Published online Nov 28, 2019. doi: 10.3748/wjg.v25.i44.6551
Peer-review started: September 6, 2019
First decision: October 14, 2019
Revised: November 8, 2019
Accepted: November 13, 2019
Article in press: November 13, 2019
Published online: November 28, 2019
Regimens involving direct-acting antiviral agents (DAAs) are recommended for the treatment of infection with hepatitis C virus (HCV) genotypes 1, 2 and 3. But real-world data is still not enough, especially in Asia.
Although high rates of sustained virological responses (SVR) have been shown in trials, results derived from controlled settings may not be representative to the real world. Drugs may have many unexpected adverse events in clinical applications. Also, data gathered from different races is insufficient. Therefore, evaluations of drugs in real-world settings are critical, especially in patients such as those from northwest China, where clinical trial data is limited.
Our study aimed to investigate the efficacy and safety of DAA-based regimens in a Chinese real-life setting in China and find out whether there are any differences in different genotypes and liver statuses.
This study included 366 patients infected with HCV genotypes 1, 2 and 3, with or without cirrhosis, who were observed between May 2015 and December 2018. They were treated with ledipasvir and sofosbuvir (SOF) (genotype 1) with or without ribavirin (RBV), SOF and RBV (genotype 2), or SOF and daclatasvir (genotype 3), with or without RBV, for 12 or more wk. The participants’ SVR at post-treatment week 12 (SVR12) was the primary endpoint. The occurrence of adverse events and drug-drug interactions were recorded.
In the 366 patients, genotype 1 (59.0%) was the most common genotype, followed by genotypes 2 (34.4%) and 3 (6.6%). Liver cirrhosis was diagnosed in 154 (42.1%) patients. Fifty (13.7%) patients were treatment-experienced. Intention-to-treat analysis revealed that SVR12 was 86.3% (316/366). For modified intention-to-treat analysis, SVR12 was achieved in 96.6% of overall patients (316/327), 96.3% in patients with genotype 1, 97.5% in those with genotype 2, and 95.0% in those with genotype 3. Most of the treatment failures were due to lack of follow-up (3 cases had non-responses, 1 had virological breakthrough, 11 relapsed and 36 did not participate in the follow-up). There was no significant difference in SVR between different genotypes and liver statuses (P < 0.05). Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12 (P < 0.05). High SVR was observed regardless of age, gender, liver status, alpha-fetoprotein, HCV RNA levels or history of antiviral therapy (P > 0.05 for all). The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%. Most of the adverse events were mild. We found two cases of special adverse events. One case involved facial and bilateral lower extremity edema, and the other case showed an interesting change in lipid levels while on medication. No severe adverse events were noted.
The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1, 2 and 3, including those with cirrhosis. In clinical applications, there are indeed unexpected adverse events.
The antiviral effect of DAAs is quite satisfying. However, in the clinic, many adverse events may occur due to combination with other medications and individual variation. Strict monitoring is required for clinical use of DAAs. Besides, the long-term efficacy and safety of DAAs need to be studied.