The Effectiveness of Sovodak in the Treatment of Patients with Chronic Hepatitis C


Background: Recently, interferon-free treatment has been considered for the treatment of chronic hepatitis C due to their high therapeutic success and lack of serious side effects. The combination of Sofosbuvir and Daclatasvir is effective in the treatment of the disease because of its pan-genotype. In the present study, the effectiveness of Sovodak, which is a combination of the aforementioned two drugs in one tablet, in the treatment of patients with chronic hepatitis C and cirrhosis was investigated.

Methods: Patients with chronic hepatitis C whose diagnosis was confirmed by HCV RNA–PCR test were included in the study. These patients received one Sovodak tablet daily (for 12 weeks for non-cirrhotic patients and 24 weeks for cirrhotic patients). Sustained virologic response (SVR) was assessed by PCR test 12 weeks after the end of the treatment and one year later. Also, serum levels of liver enzymes, platelet count, and liver stiffness (using elastography method) were measured and their levels were compared before and after treatment in patients.

Results: Findings related to the PCR test in patients showed that the level of SVR was 100% in patients 12 weeks after treatment (SVR-12). In three cirrhotic patients who received only 12 weeks of drug treatment, the disease recurred a year later. According to the results, ALT and AST serum levels were significantly decreased (P < 0.001), and platelet count level was increased (P < 0.001) one year after the end of the treatment period. Also, the liver stiffness index measured using FibroScan was significantly decreased in patients 12 weeks after the end of the treatment (P < 0.001).

Conclusion: The results of this study, in line with other studies, showed the effective role of Sovodak in completely eliminating the HCV virus in patients with chronic hepatitis C. Cirrhotic patients need to receive treatment for at least six months.

Key words: Sovodak, hepatitis C, sustained virologic response, effectiveness, liver cirrhosis

[1] Lauer, G. M. and Walker, B. D. (2001). Hepatitis C virus infection. New England Journal of Medicine, vol. 345, no. 1, pp. 41–52.
[2] Manns, M. P., Buti, M., Gane, E., et al. (2017). Hepatitis C virus infection. Nature Reviews Disease Primers, vol. 3, pp. 1–19.
[3] Merat, S., Rezvan, H., Nouraie, M., et al. (2010). Seroprevalence of hepatitis C virus: the first population-based study from Iran. International Journal of Infectious Diseases, vol. 14, no. 3, pp. e113–e116.
[4] Hatzakis, A., Chulanov, V., Gadano, A., et al. (2015). The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm–volume 2. Journal of Viral Hepatitis, vol. 22, no. 1, pp. 26–45.
[5] Penin, F., Dubuisson, J., Rey, F. A., et al. (2004). Structural biology of hepatitis C virus. Hepatology, vol. 39, no. 1, pp. 5–19.
[6] Pawlotsky, J. M. (2002). Use and interpretation of virological tests for hepatitis C. Hepatology, vol. 36, no. 1, pp. s65–s73.
[7] Pawlotsky, J. M., Lonjon, I., Hezode, C., et al. (1998). What strategy should be used for diagnosis of hepatitis C virus infection in clinical laboratories? Hepatology, vol. 27, no. 6, pp. 1700–1702.
[8] Simmonds, P., Bukh, J., Combet, C., et al. (2005). Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology, vol. 42, no. 4, pp. 962–973.
[9] Hadziyannis, S. J., Sette, Jr., H., Morgan, T. R., et al. (2004). Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Annals of Internal Medicine, vol. 140, no. 5, pp. 346–355.
[10] Jabari, H., Bayatian, A., Sharifi, A. H., et al. (2010). Safety and efficacy of locally manufactured pegylated interferon in hepatitis C patients. Archives of Iranian Medicine, vol. 13. no. 4, pp. 306–312.
[11] Hagan, L. M., Wolpe, P. R., and Schinazi, R. F. (2013). Treatment as prevention and cure towards global eradication of hepatitis C virus. Trends in Microbiology, vol. 21, no. 12, pp. 625–633.
[12] Samimi‐Rad, K., Nategh, R., Malekzadeh, R., et al. (2004). Molecular epidemiology of hepatitis C virus in Iran as reflected by phylogenetic analysis of the NS5B region. Journal of Medical Virology, vol. 74, no. 2, pp. 246–252.
[13] Sharifi, A. H., Haj-Sheykholeslami, A., Poustchi, H., et al. (2016). Efficacy of locally manufactured sofosbuvir and daclatasvir (Sovodak) in combination with ribavirin in treating patients with chronic hepatitis c and cirrhosis in Iran – preliminary report. Govaresh, vol. 21, pp. 93–97.
[14] Mehdipour, H., Moaddab, Y., Azizian, K., et al. (2019). Effects of 12-week treatment with Sovodak in patients infected by genotype 1 hepatitis C virus. Journal of Research in Clinical Medicine, vol. 7, no. 1, pp. 1–6.
[15] Merat, S. (2020). SD1000: high sustained viral response rate in 1361 patients with hepatitis C genotypes 1, 2, 3, and 4 using a low-cost, fixed-dose combination tablet of generic sofosbuvir and daclatasvir: a multicenter, phase III clinical trial. Clinical Infectious Diseases, vol. 70, no. 10, pp. 2206–2212.
[16] Pol, S., Corouge, M., and Vallet-Pichard, A. (2016). Daclatasvir–sofosbuvir combination therapy with or without ribavirin for hepatitis C virus infection: from the clinical trials to real life. Hepatic Medicine: Evidence and Research, vol. 8, p. 21.
[17] Ji, D., Chen, G.-F., Wang, C., et al. (2016). Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients. Hepatology International, vol. 10, no. 5, pp. 789–798.
[18] Welzel, T. M., Petersen, J., Herzer, K., et al. (2016). Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut, vol. 65, no. 11, pp. 1861–1870.
[19] Ahmed, O. A., Safwat, E., Khalifa, M. O., et al. (2018). Sofosbuvir plus daclatasvir in treatment of chronic hepatitis C genotype 4 infection in a cohort of Egyptian patients: an experiment the size of Egyptian village. International Journal of Hepatology, vol. 2018, aricle id. 9616234.
[20] Abdel-Moneim, A., Aboud, A., Abdel-Gabaar, M., et al. (2018). Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin: large real-life results of patients with chronic hepatitis C genotype 4. Hepatology International, vol. 12, no. 4, pp. 348–355.
[21] Omar, H., El Akel, W., Elbaz, T., et al. (2018). Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real‐world results from 18,378 patients in Egypt. Alimentary Pharmacology & Therapeutics, vol. 47, no. 3, pp. 421–431.
[22] Nelson, D. R., Cooper, J. N., Lalezari, J. P., et al. (2015). All‐oral 12‐week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY‐3 phase III study. Hepatology, vol. 61, no. 4, pp. 1127–1135.
[23] Merat, S., Sharifi, A. H., Haj-Sheykholeslami, A., et al. (2017). The efficacy of 12 weeks of sofosbuvir, daclatasvir, and ribavirin in treating hepatitis C patients with cirrhosis, genotypes 1 and 3. Hepatitis Monthly, vol. 17, no. 1, p. e44564.
[24] Leroy, V., Angus, P., Bronowicki, J. P., et al. (2016). Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: a randomized phase III study (ALLY‐3+). Hepatology, vol. 63, no. 5, pp. 1430–1441.
[25] Hung, C. H., Lee, C. M., Lu, S. N., et al. (2006). Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis. Journal of Viral Hepatitis, vol. 13, no. 6, pp. 409–414.
[26] Kasahara, A., Tanaka, H., Okanoue, T., et al. (2004). Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver‐related death. Journal of Viral Hepatitis, vol. 11, no. 2, pp. 148–156.
[27] Veldt, B., Saracco, G., Boyer, N., et al. (2004). Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut, vol. 53, no. 10, pp. 1504–1508.
[28] Maylin, S., Martinot–Peignoux, M., Moucari, R., et al. (2008). Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology, vol. 135, no. 3, pp. 821–829.
[29] Mallet, V., Gilgenkrantz, H., Serpaggi, J., et al. (2008). Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Annals of Internal Medicine, vol. 149, no. 6, pp. 399–403.
[30] D'Ambrosio, R., Aghemo, A., Rumi, M. G., et al. (2012). A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis. Hepatology, vol. 56, no. 2, pp. 532–543.
[31] George, S. L., Bacon, B. R., Brunt, E. M., et al. (2009). Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5‐year follow‐up of 150 patients. Hepatology, vol. 49, no. 3, pp. 729–738.
[32] Shiha, G., Soliman, R., Mikhail, N., et al. (2020). Changes in hepatic fibrosis stages after achieving SVR following direct‐acting anti‐viral treatment: a prospective study. GastroHep, vol. 2, no. 1, pp. 39–48.