International Autoimmune Hepatitis Group Score Research Articles

Outcomes of patients with acute severe autoimmune hepatitis: Predictors of non-response to corticosteroids and need for liver transplantation.

Acute severe autoimmune hepatitis (AS-AIH) is an evolving concept and the outcomes and optimal treatment have been less studied. In this study, we aimed to investigate the outcomes of patients with AS-AIH and predictors of non-response to corticosteroid therapy and need for liver transplantation. In a retrospective cohort, we included patients with AS-AIH admitted to our liver center. We defined AS-AIH based on the international autoimmune hepatitis group score as acute presentation of AIH with an international normalized ratio (INR)≥1.5 and without liver cirrhosis and hepatic encephalopathy. All patients received high dose corticosteroid therapy. Treatment response was defined as liver transplant free survival at 4months after presentation. Factors associated with response to corticosteroids and survival of patients were studied. In total, 61 patients with AS-AIH were included. Forty-seven patients responded to corticosteroid therapy. In the multivariate regression model, baseline INR (odds ratio [OR]: 0.184; 95% confidence interval [CI]: 0.048-0.699; p=0.013) and delayed versus early initiation of corticosteroid (after vs. before 5days of presentation) (OR: 0.189; 95% CI: 0.039-0.919; p=0.039) were independent predictors of clinical non-response to corticosteroid therapy. In the multivariable Cox regression model, baseline INR level (OR: 2.542; 95% CI: 1.188-5.440; p=0.016) and delayed initiation of corticosteroids (OR: 3.578; 95% CI: 1.084-11.812; p=0.036) were independent predictors of liver transplant free survival at 6months after diagnosis. Delayed initiation of corticosteroid therapy might be predictive of clinical non-response to medical therapy and need for liver transplantation in patients with AS-AIH.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74–100] vs. 61% [10–100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8–23] vs. 16.5 [15–17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Applicability of International Autoimmune Hepatitis Group (IAIHG) Scoring System for Autoimmune Hepatitis in Pediatrics

Many hepatologic pathologies mimic autoimmune hepatitis (AIH). Researchers developed the International Autoimmune Hepatitis Group (IAIHG) scoring system to compensate for the lack of specific diagnostic tests for AIH. The scoring system was not designed with pediatric patients in mind, so there are limits to its pediatric use. Additionally, there is limited information on the value of a liver biopsy in conjunction with its use. In this retrospective study, we evaluated the effect of liver biopsy scores on the IAIHG scoring system in patients that were 0-18 years old with suspected AIH. We also analyzed demographic data and laboratory values associated with a final AIH diagnosis. We found that interface hepatitis and predominant plasma cells found during the biopsy were significantly associated with a final AIH diagnosis. We also found that abnormal laboratory values were associated with an AIH diagnosis. We found that IAIHG scores calculated post-liver biopsy showed a greater area under the receiver operating characteristic curve (AUROC) of 0.95, which was compared to 0.88 for the scores calculated before a liver biopsy. Including biopsy metrics lowered the optimized cutoff score and test specificity. Incorporating liver histopathological features improved the performance of the IAIHG scoring system. Further studies to identify other potential elements in liver histology may improve the performance metrics of the IAIHG test in the pediatric population.

HLA and Non-HLA gene polymorphisms in autoimmune hepatitis patients of North Indian adults.

Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases.

Value and risk of percutaneous liver biopsy in patients with cirrhosis and clinical suspicion of autoimmune hepatitis

ObjectiveThe decision regarding whether to perform a liver biopsy in patients with cirrhosis and clinically suspected autoimmune hepatitis (AIH) remains a challenge. This study aimed to assess the utility and...

Hepatitis aguda por virus E con características de autoinmunidad. Reporte de un caso

We analyze the case of a 49-year-old male patient who presented with clinical signs of acute hepatitis with an initial suspicion of autoimmune etiology. Laboratory findings demonstrated positive antinuclear antibody, anti-smooth muscle antibody and high serum gamma globulin. Histology of the liver biopsy revealed changes compatible with autoimmune hepatitis, which associated with an International Autoimmune Hepatitis Group score of 7, determined the initiation of treatment with Meprednisolone and Azathioprine. During the follow-up, we received positive serological results of immunoglobulin M against hepatitis E virus with detectable viremia by reverse transcription polymerase chain reaction technique, changing the diagnosis to acute hepatitis secondary to hepatitis E virus. Immunosuppression was suspended and the patient continued with clinical and biochemical improvement. In Argentina, hepatitis E virus testing is not routinely performed, however, to avoid misdiagnosis, this etiology should be ruled out in patients with acute hepatitis before labeling it as autoimmune hepatitis. This could reduce unnecessary treatment that could endanger our patients.

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.

Immunoglobulin G4-associated autoimmune hepatitis with peripheral blood eosinophilia: a case report

BackgroundImmunoglobulin G4 (IgG4) associated autoimmune hepatitis (AIH) has been recognized as a type of autoimmune disease that responds to corticosteroid. The diagnosis is based on elevation of the serum IgG4 level, abundance of IgG4 enhanced plasma cell infiltration in the portal region of the liver, and satisfaction of the criteria for “definite AIH” under the revised International Autoimmune Hepatitis Group (IAIHG) scoring system. However, the clinical course of the disease is unclear.Case presentationA 65-year-old man with jaundice and peripheral blood eosinophilia.His IAIHG and simplified score was compatible with definite AIH and his IgG4 level was elevated. Magnetic resonance imaging did not reveal abnormalities in the hepatobiliary system or pancreas. A liver biopsy revealed interface hepatitis with IgG4 positive plasma cell infiltration in the portal region, without evidence of bile duct injury. He responded to 4-week period of induction prednisolone therapy and had no recurring symptoms under maintenance therapy of 5 mg prednisolone during the 3-year follow up.ConclusionsThis was a rare case that demonstrated an association between IgG4 associated AIH and the presence of peripheral blood eosinophilia.

S2672 Influenza a Virus as a Trigger for Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic liver disease caused by an immune-mediated destruction of the hepatocytes. Studies have shed the light on the important role of infections in triggering AIH as many viral infections and vaccines have been associated with it. We present an atypical case of AIH possibly triggered by Influenza A virus. To our knowledge, this is the first case report showing autoimmune hepatitis induced by influenza A virus. CASE DESCRIPTION/METHODS: A 52-year-old previously healthy female presented with new-onset jaundice after Influenza A viral infection. Initial laboratory investigations revealed an aspartate aminotransferase level of 1211 U/liter, an alanine aminotransferase level of 1506 U/liter, an alkaline phosphatase level of 305 U/liter, a total bilirubin level of 5.1, a direct bilirubin level of 3.4 and an international normalized ratio of 1. Serologic testing for hepatitis A, B, and C, HSV, CMV, and EBV were negative. Influenza A PCR was detected on nasopharyngeal sampling. Covid-19 test was negative. ASMA was positive with a titer of 1:80. ANA was positive with a titer of 1:80. Anti-mitochondrial antibody was negative. IgG, Alpha 1 antitrypsin, ceruloplasmin levels were within normal limits. No acetaminophen was detected in the blood. A CT abdomen showed normal biliary tree with no biliary strictures and no cirrhotic changes of the liver. Her liver biopsy showed acute hepatitis with moderate acute hepatocellular injury and hepatocellular necrosis with mixed portal infiltrates which include both plasma cells and eosinophils. Based on the revised International Autoimmune Hepatitis Group Scoring System for the Diagnosis of Autoimmune Hepatitis, her pretreatment score was 13 points. She was started on prednisone and had significant biochemical improvement. Her steroids were tapered and steroid sparing therapy with azathioprine was initiated. DISCUSSION: Influenza virus and vaccine have been proposed to cause autoimmune disease in the literature such as type 1 diabetes, narcolepsy, recurrent ITP, and multiple sclerosis. There has been an association as well between influenza vaccine and AIH. In a study published by Saski et al, they describe two cases of middle-aged women who developed autoimmune hepatitis after receiving influenza vaccine. We suggest that in our patient, the influenza A virus infection triggered autoimmune hepatitis. Autoimmune hepatitis should be considered in patients with persistently elevated liver enzymes following infections such as influenza.Figure 1.: Liver biopsy cores show findings suggestive of acute hepatitis. Dense portal inflammatory infiltrates are present, comprised of macrophages, lymphocytes, neutrophils, eosinophils and plasma cells. Piecemeal acute hepatocellular necrosis is also noted at the limiting plate (H&E, original magnification 10x).Figure 2.: Prominent bile stasis with sinusoidal Kupffer cell hyperplasia (H&E, original magnification 10x).

Acute onset of autoimmune hepatitis in children and adolescents

BackgroundAutoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). MethodsForty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). ResultsAcute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. ConclusionRapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

Usefulness of chemokine C-C receptor 7- /programmed cell death-1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis.

A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis. Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry. The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores. The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Association Between Black Race and Presentation and Liver-Related Outcomes of Patients With Autoimmune Hepatitis

Small studies have found that black patients with autoimmune hepatitis (AIH) present with more aggressive disease. We aimed to characterize the presentation and outcome in black and white patients with AIH. We performed a retrospective study, collecting information from databases of patients with AIH attending the Institute of Liver studies at King's College Hospital, London (1971-October 2015, the Royal Free Hospital, London (1982 through December 2016) and the multicenter Dutch Autoimmune Hepatitis Study Group cohort (2006-August 2016). We identified 88 black patients with AIH and we compared their clinical characteristics and outcomes to 897 white patients with AIH. Black patients presented at a younger age (median 38 years vs 45 years) (P = .007), had higher IgG levels (mean 31.0 mg/dL vs 27.5 mg/dL) (P = .04), but there were no significant differences between groups in auto-antibody profiles, International AIH Group scores, or sex distribution of disease. A higher proportion of black patients had systemic lupus erythematosus (10%) than white patients (2%) (P ≤ .001). There was no significant difference in proportions of patients with a response to standard therapy (86% for black patients vs 91% for white patients; P=.20) or in rate of relapse (57% vs 50%; P = .3). Despite this, black patients had an increased risk ofliver transplantation and liver-related death (hazard ratio 2.4, 95% confidence interval, 1.4-4.0; P < .001). Overall mortality was similar between the two groups. In a comparison of black and white patients with AIH in Europe, we found that black patients present at a younger age, have higher levels of IgG levels, and a greater proportion have SLE. We also found black patients to have a greater risk of liver transplantation and liver-related mortality, indicating more aggressive disease.

Memantine-Induced DILI

Presentations of drug-induced liver injury (DILI) are highly variable. While biochemical evidence of cholestasis is common, the extent of aminotransferase elevations and patterns of liver injury vary. Asymptomatic patients may never be diagnosed. Memantine is an increasingly used therapy in Alzheimer's dementia, reported here to cause cholestatic liver injury in an elderly male. An 86-year-old man with a history of coronary artery disease, atrial fibrillation, prostate cancer, hypothyroidism, gout and Alzheimer's disease presented with incidental elevated aminotransferases up to ten times the upper limit over 2 months. He did not have fever, chills, abdominal pain, nausea, vomiting, jaundice, pruritus or mental status changes. Longstanding medications included donepezil, lisinopril, carvedilol, apixaban, atorvastatin, levothyroxine, allopurinol and omeprazole. Memantine was initiated 2 months prior to presentation. He denied history of tobacco or alcohol use. Physical exam was unremarkable including negative Murphy's sign. The serum aspartate aminotransferase (AST) was 438 U/L, alanine aminotransferase (ALT) was 439 U/L, total and direct bilirubin were 0.9 mg/dL and 0.5 mg/dL respectively, and alkaline phosphatase (ALP) was 169 U/L. Memantine was immediately discontinued. Evaluations for viral, autoimmune, and metabolic etiologies for liver injury were unremarkable, except positive ANA (1:160 dilution), normal IgG (1376 mg/dL). Right upper quadrant ultrasound revealed only cholelithiasis. Three months after memantine withdrawal, the levels of AST (168 U/L) and ALT (140 U/L) and ALP (58 U/L) decreased significantly. Six months after memantine withdrawal, all liver associated enzymes returned to normal. The diagnosis of DILI requires a strong index of suspicion, meticulous history taking and exclusion of other etiologies. This patient was asymptomatic, presenting with a hepatocellular pattern of liver injury of unclear etiology. Although autoimmune hepatitis (AIH) remained on the differential, the decision was made to forego liver biopsy given his comorbidities. The patient's Revised Original Scoring System of the International Autoimmune Hepatitis Group score was 4 (without including liver histology or response to therapy), making AIH unlikely. Memantine induced liver injury has been rarely reported in the literature. Consideration of this diagnosis should prompt immediate discontinuation of this medication while excluding other etiologies.

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype.

ObjectiveAutoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.MethodsHLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.ResultsThe predisposing association of DRB1*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62–5.43), DRB1*04:05 (P = 1.89×10−21, Pc = 5.86×10−20, OR 3.41, 95% CI 2.65–4.38), and DQB1*04:01 (P = 4.66×10−18, Pc = 6.99×10−17, OR 3.89, 95% CI 2.84–5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32–0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10−9, OR 3.52, 95% CI 2.34–5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45–424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10−6, OR 10.64, 95% CI 3.19–35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.ConclusionsThe important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQα-β heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes.

Concurrent extrahepatic autoimmunity in autoimmune hepatitis: implications for diagnosis, clinical course and long-term outcomes.

Concurrent extrahepatic autoimmune disease (CEHAID) associated with autoimmune hepatitis (AIH) have been incorporated into the diagnostic criteria stipulated by the International Autoimmune Hepatitis Group (IAIHG). Large comprehensive cohort data on the extrahepatic autoimmunity in AIH remain scanty. To systematically assess features and clinical impact of CEHAID on AIH. Clinical records of 562 patients with AIH from two tertiary centres in the UK were retrospectively reviewed. Prevalence of CEHAID in patients with AIH was 42%. Autoimmune thyroid disease was the commonest CEHAID associated with AIH (101/562, 18%). Autoimmune skin diseases were more prevalent in AIH-2 than AIH-1 (21.9% vs 7%, P=.009). Personal history of CEHAID was more commonly found in AIH patients with than without first-degree family history of CEHAID [48/86 (55.8%) vs 169/446 (37.9%), P=.002]. AIH patients with CEHAID were more often women (85.2% vs 76.1%, P=.008), had higher post-treatment IAIHG score (22 vs 20, P<.001), less reactivity to smooth muscle antibodies (49.8% vs 65%, P<.001), more likely to have mild fibrosis at diagnosis (20.9% vs 6.5%, P<.001) and less often had ascites (6.3% vs 13.6%, P=.008) and coagulopathy (1.18 vs 1.27, P=.013) at presentation. Presence of CEHAID, however, did not significantly affect disease progression, prognosis and survival in AIH. Our study confirms the strong association of CEHAID with AIH. Association between personal and familial extrahepatic autoimmunity especially among first-degree relatives was evident. Presence of CEHAID may influence clinical phenotype of AIH at presentation, but without notable impact on the long-term clinical outcomes.

An Unusual Presentation of Auto-immune Hepatitis

Purpose: A 26-year-old Caucasian male with no significant history presented with new onset jaundice for 3 weeks. Two weeks prior to admission, he developed daily nausea and vomiting. One week prior to admission, he developed night sweats, anorexia, constipation, and generalized pruritis. In addition, he began to experience a post-prandial right upper quadrant abdominal pain with no radiation, and a 16-pound weight loss, which prompted presentation to the hospital. His medications included occasional acetaminophen/ diphenydramine PRN for insomnia. Family history was significant for cholelithiasis in his mother and lung cancer in multiple family members. The patient's social history included consumption of approximately 5 oz of spirits per week, a remote tobacco history, experimentation with intravenous heroin, as well as multiple professionally-obtained tattoos. Pertinent physical exam findings included stable vital signs, icterus, a soft and non-tender abdomen with liver edge palpated two cm below the costal margin, and percussed splenomegaly. No lymphadenopathy or asterixis were appreciated. Laboratory findings were significant for AST of 825 U/L, ALT of 596 U/L, total bilirubin of 26 mg/dL with a direct bilirubin of 20 mg/DL, and alkaline phosphatase of 118 U/L. His INR was 1.46 with a PT of 17.4, albumin of 3.1 g/dl, and total protein of 6.8 g/dl. Abdominal ultrasound revealed a nodular liver surface, hepatosplenomegaly, marked gallbladder thickening, and enlarged peripancreatic lymph nodes consistent with acute hepatitis. Hepatitis A, B, and C serologies were negative. His ferritin was 423 ng/mL with a percent saturation of 38. Anti-mitochondrial antibody, anti-LKM and alpha 1 anti-trypsin titers were within normal limits. His total IgG was 2,657 (reference range 650-1,600.) Anti smooth muscle antibody titers were measured at 36 U (reference range <20.) Given his clinical picture, along with an international autoimmune hepatitis group scoring of 10, treatment was started for autoimmune hepatitis with corticosteroids. His clinical picture improved soon thereafter. Discussion: This case represents an unusual presentation of autoimmune hepatitis. Autoimmune hepatitis is typically diagnosed in the fourth or fifth decade of life, and more commonly affects females. It typically presents with markedly elevated ASTs, compared to bilirubin and alkaline phosphatase, as was seen in this case. This presentation demonstrates, however, that this condition can present at any age, and can also affect males. Autoimmune hepatitis should, therefore, remain high on the differential in young males with hepatitis.

Anti‐nucleosome autoantibodies as markers for autoimmune hepatitis and their correlation with disease activity

To assess the prevalence of autoantibodies against nucleosomes (anti-nucleosome Ab) in patients with autoimmune hepatitis (AIH), examine the correlation between anti-nucleosome Ab and disease activity, and evaluate the effectiveness of anti-nucleosome Ab in predicting relapse. We analyzed serum anti-nucleosome Ab levels in 38 patients with AIH by enzyme-linked immunosorbent assay, and assessed their correlation with clinical characteristics. Anti-nucleosome Ab levels were significantly higher in AIH, but not in patients with chronic hepatitis B (n = 20) or chronic hepatitis C (n = 20), compared to healthy controls (n = 15). The positive prevalence of anti-nucleosome Ab was 71.1% in AIH. Anti-nucleosome Ab levels were significantly lower during remission compared to that during flares within the same patients with AIH. Total bilirubin levels were significantly higher in patients with anti-nucleosome Ab levels of 53.7 U/mL or more compared to those with less than 53.7 U/mL at disease onset. Analysis of the reduction in anti-nucleosome Ab by immunosuppressive therapy in 16 AIH patients revealed that age at disease onset was significantly lower and IgG levels and relapse rates were significantly higher in patients with a reduction rate of less than 35% compared to those with a reduction rate 35% or more. The International Autoimmune Hepatitis Group score and γ-globulin levels were also higher in patients with reduction rates of less than 35% (borderline significance). Anti-nucleosome Ab in AIH patients may be useful markers not only for disease diagnosis, but also for activity assessment and relapse prediction.

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis (AIH) with or without centrilobular necrosis (CN). Our study comprised 41 patients with biopsy-proven acute presentation (acute exacerbation phase 36, acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009. Elevated serum alanine aminotransferase (ALT) (> 5x upper limit of normal) identified acute presentation of the disease. We compared clinicopathological features of these AIH patients with or without CN. The data used for analysis included patient background (age, sex, type of disease, presence of complications with other autoimmune diseases, human leukocyte antigen, and International Autoimmune Hepatitis Group score), clinical parameters at presentation (ALT, alkaline phosphatase, IgG, anti-nuclear antibodies, and anti-smooth muscle antibodies), histology and therapy. CN was found in 13 (31.7%) patients with acute presentation (acute exacerbation phase 10, acute hepatitis phase 3) of AIH. Serum IgG levels of patients with CN were significantly lower than those of patients without CN (mean: 2307 mg/dL vs 3126 mg/dL, P < 0.05), while antinuclear antibody-negative rates were significantly higher (30.7% vs 3.5%, P < 0.05). However, other clinical features were similar between the two groups. The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN (F0-2: 84.6% vs 35.7%, F3-4: 15.4% vs 64.3%, P < 0.05). Other histological features were similar between the two groups. Although there was no significant difference between groups when evaluated using the revised original score (12 vs 14), the simplified AIH score of patients with CN was significantly lower (6 vs 7, P < 0.05). Frequency of DR4 was similar between patients with and without CN. CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH, although AIH with CN often shows clinical features of the genuine acute form.

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan

Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH. We assessed clinical characteristics and therapeutic processes in 67 patients diagnosed with AIH. Twenty patients (29.9%) suffered from relapses during tapering of corticosteroid therapy. The remaining 47 patients sustained their remission. At the onset of disease, risk factors associated with relapse were: age of 50 years or older; total bilirubin of 1.5 mg/dL or more; aspartate aminotransferase levels of 250 IU/L or more; alanine aminotransferase levels of 250 IU/L or more; prothrombin activity of 80% or more; γ-globulin levels of 3.4 g/dL or more; and International Autoimmune Hepatitis Group (IAIHG) score of 17 or more in univariate analysis. Grading of histological interface hepatitis is not significantly associated with relapse. Multivariate analysis revealed that IAIHG scores of 17 or more were significantly associated with relapse (odds ratio = 6.57, 95% confidence interval = 1.19-36.33). Seven patients who relapsed were treated with AZP and prednisolone (PSL), and all sustained remission (100%). Of the remaining 13 relapse patients who received only PSL, eight (61.5%) suffered additional relapses. Our results demonstrate the risk factors associated with relapse of AIH. We also show that early administration of AZP after the first relapse may help to prevent additional relapses.