Presentation Of Autoimmune Hepatitis Research Articles

S3467 An Unusual Presentation of Autoimmune Hepatitis - Primary Biliary Cholangitis Overlap Syndrome in a 56 Year Old Male

S3467 An Unusual Presentation of Autoimmune Hepatitis - Primary Biliary Cholangitis Overlap Syndrome in a 56 Year Old Male

Case Report: Acute presentation of autoimmune hepatitis in a male patient

Introduction: Autoimmune hepatitis (AIH) is one of the major immune mediated chronic liver diseases. It typically affects young and middle-aged females. Acute liver failure (ALF) is an unusual initial form of presentation of AIH and is particularly rare in male patients. Consequently, the clinical characteristics and optimal management of this entity remain poorly defined. Patients with AIH sometimes present features of the spectrum of primary biliary cholangitis (PBC), simultaneously or consecutively, suggesting the diagnosis of overlap syndrome (OS) PBC- AIH. Data concerning PBC-AIH has been scarcely published and mainly comprises small retrospective studies. Case presentation: Herein, we report the case of a 40-year-old man with no history of any chronic liver disease, who presented with ALF. After carrying out extensive etiological screening, we suspected him of having ALF due to auto-immune liver disease namely AIH. The positivity of anti-mitochondrial antibody (AMA) which is a significant serologic marker of PBC, suggested a diagnosis of OS PBC- AIH. Since urgent liver transplantation could not be performed in our country (Tunisia), the only available therapeutic option was the administration of corticosteroids. During the two years of follow up and treatment with ursodeoxycholic acid, azathioprine and a low dose of prednisolone, our patient is still asymptomatic with normal hepatic function tests. Conclusion: ALF due to AIH in a male patient is a very rare condition. The diagnosis should be considered in all patients with acute hepatitis of undetermined etiology. Corticosteroids were an effective and lifesaving therapeutic option. The association of AIH and PBC features could suggest an OS.

Autoimmiune Hepatitis in Children: Two Case Report

Autoimmune hepatitis (AIH) is the disease of immune mediated inflammation of liver. Presentation of AIH in children is variable, ranging from acute hepatitis to cirrhosis of liver and also as only asymptomatic raised ALT. AIH can present at any age and female are more affected. Here we are presenting two cases. Case 1 presented with jaundice and H/O epistaxis, having cutaneous echymosis, hepato-splenomegaly and ascites. Case 2 was a diagnosed case of Systemic Lupus Erythematosus (SLE) presented with only persistent raised of serum ALT. Both were diagnosed as autoimmune hepatitis on the basis of positive auto antibodies, histopathology of liver tissues and exclusion of all other causes of acute and chronic hepatitis.
 Bangladesh Med J. 2020 Jan; 49 (1): 45-50

Autoimmune Hepatitis in Children

Autoimmune hepatitis is characterized by inflammation in liver histology, circulating autoantibodies, and increased levels of immunglobulin G, in the absence of a known etiology. There are different clinical types described in children. Because of the presentation of autoimmune hepatitis with different clinical findings, establishment of diagnosis may be difficult. In the last two decades, a a 6-fold increase in the incidence of autoimmune hepatitis has been reported thanks to update of diagnostic approaches and the increase in technical possibilities. Autoimmune hepatitis should be considered in the differential diagnosis of any liver disease not caused by viral and metabolic factors. Its association with other clinical conditions such as autoimmune thyroiditis, vitiligo, collagen and connective tissue disorders is already known. Although autoimmune hepatitis is a treatable disorder, it may cause cirrhosis and fulminant hepatitis that need liver transplantation without treatment. In this review, we aimed to present the clinical findings, diagnosis and treatment methods of autoimmune hepatittis in children in the light of current literature.

Early Predictors of Short-Term Prognosis in Acute and Acute Severe Autoimmune Hepatitis.

Presentation of autoimmune hepatitis (AIH) can differ from nonacute to acute autoimmune hepatitis (A‐AIH) with jaundice and acute severe autoimmune hepatitis (AS‐AIH) with jaundice and coagulopathy. The aim of the study was to evaluate the short‐term prognosis of different presentations of AIH and the influence of liver function improvement on short‐term prognosis. In this single‐center retrospective cohort study, AIH patients with repeatedly tested liver function at diagnosis and during at least 1 year of follow‐up were included. A‐AIH was defined as bilirubin >45 µmol and international normalized ratio (INR) <1.5. AS‐AIH was defined as bilirubin level >45 µmol/L and INR ≥1.5. Of the 81 included patients, 17 (21%) presented with A‐AIH, and 14 (17%) presented with AS‐AIH. After the start of immunosuppressive therapy, bilirubin, albumin, and INR normalized in 70%, 77%, and 69%, respectively, in a median of 2.6 months, 3 months, and 4 weeks, respectively, in patients with A‐AIH and AS‐AIH. Liver transplantation (LT)–free survival rate was 100% in nonacute AIH, 94% in A‐AIH, and 57% in AS‐AIH at 12 months after diagnosis. An increase of INR or bilirubin at 2 weeks was the best predictive factor for the need of LT within 12 months with a Youden’s index of 0.85. A‐AIH was present in 21%, and AS‐AIH was present in 17% of AIH patients. In the majority of patients, bilirubin, albumin, and INR normalized in the first months of treatment. Deterioration of liver function after 2 weeks of treatment should lead to rapid evaluation for LT and consideration of second‐line medication.

S2670 Wilson Disease Presenting With Autoimmune Hepatitis Features: A Clinical Enigma

INTRODUCTION: Wilson disease (WD) is a genetic disorder that commonly presents with neuropsychiatric and hepatic symptoms due to an inherited defect in the metabolism of copper. In some cases, the presence of autoimmune hepatitis (AIH) markers despite features of WD can result in diagnostic delays. We present the case of a 25 year old woman presenting with decompensated liver cirrhosis attributed to WD with confounding factors of AIH. CASE DESCRIPTION/METHODS: A 25 year old woman presented to the emergency department with abdominal distension and bilateral lower extremity edema. Her physical exam was remarkable for abdominal ascites and bilateral pitting leg edema. Laboratory analysis demonstrated an elevated alkaline phosphatase at 211 U/L, as well as aspartate aminotransferase and alanine aminotransferase at 97 IU/L and 62 IU/L respectively. CT abdomen demonstrated small sclerotic liver with evidence for portal hypertension. Further studies were significant for a low ceruloplasmin level, positive antinuclear antibody (ANA) and low titer positive anti-smooth muscle antibodies (ASMA). She underwent upper endoscopy that revealed Grade 2 esophageal varices (Figure 1). Patient underwent liver biopsy and pathology revealed extensive bands of bridging fibrosis consistent with cirrhosis (Figure 2). Glycogenated nuclei, iron stain and alpha-1 antitrypsin test were negative with copper stain positive for occasional deposits in hepatocytes (Figure 3). After discharge, a 24 hour urinary copper level was elevated at 595μg/and dry weight copper level was 910.3 mcg/mg confirming WD. DISCUSSION: WD is a rare genetic condition that involves hepatic and neurological dysfunctions occurring in 1 to 30,000 of the worldwide population. Intriguingly, our patient did not have any neurological or psychiatric symptoms at the moment of presentation. Of note, the patient did not undergo slit lamp examination so the presence or absence of Kayser-Fleischer rings that are present in almost every patient with neurologic disease could not be determined. We report a case of a diagnosis of WD presenting with a positive ANA and ASMA initially misdiagnosed as AIH. The confounding factor of this case was the early detection of a positive ANA and ASMA suggesting AIH as the culprit for the decompensated cirrhosis. The correct identification of the etiology for this patient’s cirrhosis is critical as treatment and prognosis differ greatly between these two entities and can prevent delays in effective interventions.Figure 1.: EGD demonstrating grade II esophageal varices.Figure 2.: Liver biopsy slide with extensive thick bands of bridging fibrosis consistent with cirrhosis.Figure 3.: Liver biopsy slide showing copper deposits in hepatocytes.

Quantifying immunoregulation by autoantigen‐specific T‐regulatory type 1 cells in mice with simultaneous hepatic and extra‐hepatic autoimmune disorders

Nanoparticles (NPs) displaying autoimmune disease-relevant peptide-major histocompatibility complex class II molecules (pMHCII-NPs) trigger cognate T-regulatory type 1 (Tr1)-cell formation and expansion, capable of reversing organ-specific autoimmune responses. These pMHCII-NPs that display epitopes from mitochondrial protein can blunt the progression of both autoimmune hepatitis (AIH) and experimental autoimmune encephalomyelitis (EAE) in mice carrying either disease. However, with co-morbid mice having both diseases, these pMHCII-NPs selectively treat AIH. In contrast, pMHCII-NPs displaying central nervous system (CNS)-specific epitopes can efficiently treat CNS autoimmunity, both in the absence and presence of AIH, without having any effects on the progression of the latter. Here, we develop a compartmentalized population model of T-cells in co-morbid mice to identify the mechanisms by which Tr1 cells mediate organ-specific immunoregulation. We perform time-series simulations and bifurcation analyses to study how varying physiological parameters, including local cognate antigenic load and rates of Tr1-cell recruitment and retention, affect T-cell allocation and Tr1-mediated immunoregulation. Various regimes of behaviour, including 'competitive autoimmunity' where pMHCII-NP-treatment fails against both diseases, are identified and compared with experimental observations. Our results reveal that a transient delay in Tr1-cell recruitment to the CNS, resulting from inflammation-dependent Tr1-cell allocation, accounts for the liver-centric effects of AIH-specific pMHCII-NPs in co-morbid mice as compared with mice exclusively having EAE. They also suggest that cognate autoantigen expression and local Tr1-cell retention are key determinants of effective regulatory-cell function. These results thus provide new insights into the rules that govern Tr1-cell recruitment and their autoregulatory function.

Autoimmune hepatitis induced by bosentan in a patient with pulmonary arterial hypertension (RCD code: II‐1A.1; VIII)

Endothelin receptor antagonist (ERA) therapy‐induced increase in liver transaminases in patients with pulmonary arterial hypertension (PAH) is an adverse effect of bosentan which is not fully understood. A 62‐year‐old female with a 1.5‐year history of progressively worsening dyspnoea was diagnosed with idiopathic PAH (IPAH). After 2 months of PAH treatment with bosentan, levels of liver transaminases were elevated and autoimmune hepatitis was diagnosed. This clinical case demonstrates the challenge of diagnosing autoimmune hepatitis induced by ERA therapy in clinical practice. A thorough understanding of the pathogenesis and clinical presentation of autoimmune hepatitis, as well as the possibility to perform specific investigations with multiple serological markers are crucial for establishing the correct diagnosis. JRCD 2019; 4 (4): 101-105.

Determinants of Outcomes in Autoimmune Hepatitis Presenting as Acute on Chronic Liver Failure Without Extrahepatic Organ Dysfunction upon Treatment With Steroids

Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids. In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified. Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-daytransplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%). Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.

Overlap of concurrent extrahepatic autoimmune diseases is associated with milder disease severity of newly diagnosed autoimmune hepatitis

BackgroundConcurrent extrahepatic autoimmune disorders (CEHAID) are frequently observed in autoimmune hepatitis (AIH). It is not clear whether there is any prognostic significance of CEHAID on AIH. The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH. MethodsThis study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period (2009–2016). All records were manually screened for presence of associated autoimmune diseases. Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and liver histology. ResultsAmong the enrolled patients, 52 (80%) were female (median age 61 years, IQR 45–75). Fifty-six (86.2%) were classified as type-1 AIH. In 26 (40%) patients at least one additional extrahepatic autoimmune disease was diagnosed. Thirty-four subjects were referred to our hospital because of acute presentation of AIH (supposed by an acute elevation of hepatic enzymes) for subsequent liver biopsy resulting in initial diagnosis of AIH. This group was stratified into 3 subgroups: (A) AIH alone (n = 14); (B) overlap with primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (n = 11); and (C) with CEHAID (n = 9). AST/ALT ratio was the lowest in subgroup C (median 0.64, IQR 0.51–0.94; P = 0.023), compared to subgroup A (median 0.91, IQR 0.66–1.10) and subgroup B (median 1.10, IQR 0.89–1.36). Patients with AIH alone showed a trend to the highest grade of fibrosis (mean 2.3; 95% CI: 1.5–3.0) with no statistical significance compared to subjects with CEHAID (lowest grade of fibrosis; mean 1.5; 95% CI: 0.2–2.8; P = 0.380) whereas the ongoing inflammation was comparable. ConclusionsAST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID, compared to subjects with only AIH. Therefore, the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH, possibly caused by an earlier diagnosis or different modes of damage.

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

Histopathological analysis of autoimmune hepatitis with "acute" presentation: Differentiation from drug-induced liver injury.

Presently, no standardized definition or acceptable diagnostic criteria have been established for acute presentation of autoimmune hepatitis (AP-AIH), making it difficult to differentiate that condition from drug-induced liver injury (DILI). This study aimed to characterize clinical and histological features for distinguishing between AP-AIH and DILI. Clinical, biochemical, and histological characteristics of AP-AIH and DILI in clinically well-characterized cases were compared in a standardized manner to clarify differences. In clinical evaluations, immunoglobulin G level and rate of anti-nuclear antibody positivity were greater in AP-AIH than DILI cases. As for diagnosis of each condition, significant (P < 0.01) differences were found for 10 features: lobular necrosis/inflammation, cobblestone appearance of hepatocytes, plasma cell infiltration in liver parenchyma, centrilobular fibrosis, hepatic rosette formation in areas with cobblestone appearance, portal inflammation, interface hepatitis, prominent plasma cells in portal areas, bile duct injury, and hepatic rosette formation in periportal areas. The area under the curve and cut-off values for the combination of these 10 features were 0.95 and 9 (sensitivity 86%, specificity 90%), respectively. Combinations of histological features were found to be helpful for differentiating AP-AIH from DILI, but we were not able to statistically identify an individual feature as definitive.

Hepatitis autoinmune

Autoimmune hepatitis is a generally progressive, chronic liver disease, normally with fluctuating course, affecting both sexes of any age, mainly young women. Europe prevalence is 15-25 per 100,000 inhabitants. It is linked to other autoimmune conditions in 25% of patients. Although its pathogeny is still unknow, both genetics and environmental factors trigger a disorder of immune system regulation causing liver injury. The presentation of autoimmune hepatitis is heterogeneous, ranging from asymptomatic patients with abnormal liver functions tests to even fulminant hepatic failure. Diagnosis is complex and relies over clinical, biochemical and histologic findings. To rule out other etiologies is mandatory. Corticoids (prednisone) are the first-line treatment. Azathioprine is its maintenance treatment. Other immunosuppressants and even liver transplantation might be required when conventional therapy has failed or when disease progress.

Features and outcome of AIH patients without elevation of IgG.

Background & AimsHigh IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored.MethodsIn a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up.ResultsOut of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels.ConclusionsCompared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.Lay summaryA characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.

2229 Peripheral Eosinophilia; An Unusual Presentation of Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by elevated hepatocellular enzymes, autoantibodies, immunoglobulins, periportal inflammation and rapid improvement with steroids. Associated peripheral eosinophilia has been rarely reported. We report a case of AIH presenting with eosinophilia. CASE DESCRIPTION/METHODS: A 48-year-old Caucasian male with a past medical history of splenectomy a year ago following a motor vehicle accident presented to the emergency department with a 2-week history of diarrhea, malaise, anorexia, chills and dark urine. He also observed yellowish discoloration of his eyes 5 days prior to presentation. No history of over-the-counter medications, supplements, alcohol or drug use. Vital signs were normal while physical exam was only notable for scleral icterus. Labs on admission showed: WBC 21.9K/mL (35% eosinophils), AST 820U/L, ALT 350U/L, ALP 204U/L, total bilirubin 13mg/dl (conjugated bilirubin 8.7mg/dl), INR 1.8. Due to concerns for acute liver injury, evaluation by CT abdomen and MRCP revealed nodular contours of the liver suggestive of chronic hepatic parenchymal disease, no evidence of biliary ductal pathology. He was managed conservatively with fluids while further extensive work-up to determine etiology of liver injury and eosinophilia such as acute hepatitis panel, CMV PCR, EBV IgM, alpha-1 antitrypsin, ceruloplasmin, mycoplasma IgM, stool studies for infection and parasites, strongyloides, histoplasma antigen were negative. IgG (2084mg/dl) and IgA (732mg/dl) were elevated as ANA and smooth muscle antibody were positive. As liver enzymes, eosinophilia and INR continued to rise, a liver biopsy was performed which showed extensive bridging fibrosis, ballooning degeneration of hepatocytes, mild fatty change, mixed inflammatory infiltration with lymphocytes, plasma cells, eosinophils and occasional neutrophils in the portal areas, prominent interface changes all consistent with autoimmune hepatitis. No evidence of ductopenia, periductal fibrosis or granulomas was seen. He was started on steroids with immediate resolution of eosinophilia and improvement of symptoms and labs. DISCUSSION: With this report, we hope to draw awareness to this unusual presentation of AIH. As eosinophilia resolved rapidly with treatment of liver disease, AIH should be strongly considered in patients with elevated liver enzymes and peripheral eosinophilia especially in the absence of other predisposing conditions for eosinophilia.

3166 Autoimmune Hepatitis: When You Cannot Blame the Gallbladder Anymore

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic liver disease with varying degrees of onset severity often presenting with nonspecific symptoms such as abdominal pain, fatigue, jaundice and nausea. Although initial reports have suggested that AIH has a bimodal age distribution (with the second peak between 40 and 50 years), the condition has increasingly been recognized in all age groups, including the elderly. CASE DESCRIPTION/METHODS: A 70-year-old woman was admitted to our medical center with a 2-month history of abdominal discomfort, anorexia and fatigue. Past medical history was notable for hyperlipidemia. Five weeks prior to admission, the patient had presented to her primary provider with similar complaints and was found to have significantly elevated liver enzymes, as shown in Table 1. The patient denied alcohol use. At the time of admission, work-up showed similar transaminases with an increase in bilirubin (Table 1). Abdominal ultrasound revealed cholecystolithiasis and possible cholecystitis without intra- or extrahepatic ductal dilation. ERCP confirmed cholecystolithiasis without visualization of intraductal stones on cholangiogram or after sweeping of the biliary tree. Laparoscopic cholecystectomy was performed and pathology results revealed chronic cholecystitis. Despite these interventions, the patient was readmitted one week later for ongoing jaundice and malaise. She had no ascites on exam. Laboratory work-up showed persistently elevated liver tests (Table 1). Anti-smooth muscle antibodies (ASMA) were elevated at 1:80. Viral hepatitis panel was negative. Liver biopsy revealed marked panacinar hepatitis with cholestasis without hemosiderin deposition. The patient was diagnosed with autoimmune hepatitis and initiated on steroids with rapid resolution of symptoms. Transaminases and bilirubin decreased significantly one week after initiation of steroids and normalized after 6 weeks. DISCUSSION: The clinical presentation of AIH is often nonspecific and highly variable. Most patients present with insidious symptoms, but the spectrum of symptomatology can range from asymptomatic to severe acute disease. Acute AIH can mimic other conditions such as acute viral hepatitis and choledocholithiasis resulting in delayed diagnosis and sometimes unnecessary interventions such as ERCP and cholecystectomy. In the absence of an obvious alternative diagnosis, acute transaminitis warrants work-up that includes ASMA testing since AIH can present in virtually any age category, as highlighted in this case.

Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation?

Acute severe presentations of autoimmune hepatitis (AIH) represent a challenge for the transplant community. As a disease, it is poorly characterized, and there is a weak evidence base to guide diagnosis and treatment. Early identification of acute severe AIH is key because it determines the initiation of corticosteroids, which can be lifesaving. However, their use in this setting remains controversial. The Model for End-Stage Liver Disease score, severity of coagulopathy, and grade of encephalopathy may be predictors of outcome with corticosteroid therapy. The optimal timing of liver transplantation (LT) can be difficult to determine and, as such, the decision to proceed to transplantation should not be delayed by protracted courses of corticosteroids. The aim of this review is to better characterize this subset of patients; to differentiate them clinically, serologically, and histologically from chronic AIH and other causes of acute liver failure; and to present the role, predictors, and optimal timings of corticosteroid therapy and LT. Although this review is specific to adults, many principles hold true for the pediatric population.

Racial disparities in presentation and outcomes of paediatric autoimmune hepatitis.

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

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.

Liver Fibrosis Helps to Distinguish Autoimmune Hepatitis from DILI with Autoimmune Features: A Review of Twenty Cases.

Background and Aims: Drug-induced liver injury with autoimmune features (AI-DILI) mimics the clinical presentation, and laboratory and pathologic features of idiopathic autoimmune hepatitis (AIH). We aimed to identify histopathologic hallmarks to differentiate these entities.Methods: All liver biopsies archived for the past 10 years were reviewed retrospectively to identify cases of recently detected liver injury associated with predominantly lymphoplasmacytic interphase hepatitis, positive markers for liver autoimmunity, and negative tests for viral hepatitis. Twenty cases were divided into AIH (n = 12) or AI-DILI (n = 8) groups. Blind qualitative evaluation of necroinflammatory changes and liver fibrosis were performed according to the Scheuer scoring system. Cellular densities were determined using ImageJ (V1.51t, National Institutes of Health, Bethesda, MD, USA). Fibrosis was assessed on Masson trichrome-stained slides, and collagen deposition was estimated following a protocol of color deconvolution.Results: Necroinflammatory changes as well as densities (portal and lobular) of neutrophils and eosinophils, intracellular cholestasis, and regenerative changes did not differ between the two groups (P ≥ 0.05). Neutrophil densities but not eosinophils showed a positive correlation with the severity of hepatocellular damage (r = 0.6 and 0.58, vs. alanine aminotransferase, P < 0.05). Ceroid-laden macrophages but not histiocytic aggregates appeared to be more common in AI-DILI (P < 0.05). AIH patients presented more often with evidence of chronic damage, including higher scores of fibrosis and collagen deposition, in comparison to AI-DILI (P < 0.05).Conclusions: Although there is no histologic feature pathognomonic for AI-DILI or AIH, advanced stages of liver fibrosis can be used to support the diagnosis of AIH in some cases. Definitive diagnosis of AI-DILI requires follow-up and demonstration of complete remission after drug withdrawal with no need for immunosuppression.