Current liver fibrosis screening misses many cases in people living with HIV and could be improved with a new tool developed by researchers at The Institute.
Thanks to antiretroviral therapy and improved control of viral hepatitis (HBV and HCV), people living with HIV generally live longer and healthier lives. However, liver disease remains common in this population and is one of the leading causes of death.
A large international study found that among people living with HIV, liver fibrosis, a build-up of scar tissue in the liver that can lead to permanent damage, is common, often has no symptoms and is frequently missed by the FIB-4 blood test, the first-line screening tool used in clinical practice. Led by Dr. Giada Sebastiani at the Research Institute of the McGill University Health Centre (The Institute), the study introduces the FIB-HIV score, a new tool that could improve the identification of people at risk of liver fibrosis by incorporating metabolic and HIV-specific factors. Effective detection of liver fibrosis is critical to ensure patients receive appropriate care.
Steatotic liver disease (SLD), a condition characterized by an excessive build-up of fat in the liver, affects one in three adults worldwide and represents a major public health challenge. It can progress to liver fibrosis, cirrhosis and, in some cases, liver cancer.
Current screening misses over one-third of significant liver fibrosis cases
"People living with HIV are disproportionately affected by the more advanced forms of steatotic liver disease, formerly known as fatty liver disease. In particular, metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis are becoming an increasing burden as people living with HIV age," says Dr. Giada Sebastiani, senior scientist in the Infectious Diseases and Immunity in Global Health Program at The Institute and senior author of the study published in Hepatology. "Our study suggests that more than one third of cases of significant liver fibrosis are missed in this high-risk population."
Among the nearly 5,000 participants who had neither active viral hepatitis nor hazardous alcohol use and were followed between 2015 and 2025 at seven centres across five countries, more than one in five (21.7%) had SLD. More than one in 10 (12.6%) had significant liver fibrosis, a level of scarring that requires specialist assessment and follow-up, and 6.1% had advanced fibrosis, a more severe form of liver scarring.
The FIB-4 test showed only modest accuracy in detecting significant liver fibrosis, misclassifying 36% of fibrosis cases as low risk. Its performance was particularly poor in people with MASLD, whose liver fibrosis was more likely to go undetected.
Most participants with significant liver fibrosis who were incorrectly classified as low risk by the FIB-4 score remained in that category when the test was repeated 12 and 24 months later. As a result, they would likely not have received the clinical follow-up needed in routine practice.
In the study, the performance of the FIB-4 score, which estimates the risk of liver fibrosis based on a patient's age and blood test results, was evaluated against transient elastography, an imaging technique that measures scar tissue in the liver. Participants underwent transient elastography annually. In routine clinical practice, however, this test is generally recommended only when the FIB-4 score exceeds certain thresholds.
The FIB-HIV score: Better results through a personalized approach
The researchers analyzed the characteristics of participants whose liver fibrosis was missed by the FIB-4 test (false negatives) and found that incorporating those factors into the FIB-4 score improved risk classification. This led to the development of the FIB-HIV score, which outperformed FIB-4 in detecting significant liver fibrosis.
The FIB-HIV score incorporates traditional metabolic risk factors, such as overweight, obesity, diabetes and high blood pressure, as well as HIV-specific factors, including exposure to certain older antiretroviral drugs, duration of HIV infection, the severity of past immune suppression and viral load.
"In people living with HIV, several factors can contribute to liver damage without significantly affecting the blood markers used to calculate the FIB-4 score," says Felice Cinque, first author of the study and former postdoctoral fellow at The Institute. "This highlights the importance of accounting for individual metabolic and HIV-related factors, such as those incorporated into the FIB-HIV score, to achieve a more accurate assessment of liver fibrosis risk."
The FIB-HIV score is based on routinely available clinical information. It could help clinicians better identify patients who would benefit from transient elastography while optimizing the use of diagnostic resources, the study authors note.
"In high-income countries, nearly half of all people living with HIV are now over the age of 50. As this population continues to age, liver disease is becoming an increasingly important health concern. We hope our findings will help advance a more personalized and effective approach to liver fibrosis screening," says Dr. Sebastiani, who is also Associate Professor at McGill University and a member of the Gastroenterology and Hepatology Division at the McGill University Health Centre.
About the study
FIB-4 fails to identify significant liver fibrosis in people with HIV: A large multinational screening study by Felice Cinque, Sahar Saeed, Francesca Farina, Dana Kablawi, Jihoon Lim, Antonio Cascio, Claudia Gioè, Emmanuel Tsochatzis, Rosa Lombardi, Ahmed Cordie, Rahma Mohamed, Ahmed M. Kamel, Gamal Esmat, Alessandra Bandera, Jovana Milic, Dominik Benke, Fauzi Elamouri, Jürgen K. Rockstroh, Giovanni Guaraldi and Giada Sebastiani is published in Hepatology.
DOI: 10.1097/HEP.0000000000001773
