Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation.

BACKGROUND & AIMS: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. CONCLUSION: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.

Early Graft Failure After Living-Donor Liver Transplant.

BACKGROUND: Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. AIM: Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. METHODS: Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. RESULTS: During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60 years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). CONCLUSION: Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010-December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15-24), and high-MELD (≥25) groups. We compared outcomes between MELD-stratified LDLT groups and between MELD-stratified LDLT and donation after brain death liver transplantation recipients. We used Kaplan-Meier analysis to compare graft survival rates and multivariable Cox proportional hazards modeling to identify factors associated with graft outcomes. Of 3558 LDLTs, 1605 (45.1%) were low-MELD, 1616 (45.4%) intermediate-MELD, and 337 (9.5%) high-MELD. Over the study period, the annual number of LDLTs increased from 282 to 569, and the proportion of high-MELD LDLTs increased from 3.9% to 7.7%. Graft survival was significantly higher in low-MELD versus high-MELD LDLT recipients (adjusted HR = 1.36, 95% CI: 1.03-1.79); however, 5-year survival exceeded 70.0% in both groups. We observed no significant difference in graft survival between high-MELD LDLT and high-MELD donation after brain death liver transplantation recipients (adjusted HR: 1.25, 95% CI:0.99-1.58), with a 5-year survival of 71.5% and 77.3%, respectively. Low LDLT center volume (<3 LDLTs/year) and recipient life support requirement were both associated with inferior graft outcomes among high-MELD LDLT recipients. While higher MELD scores confer graft failure risk in LDLT, high-MELD LDLT outcomes are acceptable with similar outcomes to MELD-stratified donation after brain death liver transplantation recipients. Future practice guidance should consider the expansion of LDLT recommendations to high-MELD recipients in centers with expertise to help reduce donor shortage.

Outcomes following liver transplant for alcohol-associated liver disease: comparing alcohol-associated hepatitis and cirrhosis.

BACKGROUND: Liver transplant (LT) is a highly effective therapy for refractory severe alcohol-associated hepatitis (SAH), but optimal selection criteria remain unknown. We aim to evaluate the outcomes of patients who received LT for alcohol-associated liver disease at our center following the introduction of updated selection criteria, including the removal of the minimum sobriety requirement. METHODS: Data were collected on all patients who underwent LT for alcohol-associated liver disease from January 1, 2018, to September 30, 2020. Patients were divided into SAH and cirrhosis cohorts based on disease phenotype. RESULTS: One hundred twenty-three patients underwent LT for alcohol-associated liver disease, including 89 (72.4%) for cirrhosis and 34 (27.6%) for SAH. There was no difference in 1- (97.1 ± 2.9% vs. 97.7 ± 1.6%, p = 0.97) and 3-year (97.1 ± 2.9% vs. 92.4 ± 3.4%, p = 0.97) survival between SAH and cirrhosis cohorts. Return to alcohol use was more frequent in the SAH cohort at 1 year (29.4 ± 7.8% vs. 11.4 ± 3.4%, p = 0.005) and 3 years (45.1 ± 8.7% vs. 21.0 ± 6.2%, p = 0.005) including higher frequencies of both slips and problematic drinking. Unsuccessful alcohol use counseling (HR 3.42, 95% CI 1.12-10.5) and prior alcohol support meetings (HR 3.01, 95% CI 1.03-8.83) predicted a return to harmful alcohol use patterns in early LT recipients. Both duration of sobriety (c-statistic 0.32 (95% CI 0.34-0.43) and SALT score (c-statistic 0.47, 95% CI 0.34-0.60) were independently poor predictors of return to harmful drinking. CONCLUSION: Survival following LT was excellent in both SAH and cirrhosis cohorts. Higher rates of return to alcohol use highlight the importance of further individualized refinement of selection criteria and improved support following LT.

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation.

Content available: Audio Recording.

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation: A Meta-Analysis.

After liver transplantation (LT), the role of ursodeoxycholic acid (UDCA) is not well characterized. We examine the effect of UDCA after LT in the prophylaxis of biliary complications (BCs) in all-comers for LT and the prevention of recurrent primary biliary cholangitis (rPBC) in patients transplanted for PBC. Two authors searched PubMed/MEDLINE and Embase from January 1990 through December 2018 to identify all studies that evaluate the effectiveness of UDCA prophylaxis after LT for BCs in all LT recipients and rPBC after LT in patients transplanted for PBC. Odds ratios (ORs) were calculated for endpoints of the BC study. Pooled recurrence rates were calculated for rPBC. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. A total of 15 studies were included, comprising 530 patients in the analysis for BCs and 1727 patients in the analysis for rPBC. UDCA was associated with decreased odds of BCs (OR, 0.70; 95% confidence interval [CI], 0.52-0.93; P = 0.01) and biliary stones and sludge (OR, 0.49; 95% CI, 0.24-0.77; P = 0.004). Prophylactic use of UDCA did not affect the odds of biliary stricture. For patients transplanted for PBC, the rate of rPBC was lower with the prophylactic use of UDCA (IR 16.7%; 95% CI, 0.114%-22.0%; I2 = 36.1%) compared with not using prophylactic UDCA (IR 23.1%; 95% CI, 16.9%-29.3%; I2 = 86.7%). UDCA after LT reduces the odds of BC and bile stones and sludge in all-comer LT recipients and reduces or delays the incidence of rPBC in patients transplanted for PBC. UDCA use after LT could be considered in all LT recipients to reduce the odds of BC and may be particularly beneficial for patients transplanted for PBC by reducing the incidence of rPBC.

Managing the Symptoms and Complications of Cholestasis.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-mayo a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-mayo an interview with the author https://www.wileyhealthlearning.com/Activity/7058616/disclaimerspopup.aspx questions and earn CME.

More Than a Rash: Recurrent Hepatocellular Carcinoma After Liver Transplantation.

Recurrent hepatocellular carcinoma (HCC) after liver transplant is uncommon in patients who have favorable pretransplant characteristics. We present a 56-year-old man with a history of liver transplant 8 weeks prior for hepatitis C cirrhosis and HCC who presented for shortness of breath. He was found to have a microangiopathic hemolytic anemia and an erythematous, nodular skin rash on his left lower abdomen. Biopsy of the skin rash would demonstrate metastatic HCC, determined to be the cause of hemolysis as well. Recurrent malignancy should be considered in patients with a history of HCC who present with new, unexplained skin nodules.

Two-stage liver transplant for ruptured hepatic adenoma: A case report.

BACKGROUND: Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage. We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation. This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma. CASE SUMMARY: A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day. She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma. She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure, hepatic failure, and hemodynamic instability, known as toxic liver syndrome. In the setting of uncontrolled hemorrhage and toxic liver syndrome, a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later. She tolerated the anhepatic stage well, and has done well over one year later. CONCLUSION: When toxic liver syndrome is recognized, liver transplantation with or without hepatectomy should be considered before the patient becomes unstable.

Lymphovascular invasion on explant is associated with presenting tumor characteristics and not direct acting antiviral utilization in hepatitis C candidates undergoing liver transplantation.

AIM OF THE STUDY: Utilization of direct acting antiviral (DAA) therapy in candidates with well-compensated hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma (HCC) accruing end stage liver disease (MELD) exception points is highly variable among transplant centers based on center location, local organ procurement dynamics, HCV(+) organ availability, and patient preference. The association between DAA utilization prior to transplant and incidence of lymphovascular invasion on explant is unknown. MATERIAL AND METHODS: Retrospective evaluation from 2013-2017 of patients on a liver transplant (LT) waitlist with HCV-related cirrhosis, MELD-Na < 15, and HCC (within T2/Milan criteria). The cohort was divided into the pre-LT DAA treated group and untreated group with clinical/viral demographics collected. Tumor presenting characteristics, locoregional treatments, wait time to LT, dropout rates and explant pathology were compared. RESULTS: DAAs were used in 44 patients prior to LT (SVR12 of 37/44 [84%]) and 19 left untreated with LT performed in 81% (51/63) of the waitlisted cohort. No significant differences were found between groups with regards to clinical/viral demographics, local-regional therapy (LRT) sessions, or frequency of lymphovascular invasion on explant. The untreated cohort had a higher rate of dropout (6.3% vs. 3.2%) (p = 0.041). On subgroup analysis of 51 subjects undergoing LT, AFP > 250 ng/ml (p = 0.003) and multifocal HCC (> 1 lesion) (p = 0.006) were associated with lymphovascular invasion on explant while DAA therapy was not (p = 0.578). CONCLUSIONS: DAA therapy for waitlist active HCV candidates accruing MELD exception points has no deleterious effects on bridging LRT, nor is it associated with increased frequency of lymphovascular invasion on explant. The latter appears driven by tumor related characteristics (AFP and number of lesions) irrespective of DAA utilization prior to LT.

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis.

Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 to characterize practice patterns and perceptions of LT for SAH. We obtained responses from 45 (41.3%) of 109 surveyed centers, representing all 11 (100%) United Network for Organ Sharing regions. Half (n = 23; 51.1%) reported performing at least 1 LT for SAH, although most (n = 19; 82.6%) of those had performed ≤5 LTs for that indication. Centers expressed near consensus for selection criteria, requiring strong social support (100%), no prior presentations with SAH (91.3%), absence of a severe coexisting psychiatric disorder (91.3%), and official psychosocial evaluation (87.0%). Reported posttransplant survival of SAH patients was excellent, with 17 (73.9%) centers reporting 1-year posttransplant survival exceeding 90%. Among centers that had not performed LT for SAH, the most commonly cited reason was perceived high risk of alcohol relapse. In conclusion, our data demonstrate that LT is increasingly adopted as a therapeutic intervention for patients with SAH and that careful selection allows for excellent 1-year posttransplant survival. Despite this, nearly half of US centers do not perform LT for this indication due to perceived high risk of alcohol relapse. Our data support the use of LT for well-selected patients with SAH.

Sarcopenia is a risk factor for complications and an independent predictor of hospital length of stay in trauma patients.

BACKGROUND: Sarcopenia is an independent risk factor for adverse outcomes in critically ill patients. The impact of sarcopenia on morbidity and length of stay in a trauma population has not been completely defined. This project evaluated the influence of sarcopenia on patients admitted to the trauma service. MATERIALS AND METHODS: A retrospective review of 778 patients presenting as a trauma alert at a single institution from 2012-2014 was completed. Records were abstracted for comorbidities and hospital complications. The Hounsfield Unit Area Calculation was collected from admission computed tomography scans. Criteria for sarcopenia were based on the lowest 25th percentile of muscle density measurements. Relationships to patient outcomes were evaluated by univariate and multivariable regression or analyses of variance, when applicable. RESULTS: A total of 432 (55.6%) patients suffered a complication. Sarcopenia was associated with overall complications (P < 0.0001, relative risk 2.54, confidence interval 1.78-3.61) and was an independent risk factor for catheter-associated urinary tract infections (P = 0.011), wound infections (P = 0.011), need for reintubation (P = 0.0062), and length of hospitalization (P = 0.0007). Incorporating sarcopenia into a novel length of stay calculator showed increased prognostic ability for prolonged length of stay over Abbreviated Injury Scale alone (P = 0.0002). CONCLUSIONS: Sarcopenia is an independent risk factor for adverse outcomes and increased length of stay in trauma patients. Prognostic algorithms incorporating sarcopenia better predict hospital length of stay. Identification of patients at risk may allow for targeted interventions early in the patient's hospital course.

Sarcopenia is a Predictor of Surgical Morbidity in Inflammatory Bowel Disease.

BACKGROUND: Sarcopenia is associated with an increased risk of operative morbidity and mortality. The impact of sarcopenia in inflammatory bowel disease (IBD) has not been evaluated. This study assessed the role of sarcopenia on operative outcomes in IBD. METHODS: A retrospective review of American College of Surgeons National Surgical Quality Improvement Program data of patients with IBD was completed. Records were abstracted for comorbidities and perioperative complications. The Hounsfield unit average calculation was used from preoperative computed tomography (CT). Criteria for sarcopenia were based on the lowest 25th percentile. Complications were graded using the Clavien-Dindo classification system. Statistical analysis was completed using SAS. RESULTS: There were 178 patients included. Sarcopenic patients were more likely to be older (P = 0.001), have hypertension (odds ratio = 2.23), and be diabetic (5.27). In those patients younger than 40 years, sarcopenia was an independent predictor of complications. This subset was significantly more likely to have a normal or elevated body mass index. CONCLUSIONS: In this population, the average age of sarcopenic patients is increased from those who do not meet criteria. Among patients younger than 40 years, sarcopenia affects surgical outcomes. Assessment of sarcopenia can be used to improve preoperative management and describe risks before surgery in patients with IBD.

25-Vitamin D levels in chronic hepatitis C infection: association with cirrhosis and sustained virologic response.

BACKGROUND: Low serum 25-Vitamin D levels are associated with advanced fibrosis in hepatitis C infection. Vitamin D supplementation has been hypothesized to augment response rates to interferon-based therapy. To date, no investigation has evaluated vitamin D levels during direct-acting antiviral therapy. We aimed to evaluate the prevalence of vitamin D deficiency in cirrhotic and non-cirrhotic cohorts, the predictive value of pretreatment levels for a sustained virologic response, and the changes in 25-OH vitamin D levels during direct-acting antiviral therapy. METHODS: Two hundred eighteen patients with chronic hepatitis C who completed direct-acting antiviral therapy were consecutively enrolled. Vitamin D levels were measured using chemiluminescence immunoassay, prior to initiation and at completion of therapy. Advanced liver fibrosis (cirrhosis) was determined by biopsy, FibroSURE blood test, or imaging. RESULTS: A sustained virologic response was achieved in 79% (n=172) of patients, with 19% (n=44) relapsing. A total of 123 (56.4%) patients were cirrhotic. The prevalence of Vitamin D deficiency (10-20 ng/mL) and severe deficiency (<10 ng/mL) was significantly higher in cirrhotic patients (P=0.04). Pre-treatment vitamin D levels in cirrhotic patients were negatively correlated with Model for End-Stage Liver Disease score, total bilirubin and INR (P<0.05). Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response. CONCLUSIONS: The prevalence of vitamin D deficiency is higher in hepatitis-C-related cirrhotic cohorts compared to non-cirrhotic patients and correlates with components of hepatic function. Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response.

Genotype specific peripheral lipid profile changes with hepatitis C therapy.

AIM: To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype. METHODS: Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3. RESULTS: Three hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (ΔGT1, p and ΔGT3, p), with TCHOL increasing (+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing (+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing (+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing (-5.9, P = 0.044 and -9.80 P = 0.067). Among genotypes (ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL (+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL (+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 (P = 0.028 and P = 0.019). CONCLUSION: Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.

Pretransplant Factors and Associations with Postoperative Respiratory Failure, ICU Length of Stay, and Short-Term Survival after Liver Transplantation in a High MELD Population.

Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, p = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, p < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.