Patients with hemophilia often experience residual risk factors of chronic liver damage after hepatitis C virus (HCV) clearance and should receive a specific diagnostic work-up to evaluate liver health prior to gene therapy, according to an article published in Blood Advances.

The researchers recruited 119 patients with hemophilia who have been successfully treated for HCV and conducted a prospective hepatological screening to detect advanced fibrosis or cirrhosis. They used biochemical data, liver stiffness measurement, and ultrasound tests to evaluate risk factors for chronic liver damage.

In addition, they performed a prospective pre-/post-HCV clearance analysis, including the liver stiffness measurement, ultrasound, and noninvasive tests of fibrosis in a subgroup of 57 participants.

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According to the results, 96 participants (81%) had at least 1 potential risk factor of chronic liver damage, and the most prevalent risk factors were metabolic, such as steatosis, detected by ultrasound in 51 patients (44%).

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Moreover, 21 participants (18%) had clinical, biochemical, liver morphology, or liver stiffness measurement results indicative of advanced liver fibrosis or cirrhosis. Esophageal varices were detected in 10 patients (8%), while hepatocellular carcinoma was found in 3 (3%).

The prospective pre-/post-HCV clearance analysis showed a reduction of liver stiffness measurement and noninvasive tests of fibrosis after HCV clearance, but the ultrasound signs suggestive of cirrhosis persisted.

In 23 of 80 patients (29%) with a liver stiffness measurement lower than 10 KPa, the researchers found at least 1 ultrasound sign indicative of advanced fibrosis or cirrhosis, as well as in 18% of patients with liver stiffness measurement lower than 8 KPa.

“Patients with advanced fibrosis/cirrhosis must be excluded from gene therapy but the diagnostic work-up to rule out this condition cannot be limited to the most common non-invasive tests which do not always correspond to a histologically proven downstaging of liver damage after HCV clearance,” La Mura and colleagues explained.

People with hemophilia treated with plasma-derived products often develop an HCV infection. In the era of novel adeno-associated viral vector therapies approved for hemophilia A and B, maintaining liver health is crucial for improving disease outcomes.


La Mura V, Bitto N, Capelli C, et al. Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy. Blood Adv. Published online July 28, 2023. doi:10.1182/bloodadvances.2023010723