PERSISTENT portal hypertension after HCV cure characterized immunological mechanisms differing by HIV status in advanced cirrhosis.
Persistent Portal Hypertension After HCV Cure Remains Common
Persistent portal hypertension is a major determinant of outcomes in advanced cirrhosis and can remain unresolved even after hepatitis C virus (HCV) eradication with direct acting antivirals (DAA). In this prospective study, investigators followed 41 adults with advanced HCV related cirrhosis who achieved cure with DAA therapy, including 18 people without HIV and 23 people with HIV. The team focused on change in the hepatic venous pressure gradient (HVPG), a gold standard hemodynamic marker of portal hypertension, over 48 weeks.
At baseline, participants underwent extensive immune profiling using multiplex plasma assays and flow cytometry to characterize circulating inflammatory mediators and T cell phenotypes. Mixed effects modeling tested which baseline immune features were associated with the trajectory of HVPG improvement, with q values used to control false discoveries.
HIV Status Defines Distinct Immune Drivers of Impaired HVPG Regression
Two distinct immunological profiles emerged among individuals with impaired HVPG regression, suggesting that persistent portal hypertension after HCV cure may reflect different underlying biology depending on HIV status.
In participants without HIV, poorer HVPG regression aligned with a broader proinflammatory profile, including higher baseline TNF α, IL17A, and IL10. This pattern also coincided with widespread CD4 positive T cell activation, including increased HLA DR positivity and CD38 plus HLA DR co expression, with robust activation across central memory and effector memory subsets.
In participants with HIV, impaired HVPG regression tracked with a different signature. Associations centered on sVCAM 1, consistent with endothelial dysfunction, alongside a narrower pattern of CD4 positive T cell activation concentrated within effector memory and TemRA subsets.
Clinical Implications for Post Cure Risk Stratification
The findings suggest that HIV coinfection may reshape pathways of hepatic recovery after HCV cure, shifting from systemic inflammation toward endothelial dysfunction and T cell exhaustion. Defining these baseline immune signatures could support future efforts to stratify residual risk and develop targeted approaches to promote more complete hemodynamic recovery in advanced cirrhosis.
Reference: Martín-Escolano R et al. HIV status defines distinct immunological drivers of persistent portal hypertension after HCV cure in people with advanced cirrhosis. Front Immunol. 2026;17. doi: 10.3389/fimmu.2026.1683092.
