Impact of Religious Affiliation on Clinical Outcomes in Liver Transplant Patients.

While the impact of spirituality as it relates to quality of life post-liver transplant (LT) has been studied, there are limited data showing how religious affiliation impacts objective measures such as survival. The aim of the study is to investigate whether LT recipients who identified as having a religious affiliation had better clinical outcomes when compared to LT recipients who did not. Religious affiliation is obtained as part of general demographic information for patients within our institution (options of "choose not to disclose" and "no religious affiliation" are available). Subjects in this retrospective cohort study which conformed with the Declarations of Helsinki and Istanbul were separated into cohorts: LT recipients who self-reported religious affiliation and LT recipients who did not. All LT recipients between March 2007 and September 2018 who had available information regarding their reported religion were included. Excluded patients included those who received a multi-organ transplant, underwent re-transplantation, received a partial liver graft, and identified as agnostic. Outcomes included 30-day readmission, death, and the composite outcome of re-transplantation/death. In an unadjusted analysis of 378 patients, there were no statistically significant differences between the two groups for 30-day readmission (OR=1.15, P=0.71), death (HR=0.63, P=0.19), or re-transplantation/death (HR=0.90, P=0.75). In multivariable analysis, adjusting for age at transplant and hospital admittance status when called for transplant, results were similar. We found no statistically significant difference in the outcomes measured between patients with and without self-reported religious affiliation. Further studies into the role of participation in religious activity and the impact of engagement with a religious community should be conducted in the future.

Intrinsic Causes of Nonfibrotic Portal Hypertension-A Clinicopathologic Review of 56 Patients.

Aim: The differential diagnosis of intrinsic nonfibrotic conditions that may lead to portal hypertension include hepatoportal sclerosis (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). In this article, we characterize the clinical features and outcome of these lesions when they manifest as portal hypertension. Methods: Data was collected through retrospective patient medical records. Results: Patients (HPS: 28, NRH: 17, SOS: 11) were identified more frequently in recent years. All groups presented with signs and symptoms of portal hypertension. All patients had complex medical histories. An elevated serum alkaline phosphatase occurred in all groups and an elevated bilirubin with SOS. Imaging of the liver with HPS and NRH suggested cirrhosis, which was not seen with SOS. 11%, 12%, and 9% of patients in the HPS, NRH, and SOS respectively, underwent transjugular intrahepatic portosystemic shunt placement to manage the complications of portal hypertension, while 43%, 24%, and 36% of patients respectively, received a liver transplant. Conclusions: Patients with HPS, NRH, and SOS had complex medical histories, likely contributing to the development of these lesions. They are recognized more frequently now. In contrast to HPS and NRH, SOS occurred in liver transplant recipients, was associated with elevated serum bilirubin, and imaging did not suggest the presence of advanced fibrosis/cirrhosis. Liver transplantation appeared to be a viable treatment for complications related to HPS and NRH. Retransplantation for SOS yielded mixed results. HPS, SOS, and NRH should be considered when evaluating liver specimens from patients with unexplained nonfibrotic portal hypertension. Key message: Intrinsic nonfibrotic causes of portal hypertension appear to be increasing in frequency. The differential diagnosis includes NRH, HPS, and SOS. These conditions are associated with complex diseases and possibly due to treatments. Pathologists need to be aware of this differential diagnosis when presented with liver biopsies performed to assess portal hypertension.

Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices.

BACKGROUND: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. AIMS: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. METHODS: This study combined the data from two prospectively conducted US studies: HALT-C and SHUNT-V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). RESULTS: DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). CONCLUSIONS: DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs.

A clinical review of congenital hepatic fibrosis diagnosed in adulthood: presentation, complications, and outcomes.

INTRODUCTION AND OBJECTIVES: Congenital hepatic fibrosis (CHF) is a rare condition characterized by biliary tract changes and a geographic pattern of liver fibrosis. Liver biopsy is essential to confirm its diagnosis. The absence of specific clinical indicators in adults often leads to delays in diagnosis and management, while the natural history has not been well described. We sought to define the presentation and outcomes of adults with biopsy-proven CHF. MATERIALS AND METHODS: A retrospective chart review was conducted of patients diagnosed with CHF by liver biopsy. Continuous variables were summarized with the sample median and range. Categorical variables were summarized with number and percentage of patients. RESULTS: We identified 24 patients evaluated over a 20-year period, with a median age of 51 years (range 22-72 years) at initial presentation; 14 were male. The most common imaging findings were renal cysts (91.3%), splenomegaly (69.6%), and a cirrhotic-appearing liver (60.9%). The most commonly treated liver-related complications were cholangitis (45.8%), varices (45.8%), and hepatic encephalopathy (25%). Two patients died with a median length of follow-up of 2.9 years (range: 0.0-20.0 years). Two patients underwent transjugular intrahepatic portosystemic shunt (TIPS) placement to manage bleeding esophageal varices. Eight patients underwent liver transplantation (LT), the most common indication being decompensated disease (50%). CONCLUSIONS: CHF should be considered when patients present with cholangitis and/or complications of portal hypertension and have a cirrhotic appearing liver and renal cysts on imaging. Depending upon the disease severity, interventions such as TIPS or LT may be required.

Predictors of Respiratory Failure Development in a Multicenter Cohort of Inpatients With Cirrhosis.

INTRODUCTION: Hospitalized patients with cirrhosis can develop respiratory failure (RF), which is associated with a poor prognosis, but predisposing factors are unclear. METHODS: We prospectively enrolled a multicenter North American cirrhosis inpatient cohort and collected admission and in-hospital data (grading per European Association for the Study of Liver-Chronic Liver Failure scoring system, acute kidney injury [AKI], infections [admission/nosocomial], and albumin use) in an era when terlipressin was not available in North America. Multivariable regression to predict RF was performed using only admission day and in-hospital events occurring before RF. RESULTS: A total of 511 patients from 14 sites (median age 57 years, admission model for end-stage liver disease [MELD]-Na 23) were enrolled: RF developed in 15%; AKI occurred in 24%; and 11% developed nosocomial infections (NI). At admission, patients who developed RF had higher MELD-Na, gastrointestinal (GI) bleeding/AKI-related admission, and prior infections/ascites. During hospitalization, RF developers had higher NI (especially respiratory), albumin use, and other organ failures. RF was higher in patients receiving albumin (83% vs 59%, P < 0.0001) with increasing doses (269.5 ± 210.5 vs 208.6 ± 186.1 g, P = 0.01) regardless of indication. Admission for AKI, GI bleeding, and high MELD-Na predicted RF. Using all variables, NI (odds ratio [OR] = 4.02, P = 0.0004), GI bleeding (OR = 3.1, P = 0.002), albumin use (OR = 2.93, P = 0.01), AKI (OR = 3.26, P = 0.008), and circulatory failure (OR = 3.73, P = 0.002) were associated with RF risk. DISCUSSION: In a multicenter inpatient cirrhosis study of patients not exposed to terlipressin, 15% of patients developed RF. RF risk was highest in those admitted with AKI, those who had GI bleeding on admission, and those who developed NI and other organ failures or received albumin during their hospital course. Careful volume monitoring and preventing nosocomial respiratory infections and renal or circulatory failures could reduce this risk.

Improved outcomes of kidney after liver transplantation after the implementation of the safety net policy.

The number of kidney after liver transplants (KALT) increased after the implementation of the United Network of Organ Sharing (UNOS) safety net policy, but the effects of the policy on KALT outcomes remain unknown. Using the UNOS database, we identified KALT between 60 and 365 days from liver transplant from January 1, 2010, to December 31, 2020. The main outcome was 1- and 3-year patient, liver, and kidney graft survival. Secondary outcomes included 6-month and 1-year acute rejection (AR) of liver and kidney, and 1-year kidney allograft function. Of the 256 KALT, 90 were pre-policy and 166 post-policy. Compared to pre-policy, post-policy 1- and 3-year liver graft survival was higher (54% and 54% vs. 86% and 81%, respectively, p <0.001), while 1- and 3-year kidney graft survival (99% and 75% vs. 92% and 79%, respectively, p =0.19), and 1- and 3-year patient survival (99% and 99% vs. 95% and 89%, respectively, p =0.11) were not significantly different. Subgroup analysis revealed similar trends in patients with and without renal failure at liver transplant. Liver AR at 6 months was lower post-policy (6.3% vs. 18.3%, p =0.006) but was similar (10.5% vs. 13%, p =0.63) at 1 year. Kidney AR was unchanged post-policy at 6 months and 1 year. Creatinine at 1 year did not differ post-policy versus pre-policy (1.4 vs. 1.3 mg/dL, p =0.07) despite a higher proportion of deceased donors, higher Kidney Donor Profile Index, and longer kidney cold ischemia time post-policy ( p <0.05 for all). This 3-year follow-up after the 2017 UNOS policy revision demonstrated that the safety net implementation has resulted in improved liver outcomes for patients who underwent KALT with no increased AR of the liver or the kidney allografts.

Global Burden of Digestive Diseases: A Systematic Analysis of the Global Burden of Diseases Study, 1990 to 2019.

BACKGROUND & AIMS: This study assessed the worldwide burden of digestive diseases between 1990 and 2019. METHODS: We analyzed data from the Global Burden of Diseases study, covering 18 digestive diseases across 204 countries and territories. Key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change. RESULTS: In 2019, there were 7.32 billion incidents and 2.86 billion prevalent cases of digestive diseases, resulting in 8 million deaths and 277 million DALYs lost. Little to no decrease in global age-standardized incidence and prevalence of digestive diseases was observed between 1990 and 2019, with 95,582 and 35,106 cases per 100,000 individuals in 2019, respectively. The age-standardized death rate was 102 per 100,000 individuals. Digestive diseases accounted for a significant portion of the overall disease burden, with more than one-third of prevalent cases having a digestive etiology. Enteric infections were the primary contributor to incidence, death, and DALYs lost, whereas cirrhosis and other chronic liver diseases had the highest prevalence rate. The burden of digestive diseases was inversely related to the sociodemographic index, with enteric infections being the predominant cause of death in low and low-middle quintiles and colorectal cancer in the high quintile. CONCLUSIONS: Despite significant reductions in deaths and DALYs due to digestive diseases from 1990 to 2019, they remain prevalent. A significant disparity in the burden of digestive diseases exists among countries with different development levels.

Utility of an Artificial Intelligence Enabled Electrocardiogram for Risk Assessment in Liver Transplant Candidates.

BACKGROUND: Post-operative cardiac complications occur infrequently but contribute to mortality after liver transplantation (LT). Artificial intelligence-based algorithms based on electrocardiogram (AI-ECG) are attractive for use during pre-operative evaluation to screen for risk of post-operative cardiac complications, but their use for this purpose is unknown. AIMS: The aim of this study was to evaluate the performance of an AI-ECG algorithm in predicting cardiac factors such as asymptomatic left ventricular systolic dysfunction or potential for developing post-operative atrial fibrillation (AF) in cohorts of patients with end-stage liver disease either undergoing evaluation for transplant or receiving a liver transplant. METHODS: A retrospective study was performed in two consecutive adult cohorts of patients who were either evaluated for LT or underwent LT at a single center between 2017 and 2019. ECG were analyzed using an AI-ECG trained to recognize patterns from a standard 12-lead ECG which could identify the presence of left ventricular systolic dysfunction (LVEF < 50%) or subsequent atrial fibrillation. RESULTS: The performance of AI-ECG in patients undergoing LT evaluation is similar to that in a general population but was lower in the presence of prolonged QTc. AI-ECG analysis on ECG in sinus rhythm had an AUROC of 0.69 for prediction of de novo post-transplant AF. Although post-transplant cardiac dysfunction occurred in only 2.3% of patients in the study cohorts, AI-ECG had an AUROC of 0.69 for prediction of subsequent low left ventricular ejection fraction. CONCLUSIONS: A positive screen for low EF or AF on AI-ECG can alert to risk of post-operative cardiac dysfunction or predict new onset atrial fibrillation after LT. The use of an AI-ECG can be a useful adjunct in persons undergoing transplant evaluation that can be readily implemented in clinical practice.

Impact of Recipient Age at Liver Transplant on Long-term Outcomes.

BACKGROUND: The age of a liver transplant (LT) candidate is one of many variables used in the transplant selection process. Most research about the age at transplant has used prespecified age ranges or categories in assessing associations with transplant outcomes. However, there is a lack of knowledge about the age at transplant and survival. This study aimed to examine associations of age at transplant as a continuous variable, in conjunction with other patient and disease-related factors, with patient and graft survival after LT. METHODS: We used the Standard Transplant Analysis and Research data to identify LT recipients between January 2002 and June 2018. Cox regression models with a restricted cubic spline term for age examined associations with graft and patient survival after LT. We assessed the interactions of age with recipients' sex, race/ethnicity, region, indication for transplant, body mass index, model for end-stage liver disease score, diabetes, functional status at transplant, and donor risk index. RESULTS: Age at the time of LT showed a nonlinear association with both graft and patient survival. Each demographic, clinical, transplant-related, and donor-related factor influenced these relationships differently. CONCLUSIONS: Our results suggest that some older LT candidates may be better than some younger candidates and that clinicians should not exclusively use age to determine who receives LT.

Hepatoportal Sclerosis-A Clinicopathologic Review of 28 Cases.

Background and Aims: The aim of this study was to review a large series of cases with hepatoportal sclerosis (HPS) as a pathologically recognizable entity in liver tissue specimens and describe the associated clinical and radiographic manifestations, along with the outcomes of this entity. Methods: Data were collected through a retrospective chart review. Results: Twenty-eight patients were identified that had pathologically defined HPS. All patients had a significant past medical history and signs and symptoms of portal hypertension. The most consistent laboratory finding was an elevated alkaline phosphatase. Radiographically, 9 patients were mistakenly identified as having advanced fibrosis/cirrhosis. The initial histologic diagnosis was made on biopsy in 20 patients and after transplant in 8 patients. The severity of symptoms was variable and required transplantation in 11 patients, 3 were treated with transjugular intrahepatic portosystemic shunt, and the remaining patients were treated symptomatically. Conclusion: HPS is associated with past medical history that may be causal in nature. Signs and symptoms may be severe enough to require liver transplantation. A significant proportion of patients are radiographically misdiagnosed as cirrhosis. In this small series, overall outcomes for transplanted patients are acceptable.

Portopulmonary Hypertension in Nontransplanted Patients: Results of the Largest US Single-Institution Registry.

OBJECTIVE: To explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT). METHODS: From the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)-pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time. RESULTS: Median survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease-sodium score of 15 or higher were associated with increased risk of death. CONCLUSION: Patients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class.

ICU and Hospital Outcomes in Patients with Hepatopulmonary Syndrome Undergoing Liver Transplantation.

PURPOSE: There are limited data regarding hospital and intensive care unit (ICU) outcomes in patients with hepatopulmonary syndrome (HPS) following liver transplantation (LT). METHODS: Data were retrospectively collected from consecutive HPS adult patients who underwent LT and were immediately admitted to the ICU at three transplant centers with shared management protocols, from 2002 to 2018. Demographic, clinical, surgical, laboratory, and outcome data were extracted. RESULTS: We identified 137 patients (74 male, 54%), with a median age at LT of 58 years (IQR: 52-63). One hundred and 31 (95.6%) patients were admitted to the ICU on invasive mechanical ventilation (MV). The median time on invasive MV in the ICU was 12 hours (IQR: 5-28) and 97 patients (74%) were extubated within 24 hours of ICU admission. The median highest positive end expiratory pressure and fraction of inspired oxygen (FiO2) were 7 (IQR: 5-8) and 0.6 (IQR: 0.5-0.7), respectively. 7 patients (5%) developed severe post-transplant hypoxemia. Of all patients, 42 (30.4%) required vasopressors and the median ICU and hospital length of stay (LOS) were 3 (IQR: 1-5) and 10 (IQR: 7-20) days, respectively. The in-hospital mortality rate was 3.6% (5/137). HPS severity was not associated with hospital mortality. CONCLUSION: Most HPS patients have short durations of MV, ICU, and hospital LOS post-LT. HPS severity does not impact hospital mortality.

Skin cancer in non-white liver transplant recipients: Mayo Clinic experience.

BACKGROUND: Limited data are available on the development of skin cancer and the associated risk factors for non-White liver transplant (LT) recipients. The aim of this study is to determine the incidence of newly diagnosed skin cancer postoperatively and to identify the risk factors for the development of skin cancer in non-White LT recipients. METHODS: We conducted an initial retrospective chart review of non-White LT patients who received a transplant at our center between January 1, 2011, and December 31, 2013. RESULTS: Of the 96 patients in the study cohort, 32% were Black, 17% were Asian, 15% were White Hispanic, and 10% were Black Hispanic. One patient had a history of nonmelanoma skin cancer before transplant. No skin cancers were diagnosed during follow-up (median, 1.3 years; range, 17 days to 8.6 years). CONCLUSION: Our center's experience is consistent with the literature and suggests that the incidence of newly diagnosed skin cancer in non-White liver transplant recipients is low. Longer follow-up may provide additional insights into the specific risk factors for the posttransplant development of skin cancer.

Post-Liver Transplant Early Allograft Dysfunction Modifies the Effect of Pre-Liver Transplant Renal Dysfunction on Post-Liver Transplant Survival.

Pre-liver transplantation (LT) renal dysfunction is associated with poor post-LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post-LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre-LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre-LT renal dysfunction and post-LT EAD development. Recipients who had both pre-LT renal dysfunction and post-LT EAD had the worst unadjusted 1-year, 3-year, and 5-year post-LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre-LT renal dysfunction and post-LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58-3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86-1.45; P = 0.41). Results remained unchanged when pre-LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre-LT renal dysfunction negatively impacts post-LT survival only in patients who develop EAD. Livers at higher risk of post-LT EAD should be used with caution in recipients with pre-LT renal dysfunction.

The changing impact of pre-liver transplant renal dysfunction on post-transplant survival: results of 2 decades from a single center.

INTRODUCTION AND OBJECTIVES: Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS: We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS: Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS: Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.

Metabolic associated fatty liver disease and acute-on-chronic liver failure: common themes for common problems.

Metabolic associated fatty liver disease (MAFLD) affects 20-30% of the worldwide population and is becoming the most common cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). MAFLD is the hepatic expression of metabolic dysfunction correlated with a variety of metabolic comorbidities including obesity, dyslipidemia, hypertension and type 2 diabetes (T2DM). Obesity, altered gut permeability, chronic inflammation and dysbiosis related to MAFLD might predispose patients with cirrhosis to the development of acute-on-chronic liver failure (ACLF); however, this relationship remains unclear. ACLF is a syndrome with high short-term mortality, presenting with acute hepatic decompensation associated with organ failures in patients with underlying chronic liver disease with or without an identifiable precipitating event. While this syndrome can occur in any patient with cirrhosis, the increasing prevalence of cirrhosis due to MAFLD is of great concern because, in a recent analysis, MAFLD was the fastest rising cause of cirrhosis associated with ACLF among patients listed for LT in the US. In this review, we will discuss the current knowledge on MAFLD and the development of ACLF.

Sequential Protocol Biopsies Post-Liver Transplant From Donors With Moderate Macrosteatosis: What Happens to the Fat?

The number of steatotic deceased donor livers encountered has continued to rise as a result of the obesity epidemic. Little is known about the histological characteristics of moderately macrosteatotic livers over time in the recipient following liver transplantation (LT). All recipients undergoing LT at Mayo Clinic Florida with donor livers with moderate macrosteatosis (30%-60%) from 2000-2017 were identified (n = 96). Routine protocol liver biopsies were performed 1-week and 6-months following LT. All liver donor and protocol biopsies were read by an experienced liver pathologist. Of the 96 moderate macrosteatosis LTs, 70 recipients had post-LT protocol liver biopsies available and comprised the study cohort. Median donor allograft macrosteatosis at the time of transplant was 33% (IQR, 30%-40%) compared with 0% (IQR, 0%-2%) at 1-week (P < 0.001) and 0% (IQR, 0%-0%) at 6-months (P < 0.001) following LT. Biopsies at 1-week post-LT displayed pericentral necrosis in 57.1% of recipients and lipopeliosis in 34.3% of recipients. In the 6-month post-LT biopsies, cholestasis was seen in 3 (4.3%) of the recipients, whereas grade 2 fibrosis was seen in 6 recipients (8.6%). Graft survival at 5 years in the present cohort was 74.0%. Moderate macrosteatosis (30%-60%) in the donor allograft demonstrates complete reversal on liver biopsies performed as early as 7 days following LT and remains absent at 6-months following LT. Both pericentral necrosis and lipopeliosis are common features on day 7 biopsies. Despite these encouraging findings, the perioperative risks of using these livers (postreperfusion cardiac arrest and primary nonfunction) should not be understated. Long-term graft survival is acceptable in patients who are able to overcome the immediate perioperative risk of using moderately steatotic donor livers.

PNPLA3 Gene Polymorphism and Liver- and Extrahepatic Cancer-Related Mortality in the United States.

The palatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 G allele is associated with nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma,1 and all-cause or cardiovascular mortality in the general population.2 One recent Italian study reported an association between PNPLA3 polymorphism and liver-related events and mortality in biopsy-confirmed NAFLD.3 Regarding extrahepatic cancer-related mortality, one study showed that only women carrying the G allele without hepatic steatosis had a 60% lower risk for cancer-related mortality.4 However, owing to insufficient follow-up and selected populations, the results from these studies cannot generalize about the association between PNPLA3 polymorphism and liver- and extrahepatic cancer-related mortality at a population level. Thus, we investigated the association between PNPLA3 polymorphism and liver- and extrahepatic cancer-related mortality based on the presence of NAFLD in the U.S. general population.