Kyoto, Japan -- The hepatitis C virus -- HCV -- can persist in the livers of those infected and even lead to liver disease or failure in extreme cases. It affects tens of millions of people worldwide and there is no vaccine to prevent infection, but effective treatment can resolve most cases.
Until about a decade ago, hepatitis C infection was difficult to cure because treatment relied on prolonged interferon injections with severe side effects. The advent of oral direct-acting antivirals, or DAAs, revolutionized care for HCV. However, whether clearing HCV would also alleviate chronic immune activation remained uncertain, especially in people living with human immunodeficiency virus, or HIV, whose immune systems are already under strain.
This uncertainty is exacerbated by inequalities in research and care across international borders. Previous research on the immunological effects of DAAs has largely originated from the Global North and involved patients from those regions. None existed from Southeast Asia where viral strains, methods of transmission, host genetics, and access to care differ. This motivated a collaborative team of researchers from Kyoto University and the University of Indonesia to address this knowledge gap.
"Treatment goes beyond making patients healthier and live longer. It helps those infected lead fulfilling and stigma-free lives by, for example, allowing them to consider marriage and childbirth with peace of mind," says corresponding researcher Youdiil Ophinni of Kyoto University.
The research team conducted a prospective study in Indonesia, a country with one of the region's highest rates of HIV/HCV coinfection, or infection by two viruses. The study followed 132 coinfected subjects at the national referral hospital in Jakarta. Each patient received DAAs, specifically sofosbuvir and daclatasvir, for either 12 or 24 weeks, and the team collected blood samples both before treatment and 12 weeks afterwards to measure key markers of immune activation.
The results were highly encouraging: after treatment, 96% of participants achieved HCV clearance, accompanied by significant declines in biomarkers linked to inflammation and blood vessel dysfunction. These improvements were observed regardless of liver damage, suggesting that DAAs confer immune benefits even in advanced liver disease. Interestingly, participants with lower blood albumin -- a sign of poorer liver function -- showed the greatest biomarker reduction, indicating that those with more severe liver impairment may benefit most from DAA therapy and HCV clearance.
The study provides the first longitudinal immunological data on HIV/HCV-coinfected individuals in Southeast Asia, underscoring the importance of early hepatitis C treatment to prevent long-term immune and liver complications. Beyond its scientific impact, the findings reinforce the need for equitable access to DAA therapy among vulnerable communities, highlighting the importance of integrating long-term immune monitoring and holistic care into future antiviral treatment strategies.
