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Shortening hepatitis C treatment to 6 weeks effective but not perfect for easier-to-treat patients

Keith Alcorn
13 May 2015

Shortening hepatitis C treatment to 6 weeks for easier-to-treat patients without cirrhosis does not greatly reduce the efficacy of hepatitis C treatment for people with genotype 1 infection, according to results of a study combining grazoprevir, elbasvir and sofosbuvir in short treatment courses.

Moreover the study showed that for people with genotype 3 hepatitis C but no cirrhosis, an 8-week course of treatment was only marginally less effective than a 12-week course, even though genotype 3 infection is considered harder to treat.

The findings of the C-SWIFT study were presented to the International Liver Congress in Vienna, Austria, last month by Dr Fred Poordad of the Texas Liver Institute, University of Texas. Preliminary findings were presented previously at the American Liver Meeting in November 2014.



A type of tumour affecting the lymph nodes.

C-SWIFT is a proof-of-concept study designed to test whether the use of an especially potent regimen of grazoprevir (an HCV protease inhibitor) and elbasvir (an NS5A inhibitor) – two drugs in development by Merck – plus Gilead’s NS5B polymerase inhibitor sofosbuvir (Sovaldi) could shorten the duration of treatment for people with genotypes 1 or 3 hepatitis C.

The study tested treatment durations of 4, 6 or 8 weeks in people with genotype 1, and 8 or 12 weeks in people with genotype 3. Genotype 3 is considered harder to treat than genotype 1. The study recruited previously untreated people with hepatitis C genotypes 1 or 3 and liver enzyme (ALT and AST) levels below 350 IU/ml.

Participants in the study were randomised according to the following protocol:


Genotype 1

Genotype 3


No cirrhosis


No cirrhosis


Randomised to:

duration of treatment (n)

4 weeks (31)

6 weeks (20)

8 weeks (15)

12 weeks (12)

6 weeks (30)

8 weeks (21)

12 weeks (14)

A total of 143 people were enrolled; 66% male, 98% white and 45% Hispanic. Of the people with genotype 1, 82% had genotype 1a.

The primary efficacy analysis showed that a 4-week course of treatment in the group who did not have cirrhosis performed very poorly. Just 33% of participants achieved a sustained virological response, compared to 87% of those treated for 6 weeks in the group without cirrhosis and 80% in the group with cirrhosis. Ninety-four per cent of participants with cirrhosis treated for 8 weeks achieved a sustained virological response. No cases of viral breakthrough during treatment were observed. All but four treatment failures were cases of virological relapse; the remainder of treatment failures were due to treatment discontinuation.

In the genotype 3 group, an 8-week treatment course was marginally less effective than a 12-week treatment course among participants without cirrhosis (93% vs 100% SVR12), the difference being attributable to one case of virological relapse after completion of treatment. Ninety-one per cent of participants in the 12-week group with cirrhosis achieved a sustained virological response. A per-protocol sub-group analysis of people with genotype 3 showed a trend towards poorer virological response in people with baseline HCV RNA > 2,000,000 IU/ml, but no other substantive differences in response.

The only serious adverse events occurred in the group with cirrhosis and genotype 1. One participant discontinued treatment due to the development of B-cell lymphoma after four weeks, and one developed pyelonephritis. No cases of liver enzyme or total bilirubin elevation were observed.

Giving an overview of conference presentations on viral hepatitis treatment on the final day of the conference, Professor Michael Manns of Hannover Medical School, Germany, said that when shortening treatment for the easiest to treat patients, C-SWIFT showed that 6 weeks appears to be the barrier below which efficacy falls off.

Merck will continue research into shorter regimens, composed of grazoprevir, the experimental nucleotide inhibitor MK-3682 and either elbasvir or the experimental NS5A inhibitor MK-8408, in genotypes 1, 2, 3 and 4.


Poordad F et al. C-SWIFT: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis C virus genotype 1 infection, for durations of 4, 6 or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks. EASL 50th International Liver Congress, Vienna, S192, O006, 2015.