Source: El-Khayat H, Kamal EM, Yakoot M, et al. Effectiveness of 8-week sofosbuvir/ledipasvir in the adolescent chronic hepatitis C-infected patients. Eur J Gastroenterol Hepatol. 2019; 31(8): 1004– 1009; doi: 10.1097/MEG.0000000000001360Investigators from multiple institutions in Egypt conducted a randomized trial assessing the efficacy and safety of sofosbuvir/ledipasvir (SOF/LVD) for 8 weeks, compared to 12 weeks, for treatment of genotype 4 hepatitis C virus (HCV) infection in adolescents 12–17 years old. Study patients were randomized to a single daily dose of a combination of SOF 400 mg and LVD 90 mg for either 8 or 12 weeks. At baseline, participants underwent a FibroScan to assess liver fibrosis using a standardized classification system. Laboratory screening was conducted at baseline and throughout the 12-week study period to measure HCV RNA and assess for possible adverse events; study participants reported adverse events. The primary study outcome was the sustained virologic response (SVR) rate, defined as undetectable HCV RNA at week 12. Secondary outcomes included SVR rates at 4 weeks and adverse events.A total of 157 patients were enrolled in the study: 73 were randomized to 8 weeks of SOF/LVD treatment and 84 to 12 weeks of treatment. The mean age of study patients was 14 years, the mean (standard deviation) HCV RNA at baseline was 5.80 (0.17) IU/L, and 68% had no to mild liver fibrosis at baseline. The source of HCV infection was considered to be perinatal infection in 73% of patients, surgical or dental procedures in 10%, and unknown in 17%. Patient characteristics were similar in the 2 treatment groups.The SVR rate at 12 weeks was 98.6% (95% CI, 93%–100%) for those treated for 8 weeks and 97.6% (95% CI, 96%–100%) for patients treated for 12 weeks. SVR rates at 4 weeks were 63% and 58%, respectively, for adolescents in the 8-week and 12-week treatment groups. Adverse events were reported by 7% of those in the 8-week group, including fatigue (2 patients), and headache, epigastric tenderness, and nausea in 1 patient each. Among patients randomized to 12 weeks of treatment, 8.3% reported an adverse event, including fatigue (1 patient), epigastric tenderness (1 patient), diarrhea (2 patients), nausea (1 patient), and rash (2 patients). Laboratory screening did not reveal any significant adverse events.The authors conclude that 8 weeks of SOF/LVD is as effective as 12 weeks of treatment in adolescents with HCV infection.Dr Rosenthal has disclosed the following financial relationships relevant to this commentary: Research grant support from Gilead, AbbVie, and Merck. This commentary does contain a discussion of an unapproved/investigative use of a commercial product/device.With the advent of highly effective direct-acting antiviral (DAA) drugs for HCV therapy, chronic HCV infection is no longer the leading indication in adults requiring liver transplant.1 Although therapies for HCV in children lag behind the regimens approved in adults, all oral DAA regimens in children are also now approved by the US Food and Drug Administration (FDA) and available.2 Regimens are so effective that cure can be anticipated in 8–12 weeks of therapy. The current investigators found that an 8-week course of SOF/LVD therapy was as effective and safe as the classic 12-week course in curing adolescents of genotype 4 HCV.In the United States, approximately 75% of chronic HCV infections are caused by HCV genotype 1; 15%–20% by genotype 2 or 3; and <5% by genotypes 4, 5, or 6.3 The FDA has approved 12-week combination SOF/LVD for the treatment of pediatric patients ≥12 years of age who weigh at least 35 kg and have HCV genotype 1 infection; they can be treatment naive without cirrhosis or with compensated cirrhosis or treatment experienced without cirrhosis.4 The FDA also approved its use for 12 weeks of therapy in adolescents with genotypes 4, 5, or 6 who are treatment naive or who are treatment experienced without cirrhosis or with compensated cirrhosis.4 In treatment-experienced adolescents with genotype 1 HCV and compensated cirrhosis, therapy should consist of 24 weeks of SOF/LVD. If SOF/LVD is used, 2 warnings need to be heeded.4 Patients with HCV and hepatitis B virus coinfection need to be monitored for hepatitis B virus reactivation and hepatitis flare during HCV treatment and posttreatment follow-up. Coadministration of amiodarone with SOF/LVD is not recommended because serious bradycardia with symptoms may occur.4DAA therapies for HCV infection are approved for use in adolescents. Regimens are effective and safe.At first glance, it would appear that therapy for HCV infection is solely within the purview of gastroenterologists. Pediatricians, however, can ensure that HCV screening is performed in patients at high risk, such as children of mothers who are HCV positive, and that potentially hepatotoxic agents (eg, alcohol) are avoided in those with HCV infection. (See AAP Grand Rounds. 2019;41[4]:45.5)
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Dec 20, 2019
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