Recurrent Autoimmune Hepatitis Research Articles

Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement.

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.

Use of immunotherapy with check point inhibitors in soft tissue sarcoma: Analysis from single institution.

e23566 Background: Traditional treatments for soft tissue sarcomas include surgery, chemotherapy, and radiation. Effectiveness of Check point inhibitors for sarcoma has been unsatisfactory thus far. Major clinical trials PEMBROSARC and SARC028 revealed median PFS of 2 and 4.5 months, respectively. The FDA has approved three immunotherapy (IO) therapies for sarcoma. Atezolizumab was approved for alveolar soft part sarcoma. Dostarlimab is approved for sarcoma with DNA mismatch repair deficiency (dMMR), Sarcoma patients with high microsatellite instability (MSI-H), dMMR, or tumor mutational burden can receive pembrolizumab. A single-institution analysis of soft tissue sarcoma patients with IO is presented in this paper. Methods: All soft tissue sarcoma patients who have received IO from January 2021 to now have been included. At our institute, a total of seven patients received IO for soft tissue sarcoma. Observations were made regarding their fundamental characteristics and the progression free survival (PFS). The data was not statistically examined due to the small sample size and the heterogeneity of the data. Results: 2 of 7 trial patients were lost to follow-up. Recurrent autoimmune hepatitis terminated IO for another patient. Most of the patients are elderly with the median age of 78. Given their comorbidities and age, IO was chosen as the first line for 5 patients. Median PFS was 5.8 months. High PDL1 ( > / = 5%) patients had a median PFS of 5.6 months, while low PDL1 patients had 4.5 months. However, one patient with low PDL1 had PFS of 7 months. 5/7 patients didn’t have IO related side effects. Two patients developed Autoimmune (AI) hepatitis. Conclusions: The limited sample size prevented definitive conclusions from being drawn. Despite the unsatisfactory outcomes, it is worth mentioning that IO provided a certain degree of PFS in older patients with comorbidities who are not suitable candidates for chemotherapy. Based on limited data, patients with high PDL1 status appear to benefit more. IO alone has not shown promising results. In clinical trials, IO is being tested with chemotherapy and Tyrosine kinase inhibitors. The findings from these trials will provide valuable insights into the potential benefits of combination therapy. [Table: see text]

Liver Transplant in Patients With Autoimmune Hepatitis: A Large Single-Center Study.

Autoimmune hepatitis is a rare indication for liver transplant in Western countries. Our goal was to identify characteristics and long-term outcomes of patients who underwent liver transplant for autoimmune hepatitis-related end-stage liver disease at our center. Adult patients who underwent primary liver transplant from January 2007 to March 2022 at Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran, were enrolled in our study. Among 1107 patients enrolled in our study, mean age was 45.94 ± 12.43 years (range, 16-73 years) and 423 (38.2%) female patients were included. Autoimmune hepatitis was the underlying cause of cirrhosis in 177 patients (experimental group); the other 930 patients did not have autoimmune hepatitis (control group). All patients were followed for a median of 60 ± 40.3 months (range, 3-187 months) after transplant. In the experimental group, patient survival rates at 1 month, 1 year, and 3 years were 87%, 81%, and 78%, which were not significantly different between the 2 groups (P = .445). Recurrence of autoimmune hepatitis was detected in 8 patients (4.5%) in the experimental group. Acute allograft rejection was more significantly detected in the patients with recurrence of autoimmune hepatitis than in patients without recurrence of autoimmune hepatitis. Liver transplant in patients with autoimmune hepatitis is safe and is associated with good outcomes.

Successful Liver Retransplantation in a Patient With Disseminated Aspergillosis and Nocardiosis: A Case Report

Clinical guidelines list active fungal infection and sepsis as contraindications to liver transplantation due to the risk of worsening infection with immunosuppression postoperatively. Mortality from systemic opportunistic infections in transplant recipients is high, approaching 100% for disseminated aspergillosis. However, the optimal duration of treatment required before transplant is unclear. Additionally, delaying surgery while the infection is treated risks death from hepatic decompensation and physical deconditioning, preventing progression to transplantation. Here, we present a patient who underwent successful repeat liver transplantation for recurrent autoimmune hepatitis and graft rejection while undergoing treatment for disseminated aspergillosis and nocardiosis. He had pulmonary, hepatic, and central nervous system involvement. He had received 2 months of antimicrobials but had ongoing radiologic evidence of infection when listed for retransplantation. He remains well and infection-free 1 year postoperatively. Few cases of successful liver transplantation in the setting of disseminated aspergillosis have been reported previously. To our knowledge, this is the first successful liver transplant in a patient with disseminated nocardial infection.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH). A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6months) were excluded. The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4-53.8). Median follow-up was 87.0months (IQR, 43.5-168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR=2.9; 95% CI, 1.4-6.2; p= 0.005) and occurrence of an infectious episode within the first year after LT (HR=2.5; 95% CI, 1.2-5.1; p= 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR=2.7; 95% CI, 1.5-5.0; p= 0.001), chronic rejection (HR=2.9; 95% CI, 1.4-6.1; p= 0.005), biliary (HR=2.0; 95% CI, 1.2-3.4; p= 0.009), vascular (HR=1.8; 95% CI, 1.0-3.1; p= 0.044) and early septic (HR=2.1; 95% CI, 1.2-3.5; p= 0.006) complications. Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.

Relapse of autoimmune diseases after liver transplantation

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p<0.0001).Conclusions. The recurrence of autoimmune diseases leads to a decrease in graft survival. The effect of immunosuppression components on the risk of recurrence of autoimmune diseases in the graft has not been established.

The progression of chronicity and autoimmune hepatitis in recurrent drug-induced liver injury

Background and aimsRecurrent drug-induced liver injury (DILI) is not well documented. We retrospectively analysed the characteristics of patients who had a history of two separate DILI episodes due to different drugs. MethodsWe collected data from 57 patients with recurrent DILI from 9582 confirmed DILI cases. Demographic, laboratory, and clinical data from both episodes were collected and analysed to determine the relationship between recurrent DILI, chronic DILI, and autoimmune hepatitis (AIH). ResultsThe incidence rate of recurrent DILI in our cohort was 0.59%. Most of the 57 patients with recurrent DILI were female (73.68%). The latency period of the initial episode was 30 days, whereas that of the second episode was 13 days (P = 0.003). The pattern of liver injury was not significantly different between episodes (P = 0.52). Laboratory indicators, such as alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and total bilirubin, were significantly lower in the second episode than in the initial episode (P < 0.05). The incidence of chronic DILI was 43.86% during the initial episode and increased to 63.16% during the second episode. After the initial episode, 15 patients developed AIH during the second episode. ConclusionsThe latency period of recurrent DILI was gradually shortened. The clinical indices of liver injury tended to be less elevated during the second episode. Female post-menopausal patients with abnormal serum immunoglobulin G levels may be predisposed to AIH. The second DILI episode was more likely to have features of AIH.

From the Editor’s Desk...

The impact of recurrent autoimmune hepatitis (AIH) post-liver transplantation (LT) on patient or graft survival is not well characterised. In this large, international, and multi-centre study, Montano-Loza and coworkers aimed to identify the frequency of and risk factors associated with recurrent AIH after LT, and the impact of recurrent disease on patient and graft survival. Seven hundred and thirty-six patients (77% female, mean age, 42±1 years) with AIH who underwent LT from January 1987 to June 2020, were enrolled from 33 centres spanning North America, South America, Europe and Asia.

Autoimmune hepatitis and liver transplantation: Indications, and recurrent and de novo autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels. Liver transplantation may be required for patients with acute liver failure, decompensated cirrhosis, and hepatocellular carcinoma. Recurrence is defined as development of the same disease in the allograft following liver transplantation. Autoimmune hepatitis recurs in 36%-68% of the recipients 5 years after liver transplantation. De novo autoimmune hepatitis is the development of autoimmune hepatitis like clinical and laboratory characteristics in patients who had undergone liver transplantation for causes other than autoimmune hepatitis. Diagnostic work up for recurrent and de novo autoimmune hepatitis is similar to the diagnosis of the original disease, and it is usually difficult. Predniso(lo)ne with or without azathioprine is the main treatment for recurrent and de novo autoimmune hepatitis. Early diagnosis and treatment are vital for patient prognosis because de novo autoimmune hepatitis and recurrent autoimmune hepatitis cause graft loss and result in subsequent retransplantation if medical treatment fails.

Differential IgG4-Producing Plasma Cell Infiltration in Non- and Post-Transplant Plasma Cell Hepatitis.

Autoimmune hepatitis (AIH), post-transplant recurrent AIH (rAIH), and plasma cell-rich rejection (PCR) are clinical diagnoses with the shared histopathologic hallmark of plasma cell hepatitis (PCH). As these histologically and serologically indistinguishable diagnoses are differentiated by clinical context, it remains uncertain whether they represent distinct immunologic phenomena. Improved understanding of immunoglobulin subclass 4-producing plasma cells (IgG4-PC) has brought attention to IgG4 as an immunophenotypic biomarker. To date, degree and clinical significance of IgG4-PC infiltration in PCH remain elusive. This retrospective, single-center study assessed IgG4-PC infiltration in AIH, rAIH, and PCR via standardized immunohistochemistry analysis. Identified cases from 2005 to 2020 (n = 47) included AIH (treatment-naïve AIH (tnAIH): n = 15 and AIH-flare on treatment (fAIH); n = 10), rAIH (n = 8), and PCR (n = 14) were analyzed and correlated with clinical characteristics. IgG4-Positivity (# IgG4-PC/# pan-IgG-expressing cells) distribution was heterogenous and overlapping [tnAIH: 0.060 (IQR 0.040-0.079), fAIH: 0.000 (0.000-0.033), rAIH: 0.000 (0.000-0.035), PCR: 0.228 (0.039-0.558)]. IgG4-Positivity was inversely correlated with corticosteroid use (p < 0.001). IgG4-Positivity ≥0.500 was associated with rapid AST improvement (p = 0.03). The variable IgG4-Positivity of AIH, rAIH and PCR suggests diverse and overlapping immunopathologic mechanisms and that current diagnostic schemes inadequately capture PCH immunopathology. We propose incorporation of IgG4-Positivity to refine current PCH classification and treatment strategies.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation

Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p= 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p= 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p= 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p= 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p= 0.001). Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Outcome of liver transplantation for autoimmune hepatitis in South Africa

Background: Liver Transplantation (LT) is the definitive treatment for Autoimmune Hepatitis (AIH) in patients with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Outcomes of LT in AIH among black-Africans are not well-defined. We performed a single-center retrospective-review of adult LT patients. The study period was from 1st August 2004-31st August 2019. The primary aim was to document 1- &amp; 5- year patient and graft survival. A secondary aim was to compare the survival of black-Africans to Caucasians. Data was analyzed using survival-analysis. Results: A total of 56 LT were performed for AIH. Sixty-seven percent (n = 38/56) had confirmed AIH on explant histology. Of these, the majority i.e., 79% (30/38) were female and 21% (8/38) were male. There were equal numbers of black-African 42% (n = 16/38) and Caucasian 42% (n = 16/38) patients. Rejection was four-times higher in black-Africans as compared to Caucasians. Forty-four percent (n = 17/38) had an acute rejection episode and 13% (5/38) had chronic rejection. Recurrence was found in four black-African females. Post-LT patient survival at 1- and 5- years was 86.5% and 80.7%, and graft survival was 94% and 70.8% respectively. The 5- year patient survival was insignificantly lower for black-Africans (73.9%) as compared to Caucasians (83.7%) (p - value 0.26, CI 6.3 - 12.2). Five-year graft survival was significantly lower among black-Africans (55%) as compared to Caucasians (84.8%) (p - value 0.003 CI 3.8 - 8.1) Conclusion: Black-Africans had a four-fold higher rate of rejection compared to Caucasians. Recurrent AIH was only found in patients of black ethnicity. Similar 1- &amp; 5- year patient survival rates were observed between the two ethnicities. The 5-year graft survival among black-Africans was significantly lower than Caucasians.

Hemophagocytic lymphohistiocytosis occurring after liver transplantation: A case series and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive inflammation and tissue destruction due to a dysregulated immune response. Its secondary form is most commonly triggered by viral infection or malignancy. There have previously been 11 cases of acquired HLH described following liver transplantation in adult transplant recipients, most occurring within the first year following transplantation. Herein, we describe two cases of HLH in liver transplant recipients that both occurred remotely following transplantation. In the first case, HLH was thought to be triggered by the development of a post-transplant lymphoproliferative disorder in a patient who was initially diagnosed with recurrent autoimmune hepatitis. In the second, it was thought to be triggered by a newly acquired human herpesvirus-8 infection. In both cases, the syndrome was not recognized until treatment for the initial putative diagnoses was unsuccessful. Despite treatment, both patients unfortunately died from multiorgan failure. HLH in the post-liver transplant setting is likely under-recognized and has a high mortality; early diagnosis and intervention may lead to improved outcomes.

HLA-DR Mismatch and Black Race Are Associated With Recurrent Autoimmune Hepatitis After Liver Transplantation.

To describe the incidence, predictors, and outcomes of R-AIH. We studied patients undergoing LT for AIH during 2000-2017 at our center. Liver biopsies were performed for clinical indications. R-AIH was defined using clinical and histologic criteria. Among 75 patients undergoing LT for AIH (mean age 45 ± 16, 65% female individuals, 19% Black), 71 (95%) received antithymocyte globulin induction with tacrolimus-based immunosuppression. R-AIH developed in 20 (27%) patients at a median interval of 313 d (interquartile range, 155-1205). R-AIH was associated with level 2 HLA-DR mismatch (hazard ratio, 3.6; (95% confidence interval, 1.3-9.9; P = 0.01) and Black race (hazard ratio, 4.5; 95% confidence interval, 1.8-11.8; P = 0.002)] in the multivariable analysis. R-AIH developed in 62% of patients with level 2 HLA-DR mismatch on single-agent immunosuppression but in <20% of patients with no or 1 HLA-DR mismatch regardless of maintenance immunosuppression. R-AIH developed in 8 (57%) of 14 Black patients (71% on single-agent and 43% on dual-agent maintenance immunosuppression). Patient and graft survival were not impacted by R-AIH over a median follow-up of 8.3 y (interquartile range, 3-12). High-level HLA-DR mismatch and Black recipient race are associated with an increased risk of R-AIH. Immunosuppression did not predict R-AIH, but higher rates of disease recurrence with single-agent maintenance immunosuppression with these risk factors were observed and may guide maintenance immunosuppression in LT for AIH.

A two decade long study of disease progression of de novo and recurrent autoimmune hepatitis in the pediatric population.

Recurrent autoimmune hepatitis (rAIH) occurs in patients who undergo liver transplantation (LT) for AIH and de novo AIH (dAIH) is seen in patients who are transplanted for etiologies other than AIH. Whether these are distinct diseases with a similar phenotype remains understudied. The aim of this study was to identify clinical and immunologic factors affecting outcome in patients with dAIH and rAIH. A retrospective review of 387 LT patients from 1997 to 2014 was carried out, and they were followed until 2018. Patients with rAIH or dAIH were identified based on the pre-transplant diagnosis of AIH (or not) and characteristic histology. Liver biopsies were stained with H&E, B-cell marker CD20, and plasma cell marker CD138. Out of 387 patients, 31 were transplanted for AIH, and 8/31 developed rAIH. Of the remaining 356 patients, eight developed dAIH. Compared to the dAIH group, rAIH occurred in older patients, had an earlier onset in the allograft, and had higher IgG and serum ALT levels. It was most commonly seen in African American (AA) patients (87%). rAIH patients had significantly higher CD20 and CD138 positivity in liver biopsies. In addition, they had increased rejection episodes prior to the onset of recurrence, increased graft loss, and mortality. rAIH is a more aggressive disease, and has a preponderance of B cells and plasma cells in the liver tissue as compared to dAIH. The concurrent association with increased graft loss and patient mortality in rAIH warrants further investigations into B cell-targeted therapies.

Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta-Analyses Supporting American Association for the Study of Liver Diseases Guidelines.

Three key management decisions in autoimmune hepatitis concern the use of budesonide and azathioprine as first-line therapy, the choice of mycophenolate mofetil or calcineurin inhibitors for patients failing steroids and azathioprine, and the role of maintenance steroids in prevention of recurrence after liver transplantation. To address these questions, comprehensive searches were performed (without language restrictions) of several databases from their inceptions to January 8, 2019. From 1,712 citations identified, the full texts of 578 studies were reviewed, and 13 studies met criteria for systematic review. Budesonide and azathioprine were significantly superior to prednisone and azathioprine in normalizing serum aminotransferase levels after 6 months in non-cirrhotic adults (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.3-3.67). However, the evidence for other outcomes was of low quality. Overall, differences in endpoint criteria and insufficiencies in data analyses precluded confident conclusions about superiority of treatment regimens. There were no significant differences in the frequencies of biochemical remission in patients with an inadequate response or intolerance to steroids and azathioprine after treatment with mycophenolate mofetil or tacrolimus (OR, 1.95; 95% CI, 0.18-20.81). The frequencies of composite outcomes of death and liver transplantation were similar for both regimens (OR 1.70; 95% CI, 0.56-3.37). The frequencies of recurrent autoimmune hepatitis after liver transplantation were also similar, regardless of whether steroids were withdrawn or continued (OR 0.27; 95% CI 0.01-7.25). Conclusions: First-line treatment with budesonide and azathioprine normalizes serum aminotransferase levels more often than prednisone and azathioprine after six months in non-cirrhotic adults. Its effectiveness in treating other presentations or reducing either mortality or need for liver transplantation remains unproven. The frequencies of biochemical remission induced by mycophenolate mofetil or tacrolimus for treatment failure or drug intolerance were comparable. Continuation of steroid therapy does not prevent recurrence post-transplant. Future studies are essential to generate evidence-based therapeutic recommendations for autoimmune hepatitis.

Single-Center North American Experience of Liver Transplantation in Autoimmune Hepatitis: Infrequent Indication but Good Outcomes for Patients.

Background and AimsA 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence.MethodsSingle-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded.ResultsA total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively.ConclusionAlthough AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.

Recurrent Disease After Liver Transplantation

Liver transplantation is an effective treatment for many different types of acute and chronic liver disease. Many diseases recur following liver transplantation. This review provides an update in the latest clinical developments in recurrent disease after liver transplantation. Low-dose corticosteroids are associated with a reduction in recurrent autoimmune hepatitis following liver transplantation. “De novo” autoimmune hepatitis should be considered and treated as a form of allograft rejection. Tacrolimus has been reported to increase the risk of recurrent primary sclerosing cholangitis following liver transplantation. Autoimmune liver diseases such as primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis notably recur after transplant although the clinical significance of recurrent disease remains unclear. The clinical presentation, diagnosis, and management of recurrent autoimmune liver disease are variable and retransplantation is uncommonly needed. With the indications for liver transplantation constantly expanding, recurrence of original disease remains an important topic requiring further study.

2402 A Rare Case of IPEX Syndrome With Hepatic Complications

INTRODUCTION: Immunodysregulation, polyendocrinopathy and enteropathy X-linked (IPEX) Syndrome is a rare autoimmune illness affecting only males starting in the early few months of life. It can be associated with autoimmune hepatitis among other systemic ailments and ultimate treatment is immunosuppression or bone marrow transplant. We present a case of undiagnosed IPEX Syndrome leading to liver failure requiring eventual liver transplantation. CASE DESCRIPTION/METHODS: A 19 year-old male patient had undergone a liver transplant at age 2 for suspected autoimmune hepatitis resulting in acute liver failure. No specific cause was identified at time of diagnosis. He remained on chronic immunosuppression thereafter, eventually progressing to chronic active autoimmune hepatitis in the transplanted liver. He was diagnosed with IPEX Syndrome at age 16, for which he underwent a bone marrow transplant. He presented to the hospital with neutropenia, and hepatology was consulted for liver transplant rejection in light of mild transaminitis. On admission, vital signs were normal and pertinent labs include: AST/ALT 50/74 units/L, Alkaline Phosphatase 811 IU/L, Albumin 3.4 g/dL, WBC 0.6 × 109 cells/L. He reportedly had multiple episodes of acute rejection in the past which were treated with steroids. Chronically, he was on mycophenolate mofetil, tacrolimus, and prednisone. His liver biopsy did not show evidence of acute rejection, but suggested chronic rejection and liver fibrosis. A prior liver biopsy had suggested autoimmune hepatitis, but no evidence of a flare on current biopsy. He was continued on his current immunosuppression regimen, and he was subsequently discharged home. DISCUSSION: Due to its rarity, incidence of IPEX syndrome is not entirely known, but is estimated to be 1 in 1,609,490. Generally, it is diagnosed in infancy and is often fatal. Our case is unique as the diagnosis was missed for more than a decade during which period the patient had even received a liver transplant for autoimmune hepatitis. Autoimmune hepatitis reportedly occurs in 20% of patients with IPEX Syndrome. There are currently no reports of liver failure requiring liver transplant in such scenarios. The fact that our patient developed recurrent autoimmune hepatitis in the transplanted liver highlights the underlying defect in his genetic disorder. This case should serve as a reminder to clinicians to consider IPEX syndrome in the differential for early onset autoimmune hepatitis, as early diagnosis could reduce significant morbidity.

Racial disparities in presentation and outcomes of paediatric autoimmune hepatitis.

Most studies on autoimmune hepatitis (AIH) in children are in predominantly Caucasian cohorts. Paediatric AIH in African Americans (AA) is understudied, with a dearth of clinical predictors of outcome, often leading to serious complications and even mortality. The aim of the study was to define disease presentation, progression, response to therapy and outcomes in paediatric AIH in a well-defined, large, single centre, demographically diverse population. We conducted a review of patients with AIH who were followed at this tertiary liver transplant centre. Clinical and laboratory covariates were assessed with regard to disease presentation, progression and outcomes in AA vs Non-AA children. African Americans patients constituted 42% of this cohort. At 1-year follow-up, AA children were receiving significantly higher doses of steroids compared to non-AA. More AA presented with end-stage liver disease (ESLD) with high immunoglobulin G and GGT:platelet ratio. After adjusting for other risk factor variables like gender, age at presentation and ESLD, AA children were at 4.5 times higher risk for significant outcome liver transplant/death within the first 12months of presentation. Post-transplant, recurrent AIH was seen in 50% of AA vs 8% in non-AA. African American patients with AIH are more likely to present with ESLD and have an increased early risk for transplantation with high likelihood of disease recurrence post-transplantation. Studies are needed to delineate factors such as inherent biology, genetics and access to care. Early referral and tailored immunosuppressive regimens are required for AA patients with AIH.