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Efficacy of Direct-Acting Antivirals Compared with Older Agents for Hepatitis C


Am Fam Physician. 2017 Jun 1;95(11):online.


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1 in 4 achieved sustained viralogic response

None experienced major harms



1 in 4 achieved sustained viralogic response

None experienced major harms

Details for This Review

Study Population: Treatment-naive patients with hepatitis C virus genotype 1

Efficacy End Points: Sustained viralogic response (SVR) at 24 weeks (absence of detectable virus in the blood)

Harm End Points: Anemia, fatigue, death, hospital admission

Narrative: Hepatitis C virus is typically latent (i.e., silent) for decades; therefore, 80% to 85% of persons infected will not experience illness caused by the infection. Conversely, 15% to 20% of patients with untreated hepatitis will eventually develop liver failure or cancer.1 Standard treatment to prevent these developments includes interferon and ribavirin (Rebetol), a difficult-to-tolerate regimen that achieves SVR (i.e., the absence of virus in the blood) in approximately 50% of patients but is commonly associated with anemia and fatigue. The use of newer direct-acting antiviral agents may improve SVR rate and tolerability.2

The review summarized here addresses all major trials of second-generation direct-acting antiviral agents. To better understand the potentially unique benefits of this class, we focus on trials comparing any direct-acting antiviral-based regimen with interferon plus ribavirin. Despite 16 trials being identified, only five (all using simeprevir [Olysio]) were similar enough to be pooled. Simeprevir, when added to interferon and ribavirin, improved SVR without increasing adverse effects: 82% vs. 56% with the older regimen, a 26% absolute improvement (number needed to treat = 4).

Although pooled data for other agents such as daclatasvir (Daklinza, used in combination with sofosbuvir [Sovaldi]), ledipasvir (used in combination with sofosbuvir [Harvoni]), sofosbuvir, and paritaprevir (used in combination with ombitasvir and ritonavir [Norvir]) were unavailable (because of their indications to be used in combination with other

Author disclosure: No relevant financial affiliations.


show all references

1. Suwanthawornkul T, Anothaisintawee T, Sobhonslidsuk A, Thakkinstian A, Teerawattananon Y. Efficacy of second generation direct-acting antiviral agents for treatment naïve hepatitis C genotype 1: a systematic review and network meta-analysis. PLoS One. 2015;10(12):e0145953....

2. Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis. 2011;52(7):889–900.

3. Koretz RL, Lin KW, Ioannidis JP, Lenzer J. Is widespread screening for hepatitis C justified? BMJ. 2015;350:g7809.

4. U.S. Food Drug Administration. Direct-acting antivirals for hepatitis C: drug safety communication – risk of hepatitis B reactivating. Accessed October 1, 2016.

5. Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA. 2014;312(6):631–640.

6. Barua S, Greenwald R, Grebely J, Dore GJ, Swan T, Taylor LE. Restrictions for Medicaid reimbursment of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann Intern Med. 2015;163(3):215–223.

This series is coordinated by Dean A. Seehusen, MD, MPH, AFP Contributing Editor, and Daniel Runde, MD, from the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at



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