OATP1B3 c.699G>A Predicts a 6.3-Fold Increased Risk of Hyperbilirubinemia During OPrD Therapy for HCV

Although ombitasvir/paritaprevir/ritonavir plus dasabuvir (OPrD) therapy is highly effective for chronic hepatitis C (CHC), clinicians frequently encounter transient hyperbilirubinemia, which can be misidentified as hepatotoxicity. This study investigated the role of SLCO1B1 (OATP1B1) and SLCO1B3 (OATP1B3) genetic polymorphisms in predicting bilirubin spikes and distinguishing transporter-mediated interference from hepatocellular injury. In this prospective study of 65 patients with HCV genotype 1, genotyping for OATP1B1 (c.388A>G, c.521T>C) and OATP1B3 (c.334T>G, c.699G>A) was performed using PCR-RFLP and capillary electrophoresis (QIAxcel Advanced System). Clinical and biochemical parameters were monitored over a 12-week treatment period. Hyperbilirubinemia (total bilirubin >1.1 mg/dL) developed in 18.5% of the cohort, typically within the first month. A distinct ‘AST-dominant’ biochemical signature, elevated bilirubin and AST paired with stable ALT, was identified, suggesting transporter-specific interference rather than hepatocyte damage. Statistical analysis pinpointed the OATP1B3 c.699G>A (rs7311358) variant as the sole genetic driver (p = 0.007). Carriers of the c.699G>A allele faced a 6.3-fold higher risk of developing hyperbilirubinemia (OR: 6.30, 95% CI: 1.48–26.80, p = 0.032), while no significant associations were found for OATP1B1 variants. We conclude that OATP1B3 c.699G>A is a potent predictor of OPrD-induced hyperbilirubinemia. Identifying this genotype pre-treatment allows clinicians to anticipate transient, benign bilirubin elevations and prevent unnecessary drug discontinuation, thereby mitigating therapeutic inertia and ensuring treatment continuity for CHC patients.