What are the predictors of relapse of autoimmune hepatitis after stopping treatment, presenting with thigh pain?

From the Guidelines

Relapse of autoimmune hepatitis (AIH) after stopping treatment is highly likely, with 50-90% of patients experiencing a disease relapse within 12 months, and thigh pain is not a established predictor of AIH relapse. The predictors of relapse in AIH after treatment cessation include elevated liver enzymes (particularly ALT/AST) at the time of medication withdrawal, incomplete histological remission, and shorter duration of treatment before discontinuation 1. Patients who have not maintained normal liver enzymes for at least a period before stopping treatment are at higher risk of relapse. Other risk factors include presence of continuing active inflammation prior to treatment withdrawal, as evidenced by persistent elevation of serum transaminases and/or serum globulins and IgG, and persistence of plasma cells in portal tracts on liver biopsy 1.

Key Points to Consider

• Relapse is more likely in patients who have been slow in achieving biochemical remission 1
• Only 30% of patients with complete resolution of AIH on follow-up liver biopsy relapse 1
• Relapse also appears to be uncommon when there is an identifiable precipitant for the initial presentation such as a drug 1
• Careful monitoring of liver enzymes, IgG levels, and clinical symptoms is recommended every 3 months for at least a year after treatment discontinuation to detect early signs of relapse
• The connection to thigh pain is not established as a predictor of AIH relapse, as thigh pain is not typically associated with liver disease recurrence, however, patients on long-term corticosteroid therapy for AIH may experience musculoskeletal symptoms including thigh pain due to steroid-induced myopathy or avascular necrosis of the femoral head 1

Management of Relapse

• Patients who relapse should be retreated as for the first presentation of AIH 1
• Once in remission they should be given maintenance azathioprine, if tolerated 1
• In patients who relapse on azathioprine maintenance therapy, low-dose prednisolone (in addition to azathioprine) may be continued long-term after remission is re-attained 1

From the Research

Predictors of Relapse

The predictors of relapse of autoimmune hepatitis after stopping treatment are:

• Previous combination therapy of corticosteroids and azathioprine 2
• Concomitant autoimmune disease 2
• Younger age at time of drug withdrawal 2
• Incomplete normalization of biochemistry in the presence of normal histology, nonspecific portal hepatitis, or inactive cirrhosis 3

Relapse Rates

Relapse rates after treatment withdrawal are high, with:

• 47% of patients relapsing during follow-up 2
• 42% of patients experiencing a loss of remission 2
• 59% of patients requiring retreatment one year after drug withdrawal, increasing to 73% and 81% after 2 and 3 years, respectively 2
• Up to 90% of patients experiencing relapse after drug withdrawal, even in patients with established histological remission 4

Treatment Strategies

Treatment strategies for autoimmune hepatitis include:

• Long-term treatment with corticosteroids and/or azathioprine 2, 4
• Combination regimen of prednisone and azathioprine as preferred treatment 5, 6
• Low-dose prednisone or azathioprine therapy after multiple relapses 5, 6
• Consideration of life-long maintenance therapy in patients with multiple relapses 4