Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis

Background and aim Acute severe autoimmune hepatitis (AS-AIH) is a rare cause of acute liver failure (ALF), which is often neglected and delayed in treatment. The purpose of this study was to analyze the clinical characteristics and therapeutic effects of AS-AIH. Methods Retrospective analysis was performed. AIH was diagnosed according to the International Autoimmune Hepatitis Group (IAIHG) criteria revised in 1999. AS-AIH was defined as an acute presentation (onset of symptoms to presentation of ≤ 26 weeks) and INR of ≥ 1.5, and no histologic evidence of cirrhosis. Results Twelve patients were diagnosed as AS-AIH. At baseline, median immunoglobulin G was 28.35 g/L (range, 11.4–49.2). Ten (83.3%) patients were antinuclear antibodies and/or anti-smooth muscle antibodies positive. The prominent histologic characteristics were lobular necrosis/inflammation (91.7%) and plasma cell infiltration (100%). All patients received corticosteroid therapy. Death occurred in 2 (16.7%) patients within 30 days resulted from ALF. The average interval between the onset of symptoms and initiation of corticosteroid therapy in deceased patients was 65 days, compared with 19 days for survivors. Conclusions AS-AIH is an uncommon disease with poor outcomes. Patients with acute severe hepatitis of unknown cause should be minded the possibility of AS-AIH and corticosteroids should be considered as soon as possible.

The significance of cytoplasmic antinuclear antibody patterns in autoimmune liver disease

We aimed to determine the significance of cytoplasmic antinuclear antibody (ANA) patterns using computer-aided immunofluorescence microscopy in patients with autoimmune liver diseases (AILD). ANA staining pattern was identified by treating cultured human epithelial type 2 (HEp-2) cells with the sera of the patients. Medical records of patients with suspected AILD who had positive cytoplasmic ANA patterns between February 2017 and November 2019 were retrospectively reviewed for clinical, laboratory, and immunological data. Cytoplasmic ANA patterns of AILD and non-AILD groups were compared. Further subgroup analysis of patients with AILD who had reticular or speckled cytoplasmic ANA patterns was conducted. We found that among the 196 patients with positive cytoplasmic ANA patterns, 113 (57.6%) were diagnosed with AILD. The percentage of reticular cytoplasmic pattern was higher in the AILD group than that in the non-AILD group (64.0% vs. 21.9%, p < 0.001). Furthermore, patients with AILD who exhibited a reticular ANA pattern demonstrated a higher positive rate for anti-mitochondrial antibodies (66.7% vs. 2.6%, p < 0.001) than those who exhibited the speckled ANA pattern. Moreover, AILD patients with the reticular ANA pattern displayed a lower positive rate for anti-smooth muscle antibodies (0% vs. 45%, p < 0.001) and nuclear ANA pattern (73.2% vs. 97.5%, p = 0.003) than those with the speckled ANA pattern. Therefore, cytoplasmic ANA patterns could be used to guide AILD characterization in suspected AILD cases, especially as the reticular ANA pattern is strongly associated with AILD. Thus, it is important to check cytoplasmic ANA patterns for AILD evaluation, even when nuclear ANA patterns are negative.

Statin-induced necrotising autoimmune myopathy and autoimmune hepatitis presenting with dysphagia

Statin-induced necrotising autoimmune myopathy (SINAM) is a rare disease characterised by proximal muscle weakness and elevated creatine kinase levels that is usually in the thousands. Anti-3-hydroxy-3-methyl glutaryl co-enzyme A reductase (HMGCR) antibodies are associated with SINAM. Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that is usually of unknown aetiology but can also be associated with concurrent extrahepatic autoimmune disorders. We are reporting a case of biopsy proven AIH associated with SINAM in a patient presenting with oropharyngeal dysphagia. The patient had elevated anti-HMGCR antibodies and anti-smooth muscle antibodies. SINAM and AIH were confirmed by muscle biopsy and liver biopsy, respectively. The patient had complete resolution of his symptoms and complete normalisation of his liver function tests after 6 months of the treatment.

Autoimmune Hepatitis and Systemic Sclerosis: a Rare Association

A woman in her early 40s, with a history of excessive alcohol intake, presented with purpuric, ulcerative lesions on the lower limbs. On examination, hirsutism and generalized stiffening and thickening of the skin were noted. Laboratory investigations revealed hyperbilirubinemia, hypergammaglobulinemia and positive anti-smooth muscle antibodies. Histologic examination of the skin was compatible with scleroderma. Histologic examination of the liver was suggestive of autoimmune and alcoholic hepatitis.

Drug-Induced Autoimmune Hepatitis in a Patient Treated with Minocycline: A Rare Adverse Effect

Drug-induced autoimmune hepatitis is an acute and potentially severe adverse effect, which has been reported following the long-term use of minocycline. The condition’s typical biochemical findings include an elevated antinuclear antibody titer, hypergammaglobulinemia with elevated levels of serum immunoglobulin G, and, sometimes, positive anti-smooth muscle antibodies. Characteristically, transaminase levels are very elevated, while markers of cholestasis and bilirubin levels are mildly increased, and histological features are very similar to those observed in sporadic autoimmune hepatitis. Here, we describe an interesting case of a young female who developed drug-induced autoimmune hepatitis after taking minocycline for the treatment of acne vulgaris.

Clinical Spectrum, Evolution and Management of Autoimmune Cytopenia Associated with Angioimmunoblastic T-Cell Lymphoma: A Retrospective, Multicenter Study

Introduction Angioimmunoblastic T-cell lymphomas (AITL) are frequently associated with immune system activation such as hypergammaglobulinemia, positive direct antiglobulin test, anti-smooth muscle antibodies and clinical autoimmunity. Autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) have been reported, but to date, there is no specific study focusing on autoimmune cytopenia (AIC) in AITL. We sought to determine the clinical characteristics, evolution and response to treatment of AITL presenting with autoimmune cytopenia, including ITP, AIHA, auto-immune neutropenia (AIN) and pure red cell aplasia (PRCA) in a large cohort of patients from the multicentric T-cell lymphoma consortium (TENOMIC). Patients and methods We conducted a retrospective, multicenter study of patients diagnosed with AITL between 2001 and 2015 and presenting with at least one AIC (i.e. AHAI and/or ITP and/or AIN and/or PRCA, defined according to the international criteria). Patients were retrospectively selected from a cohort of 293 patients with AITL from a multicentric T-cell lymphoma consortium (TENOMIC). Medical charts were collected using a standardized from. Patients with AIC were matched for age and sex to control patients (5/1 ratio) diagnosed with AITL without AIC from the cohort. Results 28 patients were included, with a mean age of 63 years (range 39 - 83), and 50% were females. There were 41 AIC (AIHA, n=21 (including 5 cold agglutinin diseases), ITP, n=12, PRCA, n=7, AIN, n=1). Among them, 17 patients had only one AIC, 7 had both ITP and AIHA (Evan's syndrome) and 4 had PCRA associated with another AIC. One hundred and thirty six control patients were included (mean age 64 years (range 35 - 84), 49% female). Clinical characteristics of AITL at diagnosis showed more stage IV disease in AIC patients versus control patients (86% vs 66%, P= 0.0442), as well as more bone marrow (71% vs 34%, P=0.0005) and splenic (61% vs 19%, P< 0.0001) involvement. Immune activation markers such as anti-smooth muscle antibodies (71% vs 0.9%, P< 0.0001), gammaglobulins titers (27 g/l vs 18 g/l, P= 0.0019), and EBV replication (89% vs 61%, P= 0.0232), were significantly increased in AIC patients versus control patients. AIC were mainly concomitant with AITL diagnosis (83%). Only 2 patients had AIC before AITL diagnosis (2 and 8 months), and 4 patients developed AIC during the disease course (median 14 months (8 - 114)). Mean hemoglobin level at AIHA and PRCA diagnosis were 7.1 g/dl and 5.3 g/dl, and red blood cell transfusions were required in 52% and 86% of patients, respectively. Mean platelet count was 35 x 109/L at ITP diagnosis, and 42% of patients had bleeding manifestations, although no life threatening bleeding manifestation was observed. First line treatments of AIC included corticosteroids (88%), chemotherapy for AITL (71%), intravenous immunoglobulin (27%), or other treatments (12%), and were effective in all patients except for two patients who presented with refractory ITP. Ten patients had a relapse of AIC (5 ITP, 4 AIHA, 3 PRCA) with a median time to relapse of 4 months (1 - 18)). All AIC relapses were associated with AITL relapse. Only 3 patients had active AIC while AITL was considered in remission, including one patient who developed ITP after autologous stem cell transplantation. Sixty-four percent versus 66% of patients experienced AITL relapse in AIC and control group, respectively (P=1). Median overall survival (OS) and median progression free survival (PFS) were 77 and 12 months in the AIC group, and 41 and 12 months in the control group, respectively (P=ns). Conclusion In summary, AITL associated with AIC had more advanced disease with increased immune activation compared to our control group, although it did not impact OS and PFS. AIC were mainly inaugural and responded well to chemotherapy. Interestingly, all AIC relapses were associated with AITL relapse. These findings are of interest for management of AITL patients presenting with AIC. Disclosures Casasnovas: Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Leblond:Roche: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Michel:Amgen: Honoraria; Novartis: Honoraria. Dupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees.