Probable Autoimmune Hepatitis Research Articles

Acute Presentation of Autoimmune Hepatitis: Case Report

This case report describes the clinical presentation, diagnostic evaluation, and treatment outcome of a 38-year-old female patient presenting with yellow discoloration of eyes and urine, along with associated symptoms such as nausea, poor appetite, abdominal pain, extreme fatigue, and mild joint pain. The patient had a history of amenorrhea for three months and no family history of autoimmune disease or drug-induced liver injury. Upon examination, the patient exhibited deep icterus and mild tender hepatomegaly, but without signs of acute liver failure. Laboratory investigations revealed elevated liver function markers and positive autoimmune antibodies, including antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA), while ruling out other possible etiologies such as viral hepatitis, Wilson's disease, and hemochromatosis. Imaging studies showed features of acute hepatitis, and liver biopsy could not be performed due to prolonged prothrombin time. The patient was diagnosed with probable autoimmune hepatitis (AIH) and initiated on a treatment regimen consisting of prednisolone 40 mg daily, which was gradually tapered over time and added azathioprine 100 mg daily. The patient demonstrated significant improvement in liver function tests with this treatment approach. However, she discontinued treatment on her own accord but continued to have normal liver function during subsequent follow-up visits. During the consultation, the patient and healthcare provider engaged in a comprehensive discussion concerning the significance of sustained treatment over an extended period and the inherent possibility of relapse.

Diagnosis and presenting features of autoimmune hepatitis at a central referral hospital in South Africa.

Introduction Autoimmune hepatitis (AIH) has scarcely been reported on in patients of black African descent. Similarly, few studies have focused on the relationship between AIH and Human-Immunodeficiency Virus (HIV) infection. Aim We aim to describe the presenting features of AIH from a single referral centre in a Sub-Sahara African setting. We also compare the presenting features of HIV-infected and HIV-uninfected patients. Methods This study was a retrospective chart review. Patients were included if they fulfilled criteria for the International AIH Group simplified score for probable or definite AIH, were 18 years or older at inclusion, and attended the adult Gastroenterology clinic at Inkosi Albert Luthuli Central Hospital (IALCH) for the period 1/1/2015 to 31/12/2020 on at least 2 occasions. Results Forty cases were included, of which 33 (82.5%) were female and 33 (82.5%) were black African. Median age at diagnosis was 26 years. A diagnosis of a coexistent autoimmune disease was made in 22.5% of patients, with Systemic Lupus Erythematosus (SLE) being the most common (12.5%). Sixteen patients were HIV-infected, all of whom were female (p =0.03), with a significantly older age of disease onset as compared to their HIV-uninfected counterparts (median age 38 vs 17.5 years, p <0.001). Conclusion AIH is a disease most commonly affecting young females. Female sex and older age of onset is associated with AIH in HIV-infected individuals.

Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity.

The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system ["1999 IAIHG"], 2. simplified scoring system ["2008 IAIHG"], 3. modified histologic criteria ["2017 UCSF"], and 4. a new histologic criteria proposed by the International AIH Pathology Group ["2022 IAHPG"]) in AIH patients. Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared. Out of the 68 patients, 56 (82.4%) patients met the "probable" or "definite" AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and "probable" or "definite" AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of "probable" or "definite" AIH (62/68; 91.2%). The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥"Probable AIH") from 82.4% to 91.2%.

Autoimmune Hepatitis: Evaluation of Clinical Presentation, Diagnosis and Response to Treatment in Iraqi Patients

Introduction: Autoimmune hepatitis (AIH) is a chronic heterogeneous inflammatory disease of the liver activated by unknown triggers. The details of its pathogenesis remain unclear. Sufficient data on AIH in terms of epidemiology as well as disease phenotype amongst the Iraqi population is not available. Objectives: To evaluate and document the experience of Iraqi AIH patients with respect to clinical presentation, diagnosis, treatment and response to treatment in accordance with the IAIHG guidelines. Method: A prospective study was conducted on patients who attended the Gastroenterology Hepatology Teaching Hospital in Baghdad, Iraq. After examination, many biochemical and pathological parameters were analysed. Liver biopsy, abdominal ultrasound, and upper endoscopy were done. Results: Among the 70 respondents, jaundice, fatigue, arthralgia, and itching were the major symptoms recorded at presentation. Immunologic findings were positive for ANA (31 patients) and ASMA (25 patients) while hypergammaglobulinemia was recorded in 97% of all patients. Pre-treatment scoring revealed 56 definite and 14 probable AIH patients while post-treatment scoring yielded 13 definite and 23 probable AIH patients. Response to treatment showed 6 patients as non-responders, 34 patients (49%) exhibited complete response while 30 patients (43%) had a partial response. Conclusions: Iraqi patients with AIH presented late at the advanced stage of the disease with a majority having hypergammaglobulinemia which forms a solid base for disease suspicion. It is recommended that a complementary study with a larger sample size, longer follow-up duration and inclusion of cases of idiopathic hepatitis is needed.

Characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody

Objective: To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis. Methods: The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies. Indirect immunofluorescence assay was used to detect anti-nuclear antibody (ANA), anti-mitochondrial antibody, anti-Smooth muscle antibody (ASMA), anti-liver and kidney microsomal antibody (anti-LKM) and other autoantibodies. Normally distributed measurement data between the two groups were compared by independent-sample t-test, and the multiple groups comparison were compared by one-way analysis of variance. Non-normally distributed measurement data were compared by non-parametric rank sum test. Results: 38 anti-LC1 positive patients were detected in 23832 autoantibody tests. The age of initial diagnosis ranged from 11.0 to 84.0 (50.6 ± 16.0) years. There were 8 males (21.1%) and 30 females (78.9%). A total of 31 cases (81.6%) were positive for anti-LC1 and ANA, and the dominant karyotype was speckled pattern, accounting for 54.8%. Five cases (13.2%) were positive for ASMA, and no simultaneous positive with anti-LKM or anti-SLA. Among the 38 anti-LC1 positive patients, 9 were diagnosed with autoimmune hepatitis (AIH), 6 with possible AIH, 6 with primary biliary cholangitis (PBC), 8 with hepatitis B, 2 with hepatitis C, 1 with alcoholic liver disease, 2 with non-alcoholic fatty liver disease, 1 with drug-induced liver injury, 1 with hepatolenticular degeneration, and 2 with tumor. Confirmed and probable AIH cases accounted for 39.5% (15/38) of anti-LC1 positive cases. Among anti-LC1 positive patients, 47.4% (18/38) had entered the stage of liver cirrhosis. AIH group globulin level was higher than HBV group (P = 0.006) and other disease groups (P = 0.001). AIH group IgG level was higher than PBC group (P = 0.027), HBV group (P = 0.009) and other disease groups (P = 0.004). the of the PBC group IgM level was higher than AIH group (P = 0.003), HBV group (P = 0.003) and other disease groups (P = 0.006). Conclusion: Anti-LC1 is not only detected in AIH, but also observed in patients with primary biliary cholangitis, hepatitis B and C, alcoholic and non-alcoholic liver disease, drug-induced liver injury, hereditary metabolic liver disease and tumor. In addition, it is mainly female gender dominance and nearly half of ANA-positive young, middle-aged and elderly patients develop liver cirrhosis. For the diagnosis of type 2 autoimmune hepatitis, whether anti-LC1 is a specific antibody needs further research, but if AIH is highly suspected, this antibody can be used as a substitute.

Graves Disease (Thyroid Storm) with Polyautoimmune Disorders (Autoimmune Hemolytic Anemia and Probable Autoimmune Hepatitis)

Graves' disease is caused by IgG antibodies that bind to the Thyroid Stimulating Hormone (TSH) receptor on the surfaceof the thyroid gland. These bonds drive the growth of stimulated thyroid follicular cells causing the glands to enlarge andincrease the production of thyroid hormones. Previous studies mention the association of HLA-B8 and HLA-DR3 withGraves' disease and the Cytotoxic T-lymphocyte-associated-4 (CTLA-4) gene on chromosome 2q33 as a result of reducingT-cell regulation, resulting in autoimmune disease. Autoimmune thyroid disease is often found together with otherautoimmune disorders (polyautoimmune). A 51-year-old male complained of dyspnea, yellowing of the body, and a lumpon the neck. One year ago, he was diagnosed with hyperthyroidism. Graves' disease was suspected due to a score of 22 forthe Wayne index, FT4 96.9 pmol/L, TSHs &lt;0.01 μIU/mL, TRAb 10.8 IU/L, thyroid uptake test for toxic diffuse struma. Inaddition, the patient had atrial fibrillation and a thyroid storm with a Bruch Wartofsky index score of 65. Laboratoryexamination found normocytic normochromic anemia, thrombocytopenia, reticulocytosis, direct coomb test and autocontrol results positive one, SGOT 87 U/L, SGPT 59 U/L, alkali phosphatase 166 U/L, total bilirubin 38.13 mg/dL, directbilirubin 16.59 mg/dL, indirect bilirubin 21.54, LDH 318 U/L, establishing the diagnosis of Autoimmune Hemolytic Anemia(AIHA). Autoimmune hepatitis score: 15, so a diagnosis of probable autoimmune hepatitis was made.

S2668 Sorafenib-Induced Autoimmune Hepatitis: A Case Report,

Introduction: Drug-induced liver injury (DILI) with autoimmune hepatitis-like features (DIAIH) is a specific phenotype of DILI with clinical features indistinguishable from de-novo autoimmune hepatitis (AIH). We describe a case of DIAIH due to Sorafenib. Case Description/Methods: A 61-year-old man and teetotaller presented with 1-week history of jaundice and malaise. He was on Atorvastatin 40mg daily for 4 years for hyperlipidaemia. Sorafenib was recently initiated six weeks ago for recurrent sarcoma of the left thigh. Clinical examination was unremarkable apart from scleral icterus. Liver function test (LFT) showed severe hepatocellular (HC) injury (bilirubin 4.56 mg/dL, alkaline phosphatase 190 U/L, alanine transaminase 1004 U/L, aspartate transaminase 790 U/L peak INR 1.53). Viral hepatitis screening, AIH specific antibodies and abdominal imaging were unremarkable. Serum IgG was raised (18.6 g/L). Liver biopsy was supportive of DILI and AIH histological features were also noted (Fig.1a-f). Simplified AIH score was 6. Roussel Uclaf Causality Assessment Model (RUCAM) score was 9 for Sorafenib and 6 for Atorvastatin. Diagnosis of Sorafenib-induced AIH was made. His LFT improved spontaneously with normalization of LFT eight weeks after stopping Sorafenib. Discussion: Sorafenib often causes idiosyncratic DILI with mild elevation of transaminases. However, it rarely causes severe DILI and has no known association with DIAIH, unlike Atorvastatin and immune checkpoint inhibitors (e.g Nivolumab and Atezolizumab). To our knowledge, this is the first case report of DIAIH due to Sorafenib. In patients with severe DILI or DILI with probable AIH based on AIH scoring, liver biopsy should be considered for evaluation. However, differentiating DIAIH from de-novo AIH is often challenging as both present with HC injury, may have positive AIH specific antibodies, raised serum IgG and share similar histological findings. The key distinguishing features are the history of drug exposure within a time frame and no requirement for long term immunosuppressant. DIAIH may resolve spontaneously after stopping culprit drug. Corticosteroids should be initiated in cases without improvement upon drug cessation. In DIAIH requiring corticosteroids, relapse is rare after stopping corticosteroids and long-term immunosuppression is rarely needed. In conclusion, DIAIH should be considered in patients who present with severe HC DILI. Differentiating DIAIH from AIH is crucial as the former rarely requires long term immunosuppression.Figure 1.: Liver biopsy specimen [a] H&E 200X: A portal tract, zone 1, showing moderate chronic inflammation with interface damage and rare bile droplets. [b] H&E 200X: Lobulitis characterized by aggregates of plasma cells, swollen hepatocytes and rosetting within liver parenchyma zone 2. [c] H&E 200X: Centrilobular region zone 3 showing hepatocyte drop-out, aggregates of plasma cells, rosetting and bile pigment. Reticulin [d, 40X] and Sirius Red [e, 40X] special stains show collapse with mild early young fibrosis without elastic fibers demonstrated on Orcein [f, 40X], consistent with subacute injury. Overall, the appearances are supportive of subacute DILI in association with features suggestive of AIH (i.e. interface damage, plasma cell aggregates and resetting).

Usefulness of Clinical and Laboratory Criteria for Diagnosing Autoimmune Liver Disease among Patients with Systemic Lupus Erythematosus: An Observational Study.

Abnormal liver function tests are frequently observed during follow-up of patients with systemic lupus erythematosus (SLE) but data on co-existence with autoimmune liver diseases (AILD) are scarce. This retrospective study aimed to describe the prevalence of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) among well-characterized subjects with SLE. We also evaluated whether the presence of autoantibodies to complement protein 1q (C1q) and/or ribosomal P protein (anti-ribP) are, directly or inversely, associated with AIH, as proposed in some reports. The number of screened patients was 287 (86% females), and all cases were included in a regional Swedish cohort. Each subject of the study population met the 1982 American College of Rheumatology classification criteria and/or the Fries’ diagnostic principle. By applying the simplified diagnostic AIH criteria combined with persistent transaminasemia, 40 (13.9%) cases reached at least “probable AIH”. However, merely 8 of these had been diagnosed with AIH (overall AIH prevalence 2.8%). Neither anti-C1q nor anti-ribP associated significantly with AIH. By applying the recent PBC guidelines, 6 (2.1%) cases were found, but only 3 of them had actually been diagnosed with PBC and one additional subject was not identified by the guidelines (overall PBC prevalence 1.4%). Compared to prevalence data from the general Swedish population, both AIH and PBC were highly overrepresented in our study population. The sensitivity of the diagnostic AIH criteria was impeccable but the specificity was less impressive, mainly due to positive ANA and hypergammaglobulinemia. Based on our findings, among subjects with SLE, the AIH criteria are less useful and liver biopsy combined with detection of other AILD-associated autoantibodies should be performed.

Validating a novel algorithm to identify patients with autoimmune hepatitis in an administrative database.

Population-level studies on the treatment practices and comparative effectiveness of therapies in autoimmune hepatitis (AIH) are lacking due to the absence of validated methods to identify patients with AIH in large databases, such as administrative claims or electronic health records. This study ascertained the performance of International Classification of Diseases (ICD) codes for AIH, and developed and validated a novel algorithm that reliably identifies patients with AIH in health administrative data and claims. This was a cross-sectional study of patients with ≥1 inpatient or ≥2 outpatient ICD codes for AIH between 2008 and 2019 at a single health system. In a random sample of 250 patients, definite or probable AIH was determined using the Simplified AIH score, Revised AIH score or expert adjudication. The positive predictive value (PPV) was obtained. Variations of this base algorithm were evaluated using additional criteria to increase its performance. Of the 250 patients, 143 (57.2%) patients had sufficient records available for review. The PPV of the base algorithm was 77.6% (95% CI: 69.9-84.2%). Exclusion of patients with ≥1 ICD code for primary biliary cholangitis or primary sclerosing cholangitis yielded a PPV of 89.7% (95% CI: 82.8-94.6%). Further exclusion of patients with recent immune checkpoint inhibitor therapy increased the PPV to 92.9% (95% CI: 86.5-96.9%). The use of ICD codes for AIH alone are insufficient to reliably identify patients with AIH in health administrative data and claims. Our proposed algorithm that includes additional diagnostic and medication-related coding criteria demonstrates excellent performance.

Prognosis of probable autoimmune hepatitis patients: a single-center study in Japan.

Autoimmune hepatitis (AIH) is an idiopathic inflammatory liver disease with genetic susceptibility and unknown environmental triggers. The gold standard for diagnosis, International Autoimmune Hepatitis Group (IAIHG) scoring system, classifies AIH as definite or probable. Conventional research on probable AIH has focused on the Caucasian population and there is little data pertaining to the Asian population. This study aimed to assess and compare the prognosis of Japanese patients with probable and definite AIH. In the current study, patients with probable and definite AIH diagnosed based on IAIHG scores between 1987 and 2018 were enrolled. As a result, 72 patients with definite AIH and 49 patients with probable AIH were evaluated. Univariate analysis revealed age, fibrosis stage 4, and the fibrosis-4 index were prognostic factors for overall survival. Multivariate analysis indicated that age and liver cirrhosis significantly affected the overall survival. When the cut off albumin-bilirubin score was set appropriately, cirrhosis was differentially diagnosed using albumin-bilirubin score with 100% sensitivity and 70.5% specificity. Classification of probable or definite disease did not alter overall survival with statistical significance. In conclusion, our findings suggest that probable AIH should be managed as definite AIH is managed in Japanese population. The albumin-bilirubin score helps identify liver cirrhosis and is a prognostic biomarker for overall survival.

3164 The Unhelpful Biopsy: Autoimmune Hepatitis in a Young Woman With Kikuchi Fujimoto Disease

INTRODUCTION: Kikuchi Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, immune-mediated condition usually seen in young Asian females. There are only two reported cases of autoimmune hepatitis (AIH) in a patient with KFD. Systemic lupus erythematosus (SLE) has a strong association with KFD and introduces diagnostic uncertainty in differentiating AIH and SLE-hepatitis. We present a challenging case of acute hepatitis in a woman with KFD, positive rheumatologic signal and bland liver biopsy. CASE DESCRIPTION/METHODS: A 33-year-old female presented with non-bloody emesis. Her history was significant for KFD and exam was notable for jaundice and a diffuse maculopapular rash involving palms and soles. She had normal vitals and was previously known to have a positive ANA (1:640) and anti-dsDNA. Labs were notable for ALT 843, AST 646, alkaline phosphatase 173, total bilirubin 10.6 with direct bilirubin 8.6. Given her elevation in transaminases, additional serologies and imaging were performed demonstrating a mildly elevated transferrin, no sign of viral hepatitis and a right upper quadrant ultrasound and MRCP with nonspecific hepatitis. She was admitted for expedited workup and further laboratory evaluation was notable for a mildly elevated IgG and negative for abnormalities in ASMA as well as p-ANCA, Anti-LKM1, and ALC-1. Serologies were overall consistent with a probable diagnosis of AIH and a liver biopsy was planned to secure a definitive diagnosis. However this demonstrated non-specific necrosis and cholestasis, inconsistent with AIH. After a prompt response to steroids and a negative antiribosomal P antibody, probable AIH was suggested and she recovered uneventfully. DISCUSSION: Diagnosis of AIH can be made with clinical presentation, laboratory evaluation and biopsy. Our patient presented with a probable diagnosis of AIH (score of 14 by AASLD guidelines), yet a negative ASMA, bland biopsy and a positive SLE signal (though not meeting formal diagnostic criteria) were significant confounders. Treatment response to steroids suggested AIH by AASLD scoring, yet SLE hepatitis is also steroid responsive. Negative anti-ribosomal P antibody may suggest decreased likelihood of SLE hepatitis, and this distinction is critical given the more benign course of SLE-hepatitis. This is a rare case of KFD associated, probable AIH, yet there remains much overlap with SLE-hepatitis. We recommend additional research to determine clinical or laboratory criteria to differentiate these diagnoses.

Role of age in presentation, response to therapy and outcome of autoimmune hepatitis

BackgroundFew studies with diverging results and a small sample size have compared autoimmune hepatitis (AIH) in the elderly to younger patients.AimTo unbiasedly investigate the role of age in behaviour and treatment outcome of AIH.MethodsAll patients with probable or definite AIH type 1 in four tertiary academic centres were included in this retrospective—and since 2006 prospective—cohort study. Influence of age on presentation, remission and outcome of AIH were investigated.Results359 patients were included. Presence of cirrhosis at AIH diagnosis around 30% was independent of age. ALAT was higher at age 30–60 years on AIH diagnosis, and above age 60 there were less acute onset, less jaundice and more concurrent autoimmune disease. Remission was reached in 80.2%, incomplete remission in 18.7%, only 1.1% (all aged 50–65) was treatment-refractory. Age was not an independent predictor of remission, while cirrhosis was. Above age 45 there was more diabetes, above age 60 more loss of remission. Rate of progression to cirrhosis was 10% in the 10 years after diagnosis and unrelated to age at AIH diagnosis. With onset below age 30, there was more development of decompensated cirrhosis over time. With higher age at AIH diagnosis there was a lower survival free of liver-related death or liver transplantation.ConclusionsAIH presents at all ages. Age influences features at diagnosis, but not response to treatment, while survival without liver-related death or liver transplantation decreases with higher age at diagnosis.

Suitability of the simplified autoimmune hepatitis score for the diagnosis of autoimmune hepatitis in a German cohort.

Several years ago the International Autoimmune Hepatitis Group simplified the previous revised original scoring system for diagnosis of autoimmune hepatitis (AIH) into a scoring system based on only four instead of 13 parameters. We aimed to evaluate the suitability of the simplified AIH score for diagnosis of AIH in a German cohort with chronic liver diseases. In this retrospective single-center study, we compared the accuracy of both AIH scores in 70 patients with AIH and 211 patients with chronic liver diseases (PBC (n = 52), PSC (n = 27), NASH (n = 67), DILI (n = 15), CHB/C (n = 50)). Sensitivity, specificity and predictability of each scoring system were calculated. Using the simplified AIH score, the sensitivity and specificity of detecting a probable AIH (scores ≥ 6) were 96% and 97% with a positive and negative predictive value of 92% and 99%, respectively. For diagnosis of definite AIH (scores ≥ 7), the sensitivity and specificity were 43% and 100% with a positive and negative predictive value of 97% and 84%, respectively. The concordance with the revised original criteria was 63%. The specificity for excluding AIH was excellent in both scoring system. The simplified diagnostic criteria allow a reliable diagnosis of AIH in a German cohort.

Transient Exacerbation After Infections in Patients With Autoimmune Hepatitis

Aims Although the pathogenesis of autoimmune hepatitis (AIH) is unknown, many recent studies have demonstrated that infection can act as a trigger for the onset of AIH. The existence of a pathogenetic link between AIH and infections has not been confirmed. If AIH is triggered by infections, it is possible that infections may transitorily worsen liver function in patients with AIH. We investigated the association between the effects of infections and the exacerbation of liver dysfunction in patients with AIH. Methods We determined the changes in liver function before and after infections in 20 patients with definite AIH, 33 with probable AIH, 24 with primary biliary cholangitis (PBC), 30 with chronic hepatitis C (CH(C)), and 23 control subjects. Results During the study period, 19 of the 20 patients (95%) with AIH experienced one or more signs of liver dysfunction after infection. Seventy-three (59%) out of the 124 total occurrences of infectionsin 19 patients met the criteria for transient exacerbation of liver dysfunction. The incidence of liver dysfunction and the serum IgG levels after infection were significantly higher in the patients with definite AIH than in the patients with probable AIH, PBC and CH(C), and in the control subjects. Serum IgG level was a significant independent predictor of liver dysfunction. Conclusion The present study results suggested that infection was one cause of exacerbation of liver dysfunction in patients with AIH, and that serum IgG level was a significant independent predictor of exacerbation of liver dysfunction after infection.

Comparative Analysis of the Clinical Outcomes of Liver Transplantation for Probable and Definite Auto-immune Hepatitis by International Diagnostic Scoring Criteria

BackgroundLiver transplantation (LT) is an effective treatment for patients with end-stage liver disease caused by auto-immune hepatitis (AIH). However, diagnosis of AIH can be challenging for patients with end-stage liver disease at the time of transplantation. We classified patients into “probable” or “definite” AIH groups, using the diagnostic criteria of the International Autoimmune Hepatitis Group, and compared the clinical outcomes of AIH after LT in these 2 groups. MethodsWe performed a retrospective study of 18 patients who were diagnosed with AIH and underwent LT from March 2003 to March 2015 at a single institute. Of the 18 patients, 8 were diagnosed with definite AIH and 10 were diagnosed with probable AIH, according to the international scoring criteria. We evaluated the patient characteristics, recurrence rate, graft loss, and survival rates after LT. ResultsThe mean follow-up duration was 59.3 months. Age, sex, medical condition at transplantation, warm ischemic time, cold ischemic time, and Model for End-Stage Liver Disease score did not differ significantly between the 2 groups. No patient died after LT in either group, but 1 patient in the definite AIH group had graft failure. In Kaplan-Meier analysis, the 5-year recurrence rates of the definite and probable groups were 14.3% and 0%, respectively (P = .992). ConclusionsThe recurrence of definite AIH appeared to be higher than that of probable AIH. However, careful immunosuppressive therapy allowed the long-term survival of both definite and probable AIH patients after LT.

Autoimmune hepatitis: review of histologic features included in the simplified criteria proposed by the international autoimmune hepatitis group and proposal for new histologic criteria

Simplified criteria for diagnosis of autoimmune hepatitis are based on autoantibodies, serum immunoglobulin G, histologic features, and negative viral serology. A score of 6 points is necessary for the designation of probable autoimmune hepatitis and 7 points or more for definite autoimmune hepatitis. The presence of three histologic features is required for categorizing a case as typical (2 points): interface hepatitis with portal lymphocytic/lymphoplasmacytic cells extending into lobule, emperipolesis, and rosettes. In the absence of all three features, a chronic hepatitis picture is considered compatible with autoimmune hepatitis (1 point). This study examines the validity of these histologic features for the diagnosis of autoimmune hepatitis. Clinical data and liver biopsies were reviewed for 88 autoimmune hepatitis, 20 primary biliary cholangitis, and 13 non-autoimmune acute hepatitis cases. Interface/lobular activity, number of plasma cells, copper/CK7 stains, and presence/absence of biliary features were assessed in autoimmune hepatitis and primary biliary cholangitis cases. The simplified criteria score was calculated. Modified histologic criteria were formulated on the basis of interface/lobular activity, number of plasma cells, and presence/absence of biliary features. Using the proposed histologic features, histologic score of 2 increased from 8 to 77%, while total simplified score of >6 increased from 69 to 86%. There was no increase in total simplified score for primary biliary cholangitis or non-autoimmune acute hepatitis. Rosettes and emperipolesis are difficult to interpret, and lack sensitivity and sensitivity for autoimmune hepatitis diagnosis. The current histologic criteria used in the current simplified score lead to underscoring of autoimmune hepatitis cases. The modified histologic criteria based on the inflammatory activity, extent of plasma cells, and results of copper/CK7 staining increased the histologic score in autoimmune hepatitis and led to a probable/definite diagnosis of autoimmune hepatitis in 17% of cases that would have otherwise been classified as non- autoimmune hepatitis by simplified score.

Overlap Syndrome of Autoimmune Hepatitis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis in a Patient with Systemic Lupus Erythematosus: A Case Report of Complex Autoimmune Liver Disease

Introduction: Overlap syndrome is a spectrum of clinical manifestations between Autoimmune hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Overlap syndromes between AIH-PBC and AIH-PSC are well recognized. Overlap between PBC-PSC has only been reported in a few patients. To our knowledge, it is extremely rare for PBC, PSC and probable AIH overlap syndrome to occur in the same patient.Figure 1Figure 2Case report: The patient is a 48-year old Hispanic male with liver cirrhosis and SLE. His cirrhosis was complicated by esophageal varices, thrombocytopenia, coagulopathy, hypoalbuminemia, and chronic portal vein thrombosis. His biochemical profile revealed elevated ALT (2X upper limit of normal (ULN)) and AST (4X ULN), persistently elevated alkaline phosphatase (3X ULN) and elevated bilirubin (2X ULN). Investigations for etiology of cirrhosis included a detailed social history were done. Viral hepatitis serology, iron studies, celiac panel, ceruloplasmin and alpha-1 antitrypsin level were unremarkable. Anti-nuclear antibody (ANA) was positive with a titer of 1:320, anti-smooth muscle antibody (ASMA) was positive with a serum level of 20 (Normally < 20) and P-ANCA was positive. Anti-Soluble liver antigen (anti-SLA) and anti-liver kidney microsomal 1 antigen (Anti-LKM1) were negative. Gamma globulin level was elevated at 2501 mg/dL (normal range 694-1617). Anti-mitochondrial antibody (AMA) was positive with a level of 71.9 units (Normally < 20). The more specific antibody for PBC, AMA-M2, was also positive as well. He also had a positive anti-dsDNA. The patient met criteria for AIH-PBC overlap syndrome based on Paris Criteria. He was on prednisone for autoimmune thrombocytopenia and was started on oral Ursodeoxycholic acid. We also performed an ERCP with cholangiography which showed segmental irregularities of intrahepatic bile ducts with beaded appearance suggestive of sclerosing cholangitis. Based on patient's liver enzymes profile, autoimmune markers, and ERCP findings; he was diagnosed with AIH-PBC-PSC overlap syndrome. We wanted to obtain a liver biopsy, however it could not be done as patient deceased due to septic shock. Conclusion: We are presenting a case with complex clinical spectrum of autoimmune liver diseases which include AIH, PBC, and PSC. To our knowledge, this is only the second reported case of all these diseases overlapping in the same patient; and the first reported case in a patient with SLE.

Long-term follow-up of children and adolescents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis

Sclerosing cholangitis (SC) is a chronic cholestatic hepatobiliary disease with uncertain long-term prognosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC. We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangiographic findings. Patients fulfilling diagnostic criteria for probable or definite autoimmune hepatitis at the time of diagnosis were defined as having autoimmune sclerosing cholangitis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hypertension, advanced liver disease and death associated with the primary disease. Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were significantly younger at the time of diagnosis (12.3 vs 15.4 years, P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L, P=0.003). The mentioned complications occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications. In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.

PTU-083 Long-Term Follow-Up of Patients with Autoimmune Hepatitis after Withdrawal of Immunosuppressant Therapy

Introduction If immunosuppressant therapy (IST) is withdrawn in patients with autoimmune hepatitis (AIH) when remission is achieved, 50–70% will have a disease relapse within 12 months. Thus, many patients receive long-term maintenance IST. However, IST has potential side effects, including an increased cancer risk. Recent studies suggest a lower AIH relapse rate if IST is withdrawn at a later stage in the disease. Data are lacking in regard to long-term outcome following IST withdrawal. Methods Retrospective audit of long-term outcome of AIH following withdrawal of IST. A total of 282 patients with definite or probable AIH by International AIH Group criteria, had presented to our Unit between 1971–2015 and had achieved normalisation of serum ALT within 12 months of starting IST (prednisolone plus azathioprine, or mycophenolate if azathioprine intolerant). From these, we found 25 patients in whom all IST was subsequently discontinued. We assessed outcome in these patients, in comparison to those who continued IST. Follow-up was until last serum ALT for calculating relapse rate and until death or last known to be alive for calculating survival rates. Results The 25 patients (21 female, age at diagnosis 50 (8–68) years) had been on IST before withdrawal for 3.9 (0.1–22.4) years. Five had cirrhosis at presentation. All patients had normal serum ALT and globulins at time of withdrawal except one patient with acute pancreatitis. Reasons for IS withdrawal were: cancer (6), infections (3), side effects (4), frailty (6) patient choice (6), doubt about diagnosis (subsequently resolved) (1). Relapses occurred in 7 patients (28%) after 1.6 (0.5–9.6) years. Relapse rates were 15%, 20% and 28% after 2, 5 and 10 years respectively. All patients achieved re-normalisation of serum ALT within 3 months of re-starting therapy (prednisolone 10–40 mg/day) plus (in 5 patients) azathioprine or mycophenolate, subsequently continued as maintenance therapy. Over follow up (from IST withdrawal) of 4.2 (1.2–25.1 years), no patient developed liver decompensation, variceal bleeding or hepatocellular carcinoma. Six patients died after 4 (3.3–15.9) years; none due to liver disease or following AIH relapse. Patients stopping IST (n = 25) had, compared to those who continued IST (n = 257) higher 10- and 20 year survival (99±4% and 79±9% respectively vs 78±3% and 48±4% p = 0.021). Conclusion In patients with AIH who achieve remission a trial of withdrawal of IS therapy is associated with (a) a lower disease relapse rate than previously reported, (b) no liver adverse events and (c) no reduction in long-term survival compared with patients who continue on long-term IS therapy. Disclosure of Interest None Declared

Probable autoimmune hepatitis and systemic sclerosis complicated by reversible posterior leukoencephalopathy syndrome: An unusual association

Summary Systemic sclerosis is a multisystem autoimmune rheumatic disorder characterized by fibrosis in the skin and internal organs but rarely with hepatic or brain involvement. Reversible posterior leukoencephalopathy syndrome is characterized by a unique pattern of brain vasogenic edema in the setting of neurotoxicity predominantly in the parietal and occipital regions. We report a case of systemic sclerosis associated with probable autoimmune hepatitis that progressed rapidly to reversible posterior leukoencephalopathy syndrome with loss of vision, seizures, and coagulopathy. Brain computed tomography showed faint low density in the bilateral occipital lobes and posterior parietal lobes with edematous change. Fortunately, the patient's clinical condition considerably improved 2 days following the initiation of 100 mg intravenous hydrocortisone infusion.