The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration.

Background: The high cost of new hepatitis C (HCV) treatments has resulted in "watchful waiting" strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS).

Objective: To document if delayed VLS adversely impacted patient risk for adverse events and death.

Methods: 187,860 patients were selected from the Veterans Administration's (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999-2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response.

Results: Achieving an undetectable viral load before the patient's FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33-35% and death by 21-26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response.

Conclusions: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.