Esteato-hepatite não alcoólica no pós-transplante de fígado: artigo de revisão

Andrade, Antônio Ricardo Cardia Ferraz de; Cotrim, Helma P.; Bittencourt, Paulo L.; Almeida, Carolina G.; Sorte, Ney Christian Amaral Boa

doi:10.1590/1806-9282.64.02.187

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Sumário

REVIEW ARTICLES • Rev. Assoc. Med. Bras. 64 (2) • Fev 2018 • https://doi.org/10.1590/1806-9282.64.02.187 copiar

Esteato-hepatite não alcoólica no pós-transplante de fígado: artigo de revisão

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

Introdução:

A doença hepática gordurosa não alcoólica (DHGNA) é a terceira causa de transplante hepático no mundo. Tem elevada prevalência após transplante hepático (TH) e é representada pela recorrência da esteato-hepatite (NASH), ou por NASH de novo, que ocorre em pacientes transplantados por outra etiologia.

Objetivo:

Realizar uma revisão da literatura para avaliar a relevância da recorrência ou do NASH de novo em pacientes transplantados de fígado.

Método:

Realizada revisão da literatura através de artigos indexados no Medline, Scielo e Lilacs até 2016 publicados em inglês e português. Foram considerados elegíveis estudos que incluíram local e ano de publicação, prevalência e características clínicas dos pacientes.

Resultados:

Foram identificados 110 artigos e selecionados 63, que avaliaram a recorrência de NASH, NASH de novo e sobrevida após o TH. A sobrevida foi de 90% a 100% em um ano e de 52-100% em 5 anos. A recorrência de esteatose variou de 15-100% e a de NASH de 4-71%, enquanto esteatose e NASH de novo variaram de 18-67% e 3-17%, respectivamente. A frequência de síndrome metabólica, diabetes, dislipidemia e hipertensão variaram de 45-58%, 18-59%, 25-66% e 52-82%, respectivamente.

Conclusão:

No pós-transplante de fígado, os pacientes apresentam elevada prevalência de recorrência, de NASH de novo e de distúrbios metabólicos. Entretanto, essas alterações parecem não influenciar a sobrevida dos pacientes.

Palavras-chave:
Hepatopatia Gordurosa Não Alcoólica; Transplante de Fígado; Fígado Gorduroso; Síndrome Metabólica; Diabetes Mellitus

Reference	Patients N	Survival 1 year (%)	Survival 3 years (%)	Survival 5 years (%)
Charlton et al.⁶6 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(4):1249-53.	1,840	84	78	-
Afzali et al.¹⁸18 Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States. Liver Transpl. 2012; 18(1):29-37.	1,810+3,843^cc cc Cryptogenic cirrhosis was evaluated in conjunction with patients transplanted due to NASH in these studies.	87	81	75
El Atrache et al.^# # Survival in a patient with metabolic syndrome. ¹⁹19 El Atrache MM, Abouljoud MS, Divine G, Yoshida A, Kim DY, Kazimi MM, et al. Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome. Clin Transpl. 2012; 26(5):E505-12.	83	-	-	52
Dureja et al.²⁰20 Dureja P, Mellinger J, Agni R, Chang F, Avey G, Lucey M, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011; 91(6):684-9.	11	78	-	-
Agopian et al.²¹21 Agopian VG, Kaldas FM, Hong JC, Whittaker M, Holt C, Rana A, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg. 2012; 256(4):624-33.	144	84	75	70
Kennedy et al.²²22 Kennedy C, Redden D, Gray S, Eckhoff D, Massoud O, McGuire B, et al. Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases. HPB (Oxford). 2012; 14(9):625-34.	129	90	88	85
Barritt et al.²³23 Barritt AS 4th, Dellon ES, Kozlowski T, Gerber DA, Hayashi PH. The influence of nonalcoholic fatty liver disease and its associated comorbidities on liver transplant outcomes. J Clin Gastroenterol. 2011; 45(4):372-8.	21	76	76	-
Yalamanchili et al.²⁴24 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(4):431-9.	18+239^cc cc Cryptogenic cirrhosis was evaluated in conjunction with patients transplanted due to NASH in these studies.	86	-	71
Heuer et al.²⁵25 Heuer M, Kaiser GM, Kahraman A, Banysch M, Saner FH, Mathé Z, et al. Liver transplantation in nonalcoholic steatohepatitis is associated with high mortality and post-transplant complications: a single-center experience. Digestion. 2012; 86(2):107-13.	40	75	-	-
Bhagat et al.²⁶26 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(12):1814-20.	71	82	79	75
VanWagner et al.²⁷27 VanWagner LB, Bhave M, Te HS, Feinglass J, Alvarez L, Rinella ME. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology. 2012; 56(5):1741-50.	30	81	73	60
Houlihan et al.²⁸28 Houlihan DD, Armstrong MJ, Davidov Y, Hodson J, Nightingale P, Rowe IA, et al. Renal function in patients undergoing transplantation for nonalcoholic steatohepatitis cirrhosis: time to reconsider immunosuppression regimens? Liver Transpl. 2011; 17(11):1292-8.	48	88	82
Tanaka et al.²⁹29 Tanaka T, Sugawara Y, Tamura S, Kaneko J, Takazawa Y, Aoki T, et al. Living donor liver transplantation for non-alcoholic steatohepatitis: A single center experience. Hepatol Res. 2014; 44(10):E3-E10.	7	100	100	100
Singal et al.³⁰30 Singal AK, Guturu P, Hmoud B, Kuo YF, Salameh H, Wiesner RH. Evolving frequency and outcomes of liver transplantation based on etiology of liver disease. Transplantation. 2013; 95(5):755-60.	1,368	86	82	80
Malik et al.³¹31 Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant. 2009; 9(4):782-93.	98	79	74	72
Hejlova et al.^* * Evaluated the survival of patients with de novo NAFLD. In this study, the 10-year survival rate was 81%. ³²32 Hejlova I, Honsova E, Sticova E, Lanska V, Hucl T, Spicak J, et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016; 22(5):644-55.	309	-	100	94

Reference	Patients N	Follow-up (months)	Recurrence		De novo
Reference	Patients N	Follow-up (months)	NAFLD (%)	NASH (%)	NAFLD (%)	NASH (%)
Yalamanchili et al.²⁴24 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(4):431-9.	18	60	45	4
Tanaka et al.²⁹29 Tanaka T, Sugawara Y, Tamura S, Kaneko J, Takazawa Y, Aoki T, et al. Living donor liver transplantation for non-alcoholic steatohepatitis: A single center experience. Hepatol Res. 2014; 44(10):E3-E10.	7	120	14	-
Bhagat et al.²⁶26 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(12):1814-20.	71	60	-	33
Contos et al.⁹9 Contos MJ, Cales W, Sterling RK, Luketic VA, Shiffman ML, Mills AS, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001; 7(4):363-73.	27	>12	52	11
Charlton et al.³⁹39 Charlton M, Kasparova P, Weston S, Lindor K, Maor-Kendler Y, Wiesner RH. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl. 2001; 7(7):608-14.	15	>12	60	33
Dureja et al.²⁰20 Dureja P, Mellinger J, Agni R, Chang F, Avey G, Lucey M, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011; 91(6):684-9.	88	>12	39	28
El Atrache et al.¹⁹19 El Atrache MM, Abouljoud MS, Divine G, Yoshida A, Kim DY, Kazimi MM, et al. Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome. Clin Transpl. 2012; 26(5):E505-12.	83	45	-	24
Ong et al.¹⁰10 Ong J, Younossi ZM, Reddy V, Price LL, Gramlich T, Mayes J, et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl. 2001; 7(9):797-801.	51	>24	25.5	16
Vallin et al.⁸8 Vallin M, Guillaud O, Boillot O, Hervieu V, Scoazec JY, Dumortier J. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014; 20(9):1064-71.	11	>60	100	71.4
Malik et al.³¹31 Malik SM, deVera ME, Fontes P, Shaikh O, Ahmad J. Outcome after liver transplantation for NASH cirrhosis. Am J Transplant. 2009; 9(4):782-93.	98	60	-	25
Agopian et al.²¹21 Agopian VG, Kaldas FM, Hong JC, Whittaker M, Holt C, Rana A, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg. 2012; 256(4):624-33.	144	60	15	8
Seo et al.⁴⁰40 Seo S, Maganti K, Khehra M, Ramsamooj R, Tsodikov A, Bowlus C, et al. De novo nonalcoholic fatty liver disease after liver transplantation. Liver Transpl. 2007; 13(6):844-7.	68	28			18	9
Sprinzl et al.⁴¹41 Sprinzl MF, Weinmann A, Lohse N, Tönissen H, Koch S, Schattenberg J, et al. Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation. Transpl Int. 2013; 26(1):67-74.	129	24			34	5.4
Dumortier et al.¹²12 Dumortier J, Giostra E, Belbouab S, Morard I, Guillaud O, Spahr L, et al. Non-alcoholic fatty liver disease in liver transplant recipients: another story of "seed and soil". Am J Gastroenterol. 2010; 105(3):613-20.	421	>6			31	5.3
Kim et al.⁴³43 Kim CW, Chang Y, Sung E, Shin H, Ryu S. Serum ferritin levels predict incident non-alcoholic fatty liver disease in healthy Korean men. Metabolism. 2012; 61(8):1182-8.	156	>12			27	6.7
Hejlova et al.³²32 Hejlova I, Honsova E, Sticova E, Lanska V, Hucl T, Spicak J, et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016; 22(5):644-55.	546	>120			56.7	10
Lim et al.³⁷37 Lim LG, Cheng CL, Wee A, Lim SG, Lee YM, Sutedja DS, et al. Prevalence and clinical associations of posttransplant fatty liver disease. Liver Int 2007; 27(1):76-80.	30	44			40	13
Vallin et al.⁸8 Vallin M, Guillaud O, Boillot O, Hervieu V, Scoazec JY, Dumortier J. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014; 20(9):1064-71.	80	>60			67	17.2

Reference	Patients N	Follow-up (months)	MetS (%)	DM (%)	NODAT (%)	Dyslipid (%)	HBP (%)
Sprinzl et al.⁴¹41 Sprinzl MF, Weinmann A, Lohse N, Tönissen H, Koch S, Schattenberg J, et al. Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation. Transpl Int. 2013; 26(1):67-74.	44	24	48				52
Seo et al.⁴⁰40 Seo S, Maganti K, Khehra M, Ramsamooj R, Tsodikov A, Bowlus C, et al. De novo nonalcoholic fatty liver disease after liver transplantation. Liver Transpl. 2007; 13(6):844-7.	68	28		38		25	69
El Atrache et al.¹⁹19 El Atrache MM, Abouljoud MS, Divine G, Yoshida A, Kim DY, Kazimi MM, et al. Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome. Clin Transpl. 2012; 26(5):E505-12.	83	45	53	76			71
Hanouneh et al.⁴⁴44 Hanouneh IA, Macaron C, Lopez R, Feldstein AE, Yerian L, Eghtesad B, et al. Recurrence of disease following liver transplantation: nonalcoholic steatohepatitis vs hepatitis C virus infection. Int J Organ Transplant Med. 2011; 2(2):57-65.	148	60	53	59			60
Bianchi et al.⁴⁵45 Bianchi G, Marchesini G, Marzocchi R, Pinna AD, Zoli M. Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression. Liver Transpl. 2008; 14(11):1648-54.	296	38	45	38	29.4	50	52.7
Laryea et al.⁴⁶46 Laryea M, Watt KD, Molinari M, Walsh MJ, McAlister VC, Marotta PJ, et al. Metabolic syndrome in liver transplant recipients: prevalence and association with major vascular events. Liver Transpl. 2007; 13(8):1109-14.	118	>60	58			48	62
Laish et al.³⁵35 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(1):15-22.	252	>60	52
Anastácio et al.⁴⁷47 Anastácio LR, Ferreira LG, Ribeiro HS, Liboredo JC, Lima AS, Correia MI. Metabolic syndrome after liver transplantation: prevalence and predictive factors. Nutrition. 2011; 27(9):931-7.	148	>60	50				60
Yalamanchili et al.²⁴24 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(4):431-9.	257	60		36.8			52
Lv et al.⁴⁸48 Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, et al. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes. 2015;7(6):881-90.	438	60		18
Dumortier et al.¹²12 Dumortier J, Giostra E, Belbouab S, Morard I, Guillaud O, Spahr L, et al. Non-alcoholic fatty liver disease in liver transplant recipients: another story of "seed and soil". Am J Gastroenterol. 2010; 105(3):613-20.	421	>6		23.5		12	51.8
Marroni et al.¹⁶16 Marroni CA, Hoppe L, Diehl JL, Leipnitz I, Brandão AB, Cassal AP, et al. Diabetes mellitus and liver transplantation in adults. Transplant Proc. 1999; 31(7):3046.	75	>3		38
Kennedy et al.²²22 Kennedy C, Redden D, Gray S, Eckhoff D, Massoud O, McGuire B, et al. Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases. HPB (Oxford). 2012; 14(9):625-34.	129	>60		59
Ong et al.¹⁰10 Ong J, Younossi ZM, Reddy V, Price LL, Gramlich T, Mayes J, et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl. 2001; 7(9):797-801.	13	>60		53
Agopian et al.²¹21 Agopian VG, Kaldas FM, Hong JC, Whittaker M, Holt C, Rana A, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg. 2012; 256(4):624-33.	144	60		57			50
Vallin et al.⁸8 Vallin M, Guillaud O, Boillot O, Hervieu V, Scoazec JY, Dumortier J. Recurrent or de novo nonalcoholic fatty liver disease after liver transplantation: natural history based on liver biopsy analysis. Liver Transpl. 2014; 20(9):1064-71.	80	>60		37.8			52
Parolin et al.¹⁷17 Parolin MB, Zaina FE, Araújo MV, Kupka E, Coelho JC. Prevalence of new-onset diabetes mellitus in Brazilian liver transplant recipients: association with HCV infection. Transplant Proc. 2004; 36(9):2776-7.	82	20			18.9
Mirabella et al.⁴⁹49 Mirabella S, Brunati A, Ricchiuti A, Pierini A, Franchello A, Salizzoni M. New-onset diabetes after liver transplantation. Transplant Proc. 2005; 37(6):2636-7.	830	10			10.8
Ling et al.⁵⁰50 Ling Q, Xu X, Xie H, Wang K, Xiang P, Zhuang R, et al. New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry. Liver Int. 2016; 36(5):705-12.	10,204	30			24.3
Carey et al.⁵¹51 Carey EJ, Aqel BA, Byrne TJ, Douglas DD, Rakela J, Vargas HE, et al. Pretransplant fasting glucose predicts new-onset diabetes after liver transplantation. J Transplant. 2012:614781.	225	>12			17.3
Saliba et al.⁵²52 Saliba F, Lakehal M, Pageaux GP, Roche B, Vanlemmens C, Duvoux C, et al. Risk factors for new-onset diabetes mellitus following liver transplantation and impact of hepatitis C infection: an observational multicenter study. Liver Transpl. 2007; 13(1):136-44.	211	24			22.7
Moon et al.⁵³53 Moon JI, Barbeito R, Faradji RN, Gaynor JJ, Tzakis AG. Negative impact of new-onset diabetes mellitus on patient and graft survival after liver transplantation: Long-term follow up. Transplantation. 2006; 82(12):1625-8.	778	57			36.5
Gisbert et al.⁵⁴54 Gisbert C, Prieto M, Berenguer M, Bretó M, Carrasco D, Juan M, et al. Hyperlipidemia in liver transplant recipients: prevalence and risk factors. Liver Transpl Surg. 1997; 3(4):416-22.	85	>12				66
Trotter et al.^# # The authors found 30% in patients who used cyclosporine and 6% with tacrolimus. ⁵⁵55 Trotter JF, Wachs ME, Trouillot TE, Bak T, Kugelmas M, Kam I, et al. Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus. Liver Transpl. 2001; 7(5):401-8.	57	>6				30
Dehghani et al.^* * The authors found 70% of hypertriglyceridemia and 15% of hypercholesterolemia. ⁵⁶56 Dehghani SM, Taghavi SA, Eshraghian A, Gholami S, Imanieh MH, Bordbar MR, et al. Hyperlipidemia in Iranian liver transplant recipients: prevalence and risk factors. J Gastroenterol. 2007; 42(9):769-74.	170	>12				70
Marroni et al.¹⁵15 Marroni CA, Diehl JL, Leipnitz I, Pires LM, Brandão AB, Cassal AP, et al. Prevalence of high blood pressure in patients submitted to liver transplantation at the ISCMPA. Transplantation Proc. 1999; 31(7):3047.	75	> 3					14^ Only new cases of posttransplant hypertension.
Darstein et al.⁵⁷57 Darstein F, König C, Hoppe-Lotichius M, Grimm D, Knapstein J, Zimmermann A, et al. New onset of diabetes after transplantation is associated with improved patient survival after liver transplantation due to confounding factor. Eur J Intern Med. 2015; 26(6):439-44.	255	>60					55
Hejlova et al.³²32 Hejlova I, Honsova E, Sticova E, Lanska V, Hucl T, Spicak J, et al. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016; 22(5):644-55.	309	>120					67
Canzanello et al.^¥ ¥ The authors found 82% for cyclosporine and 64% for tacrolimus. ⁵⁸58 Canzanello VJ, Textor SC, Taler SJ, Schwartz LL, Porayko MK, Wiesner RH, et al. Late hypertension after liver transplantation: a comparison of cyclosporine and tacrolimus (FK 506). Liver Transpl Surg. 1998; 4(4):328-34.	158	>24					82

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