The era of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) began in May 2011 with the addition of boceprevir and telaprevir to the backbone of peginterferon and ribavirin combination therapy for genotype-1 infection.1,2 Sustained virologic response (SVR) rates improved with these triple therapies compared with traditional combination therapy, including for patients with cirrhosis.3-7 Although treatment duration was shortened for many patients, it could still be as long as 48 weeks for some.2 Sofosbuvir, recently approved in combination with peginterferon and ribavirin, also offers improved SVR rates compared with peginterferon and ribavirin but with a dramatically reduced treatment duration of only 12 weeks for treatment-naive patients.8,9
A 68-year-old Hispanic male presented to you for a discussion of HCV treatment options. He was recently diagnosed with chronic HCV when his physician ordered an HCV screening test in response to the 2012 recommendation by the Centers for Disease Control and Prevention that all individuals born between 1945 and 1965 be tested for HCV, regardless of other risk factors.10 He likely acquired the infection approximately 30 years ago from a blood transfusion while in the military. His past medical history includes arthritis, hyperlipidemia, and diabetes, treated with ibuprofen, atorvastatin, and metformin, respectively. He is currently retired but travels extensively with his wife to visit their grandchildren.
Follow-up HCV testing showed genotype-1b infection and a viral load of 6.2 million copies/mL. An imaging study and ultrasound of his liver demonstrated a nodular liver with mild splenomegaly. Endoscopy demonstrated no esophageal varices. Blood work showed a hemoglobin level of 13.2 g/dL, a platelet count of 108,000/mm3, an aspartate aminotransferase of 94 IU/L, and an alanine aminotransferase of 79 IU/L. Bilirubin, international normalized ratio, and albumin were in the normal range.
Physical examination was normal. His blood pressure was 128/70 mmHg, respirations 16. There was no hepatomegaly and no apparent splenomegaly. He had mild central obesity (94 kg), no muscle wasting, and no palmar erythema.
You reviewed his results with him and explained that he had compensated cirrhosis.
You discussed treatment options with him, including approved therapies in combination with peginterferon and ribavirin as well as the option of entering a clinical trial. In particular, you discussed the efficacy and safety of recently approved sofosbuvir and simeprevir, both in combination with peginterferon and ribavirin. He voiced concern about entering a clinical trial due to his cirrhosis, preferring instead an approved therapy. He elected to begin sofosbuvir-based triple therapy due to its treatment duration of only 12 weeks versus 48 weeks with simeprevir-based triple therapy (extension from 24—48 weeks for cirrhotics).11,12 Because sofosbuvir is excreted in the urine, no dose adjustments were needed for his other prescribed drugs.11
At treatment week 2, blood work showed a mild reduction in hemoglobin, from 13.2 g/dL at baseline down to 11.2 g/dL, but the patient reported feeling well other than mild fatigue and insomnia. At week 4, his viral load was undetectable. He said he was “doing reasonably well” except for the ongoing insomnia, for which he had started taking zolpidem. He continued therapy through week 12 and showed undetectable HCV RNA at end of treatment. Twelve weeks later he returned and SVR12 was documented. The patient was instructed that he would require ongoing close surveillance for hepatocellular carcinoma and decompensation. Nonetheless, achieving SVR has been well reported to reduce the risk of liver failure, hepatocellular carcinoma, and all-cause and liver-related mortality in patients with advanced fibrosis.13
Since his 12-week appointment, the patient has begun traveling again.
Sofosbuvir, a nucleotide polymerase inhibitor, in combination with peginterferon and ribavirin for treatment-naive patients was evaluated in the phase III NEUTRINO trial. This trial was a single-arm open-label study enrolling treatment-naive patients with genotypes 1, 4, 5, or 6 infection (genotype 1, 98%).8 All patients received sofosbuvir 400 mg orally once daily plus peginterferon alfa-2a 180 micrograms and weight-based ribavirin for 12 weeks.8 Of the 327 treated patients, 17% had cirrhosis.8
Explore Figure 2: How Parity Affects Risk of First Demyelinating Event Among Women12
Overall, 90% of patients achieved SVR12, including 80% for patients with cirrhosis.8 See the Table for SVR per patient group.8 The most common adverse effects were fatigue, headache, nausea, and insomnia.8 Based on these findings, sofosbuvir in combination with peginterferon and weight-based ribavirin for 12 weeks is now the recommended regimen for treatment-naive patients with genotype-1 infection who are eligible to receive interferon according to the newly released treatment guidelines issued by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.9 This regimen is also the recommended regimen for treatment-naive genotype-1 cirrhotic patients.9
This case demonstrates that high SVR rates can be achieved by treatment-naive genotype-1 patients using interferon-based therapies, such as sofosbuvir in combination with peginterferon and ribavirin, with a total treatment duration of only 12 weeks. Importantly, this patient with cirrhosis, who had much to gain by achieving SVR, was able to complete therapy with no ribavirin dose reduction and minimal side effects.
Jacobson IM, Pawlotsky JM, Afdhal NH, et al. A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C. J Viral Hepat. 2012;19(suppl 2):1-26.
Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433-1444.
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.
Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.
Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417-2428.
Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207-1217.
Forestier N, Zeuzem S. Telaprevir for the treatment of hepatitis C. Expert Opin Pharmacother. 2012;13:593-606.
Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878-1887.
American Society for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating Hepatitis C. January 2014. Accessed 4/16/14 at: http://www.hcvguidelines.org/sites/default/files/full_report.pdf.
Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR. 2012:61(RR-04):1-18.
Sovaldi [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2013.
Olysio [package insert]. Titusville, NJ: Janssen Products, LP; December 2013.
van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584-2593.