1249. Rise in ALT after Hepatitis C Treatment is a Highly Sensitive Marker of Treatment Failure

Abstract Background Hepatitis C nucleic acid testing to confirm sustained virological response (SVR) after antiviral treatment is technical and expensive, hampering scale-up and decentralisation of care in resource-poor settings. Serial liver function testing may offer a cheaper means of screening for treatment failure. Methods In an HCV treatment shortening study in Vietnam (n=51), we analysed whether a change in ALT or AST from EOT to EOT+ 12 weeks (ΔALT; ΔAST) was a sensitive surrogate for HCV RNA in detecting treatment failure. We compared ΔALT and ΔAST between cures (38) and failures (13), and assessed sensitivity, specificity and area under receiver-operator curves (AUROC) vs gold standard HCV RNA. We validated our findings in a second, larger study population from a UK treatment shortening study (n=202). Both study populations had mild liver disease, and all participants were treated with 4-8 weeks direct acting antiviral therapy. Results In Vietnam, among 46 HCV genotype 1 or 6-infected individuals who supressed ALT on therapy, 11 failed to achieve SVR. Median ΔALT was -1 IU/L in cures vs +24 IU/L in treatment failures (p< 0.001). Increase in ALT (ΔALT > 0) after end-of-treatment was 100% (95% C.I. [66.4 – 100]) sensitive and 48% [26.8 – 69.4] specific vs HCV RNA in identifying failures (AUROC = 0.99). These results were validated among 193 genotype 1 or 4-infected individuals who supressed ALT on treatment in a UK study (in which 60 failed to achieve SVR). Median ΔALT was +1 IU/L in cures vs +45 IU/L in treatment failures (p< 0.001). ΔALT > 0 was 100% sensitive (95% C.I. [94.6 – 100]) and 47% [38.3-56.3] specific (AUC = 0.98). ΔAST performed similarly. Figure 1Change in ALT from EOT to EOT+12 in cures and from EOT to start of retreatment (EOT+6 to 24) in treatment failures in a) Vietnam study b) UK study Conclusion ΔALT from EOT to EOT+12 is a highly sensitive screen for identifying DAA treatment failures. Using this strategy, only around half of treated individuals require HCV RNA testing 12 weeks after end of treatment, offering substantial benefits in terms of cost reductions and decentralisation of care. Disclosures All Authors: No reported disclosures.