Pomposelli JJ, Jenkins RL, Khettry U. Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation. Hum Pathol 2002; 33: 1098-1104 [PMID: 12454814 DOI: 10.1053/hupa.2002.129419]
59. Malik SM, Devera ME, Fontes P, Shaikh O, Sasatomi E, Ahmad J. Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Transpl 2009; 15: 1843-1851 [PMID: 19938117 DOI: 10.1002/lt.21943]
60. Yalamanchili K, Saadeh S, Klintmalm GB, Jennings LW, Davis GL. Nonalcoholic fatty liver disease after liver transplantation for cryptogenic cirrhosis or nonalcoholic fatty liver disease. Liver Transpl 2010; 16: 431-439 [PMID: 20373454 DOI: 10.1002/lt.22004]
61. Albeldawi M, Aggarwal A, Madhwal S, Cywinski J, Lopez R, Eghtesad B, Zein NN. Cumulative risk of cardiovascular events after orthotopic liver transplantation. Liver Transpl 2012; 18: 370-375 [PMID: 22140067 DOI: 10.1002/lt.22468]
62. Hanouneh IA, Feldstein AE, McCullough AJ, Miller C, Aucejo F, Yerian L, Lopez R, Zein NN. The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation. Liver Transpl 2008; 14: 1287-1293 [PMID: 18756451 DOI: 10.1002/lt.21524]
63. Phung N, Pera N, Farrell G, Leclercq I, Hou JY, George J. Pro-oxidant-mediated hepatic fibrosis and effects of antioxidant intervention in murine dietary steatohepatitis. Int J Mol Med 2009; 24: 171-180 [PMID: 19578790]
64. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362: 1675-1685 [PMID: 20427778 DOI: 10.1056/NEJMoa0907929]
65. Diehl AM. Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8: 619-638, x [PMID: 15331067 DOI: 10.1016/ j.cld.2004.04.012]
66. Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 2011; 54: 1610-1619 [PMID: 21748765 DOI: 10.1002/hep.24544]
67. Zein CO, Lopez R, Fu X, Kirwan JP, Yerian LM, McCullough AJ, Hazen SL, Feldstein AE. Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. Hepatology 2012; 56: 1291-1299 [PMID: 22505276 DOI: 10.1002/hep.25778]
68. Li W, Zheng L, Sheng C, Cheng X, Qing L, Qu S. Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease. Lipids Health Dis 2011; 10: 49 [PMID: 21477300 DOI: 10.1186/1476-511X-10-49]
69. Colmenero J, Bataller R, Sancho-Bru P, Domínguez M, Moreno M, Forns X, Bruguera M, Arroyo V, Brenner DA, Ginès P. Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C. Am J Physiol Gastrointest Liver Physiol 2009; 297: G726-G734 [PMID: 19628656 DOI: 10.1152/ajpgi.00162.2009]
70. Enjoji M, Kotoh K, Kato M, Higuchi N, Kohjima M, Nakashima M, Nakamuta M. Therapeutic effect of ARBs on insulin resistance and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study. Int J Mol Med 2008; 22: 521-527 [PMID: 18813860]
71. Sookoian S, Fernández MA, Castaño G. Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: a pilot study. World J Gastroenterol 2005; 11: 7560-7563 [PMID: 16437678]
72. Terui Y, Saito T, Watanabe H, Togashi H, Kawata S, Kamada Y, Sakuta S. Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C. Hepatology 2002; 36: 1022 [PMID: 12297856 DOI: 10.1053/jhep.2002.32679]
73. Warner FJ, Lubel JS, McCaughan GW, Angus PW. Liver fibrosis: a balance of ACEs? Clin Sci (Lond) 2007; 113: 109-118 [PMID: 17600527 DOI: 10.1042/CS20070026]
74. Paschos P, Tziomalos K. Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment. World J Hepatol 2012; 4: 327-331 [PMID: 23355909 DOI: 10.4254/wjh. v4.i12.327]
75. Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU, Kipnes M, Adorini L, Sciacca CI, Clopton P, Castelloe E, Dillon P, Pruzanski M, Shapiro D. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145: 574-582. e1 [PMID: 23727264 DOI: 10.1053/j.gastro.2013.05.042]
76. Reuben A. Long-term management of the liver transplant patient: diabetes, hyperlipidemia, and obesity. Liver Transpl 2001; 7: S13-S21 [PMID: 11689772 DOI: 10.1053/jlts.2001.29167]
77. Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ 2005; 172: 899-905 [PMID: 15795412 DOI: 10.1503/cmaj.045232]
78. Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O'Dea K, Desmond PV, Johnson NA, Wilson AM. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013; 59: 138-143 [PMID: 23485520 DOI: 10.1016/ j.jhep.2013.02.012]
79. Sheiner PA, Magliocca JF, Bodian CA, Kim-Schluger L, Altaca G, Guarrera JV, Emre S, Fishbein TM, Guy SR, Schwartz ME, Miller CM. Long-term medical complications in patients surviving & gt; or = 5 years after liver transplant. Transplantation 2000; 69: 781-789 [PMID: 10755526]
80. Textor SC, Canzanello VJ, Taler SJ, Schwartz L, Augustine J. Hypertension after liver transplantation. Liver Transpl Surg 1995; 1: 20-28 [PMID: 9346597]
81. Roy A, Kneteman N, Lilly L, Marotta P, Peltekian K, Scudamore C, Tchervenkov J. Tacrolimus as intervention in the treatment of hyperlipidemia after liver transplant. Transplantation 2006; 82: 494-500 [PMID: 16926593 DOI: 10.1097/01. tp.0000231711.82193.41]
82. Luzi L, Perseghin G, Regalia E, Sereni LP, Battezzati A, Baratti D, Bianchi E, Terruzzi I, Hilden H, Groop LC, Pulvirenti A, Taskinen MR, Gennari L, Mazzaferro V. Metabolic effects of liver transplantation in cirrhotic patients. J Clin Invest 1997; 99: 692-700 [PMID: 9045872 DOI: 10.1172/JCI119213]
83. Marchetti P, Navalesi R. The metabolic effects of cyclosporin and tacrolimus. J Endocrinol Invest 2000; 23: 482-490 [PMID: 11005276]
84. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142: 1592-1609 [PMID: 22656328 DOI: 10.1053/j.gastro.2012.04.001]
85. Shields WW, Thompson KE, Grice GA, Harrison SA, Coyle WJ. The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial. Therap Adv Gastroenterol 2009; 2: 157-163 [PMID: 21180541 DOI: 10.1177/1756283X09105462]
86. Idilman R, Mizrak D, Corapcioglu D, Bektas M, Doganay B, Sayki M, Coban S, Erden E, Soykan I, Emral R, Uysal AR, Ozden A. Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008; 28: 200-208 [PMID: 18445142 DOI: 10.1111/j.1365-2036.2008.03723.x]
87. Omer Z, Cetinkalp S, Akyildiz M, Yilmaz F, Batur Y, Yilmaz C, Akarca U. Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2010; 22: 18-23 [PMID: 19667999 DOI: 10.1097/MEG.0b013e32832e2baf]
88. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34: 274-285 [PMID: 21623852 DOI: 10.1111/j.1365-2036.2011.04724.x]
89. Kallwitz ER. Metabolic syndrome after liver transplantation: preventable illness or common consequence? World J Gastroenterol 2012; 18: 3627-3634 [PMID: 22851856 DOI: 10.3748/ wjg.v18.i28.3627]
90. Neal DA, Gimson AE, Gibbs P, Alexander GJ. Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight. Liver Transpl 2001; 7: 533-539 [PMID: 11443583 DOI: 10.1053/ jlts.2001.24637]
91. Canzanello VJ, Schwartz L, Taler SJ, Textor SC, Wiesner RH, Porayko MK, Krom RA. Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506). Liver Transpl Surg 1997; 3: 1-9 [PMID: 9377752]
92. Stegall MD, Wachs ME, Everson G, Steinberg T, Bilir B, Shrestha R, Karrer F, Kam I. Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus. Transplantation 1997; 64: 1755-1760 [PMID: 9422416]
93. Williams R, Neuhaus P, Bismuth H, McMaster P, Pichlmayr R, Calne R, Otto G, Groth C. Two-year data from the European multicentre tacrolimus (FK506) liver study. Transpl Int 1996; 9 Suppl 1: S144-S150 [PMID: 8959812]
94. Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant 2004; 4: 583-595 [PMID: 15023151 DOI: 10.1046/j.1600-6143.2003.00372.x]
95. Navasa M, Bustamante J, Marroni C, González E, Andreu H, Esmatjes E, García-Valdecasas JC, Grande L, Cirera I, Rimola A, Rodés J. Diabetes mellitus after liver transplantation: prevalence and predictive factors. J Hepatol 1996; 25: 64-71 [PMID: 8836903]
96. Saab S, Shpaner A, Zhao Y, Brito I, Durazo F, Han S, Farmer DG, Ghobrial RM, Yersiz H, Goldstein LI, Tong MJ, Busuttil RW. Prevalence and risk factors for diabetes mellitus in moderate term survivors of liver transplantation. Am J Transplant 2006; 6: 1890-1895 [PMID: 16889544 DOI: 10.1111/ j.1600-6143.2006.01385.x]
97. Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev 2006; (4): CD005161 [PMID: 17054241 DOI: 10.1002/14651858.CD005161.pub2]
98. Heimbach JK, Watt KD, Poterucha JJ, Ziller NF, Cecco SD, Charlton MR, Hay JE, Wiesner RH, Sanchez W, Rosen CB, Swain JM. Combined liver transplantation and gastric sleeve resection for patients with medically complicated obesity and end-stage liver disease. Am J Transplant 2013; 13: 363-368 [PMID: 23137119 DOI: 10.1111/j.1600-6143.2012.04318.x]
99. Cotler SJ, Vitello JM, Guzman G, Testa G, Benedetti E, Layden TJ. Hepatic decompensation after gastric bypass surgery for severe obesity. Dig Dis Sci 2004; 49: 1563-1568 [PMID: 15573905]
100. Shimizu H, Phuong V, Maia M, Kroh M, Chand B, Schauer PR, Brethauer SA. Bariatric surgery in patients with liver cirrhosis. Surg Obes Relat Dis 2013; 9: 1-6 [PMID: 23201210 DOI: 10.1016/j.soard.2012.07.021]
101. Weingarten TN, Swain JM, Kendrick ML, Charlton MR, Schroeder BJ, Lee RE, Narr BJ, Ribeiro TC, Schroeder DR, Sprung J. Nonalcoholic steatohepatitis (NASH) does not increase complications after laparoscopic bariatric surgery. Obes Surg 2011; 21: 1714-1720 [PMID: 21948267 DOI: 10.1007/ s11695-011-0521-z]