Diagnostic Performance of Attenuation to Stage Liver Steatosis with MRI Proton Density Fat Fraction as Reference: A Prospective Comparison of Three US Machines.

Background US tools to quantify liver fat content have recently been made clinically available by different vendors, but comparative data on their accuracy are lacking. Purpose To compare the diagnostic performances of the attenuation parameters of US machines from three different manufacturers (vendors 1, 2, and 3) in participants who underwent liver fat quantification with the MRI-derived proton density fat fraction (PDFF). Materials and Methods From July 2020 to June 2021, consecutive participants with chronic liver disease were enrolled in this prospective single-center study and underwent MRI PDFF quantification (reference standard) and US on the same day. US was performed with two different machines from among three vendors assessed. Areas under the receiver operating characteristic curve (AUCs) for the staging of liver steatosis (MRI PDFF: ≥5.5% for grade ≥S1 and ≥15.5% for grade ≥S2) were calculated in test and validation samples and then compared between vendors in the study sample. Results A total of 534 participants (mean age, 60 years ± 13 [SD]; 320 men) were evaluated. Failure of measurements occurred in less than 1% of participants for all vendors. Correlation coefficients with the MRI PDFF were 0.71, 0.73, and 0.54 for the attenuation coefficients of vendors 1, 2, and 3, respectively. In the test sample, AUCs for diagnosis of steatosis grade S1 and higher and grade S2 and higher were 0.89 and 0.93 for vendor 1 attenuation, 0.88 and 0.92 for vendor 2 attenuation, and 0.79 and 0.79 for vendor 3 attenuation, respectively. In the validation sample, a threshold value of 0.65 for vendor 1 and 0.66 for vendor 2 yielded sensitivity of 77% and 84% and specificity of 78% and 85%, respectively, for diagnosis of grade S1 and higher. Vendor 2 attenuation had greater AUCs than vendor 3 attenuation (P = .001 and P = .003) for diagnosis of grade S1 and higher and grade S2 and higher, respectively, and vender 2 had greater AUCs for attenuation than vendor 1 for diagnosis of grade S2 and higher (P = .04). For all vendors, attenuation was not associated with liver stiffness (correlation coefficients <0.05). Conclusion To stage liver steatosis, attenuation coefficient accuracy varied among US devices across vendors when using MRI proton density fat fraction quantification as the reference standard, with some demonstrating excellent diagnostic performance and similar cutoff values. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Dubinsky in this issue.

Mycophenolate mofetil decreases humoral responses to three doses of SARS-CoV-2 vaccine in liver transplant recipients.

BACKGROUND AND AIMS: After 2 doses, the efficacy of anti-SARS-CoV-2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non-responsiveness in liver transplant recipients. METHODS: We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021. RESULTS: 598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti-SARS-Cov-2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre >260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti-SARS-CoV-2 antibodies after vaccination (OR 0.458; 95%CI 0.258-0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194-4.227; p = .012) and receiving an mRNA vaccine (vs a non-mRNA vaccine) (OR 4.107, 95%CI 1.145-14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events. CONCLUSIONS: Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Impact of calcineurin inhibitor-free immunosuppression on de novo donor-specific antibody formation in liver transplant recipients.

BACKGROUND & AIMS: Low calcineurin inhibitor (CNI) levels expose liver transplant recipients to rejection episodes and potentially to antibody-mediated rejection. There are little data on the impact of CNI-free immunosuppression on de novo donor-specific HLA antibody (dnDSA) development. Here we evaluated the prevalence of dnDSA in liver transplant recipients on CNI-free maintenance regimens and their associations with histopathological abnormalities of allografts. METHODS: Seven hundred and twenty-seven liver transplant recipients underwent a first liver transplant between 2000 and 2018 in three French transplant centres and had protocolized follow-up with dnDSA screening and allograft biopsy 1, 5 and 10 years after transplantation. RESULTS: CNIs were withdrawn in 166 (22.8%) patients with or without conversion to mammalian target of rapamycin inhibitors and/or maintenance with mycophenolic acid. DSA were present after withdrawal in 30.1% (50/166) patients on CNI-free immunosuppression compared with 16% (90/561) on CNI maintenance therapy (p < 0.001). The cumulative incidence of dnDSA 10 years after transplant was 20% in the CNI group versus 28% in the CNI-free group (p < 0.01). dnDSAs were associated with histological graft abnormalities (significant allograft fibrosis or rejection) (HR 2.24, 95% CI 1.2-4.1; p = 0.01). In univariate Cox regression analysis, being on a CNI-free regimen did not impact graft histology. CONCLUSIONS: Patients on a CNI-free IS regimen have a higher prevalence of dnDSA than patients on a standard IS regimen. dnDSAs but not CNI-free immunosuppression were associated with abnormal allograft histology.

Liver transplantation for NAFLD cirrhosis: Age and recent coronary angioplasty are major determinants of survival.

BACKGROUND AND AIMS: Liver transplantation (LT) is the treatment of end-stage non-alcoholic liver disease (NAFLD), that is decompensated cirrhosis and/or complicated by hepatocellular carcinoma (HCC). Few data on long-term outcome are available. The aim of this study was to evaluate overall patient and graft survivals and associated predictive factors. METHOD: This retrospective multicentre study included adult transplant patients for NAFLD cirrhosis between 2000 and 2019 in participating French-speaking centres. RESULTS: A total of 361 patients (69.8% of male) were included in 20 centres. The median age at LT was 62.3 years [57.4-65.9] and the median MELD score was 13.9 [9.1-21.3]; 51.8% of patients had HCC on liver explant. Between 2004 and 2018, the number of LT for NAFLD cirrhosis increased by 720%. A quarter of the patients had cardiovascular history before LT. Median follow-up after LT was 39.1 months [15.8-72.3]. Patient survival at 1, 5 and 10 years after LT was 89.3%, 79.8% and 68.1% respectively. The main causes of death were sepsis (37.5%), malignancies (29.2%) and cardiovascular events (22.2%). In multivariate analysis, three risk factors for overall mortality after LT were recipient pre-LT BMI < 32 kg/m2 at LT time (OR: 2.272; p = .012), pre-LT angioplasty during CV check-up (OR: 2.916; p = .016), a combined donor and recipient age over 135 years (OR: 2.020; 95%CI: p = .035). CONCLUSION: Survival after LT for NAFLD cirrhosis is good at 5 years. Donor and recipient age, and cardiovascular history, are major prognostic factors to consider.

Progression of AFP SCORE is a Preoperative Predictive Factor of Microvascular Invasion in Selected Patients Meeting Liver Transplantation Criteria for Hepatocellular Carcinoma.

Microvascular invasion (MVI) is one of the main prognostic factors of hepatocellular carcinoma (HCC) after liver transplantation (LT), but its occurrence is unpredictable before surgery. The alpha fetoprotein (AFP) model (composite score including size, number, AFP), currently used in France, defines the selection criteria for LT. This study's aim was to evaluate the preoperative predictive value of AFP SCORE progression on MVI and overall survival during the waiting period for LT. Data regarding LT recipients for HCC from 2007 to 2015 were retrospectively collected from a single institutional database. Among 159 collected cases, 34 patients progressed according to AFP SCORE from diagnosis until LT. MVI was shown to be an independent histopathological prognostic factor according to Cox regression and competing risk analysis in our cohort. AFP SCORE progression was the only preoperative predictive factor of MVI (OR = 10.79 [2.35-49.4]; p 0.002). The 5-year overall survival in the progression and no progression groups was 63.9% vs. 86.3%, respectively (p = 0.001). Cumulative incidence of HCC recurrence was significantly different between the progression and no progression groups (Sub-HR = 4.89 [CI 2-11.98]). In selected patients, the progression of AFP SCORE during the waiting period can be a useful preoperative tool to predict MVI.

Alcohol Consumption the Day of Liver Transplantation for Alcohol-Associated Liver Disease Does Not Affect Long-Term Survival: A Case-Control Study.

Alcohol abstinence before liver transplantation (LT) for alcohol-associated liver disease (ALD) is required for every candidate. Some listed patients might relapse, resulting in LT for patients nonabstinent during the pretransplant period. Long-term survival outcomes of these patients have never been studied. We sought to determine whether alcohol consumption on the day of the LT influenced long-term survival after LT. We conducted a retrospective case-control study among French LT centers. Cases were defined as recipients between January 1995 and December 2007 having positive blood and/or urine alcohol levels the day of LT. Each case was paired with 2 controls corresponding to patients transplanted for ALD during the same trimester. Patients were classified into 3 categories per alcohol consumption: abstainers, occasional or transitory excessive consumers, or patients with a sustained excessive consumption (daily consumption >20-30 g/day). During the study period, 3052 LTs for ALD were conducted in France. We identified 42 cases paired with 84 controls. Median blood alcohol level was 0.4 g/L (range 0.1-4.1 g/L) and median urine alcohol level was 0.2 g/L (range 0.1-2.0 g/L). Median follow-up period until death or censoring was 12.9 years (CI95% = [12.3; 13.6]). Long-term survival was not different between the groups. Relapse to any alcohol consumption rate was higher in the case group (59.5%) than in the control group (38.1%, odds ratio 2.44; CI95% = [1.13; 5.27]), but sustained excessive consumption was not significantly different between the groups (33.3% versus 29.8% in case and control groups respectively, χ2  = 0.68). Rates of recurrent cirrhosis and cirrhosis-related deaths were more frequent in the case group. Liver transplantation for nonabstinent patients during the immediate pretransplant period does not result in impaired long-term survival despite higher relapse and recurrent cirrhosis rates.

Natural History of Recurrent Alcohol-Related Cirrhosis After Liver Transplantation: Fast and Furious.

Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). Severe alcohol relapse can rapidly lead to recurrent alcohol-related cirrhosis (RAC) for the graft. The aim of this study was to describe the natural history of RAC and the overall survival after LT and after an RAC diagnosis. From 1992 to 2012, 812 patients underwent primary LT for ALD in 5 French transplant centers. All patients with severe alcohol relapse and an RAC diagnosis on the graft were included. The diagnosis of cirrhosis was based on the analysis of liver biopsy or on the association of clinical, biological, radiological, and/or endoscopic features of cirrhosis. RAC was diagnosed in 57/162 patients (35.2%) with severe alcohol relapse, and 31 (54.4%) of those patients had at least 1 episode of liver decompensation. The main types of decompensation were ascites (70.9%), jaundice (58.0%), and hepatic encephalopathy (9.6%). The cumulative probability of decompensation was 23.8% at 5 years, 50.1% at 10 years, and 69.9% at 15 years after LT. During the follow-up, 36 (63.2%) patients died, the main cause of death being liver failure (61.1%). After diagnosis of cirrhosis, the survival rate was 66.3% at 1 year, 37.8% at 5 years, and 20.6% at 10 years. In conclusion, RAC is associated with a high risk of liver decompensation and a poor prognosis. Prevention of severe alcohol relapse after LT is a major goal to improve patient survival.

Immunosuppression Minimization Trials in Liver Transplantation: Can We Predict Humoral Response to Assess Eligibility?

We have read with great interest the article by Jucaud et al. (1) reporting that de novo donor-specific HLA antibodies (dnDSA) development during immunosuppression (IS) withdrawal in liver transplantation (LT) was associated with acute rejection and prevented further attempts of IS withdrawal. This article is protected by copyright. All rights reserved.

Integration of an Addiction Team in a Liver Transplantation Center.

Up to 50% of liver transplantation (LT) recipients with known or clandestine alcohol-use disorder (AUD) before surgery return to alcohol use after LT. However, only severe alcohol relapse, which varies in frequency from 11% to 26% of patients, has an impact on longterm survival and significantly decreases survival rates after 10 years. Therefore, it is crucial to identify patients with the highest risk of severe relapse in order to arrange specific, standardized monitoring by an addiction team before and after LT. The aims of this study were to describe the effects of combined management of AUD on the rate of severe alcohol relapse and to determine the risk factors before LT that predict severe relapse. Patients transplanted between January 2008 and December 2014 who had met with the LT team's addiction specialist were included in the study. Patients who exhibited alcohol-related relapse risk factors received specific addiction follow-up. A total of 235 patients were enrolled in the study. Most of them were men (79%), and the mean age at the time of the LT was 55.7 years. Severe relapse occurred in only 9% of the transplant recipients. Alcohol-related factors of severe relapse were a pretransplant abstinence of 6 months and family, legal, or professional consequences of alcohol consumption, whereas the nonalcohol-related factors were being single and being eligible for a disability pension. In conclusion, the integration of an addiction team in a LT center may be beneficial. The addiction specialist can identify patients at risk of severe relapse in the pretransplantation period and hence arrange for specific follow-up.

The Influence of Alcohol Use on Outcomes in Patients Transplanted for Non-alcoholic Liver Disease.

Alcohol relapse after liver transplantation (LT) for alcoholic liver disease (ALD) is a common event that has been extensively studied. In contrast, alcohol consumption has usually been neglected in patients transplanted for other liver diseases. First off, patients can be mislabeled as 'non-ALD' when they suffer from another chronic liver disease. Then, alcohol consumption is not systematically tracked after LT in recipients having a primary indication other than ALD, although there are increasing data incriminating alcohol as responsible for graft damage and impaired survival. This review discusses the potential consequences of alcohol after liver transplantation, focusing on patients transplanted for non-alcoholic liver disease, as well as the legitimate role of an addiction specialist, before and after LT. SHORT SUMMARY: Alcohol relapse after liver transplantation (LT) for alcoholic liver disease (ALD) is a common event that has been extensively studied. In contrast, alcohol consumption has usually been neglected in patients transplanted for other liver diseases. There are increasing data showing that alcohol consumption and its consequences should be tracked in every transplant candidate and recipient.

Follow-Up of Alcohol Consumption After Liver Transplantation: Interest of an Addiction Team?

BACKGROUND: Alcohol relapses after liver transplantation (LT) constitute a critical issue. Because there is no widely accepted definition of LT, its prevalence varies from 7 to 95% across studies. Only a severe relapse, the frequency of which is estimated to be 11 to 26%, decreases life expectancy after 5 years of LT and requires specific care. To improve the early identification of alcohol consumption among transplanted patients, liver transplant teams may be helped by input from an addiction team. Nevertheless, added benefit of involvement by addiction specialists in treating posttransplant patients has not been demonstrated. Thus, the aim of this study was to compare the evaluation of the alcohol consumption after LT performed routinely during the transplant consultation or obtained from a specific addiction consultation. METHODS: This was a prospective single-site study. Patients were seen consecutively by their hepatologist and by an addiction specialist, and they completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Thus, the patient's alcohol status was assessed using 3 different sources of information: the hepatologist's interview, the AUDIT-C score, and the addiction specialist visit. RESULTS: One hundred forty-one patients were consecutively evaluated. Alcohol consumption was identified by the hepatologist in 31 patients (21.9%), in 52 (36.8%) using the AUDIT-C questionnaire, and in 58 (41.1%) by the addiction specialist. The 31 patients concerned reported an average of 6.5 alcohol units/wk to the transplant physician, a number which was significantly greater (p = 0.001) by 8.6 units/wk when they were interviewed by the addiction specialist. CONCLUSIONS: This study highlights the clinical utility of a systematic addiction consultation among liver transplant patients, irrespective of the reason for transplantation.

Recurrent alcoholic cirrhosis in severe alcoholic relapse after liver transplantation: a frequent and serious complication.

OBJECTIVES: Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT). Recurrent alcoholic cirrhosis (RAC) after LT can occur but has not been studied. The aims of this study were to estimate the prevalence, predictive factors, and natural history of RAC after LT. METHODS: All patients transplanted for ALD between 1990 and 2007 in three French centers were included. The diagnosis of RAC was based on histological evidence or a series of features combined with severe alcoholic relapse. RESULTS: Among 1,894 adult LT patients, 712 were transplanted for alcoholic cirrhosis and survived >6 months. After a mean follow-up of 9 years, 128 patients (mean age at LT 47.2±7.1 years old, 78.9% men) experienced severe alcoholic relapse (18.0% of cases). Severe alcoholic relapse occurred after a median delay of 25 months (range 4-157) after LT. RAC was diagnosed in 41 patients with severe relapse (32%). The diagnosis of RAC was made after a median delay of 5.1 years (range 1.8-13.9) after LT and of 4.0 years (range 1.2-11.5) after relapse. RAC was significantly associated with younger age and a shorter period of pre-LT abstinence. One-, 5-, 10-, and 15-year survival was 100, 87.6, 49.7, and 21.0%, respectively, for RAC patients vs. 100, 89.4, 69.9, and 41.1%, respectively, for the patients without RAC (P<0.001). CONCLUSIONS: RAC occurs in <6% of ALD transplant patients. One-third of severe alcoholic relapse patients develop RAC <5 years after transplantation with a very poor prognosis.

Incidence of solid organ cancers after liver transplantation: comparison with regional cancer incidence rates and risk factors.

BACKGROUND & AIMS: Increased rates of solid organ cancers post-liver transplantation have been reported, but the contribution of environmental factors and immunosuppressive therapy is not clear. This study's aims were to compare the incidence of de novo solid organ cancers after liver transplantation; identify risk factors independent of immunosuppressive therapy associated with these cancers; and assess the influence of calcineurin inhibitors on the appearance of these cancers. METHODS: This single-centre study from 1991 to 2008 included 465 liver recipients who had survived for ≥1 year. Gross incidence rates were standardized by age and sex, using the global population as a reference. In addition, 322 of the 465 patients treated for ≥1 year with calcineurin inhibitors were studied. RESULTS: Sixty-five (13.9%) of the 465 patients developed de novo solid cancers. The overall relative risk was 3.7. Significantly increased relative risks were observed for digestive, oesophageal, colorectal, oral and lung cancers, but not for genito-urinary and breast cancers. Among the 65 patients who developed solid organ cancers, 43 died (66.1%), 41 from cancer. The two independent risk factors were pretransplant smoking [P < 0.0001; odds ratio = 5.5 (.5; 12)] and obesity [P = 0.0184; odds ratio = 2.2 (1.1; 4.3)]. Of the 322 patients on calcineurin inhibitors, 55 (17%) developed de novo solid cancers. Tacrolimus exposure level was a risk factor for de novo solid cancers [P < 0.0001; OR = 15.3 (4.5; 52.2)]. CONCLUSIONS: We recommend a change in immunosuppressive protocols with lifestyle/dietary guidelines and smoking cessation.

Integrating an addiction team into the management of patients transplanted for alcohol-associated liver disease reduces the risk of severe relapse.

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

Bariatric surgery and liver transplantation, here we are now: A French nationwide retrospective study.

At the time of the growing obesity epidemic worldwide, liver transplantation (LT) and metabolic syndrome are closely linked: non-alcohol-related fatty liver disease (NAFLD) is one of the leading indications for liver transplantation, and metabolic syndrome can also appear after liver transplantation, in relation to immunosuppressive medications and weight gain, whatever was the initial liver disease leading to the indication of LT. Therefore, the role of bariatric surgery (BS) is important due to its longer-lasting effect and efficacy. We performed a retrospective review of all 50 adult French liver transplant recipients who had a history of bariatric surgery, including 37 procedures before transplantation, and 14 after. There were three significantly different characteristics when comparing pre-and post-LT BS: patients were older (at the time of BS), presented more frequently arterial hypertension (at the time of LT), and the proportion of NAFLD as initial liver disease leading to LT was lower, in the post-LT group. Regarding pre-LT BS, in one case BS was complicated by liver failure leading to the rapid indication of LT; it was the single patient for whom the delay between BS and LT was less than 1 year; there was no patient who specifically underwent BS for the purpose of LT listing.

Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort.

Background & Aims: Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer therapy. Liver toxicity occurs in up to 25% of patients treated with ICIs. The aim of our study was to describe the different clinical patterns of ICI-induced hepatitis and to assess their outcome. Methods: We conducted a retrospective observational study of patients with checkpoint inhibitor-induced liver injury (CHILI) discussed in multidisciplinary meetings between December 2018 and March 2022 in three French centres specialised in ICI toxicity management (Montpellier, Toulouse, Lyon). The hepatitis clinical pattern was analysed by the ratio of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (R value = (ALT/ULN)/(ALP/ULN)) for characterisation as cholestatic (R ≤2), hepatocellular (R ≥5), or mixed (2

Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis.

Background & Aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it. Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies. Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence. Conclusion: Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated. Impact and implications: Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.