Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances

Table 1 Liver transplantation for non-alcoholic fatty liver disease

Ref.	Patient	Population	Follow up	Graft survival	Patient survival	NAFLD recurrence in graft	Predictors of NAFLD recurrence	Predictors of survival
National registry data
Charlton et al[13]	35781 adults adult liver transplant recipientNASH primary or secondary indication for 1959 recipient	SRTR (US national data) of liver transplant recipients from 2001 to 2009Included NASH plus 50% of CRC and NASH plus CRC with BMI > 30 kg/m2)	3 yr post-transplant survival reported	NASH 3-yr survival 76% (similar to other indications)	NASH 1-yr survival 84% and 3-yr 78% CRC 1 -yr survival 86% and 3 -yr 79%Other Diagnoses 1-yr survival 87% and 3-yr 78% (P = 0.67)	Not reported	Not reported	Not reported
Singal et al[18]	54687 adult liver transplant recipientNASH 1368 recipients	UNOS adult liver transplant recipients from 1994 to 2009	10-yr survival reported	1-yr, 3-yr, 50-yr and 10-yr survival NASH: 86%, 82%, 80% and 80%NAFLD post-transplant survival similar to cholestatic liver disease, HBV and better than ALD, CRC, HCV and HCC	1-yr, 3-yr, 5-yr and 10-yr survival NASH: 89%, 85%, 84% and 84% NAFLD post-transplant survival similar to cholestatic liver disease, HBV and better than ALD, CRC, HCV and HCC	Not reported	Not reported	For all recipients, age of recipient, male recipient black race, ventilator support pre transplant and MELD score as well as donor risk index associated with worse patient survival
Afzali et al[17]	53738 adult liver transplant recipientsNASH 1810recipients	UNOS adult liver transplant recipients from 1997 to 2010	5-yr survival reported	Not reported	1-yr, 3-yr and 5-yr survivalNASH: 88%, 82% and 77%Overall adjusted HR for NASH post-transplant mortality compared to other etiologies was 0.75 (95%CI: 0.66-0.85)Adjusted survival was better for NASH than for ALD, HCV, and HCC.NASH survival was worse than cholestatic liver disease, AIH, HBV	Not reported	Not reported	Not specified- although state survival adjusted for several donor, recipient characteristics (individual Hazards ratios not reported)
Single center studies
Tanaka et al[57]	7 patient with NAFLD (425 total LDLT recipients)	Patients with NAFLD that underwent Live donor liver transplant at a single center in Japan between 1996 and 2013	Median follow up 5.3 yr	100% at last follow up	100% at last follow up	1/7 (14%) had recurrent NASH	Not reported	Not reported
El Atrache et al[27]	83 recipient, NALFD[46] and CRC[37]	Liver transplant recipients at a single US center between 1996 and 2008	Mean follow up 46 mo	12/83 underwent re-transplantation	12 recipients died. Overall survival not reported	NAFLD recurrence in 20/83 recipients (15 with NASH pre-transplant and 5 with CRC pre-transplant	Predictors of recurrence were metabolic syndrome, hypertension and Insulin use as well as hyperlipidemia after transplant	Five year survival worse for those with metabolic syndrome, hypertension and insulin useNo difference in survival between those with NASH recurrence and those without
Dureja et al[26]	88 recipients with NAFLD	Liver transplant recipients at a single US center between 1993 and 2007	Mean follow up 82 mo	Not reported	5-yr patient survival similar between those with NAFLD recurrence and those without NAFLD recurrence (P = 0.78)	NAFLD Disease Recurrence in 34/88 (39%)	Pre and post-transplant BMI. Triglyceride levels and prednisone dose was higher in those with NAFLD recurrence	Post-transplant survival was worse in NAFLD patients with post-transplant cardiac disease (HR 3.2, 95%CI: 1.3-7.7)
Agopian et al[20]	144 recipients with NAFLD (total 1294 transplants)	Liver transplant recipients at a single US center between 1993 and 2011	Mean follow up 2.3 yr	Graft survival similar between NAFLD and non NAFLD (90 d survival 86% for NASH) and lower only than PBC/PSC (90 d graft survival of 94%)5-yr graft survival for NASH 63% similar to ALD, HBV, CC and PBC/PSC but better than HCV	Patient survival similar between NASH and non-NASH. 90 d survival 90% for NASH5-yr patient survival for NASH (70%) similar to ALD, HBV, CC and PBC/PSC but better than HCV	NASH recurrence in 23 (16%)	Not reported	Post-transplant BMI > 35 kg/m2independent factor for mortality in NAFLD recipients only. Pretransplant dialysis also had worse survival in NASH patients
Kennedy et al[21]	129 recipients with NAFLD and 775 with other liver disease	Liver transplant recipients at a single US center between 1999 and 2009	5-yr survival reported	Graft survival not reported	1-yr, 3 -yr, and 5-yr survivalNASH: 90%, 88% and 85% Non-NASH: 92%, 86% and 80% (P = NS) Mortality within 4 mo higher in NASH -8.5% vs non –NASH 4.2%, P = 0.04	Not reported	Not reported	No predictors of survival found
Barritt et al[24]	21 recipients with NAFLD and 97 with other liver disease	Liver transplant recipients at a single US center between 2004 and 2007	3-yr survival reported	30-d graft survival worse in NAFLD (81%) vs non-NAFLD (95%), P = 0.021-yr survival for NAFLD and non-NAFLD patients was 76% vs 83%, P = 0.32 3-yr survival was 76% for NAFLD vs 73% for non-NAFLD, P = 0.78	30-d patient survival worse in NAFLD (81%) vs non-NAFLD (97%), (81% vs 97%, P = 0.001)1-yr survival for NAFLD and non-NAFLD patients was 76% vs 90%, P = 0.06 3-yr survival was 76% for NAFLD vs 84% for non-NAFLD, P = 0.23	Not reported	Not reported	3-yr survival was significantly worse for diabetic patients compared to non-diabetics (63% vs 89%, P = 0.006)
Yalamanchili et al[22]	40 recipients with NAFLD	Liver transplant recipients at a single German center between 2007 and 2011	1-yr survival reported	Not reported	30 d mortality for NAFLD patients was 25% and 1-yr mortality was 35%	Not reported	Not reported	Patients with BMI > 35 kg/m2had worse graft survival (1-yr graft failure 55%) than those with lower BMI
Contos et al[32]	30 recipients with CRC and NASH compared to patients with ALD[16] and PBC/PSC[12]	Liver transplant recipients at a single US center between 2004 and 2007	Median follow up 3.5 yr	Graft survival similar between NAFLD and non-NAFLD patients (P = 0.32)	Patient survival similar between NAFLD and non-NAFLD patients (P = 0.32)	100% of the 30 NAFLD patients had steatosis in the graft by 5-yr post-transplant compared to 25% in the ALD and PBC/PSC groups	Steroid dose post-transplant associated with NAFLD recurrence	Not reported
Ong et al[31]	51 recipients with CRC	Liver transplant recipients at a single US center between 2004 and 2007	> 6 mo post-transplant, not reported	Not reported	Not reported	Post-transplant NAFLD developed in 25% and NASH in 16%	Predictors of post-transplant NAFLD was pre or post-transplant diabetes and triglyceride levels	Not reported
Bhagat et al[19]	71 NAFLD patients compared to 83 ALD patients	Liver transplant recipients at a single US center between 1997 and 2007	Median follow up 1517 d in NAFLD group and 1686 d in ALD group	Graft survival similar between NAFLD (76%) and ALD (82%)	1-yr, 3-yr, 5-yr, and 9-yr survival NASH: 82%, 79%, 75%, and 62% ALD: 92%,86%, 86%, and 76% (P = 0.17)	NAFLD recurrence was 33% (21/64 NASH patients)	None reported	No predictive factors in NAFLD
Malik et al[23]	98 NAFLD recipients compared to 196 with PBC/PSC196 with ALD 196, with HCV 98, with CR	Liver transplant recipients at a single US center between 2004 and 2007	Mean follow-up was 994 d	Not reported	Survival similar between NAFLD and non-NAFLD recipients30-d mortality in NAFLD 6.1% 1-yr mortality 21.4% in NAFLD (similar to controls)3-yr mortality in NAFLD 25% similar to controls, less in PBC (15%) 5-yr mortality (28%) similar in NAFLD patients and controls	Not reported	Not reported	Sepsis accounted for more deaths in NAFLD transplant recipientsLiver recipients transplanted for NASHcirrhosis who died within the first post-transplant year were more likely tobe older (≥ 60 yr), more obese (BMI ≥ 30 kg/m2) and have both pretransplant diabetes and Hypertension

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; ALD: Alcoholic liver disease; PBC: Primary biliary cirrhosis; CRC: Cryptogenic cirrhosis; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; PSC: Primary sclerosing cholangitis; CR: Cryptogenic cirrhosis; LDLT: Living donor liver transplantation.