Seronegative Autoimmune Hepatitis Research Articles

Frequency of seronegative cases in autoimmune hepatitis and their association with the systemic immune inflammation index

Aims: It is suggested that a deficiency in B cells plays a role in pathogenesis of seronegative autoimmune hepatitis (snAIH). The lack of B cells leads to notable changes in the variety of leukocyte types within the bloodstream. This study aimed to determine the frequency of snAIH in patients with autoimmune hepatitis, as well as to explore the relationship between snAIH and leukocyte-based inflammatory indices.
 Methods: In this retrospective study, 57 patients newly diagnosed with autoimmune hepatitis were included. According to clinical and pathological findings, patients were classified into seropositive autoimmune hepatitis (spAIH) and snAIH groups. The inflammation indices included the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammation index (SII).
 Results: The frequency of snAIH was 26.3%. The snAIH group exhibited higher NLR (3.0 vs. 1.5, p

Immunological Remission as a Basis for Dose Reduction of Immunosuppressors in Autoimmune Hepatitis: Results of Monocenter Surveillance Study

Aim of the study: evaluate the role of normalization of humoral immunity to address dose reduction or discontinuation of immunosuppressors in patients with autoimmune hepatitis (AIH).Patients and methods. The data of 47 patients with AIH who received immunosuppressive therapy from April 2001 to August 2023 were analyzed: 10 men (21 %), 37 women (79 %); the average age was 37 (17–66) years. The follow-up period was 10–180 months. Type 1 AIH was diagnosed in 37 patients, type 2 AIH — in 7 patients, seronegative AIH — in 3 patients. The diagnosis was established according to the IAIHG point system. To confirm the diagnosis, a liver biopsy was performed in 17 patients, a histological picture of AIH was detected in all of them. The most used combination was prednisolone and azathioprine — in 25 patients (53.2 %), as well as methylprednisolone and azathioprine — in 8 patients (17 %).Results. In some patients, when the immunosuppressive therapy decreased below the recommended dose, a relapse of the disease developed (Group 1), and in others, remission persisted (Group 2). The concentration of гамма-globulins in patients of Group 1 was 22.5 mg%, in Group 2 — 17.95 mg% (p = 0.00055). IgG level after achieving remission in Group 1 was 1709.7 mg/dL, in Group 2 — 1381.7 mg/dL (p = 0.000001). The terms of ALT normalization in Group 1 were 2.14 months, in Group 2 — 1.47 months (p = 0.037); AST normalization in Group 1 made 2.22 months, in Group 2 — 1.48 months (p = 0.026).Conclusions. Normalization of humoral immunity, as well as rapid normalization of ALT and AST can be considered as markers of maintaining AIH remission when immunosuppressor doses are reduced below standard doses, and in individual patients — the possibility of immunosuppressive therapy withdrawal. This will reduce the risk of adverse events and increase adherence to the therapy. We propose introducing the term “immunological remission” into the clinical lexicon, which, along with biochemical and histological remission, acts as a predictor of persistent remission of AIH.

Seronegative autoimmune hepatitis in childhood.

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children, although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis. Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated. The absence of autoantibody positivity, hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease. In general, seronegative autoimmune hepatitis often presents with acute hepatitis, and its treatment and prognosis similar to seropositive autoimmune hepatitis. The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood, and those of which current knowledge is vague.

Clinical Characteristics of Autoimmune Hepatitis in a Middle Eastern Population: A Tertiary Care Center Experience.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause, and its manifestations appear to vary by race and ethnicity. The literature on AIH in the Middle East, including Jordan, is scarce; therefore, this study aimed to determine the clinical characteristics of AIH in an understudied population. This retrospective chart review study was conducted on AIH patients who presented to Jordan University Hospital over a seven-year period (2014-2020). Retrieved data included sociodemographics, liver function tests, autoimmune serologic markers, viral hepatitis serology, findings on liver biopsies, treatment regimens, post-therapy outcomes and treatment-related complications. The total number of AIH patients included in the study was 30, divided as follows: type 1 AIH (n = 17, 56.7%), type 2 AIH (n = 2, 6.7%), seronegative AIH (n = 9, 30.0%), and two patients who had AIH-primary biliary cirrhosis overlap syndrome (6.7%). The mean age at diagnosis was 44 years (standard deviation: 17 years), with a female predominance (n = 25, 83.3%). Acute presentation was seen among 18 patients (60.0%). Mild to moderate fibrosis (F1 and F2 on METAVIR scoring system) without cirrhosis was observed among patients who underwent liver biopsies (10/19, 52.6%). The majority of patients (73.3%) were initially treated with prednisone, with azathioprine combination in 16.7% of the patients. At 6 months post initial treatment, twenty patients (66.7%) achieved biochemical remission, four patients had incomplete response, two patients failed to improve (one died during the induction of remission period due to AIH-related complications), and four patients were lost to follow-up. This study provided an updated overview of AIH in Jordan. The results showed typical female predominance, and interestingly high rates of acute presentation and seronegative disease. Future longitudinal studies are recommended to address the nature and long-term prognosis of AIH in Jordan.

S3329 An Unusual Presentation of Seronegative Autoimmune Hepatitis

Introduction: Seronegative autoimmune hepatitis presenting as acute liver failure is uncommon. Case Description/Methods: A 74-year-old woman with past medical history of GERD and moderate Alzheimer’s dementia was noted to have transaminitis on routine outpatient labs (ALT 272, AST 183), which did not resolve over four months. Her only medications were calcium and famotidine. She took no supplements or substances. She presented to the hospital after recent repeat chemistries showed worsening transaminitis. Upon admission, she appeared fatigued and jaundiced. Family noted she was unable to care for herself as usual. Initial labs revealed: total bilirubin 14.8 mg/dL, direct bilirubin 10.0 mg/dL, INR 1.7, AST / ALT 1428 and 1224 IU/L, Alk Phos 168 IU/L , Albumin 3.4 g/dL. Toxicology, immunologic serologies, including anti-smooth muscle antibodies (ASMA), and infectious testing were unremarkable. Immunoglobulin G was elevated (2700). CT of the abdomen and pelvis noted a small lesion in the pancreas and pancreatic and periportal adenopathy, and an enlarged gallbladder with sludge. She was admitted to medical oncology with a presumed diagnosis of pancreatic cancer. She could not complete MRI and underwent endoscopic ultrasound (EUS) on hospital day 4, which revealed normal pancreas and bile ducts. EUS-guided biopsy of the liver was done. On hospital day 6, she developed acute liver failure and methylprednisolone and N-acetylcysteine were started. Due to dementia, she was ineligible for liver transplant. On hospital day 8, pathology confirmed autoimmune hepatitis with bridging fibrosis. By hospital day 10, liver function improved (Figure 1 A-B); however, she developed fever and, despite broad-spectrum antibiotics, suffered from septic shock and expired on day 11. Discussion: Fulminant-onset autoimmune hepatitis (AIH) with hepatic encephalopathy is rare, occurring in < 6% of patients with AIH. The frequency of seronegative autoimmune hepatitis in acute and severe AIH is further estimated to be ≤7%. This case illustrates the challenge in diagnosis, particularly when confounding factors are present. Our patient suffered from dementia and aphasia, which masked developing hepatic encephalopathy, and pancreatic cancer was initially suspected as the cause of her painless jaundice, which delayed steroid treatment. A high index of suspicion for AIH is needed in patients with liver failure of uncertain etiology, as early treatment with steroids may improve the clinical outcome.Figure 1.: (A-B).

S3254 A CCase of Seronegative Autoimmune Hepatitis During Pregnancy

Introduction: Autoimmune hepatitis (AIH) is a rare disease that usually affects women at reproductive age and is associated with an increased risk of adverse maternal and fetal outcomes. Diagnosis of AIH during pregnancy, particularly in absence of autoantibodies, poses a challenge for clinicians. We present the case of a patient with new-onset seronegative AIH during pregnancy. Case Description/Methods: A 29-year-old Hispanic female, G2P101 at 19 weeks presents complaining of yellowing of her skin and eyes for 1 week, associated with nocturnal pruritus. Physical exam showed generalized jaundice and scleral icterus. Laboratory investigations showed significantly elevated AST (452 U/L), ALT (165 U/L), alkaline phosphatase (182 U/L), hyperbilirubinemia, elevated bile acids, and elevated INR. Hepatitis panel and autoimmune work up, were negative. Abdominal ultrasound was normal. MRCP showed nonspecific hepatic parenchyma heterogeneity on T2 signal suggestive of infiltrative process. A diagnosis of intrahepatic cholestasis of pregnancy (IHCP) with atypical presentation was made, and patient was started on ursodeoxycholic acid, which improved her symptoms. At day 15, she developed lower abdominal and vaginal bleeding, caused by placental abruption. The fetus was deemed non-viable and an emergent C-section was performed. Patient was eventually discharged with outpatient GI follow up. At follow up, recurrent rise in liver function tests were noted, and repeat autoimmune work up showed elevated IgG (3600). Liver biopsy was performed, which showed active chronic inflammation with lymphoplasmacytic infiltrates, moderate interface hepatitis with ballooning degeneration and emperipolesis, and moderate portal fibrosis with bridging fibrosis, suggestive of autoimmune hepatitis. Patient was subsequently started on steroid therapy, with appropriate response as symptoms progressively resolved and liver function tests normalized. Discussion: AIH is a rare condition that can manifest with antepartum and postpartum flares, having negative consequences to fetal and maternal outcomes, hence the importance of controlling AIH activity throughout pregnancy and in the postpartum period. Liver biopsy should be considered in cases of antibody negative AIH, however there is paucity of data regarding its safety in pregnancy. We present the rare case of an initially seronegative AIH flare during pregnancy, possibly attributed to the potential physiologic effects of pregnancy in the regulation of immune system mechanisms.

S3148 Seronegative Autoimmune Hepatitis: A Rare Manifestation of COVID-19

Introduction: Hepatic dysfunction is seen in 14-53% of patients with COVID-19, particularly in those with significant comorbidities. There have been reports of the development of autoimmune hepatitis (AIH) following COVID-19 vaccination and/or infection. AIH is usually associated with circulating autoantibodies but 10-20% of AIH patients are initially seronegative. We present the first reported episode to our knowledge of a case of seronegative AIH in the setting of concurrent COVID-19 infection. Case Description/Methods: A 39-year-old otherwise healthy female with a family history of mother with rheumatoid arthritis presented with 2 weeks of nausea, diarrhea, abdominal pain, and jaundice. She had significant transaminitis in the 1000 s and a conjugated hyperbilirubinemia. Despite previous vaccination and no respiratory symptoms, the patient tested positive for COVID-19. The patient denied taking hepatotoxic agents, and the workup was negative for acute viral hepatitis. The antinuclear, alpha-1-antitrypsin, ceruloplasmin, IgG, anti-smooth muscle, anti-mitochondrial, anti-neutrophil cytoplasmic, and anti-liver/kidney microsomal-1 antibodies were all unremarkable. Imaging was only remarkable for hepatic hemangiomas. Liver biopsy was ultimately performed showing active lymphoplasmacytic hepatitis with prominent regenerative changes and areas of confluent necrosis, consistent with autoimmune hepatitis. The patient’s symptoms and transaminitis improved following initiation of steroids (Figure 1). Discussion: We present a unique case of AIH as a manifestation of COVID-19 infection despite negative serology. Hepatic injury from COVID-19 is thought to be mediated by multitude of mechanisms including upregulation of ACE2 and DPP4 receptors, which are involved in RAS signaling pathways and regulation of the immune system. Further research is needed to better understand if there is a causal link between COVID-19 and hepatic autoimmune dysfunction and the underlying molecular mechanisms. Identifying autoimmune dysfunction following COVID-19 infection may allow us to recognize and treat these cases early on, leading to better hospitalization outcomes.Figure 1.: Liver biopsy showing marked interface activity and areas of confluent necrosis consistent with autoimmune hepatitis (AIH). A representative portal tract (PT) and central vein (CV) are illustrated.

Seronegative Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 people. It is characterized by the presence of auto-antibodies. However, an average of 10% of AIH cases have AIH symptoms and pathology but lack autoimmune serology. For such seronegative AIH (snAIH) cases, there is currently no established diagnostic algorithm for diagnosis. and improper or delayed diagnosis of snAIH can lead to no or inappropriate treatment that results in progression to fulminant hepatitis or cirrhosis. This review aims to review the current literature and to present an update of seronegative autoimmune hepatitis, including its pathophysiology, clinical presentation, methods of diagnosis, and treatment in order to increase awareness and emphasize the necessity for timely management.

Hepatitis-associated Aplastic Anemia.

Hepatitis-associated aplastic anemia (HAAA) accounts for 4% of autoimmune hepatitis in children. An episode of seronegative autoimmune hepatitis is followed a few days or months later by aplastic anemia or full aplasia. This autoimmune disease could be due to a regulation defect in the immune response to a viral trigger, in a genetically predisposed individual. Other causes of hepatitis or aplastic anemia have to be ruled out. Steroids and azathioprine usually control the liver damage but do not prevent the development of aplastic anemia. Aplastic anemia is treated with either hematopoietic stem cell transplantation in patients with a sibling donor or anti-thymocyte globulins and cyclosporine. We propose guidelines to explore and treat this rare disease. We emphasize on the necessary close collaboration between hepatologists and hematologists.

Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis.

Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray. During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD. pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.

S2642 A Case of Syphilis Masked as Seronegative Autoimmune Hepatitis

Introduction: Syphilis is a sexually transmitted infection that infects individuals at increasing rates every year. Syphilitic hepatitis (SH) is known to be a very rare complication of the infection, and can often be missed as a diagnosis.1 Here we present a unique case of SH disguised as what appears to be seronegative autoimmune hepatitis (AIH). Case Description/Methods: A 25 year old African-American female with history of tobacco and cannabis use presented with a 1 month history of fatigue, lymphadenopathy, that went away prior to presentation, and recent onset of pruritus, nausea and vomiting. She denied any risk factors for viral hepatitis or new medications. Physical exam was unremarkable except for sublingual and conjunctival icterus. Labs were significant for AST 1042 [12-39 U/L], ALT 877 [7-52 U/L], and ALP 189 [37-117 U/L]. Total bilirubin was 19.7 (direct 17.3). GGT and IgG were normal. Acute hepatitis panel, ANA, ASMA, AMA, and anti-LKM titers were negative. Wilson’s disease and alpha-1-antitrypsin deficiency were ruled out. Rapid plasma reagin (1:128) and Treponema antibody levels were positive. She had hepatomegaly with no ductal dilatation on ultrasound and MRCP. Liver biopsy was significant for peri-central and patchy sinusoidal congestion, canalicular cholestasis, and inflammatory portal tract infiltrates with bridging inflammation. Iron, PAS, VZV and spirochetes stains were negative. The patient was treated with penicillin for syphilis and started on prednisone for a suspicion of seronegative AIH. Steroid treatment was discontinued after a month due to concern for SH. Repeat liver enzymes were within normal limits 2 weeks after the prednisone was stopped and continued to remain normal. Discussion: SH is known to cause higher elevations in GGT and ALP, unlike our case, along with moderately impressive total bilirubin rise. There has been one report to date that identifies a case of concurrent SH and AIH, with a more impressive rise of AST and ALT.2 Our case is the first to present as SH with a questionable diagnosis of seronegative AIH.

S2841 Autoimmune Hepatitis: Possible Relation to the Pfizer-BioNTech COVID-19 Vaccine?

Introduction: Autoimmune Hepatitis (AIH) is a rare liver injury known to cause approximately 13% of acute liver failure cases in the United States. Drug-induced AIH has similar clinical, serological and histological features of AIH but is less likely to require long term immunosuppression or to relapse after discontinuation of immunosuppressants. It is mostly associated with nitrofurantoin, minocycline, hydralazine, and methyldopa, however other medications may be culprits. Herein, we present a patient with drug-induced AIH with possible relation to Pfizer-BioNTech COVID-19 vaccine. Case Description/Methods: A 38-year-old female with a history of Helicobacter pylori treated with amoxicillin and pantoprazole three months ago and recent COVID-19 vaccination presented with two weeks of right upper quadrant pain and diarrhea. Patient received second dose of vaccination two weeks prior to symptom onset. Five days post-symptom onset, she developed a pruritic rash with vomiting and yellowing of her skin. Physical examination was notable for normal mentation, scleral icterus, jaundice, and a maculopapular rash. Initial blood workup showed international normalized ratio 2.4, alkaline phosphatase 212 U/L, ALT 3769 U/L, AST 1572 U/L and total bilirubin of 23.8 mg/dL. Viral hepatitis serologies, chronic liver disease workup and autoimmune serologies were normal. Imaging demonstrated no intra- or extra-hepatic biliary ductal dilation. Liver biopsy showed portal inflammation with interface activity, diffuse lobular inflammation, and perivenulitis with abundant lymphocytes and plasma cells consistent with seronegative AIH or drug induced AIH. The patient developed altered mental status meeting the criteria of acute liver failure, she was started on corticosteroids as well as supportive care with resolution of encephalopathy and was discharged home on prednisone. Discussion: Several etiologies of drug-induced AIH are well-established, however cases secondary to COVID-19 vaccination have been minimally reported. Common adverse events for COVID-19 vaccination have been noted such as fever, chills, fatigue, headache, and muscle pain. Several rare side effects have occurred including immune thrombocytopenia and one other suspected case of Pfizer-BioNTech COVID-19 vaccination-induced AIH reported in the literature. In that case the patient developed symptoms within one week of the first dose. This case serves to report a potential association and not necessarily causation between the Pfizer-BioNTech COVID-19 vaccination and AIH.Figure 1.: Severely active lymphoplasmacytic hepatitis with frequent apoptotic hepatocytes with confluent necrosis.

Seronegative autoimmune hepatitis in children: a single-center experience

Seronegative autoimmune hepatitis (AIH) is a diagnostic challenge with unclear prognosis. This study describes the features and outcomes of seronegative AIH in children. Patients under 18 years of age, who had been diagnosed with AIH between April 2014 and April 2020, were retrospectively evaluated. Seronegative AIH was identified by the absence of the three conventional non-organ-specific autoantibodies (anti-nuclear antibody [ANA], anti-smooth muscle antibody [ASMA], and anti-liver kidney microsomal [anti-LKM] type 1 antibody), alongside the characteristic AIH liver histopathology and a positive response to immunosuppressive therapy in the absence of other liver diseases. The study included 54 patients with AIH. 15 (27.77%) were seronegative at the time of diagnosis. 13 of the 15 seronegative patients presented with acute hepatitis or acute liver failure (ALF). Mean follow-up duration was 27.48 months in seronegative patients. Two seronegative patients had lymphocytopenia on admission, and, although the liver disease improved after corticosteroid treatment, they developed aplastic anemia (AA). Other seronegative patients responded well to immunosuppressive therapy. Patients with seronegative AIH present frequently with acute hepatitis or ALF. AIH diagnosis can be confirmed by observing the effects of corticosteroid therapy in seronegative patients with characteristic AIH liver histopathological features. However, the presence of lymphocytopenia in seronegative patients is a sign of bone marrow failure.

Kupffer Cell Hyaline Globules in Children With Autoimmune Hepatitis

Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs). This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson's disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings. Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P<0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), (P<0.05). In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), (P<0.05), but not to histopathological findings or hepatic fibrosis and activity. KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

S2433 It's Still the Drug's Fault: A Case of Infliximab-Induced Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is an inflammatory disorder of the liver with a wide spectrum of disease presentation, from asymptomatic elevations in liver associated enzymes (LAEs) to acute liver failure. Recently, biologic agents have been thought to induce AIH in some patients. AIH is associated with elevated immunoglobulins and autoantibodies, although approximately twenty percent of patients with features of AIH lack circulating antibodies. We present a case of infliximab induced seronegative AIH responding to budesonide therapy with successful alteration of ulcerative colitis (UC) treatment regimen to vedolizumab. CASE DESCRIPTION/METHODS: A 31-year-old male with a history of UC on infliximab was noted to have a substantial increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to 181 and 75 U/L, respectively. Broad workup to include serum immunoglobulins, smooth muscle antibody, antimitochondrial antibody, liver kidney microsomal antibody, antinuclear antibody, and tissue transglutaminase antibody were unremarkable. Infliximab was discontinued and the patient was started on vedolizumab for management of his UC. Liver biopsy demonstrated interface hepatitis with lymphoplasmacytic infiltrate, consistent with early AIH vs. drug-induced liver injury (DILI). Three months after discontinuation of infliximab, his liver injury continued to worsen, with increase in ALT and AST to 440 and 168 as well as new elevation in alkaline phosphatase to 137. Given the evidence of ongoing hepatic injury and increasing concern for AIH, high dose oral budesonide was initiated and there was rapid improvement in his LAEs. Azathioprine was added and once his LAEs began to normalize, budesonide tapering was initiated. The patient’s LAEs normalized within two months of starting budesonide and his UC symptoms remain well controlled on vedolizumab. DISCUSSION: Definitive diagnosis of true drug-induced AIH is challenging, as there is considerable overlap with drug-induced AIH-like liver injury, although in this case, histologic findings combined with a brisk response to steroids provided adequate evidence. This case also demonstrated the utility of vedolizumab as a safe and effective therapeutic option for patients with severe IBD after IFX-induced AIH.Figure 1.: Liver biopsy demonstrating mild to moderate portal and parenchymal inflammatory activity with focal interface hepatitis.Figure 2.: Higher power view of the same biopsy featuring inflammatory cells, predominantly lymphocytes with scattered plasma cells (arrow), eosinophils, and macrophages.

Сlinical, immunological and morphological features in different types of autoimmune hepatitis

To studying the clinical, biochemical, immunological and morphological markers in patients with seronegative (SN) and seropositive (SP) AIH and the qualities of their response to the IST. This retrospective cohort study included 82 AIH patients over the course of the years 20142019. All patients were selected in accordance with the criteria of the simplified assessment system of the IAIHG. Clinical, laboratorial and morphological characteristics of the AIH were analyzed. Therapy response was evaluated by the level of the ALT and IgG in 612 months after the start of the IST. The study material underwent statistical analysis using methods of parametrical and nonparametrical analysis. Statistical analysis was performed in the Statistica 13.3 (developed by StatSoft Inc., USA). 67/82 (81.70%) of the patients studied were women, median age of 54 years old [38; 70]. Patients with the diagnosis of the possible AIH according to the IAIHG made 85.4% (70 people). Almost everyone 96% (79/82) had morphological features of the interface-hepatitis with the lymphocytic/plasmocytic infiltration; emperipolesis was discovered in 63% of patients (49/82), hepatocellular rosette in 23% (19/82). Patients with SN AIH comprised 36.5% (30/82), with SP 63.4% (52/82). Comparative analysis demonstrated that the clinical profile in patients with SN and SP AIH is the same, while the incidence of immuno-associated diseases is significantly higher in the group of seronegative AIH. The morphological profile in the two AIH groups is identical in both typical and atypical manifestations. The number of responders to IST was 63% (19/30) SN AIH vs 67% SP AIH (35/52), did not differ significantly (p=0.529).However, that the number of patients with liver cirrhosis in the SN AIH group was twice as big as the ones with SP: 37% vs 17% (p=0.089). A comparative analysis of clinical, laboratory, morphological and clinical manifestations in the SN and SP AIH groups did not detected statistically significant significant differences, which may indicate that SN and SP AIH are the faces of one disease. It is possible that AB cannot be identified within the known spectrum of antibodies, or antibodies have slow expression, or are suppressed by the immune system. In any case, suspicions of AIH, in the absence of antibodies, it is recommended that liver biopsy be performed for the timely diagnosis of AIH and IST. Сirrhosis was more often diagnosed in the group SN AIH, which may be due to a later diagnosis, and therefore to untimely IST. The found frequent association of SN AIH with other immune-associated diseases requires a carefully study of this problem. The variety of clinical manifestations of AIH requires further study, the identification of clinical phenotypes with certain feature. This can help in the future to timely identify potentially problematic patients and predict a response to IST.

Characteristics and Outcomes of Autoimmune Hepatitis from a Tertiary Paediatric Centre, Cape Town, South Africa

To describe the clinical characteristics, biochemical and histological features, outcomes and predictors of prognosis of children with autoimmune hepatitis (AIH) from a paediatric centre in South Africa. Thirty-nine children diagnosed with AIH at Red Cross War Memorial Children's Hospital between 2005 and 2015 were included. Relevant patient's data were retrieved from the hospital's medical records and database. Liver biopsy slides were reviewed. Ethical approval was obtained. Data were analysed using SPSS. Females were 29 (74%). Mean age at presentation was 7.27 ± 3.35 years and the mean follow-up was 4.5 ± 2.4 years. Jaundice was present in 97% of patients at presentation. An acute presentation was observed in 26 (67%) even though cirrhosis was detected in 22 (56%). Autoantibody screening was completed in 35 patients, 20 (57%) were AIH-1, 1 (3%) was AIH-2 and 14 (40%) were seronegative AIH. Of the 25 patients who underwent magnetic resonance cholangiography 17 (68%) had associated autoimmune sclerosing cholangitis. The remission rate was 79%. However, 11 children relapsed later. One child required liver transplantation and one demised. Seronegative and seropositive patients have comparable characteristics and outcomes. While a higher alanine transaminase (ALT) level at presentation is a significant predictor of remission, a lower ALT level and cirrhosis are significant risk factors for unfavourable outcome. Overall survival rate was 97%. AIH responds well to therapy with excellent survival. Hence, it should be considered in any child presenting with viral screen negative hepatitis and start therapy timeously to prevent disease progression.

2100 Linear IgA Bullous Dermatosis, Ulcerative Colitis, and Autoimmune Hepatitis: A Unique Triad

INTRODUCTION: Linear immunoglobulin IgA bullous dermatosis (LABD) is an autoimmune bullous disease characterized by formation of subepidermal blisters and linear deposition of IgA antibodies along the basement membrane zone. The link between LABD and ulcerative colitis (UC) has been previously documented and hypothesized to be due to immune exposure to autoantigens present in the colon, and subsequent targeting of these autoantigens in the skin. However, there have been no associated cases with autoimmune hepatitis. We report a unique triad of all three autoimmune conditions that presented concomitantly. CASE DESCRIPTION/METHODS: A 21-year-old male presented with vesicular and pustular rash on the skin of the hands, arms, abdomen, and legs (Figure 1). Histopathology revealed subepidermal blister with perivascular inflammation and linear C3 and IgA deposition along dermoepidermal junction consistent with LABD. The rash did not respond to topical corticosteroids. Liver enzymes were markedly elevated (AST 535 unit/L, ALT 436 unit/L, ALP 292 unit/L, bilirubin 0.3 mg/dL). He had iron deficiency anemia (Hgb 10.9 gm/dL, MCV 72.3 FL) with low ferritin. Autoimmune markers including antinuclear antibody, anti-smooth muscle, F-actin, anti-mitochondrial antibody, anti-liver kidney microsomal antibody, and anti-neutrophil cytoplasmic antibody were negative. Viral markers including Epstein Barr virus, cytomegalovirus, hepatitis A, B, C, E were negative, as were markers of metabolic liver disease. Celiac serologies were negative. Liver ultrasound was significant for hepatomegaly. Upper endoscopy with small bowel biopsies were normal. Colonoscopy revealed a patchy pancolitis consistent with ulcerative colitis, confirmed on biopsies. Prednisone 40 mg daily was administered, resulting in rapid resolution of the rash and elevated liver enzymes. Rapid improvement of transaminases with corticosteroids favors seronegative autoimmune hepatitis. He remains in clinical remission of his LABD, ulcerative colitis, and seronegative autoimmune hepatitis after gradual tapering off corticosteroids and on mesalamine alone. DISCUSSION: This is the first case, to our knowledge, where LABD, UC, and autoimmune hepatitis coexisted and had a successful therapeutic response to systemic corticosteroids. It is imperative to consider concomitant autoimmune diseases when a patient presents with such skin manifestations in order to guide early treatment.

SERONEGATIVE AUTOIMMUNE HEPATITIS – A CASE REPORT

Autoimmune hepatitis (AIH) is a complex liver disease. It is reported in children and adults of all age groups. An 11-year-old male&nbsp;child was admitted in our hospital for anorexia and yellowish discoloration of eyes, skin, and urine for 2 months. He had fever,&nbsp;itching was passing pale-colored stools. The child had hepatosplenomegaly and viral hepatitis markers as well as autoimmune&nbsp;markers were negative. Liver biopsy was suggestive of AIH. The child was started on prednisolone and showed drastic improvement&nbsp;clinically as well as biochemically. This was a case of seronegative AIH, which responded very well to corticosteroids. Hence, high&nbsp;index of suspicion is required to diagnose the case of seronegative AIH.

Autoimmune Hepatitis-Profile and Response to Treatment in Indian Patients

Introduction: Autoimmune hepatitis (AIH) can have varied manifestations, commonest presentation being as chronic liver disease. The data on the disease profile in India is scanty compared to the West. Aim: To study the clinical, biochemical, histological profile and response to treatment in patients with Auto-immune Hepatitis in Indian population. Methods: This is a Retrospective analysis of the twenty one (12 M = 57.1%; 9 F = 42.9%) patients diagnosed with AIH according to simplified criteria for diagnosis of AIH, in the last three years (2017-2019) in the department of medical gastroenterology, Vydehi Institute of Medical Sciences, Bangalore, Karnataka, India. Results: AIH accounted for 4.3% of all the liver diseases diagnosed during the last three years. Incidence of AIH was higher in males (12 M = 57.1%; 9 F = 42.9%; male to female ratio was 1.3:1), most common presenting symptom was jaundice, sixteen (57.1%), followed by ascites seven (33%) patients. Extra-hepatic manifestation was seen in fourteen (66.7%) patients. Eleven (52.3%) patients had cirrhosis with four (19%) patients having compensated cirrhosis, five (23.8%) patients having de-compensated cirrhosis, two (9.5%) patients presenting with features of acute on chronic liver failure, two (9.5%) patients presenting with acute hepatitis and seven (33.3%) patients presenting with features of chronic hepatitis. Nineteen (91%) patients had Type I AIH, one (4.5%) patient had Type II AIH and 1 patient had seronegative AIH. Oral budesonide was started in 11(52%) of patients, 8(38%) were started on oral prednisolone and 2(10%) patients were started on intravenous methyl prednisolone in view of severe auto-immune hepatitis. Azathioprine was added in 19 patients and dose was modified according to the clinical response and side effects. Four (21.05%) patients developed drug intolerance, out of which one patient had severe adverse effect in the form of acute pancreatitis secondary to Azathioprine. Mycophenolate Mofetil (MMF) was given with good response. Mortality was noted in two (9.52%) patients.