infohep is no longer being updated. Visit for HIV and hepatitis news.

Three-drug regimen plus ribavirin cures the hardest-to-treat hepatitis C patients

Keith Alcorn
08 December 2021
Olya Maximenko/

People who have experienced failure of multiple courses of direct-acting antiviral treatment can be cured of hepatitis C with a combination of three direct-acting antivirals plus ribavirin, a review of heavily treatment-experienced patients in the United States shows.

The review, presented last month at The Liver Meeting, found that even a patient who had undergone five unsuccessful courses of treatment was cured. None of the patients treated with the regimen experienced treatment failure. The findings offer hope that eventually, everyone can be cured of hepatitis C, even if they do not respond to recommended first- and second-line regimens.

Direct-acting antiviral therapy cures 90-95% of people with hepatitis C after the first course of treatment and those who experience failure of the first regimen are usually cured by a second course of treatment of sofosbuvir, velpatasvir and voxilaprevir (Vosevi). In the rare cases that the second-line regimen fails, EASL and AASLD guidelines recommend 16-24 weeks of treatment with sofosbuvir, glecaprevir and pibrentasvir (Maviret), and ribavirin. But this recommendation is based on two case reports and more evidence is needed to show if this regimen is effective.


compensated cirrhosis

The earlier stage of cirrhosis, during which the liver is damaged but still able to perform most of its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.


Partial recovery from an illness, an alternative word for regression.

Dr Varun Saxena of University of California San Francisco reported on the outcomes of people who had experienced failure of a previous regimen containing sofosbuvir, velpatasvir and voxilaprevir (Vosevi) and who were re-treated with the combination of sofosbuvir, glecaprevir and pibrentasvir, and ribavirin.

The retrospective study of patients receiving hepatitis C treatment in the Kaiser Permanente Northern California healthcare system and at University of California San Francisco identified 12 people who received sofosbuvir, glecaprevir and pibrentasvir, and ribavirin. Ten were male, ten were White and the cohort had a median age of 66 years. Eight people had genotype 1a infection, four had genotype 3 infection. Half had compensated cirrhosis (F4 fibrosis) and the remainder had F0-F2 stage liver fibrosis. Three had hepatocellular carcinoma, in remission for at least three months prior to starting treatment. One person had received a liver transplant.

Each of the patients who received sofosbuvir, glecaprevir and pibrentasvir, and ribavirin achieved a sustained virologic response 12 weeks after completing treatment.

In seven out of 12 cases, patients were treated for 16 weeks. Four of the seven treated for 16 weeks had pre-treatment resistance and three had cirrhosis. Two of the seven had received three previous regimens, the remainder had received two.

In five out of 12 cases, patients were treated for 24 weeks. Four out of five had pre-treatment resistance mutations, two had received three previous courses of treatment and one had received five.

Dr Saxena noted that although four of the 12 participants did not have detectable resistance mutations, the gap between treatment regimens meant that it was possible that resistance mutations may have ceased to become detectable.

Ribavirin was dosed by weight in six patients and at 600mg per day in six. Nine patients underwent ribavirin dose reduction during their course of treatment, but none discontinued ribavirin or needed epoetin alpha or hospitalisation due to side effects.


Saxena V et al. Excellent efficacy and safety of sofosbuvir, glecaprevir, pibrentasvir and ribavirin for retreatment of chronic hepatitis C after sofosbuvir, velpatasvir and voxilaprevir failure. The Liver Meeting, abstract 98, 2021. Published as: Hepatology, 74 (suppl 1): 66a, 2021.