Natural History Of Autoimmune Hepatitis 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.

1013 The Effect of Steatosis on the Clinical Course of Autoimmune Hepatitis

INTRODUCTION: Nonalcoholic Fatty Liver Disease (NAFLD) is a common liver disease in western developed countries. NAFLD is increasingly encountered alongside other chronic liver diseases, such as autoimmune hepatitis (AIH). The impact of NAFLD on the clinical course of AIH is unclear and one recent single center study suggested a worse clinical outcome for patients with AIH and concurrent steatohepatitis. We aimed to determine the frequency of steatosis and steatohepatitis in patients with AIH and the effect on treatment outcomes. METHODS: The cohort consisted of 61 AIH patients from a single, large, tertiary referral center with pre-treatment liver biopsies and available clinical data. Biliary overlap syndromes were excluded. Two liver pathologists recorded histological findings, including quantification of steatosis and steatohepatitis. One clinical reviewer recorded 96 clinical/laboratory variables. Non-parametric (Spearman rho) tests were used and correlations with P < 0.05 were deemed significant. Non parametric t-tests were used to compare various degrees of steatosis (none, mild/moderate) with clinical variables and P < 0.05 were deemed significant. RESULTS: Patients were followed for mean of 3.1 ± 3 years after diagnosis. Mean age at diagnosis was 49.9 ± 19.1 years and mean BMI at diagnosis was 28.3 ± 7. In this cohort, 31.7% of patients had steatosis on histology, and out of those 75.0% had mild and 25.0% had moderate degree of steatosis. Strikingly, there were no cases of steatohepatitis. The degree of steatosis was positively correlated with increasing age and BMI, (r = 0.44, CI 0.17-0.65, P ≤ 0.001and r = 0.49, CI 0.15-0.73, P = 0.01, respectively). However, there was no correlation between degree of steatosis and initial treatment failure, ALT at 12 months of treatment, chances of biochemical remission, development of cirrhosis, or the dose of steroid required for biochemical remission. Furthermore, there was no difference in these outcomes when those with versus without steatosis were compared. CONCLUSION: Data from this single center study suggest that AIH patients with mild and moderate steatosis have the same clinical course and response to treatment as those without steatosis.. The increasing prevalence of superimposed NAFLD in AIH warrants longitudinal observational multi-center studies focused on the frequency of steatohepatitis, and the impact of steatosis on the natural history of AIH.

Increased incidence of autoimmune hepatitis is associated with wider use of biological drugs.

Population-based studies on the epidemiology of autoimmune hepatitis (AIH) are scarce. Drug-induced AIH (DIAIH) is increasingly recognized in association with immunomodulatory therapy. We aimed to determine the incidence, prevalence and natural history of AIH in a population-based setting. We collected data of new diagnosis of AIH in Iceland from 2006 to 2015. Cases were identified through search of diagnostic codes and text search for AIH within electronical medical records of all hospitals in Iceland and through records of smooth muscle antibodies (SMA) test results by the only laboratory in the country analyzing SMA. Patients were included in the final analysis if they received the clinical diagnosis of AIH or were started on immunosuppressive therapy. The mean annual incidence of AIH in Iceland was 2.2 cases per 100000 inhabitants. Point prevalence on 31 December 2015 was 27/100000. The median age at diagnosis was 56years and 86% of patients were of female gender. DIAIH was suspected in 13 of 71 patients (18%) of which eight cases were related to infliximab. Immunosuppressive treatment was started in all but two patients. At the end of follow-up (median 4.8years) 66 of 71 (93%) patients were alive. The incidence and prevalence rates of AIH in Iceland are the highest reported so far in a population-based setting. Higher incidence can partly be explained by the increasing use of biological drugs. Immunosuppressive therapy was very effective in achieving remission and prognosis was favorable.

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.

Autoimmune hepatitis in children—Impact of cirrhosis at presentation on natural history and long-term outcome

Little is known regarding the natural history of autoimmune hepatitis in children. The aims of this longitudinal cohort study were to determine the long-term prognosis of children with autoimmune hepatitis and to determine the effect of cirrhosis at presentation on survival. Methods Thirty-three children with autoimmune hepatitis who were seen at our institution over a 25-year period were studied retrospectively. Results The median age of diagnosis was 12.9 years (2.7–18.1) with a female predominance of 3:1. Liver biopsies showed cirrhosis in 18 (55%) patients at time of diagnosis. Patients with cirrhosis at baseline had a similar 10-year survival 85% (70–100%) to those without cirrhosis 75% (49–100%) ( p = 0.97). The overall survival was significantly lower than the expected in the age- and gender-matched U.S. population (log-rank test; p < 0.001). In Cox regression models, weight loss ( p = 0.037), baseline elevated bilirubin ( p = 0.028), prolonged International Normalized Ratio (INR) ( p = 0.013), and positive LKM-1 antibodies ( p = 0.007) were associated with shorter survival. Conclusion AIH in children is associated with a significant shorter survival rate than the expected in the general population. Cirrhosis on initial liver biopsy does not seem to impact long-term survival in children with AIH.

Liver failure as initial presentation of autoimmune hepatitis: Clinical characteristics, predictors of response to steroid therapy, and outcomes

In a recent study, we had reported the impact of ethnicity on the natural history of autoimmune hepatitis (AIH).1 We did a further subgroup analysis of those with initial presentation with liver failure (LF), defined as either international normalized ratio (INR) ≥ 2 and or any degree of hepatic encephalopathy. Twenty patients (20/101, 19.8%) presented with LF, and they were more likely to be black (70% versus 7.4%, P = 0.001), require referral for liver transplantation (LT) (70% versus 24.6%, P < 0.0001), and have a higher mortality (45% versus 4.9%, P < 0.0001), compared to those without LF. Of the 14 (70%) patients with LF who were treated medically with steroids, seven (50%) responded (Table 1). Responders had a Model for End-Stage Liver Disease (MELD) score at admission ≤ 28 and were more likely to have cirrhosis (71.1% versus 28.5%); they showed a stable trend in serum bilirubin (mg/dL) (15.2 ± 13.2 versus 14.1 ± 14.1) and INR (1.8 ± 0.4 versus 1.8 ± 0.5) after a mean of 3.7 ± 0.6 days of steroid therapy. In contrast, nonresponders showed a worsening of serum bilirubin (22.5 ± 4.2 versus 23.1 ± 5.6) and INR (3.0 ± 1.5 versus 3.6 ± 2.1). All responders survived without need for a LT, whereas all nonresponders had a fatal outcome (of whom one died after LT). Six patients (30%) with LF were not treated medically, of whom five had submassive necrosis on liver biopsy. Five of these six patients underwent transplantation and all but one survived. One could not undergo transplantation due to development of fatal cholangitis. In conclusion, about 20% of patients with AIH have LF at initial presentation. A lower MELD score at admission (≤ 28), more severe hepatic fibrosis, and an early (within 4 days of steroid therapy) improvement or stabilization in serum bilirubin and INR identify those who are likely to respond to steroid therapy, and thus survive without LT. Our observations need further corroboration, but if confirmed, such a stratification strategy could optimize care of patients with AIH who present with LF. Sumita Verma*, Anurag Maheshwari , Paul Thuluvath , * Gastroenterology/Hepatology, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, UK, Gastroenterology and Hepatology, Johns Hopkins University Hospitals, Baltimore, MD, Mercy Medical Center, Institute for Digestive Health and Liver Diseases, Baltimore, MD.

The impact of ethnicity on the natural history of autoimmune hepatitis

The impact of ethnicity on the natural history of autoimmune hepatitis (AIH) has not been well characterized. The aim of this study was to assess the natural history of AIH in blacks in comparison with others (nonblacks). This was a 10-year (June 1996 to June 2006) retrospective analysis of patients with AIH from a single tertiary care center. The diagnosis of AIH was defined by the criteria established by the International Autoimmune Hepatitis Club. A poor outcome was defined as liver failure at presentation, failure to achieve remission, need for liver transplantation, and/or death. One hundred one patients with AIH were eligible for the study. Black patients were more likely to have cirrhosis (56.7% versus 37.5%, P = 0.061), have liver failure at the initial presentation (37.8% versus 9.3%, P = 0.001), and be referred for liver transplantation (51.3% versus 23.4%, P = 0.004). The overall mortality was also significantly higher in black patients (24.3% versus 6.2%, P = 0.009). Compared with nonblacks, blacks had more advanced hepatic fibrosis (3.6 +/- 2.7 versus 2.1 +/- 2.4, P = 0.013). A Kaplan-Meier analysis showed that the probability of developing a poor outcome was significantly higher in blacks (P = 0.003). Independent predictors of poor outcome were black ethnicity, the presence of cirrhosis, and the fibrosis stage at presentation. Black males were the group most likely to have a poor outcome (85.7%). Blacks, especially black men with AIH, have more aggressive disease at the initial presentation, are less likely to respond to conventional immunosuppression, and have a worse outcome than nonblacks.

Cirrhosis-associated mortality: Frankly, Scarlet, do we really make a damn?

Cirrhosis-associated mortality: Frankly, Scarlet, do we really make a damn?

Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome

Although the natural history of autoimmune hepatitis (AIH) has been characterized, little is known about patients who present asymptomatically. Consequently, whether they require immunosuppressive therapy with its associated complications is unclear. To compare the natural history of asymptomatic AIH with symptomatic AIH, a large cohort of patients from a single center was examined. All patients with a clinical diagnosis of AIH were reassessed using the revised criteria of the International Autoimmune Hepatitis Group. Liver histology, response to therapy, and survival were assessed. Patients asymptomatic at presentation (n = 31) had lower serum aminotransferase, bilirubin, and immunoglobulin G (IgG) values at baseline. Half of the asymptomatic patients received no therapy, and their survival was no different from that of the total cohort. Ten-year survival was 80.0% (62.5%-97.5%) in the asymptomatic group and 83.8% (75.1%-92.6%) in the symptomatic patients (P = NS). Survival to liver-related endpoints at 10 years was similar in both groups: 89.5% (75.7%-100%) asymptomatic and 83.8% (75.1%-92.6%) symptomatic patients (P = NS). Patients with cirrhosis at baseline had poorer 10-year survival (61.9% [CI 44.9%-78.9%]) than those without cirrhosis at presentation (94.0% [CI 87.4%-100%]) (P = .003) regardless of whether they presented with symptoms or whether they received immunosuppressive therapy. In conclusion, patients with AIH who are asymptomatic at presentation have a good prognosis and may not require immunosuppressive therapy. Cirrhosis on initial liver biopsy portends a poor prognosis in all patients with AIH.

Review article: immunopathogenetic and therapeutic aspects of autoimmune hepatitis.

Autoimmune hepatitis is a chronic, progressive liver disease that responds well to immunosuppressive therapy, but has a poor prognosis if untreated. Possible triggering factors include viruses, other autoimmune disorders and drugs. The molecular mechanisms contributing to the pathogenesis include: reactions of autoantibodies against their corresponding autoantigens; aberrant expression of histocompatibility antigen class I and II molecules, cell adhesion molecules and cytokines; increased oxidative stress; and the occurrence of angiogenesis. The prevalence of the disease is highest in Caucasians, Europeans and women. The natural history of autoimmune hepatitis shows a poor prognosis, with frequent progression to cirrhosis and hepatic insufficiency in untreated patients. The occurrence of hepatocellular carcinoma is rare and is found only in long-standing cirrhosis. Corticosteroids as monotherapy or in combination with azathioprine are the treatments of choice; different therapeutic schedules and particularities of treatment for pregnant women and children have been established. To avoid treatment-associated adverse effects, alternative therapies have been proposed, including ciclosporin, budesonide, tacrolimus, mycophenolate mofetil, ursodeoxycholic acid, methotrexate, cyclophosphamide, mercaptopurine and free radical scavengers. Liver transplantation is indicated for patients refractory to or intolerant of immunosuppressive therapy.

Autoimmune hepatitis

OBJECTIVE: To review an update of autoimmune hepatitis in children, based on classification, diagnostic and therapeutic criteria. METHODS: Articles on the theme were selected and updated, and the author's experience at the Liver Unit, Children's Hospital, School of Medicine, Universidade de São Paulo, was considered as well. RESULTS AND CONCLUSIONS: Autoimmune hepatitis has clinical features suggestive of acute viral hepatitis; however, other clinical features, laboratory tests, endoscopic and histological findings pointed to chronic liver disease, and the majority of the cases evolved to hepatic cirrhosis. The treatment with corticosteroids and/or azathioprine altered the natural history of autoimmune hepatitis, and the survival was 80% in 10 years, although hepatic cirrhosis was present at the beginning, without hepatic decompensation.