Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea

Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea
Cho Y1, Cho EJ1, Lee JH1, Yu SJ1, Yoon JH1, Kim YJ1.

CMH 2015 December;21:358-364.
Published online 2015 December 28.
Copyright © 2015 The Korean Association for the Study of the Liver

Abstract
BACKGROUND/AIMS:
The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein.

METHODS:
Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin.

RESULTS:
This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naïve patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy.

CONCLUSIONS:
In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy.

DISCUSSION ONLY
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In this retrospective study analyzing the efficacy of sofosbuvir based therapy for the CHC patients in Korea, a remarkable SVR 12 rate was noted, as high as 100% in both HCV genotype 1b and 2, and in both treatment-naїve and previously-treated patients.

For the HCV genotype 1b patients with previous history of IFN-based therapy, HCV RNA was slowly suppressed by sofosbuvir-based therapy. However, SVR rate was not different among treatment-naїve patients and patients with previous history of IFN-based therapy.

Sofosbuvir-based IFN-free therapy showed high response rates among patients with both HCV genotype 1b and 2 with negligible adverse effects. Hemoglobin slightly decreased after sofosbuvir or sofosbuvir/ledipasvir + ribavirin. However, no patient needed transfusion, and there was no premature discontinuation of sofosbuvir-based therapy.

The presence of liver cirrhosis significantly increased the risk of failure for virologic response at week 4. However, SVR 12 rate was as high as 100%. No clinically significant treatment-emergent adverse events were noted in patients receiving sofosbuvir or sofosbuvir/ledipasvir + ribavirin combination. Hematological abnormality except for mild anemia was noted in patients receiving ribavirin.

The low incidence of adverse events related with the relatively short duration of treatment as compared to IFN-based therapy might improve treatment adherence and completion. Among patients with HCV infection and liver cirrhosis in whom pegylated IFN + ribavirin treatment has failed, SVR rates to retreatment with IFN-containing regimens are as low as 14%.16-21

In addition, treatment for HCV infection, especially with IFN-based regimens, in patients with liver cirrhosis is associated with increased toxic effects.22,23 In this study, we found that sofosbuvirbased therapy shows potent antiviral effect even in CHC patients with liver cirrhosis.

However, slightly slow response rate was noted among the patients with cirrhosis which is known as a factor associated with a poor response. Cirrhotic patients with HCV infection have experienced low response rate with interferon-based therapy or protease-inhibitor containing regimen in many studies.16,18,19,24,25

The exact mechanism of cirrhosis on response to treatment has not been identified yet. Serum HCV RNA declines in two phases: the rapid first phase and followed by a more gradual second phase of decline. Cirrhotic patients experience slower second phase decline as compared to non-cirrhotic patients.26

Therefore, close follow-up and monitoring HCV RNA is needed for cirrhotic CHC patients and sufficient duration of DAAs-combination is warranted to achieve SVR 12, as high as 100%.18,19,24,27 In EASL guideline, 8 weeks of duration for sofosbuvir/ledipasvir is also recommended for CHC genotype 1 patients without cirrhosis.8

However, all patients included in this study received sofosbuvir/ledipasvir plus ribavirin for more than 12 weeks, due to lack of Korean experiences. Based on our results, 8 weeks of sofosbuvir/ ledipasvir plus ribavirin might be sufficient to achieve SVR 12 in CHC genotype 1 patients without cirrhosis in Korea. Moreover, efficacy of sofosbuvir/ledipasvir without ribavirin in Korea should be further investigated.

Combinations of DAAs for 12–24 weeks have established the potential of IFN-free regimens for both treatment-naive patients and IFN-experienced patients with HCV genotype 1b or 2 infections.28-32 IFN-free regimens are becoming the new standard of treatment for CHC patients in Western countries. Official approval for DAAs in Asia countries lags behind that in the Western countries. However, several DAAs are becoming available for clinical use in Korea. This study demonstrates real-life management data of initial experiences for sofosbuvir-based therapy which has highly potent antiviral activity against HCV, and has been approved and will be commercially available in a few months in Korea. Our initial experience might provide helpful guidance for clinical use of DAAs, as to the best strategies for CHC management in Korea.

In conclusion, sofosbuvir-based IFN-free therapy could provide a short, all-oral treatment which is effective in both treatment-naive and previously treated CHC patients. Further large scale real world studies are warranted when sofosbuvir-based therapy is commercially available in Korea. Importantly, sofosbuvir-based IFN-free therapy might be highly effective and safe in CHC patients including those who have not responded to standard of care IFN-based regimens.

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