Introduction
Autoimmune hepatitis (AIH) is a rare and complex disease first described in Sweden in 1950. Its pathogenesis remains incompletely understood, but it is known that hepatocyte injury occurs through an inflammatory cascade triggered by an alteration in the immune system involving antigenic tolerance in genetically predisposed individuals. The presentation spectrum is broad, ranging from mild hepatitis to acute liver failure, though the latter is infrequent. Approximately 30% of patients exhibit insidious and asymptomatic disease, while nearly 70% may present with cirrhosis. Treatment primarily involves immunosuppression, resulting in a favorable biochemical response for most patients. However, complete histological remission and corticosteroid-free remission are less common.
Study Objectives
This study investigates clinical and biochemical markers associated with response to immunosuppression in patients with AIH. The secondary aim is to describe the epidemiological profile of AIH in this population, including the severity of presentation, relapses, liver transplant rates, and mortality.
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.
Clinical Features at Disease Onset
The overall cohort comprised 102 patients with clearly diagnosed AIH, of whom 80.3% were women, with a median age at disease onset of 24.5 years (2.5−71.0 years). At diagnosis, 59% of the patients presented with cirrhosis, most exhibiting clinically significant portal hypertension. Most showed significant alterations in aminotransferases, positive autoantibodies, moderate to severe inflammatory activity, and fibrosis upon biopsy.
Outcome Rates and Time Occurrence
Biochemical remission one year after diagnosis occurred in 55.7% of patients. Cirrhosis was associated with lower odds of remission. The histological remission rate was even lower at 30.3%. In this population, 5.9% required a liver transplant; one patient died 26 months post-procedure due to complications, while the other five remained alive without disease relapse. Mean transplant-free survival was 304 months, with an 82% cumulative rate at 336 months. Biochemical remission within one year is associated with higher transplant-free survival.
Discussion
This study reports a high frequency of cirrhosis at disease onset, which was associated with older age and a reduced chance of achieving one-year biochemical remission. The biochemical and histological remission rates were lower compared to North American and European data, suggesting that AIH has an aggressive phenotype among Brazilians. One-year biochemical remission was a protective factor for a liver transplant performed in 6% of patients. Ascites at disease onset was associated with a higher AST/ALT ratio and elevated MELD score. The presence of ascites represented a significant increase in mortality rate by 20 times.
Gender and Age Variability
The female-to-male ratio was found to be 5:1, higher than the ratio reported in international literature of 2−4:1. A study conducted at King’s College showed a better long-term prognosis and survival in male patients, while in Colombia, a higher proportion of men developed cirrhosis due to AIH. Nevertheless, we did not find any association between gender and prognosis. The age variability was very wide, ranging from 2.5 to 71 years, showing that AIH diagnosis is possible regardless of age. In South America, 76.5% of patients are diagnosed under 25 years old, while in North America, the median age at diagnosis is 48 years old.
Histological and Biochemical Remission
The one-year biochemical (55.7%) and histological (30.3%) remission rates were low but similar to the University of Sao Paulo cohort that reports 51.5% and 36.2%. Higher remission rates have been reported, such as 66−91% and 25−80% for biochemical and histological remission, respectively. The lower rates of treatment response seen in Latin American studies of AIH may be attributed to several factors, including a higher prevalence of cirrhosis, more severe hepatitis, and younger age at onset. In addition, different susceptibility HLA alleles may present in this geographic region, which could also contribute to treatment outcomes.
Conclusion
In conclusion, AIH presents an aggressive clinical phenotype in Brazilians, with high rates of cirrhosis at disease presentation and lower remission rates. This study highlights the need for early diagnosis and treatment, ideally in a pre-cirrhotic stage, to improve the chances of achieving biochemical remission. The significant association between ascites and mortality emphasizes the importance of monitoring patients for the development of ascites and prompt intervention if it occurs.
Overall, multicentric research is needed to understand better the prognostic factors of AIH in Brazil and Latin America. This will require increased funding, collaboration between researchers and healthcare providers, and the development of standardized diagnostic criteria and treatment guidelines for this condition in the region.
Funding
This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author Contributions
Conceptualization: L.R.G., G.G.L.C, F.M.F.O., L.C.F, C.A.C. Formal Analysis: L.R.G. Investigation: L.R.G., B.C.S., L.S.J. Writing −Original Draft Preparation: L.R.G., G.G.L.C., M.J.N. Writing −Review & Editing: L.R.G., G.G.L.C., L.C.F., C.A.C. Responsible for integrity: L.R.G.
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