Is hepatitis serology justified before starting Methotrexate (MTX)?

From the Guidelines

Yes, hepatitis serology testing is justified before starting methotrexate (MTX) to minimize the risk of liver damage and exacerbation of existing viral hepatitis. MTX is a potent immunosuppressive and hepatotoxic medication that can cause liver damage and potentially exacerbate existing viral hepatitis. Prior to initiating MTX therapy, patients should undergo baseline hepatitis B virus (HBV) and hepatitis C virus (HCV) serologic testing, including HBsAg, anti-HBc, anti-HBs, and anti-HCV antibodies, as recommended by the British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016 1. This screening is essential because MTX can reactivate latent HBV infection or worsen active hepatitis, leading to severe liver damage or even fulminant hepatic failure in some cases. For patients with positive hepatitis serology, consultation with a hepatologist is recommended to determine appropriate management, which may include antiviral prophylaxis before starting MTX, as suggested by the 2020 joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies 1.

Key Considerations

• Hepatitis B and C screening should be performed before initiating MTX therapy, considering the individual patient's risk factors 1.
• Patients with active hepatitis may need alternative treatment options instead of MTX, and those with past infection should be aware of the low risk of reactivation of the infection while on treatment 1.
• Regular liver function monitoring is necessary during MTX therapy, with testing typically performed every 1-3 months depending on risk factors and treatment duration.
• The long-term effects of MTX on chronic hepatitis C are unknown, but both hepatitis C and MTX can cause hepatic fibrosis, potentially leading to a synergistic effect and more rapid progression of liver fibrosis 1.

Recommendations

• Hepatitis serology testing, including HBsAg, anti-HBc, anti-HBs, and anti-HCV antibodies, should be performed before starting MTX to minimize the risk of liver damage and exacerbation of existing viral hepatitis.
• Consultation with a hepatologist is recommended for patients with positive hepatitis serology to determine appropriate management.
• Regular liver function monitoring and consideration of alternative treatment options are necessary to ensure safer use of MTX therapy.

From the FDA Drug Label

Pretreatment liver biopsy should be performed for patients with a history of excessive alcohol consumption, persistently abnormal baseline liver function test values or chronic hepatitis B or C infection

Methotrexate therapy may be associated with an increased risk of hepatotoxicity, particularly in patients with a history of liver disease or chronic hepatitis B or C infection.

• Hepatitis serology is justified before starting methotrexate in patients with a history of liver disease or chronic hepatitis B or C infection.
• The presence of hepatitis B or C infection is a risk factor for hepatotoxicity, and pretreatment liver biopsy should be performed in these patients 2.
• Patients with chronic hepatitis B or C infection should be closely monitored for signs of hepatotoxicity during methotrexate therapy 2.

From the Research

Hepatitis Serology Before Starting Methotrexate (MTX)

• The decision to perform hepatitis serology before starting MTX is crucial in preventing hepatitis B reactivation, especially in patients with a history of hepatitis B infection 3, 4, 5.
• A study found that long-term use of MTX does not result in hepatitis B reactivation in rheumatologic patients, but it is essential to screen for HBV seromarkers before starting treatment 3.
• Another study recommended that HBV-infected patients should be referred to a hepatologist for expert clinical management whenever antiviral therapy is deemed necessary or hepatitis reactivation occurs 4.
• The screening of patients before biological treatment and the application of a prophylactic treatment, particularly with respect to latent HBV infections, are recommended when necessary 5.
• Isolated anti-HBc (IAHBc) is a particular serological pattern that is commonly found in immunocompromised patients, and the risk of HBV reactivation depends on host factors and viral factors 6.
• A case report highlighted the importance of screening for HBV before starting MTX, as a patient with rheumatoid arthritis developed de-novo hepatitis B virus-related hepatitis after MTX therapy 7.

Risk of Hepatitis B Reactivation

• The risk of hepatitis B reactivation is higher in patients with a history of hepatitis B infection, especially those who are HBsAg positive or have positive HBV seromarkers 3, 4.
• Patients with isolated anti-HBc are at risk of HBV reactivation, especially if they are immunocompromised or receiving immunosuppressive therapy 6.
• The use of MTX can increase the risk of HBV reactivation, especially in patients with a history of hepatitis B infection 3, 7.

Recommendations

• Patients should be screened for HBV seromarkers before starting MTX, especially if they have a history of hepatitis B infection or are immunocompromised 3, 4, 5.
• Prophylactic treatment should be considered for patients with positive HBV seromarkers or those who are at high risk of HBV reactivation 4, 5.
• Patients with isolated anti-HBc should be monitored closely for signs of HBV reactivation, and prophylactic treatment should be considered if necessary 6.