Onset Of Autoimmune Hepatitis Research Articles

Paediatric-onset autoimmune liver disease: Insights from a monocentric experience

BackgroundAutoimmune liver disease (AILD) encompasses autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC) and primary sclerosing cholangitis (PSC). A unified disease process evolving over time through these entities has been recently suggested. From this perspective, this study aimed to compare the characteristics of childhood-onset AILD at baseline and after a medium-to-long term follow-up period. MethodsPaediatric-onset cases of AILD diagnosed between 1992 and 2023 at a tertiary-care centre were reviewed. Patients transitioned to adult-care by the time of data collection were asked for clinical updates. ResultsFifty-five patients were included (AIH = 20, ASC =22, PSC =13). AIH, ASC and PSC exhibited increasing age at the onset (AIH to PSC, p < 0.01). The area under the receiver operating characteristic curve for gamma-glutamyltranspeptidase (GGT) combined with alkaline phosphatase/aspartate aminotransferase (ALP/AST) ratio in predicting sclerosing cholangitis was 0.94, with a sensitivity of 86 % and a specificity of 94 %. At the last follow-up (median duration 5,8 years, interquartile range [IQR] 2,9–10,2, n = 45), 15 patients (33 %) developed portal hypertension, 2 patients (4 %) underwent liver transplantation, no patient died. ConclusionA cohort of childhood-onset AILD managed at a single centre reveals a temporal trend in the onset of AIH, ASC and PSC, with progressively older ages. Elevated GGT levels combined with a high ALP/AST ratio predict the diagnosis of sclerosing cholangitis. The occurrence of liver-related adverse events in one-third of patients highlights the progressive nature of paediatric-onset AILD.

Diagnostic features of autoimmune hepatitis in SARS‑CoV‑2‑vaccinated vs. unvaccinated individuals.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of lives, leading to significant morbidity and mortality. With >772 million cases and nearly seven million deaths reported worldwide to date, the development of vaccines has been a critical step in mitigating the impact of COVID-19. However, concerns have arisen regarding the potential for SARS-CoV-2 mRNA vaccination to trigger autoimmune diseases, including autoimmune hepatitis (AIH). The present single-center, retrospective study aimed to compare the clinical and pathological features of AIH in patients with or without a history of SARS-CoV-2 mRNA vaccination. A total of 72 patients with AIH were examined. Among them, 10 had received the SARS-CoV-2 mRNA vaccination prior to AIH onset. These patients exhibited more pronounced CD4+ T cell infiltration into the liver tissue compared with those who were unvaccinated. No significant differences in the levels of other liver enzymes, autoimmune antibodies, or CD8+ T cell infiltration were observed between the groups. Moreover, the AIH patients with a history of SARS-CoV-2 mRNA vaccination had more extensive CD4+ T cell infiltration in their liver tissues than the unvaccinated patients. These findings suggested that the immune response to SARS-CoV-2 mRNA vaccination may influence the pathogenesis of AIH, highlighting the need for further research into the relationship between SARS-CoV-2 mRNA vaccination and autoimmune liver diseases. Such studies will also help clarify the distinction between vaccine-induced liver injury and traditional AIH.

Analysis of autoimmune hepatitis with acute presentation in the early stage of illness.

There is no gold standard for making the diagnosis of autoimmune hepatitis (AIH), and the diagnosis of acute onset AIH (A-AIH) is most challenging. A-AIH sometimes develops into acute liver failure with poor prognosis if the diagnosis is delayed. Therefore, it is most important for the better prognosis to diagnose non-severe A-AIH early and treat appropriately. However, features in the early stage of A-AIH are unclear. We examined initial characteristics of non-severe A-AIH in detail and tried to find novel clinical features for the early diagnosis. Clinical, biochemical, immunological, radiological, and histological features of 71 patients (54 women, mean age 57.9±14.3years) with non-severe A-AIH admitted to community hospitals between 2001 and 2022 were analyzed retrospectively. Forty-six had no symptom on onset and liver injuries were discovered by regular medical checkups. The mean duration from onset to consultation was 25.0±29.3days. Liver histology showed acute hepatitis in 59% and chronic hepatitis in 41%. Patients with symptoms revealed more male sex (P=0.039), higher alanine aminotransferase (P<0.001), higher total bilirubin (P<0.001), and higher rate of histological acute hepatitis (P=0.0013) than those without symptoms significantly. Male sex, presence of symptoms on onset, occurrence of jaundice in the course, and histological acute hepatitis were correlated. Sixty-five percent of non-severe A-AIH patients were asymptomatic on onset, suggesting that A-AIH would develop insidiously and present a longer clinical course than that reported. Male patients more often revealed true acute hepatitis clinically, biochemically, and histologically than female ones.

Increased IgD and CD27 Double Negative (DN) B cell population in pediatric onset autoimmune hepatitis

Autoimmune hepatitis (AIH) is a chronic, inflammatory liver disease of unknown aetiology which requires lifelong immunosuppression. Most therapeutic and outcome studies of AIH have been conducted predominantly in Caucasian (European Ancestry, EA) cohorts, with the exclusion of African American (AA) patients due to inadequate sample size. It is known that AA patients have a severe phenotype of autoimmune diseases and demonstrate a poor response to conventional medical therapy. Understanding cellular and molecular pathways which determine AIH severity and progression in AA patients is likely to lead to the discovery of novel, personalised and better tolerated therapies. The aim of the study is to determine the distinct effector B cell phenotypes which contribute to disease severity and progression of AIH in AA children as compared to their EA cohorts. PBMCs were isolated from blood samples collected from patients visiting Children’s Healthcare of Atlanta (CHOA) and were grouped into AA, (n = 12), EA, (n = 11) and controls (n = 12) and were processed for flow cytometry. Markers of B cell development, maturation and activation were assessed namely CD19, CD21, IgD, CD27, CD38, CD11c, CD24, CD138. AA children with AIH demonstrated an expansion of CD19 + ve, Activated Naïve (aN), (CD19+ IgD-/CD27- Double Negative (DN2) ([CD19+/IgD-/CD27++CD38++) cells. Plasmablasts were significantly higher along with Signalling Lymphocytic activation molecule F7 (SLAMF7). Unswitched memory [CD19+] IgD+CD27+ (USM) B cells were significantly contracted in AA patients with AIH. B cell phenotyping reveals a distinct profile in AA AIH patients with a major skewing towards the expansion of effector pathways which have been previously characterised in severe SLE in AA patients. These results suggest that the quantification and therapeutic target of B cell pathway could contribute substantially to the clinical approach to AIH especially in the AA population.

Management of hepatocellular carcinoma, an important cause of death in Japanese autoimmune hepatitis patients

BackgroundHepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH is unknown, and treatment has not been established.AimTo investigate the risk factors and prognosis of HCC in patients with AIH and identify appropriate management strategies.MethodsWe studied patients with AIH including background liver disease, sex, age, complications, treatment, response to treatment, liver fibrosis, prognosis, and treatment.ResultsIn 131 patients, deaths due to liver failure were more common early after the onset of AIH; however, deaths due to HCC increased gradually. HCC was observed in 12 patients (median age, 70 years; male/female, 4/8; cirrhosis at onset, 11; median time to carcinogenesis, 7 years). Cirrhosis at diagnosis was identified as a risk factor for carcinogenesis in the multivariate analysis (odds ratio, 41.36; p < 0.0001) and cumulative cancer rates were high. Multidisciplinary therapy other than immune checkpoint inhibitors was administered as treatment for HCC. Two of the three patients who used molecular-targeted drugs discontinued the treatment because of adverse events.ConclusionHCC is an important cause of death in patients with AIH. Currently available drug therapies are limited and early detection is desirable.Trial registrationThis trial was retrospectively registered in the Ethics Committee of Kagawa University School of Medicine under the identifier 2019 − 238, registered on 4 Feb 2020.

Concomitant Acute Hepatitis E Infection and Autoimmune Hepatitis

Abstract: The role of viral infections as precipitants for autoimmune hepatitis (AIH) has been previously suggested, yet the direct link between acute hepatitis E virus (HEV) infection and the onset of AIH remains to be elucidated.

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45(14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

Клинический случай аутоиммунного гепатита 1 типа у ребенка 10 лет

Aim. To demonstrate a clinical case of autoimmune hepatitis type 1 in a patient aged 10 years. Key points. Certain infections can cause frequently asymptomatic and self-limited hepatitis, while others may result to severe acute hepatitis and/or act as a trigger for autoimmune hepatitis in young children. We present the case of a previously healthy 10-year-old girl with a syndrome of cytolysis and cholestasis who had elevated serum transaminases, Epstein — Barr virus (EBV) serology compatible with recent EBV infection, and positive anti-smooth muscle antibody characteristic of onset autoimmune hepatitis type 1. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation and interface hepatitis. Persistent EBV-related hepatitis was excluded by negative serum EBV-PCR. Conclusion. The presented clinical case suggests that in children with cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, a liver biopsy seems mandatory to achieve a correct and on-time diagnosis of a poor prognostic disease such as autoimmune hepatitis. Keywords: autoimmune hepatitis, Epstein — Barr virus, liver transaminase elevation, anti-smooth muscle antibody

Analysis of non-severe acute onset autoimmune hepatitis according to the presence of radiological heterogeneity.

Diagnosis of acute onset autoimmune hepatitis (A-AIH) has been difficult in that patients may not have typical clinicopathological features of AIH. In our previous reports of severe and fulminant AIH, two-thirds of them showed radiological heterogeneity: hepatic heterogeneous hypoattenuation on unenhanced computed tomography (CT) reflecting heterogeneous distribution of massive hepatic necrosis (severe centrilobular necrosis), which would be beneficial for the diagnosis. In the present study, we analyzed non-severe A-AIH patients with or without radiological heterogeneity and tried to find novel clinical features for supporting the early diagnosis. Clinical, biochemical, immunological, radiological and histological features of 42 patients with non-severe A-AIH at community hospitals between 2010 and 2020 were analyzed. Of 42, 28 patients on whom CT scans were performed and who could be fully analyzed were enrolled. Five patients showed hepatic heterogeneous hypoattenuation on unenhanced CT. There was no significant difference in clinical, biochemical, immunological and histological features at diagnosis between the two groups according to the presence of radiological heterogeneity, although mean minimum prothrombin time activity during the course was lower in patients with heterogeneity without statistical significance (p=0.080). All responded to treatment well and achieved initial remission within 3months. It is possible that patients with non-severe A-AIH show radiological heterogeneity reflecting centrilobular necrosis which is one of important diagnostic features of A-AIH. Accordingly, radiological heterogeneity might be beneficial for the diagnosis of A-AIH in combination with conventional clinicopathological features if it is detected in the absence of features suggestive of other liver diseases.

Autoimmune hepatitis in pregnancy: Pearls and pitfalls.

Autoimmune hepatitis (AIH) in pregnancy has many unique considerations. Evidence provided from single center studies with patient level data and nationwide population studies provide valuable insight into this complex situation. Because a planned pregnancy is a safer pregnancy, preconception counseling is a crucial opportunity to optimize care and risk stratify women with AIH. Women with chronic liver disease who receive preconception advice and counseling are more likely to achieve stable liver disease at conception and undergo appropriate variceal surveillance. Loss of biochemical response in pregnancy is associated with adverse outcomes in unstable disease. New onset AIH in pregnancy should be managed with classical treatment regimens. The continued use of immunosuppression in pregnancy, with the exception of mycophenolate mofetil, has not shown to adversely affect the rates of stillbirth or congenital malformation. Previously adopted immunosuppression withdrawal paradigms in pregnancy should no longer be considered advantageous, because remission loss postdelivery is likely (12%-86%). Population studies, report improved outcomes with preterm birth rates falling from 20% to 9%-13% in AIH pregnancies over a 20-year period. Newer data have also demonstrated an increased risk of gestational diabetes and hypertensive complications in AIH pregnancy, which has implications for management and preeclampsia prevention with aspirin use. This review aims to provide the framework to guide and manage pregnancy in AIH outlining pearls and pitfalls to ensure optimal outcomes for mother, baby and to reduce variation in practice.

Clinical features of patients with new onset of autoimmune hepatitis following SARS-CoV-2 vaccination

Introduction: Autoimmune hepatitis (AIH) is a relatively rare chronic immune-mediated liver disease, which develops in genetically predisposed individuals following an environmental trigger. A few cases of AIH have been recently reported after the SARS-CoV-2 vaccination. Aims: The aim of this study was to describe clinical-epidemiological profile of a series of adult patients who experienced AIH onset following SARS-CoV-2 vaccination. Materials and Methods: This multicentric observational study collected clinical data of adult patients who had received SARS-CoV-2 vaccination and thereafter were diagnosed with AIH between 03/2021 and 10/2021 in Italy, using an online survey among members of the Italian Association for the study of the Liver (AISF). Results: Among the 12 patients included: 50% were females, median age 62 years (range 32-80), 6 (50%) had preexisting extrahepatic autoimmune disease (3 thyroiditis, 2 rheumatoid arthritis, 1 systemic lupus erythematosus), 7 patients have received Comirnaty (BioNTech/Pfizer) vaccine, 2 Spikevax (Moderna Biotech) and 3 Vaxzevria (AstraZeneca). Ten patients (83%) had acute onset of AIH with transaminase levels ≥10 times the upper limit of normal (ULN, range 13-77 x ULN), 8 (67%) with jaundice (total bilirubin 3.5-18.6 x ULN). At AIH diagnosis (median time from first and second vaccine dose: 48 and 10 days, respectively) median AST was 18 x ULN (range 5-85), ALT 23.8 x ULN (range 7-83), total bilirubin 3.8 x ULN (range 0.6-18.6), alkaline phosphatase 1.3 x ULN (range 0.8-7.1), immunoglobulin G 1.2 x ULN (median 0.8-1.5). Eight (67%) patients had autoantibodies: 6 ANA, 1 SMA, 1 LKM-1. Liver biopsy was typical for AIH in 8 and compatible in 3 patients. After 3 months 58% achieved complete biochemical response to standard immunosuppressive treatment. Conclusion: While intensive vaccination against SARS-CoV-2 continues, the diagnosis of AIH secondary to vaccines should be included in the differential diagnosis in cases of acute hepatitis of unexplained aetiology.

Pregnancy outcome in women with childhood onset autoimmune hepatitis and autoimmune sclerosing cholangitis on long-term immunosuppressive treatment

IntroductionAutoimmune hepatitis and autoimmune sclerosing cholangitis may lead to maternal and fetal complications in pregnant women diagnosed during childhood and treated long-term with immunosuppressive drugs. Immunosuppressive treatment with azathioprine is usually employed during pregnancy to maintain remission but his safety is still controversial. The aim of our study is to investigate pregnancy outcomes after maternal long-term immunosuppressive treatment for autoimmune hepatitis/sclerosing cholangitis. MethodsWe conducted a retrospective cohort study including all pregnant women who received a diagnosis of autoimmune hepatitis or autoimmune sclerosing cholangitis during childhood and followed-up from 1989 to 2021. ResultsFifteen pregnancies in 12 women were observed. The median follow-up from disease onset was 26.7 years. All patients had been treated with prednisone and azathioprine (AZA) as first line therapy. At the beginning of the pregnancy, 11/12 (91.6%) patients were in spontaneous or pharmacologically induced clinical and biochemical remission and one had received a liver transplant. During pregnancy, 8 patients continued azathioprine. No relapse during pregnancy occurred in any patient. One woman presented a flare five months after delivery and a second one, one year after delivery when AZA was discontinued. The 15 pregnancies resulted in 13 livebirths (86.6%) with 9 (69.2%) full-term healthy neonates. Two miscarriages (13.3%) were recorded and cesarean section was performed in 3 women (23%). No congenital malformations were observed. ConclusionsPregnancy in women diagnosed during pediatric age with autoimmune hepatitis or autoimmune sclerosing cholangitis and treated long-term with immunosuppressants is possible with good maternal and neonatal outcomes. Azathioprine allows, in most cases, to maintain remission with a good safety profile. Careful monitoring of these patients during pregnancy is, however, mandatory.

A practical histological approach to the diagnosis of autoimmune hepatitis: experience of an Italian tertiary referral center.

Liver biopsy is crucial for the diagnosis of autoimmune hepatitis (AIH), and new reproducible histological criteria would be highly desirable, especially in acute-on-chronic cases. The aims of the present study were (i) to evaluate the AIH histopathological criteria as a function of the time and modality of AIH onset, and (ii) to validate the count of apoptotic bodies in the portal tracts as a histopathological criterion for AIH diagnosis. Sixty-five patients were retrospectively enrolled: 20 underwent biopsy for the first diagnosis and 45 had a previous histological AIH diagnosis. Biopsies were revised, and all histological variables were collected, including the lymphocytic apoptotic bodies in the portal tracts. Clinical and serological data were revised as well. First-diagnosis patients showed a higher grade of inflammation (p = 0.001), but also worse portal fibrosis (p = 0.001). The apoptotic body count was higher in first-diagnosis patients than in follow-up patients (p = 0.002), and it was strongly correlated to inflammation. Using the apoptotic body count among the simplified AIH score variables, the first-biopsy patients in the “definite” category rose from 42 to 68%. Our results confirm the histopathological criteria proposed by the literature and introduce the count of portal apoptotic bodies for the diagnosis of active AIH, especially in first biopsies without other classic features, as well as in AIH diagnostic score, albeit future studies are required to find a definite cutoff.

Environmental risk factors are associated with autoimmune hepatitis.

BackgroundFailure of immunologic homeostasis and resultant hepatocyte destruction in autoimmune hepatitis (AIH) is likely the result of environmental triggers within a permissive genetic architecture.AimsWe aimed to identify risk factors associated with AIH in a well‐phenotyped AIH cohort.MethodsWe prospectively collected environmental questionnaires from 358 AIH cases and 563 healthy controls. Response frequencies were compared using logistic regression, adjusting for age at recruitment, sex and education.ResultsAIH cases were more likely to ever have a urinary tract infection (UTI) (53.6% vs 33.9%, P < .001) and recurrent UTI (more than 1 per year) (23.5% vs 15.9%, P = .002) compared to controls. Female cases more frequently had ever used oral contraceptives (83.0% vs 73.7%, P = .006), fewer pregnancies (median = 1 vs 3, P < .001) and less often used hormone replacement therapy compared to controls (28.5% vs 60.1%, P < .001). Current smoking was more prevalent in cases (18.9% vs 7.4%, P = .022), yet no difference according to historical smoking behaviours was observed. Finally, cases were less likely to have history of mumps (32.4% vs 53.1%, P = .011) and rheumatic fever (1.1% vs 4.4%, P = .028), but reported higher vaccination frequency to chicken pox (38% vs 28.1%), measles (66.5% vs 39.3%), mumps (58.7% vs 34.6%), rubella (55.3% vs 32.7%), pertussis (59.8% vs 40.1%) and pneumococcus (47.2% VS 39.4%) (P < .002).ConclusionsEnvironmental factors are important in AIH pathogenesis. Replication of these findings and prospective examination may provide new insight into AIH onset and outcomes.

Limitation of the simplified scoring system for the diagnosis of autoimmune Hepatitis with acute onset.

Autoimmune Hepatitis (AIH) is a chronic inflammatory liver disease of unknown aetiology characterized by the presence of autoantibodies, hypergammaglobulinaemia with specific IgG increase and interface hepatitis on liver histology. The clinical course of AIH is classically characterized by fluctuating periods of decreased or increased disease activity and therefore its clinical spectrum is variable ranging from no symptoms to severe acute hepatitis and even fulminant hepatic failure. Acute presentation may not differ from acute hepatitis of other causes and diagnosis can be difficult. We describe our experience on diagnostic performance of the two AIH scoring systems in acute onset of AIH and found that revised version of the original criteria (1999) achieves the diagnosis in about 30% of patients who presented with normal IgG serum levels and lower frequency of autoantibody positivity in whom the simplified score did not allow the diagnosis.

S2656 New Diagnosis of Autoimmune Hepatitis in a Patient With Remote History of SVR From DAA-Based Hepatitis C Treatment

INTRODUCTION: Autoimmune hepatitis (AIH) is characterized by increased aminotransferases, often in the presence of autoantibodies, and biopsy evidence of interface hepatitis. The cause of AIH is not known but it is likely due to a “triggering event” which leads to a T-cell mediated response directed against liver autoantigens. Hepatitis C virus (HCV) and its treatment with direct antiviral agents (DAA) have both has been suspected as risk factors for the development of AIH. We describe a patient with remote history of DAA-cured HCV who later developed decompensated cirrhosis secondary to AIH requiring liver transplantation. This case raises the question as to whether immunologic changes associated with HCV viral clearance are the cause of AIH in some cases. CASE DESCRIPTION/METHODS: A 67-year-old male was referred to our clinic for abnormal liver function tests. He was diagnosed with HCV cirrhosis, treated with 12 weeks of sofosbuvir/ledipasvir and achieved sustained virologic response (SVR). He was well for nearly five years until he developed new-onset ascites and worsening MELD-Na. Acute viral hepatitis serologies for hepatitis A/B/E were negative and HCV RNA levels were undetectable. CT imaging was negative for HCC or thrombus and he denied alcohol use. Smooth muscle IgG antibody was strongly positive and IgG was elevated at 3g/dL; ANA and LKM antibodies were negative. He was on not on any medications traditionally associated with AIH. His liver disease rapidly progressed and he was transplanted without receiving steroids. He is now well post-transplant. Explant biopsy demonstrated interface activity and lobular hepatitis with lymphoplasmacytic inflammation and plasma cells cluster (Figures 1 and 2). DISCUSSION: HCV has been linked to the development of AIH, likely through a process of molecular mimicry whereby the immune system reacts to hepatic autoantigens. While rare, this association has only been documented during active HCV infection or during treatment with DAAs. Our patient had successfully completed treatment for HCV with DAA therapy five years before onset of AIH. We present this case not only to highlight an atypical timeline for development of HCV-induced AIH but to emphasize that providers need to maintain a high index of suspicion for AIH in patients with prior history of HCV treated with DAAs who experience subsequent liver injury.Figure 1.: Low magnification (10x) view of liver section obtained from liver explant, demonstrating interface activity and lobular hepatitis with lymphoplasmacytic inflammation.Figure 2.: Higher magnification (40x) view of the liver section demonstrating plasma cells cluster.

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.

Single-Center North American Experience of Liver Transplantation in Autoimmune Hepatitis: Infrequent Indication but Good Outcomes for Patients.

Background and AimsA 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence.MethodsSingle-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded.ResultsA total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively.ConclusionAlthough AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.

Differences in autoimmune hepatitis based on inflammation localization.

Histopathology is essential for the diagnosis and evaluation of disease activity of autoimmune hepatitis (AIH). We aimed to elucidate the characteristics of AIH from the localization of inflammation. We re-evaluated a nationwide survey that was performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017. A total of 303 patients were enrolled, and the clinical and treatment characteristics were compared between the patients with predominantly portal inflammation (230 patients) or lobular inflammation (73 patients). AIH patients with lobular inflammation had a higher probability of being diagnosed with acute hepatitis than those with portal inflammation. Liver enzyme levels were higher in patients with lobular inflammation, whereas immunoglobulin G levels were higher in patients with portal inflammation. The prevalence of an alanine aminotransferase level < 30 U/L after 6months of treatment was significantly higher in patients with lobular inflammation than in those with portal inflammation (81.7% vs. 67.3%, P = 0.046). The localization of inflammation may be useful for evaluating the onset of AIH.

Soluble PD1 levels are increased with disease activity in paediatric onset autoimmune hepatitis and inflammatory bowel disease

Introduction: Immune mediated liver diseases entail a broad category which are associated with increased morbidity and mortality amongst the paediatric population. Programmed Death 1 (PD1) is an inhibitory receptor mainly expressed by T cells, and when activated shed into plasma as soluble PD1(sPD1). The AIM of this study was to evaluate sPD1 levels in plasma of paediatric patients with Autoimmune Hepatitis (AIH), Primary Sclerosing Cholangitis (PSC), AIH and PSC overlap, Inflammatory Bowel Disease (IBD) alone, and concurrent PSC/IBD and AIH/IBD in order to identify a biomarker to response or predict relapse verses remission.Methods: Plasma samples were collected from 41 paediatric patients. AIH patients were further categorized into active, incomplete responders and responders, based on response to standard therapy. sPD1 levels were measured and compared between PSC, PSC/AIH, IBD alone, PSC/IBD and AIH/IBD patients and between active AIH, incomplete responders and responders. Flow cytometry was performed to further analyze CD45RA+, CD3CD4, CD8, CCR7, CXCR3, CD38 and PD1.Results: In the AIH group, those with active disease demonstrated a significantly higher sPD1 levels in comparison to responders (*p > .001). However, the incomplete responders didn’t show a reduction in sPD1 in comparison to active AIH and patients with IBD alone. Interestingly, patients with PSC showed significantly lower level of sPD1 compared to active AIH (*p < .002), whereas, patients with PSC in conjunction with AIH (*p < .006) or IBD (*p < .02) demonstrated a significant increase in sPD1. In addition, we have observed increased levels of circulating CD4 and CD8 bound PD1 in active AIH but not in PSC or responders suggesting T cells activation. CD4+ PD1 double positive cells demonstrated increased expression of CXCR3. Thus, suggesting the activation of PD1 + T cells is mediating through CXCR3 in Autoimmune hepatitis.Conclusions: Our study demonstrates that sPD1 levels correlate with active disease state of AIH and IBD. sPD1 levels did not correlate with PSC. However, PSC in conjunction with AIH or IBD showed higher levels of sPD1. This suggests that T cell activation plays a critical role in active AIH and IBD but not in PSC. Soluble PDI levels could be used as a clinical biomarker to assess response in patients with AIH and for prospectively monitoring PSC patients for development of IBD or AIH.