Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.

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.

Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [ p <0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [ p <0.05]). There were no differences in the 1-, 3-, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p =0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [ p >0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Post-Transplant Management and Complications of Autoimmune Hepatitis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis including Disease Recurrence.

Autoimmune liver diseases have unique post-transplant considerations. These recipients are at increased risk of rejection, and recurrent disease may also develop, which can progress to graft loss and increase mortality. Monitoring for and managing these complications is therefore important, though data on associated risk factors and immunosuppression strategies has in most cases been mixed. There are also other disease-specific complications that require management and may impact these decisions, including inflammatory bowel disease in PSC. Further work to better understand the optimal management strategies for these patients post-transplant is needed.

Influence of socioeconomic factors on liver transplant survival outcomes in patients with autoimmune liver disease in the United States.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) have different survival outcomes after liver transplant (LT). Outcomes are influenced by factors including disease burden, medical comorbidities, and socioeconomic variables. MATERIALS AND METHODS: Using the United Network for Organ Sharing database (UNOS), we identified 13,702 patients with AILDs listed for LT between 2002 and 2021. Outcomes of interest were waitlist removal, post-LT patient survival, and post- LT graft survival. A stepwise multivariate analysis was performed adjusting for transplant recipient gender, race, diabetes mellitus, model for end-stage liver disease (MELD) score, and additional social determinants including the presence of education, reliance on public insurance, working for income, and U.S. citizenship status. RESULTS: Lack of college education and having public insurance increased the risk of waitlist removal (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.09; 95 % CI, 1.00-1.18; respectively), and negatively influenced post-LT patient survival (HR, 1.16; 95 % CI, 1.06-1.26, and HR, 1.15; 95 % CI, 1.06-1.25; respectively) and graft survival (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.15; 95 % CI, 1.06-1.25; respectively). Not working for income proved to have the greatest detrimental impact on both patient survival (HR, 1.41; 95 % CI, 1.24-1.6) and graft survival (HR, 1.21; 95 % CI, 1.09-1.35). CONCLUSIONS: Our study highlights that lack of college education and public insurance have a detrimental impact on waitlist mortality, patient survival, and graft survival. Not working for income negatively affects post-LT survival outcomes. Not having U.S. citizenship does not affect survival outcomes in AILDs patients.

The Influence of Hepatic Steatosis and Fibrosis on Postoperative Outcomes After Major Liver Resection of Perihilar Cholangiocarcinoma.

BACKGROUND: Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS: Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS: Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION: In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.

Liver transplantation for iatrogenic bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) is an infrequent but serious complication of cholecystectomy, often with life-changing consequences. Liver transplantation (LT) may be required following severe BDI, however given the rarity, few large studies exist to guide management for complex BDI. METHODS: A systematic review was performed to assess post-operative complications, 30-day mortality, retransplant rate and 1-year and 5-year survival following LT for BDI in Medline, EMBASE, Web of Science or Cochrane Clinical Trials Database. RESULTS: Seven articles met inclusion criteria, describing 179 patients that underwent LT for BDI. Secondary biliary cirrhosis (SBC) was the main indication for LT (82.2% of patients). Median model for end-stage liver disease (MELD) scores at time of LT ranged from 16 to 20.5. Median 30-day mortality was 20.0%. The 1-year and 5-year survival ranges were 55.0-84.3% and 30.0-83.3% respectively, and the overall retransplant rate was 11.5%. CONCLUSION: BDI is rarely indicated for LT, predominantly for SBC following multiple prior interventions. MELD scores poorly reflect underlying morbidity, and exception criteria for waitlisting may avoid prolonged LT waiting times. 30-day mortality was higher than for non-BDI indications, with comparable long term survival, suggesting that LT remains a viable but high risk salvage option for severe BDI.

The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis.

BACKGROUND & AIMS: In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). METHODS: The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. RESULTS: There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n = 1581), those with gender-mismatch (male donors, n = 769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n = 304), no associations were found between gender-mismatch (female donors, n = 108) and all-cause mortality or graft failure. CONCLUSION: This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.

Zero Mortality in Living-Donor Liver Transplantation for Primary Biliary Cholangitis in Patients With a Meld Score of <20.

BACKGROUND: Although primary biliary cholangitis (PBC) is considered a good indication for living-donor liver transplantation (LDLT), the postoperative results are not well known. METHODS: At Jikei University Hospital, 14 patients with PBC underwent LDLT from February 2007 to June 2022. We consider PBC with a Model for End-Stage Liver Disease (MELD) score of <20 to indicate LDLT. We performed a retrospective analysis of the patients' clinical records. RESULTS: The patients' median age was 53 years, and 12 of the 14 patients were female. A right graft was used in 5 patients, and 3 ABO-incompatible transplants were performed. The living donors were children in 6 cases, partners in 4 cases, and siblings in 4 cases. The preoperative MELD scores ranged from 11 to 19 (median, 15). The graft-to-recipient weight ratio ranged from 0.8 to 1.1 (median, 1.0). The median operative time for donors and recipients was 481 and 712 minutes, respectively. The median operative blood loss of donors and recipients was 173 and 1,800 mL, respectively. The median postoperative hospital stay of donors and recipients was 10 and 28 days, respectively. All recipients recovered satisfactorily and remained well during a median follow-up of 7.3 years. Three patients underwent a liver biopsy after LDLT because of acute cellular rejection without histologic findings of PBC recurrence. CONCLUSIONS: Living-donor liver transplantation provides satisfactory long-term survival for patients with PBC with a graft-to-recipient weight ratio of >0.7 and MELD score of <20 without hepatocellular damage and only portal vein hypertension.

Ursodeoxycholic Acid Treatment-Induced GLOBE Score Changes Are Associated With Liver Transplantation-Free Survival in Patients With Primary Biliary Cholangitis.

INTRODUCTION: Treatment of primary biliary cholangitis (PBC) can improve the GLOBE score. We aimed to assess the association between changes in the GLOBE score (ΔGLOBE) and liver transplantation (LT)-free survival in patients with PBC who were treated with ursodeoxycholic acid (UDCA). METHODS: Among UDCA-treated patients within the Global PBC cohort, the association between ΔGLOBE (ΔGLOBE 0-1 : during the first year of UDCA, ΔGLOBE 1-2 : during the second year) and the risk of LT or death was assessed through Cox regression analyses. RESULTS: Overall, 3,775 UDCA-treated patients were included; 3,424 (90.7%) were female, the median age was 54.0 (interquartile range [IQR] 45.9-62.4) years, and the median baseline GLOBE score was 0.25 (IQR -0.47 to 0.96). During a median follow-up of 7.2 (IQR 3.7-11.5) years, 730 patients reached the combined end point of LT or death. The median ΔGLOBE 0-1 was -0.27 (IQR -0.56 to 0.02). Cox regression analyses, adjusted for pretreatment GLOBE score and ΔGLOBE 0-12 , showed that ΔGLOBE was associated with LT or death (adjusted hazard ratio 2.28, 95% confidence interval 1.81-2.87, P < 0.001). The interaction between baseline GLOBE score and ΔGLOBE 0-1 was not statistically significant ( P = 0.296). The ΔGLOBE 1-2 was associated with LT or death (adjusted hazard ratio 2.19, 95% confidence interval 1.67-2.86, P < 0.001), independently from the baseline GLOBE score and the change in GLOBE score during the first year of UDCA. DISCUSSION: UDCA-induced changes in the GLOBE score were significantly associated with LT-free survival in patients with PBC. While the relative risk reduction of LT or death was stable, the absolute risk reduction was heavily dependent on the baseline prognosis of the patient.

Trends in liver transplantation for autoimmune liver diseases: a Canadian study.

BACKGROUND: To our knowledge, no analysis of data from liver transplantation registries exists in Canada. We aimed to describe temporal trends in the number of liver transplantation procedures, patient characteristics and posttransplantation outcomes for autoimmune liver diseases (AILDs) in Canada. METHODS: We used administrative data from the Canadian Organ Replacement Register, which contains liver transplantation information from 6 centres in Canada. This study included transplantation information from 5 of the centres, as liver transplantation procedures in children were not included. We included adult (age ≥ 18 yr) patients with a diagnosis of primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) or overlap syndrome (PBC-AIH or PSC-AIH) who received a liver transplant from 2000 to 2018. RESULTS: Of 5722 primary liver transplantation procedures performed over the study period, 1070 (18.7%) were for an AILD: 489 (45.7%) for PSC, 341 (31.9%) for PBC, 220 (20.6%) for AIH and 20 (1.9%) for overlap syndrome. There was a significant increase in the absolute number of procedures for PSC, with a yearly increase of 0.6 (95% confidence interval 0.1 to 1.2), whereas the absolute number of procedures for PBC and AIH remained stable. The proportion of transplantation procedures decreased for PBC and AIH but remained stable for PSC. Recipient age at transplantation increased over time for males with PBC (median 53 yr in 2000-2005 to 57 yr in 2012-2018, p = 0.03); whereas the median age among patients with AIH decreased, from 53 years in 2000-2005 to 44 years in 2006-2011 (p = 0.03). The Model for Endstage Liver Disease score at the time of transplantation increased over time for all AILDs, particularly AIH (median 16 in 2000-2005 v. 24 in 2012-2018, p < 0.001). There was a trend toward improved survival in the PBC group, with a 5-year survival rate of 81% in 2000-2005 and 90% in 2012-2018 (p = 0.06). CONCLUSION: Between 2000 and 2018, the absolute number of liver transplantation procedures in Canada increased for PSC but remained stable for PBC and AIH; proportionally, PBC and AIH decreased as indications for transplantation. Posttransplantation survival improved only for the PBC group. An improved understanding of trends and outcomes on a national scale among patients with AILD undergoing liver transplantation can identify disparities and areas for potential health care improvement.

Liver transplant-free survival according to alkaline phosphatase and GLOBE score in patients with primary biliary cholangitis treated with ursodeoxycholic acid.

BACKGROUND: After 1 year of ursodeoxycholic acid (UDCA), patients with primary biliary cholangitis (PBC) may have a normal GLOBE score despite high alkaline phosphatase (ALP) levels. AIM: To assess the association between ALP and liver transplantation (LT)-free survival according to the GLOBE score METHODS: Among patients with a normal or elevated GLOBE score in the Global PBC cohort, the association between ALP after 1 year of UDCA and the risk of LT/death was assessed. The LT-free survival was compared with that of a matched general population. RESULTS: After 1 year of UDCA, ALP was associated with the risk of LT/death (aHR 1.31, 95% CI 1.003-1.72, p = 0.048) among 2729 patients with a normal GLOBE score. The 10-year LT-free survival among these patients with an ALP >2.0 × ULN was 94.0% (95% CI 90.1-97.9) for those <50 years, and 82.6% (95% CI 76.5-88.7) for those ≥50 years, which was significantly lower (p = 0.040) and similar (p = 0.736) to that of the matched population, respectively. The 10-year LT-free survival in patients ≥50 years with normal GLOBE score and normal ALP (90.8%, 95% CI 87.7-93.9) was significantly higher (p = 0.022) than the matched population. Among 1045 patients with an elevated GLOBE score, ALP was associated with LT/death only in those <50 years (aHR 1.38, 95% CI 1.06-1.81, p = 0.016). CONCLUSION: The LT-free survival of patients with PBC with a normal GLOBE score is optimal in case of normal ALP levels, also in relation to the general population. Despite their generally favourable prognosis, an elevated ALP level may still indicate a need for add-on therapy.

Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls.

BACKGROUND & AIMS: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls. METHODS: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. RESULTS: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10-0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12-0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation. CONCLUSIONS: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.

Pretransplant Evaluation and Liver Transplantation Outcome in PBC Patients.

Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic liver disease characterized by progressive cholangiocyte and bile duct destruction leading to fibrosis and finally to liver cirrhosis. The presence of disease-specific serological antimitochondrial antibody (AMA) together with elevated alkaline phosphatase (ALP) as a biomarker of cholestasis is sufficient for diagnosis. Ursodeoxycholic acid (UDCA) is the first treatment option for PBC. Up to 40% of patients have an incomplete response to therapy, and over time disease progresses to liver cirrhosis. Several risk scores are proposed for better evaluation of patients before and during treatment to stratify patients at increased risk of disease progression. GLOBE score and UK PBC risk score are used for the evaluation of UDCA treatment and Mayo risk score for transplant-free survival. Liver transplantation (LT) is the only treatment option for end-stage liver disease. More than 10 years after LT, 40% of patients experience recurrence of the disease. A liver biopsy is required to establish rPBC (recurrent primary biliary cholangitis). The only treatment option for rPBC is UDCA, and data show biochemical and clinical improvement, plus potential beneficial effects for use after transplantation for the prevention of rPBC development. Additional studies are required to assess the full impact of rPBC on graft and recipient survival and for treatment options for rPBC.

Waitlist mortality in patients with autoimmune liver diseases.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis are the primary indication for ∼24% of total liver transplants. The liver transplant allocation system is currently based upon the Model for End-Stage Liver Disease and it often underestimates the severity of autoimmune liver diseases. We aim to compare the rate of adverse waitlist removal among patients with all autoimmune liver diseases and other indications for liver transplant in the Model for End-Stage Liver -Na era. MATERIALS AND METHODS: Using the United Network for Organ Sharing database, we identified all patients listed for liver transplant from 2016 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to evaluate the waitlist survival. RESULTS: Patients with autoimmune hepatitis had a higher risk of being removed from the waitlist for death or clinical deterioration (SHR 1.37, 95% CI 1.08-1.72; P<0.007), followed by primary biliary cholangitis (SHR 1.34, 95% CI 1.07-1.68; P<0.011). CONCLUSIONS: High waitlist death or removal for clinical deterioration was observed in patients with PBC and AIH when compared to other etiologies. It may be useful to reassess the process of awarding MELD exception points to mitigate such disparity.

Excess liver transplant waitlist mortality for patients with primary biliary cholangitis under MELD-Na allocation.

BACKGROUND: Historically, patients with primary biliary cholangitis (PBC) experience waitlist mortality and low rates of liver transplant (LT). Herein, the impact of MELD-Na based allocation on PBC waitlist mortality was examined. METHODS: Adult patients with PBC were compared to those with alcohol-related liver disease (ALD) or non-alcoholic steatohepatitis (NASH) listed for LT from 2013 to 2019 in OPTN. Competing risk regression evaluated waitlist mortality in the MELD and MELD-Na eras using propensity score weights. RESULTS: Overall, 1508 patients with PBC, 13581 with ALD, and 10455 with NASH were examined. In the MELD-Na era, 24-month cumulative incidence of waitlist mortality for PBC was 23.0% (95%CI 19.7-26.5%), ALD 13.9% (95%CI 13.1-14.8%), and NASH 20.0% (95%CI 18.9-21.2%). Using propensity score weights, adjusted risk of waitlist mortality was higher for PBC versus ALD (HR = 1.45, 95%CI 1.22-1.71) and NASH (HR = 1.32, 95%CI 1.14-1.55). Furthermore, among PBC, waitlist mortality risk per five-point elevation in MELD-Na (HR = 1.22, 95%CI 1.11-1.35) and Karnofsky score ≤30% (HR = 2.02, 95%CI 1.39-2.92) was significantly higher than among ALD (HR = 1.08, 95%CI 1.04-1.13; HR = 1.28, 95%CI 1.10-1.49) and NASH (HR = 1.05, 95%CI 1.00-1.09; HR = 1.16, 95%CI .99-1.37; all P-interactions < .05). CONCLUSIONS: The MELD-Na score continues to underestimate risk of waitlist death for patients with PBC relative to ALD and NASH and highlights need for additional score modifications or exceptions.

Primary biliary cholangitis has the highest waitlist mortality in patients with cirrhosis and acute on chronic liver failure awaiting liver transplant.

BACKGROUND: Data are sparse on etiology specific outcomes on waitlist (WL) and post-transplant outcomes among patients with acute on chronic liver failure (ACLF). METHODS AND RESULTS: In a retrospective cohort of 14,774 adults from United network for organ sharing (UNOS) database listed for Liver transplantation (LT) with cirrhosis and ACLF (January 2013-June 2019), 40% were due to alcohol-associated liver disease (ALD), followed by hepatitis C virus (HCV) at 20%, non-alcoholic steatohepatitis (19%), cryptogenic cirrhosis (7%), autoimmune hepatitis (5%), primary sclerosing cholangitis (PSC) at 3%, and 2% each for hepatitis B, primary biliary cholangitis (PBC), and metabolic etiology. Using competing risk analysis, cumulative risk of WL mortality was highest for PBC at 20.5% and lowest for PSC at 13.3%, P < .001. Compared with ALD as reference, WL mortality was higher for PBC (1.45 [1.16-1.82]), and similar for other etiologies, P < .001. Of this cohort, 9650 (65.3%) patients received LT, with 1-year. patient survival of 91.6% for PBC, worst for cryptogenic cirrhosis (89.5%) and best for PSC and ALD (93.4%), P < .001. CONCLUSION: Among listed candidates with ACLF, those with PBC have highest WL mortality 1-year. post-transplant survival was excellent among recipients for PBC. If these findings are validated in prospective studies, liver disease etiology should be considered for LT selection among patients in ACLF.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature.

BACKGROUND: Autoimmune enteropathy (AIE) and primary biliary cholangitis (PBC) are both immune-mediated diseases. AIE or PBC complicated with ulcerative colitis (UC) are rare. There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before, and the pathogenesis of these comorbidities has not been revealed. CASE SUMMARY: A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease, and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016. A few months after the neoileostomy, she began to suffer from recurrent episodes of watery diarrhea. She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect. However, her symptoms of diarrhea relapsed in 2019, with different histological features of endoscopic biopsies compared with 2016, which showed apoptotic bodies, a lack of goblet and Paneth cells, and villous blunting. A diagnosis of AIE was established, and the patient's stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d. Meanwhile, her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC, and treatment with ursodeoxycholic acid (16 mg/kg per day) achieved satisfactory results. CONCLUSION: Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients. Continuous follow-up is essential for UC patients with postoperative complications.

Successful pregnancy and follow-up after in vitro fertilization of a kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and hypothyroidism.

This report describes the case of a female kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and postsurgical hypothyroidism due to Grave's disease who had a healthy newborn after in vitro fertilization (IVF). Cases of successful pregnancy involving women who underwent IVF after kidney transplantation have been reported. Normal and stable renal function, adequate immunosuppressant therapy, and well-managed blood pressure are requirements to be eligible for IVF and pregnancy. Primary biliary cholangitis without cirrhosis does not seem to worsen during pregnancy and IVF must be individualized in patients with systemic lupus erythematosus. There are no similar case reports involving kidney transplant patients or individuals with autoimmune disorders, so the decision to perform IVF had to be individualized in order to avoid complications for the mother and fetus.

Quality of life 5 years following liver transplantation.

BACKGROUND: Data on quality of life (QOL) among liver transplant recipients from India is scarce. We conducted a prospective assessment of QOL and incidence of complications 5 years following liver transplantation (LT). METHODS: Demographic data of 130 patients (M:F = 98:32, mean age 38.4 ± 14.9 years) who had completed at least 5 years after LT were collected and the incidence of new onset metabolic complications and renal dysfunction was analyzed. Liver transplant database (LTD QOL) questionnaire was given to 100 patients and scoring was done on five QOL domains. This was compared to a historical cohort from the liver transplant database of three transplant centres from North America, who had completed the same questionnaire before and 1 year after LT. RESULTS: The incidence of new onset dyslipidemia, diabetes mellitus, renal dysfunction, hypertension and overweight/obesity was 43%, 26.7%, 25%, 16.4% and 15.4%, respectively. Although ethanol-related cirrhosis was the etiology for transplant in 38%, recidivism was not evident in any recipient in this cohort even after 5 years. Significant improvement in QOL was observed in all five domains, namely measures of disease (p=0.001), psychological status (p=0.001), personal function (p=0.001), social and role function (p=0.001) and general health perception (p=0.001) in our patients 5 years after transplant compared to historical data. CONCLUSION: Although metabolic disease is common after LT, there is significant improvement in long-term QOL. Recidivism appeared to be rare in our study population.