Researchers in several countries—including France, New Zealand, the U.K. and the U.S.—reviewed the records of several thousand people who had been cured of HCV using direct-acting antivirals (DAAs) and found very high rates of cure that were sustained up to three years after cessation of therapy. That is, once cured, the vast majority of participants stayed cured. Rates of relapse, reinfection and liver cancer were very low after cure was achieved.

Study details

Participants in Gilead Sciences’ sponsored studies were encouraged to enroll in an observational study that monitored them for up to three years after cure was achieved. As part of this observational study, participants regularly visited study clinics where their blood was drawn for analysis.

There were 5,433 participants enrolled and their average profile upon entering the study was as follows:

• age – 54 years
• 63% men, 37% women
• 20% had severe liver injury (cirrhosis)
• most (99%) had been infected with genotypes 1, 2, 3 or 4

Results—Keeping track of HCV

Researchers found the following:

• 99.7% of participants maintained their cure status.
• 0.1% of participants had evidence of late relapse.
• Participants who relapsed tended to have HCV genotype 1a or 3. Historically these genotypes have tended to respond poorly to treatment.
• 0.2% of participants had evidence of HCV re-infection.
• Reinfections began to occur as early as eight months after cure was achieved.

Results—Monitoring liver cancer

Cases of liver cancer were detected after treatment cessation but were low. This is likely due to the smaller proportion of people with cirrhosis in this study compared to the previously reported French study (where more than 60% of participants had cirrhosis).

Most cases of liver cancer were distributed among people with pre-existing cirrhosis and occurred within the first year after treatment cessation.

Liver cancer diagnosed upon study entry

• among people with cirrhosis – 5 cases
• among people without cirrhosis – 3 cases

Liver cancer diagnosed 24 weeks after study entry

• among people with cirrhosis – 5 cases
• among people without cirrhosis – 1 case

Liver cancer diagnosed 48 weeks after study entry

• among people with cirrhosis – 6 cases
• among people without cirrhosis – 0 cases

Liver cancer diagnosed 72 weeks after study entry

• among people with cirrhosis – 3 cases
• among people without cirrhosis – 0 cases

After week 72, there were no further cases of liver cancer.

Other liver-related issues

A similar trend (a decrease over time) was seen with the relatively small proportion of cases of liver-related complications that were detected after treatment cessation. Complications included the following:

• build-up of fluid in the abdomen (ascites)
• internal bleeding
• brain-related issues
• yellowing of the skin and whites of the eyes (jaundice)

Over time there were fewer cases of these and by the third year of the study, there were no reports of these complications.

There was also a similar trend with analyses of blood tests with a trend to normalization over time.

Overall, the findings from this review are reassuring and show that the vast majority of people who are cured with DAAs remain cured. Rates of complications, including liver cancer, were lower than those found in another study from France (reported in this this issue of TreatmentUpdate). The lower rate of liver cancer seen in the present study likely arose because most participants were treated relatively early in the course of liver disease, before the onset of cirrhosis.

—Sean R. Hosein

REFERENCE:

Lawitz E, Ruane P, Stedman C, et al. Long-term follow-up of patients with chronic HCV infection following treatment with direct-acting antiviral regimens: maintenance of SVR, persistence of resistance mutations and clinical outcomes. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract 166.