Persistent normalization of serum alanine aminotransferase levels improves the prognosis of type 1 autoimmune hepatitis

doi:10.1016/j.jhep.2005.06.006

Journal of Hepatology

Volume 43, Issue 6, December 2005, Pages 951-957

https://doi.org/10.1016/j.jhep.2005.06.006 Get rights and content

Background/Aims

Autoimmune hepatitis shows a good response to immunosuppressive treatment, and the prognosis may be determined by the clinical course. The present study was conducted in order to analyze the factors contributing to the outcomes of patients with type 1 autoimmune hepatitis.

Methods

Eighty-four consecutive patients with type 1 autoimmune hepatitis were followed up regularly for a median follow-up period of 70.5 months (16.2–163 months). We analyzed the prognostic factors using time-fixed and time-dependent Cox proportional hazard models. The end point was progression of the disease to decompensated liver cirrhosis.

Results

Seventy-seven patients (92%) were treated with prednisolone during the follow-up period, and 11 patients (13%) developed decompensated liver cirrhosis. Using a time-dependent multivariate model, the starting dose of corticosteroid (dose of prednisolone <20 mg/day), relapse within 3 months after the normalization of serum alanine aminotransferase levels with initial treatment, and elevated serum alanine aminotransferase levels during the follow-up period (>40 IU/L), all showed a significant association with progression of the disease.

Conclusions

The prognosis of type 1 autoimmune hepatitis on adequate immunosuppressive treatment improves when the serum alanine aminotransferase level persists at ≤40 IU/L. Factors existing prior to medical treatment may not affect the prognosis.

Introduction

Autoimmune hepatitis is a chronic, mainly periportal, hepatitis associated with hypergammaglobulinemia and circulating autoantibodies [1]. It shows a striking female preponderance. The natural history and prognosis of autoimmune hepatitis were reported during the 1960s and 70s. Patients with biochemical or histological indicators of severe autoimmune hepatitis, such as a high alanine aminotransferase level, hypergammaglobulinemia (>2-fold the upper normal limit), or bridging or multilobular necrosis, exhibit a 5-year mortality of 50%, and a 10-year mortality of 90%, if untreated [2], [3], [4], [5].

The response to immunosuppressive treatment is generally good in patients with autoimmune hepatitis. Complete biochemical and histological resolution of inflammation is achieved in 87% of patients within 3 years after the introduction of medical treatment [6]. Even in patients with established liver cirrhosis, appropriate treatment improves the histological fibrosis, and the 10-year life expectancy exceeds 90% [7], [8]. These facts show that prognosis may not be determined by factors existing prior to medical treatment, but by the response to medical treatment.

Recent studies have revealed that a time-dependent proportional hazard model is useful to estimate the prognosis of primary sclerosing cholangitis and primary biliary cirrhosis [9], [10]. Such models incorporate follow-up data, and can be used to update a patient's prognosis based on changes in the clinical condition.

Since estimation of the prognosis of type 1 autoimmune hepatitis using a time-dependent model has yet to be fully implemented, we analyzed the factors contributing to the prognosis using a time-dependent Cox proportional hazard model.

Section snippets

Patients

Ninety-nine consecutive patients with type 1 autoimmune hepatitis were admitted to Okayama University Hospital and seven affiliated hospitals between November 1988 and June 2001. All patients, who were seronegative for hepatitis B surface antigen, anti-hepatitis C virus antibody, hepatitis C virus-RNA (as determined via polymerase chain reaction after reverse transcription), and anti-mitochondrial antibody, underwent liver biopsy and were graded according to the revised scoring system proposed

Clinical and laboratory findings of 84 patients with type 1 autoimmune hepatitis

The clinical and laboratory findings are shown in Table 1A, Table 1B. Forty-nine asymptomatic patients (58%) were diagnosed with autoimmune hepatitis at a general medical checkup, and 37 of them satisfied the criteria of a definite diagnosis of autoimmune hepatitis. The other 35 patients (42%) visited the hospitals with symptoms, such as jaundice, general fatigue, and poor appetite, and 27 of them satisfied these criteria. Twenty-two patients (26%) had symptomatic concurrent autoimmune disease:

Discussion

This study shows that the disease progresses to liver failure in some patients despite immunosuppressive treatment, although the prognosis of patients with type 1 autoimmune hepatitis is generally good with corticosteroid treatment, and that the starting dose of corticosteroid (dose of prednisolone <20 mg/day), relapse within 3 months after the normalization of serum alanine aminotransferase levels with initial treatment, and elevated serum alanine aminotransferase levels during the follow-up

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Persistent normalization of serum alanine aminotransferase levels improves the prognosis of type 1 autoimmune hepatitis

Background/Aims

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Clinical and laboratory findings of 84 patients with type 1 autoimmune hepatitis

Discussion

J Hepatol

Lancet

Gastroenterology

Gastroenterology

J Hepatol

Gastroenterology

Hepatology

Gastroenterology

Gastroenterology