A multi-society panel released new guidance on managing liver disease in patients with congenital bleeding disorders.

In 2022, the World Federation of Hemophilia estimated that 427,685 patients may have bleeding disorders globally, 86% of whom may be affected by hemophilia A or B or von Willebrand disease.

The guidelines, published in the Journal of Thrombosis and Haemostasis, provided recommendations for protecting liver health and managing liver complications in this patient population.

Among the key recommendations were:

• All patients exposed to clotting factor concentrates or blood products should be tested at least once for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.
• Patients with abnormal liver tests or risk factors for nonviral liver diseases should be screened for steatotic liver disease and other etiologies.
• Those with active HBV/HCV infections should be managed by a hepatologist or infectious disease specialist for antiviral treatment.
• Patients who have cleared HBV/HCV infections should still be evaluated for signs of advanced chronic liver disease and additional risk factors.
• Noninvasive tests like Fibroscan and blood-based markers should be used to assess patients for advanced fibrosis/cirrhosis when chronic liver disease is diagnosed.
• Patients with decompensated cirrhosis should be evaluated for liver transplantation using standard criteria.

The guidelines noted that obesity, diabetes, and excess alcohol intake are frequently observed in patients with bleeding disorders and can contribute to liver disease risk.

For noninvasive testing, the guidelines recommended using FIB-4 score ≥ 1.30 as a first-line diagnostic tool to identify patients who may benefit from liver stiffness measurement.

Clinically significant portal hypertension was defined as hepatic venous pressure gradient ≥ 10 mmHg and can be detected noninvasively using liver stiffness measurement and platelet count.

The guidelines also provided recommendations on liver assessment prior to and following gene therapy for hemophilia. It suggested detailed hepatic workup before gene therapy to rule out chronic active hepatitis and advanced fibrosis/cirrhosis. The guidelines noted more hepatotoxicity has been observed in Factor VIII gene therapy trials compared with Factor IX trials.

For post–gene therapy monitoring, the guidelines recommended periodic liver function tests, with frequency differing among patients with hemophilia A and B. They also suggested liver ultrasound every 6 months to screen for hepatocellular carcinoma in at-risk populations.

A study of 309 people with bleeding disorders in the Netherlands found a 4% overall risk of liver-related complications despite HCV infection clearance, with hepatocellular carcinoma being the dominant adverse event.

The guidance was developed by experts from the European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, International Society on Thrombosis and Haemostasis, and World Federation of Hemophilia. It addressed liver issues that can affect patients with bleeding disorders, who historically had high rates of viral hepatitis from contaminated blood products.

Conflict of interest disclosures can be found in the journal.