International Autoimmune Hepatitis Group Criteria Research Articles

Long-term outcomes of patients with autoimmune hepatitis induced cirrhosis after immunosuppressive treatment.

Autoimmune hepatitis is an immune-mediated liver disease that results in hepatic inflammation and subsequent fibrosis. We aimed to assess the natural history of autoimmune hepatitis in patients who had cirrhosis at the time of diagnosis. We examined consecutive patients with autoimmune hepatitis (based on the revised International Autoimmune Hepatitis Group criteria) and cirrhosis who had long-term follow-up between 2012 and 2018. Complete clinical data, including longitudinal data, was obtained for each patient to determine clinical and biochemical outcomes. Decompensating events were defined as complications of portal hypertension. Thirty-four patients presenting with autoimmune hepatitis induced cirrhosis (age 50, 17-81; 71% women) were followed for an average of 8 years post-diagnosis. Fourteen (41%) patients had a decompensating event at diagnosis. All patients were begun on treatment; index decompensating events resolved in all patients. Twenty-six (76%) patients had normalization of transaminases; in this group, 4 (15%) patients developed one or more new decompensating events and 1 patient (4%) died. Of the 8 (24%) patients who did not have transaminase normalization, 6 (75%) developed one or more new decompensating events and 5 (62%) died or underwent liver transplant. There was a significant association between achieving normalization of transaminases and protection from developing a decompensating event ( P = 0.003) and liver transplant or death ( P = 0.001). Most patients with autoimmune hepatitis with cirrhosis at presentation achieved normalization of transaminases with treatment and rarely developed further decompensating events. We speculate that some of these patients had stabilization or reversal of portal hypertension.

Long-term outcomes of drug-induced autoimmune-like hepatitis after pulse steroid therapy.

Pulse steroid therapy occasionally causes drug-induced autoimmune-like liver hepatitis (DI-ALH), but the long-term outcome of treated patients is not well known. In this study, we investigated the long-term outcomes of DI-ALH due to pulse steroid therapy. We retrospectively reviewed medical records of 405 patients treated with pulse high-dose methylprednisolone in Kurashiki Central Hospital between January 2011 and December 2017. The frequency and clinicopathological characteristics of acute liver injury that occurred within 3 months after the therapy were analyzed. The diagnosis of DI-ALH was made according to the revised international autoimmune hepatitis group criteria. Among the 405 patients treated with methylprednisolone, 61 (15.1%) had acute liver injury after the pulse steroid therapy, and DI-ALH was diagnosed in 5 patients (1.2%). Absence of oral prednisolone tapering after the pulse steroid therapy was a significant risk factor for the subsequent development of DI-ALH (odds ratio, 11.9; P = 0.017). One patient was treated with 3 days of intravenous methylprednisolone followed by oral prednisolone. Two patients were treated with glycyrrhizin followed by oral prednisolone due to ineffectiveness of glycyrrhizin. Remission was achieved with glycyrrhizin alone, and spontaneous remission without drug therapy occurred in one patient each. During the median follow-up period of 34 months, no relapse was evident in all the patients without maintenance therapy. Pulse steroid therapy can cause DI-ALH, especially when subsequent prednisolone is not tapered. Prednisolone is effective for DI-ALH due to pulse steroid therapy and can be safely withdrawn once remission is achieved. This article is protected by copyright. All rights reserved.

A clinical case of diagnosis of autoimmune hepatitis at the stage of liver cirrhosis

The aim of the work is to analyze a clinical case of autoimmune hepatitis (АІН) diagnosis at the stage of cirrhosis in a 40-year-old female patient and to remind practicing doctors about the serious consequences of this disease. Materials and methods. A clinical case of AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (2008) at the stage of cirrhosis in a 40-year-old female patient was analyzed. A puncture liver biopsy with a morphological study of the hepatobioptate was also performed to verify the diagnosis. Results. The analysis of the clinical case of AIH in a 40-year-old female patient revealed a delayed diagnosis of AIH at the cirrhosis stage. This was due to the absence of any clinical symptoms of the disease for a long period of time, and the lack of attention of practicing doctors in investigating the reasons for the long-term increase in transaminase activity. The trigger factor for the clinical manifestations of cirrhosis, which developed due to the long-term course of AIH, was emotional stress resulting from leaving the combat zone. The application of the International Autoimmune Hepatitis Group criteria in clinical practice was demonstrated, specifically the combination of elevated antinuclear antibodies and total IgG, characteristic histological changes in the liver, and exclusion of hepatotropic viral infections, which allowed for a reliable diagnosis of AIH. Medical treatment resulted in certain positive changes in clinical and laboratory indicators. However, according to the transplant doctor’s opinion, at this stage of the AIH course, the patient required a liver transplant and therefore was added to the waiting list. Conclusions. This clinical case highlights the late diagnosis of AIH at the cirrhosis stage in a 40-year-old female patient due to the absence of clinical manifestations over several years and the lack of vigilance among doctors, possibly primary care physicians or specialists, to investigate the persistent increase in transaminase activity. The application of the International Autoimmune Hepatitis Group criteria helped confirm the diagnosis of AIH.

The Spectrum of Autoimmune Liver Disorders, Clinical Presentation, and Autoantibodies in Patients From a Tertiary Care Center in Pakistan.

BackgroundThe autoimmune illnesses that affect the liver include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and overlap syndrome. In our patients, we aimed to address the complete spectrum of autoimmune liver disorders, clinical presentation, and autoantibodies.MethodsThe study included all the patients diagnosed with autoimmune liver disorder irrespective of age, gender, and ethnic background presented at the liver clinic of the hospital in the last two years. The diagnosis was based on characteristic clinical and laboratory findings, the presence of one or more characteristic autoantibodies, and/or histological abnormalities. The diagnosis of AIH was further validated by revised International AIH Group criteria using a scoring calculator. The diagnostic criteria for PBC required the presence of chronic elevation of alkaline phosphatase (ALP) with positive antimitochondrial antibody (AMA) or positive PBC-specific anti-nuclear antibodies (ANA) (sp-100, gp-210) tests and/or compatible histology. The patients of AIH-PBC overlap syndrome fulfilled the criteria for AIH in the setting of PBC. Patients having liver involvement in other autoimmune disorders were included in the study.ResultsThe total number of patients was 124; 83 (67%) were females; mean age ± standard error of mean (SEM) was 44.97 ± 1.47 years with a range of 09-84 years. Type-1 AIH was seen in 68 (54.8%) patients, type-2 AIH in 10 (8.1%) patients, PBC in 22 (17.7%) patients, overlap of PBC with AIH in 10 (8.1%) patients, IgG4 disease in four (3.2%) patients, psoriasis-specific immune hepatitis in four (3.2%) patients, celiac disease-related hepatitis in three (2.4%) patients, sarcoidosis in two (1.6%) patients, and ichthyosis-associated hepatitis in one (0.8%) patient. There was a high prevalence of cirrhosis (50%) at the time of presentation; 19% of patients had decompensated liver disease. ANA was positive in 52/68 cases of AIH type-1, but anti-smooth muscle antibody (ASMA) was reactive only in nine cases and anti-soluble liver antigen (SLA) in five cases. There was no female preponderance in type-2 AIH (M:F = 6:4). AMA was reactive in 25 (78%) cases of PBC and overlap syndrome. Antibodies prevalent in PBC (AMA-M2, AMA-M2-3E, sp-100, gp-210, anti-Ro52) were also seen in some cases of AIH, though they did not fulfill the criteria of the overlap syndrome.ConclusionThere is an unmet need for the early diagnosis of autoimmune liver diseases and the initiation of appropriate management to prevent complications.

Incidence of de novo autoimmune hepatitis in children and adolescents with increased autoantibodies after liver transplantation: a meta-analysis.

The objective of this meta-analysis was to assess the incidence of de novo autoimmune hepatitis (AIH) in children and adolescents with increased autoantibodies after liver transplantation. We systematically retrieved studies from PubMed, Embase, Central, CNKI, VIP and Wanfang published before February 1, 2020. All analyses were conducted using R-4.0.1 statistical package (Meta). Seven studies with high quality were pooled in our final analysis (N=251 participants). The incidence of de novo AIH was 9% [95% confidence interval (CI) 1-23%, I2 =86%]. Subgroup analysis suggested that publications not using the International Autoimmune Hepatitis Group (IAIHG) criteria have marginally significantly higher incidence of de novo AIH than those using IAIHG criteria (P for interaction=0.08). The incidence of chronic rejection was 8% (95% CI 2-17%, I2 =72%). Meta-regression indicated significant correlation (P=0.04; estimate: 1.51) between the incidence of de novo AIH and the rate of increase of antibodies to liver/kidney microsome (anti-LKM). It is still challenging to distinguish de novo AIH and chronic rejection in children and adolescents with increased autoantibodies after liver transplantation. The diagnostic criteria for de novo AIH in children and adolescents and the role of anti-LKM in the development of de novo AIH deserve future investigation.

Seamless Management of Juvenile Autoimmune Liver Disease: Long-Term Medical and Social Outcome

To report baseline features and long-term medical/social outcomes of juvenile autoimmune liver disease, including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), managed in a single tertiary center. Retrospective study of children diagnosed in 2000-2004 with AIH/ASC followed up to date. Patients with abnormal cholangiogram were classified as ASC. Presentation and outcome features were compared. Eighty-three children were included (42 female, median age 12.1years [8.5-14.1years], AIH=54, ASC=29). Most (65%) had antinuclear and/or anti-smooth muscle autoantibodies; 6% presented with acute liver failure; 29% had histologic evidence of cirrhosis. The 1999 and simplified International Autoimmune Hepatitis Group criteria failed to diagnose up to 26% of patients with AIH and 48% with ASC, and the proposed the European Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria were accurate. Response to treatment was excellent with 95% achieving normal transaminase levels. During follow-up, 31% had at least 1 relapse episode; 3 patients with AIH developed cholangiopathy and 5 patients with ASC developed progressive bile duct injury. At last follow-up (median of 14.5years, 10.4-16.8), 99% were alive, 11 underwent transplantation and 1 is listed for transplant. Five-, 10-, and 15-year transplant-free survival rates were 95%, 88%, and 83%; patients with ASC and those relapsing being more likely to require transplant. Social outcome was excellent with 93% in employment/education. Seamless management of juvenile autoimmune liver disease leads to excellent clinical and social outcomes. Despite good response to immunosuppressive treatment, patients with ASC have a worse prognosis than those with AIH. Diagnostic models developed for adults are unsatisfactory to correctly diagnose juvenile autoimmune liver disease.

Autoimmune hepatitis in 847 childhood-onset systemic lupus erythematosus population: a multicentric cohort study

ObjectiveTo evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients.MethodsThis retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni’s correction (p < 0.0033).ResultsAIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0–8.5) vs. 0.12 (0–8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0–26) vs. 7 (0–41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033).ConclusionsOverlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.

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

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

Overlap Syndromes

Background: Some patients present with features of both primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) on the one hand and autoimmune hepatitis (AIH) on the other hand, either simultaneously or consecutively. The term ‘overlap syndrome (OS)' is used to describe these settings, but lack of universal agreement on what precisely constitutes an OS has generated considerable confusion. The low prevalence of OS (roughly 10% of PBC or PSC) has made it impracticable to perform randomized controlled trials. It remains unclear whether this syndrome forms a distinct entity or is a variant of PBC, PSC or AIH. Key Messages: Moderate to severe interface hepatitis is a fundamental component and histology is vital in evaluating patients with overlap presentation. Use of the International Autoimmune Hepatitis Group criteria for the diagnosis of OS is not recommended. For PBC-AIH OS, EASL has provided diagnostic criteria and, in most cases, it is possible to define one primary disorder (‘dominant' disease), usually PBC. Patients with OS seem to have a more severe disease compared to conventional PBC. PSC-AIH OS is assumed to exist in a considerable part of mainly young patients with autoimmune liver disease and long-term progression towards cirrhosis seems to occur in the majority of cases. In children, the hepatitic feature can be very dominant, and up to 50% of pediatric AIH have cholangiographic abnormalities suggestive of PSC (autoimmune sclerosing cholangitis). Treatment of OS is empiric and includes ursodeoxycholic acid for the cholestatic component (depending on local policy for PSC) and immunosuppressive agents for the hepatitic component, either simultaneously or sequentially. The dominant clinical feature should be treated first and therapy adjusted according to the response. Conclusions: OS is not uncommon but should not be over-diagnosed in order not to expose unnecessarily PBC or PSC patients to the risk of steroid side effects. Therapy has to be individualized and not be static.

Clinical Profile and HLA Typing of Autoimmune Hepatitis From Pakistan

BackgroundHuman leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH) has been investigated in different populations and ethnic groups, but no such data is available from Pakistan.ObjectivesThe aim of this study was to evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the associated antigens and alleles by performing HLA typing.Patients and MethodsA total of 58 patients, diagnosed and treated as AIH in the last 10 years were reviewed. Diagnosis was based on International AIH Group criteria. Forty one patients underwent liver biopsy. HLA typing was performed in 44 patients and 912 controls by serological method for HLA A and B, and by PCR technique using sequence specific primers for DR alleles.ResultsOf 58 cases, 35 were females (60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10-22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients (84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of presentation. Among 41 patients who underwent liver biopsy, thirty-two had advance stages III and IV disease, and twenty had severe grade of inflammation. Fifteen patients had other associated autoimmune diseases and one developed hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10 (25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40 (61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032) and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical significance than controls.ConclusionsAIH in our region presents with advanced disease affecting predominantly children and adolescents. There is a genetic association of HLA DR6 along with other alleles and antigens in our patients with AIH.

Epigenetic considerations and the clinical reevaluation of the overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis

Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndromes, we evaluated a large series of consecutive patients with PBC (n = 565) and AIH (n = 196) to identify a group of patients with corticosteroid-responsive PBC-AIH overlap syndrome. Within this series, a total of 490 patients were biopsied based upon staging or diagnostic needs. Review of the biopsies in conjunction with the International AIH Group criteria identified 80 patients with suspected overlap syndrome and 52 patients agreed to participate in the study and were prospectively treated with corticosteroids. Of these, 40/52 (77%) achieved a complete biochemical response (i.e. normal ALT, AST, and IgG) within 12 months of treatment. A survey of pre-treatment characteristics of the 40 responders revealed more severe interface hepatitis. Serum IgG levels ≥1.3x the upper limit of normal had 60% sensitivity and 97% specificity rates for steroid-responsiveness while the use of a higher threshold (≥2.0x) reduced sensitivity to 10%. When the Paris criteria for PBC-AIH were applied to the steroid-responsive patients, 29/40 (73%) cases fulfilled at least two of the three Paris criteria. Applying the recently designed simplified IAIHG scoring system, 35/40 (88%) had a “definite” diagnosis of AIH. This study supports the hypothesis that a complete response to corticosteroids may denote a variant of a PBC-AIH overlap syndrome which could be identified prior to treatment by modified Paris criteria in concert with the simplified IAIHG scoring system.

Clinical Features and Long Term outcome of 102 Treated Autoimmune Hepatitis Patients

There is limited data on the natural history of autoimmune hepatitis (AIH) and on the long-term follow-up of AIH patients who have been referred for regular medical attention. We evaluated the clinical presentation and natural history of AIH in a large cohort of type I AIH patients from Iran. Between 1997 and 2008, 102 patients were enrolled in the study. Patients were diagnosed using the International Autoimmune Hepatitis Group criteria and were followed up for an average of 60 months. Clinical and biochemical data were gathered from all the patients at both the beginning and the end of the follow-up period. Liver biopsy was performed in all patients before treatment, and the biopsies were performed in 28 patients after treatment. Biochemical remission was achieved by 80 (79.4%) patients. Of these, 53 (66.5%) showed near-normal liver histology or liver function test results and sonogram. The remaining 27 (33.5%) patients also achieved clinical and biochemical remission, but developed compensated cirrhosis. After a period of remission, 24 patients (32.5%) relapsed. Among the 22 (21.6%) patients who showed ultimate treatment failure, 6 underwent orthotopic liver transplantation and 3 died of liver failure while awaiting a transplant. Sixteen (72.7%) of the 22 patients who did not respond to therapy were non-compliant with medications and had irregular follow-up. The overall 10-year survival rate in the cohort was 96%. Long-term survival in AIH patients is very good. Prompt diagnosis and appropriate first-line and salvage therapy that includes close follow-up will make liver transplantation a rare necessity in the treatment of this disease.

The Impact of Race/Ethnicity on the Clinical Epidemiology of Autoimmune Hepatitis

To evaluate race/ethnicity-specific variations in autoimmune hepatitis (AIH) with a focus on Asians and Hispanics, the fastest growing populations in the United States. AIH is a chronic inflammatory disease in which race/ethnicity-specific variations in clinical epidemiology have been reported. However, earlier studies were small or did not include a comprehensive analysis of Asians and Hispanics, the 2 fastest growing population cohorts in the United States. A retrospective study analyzing patient data from 1999 to 2010 in a large tertiary-care community hospital to assess AIH epidemiology among a racially diverse population. One hundred eighty-three patients with AIH were included in the study with 81 patients having "definite" AIH by International Autoimmune Hepatitis Group criteria and 63 were diagnosed with overlap syndromes. Women and whites were the largest cohorts. The average age of diagnosis was similar among all groups. Biopsy-confirmed cirrhosis was present in 34% of AIH patients with Hispanics demonstrating the highest prevalence of cirrhosis (55%). When compared with whites, Asians had higher international normalized ratio (INR) (1.4 U vs. 1.1 U, P<0.01), and Hispanics had lower serum albumin (3.3 g/dL vs. 3.7 g/dL, P<0.001) and platelets (123.8 thousand/mcL vs. 187.5 thousand/mcL, P<0.001) and higher international normalized ratio (1.5 U vs. 1.1 U, P=0.05). Kaplan-Meier survival analysis demonstrated a trend toward worse outcomes among Asians. Among AIH patients, Hispanics had the highest prevalence of cirrhosis, and Asians had poorer survival outcomes. Race/ethnicity-specific disparities in AIH epidemiology may reflect underlying genetic differences, contributing to variations in disease severity, response to therapy, and overall mortality.

Autoimmune Hepatitis Type 2 in a Child With IPEX Syndrome

Autoimmune Hepatitis Type 2 in a Child With IPEX Syndrome

Acoustic Radiation Force Elastography and Transient Elastography in Autoimmune Hepatitis: Left Liver Lobe Measurement Shows Better Accuracy for Early Detection of Fibrosis

Autoimmune hepatitis (AIH) can cause liver fibrosis and cirrhosis. We evaluated the performance of ARFI and transient elastography (TE) for staging in AIH patients. AIH was defined according to the International Autoimmune Hepatitis Group criteria. ARFI was performed in both liver lobes (l_ARFI and r_ARFI) and TE in the right lobe. Elastography results were compared with three different clinical patterns based on histology, laboratory values, and sonomorphology: (i) cirrhosis, (ii) pathological sonomorphology, (iii) AIH in remission with normal sonomorphology. 47 AIH patients were recruited (10 males, 37 females, age 54.2 years). Patients with normal liver morphology (n = 14) had a shear-wave velocity of 1.26±0.17 m/s (l_ARFI) and 1.18 ± 0.15 m/s (r_ARFI). TE revealed a liver stiffness of 4.75 ± 2.24 kPa. Individuals with liver cirrhosis (n = 17) had a significant increase of liver stiffness: 1.91±0.5 2m/s (l_ARFI), 1.91±0.65m/s (r_ARFI) and TE 19.59±17.43 kPa (p<0.05, respectively). Diagnostic performance for cirrhosis detection was comparable: AUROC was 0.778 (l_ARFI), 0.862 (r_ARFI) and 0.884 (TE). Group II (n = 16) had an increase in l_ARFI (1.66±0.37m/s, p<0.001) while r_ARFI (1.22±1.28 m/s) and TE (6.07±2.24 kPa) showed no increase: AUROC was 0.887 (l_ARFI), 0.685 (r_ARFI) and 0.815 (TE). ARFI and TE can reliably detect liver cirrhosis in autoimmune hepatitis with comparable accuracy. l_ARFI has a better accuracy for early detection of fibrosis than r_ARFI or TE.

Long-term Outcomes of Patients With Autoimmune Hepatitis Managed at a Nontransplant Center

The long-term outcomes of patients treated for autoimmune hepatitis (AIH) are considered to be good. However, follow-up data beyond 10 years are limited and confined to tertiary referral centers. We assessed long-term outcomes and determinants of outcome in patients with AIH from a nontransplant center. We studied 245 patients (204 women; median age, 56 years; range, 2.5-87 years) with AIH (167 definite by International AIH Group criteria) managed at a single nontransplant center from 1971 to 2007. 229 patients (93%) achieved normal serum levels of alanine aminotransferase within 12 months after treatment. After a median follow-up period of 9.4 years (range, 0.01-36 years), 11 patients received liver transplants (2 subsequently died). Seventy other patients died (30 from liver disease), 15 were censored (moved away, defaulted, or developed primary biliary cirrhosis), and 149 were still being followed up on December 31, 2007. Survival rates from all-cause death or transplantation were 82%±3% and 48%±5% after 10 and 20 years, respectively, and from liver-related death or transplantation were 91%±2% and 70%±5%, respectively. The standardized mortality ratio was 1.63 for all-cause death (95% confidence interval [CI], 1.25-2.02), 1.86 also considering liver transplant as "death" (95% CI, 1.49-2.26), and 0.91 for non-liver-related death (95% CI, 0.62-1.19). By Cox regression analysis, liver decompensation, cirrhosis at any time, failure to normalize levels of alanine aminotransferase within 12 months, and >4 relapses per decade were significantly associated with liver-related death or transplant. Despite a good initial response to immunosuppression, long-term mortality of patients with AIH is greater than that of the general population.

Systemic lupus erythematosus and autoimmune hepatitis

Liver involvement in patients with connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis, Sjogren’s syndrome and rheumatoid arthritis is not an uncommon condition. Hepatotoxic drugs, hepatosteatosis, coincident viral hepatitis and autoimmune hepatic diseases are main causes of liver enzymes abnormality in these patients [1]. We read with great interest the study report of Leonardo et al. regarding the coexistence of autoimmune hepatitis (AIH) and SLE [2]. Hepatic lesions due to AIH in patients with SLE are thought to be rare, but some studies showed that AIH is a common cause of liver enzymes abnormality in patients with SLE. Recently, Her et al. [3] reported 46 and Chowdhary et al. [4] 40 patients with SLE and concomitant liver enzyme abnormalities, the diagnosis of AIH was made 5 (11%) and 6(15%), respectively. Although SLE and AIH are diVerent entities, they have very similar features such as female predominance, genetic susceptibility, polyarthralgia, hypergammaglobulinemia, ANA, ASMA, anti-ribonucleoprotein and ds-DNA positivity, hemolytic anemia and the good response to corticosteroid therapy [1, 5]. Therefore, merely reliance on serologic criteria may lead to a diagnostic confusion. Malar rash, oral ulcer, serositis, renal and cranial involvement, and hypocomplementemia are speciWc clinical and laboratory indicators of SLE. These Wndings can help to diVerentiate SLE from AIH [1]. The diagnosis of AIH is also diYcult in patients with SLE due to clinical and laboratory similarities. International Autoimmune Hepatitis Group criteria [6] has a low sensitivity and speciWcity for this condition. For deWnitive diagnosis, speciWc biopsy Wndings are necessary periportal piecemeal necrosis associated with lobular activity, and lymphoid inWltration and rosette formation are characteristic in AIH, while in SLE, paucity of lymphoid inWltrates is observed in lobular and occasionally portal areas [1]. In conclusion, as explained earlier, the coexistence of these two entities is common. Although the diagnosis of SLE in patients with AIH could be made by speciWc clinical Wndings, the diagnosis of AIH in patients with SLE should be made based on speciWc biopsy Wndings of AIH.

Autoimmune Hepatitis–PBC Overlap Syndrome: A Simplified Scoring System May Assist in the Diagnosis

Primary biliary cirrhosis (PBC) with features consistent with autoimmune hepatitis (AIH) has been described as an overlap syndrome. Recently, a simplified AIH scoring system has been proposed by the International Autoimmune Hepatitis Group (IAIHG), which is based on only four clinical components. We aimed to evaluate the performance of the new simplified AIH scoring system as a diagnostic instrument for PBC-AIH overlap syndrome compared with the revised 1999 IAIHG criteria. Furthermore, we sought to compare the outcome in PBC patients with and without the features of AIH overlap. Retrospective analysis of PBC patients was carried out. Parameters relevant to the revised criteria were recorded, and outcomes were compared between those with and without features of overlap. Of 368 patients (318 females) with a definite diagnosis of PBC, 43 (12%) were diagnosed as probable PBC-AIH overlap with the revised criteria and 23 (6%) with the simplified criteria. In both scoring systems the frequency of cirrhosis, portal hypertension, gastrointestinal (GI) bleeding, ascites, and esophageal varices was significantly higher in the overlap group at the time of follow-up. Patients with features of overlap according to the new criteria had more frequent liver-related death and liver transplantation (P=0.0025, log rank test). The simplified AIH scoring system appears to be more specific in patients with PBC and could assist in clinical assessment. Worse outcome was observed in patients with overlap features, demonstrated as increased liver-related mortality with the new criteria. The new criteria should be able to replace the revised criteria for the diagnosis of PBC-AIH overlap syndrome.

Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group (IAIHG) criteria in acute and chronic liver disease

Diagnostic criteria for autoimmune hepatitis (AIH) have been created and revised by the International Autoimmune Hepatitis Group (IAIHG). Simplified criteria have been created, but remain independently unvalidated. We report on the diagnostic accuracy of the simplified criteria in patients across a range of diagnoses, including a subset of patients presenting with fulminant liver failure who required liver transplant. Patients with AIH and non-AIH etiologies of liver disease were identified from dedicated patient databases. Parameters relevant to the simplified and 1999 IAIHG criteria were recorded, and sensitivity, specificity, and positive and negative predictive values for scores of >or=6 (probable AIH) and >or=7 (definite AIH) were calculated. A total of 549 patients with chronic liver disease were evaluated, (221 with AIH, 26 with variant syndromes, and 302 with non-AIH). For scores >or=6, sensitivity was 90%, and specificity was 98% with positive and negative predictive values of 97% and 92%, respectively. For scores >or=7; sensitivity was 70%, and specificity was 100% with positive and negative predictive values of 100% and 74%, respectively. Seven false positive diagnoses of AIH occurred, all with simplified scores of 6. Concordance with 1999 criteria was 90% for probable and 61% for definite AIH. The frequency of an overall diagnosis of AIH (probable or definite AIH) among the 70 patients with fulminant liver failure was 24% for simplified criteria and 40% for 1999 criteria, respectively. The simplified criteria retain high specificity but exhibit lower sensitivity for scores of >or=7. The explanations for this are unclear but may relate to loss of such discriminating information as response to corticosteroids. Prospective evaluation of these criteria is required to corroborate these observations.

Mycophenolate Mofetil as Second Line Therapy in Autoimmune Hepatitis?

In patients with autoimmune hepatitis, efficient immunosuppressive therapy is essential to avoid progression to cirrhosis. There is no established second line therapy for patients failing standard therapy with steroids and azathioprine. The aim of this study was to examine the possible role of mycophenolate mofetil (MMF) as second line treatment of autoimmune hepatitis (AIH). We were able to identify 37 patients (29 women, 8 men) with AIH proven according to International AIH Group criteria who failed standard therapy. One patient on MMF was excluded due to non-compliance. A total of 28 of 36 patients had experienced side effects necessitating stop of treatment. One patient stopped azathioprine due to pregnancy. A total of nine patients did not respond sufficiently to azathioprine. A total of four patients with a treatment duration of 3 months or less because of severe side effects were considered as intolerant to MMF. Remission was defined as aspartate transaminase (ASP) < twice upper normal limit (UNL). Of 36 patients on MMF included in the analysis, 14 patients (39%) experienced remission. A total of 22 patients (61%) did not respond sufficiently to MMF. The response rate to MMF was dependent on the cause of treatment cessation of azathioprine. Of eight patients with prior nonresponse to azathioprine, six (75%) did not respond to MMF and only two (25%) reached biochemical remission. Of 28 patients with azathioprine intolerance in 16 (57%) patients, the response to MMF was insufficient and in 12 patients (43%) remission was reached. The difference did not reach statistical significance due to the relatively small numbers included. In the light of its good tolerability, MMF seems to be an alternative for patients who could not tolerate azathioprine previously. However, our data suggest that a majority of patients fail MMF particularly if they are switched because of an insufficient response to azathioprine.