Hepatitis C eradication with direct-acting anti-virals reduces the risk of variceal bleeding

Background: The real-world, long-term benefits of sustained virologic response (SVR) on the risk of variceal bleeding remain unclear. Aim: To assess the association between DAA-induced SVR and post-treatment variceal bleeding. Methods: We identified patients who initiated DAA-only anti-viral treatments in the United States Veterans Affairs healthcare system from 2013 to 2015. We followed patients until 1 January 2019 for the development of gastro-oesophageal variceal bleeding defined by diagnostic codes. We used multivariable Cox proportional hazards regression to assess the association between SVR and development of variceal bleeding, adjusting for potential confounders. Results: Among 33 582 DAA-treated patients, 549 (1.6%) developed variceal bleeding after treatment (mean follow-up 3.1 years). Compared to no SVR, SVR was associated with a significantly lower incidence of variceal bleeding among all patients (0.46 vs 1.26 per 100 patient-years, adjusted hazard ratio [AHR] 0.66, 95% CI 0.52-0.83), among patients with pre-treatment cirrhosis (1.55 vs 2.96 per 100 patient-years, AHR 0.73, 95% CI 0.57-0.93) and among patients without pre-treatment cirrhosis (0.07 vs 0.29 per 100 patient-years, AHR 0.33, 95% CI 0.17-0.65). The risk of variceal bleeding after treatment was lower in those who achieved SVR vs no SVR among patients who had non-bleeding varices (3.5 vs 4.9 per 100 patient-years) or bleeding varices (12.9 vs 16.4 per 100 patient-years) diagnosed before treatment, but these differences were not statistically significant in adjusted analyses. Conclusion: DAA-induced SVR is independently associated with a lower risk of variceal bleeding during long-term follow-up in patients with and without pre-treatment cirrhosis. These findings demonstrate an important real-world benefit of DAA treatment

A Scalable Variational Inequality-Based Formulation That Preserves Maximum Principles for Darcy Flow with Pressure-Dependent Viscosity

The overarching goal of this thesis is to present a robust and scalable finite element computational framework based on Variational inequalities (VI) which models nonlinear flow through heterogeneous and anisotropic porous media without violating discrete maximum principles (DMP) for pressure. VI is an optimization technique that places bounds on the numerical solutions of partial differential equations, and previous studies have shown that the VI approach can enforce DMP for linear and semi linear subsurface flow and transport problems. Herein, the same VI framework is extended to the nonlinear Modified Darcy flow (MDF) model which incorporates pressure dependent viscosity. Although it can be proven that the MDF model satisfies maximum principles, most finite element formulations, including the classical Galerkin formulation with Raviart-Thomas elements and the variational multi-scale formulation, will not adequately enforce the DMP if strong levels of anisotropy are present. Several representative reservoir problems with realistic parameters are presented, and both the algorithmic and parallel scalability of the proposed computational framework are studied.Civil and Environmental Engineering, Department o