Prevalence of Acute on Chronic Liver Failure in Autoimmune Hepatitis, Treatment Response and Mortality Burden Assessment: A Region-Predominant Systematic Review and Meta-Analysis.

Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.

Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [ p <0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [ p <0.05]). There were no differences in the 1-, 3-, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p =0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [ p >0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Clinical, biochemical and histological features related to treatment response and prognosis in autoimmune hepatitis.

INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a rare disease with a complex and not fully understood pathogenesis. Prognostic factors that might influence treatment response, relapse rates, and transplant-free survival are not well established. This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. MATERIALS AND METHODS: This retrospective cohort study included 102 patients with AIH treated with immunosuppressants and followed at the Federal University of Minas Gerais, Brazil, from 1990 to 2018. Pretreatment data such as clinical profiles, laboratory, and histological exams were analyzed regarding biochemical response at one year, histological remission, relapse, and death/transplantation rates. RESULTS: Cirrhosis was present in 59 % of cases at diagnosis. One-year biochemical remission was observed in 55.7 % of the patients and was found to be a protective factor for liver transplant. Overall survival was 89 %. Patients with ascites at disease onset showed a higher aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio and elevated Model of end-stage liver disease (MELD) score. The presence of ascites was significantly associated with a 20-fold increase in mortality rate. CONCLUSIONS: AIH has a severe clinical phenotype in Brazilians, with high rates of cirrhosis and low remission rates. Early diagnosis and treatment are essential for achieving remission and reducing complications. The presence of ascites is significantly associated with mortality, emphasizing the importance of monitoring and prompt intervention. This study also stresses the need for further research on AIH in Latin America.

Treatment response and clinical event-free survival in autoimmune hepatitis: A Canadian multicentre cohort study.

BACKGROUND & AIMS: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH. METHODS: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. RESULTS: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. CONCLUSION: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. IMPACT AND IMPLICATIONS: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects.

Influence of socioeconomic factors on liver transplant survival outcomes in patients with autoimmune liver disease in the United States.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs): autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) have different survival outcomes after liver transplant (LT). Outcomes are influenced by factors including disease burden, medical comorbidities, and socioeconomic variables. MATERIALS AND METHODS: Using the United Network for Organ Sharing database (UNOS), we identified 13,702 patients with AILDs listed for LT between 2002 and 2021. Outcomes of interest were waitlist removal, post-LT patient survival, and post- LT graft survival. A stepwise multivariate analysis was performed adjusting for transplant recipient gender, race, diabetes mellitus, model for end-stage liver disease (MELD) score, and additional social determinants including the presence of education, reliance on public insurance, working for income, and U.S. citizenship status. RESULTS: Lack of college education and having public insurance increased the risk of waitlist removal (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.09; 95 % CI, 1.00-1.18; respectively), and negatively influenced post-LT patient survival (HR, 1.16; 95 % CI, 1.06-1.26, and HR, 1.15; 95 % CI, 1.06-1.25; respectively) and graft survival (HR, 1.13; 95 % CI, 1.05-1.23, and HR, 1.15; 95 % CI, 1.06-1.25; respectively). Not working for income proved to have the greatest detrimental impact on both patient survival (HR, 1.41; 95 % CI, 1.24-1.6) and graft survival (HR, 1.21; 95 % CI, 1.09-1.35). CONCLUSIONS: Our study highlights that lack of college education and public insurance have a detrimental impact on waitlist mortality, patient survival, and graft survival. Not working for income negatively affects post-LT survival outcomes. Not having U.S. citizenship does not affect survival outcomes in AILDs patients.

Hepatitis autoinmune en niños: clínica y manejo / Autoimmune hepatitis in children: clinical and management

La hepatitis autoinmune (HAI), es una enfermedad inflamatoria crónica y progresiva, que se caracteriza histológicamente por un denso infiltrado de células mononucleares en vías portales, y cuya patogenia se le atribuye a una reacción inmune frente a autoantígenos hepatocelulares demostrado serológicamente por la presencia de autoanticuerpos específicos y aumento en los niveles de las aminotransferasas y de inmunoglobulina tipo IgG, en ausencia de una etiología conocida. Son reconocidos dos tipos de HAI en la infancia: HAI tipo I, que se caracteriza por la presencia de anticuerpos (anti músculo liso SMA) y/o antinucleares (ANA), y la HAI tipo II,que se caracteriza por anticuerpos antimicrosomales de riñón hígado (anti-LKM). La etiología de la HAI es desconocida, aunque tanto factores genéticos como ambientales están implicados en su expresión. El fenotipo clínico de la HAI en niños varía en gran medida, va desde una evolución leve a un curso fulminante. La HAI es sensible a la terapia inmunosupresora. El trasplante hepático está indicado en pacientes que presentan insuficiencia hepática fulminante (encefalopatía) y los que desarrollan enfermedad hepática terminal.

Autoimmune hepatitis (HAI) is a chronic and progressive inflammatory disease, characterizedhistologically by a dense infiltrate of mononuclear cells in the process portals, and whose pathogenesis is attributed to an immune response against hepatocellular autoantigens demonstratedserologically by the presence of specific autoant ibodies and increased levels of aminotransferases and immunoglobulin IgG, in the absence of known etiology. Recognized two types of HAI in childhood: type I, characterized by the presence of antibodies (smooth muscle anti SMA) and / or antinuclear (ANA) and type II, characterized by anti-microsomal antibodies liver kidney (anti-LKM). The etiology of HAI is unknown, a l though both gene t i c and environmental factors are involved in its expression. The clinical phenotype of the HAI in children varies greatly, ranging from a slight evolution to a fulminant course. The HAI is sensitive to immunosuppressive therapy. Liver transplantation is indicated in patients with fulminant hepatic failure (encephalopathy) andthose who develop end-stage liver disease.