Recurrence Of Nonalcoholic Steatohepatitis Research Articles

Impact of living donor liver transplantation on long-term cardiometabolic and graft outcomes in cirrhosis due to nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). This study aimed to determine whether living donor LT (LDLT) recipients experienced less recurrent NASH, cirrhosis, and cardiometabolic complications compared to deceased donor LT (DDLT). Patients with LDLT and DDLT for NASH between February 2002 and May 2018 at University Health Network (UHN) were compared. Cox Proportional Hazard model was used to analyze overall survival (OS), Fine and Gray's Competing Risk models were conducted to analyze cumulative incidence of post LT outcomes. One hundred and ninety-nine DDLTs and 66 LDLTs were performed for NASH cirrhosis. Time and rate of recurrence of NAFLD and NASH were comparable in both groups. Graft cirrhosis was more common in DDLT recipients (n=14) versus LDLT (n=0) (p<.0001). Significant fibrosis (Fibrosis≥F2) developed in 50 recipients (12 LDLT and 38 DDLT) post LT (DDLT vs. LDLT: HR=1.00, 95% CI=(.52-1.93), p=.91) and there was no difference in time to significant fibrosis (p=.57). There was no difference in development of post-transplant diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, and cancers. LDLT group had better renal function at 10years (MDRD eGFR of 57.0mL/min vs. 48.5mL/min, p=.047). Both groups had a comparable OS (HR=1.83 (95% CI=.92-3.62), p=.08). Overall, LDLT recipients had significantly better renal function by virtue of having early transplantation in their disease course. LDLT was also associated with significantly less graft cirrhosis, although OS and cardiometabolic outcomes were comparable between LDLT and DDLT.

Relatively Poor Long-term Outcomes Following Liver Transplantation for NASH in the United States.

Nonalcoholic steatohepatitis (NASH) continues to increase in frequency as an indication for liver transplantation (LT). Data on long-term outcomes for these patients are limited. We aimed to compare long-term patient and graft survival in patients undergoing LT for NASH in the United States to other indications. We analyzed data from the Scientific Registry of Transplant Recipients of adult patients who underwent primary deceased-donor LT from January 1, 2005, to December 31, 2019. NASH has increased as an indication for LT by 4.5-fold, from 5.2% in 2005 to 23.4% in 2019. Patient (61.2%) and graft survival (59.2%) at 10 y are significantly poorer for NASH than for all other indications other than alcohol. Patients transplanted for NASH have higher body mass index (32.2 versus 27.6) and greater frequency of diabetes (13% versus 11.6%) than any other indication ( P < 0.001). Portal vein thrombosis, location in intensive care unit, dialysis, and pre-LT diabetes ( P < 0.001 for all) are independently predictive of patient death and graft loss. Body mass index is not predictive. NASH patients undergoing simultaneous liver kidney have markedly worse 10-y patient and graft survival than liver-only (52.3% versus 62.1%). Graft loss was attributed to recurrence of NASH in <1% of patients. LT for NASH is associated with relatively poor long-term patient and graft survival when compared with patients transplanted for other indications, NASH patients undergoing simultaneous liver kidney have the worst long-term outcomes.

A Single-Center Study of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Recurrence in Recipients of Liver Transplant for Treatment of Nonalcoholic Steatohepatitis Cirrhosis.

Nonalcoholic steatohepatitis is a growing indication for liver transplant. We examined multiple granular elements to determine risk factors for recurrence of nonalcoholic steatohepatitis or recurrence of nonalcoholic fatty liver disease. This is a retrospective, single-center study of patients who underwent liver transplant for nonalcoholic steatohepatitis. Demographic differences were assessed with the Wilcoxon and Pearson tests for continuous and discrete variables, respectively. We used a linear mixed effects model to estimate mean changes in body mass index and laboratory measurements. Time to graft loss was analyzed with the Cox proportional hazards model. From 1998 to 2017, there were 275 patients at our center who underwent liver transplant as treatment for nonalcoholic steatohepatitis cirrhosis. Of these patients, 31 (11%) were diagnosed with recurrent nonalcoholic steatohepatitis and 60 (22%) had recurrent nonalcoholic fatty liver disease. Patients with or without recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease were similar with regard to Model for End-Stage Liver Disease score, body mass index, sex, ethnicity, comorbidity, and donor characteristics, including donor macrosteatosis. Exposures to several medication classes were examined, but there was no association with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. Changes in aspartate aminotransferase and alanine aminotransferase levels over time were correlated with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease versus levels observed in the groups with no recurrent disease. There was no difference in graft survival for the groups with recurrence of either nonalcoholic steatohepatitis or nonalcoholic fatty liver disease. Recurrence of nonalcoholic fatty liver disease and recurrence of nonalcoholic steatohepatitis were not associated with increased mortality after liver transplant. There were notable steady increases in body mass index after transplant for all patients who received liver transplant as treatment for nonalcoholic steatohepatitis.

Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation.

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible.

P-114 LIVER TRANSPLANTATION FOR NON-ALCOHOLIC STEATOHEPATITIS: OUTCOMES IN THE MAIN TRANSPLANT CENTER IN PERU

Actually, Metabolic associated Fatty Liver Disease (MAFLD) is the most prevalent liver disease in the world and Non-Alcoholic Steatohepatitis (NASH) cirrhosis is the main indication for liver transplantation (LTx). To describe the frequency, characteristics, and outcomes of liver transplantation for patients with NASH in the main transplant center in Lima, Peru. We analyzed data from liver transplant patients from March 2000 to December 2020 using the electronic data. A sample of 89 patients was selected from a total of 286 liver transplants. Inclusion criteria: Patients with Liver biopsy performed 12 months after LTx. Patients under 14 years of age or those who had hepatic steatosis with an etiological diagnosis of virus C or post-transplant alcohol consumption were excluded. The most frequent etiologies of liver cirrhosis in transplant patients in general were NASH, Autoimmune Hepatitis and Alcoholic liver disease: 34.83%, 19.10% and 12.36% respectively, with a mean BMI of 25.68 (SD=4.48). In pre transplant setting: NASH had a BMI of 28.38 (SD=4.44) and those who did not have 24.39 (SD=3.91). 32.58% (n=29). NASH post-transplant recurrence: 23.60% (n=21) and only 8.99% (n=8) mild steatosis. The recurrence of NAFLD and NASH was 62.07% (n=18) and 61.90% (n=13) respectively, while the presentation of NAFLD and NASH de novo was 37.93% (n=11) and 38.10% (n=8). The prevalence of NASH post-liver transplantation is high in Peru. Post-transplant MAFLD/NASH recurrence was higher than de novo cases and BMI was high in this group.

NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.

Nonalcoholic steatohepatitis recurrence after liver transplant.

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplant (LT)worldwide and is deemed to be the foremost indication in the near future. Recurrence of NASH can occur post LT and has been observed to be a common phenomenon. Baseline metabolic co-morbidities and worsening of metabolic profile post LT are the principal drivers of NASH recurrence. Liver biopsy remains the gold standard for establishing the diagnosis. However, noninvasive methods including transient elastography (TE) and magnetic resonance imaging (MRI) seem to be promising. The implications of recurrent NASH on post LT outcomes, graft steatosis, progression to fibrosis, overall survival, and cardiovascular associations warrant careful evaluation. Control of metabolic parameters and weight gain along with tailored immunosuppression remain the cornerstone of management. Extrapolation of the ever-increasing armamentarium of NASH pharmacotherapy specifically in this population of recurrent NAFLD remains a challenge for the future.

Incidence and Risks for Nonalcoholic Fatty Liver Disease and Steatohepatitis Post-liver Transplant: Systematic Review and Meta-analysis.

The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT. MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale. Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes. There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.

2444 Beyond Weight Loss: Bariatric Surgery as Treatment for NAFLD in the Post-Transplant Patient

INTRODUCTION: Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG), has previously demonstrated reversal of abnormal liver histology in non-alcoholic fatty liver disease (NAFLD). However, bariatric surgery following orthotopic liver transplant (OLT) performed for non-alcoholic steatohepatitis (NASH) cirrhosis is less well studied, with only a few retrospective studies cited in the literature. We present the case of bariatric surgery performed in a patient status post OLT with successful reversal of NAFLD. CASE DESCRIPTION/METHODS: The patient is a 69-year-old female with past medical history of metabolic syndrome (diabetes, hypertension, dyslipidemia, obesity) and cirrhosis secondary to NASH and alcohol who underwent deceased donor OLT. Eighteen months postoperatively, the patient had gained 20 pounds and required multiple medications to control her blood pressure and diabetes. Subsequent abdominal ultrasound with doppler demonstrated hepatic steatosis, patent transplant vasculature and no ascites. Despite dietary and lifestyle modifications, the patient could not lose weight. She continued to have elevated transaminases (up to aspartate aminotransferase 58, alanine aminotransferase 82) prompting suspicion for recurrent NASH. The patient was ultimately referred for LSG. Her BMI prior to LSG was 37; seven weeks postoperatively it decreased to 32. Her liver function test normalized, and she no longer required Metformin. DISCUSSION: NAFLD is the most common chronic liver disorder in developed countries, and NASH cirrhosis is the second most common cause for liver transplant in the United States. Approximately 3-5% of the population in the United States lives with NASH, and this number is expected to rise with the obesity epidemic. Further troubling is NASH and cryptogenic cirrhosis seen in post-OLT patients, with one study citing 39% of those transplanted for NAFLD-related cirrhosis show steatosis on biopsy six months after transplant. Bariatric surgery, both RYGB and LSG, can reverse NAFLD histology, and only recently have retrospective reviews examined bariatric surgery as a successful means of halting and reversing NAFLD in the post-transplant patient. As with the case of our patient, bariatric surgery can provide an effective means of treating NAFLD in the post-OLT patient with metabolic syndrome. More research is currently needed to establish optimal patient selection criteria and long term efficacy in this regard.

223-OR: Pioglitazone Discontinuation in Patients with Nonalcoholic Steatohepatitis (NASH) Is Associated with Disease Recurrence

Pioglitazone (PIO) therapy results in a ∼60% resolution of NASH in patients with prediabetes or T2DM. However, the effects of treatment discontinuation have not been carefully examined. To this end, we assessed plasma aminotransferases (LFTs) after study drug discontinuation among patients who had completed 36 months (n=63) of our randomized, controlled trial (RCT) of PIO for NASH (Cusi, et al. Ann Intern Med 2016). This was an 18 month RCT of PIO 45mg QD vs. placebo (and dietary counseling in all), followed by 18 months of open label PIO. We retrospectively assessed LFTs for 18 months following study discontinuation. PIO normalized plasma ALT, an indicator of hepatocyte injury in NASH, within 3 months of therapy initiation (from 61±5 to 35±2 U/L; p&amp;lt;0.001) and for the duration of treatment (Figure 1). However, PIO discontinuation resulted in a rapid rebound of LFTs after 3 months (from 30±2 to 42±7 U/L, p=0.02), and continued to increase over time, reaching the highest levels 18 months after discontinuation (59±12 U/L, p&amp;lt;0.001 vs. end of the trial). Plasma AST followed a similar pattern during treatment and after discontinuation. Conclusion: PIO rapidly normalizes LFTs in NASH and improves liver histology, but its discontinuation results in an abrupt increase in LFTs, likely reflecting NASH recurrence. Therefore, PIO therapy for NASH should be considered as a long-term management approach. Disclosure F. Bril: None. R. Lomonaco: None. S. Kalavalapalli: None. J. Lai: None. K. Cusi: Consultant; Self; Allergan, AstraZeneca, Genentech, Inc., Novo Nordisk Inc., Poxel SA, ProSciento. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Research &amp; Development, Novartis AG, Novo Nordisk Inc. Funding American Diabetes Association (1-08-CR-08 to K.C.); Burroughs Wellcome Fund; National Center for Research Resources (M01-RR-01346); University of Texas Health Science Center at San Antonio; U.S. Department of Veterans Affairs

Characteristics and risk factors for recurrence of nonalcoholic steatohepatitis following liver transplantation

Objectives: Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), is known to recur after LT. Since the recurrence of NASH can lead to graft failure, the identification of predictive factors is needed and preventive strategies should be implemented.Methods: We retrospectively examined 95 patients who had undergone LT for NASH or alcoholic liver disease (ALD) as a primary indication. We evaluated peritransplant characteristics and histological findings 1-year post LT among liver transplant patients due to NASH or ALD.Results: Pre-LT body mass index (BMI) was higher and pre-LT diabetes was more prevalent in NASH patients than in ALD patients (p < .01). The difference of BMI persisted at 3 months and 1 year after LT. There were no differences between the groups regarding histopathological findings including the degree of steatosis and fibrosis in 1-year biopsy. In multivariate analysis, recipient age and 1-year BMI were independent risk factors for post-LT fatty liver disease development. Regarding predictive factors of NASH recurrence, the prevalence of pre-LT insulin-dependent diabetes was significantly higher in patients who developed NASH recurrence than those who did not. The increase of HbA1c at 1-year post-LT checkup was higher in patients who developed recurrence than those who did not, although the difference did not reach statistical significance.Conclusions: The results of this study suggest that insulin-dependent diabetes has detrimental effects on NASH recurrence following LT. Optimal glycemic control should be recommended, but studies are needed to prove its preventive effect on NASH recurrence.

Characteristics and risk factors of fatty liver disease development and nonalcoholic steatohepatitis recurrence after liver transplantation

Introduction: Nonalcoholic steatohepatitis (NASH), which is a common and increasing indication for liver transplantation (LT), is known to recur after LT. Since the recurrence of NASH can lead to graft failure, the identification of predictive factors and preventive strategies need to be implemented. Method: We retrospectively identified 694 consecutive patients who had undergone LT at Karolinska University Hospital between June 2007 and February 2017. Of these, 95 patients who received LT for NASH or alcoholic liver disease (ALD) as a primary indication were included. Peritransplant characteristics and histological findings 1 year post-LT among NASH patients were evaluated in comparison with ALD patients. Risk factors of post-LT fatty liver disease development and NASH recurrence were assessed. Result: Among 27 NASH patients, pre-LT body mass index (BMI) was higher (31.3 vs. 28.6, p=0.0095) and pre-LT diabetes was more prevalent than in ALD patients (p<0.0001). The difference of BMI persisted at 3 months and 1 year after LT. There were no differences between the groups regarding histopathological findings including the degree of steatosis and fibrosis in 1-year biopsy. In multivariate analysis, recipient age and 1-year BMI were independent risk factors for post-LT fatty liver disease development. Regarding predictive factors of NASH recurrence, the prevalence of pre-LT insulin dependent diabetes was significantly higher in patients who developed NASH recurrence than those who did not. The increase of HbA1c at 1-year post-LT check-up was higher in patients who developed recurrence than those who did not, although the difference did not reach statistical significance (Δ 15 vs. 5 mmol/mol, p=0.051). Conclusion: The results of this study suggests that insulin dependent diabetes has detrimental effects on NASH recurrence following LT. Optimal glycemic control should be recommended, but studies are needed to prove its preventive effect on NASH recurrence.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

Incidence of Recurrent NASH-Related Allograft Cirrhosis.

Cirrhosis secondary to nonalcoholic steatohepatitis (NASH) is projected to become the leading indication for liver transplantation (LT) in the USA in the next decade. The long-term implications of post-LT NASH, specifically on the development of allograft cirrhosis, are not well known. A retrospective cohort of patients at a single large center undergoing LT for NASH from 2000 to 2015 was identified using a prospectively collected database. A total of 226 patients undergoing LT for NASH were identified. Mean follow-up for the cohort was 7years. Seventy-five percent of patients underwent at least one liver biopsy post-LT. Eighty-one patients (36%) developed recurrence of biopsy-proven NASH. Fifteen patients developed bridging fibrosis but only four patients (1.8%) progressed to recurrent NASH cirrhosis at a mean of 9years post-LT. Body mass index at the time of LT was statistically higher in the NASH allograft cirrhosis group. Recurrent disease was less common and less severe in those transplanted with black donors. All four patients with recurrent NASH cirrhosis developed evidence of portal hypertension, but all remained alive at follow-up. Although recurrent NASH following LT is common, the development of allograft cirrhosis is rare. These findings are useful when counseling patients and important to consider during their post-LT care.

Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft.

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

Sleeve gastrectomy decreases the incidence of metabolic syndrome in obese post-liver transplant patients

Background: Metabolic syndrome (MS) after liver transplant poses a significant heath burden, with one-third of post liver transplant (OLT) patients developing recurrent non-alcoholic steatohepatitis (NASH). Bariatric surgery improves MS and NASH in the general population, however, this benefit is unknown in OLT patients. We aim to evaluate the efficacy of laparoscopic sleeve gastrectomy (LSG) as treatment of MS following OLT. Methods: A retrospective review of a single high-volume transplant center experience was performed. Over a 2-year period, 16 obese patients with a history of OLT were referred to our institution's metabolic surgery clinic. Of these, 11 patients underwent LSG. Patient demographics, comorbidities, body mass index (BMI), and 30-day complications were analyzed. Results: Median patient age was 61 years, pre-OLT BMI was 42.7 kg/m2 , and BMI prior to LSG was 40.0 kg/m2 . Median interval from transplant to LSG was 2.7 years and median follow-up after LSG was 375 days. For patients with 1 year follow-up (n = 7), median BMI was 33.3 kg/m2 , mean percent excess weight loss was 48.0% ± 21.0% and mean percent total body weight loss was 23.4% ± 8.9%. Incidence of MS was reduced by 75%. A 53% reduction in anti-hypertensive medications was seen and 2 of 3 patients discontinued insulin completely. While one patient required two units of blood post-operatively, there were no other complications. Patients without a LSG (n = 5) did not experience weight loss with a medical weight loss program (median pre-OLT BMI 33.7 kg/m2 , median post-OLT BMI 40.3 kg/m2 , and most recent median BMI 39.7 kg/m2 ) and none achieved resolution of MS. Conclusion: LSG is safe and effective for the management of obesity and metabolic syndrome in the post OLT population. By reducing the prevalence of MS after OLT, LSG may decrease the incidence of recurrent NASH.

Long-term Outcomes in Patients Undergoing Liver Transplantation for Nonalcoholic Steatohepatitis-Related Cirrhosis.

Nonalcoholic steatohepatitis (NASH), a clinically aggressive variant of nonalcoholic fatty liver disease (NAFLD), is becoming an increasingly common indication for liver transplantation (LT); however, relatively little is known regarding its clinical course post-LT. The aim of the current study is to describe disease recurrence and clinical course after LT. All surviving patients transplanted for NASH at the authors' institution had transient elastography (TE) to evaluate hepatic steatosis and fibrosis. The charts of deceased patients were reviewed for liver biopsy to evaluate for disease recurrence. Finally, causes of mortality in these patients were evaluated. Of the 103 patients who met criteria, 56 had TE, whereas 34 had a liver biopsy. Steatosis was detected in 49 (87.5%) of the patients who had a TE and were defined to have recurrent NAFLD. Most patients had liver stiffness measurements consistent with no fibrosis (42.9%) or F1-F2 fibrosis (30.4%). Advanced fibrosis was noted in 26.8%, whereas 5.4% had cirrhosis but were clinically compensated. In patients with liver biopsy, 88.2% had recurrent NAFLD, whereas 41.2% had recurrent NASH. Bridging fibrosis was noted in 20.6% of patients but no patients had cirrhosis. Within the cohort, 32 patients died with the leading cause of mortality cancer (25%), infectious complications (25%), and cardiovascular disease (21.9%). Only 9% of deaths were attributable to graft cirrhosis. Recurrent NAFLD is common post-LT occurring in nearly 88% of all patients, whereas nearly a quarter of patients were noted to have advanced fibrosis.

Nonalcoholic steatohepatitis recurrence and rate of fibrosis progression following liver transplantation.

Nonalcoholic steatohepatitis (NASH) is known to recur following liver transplantation (LT). Metabolic risk factors increase with immunosuppression. However, the rate of fibrosis progression following LT for NASH while on immunosuppression is less clear. The incidences of steatosis, NASH, and fibrosis following LT for NASH were quantified and compared with those transplanted for alcoholic liver disease (ALD). Records of all NASH patients and 1 : 2 match with ALD transplant recipients between 2001 and 2006 were reviewed retrospectively. Patients without liver biopsies beyond 2 months following LT were excluded. NASH patients (n=77) were older (P=0.0006) and less likely male (P<0.001) than ALD patients (n=108). The incidence of steatosis, NASH, and fibrosis stage increased at 1, 3, and 5 years in both groups. Although steatosis and nonalcoholic fatty liver disease activity scores were higher, fibrosis was lower in NASH compared with ALD (0.43 vs. 1.0 stage/year; P=0.0045). The incremental increase in the rate of fibrosis was faster in the first year compared with 4-5 years (0.8 vs. 0.04 stage/year) following LT. The rate of fibrosis progression during 4-5 years was decreased in NASH compared with ALD recipients (0.04 vs. 0.33 stage/year; P=0.015). NASH etiology was associated with reduced rate of fibrosis progression (odds ratio=0.67) on multivariate analysis. Despite having more steatosis and inflammation, progression of fibrosis was slower in NASH compared with ALD recipients. Fibrosis progression slows with time following LT on immunosuppression and approximates the pretransplant progression rate by year 5.

NASH cirrhosis as an increasing cause for liver transplantation – the Viennese experience

Background: Non-alcoholic steatohepatitis (NASH) represents the hepatic manifestation of the metabolic syndrome and can ultimately lead to liver cirrhosis. Since the global prevalence of the metabolic syndrome is increasing, NASH cirrhosis has become a leading cause for orthotopic liver transplantation (OLT). NASH recurrence may be observed after transplantation, not only due to host factors but also due to immunosuppressive therapy's side-effects. Some cases of NASH might have been misclassified as cryptogenic cirrhosis (CC) in the past, while the awareness for NASH cirrhosis has increased in recent years. Here we aimed to evaluate explant histology and the clinical course after OLT for CC versus NASH cirrhosis.

Recurrence of graft steatosis after liver transplantation for cryptogenic cirrhosis in recently commenced liver transplant program

Non-alcoholic fatty liver disease (NAFLD) seems to recur in at least one third of patients transplanted for non-alcoholic steatohepatitis (NASH)-related cirrhosis. While, NASH recurrence does not seem to affect overall graft and patient survival up to 10 years, cardiovascular and infection-related morbidity and mortality seem to be increased in these patients. This report looks at the graft histology in patients who were transplanted for NASH-related cirrhosis after short-term follow up. We report a high prevalence of recurrent NAFLD in liver grafts post-transplant among five patients. The degree of steatosis noted among the recipients is alarming.