Harel Dahari

Q: What prompted this study?


A: The advent of direct-acting antiviral (DAA) therapy has revolutionized treatment of hepatitis C viral (HCV) infection, giving doctors the tools to cure the majority of patients.  However, one of the major challenges in eliminating this disease is the high cost of treatment. The goal of our study was to examine whether response-guided therapy based on mathematical modeling of viral kinetics during the first 2 weeks of DAA therapy would enable optimization of the length of treatment on an individualized basis. If the length of treatment can be shortened based on customized treatment plans, then two benefits result. There is a substantial reduction in cost and patients are subjected to shorter treatment schedules and side effects.


Additional benefits of shortening treatment are highlighted in two special subgroups:

  • PWID (People who inject drugs)

Due to the profile and lifestyle of this population, adherence to therapy regimens and schedules can be suboptimal. Therefore, administering DAA treatment for the shortest time possible could lead to increased success in treatment.

  • Pregnant Women Infected with HCV
    Treatment can prevent vertical transmission of HCV from mother to child, however most clinicians defer therapy due to concerns of possible DAA toxicity to the fetus. Treatment during 2nd or 3rd trimester in a response guided approach would enable minimal drug exposure time in a substantial number of patients. The dual benefits are the ability to treat the mother without delay and prevent the virus in newly born children.

Q: What are the key findings?


A: The following link presents additional analysis of the results of a pilot study published by our group in 2020 (Scientific Reports). In that study we showed for the first time that implementation of real time response-guided therapy approach, allowed shorter treatment schedules in approximately 40% of patients receiving DAA therapy. This goal was accomplished without compromising treatment efficacy that was comparable to standard of care (96% cure rate).


The model was derived from analysis of individual kinetic patterns of viral decline obtained from blood samples taken at baseline, day 2, week 1, week 2, and week 4 after the initiation of DAA treatment.  For each patient calculation of time-to-cure (based on the mathematical model) was done after the fourth week via blood sample. Then, according to the model’s estimation, patients were instructed to either continue therapy according to standard-of-care norms (either 12 or 8 weeks depending on the specific DAA regimen) or to shorten therapy as determined by the model. 


In the current publication (10.1038/s41598-020-74568-x) we reanalyzed the results trying to see whether omission of specific time points of viral load determination would be possible without compromising its accuracy. The rationale for this analysis was that reducing frequency of blood draws would simplify the implementation of our response-guided approach and facilitate its adoption on a broader scale. Key results were that omission of day 2 and week 4 blood draws did not significantly alter the accuracy of the model for determining expected time-to-cure.


Q: What is the clinical take-away?

A: In brief, treatment of HCV infection does not mandate a fixed duration in all patients. Treatment length can be individualized by utilizing a simple mathematical model for prediction of time-to-cure in a response-guided therapy approach. Implementation of this approach on a broader scale could lead to significant cost-saving and optimize therapy duration in specialized populations such as PWID and pregnant women.