Received Liver Transplantation Research Articles

Outcomes of Pregnancy in Recipients of Liver Transplants

Despite increasing reports of pregnancy in women who received liver transplants, it is not clear how transplantation and immunosuppression affect pregnancy. We collected data from liver transplant recipients who became pregnant on immunosuppression regimens, pregnancy management, graft morbidity, and outcomes of mothers and neonates. We searched the liver transplant database in Birmingham, United Kingdom, for women who reported pregnancy after liver transplantation from August 1986 through May 2016. We collected information on morbidities and outcomes of 139 pregnancies in 83 women (median age at conception, 27 y; range, 15-46 y). Fisher exact tests were used to compare categoric variables and Mann-Whitney U and Kruskal-Wallis tests were used to compare continuous variables. The primary outcome was the live birth rate in the entire cohort. Additional outcomes analyzed included differences in immunotherapy regimens, and outcomes associated with exposure to cyclosporine and tacrolimus, time to transplantation (<12 vs >12 mo), and time period of pregnancy (1986-2000 vs 2001-2016). Of the pregnancies, 69% resulted in live births, 19% resulted in miscarriages or still births, and 9% were terminated. A higher proportion of patients who conceived more than 1 year after liver transplantation had live births than of women who conceived before this time (98% vs 80%; P= .006). Tacrolimus exposure was associated with higher risks of premature delivery (P= .045) and caesarian section (P= .031) than cyclosporine exposure. Compared with the period from 1986 to 2000, women who conceived from 2001 to 2016 had a significantly shorter time between transplantation and conception (median, 3 vs 7 y; P= .027), frequent use of tacrolimus vs cyclosporine (84% vs 26%; P= .001), and a higher incidence of cesarean section (44% vs 32%; P= .025). Almost 70% of women who conceive after liver transplantation have live births, although this rate is lower than that of women in the overall population. These cases require involvement of hepatologists and obstetricians.

Racial Disparities in Liver Transplantation for Hepatocellular Carcinoma Are Not Explained by Differences in Comorbidities, Liver Disease Severity, or Tumor Burden.

Black patients have higher mortality and are less likely to receive liver transplantation for hepatocellular carcinoma (HCC) than white patients. Reasons for these disparities have not been fully elucidated. Comorbid disease, liver disease severity, cirrhosis etiologies, and tumor characteristics were compared between black and white patients with HCC seen at the Indiana University Academic Medical Center from January 2000 to June 2014. Logistic regression was used to investigate the primary outcome, which was liver transplantation. Log‐rank testing was used to compare survival between the two groups. Subgroup analysis explored reasons for failure to undergo liver transplantation in patients within Milan criteria. The cohort included 1,032 (86%) white and 164 (14%) black patients. Black and white patients had similar Model for End‐Stage Liver Disease (MELD) and Child‐Pugh scores (CPSs). There was a trend toward larger tumor size (5.3 cm versus 4.7 cm; P = 0.05) in black patients; however, Barcelona Clinic Liver Cancer (BCLC) staging and Milan criteria were similar. Black patients were less likely to undergo liver transplantation than white patients; this was a disparity that was not attenuated (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.21‐0.90) on multivariable analysis. Substance abuse was more frequently cited as the reason black patients within Milan criteria failed to undergo transplantation compared to white patients. Survival was similar between the two groups. Conclusion: Racial differences in patient and tumor characteristics were small and did not explain the disparity in liver transplantation. Higher rates of substance abuse in black patients within Milan criteria who failed to undergo transplantation suggest social factors contribute to this disparity in this cohort.

Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation.

Background/AimsHypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC.Materials and MethodsWe retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid‐stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence‐free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results.ResultsA total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44‐4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses.ConclusionHypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation.

Statin Use Is Associated With Improved Outcomes of Patients With Primary Sclerosing Cholangitis

There is increasing evidence that statins can benefit patients with chronic liver diseases, but their effects have not been studied in patients with primary sclerosing cholangitis (PSC). We performed a nationwide study in Sweden to determine the effects of exposure to drugs, including statins, in patients with PSC. We studied a population-based cohort of patients in Sweden with PSC and concomitant ulcerative colitis or Crohn's disease from 2005 through 2014 (n = 2914), followed through 2016. We collected analyzed data from the patient register, the prescribed drug register, the death certificate register and the cancer register. We calculated risk or death, liver transplantation, bleeding of esophageal varices, and cancer in relation to drug exposure. The mean age of patients at the time of diagnosis with PSC was 41.4 years (inter-quartile range [IQR], 25.6-56.1 years). The total follow-up time was 11769 person-years, during which 3.4% of patients received liver transplants and 19.9% died. Proportions of patients exposed to drugs were: ursodeoxycholic acid, 60.2%; 5-aminosalicylic acid, 74.4%; azathioprine or mercaptopurins, 33.7%; and statins, 13.9%. Statin use was associated with a reduced risk of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.54-0.88) and death or liver transplantation (HR, 0.50; 95% CI, 0.28-0.66). Use of azathioprine was also associated with reduced mortality (HR, 0.66; 95% CI, 0.52-0.84) and risk of death or liver transplantation (HR, 0.65; 95% CI, 0.50-0.83). Exposure to ursodeoxycholic acid did not affect mortality (HR, 1.04; 95% CI, 0.87-1.25). In a population-based cohort of patients in Sweden with PSC, we associated use of statins and azathioprine with decreased risks of death and death or liver transplantation. Exposure to ursodeoxycholic acid was not associated with reduced mortality.

Portal vein thrombosis prevalence and associated mortality in cirrhosis in a nationally representative inpatient cohort.

Portal vein thrombosis (PVT) is increasingly common in cirrhotics, but its impact on mortality and outcomes is unclear. Studies evaluating PVT have been limited by small sample size. This study analyzes the trend of the prevalence of PVT and its associated mortality in hospitalized decompensated cirrhotics. The Nationwide Inpatient Sample, the largest nationally representative database of hospital discharges, was queried from 1998 to 2014. Inpatients older than 18years with decompensated cirrhosis were included, while those who received liver transplantation or had hepatocellular carcinoma were excluded. The primary outcomes were the trend in prevalence and associated mortality with PVT. Secondary outcomes included identifying risk factors of PVT and the effect of PVT on complications of portal hypertension. Multivariable logistic regression evaluated the outcomes. A total of 3045098 discharges were included, of which 1.5% had PVT. PVT prevalence increased from 0.7% to 2.4%, annual percent change of 9%. Mortality associated with PVT declined from 11.9% to 9.1%, annual percent change of -3.0%. In multivariable analysis controlling for factors associated with mortality in cirrhotics, PVT was associated with an increased risk of mortality (OR 1.12, P<0.001). Multivariable logistic regression also demonstrated that PVT significantly increased the risk of acute kidney injury (OR 1.75, P<0.001) and hepatorenal syndrome (OR 1.62, P<0.001). The prevalence of PVT is increasing while its associated mortality is decreasing. However, PVT still is associated with risk of mortality and kidney injury, implying a significant impact on cirrhotic outcomes.

Hypoalbuminemia is Associated With Significantly Higher Liver Transplant Waitlist Mortality and Lower Probability of Receiving Liver Transplant.

To evaluate the predictive value of hypoalbuminemia on liver transplant (LT) waitlist survival and probability of receiving LT among adults with end-stage liver disease (ESLD). Growing evidence reports on the negative prognostic value of hypoalbuminemia among ESLD patients awaiting LT. Using 2003 to 2015 United Network for Organ Sharing data, we retrospectively evaluated the impact of mild-moderate (2.5 to 3.4 g/dL) and severe hypoalbuminemia (<2.5 g/dL) on waitlist survival and probability of receiving LT among US adults awaiting LT. Outcomes were stratified by liver disease etiology and presence of hepatocellular carcinoma (HCC), and evaluated using Kaplan-Meier and multivariate Cox proportional hazards models. Among 128,450 adults listed for LT, 27.1% had normal albumin (≥3.5 g/dL), 53.7% mild-moderate hypoalbuminemia (2.5 to 3.4 g/dL), and 19.2% severe hypoalbuminemia (<2.5 g/dL) at time of listing. Patients with severe hypoalbuminemia had significantly lower 1-year waitlist survival compared with those with normal albumin (80.4% vs. 95.2%; P<0.001). On multivariate regression, severity of hypoalbuminemia was associated with increasing waitlist mortality, even after correcting for model for end stage liver disease-sodium and HCC [albumin, 2.5 to 3.4 g/dL: hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.62-2.01; P<0.001; <2.5 g/dL: HR, 2.46; 95% CI, 2.20-2.76; P<0.001]. Patients with hypoalbuminemia had significantly lower probability of receiving LT compared with those with normal albumin (albumin <2.5 g/dL: HR, 0.80; 95% CI, 0.78-0.83; P<0.001). ESLD patients with hypoalbuminemia have lower probability of LT despite significantly higher waitlist mortality compared with patients with normal albumin. If validated by further studies, incorporation of albumin into prognostication systems may improve the performance of US donor organ allocation systems.

Cost-effectiveness of liver transplantation in patients with colorectal metastases confined to the liver.

Patients with non-resectable colorectal metastases are currently treated with chemotherapy. However, liver transplantation can increase the 5-year survival rate from 9 to 56 per cent if the cancer is confined to the liver. The aim of this study was to estimate the cost-effectiveness of liver transplantation for colorectal liver metastases. A Markov model with a lifetime perspective was developed to estimate the life-years, quality-adjusted life-years (QALYs), direct healthcare costs and cost-effectiveness for patients with non-resectable colorectal liver metastases who received liver transplantation or chemotherapy alone. In non-selected cohorts, liver transplantation increased patients' life expectancy by 3·12 life-years (2·47 QALYs), at an additional cost of €209 143, giving an incremental cost-effectiveness ratio (ICER) of €67 140 per life-year (€84 667 per QALY) gained. In selected cohorts (selection based on tumour diameter, time since primary cancer, carcinoembryonic antigen levels and response to chemotherapy), the effect of liver transplantation increased to 4·23 life-years (3·41 QALYs), at a higher additional cost (€230 282), and the ICER decreased to €54 467 per life-year (€67 509 per QALY) gained. Given a willingness to pay of €70 500, the likelihood of transplantation being cost-effective was 0·66 and 0·94 (0·23 and 0·67 QALYs) for non-selected and selected cohorts respectively. Liver transplantation was cost-effective but only for highly selected patients. This might be possible in countries with good access to grafts and low waiting list mortality.

Excellent Outcomes of Deceased Donor Liver Transplantation Using Grafts From Older Donors: A U.S. Single-Center Experience

Introduction: One of the major challenges in deceased donor liver transplantation (DDLT) is the scarcity of donor allografts, which results in high wait-list mortality. Transplant centers tackle the donor graft scarcity by utilizing expanded criteria donors including older donors. UNOS reported that the percentage of donor age > 50 years rose from 24% in 1989 to 33% in 2013. The literature on the impact of older donor age on liver graft function, survival and complications have described contradictory results. In this study, we aim to evaluate patient and graft survival outcomes of DDLT recipients in 2 groups: donor age ≥65 years and donor age < 65 years. Methods: Setting: Single center Retrospective cohort study at a large volume US liver transplant center Inclusion criteria: All primary deceased liver transplants (DDLT) in our institution between October 2012 to October 2016 Exclusion criteria: age <18, split and reduced-size livers and multi-organ transplants were excluded from the study Outcomes: Comparison of 1-year /overall patient and graft survival in 2 groups: donor age ≥65 years and donor age < 65 years. Results: In total, 646 patients met inclusion criteria. Among patients who underwent DDLT, 70 (11%) received DDLT from older (>65 years) donors. There was no difference in age, sex, ethnicity, hepatocellular carcinoma, warm/cold ischemia time, donor sex, donor ethnicity, donor BMI in both groups. Patients who received liver transplantation from donor age >65 had lower HCV infection (20% vs 41%), lower MELDNa score (19±6 vs 21±9), and lower donor HCV-positive graft (3% vs 13%) [Table 1]. Recipients of donor age ≥65 had similar outcomes including 1-year patient survival (96% vs 92%, p = NS), 1-year graft survival (93% vs 90%, p =NS), overall patient survival (94% vs 86%, p =NS) and overall graft survivals (90% vs 84%, p=NS) comparing to recipients of donor age <65, respectively [Table 2 and Figure 1].1014_A Figure 1. Baseline charecteristicsConclusion: In our study, careful allocation of grafts from older donors to appropriate recipients resulted in excellent 1-year and longer-term patient and graft survival comparable with outcomes in recipients from donor grafts age <65 years. Increasing utilization of grafts from older donors can expand the donor pool to decrease the national organ donor shortage.1014_B Figure 2. Results1014_C Figure 3. Kaplan Meier survival graphs

N-Acetylcysteine inhalation improves pulmonary function in patients received liver transplantation.

Postoperative pulmonary complications (PPCs) following orthotopic liver transplantation (OLT) are associated with high morbidity and mortality rates. The effect of N-acetylcysteine (NAC) inhalation on the incidence of PPCs and the outcomes of patients undergoing OLT is unknown. This prospective randomized controlled clinical trial was conducted to investigate the effect of NAC inhalation during OLT on PPCs. Sixty patients were randomly assigned to the NAC group (n = 30) or the control group (n = 30) to receive inhaled NAC or sterilized water, respectively, for 30 min before surgery and 3 h after reperfusion. The incidence of early PPCs and outcomes including survival rate were assessed. Biomarkers including tumor necrosis factor (TNF)-α, interleukin (IL)-8, Clara cell secretory protein (CC16), intercellular adhesion molecule (ICAM)-1, and superoxide dismutase (SOD) were measured in exhaled breath condensate (EBC) at T1 (before surgery) and T2 (at the end of operation) as well as in serum at T1, T2, T3 (12 h after operation), and T4 (24 h after operation). A total of 42 patients (20 in the NAC group and 22 in the control group) were enrolled in the final analysis. Atomization inhaled NAC significantly reduced the incidence of PPCs after OLT. The levels of TNF-α, IL-8, CC16, and ICAM-1 in EBC were significantly lower, and SOD activity was higher, at T2 in the NAC group; similar data were found in serum at T2, T3, and T4. In summary, perioperative NAC inhalation may reduce the incidence of PPCs and improve patient outcomes after OLT.

Prognostic parameters of pediatric acute liver failure and the role of plasma exchange

This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF). Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis. Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (<190μmol/L), and peak AFP level for predicting NLR in children with ALF. Pediatric ALF with idiopathic etiology, high peak ammonia level, and low peak AFP level are associated with fewer cases of NLR. Plasma exchange for more than six times probably offers little benefit with regard to patient survival if liver transplantation is not performed promptly.

Liver Transplantations and Brain Dead Donors With Alcohol Abuse

Background and aimLiver grafts from donors with chronic and active history of alcohol abuse are usually immediately ruled out for use in liver transplantation (LT). The aim of our study is to evaluate the use of those grafts. MethodsFrom 2011 to 2016, a study group (Group 1) composed of 5 adult LT patients transplanted with livers from donors with alcohol abuse, was compared with a control group (Group 2) of 10 randomly matched patients who received liver transplants. Preoperative, intraoperative, and postoperative data were compared. ResultsAmong donors, serum gamma-glutamyl transferase values were significantly higher in Group 1. In recipients, post-LT laboratory exams showed significantly higher peak values of aspartate transaminase and alanine transaminase in Group 1; higher values of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in Group 1 were also recorded on day 0. Early allograft dysfunction occurred at higher rates in Group 1 (80% vs 20%, P = .025), with no differences in early rejection episodes or early surgical repeat interventions. All patients from both groups were alive after 20 ± 10 (range 6–35) months from LT. ConclusionDespite higher rates of early allograft dysfunction, selected liver grafts from donors with alcohol abuse can be accepted for LT with good clinical results.

Predictive Factors for Survival in Children Receiving Liver Transplants for Wilson's Disease: A Cohort Study Using European Liver Transplant Registry Data.

Liver transplantation (LT) is a rescue therapy for life-threatening complications of Wilson's disease (WD). However, data on the outcome of WD patients after LT are scarce. The aim of our study was to analyze a large pediatric WD cohort with the aim of investigating the longterm outcome of pediatric WD patients after LT and to identify predictive factors for patient and transplant survival. This is a retrospective cohort study using data of all children (<18 years) transplanted for WD enrolled in the European Liver Transplant Registry from January 1968 until December 2013. In total, 338 patients (57.6% female) transplanted at 80 different European centers (1-26 patients per center) were included in this study. The median age at transplantation was 14.0 years (interquartile range [IQR], 11.2-16.1 years); patients were followed up for a median of 5.4 years (IQR, 1.0-10.9 years) after LT. Overall patient survival rates were high with 87% (1-year survival), 84% (5-year survival), and 81% (10-year survival); survival rates increased considerably with the calendar year (P < 0.001). Early age at LT, living donation, and histidine tryptophan ketoglutarate preservation liquid were identified as risk factors for poor patient survival in the multivariate analysis. LT is an excellent treatment option for pediatric patients with WD and associated end-stage liver disease. Longterm outcome in these patients is similar to other pediatric causes for LT. Overall patient and graft survival rates improved considerably over the last decades. To improve future research in the field, the vast variability of allocation strategies should be harmonized and a generally accepted definition or discrimination of acute versus chronic WD needs to be found.

More severe deficits in functional status associated with higher mortality among adults awaiting liver transplantation.

The impact of functional status on liver transplant (LT) waitlist outcomes is not well studied. Early evidence suggests frailty portends increased mortality. We aim to evaluate the association of functional status with LT waitlist survival and the probability of receiving LT among adults with cirrhosis. Using 2005-2016 United Network for Organ Sharing (UNOS) data, we retrospectively assessed the association of functional status, as determined by Karnofsky Performance Status Score (KPSS) with LT waitlist survival and the probability of receiving LT using Kaplan-Meier and multivariate Cox proportional hazard models. Among 118954 patients listed for LT, patients with worse Karnofsky scores, indicating poor functional status, were progressively more likely to receive liver transplantation compared to patients with better scores, with the most functionally disabled group having 68% higher probability of receiving LT (HR 1.68; 95% CI 1.61-1.75, P<0.001). Worse functional status was associated with increased waitlist mortality, with the most functionally disabled group 97% more likely to die on the waitlist (HR 1.97; 95% CI 1.81-2.16, P<0.001). In conclusion, among patients awaiting LT, worse functional status was associated with significantly higher waitlist mortality.

Adrenal Metastasis of Hepatocellular Carcinoma in Patients following Liver Resection or Liver Transplantation: Experience from a Tertiary Referral Center.

Introduction Adrenal metastasis of hepatocellular carcinoma (HCC) is a rare entity and can be treated by resection, local ablative therapy, or systemic therapy. Unfortunately, data about treatment outcome, especially in liver transplant recipients, are rare. Patients and Methods From 2005 to 2015, 990 liver resections and 303 liver transplantations because of HCC were performed at our clinic. We retrospectively analyzed treatment outcome of the patients with metachronous adrenal metastasis of HCC, who received either resection, local ablation, or surveillance only. Results 10 patients were identified (0.8%). 7 patients received liver transplantation for primary HCC therapy, 3 liver resection, and 1 a local ablative therapy. 8 patients underwent adrenalectomy (one via retroperitoneoscopy), one was treated with local ablation, and one had surveillance only. Seven out of eight patients had no surgical complications and one experienced a pancreatic fistula, treated conservatively. 37.5% of the resected patients had recurrence 1 year after adrenalectomy and 75% after 2 years. The mean survival time after primary diagnosis of HCC was 96.6±22.4 months. After adrenalectomy, the mean survival time was 112.4±25.2 months. The mean time until tumor recurrence was 13.2±3.8 in the total cohort and 15.8±3.8 months in patients after adrenalectomy. The estimated overall survival after adrenalectomy was 77.2±17.4 months. Conclusion Metachronous adrenal metastasis occured in less than 1% of HCC patients. Adrenalectomy is a safe procedure and leads to acceptable survival rates even after liver transplantion. Therefore, it should be performed whenever the primary tumor is well controlled and the patient is in adequate physical condition.

Liver transplantation from a live donor to a patient with maple syrup urine disease: Two case reports

Liver transplantation were reported in patients with classic maple syrup urine disease in the literature. Branched chain alpha keto acid dehydrogenase activity can be improved in patients after transplant, and a protein-restricted diet is usually not needed. The first patient was a boy aged 2,5 years who presented with frequent ketosis attacks and epileptic seizures, and the second patient was an 11-month-old boy who also presented with frequent ketosis episodes, both despite adherence to diet therapy. Both patients received liver transplantations from live donors. A low protein diet was no longer required and no decline in cognitive functions was observed in either patient in the follow-up. We wanted to present these cases to show that despite a normal diet, plasma levels of branched- chain amino acids remained normal without any decline in cognitive function after liver transplantation in patients with classic maple syrup urine disease patients.

Transient elastography is useful in diagnosing biliary atresia and predicting prognosis after hepatoportoenterostomy.

LSM assessment during the workup of cholestatic infants may facilitate the diagnosis of BA. LSM post-HPE may predict complications and the need for early LT in infants with BA. (Hepatology 2018).

Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study

Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD. We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n= 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes. During a mean follow-up time of 5.5 years (range, 2.7-8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%-99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%-89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%-29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%-60% vs 6%, 95% CI, 2%-13%) or hepatocellular carcinoma (17%; 95% CI, 8%-31% vs 2.3%, 95% CI, 1%-12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%-18%) than cirrhosis (2%; 95% CI, 0%-6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%-23%) than cirrhosis (6%; 95% CI, 2%-15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcoholconsumption was associated with these outcomes onlyin patients with cirrhosis. Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.

Sa1462 - Race/Ethnicity-Specific Disparities in Waitlist Mortality, Probability of Receiving Liver Transplantation, and Post Transplant Survival Among U.S. Adults with Alcoholic Liver Disease

Sa1462 - Race/Ethnicity-Specific Disparities in Waitlist Mortality, Probability of Receiving Liver Transplantation, and Post Transplant Survival Among U.S. Adults with Alcoholic Liver Disease

Bilirubin reversibly affects cell death and odontogenic capacity in stem cells from human exfoliated deciduous teeth.

Hyperbilirubinemia in patients with biliary atresia causes deciduous tooth injuries such as green pigmentation and dentin hypoplasia. In patients with biliary atresia who received liver transplantation, tooth structure appears to be recovered radiographically. Nevertheless, little is known about cellular mechanisms underlying bilirubin-induced damage and suppression of deciduous tooth formation. In this study, we examined the effects of bilirubin in stem cells from human exfoliated deciduous teeth (SHED) in vitro. SHED were cultured under exposure to excess of bilirubin and then interruption of bilirubin stimulation. Bilirubin induced cell death and inhibited the odontogenic capacity of SHED by suppressing AKT and extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathways and enhancing nuclear factor kappa B p65 (NF-κB p65) pathway. The interruption of bilirubin stimulation reduced cell death and recovered the inhibited odontogenic capacity of bilirubin-damaged SHED. The bilirubin interruption also normalized the impaired AKT, ERK1/2, and NF-κB p65 signaling pathways. These findings suggest that tooth hypodontia in patients with hyperbilirubinemia might be due to bilirubin-induced cell death and dentinogenic dysfunction of odontogenic stem cells via AKT, ERK1/2, and NF-κB pathways and also suggested that bilirubin-induced impairments in odontogenic stem cells were reversible when bilirubin stimulation is interrupted.

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis

The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P= .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P= .01). In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1year (94%) and 3 years (84%), similar to patients receiving livertransplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.