Early HCV Treatment Discontinuation Does Not Inhibit Sustained Virologic Response

Robert Flisiak, MD, PhD

Credit: Medical University of Bialystok

Premature discontinuation of direct-acting antiviral (DAA) therapy does not preclude treatment efficacy in patients with hepatitis C virus (HCV), according to findings from a recent study.¹

Results highlight a 78% sustained virologic response (SVR) rate among patients who discontinued treatment, with a similar treatment efficacy rate observed among patients who were treated for > 4 weeks compared to those who completed therapy. Of note, even patients who discontinued therapy before the end of the second week of treatment experienced therapeutic success, especially those with a low baseline viral load.¹

“Considering even the small percentage of patients who discontinue antiviral treatment, it should not be forgotten that this is also a population that is important to the goal of eliminating HCV infection as a public health threat created by World Health Organization,” Robert Flisiak, MD, PhD, head of the department of infectious diseases and hepatology of the Medical University of Bialystok in Poland, and colleagues wrote.¹

In 2016, the World Health Assembly unanimously adopted a resolution calling for the elimination of viral hepatitis by 2030. In the same year, the World Health Organization published a Global Health Sector Strategy on viral hepatitis to reach this goal, defining elimination as a 90% reduction in incidence and a 65% reduction in mortality for hepatitis B and C from 2015 to 2030.² Although 12-24 weeks of treatment with DAAs offers a viable cure for 95% of persons with HCV, some patients discontinue treatment prior to completion, and little is known about the effectiveness of DAAs when discontinued, especially before 4 weeks.³

To determine whether premature discontinuation of HCV treatment still enables SVR, investigators analyzed data for patients from the EpiTer-2 database, a retrospective, multicenter, real-world experience, national program initiated by the Polish Association of Epidemiologists and Infectiologists examining therapies for chronic hepatitis C. The initial study population consisted of 16,815 patients treated with interferon-free regimens enrolled in EpiTer-2 between 2015 and 2023. For inclusion in the present study, patients were required to have not completed an interferon-free therapy regimen on time with a known time of treatment discontinuation and documented HCV RNA assessment 12 weeks after the end of treatment.¹

Of the 16,815 patients registered in the EpiTer-2 database, 195 (1.2%) discontinued therapy, of which 97 had both the assessment of SVR and the time of therapy discontinuation available. Of these patients, 23 discontinued pan-genotypic therapy and 74 discontinued genotype-specific therapy, including 1 and 35 patients who received additional ribavirin, respectively.¹

Investigators noted the majority of patients (n = 62; 63.9%) discontinued treatment after 4 weeks. Of the 35 patients who discontinued treatment before 4 weeks, 12 stopped therapy within 2 weeks. Regardless of the type of treatment used, the most common reason for discontinuing therapy was hepatic decompensation (20.6%) or the patient's personal decision (18.6%), and less frequently, increased transaminase activity, cardiovascular or gastrointestinal symptoms, and anemia.¹

Investigators pointed out patients who discontinued treatment were significantly older, more frequently therapy-experienced, and more likely to have cirrhosis, a history of decompensation, and a Child-Pugh B or C classification than those who completed treatment. Additionally, patients who discontinued therapy before the 4th week were significantly more likely to receive pan-genotypic drugs whereas those who discontinued therapy after 4 weeks were more often treated with genotype-specific therapy.¹

SVR was achieved by 76 (78.4%) patients who discontinued treatment. Specifically, SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% of those who discontinued treatment at weeks 3 or 4, and 33.3% of those who discontinued treatment before the end of the second week.¹

Investigators noted the SVR rate was significantly reduced in patients who discontinued therapy before the end of week 4 compared to those who discontinued it later or completed the therapy as planned, regardless of whether they were treated with pan-genotypic or genotype-specific therapy.¹

In both pan-genotypic and genotype-specific patients, the SVR rate was significantly lower in patients who discontinued therapy before the end of week 4 compared to those who discontinued it later or completed the therapy as planned. While patients on pan-genotypic therapy who discontinued treatment after 4 weeks had the same chance of achieving SVR as those who completed therapy as planned, investigators pointed out patients discontinuing genotype-specific therapy after 4 weeks had a significantly lower chance of therapeutic success.¹

Closer examination of the 4 patients who achieved SVR despite ≤ 2 weeks of treatment revealed elimination of HCV infection was not hindered by male gender, severe liver disease, or overweight, all of which are generally recognized as factors worsening prognosis. Of note, none of these 4 patients had a baseline viral load exceeding 400,000 IU/mL.¹

Investigators acknowledged multiple limitations to these findings, including the retrospective, observational nature of the study introducing the potential for missing data and bias as well as the low discontinuation rate resulting from high patient adherence to the therapeutic program.¹

“Despite discontinuation of therapy after week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load,” investigators concluded.¹

References

1. ^{Flisiak R, Zarębska-Michaluk D, Janczewska E, et al. Sustained Virological Response After Early Discontinuation of Hepatitis C Treatment. Journal of Viral Hepatitis. https://doi.org/10.1111/jvh.13991}
2. ^{Coalition for Global Hepatitis Elimination. About Hepatitis Elimination. July 22, 2024. Accessed August 12, 2024. https://www.globalhep.org/about/about-hepatitis-elimination}
3. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed August 12, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}