Published online Sep 27, 2020. doi: 10.4254/wjh.v12.i9.672
Peer-review started: April 10, 2020
First decision: April 26, 2020
Revised: July 12, 2020
Accepted: July 26, 2020
Article in press: July 26, 2020
Published online: September 27, 2020
In real-world settings, elderly patients infected with hepatitis C virus (HCV) represent a substantial and growing population and carry a high risk of advanced liver diseases such as cirrhosis and hepatocellular carcinoma. Therefore, these patients should be treated as soon as possible. Clinical trials of interferon-free direct-acting antiviral agent regimens using sofosbuvir and ribavirin for patients with genotype 2 HCV have been reported since 2013. However, patients ≥ 75-years-old were not included in the sofosbuvir plus ribavirin regimen of those clinical trials. The safety and effectiveness of sofosbuvir plus ribavirin for elderly patients ≥ 75-years-old has thus remained unclear.
In recent HCV treatment guidelines from Western countries, sofosbuvir plus ribavirin therapy is no longer recommended because of the adverse effects of ribavirin and the relatively lower sustained viral response (SVR) rate compared to other direct-acting antiviral agent therapies. However, in consensus statements and recommendations on the treatment of hepatitis C from the Asian-Pacific Association for the Study of the Liver, sofosbuvir plus weight-based ribavirin for 12 wk is recommended as a first-line treatment, and SVR rates from Asian real-world data were similar to those of the phase III trial. Sofosbuvir plus ribavirin therapy also offers advantages in terms of both cost and real-world evidence. The real-world safety and efficacy of sofosbuvir plus ribavirin for elderly patients ≥ 75-years-old can provide useful information regarding treatment strategy for elderly patients with HCV in the Asia-Pacific region.
The aim of the present study is to evaluate the real-world safety and efficacy of sofosbuvir plus ribavirin for elderly patients ≥ 75-years-old compared to non-elderly patients
This is a multicenter post-marketing prospective cohort study of sofosbuvir plus ribavirin therapy for patients infected with genotype 2 HCV in a real-world clinical setting. We treated 265 patients with genotype 2 HCV using standard approved doses of sofosbuvir (400 mg/d) plus ribavirin adjusted by body weight, administered orally for 12 wk. In the present study, 31% of patients were ≥ 75-years-old, and 12% had a history of hepatocellular carcinoma (HCC) treatment. Furthermore, 34% of enrolled patients had cirrhosis, and 20% had moderate chronic kidney disease. The primary end point of the present study was SVR at 24 wk after the end of therapy.
Regarding efficacy, SVR rates for the overall cohort, patients < 65-years-old, ≥ 65-years-old but < 75-years-old, and ≥ 75-years-old were 97% (258/265), 98% (93/95), 97% (84/87), and 98% (81/83), respectively (P = 0.842). Among patients ≥ 75-years-old with a history of interferon plus ribavirin therapy, the SVR rate was 100% (14/14). Furthermore, the SVR rate of cirrhotic patients ≥ 75-years-old was also extremely high (98%, 40/41). From these results, a high SVR rate (> 95%) would be expected even in patients ≥ 75-years-old, irrespective of cirrhosis or history of interferon treatment. Logistic regression analyses identified history of HCC treatment and alpha-fetoprotein as factors significantly associated with SVR. SVR rate was significantly lower for patients with HCC treatment (91%) than for patients without history of HCC treatment (98%, P = 0.004). Regarding safety, although dose reduction or interruption of ribavirin due to anemia was required in 21.7% of patients ≥ 75-years-old and 7.7% of patients < 75-years-old, treatment discontinuation was required for only one patient (0.4%). Therefore, this treatment appears tolerable even in patients ≥ 75-years-old.
Sofosbuvir and ribavirin represent an acceptable and effective treatment even for patients ≥ 75-years-old in a real-world setting. An extremely high SVR rate can be achieved when adequate management for adverse effects is performed to avoid discontinuation of treatment, irrespective of age.
Sofosbuvir plus ribavirin might be less effective in patients with a history of HCC treatment or high alpha-fetoprotein level, irrespective of age. These patients should probably be treated using some other ribavirin-free direct-acting antiviral agent therapy.