Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis

Abstract

Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25–53 years) with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet) and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100%) achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU/mL. The treatment was well tolerated: none of the patients presented with a serious adverse event requiring hospital admission and none had anemia or any significant changes in blood count. One patient had a short period of diarrhea, which was resolved with antibiotic treatment. The combination of reduced-dose SOF and full-dose DCV, daily, was a safe and effective treatment in our group of hemodialyzed patients infected with HCV genotype 3.

Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis

“…The included studies were published from 2015 to 2020 and contained extractable data on 514 patients enrolled from 2014 to 2016. Four studies were retrospective [10][11][12][13] and 16 were prospective [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] . Nine of the studies were conducted in India 10,12,14,16,18,20,22,25,29 , 2 in the USA 15,21 , 2 in Pakistan 24,28 , 2 in China 19,27 , 1 in France 17 , the Czech Republic 11 , Korea 13 , Iraq 26 , and 1 enrolled patients from multiple countries 23 .…”

“…A total of 19 studies reported extractable data on the SOF dose [10][11][12][13][14][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and the other DAA included in the treatment regimen. In nine studies [10][11][12][13]16,19,[21][22][23] , the same treatment regimen was used for all study participants. Six studies partitioned the study participants into subgroups and followed a different treatment strategy for each subgroup 14,17,18,20,24,25 .…”

“…A sub-group analysis was not performed for the various other DAA used in the treatment regimens, due to the large variability of DAA used. Ribavirin was used in 6 studies 10,13,14,16,18,28 , simeprevir in 3 15,17,21 , ledipasvir in 8 17,[20][21][22][25][26][27]29 , daclatasvir in 9 10,11,14,[16][17][18][19][20][24][25][26][27][28][29] and velpatasvir in 2 studies 12,23 (Table 1).…”

“…A total of 16 studies reported extractable data on adverse events [10][11][12][13][14][16][17][18][19][21][22][23]25,[27][28][29] ( Table 2). The most commonly reported adverse events were anemia (10 studies) 10,[12][13][14][16][17][18]21,23,28 , headache (8 studies) 12,17,[21][22][23]25,27,29 , fatigue (6 studies) 13,16,17,19,23,25 , nausea or vomiting (5 studies) 19,21,23,25,29 , insomnia (5 studies) 13,19,21,23,29…”

Safety, efficacy and cost of two direct‐acting antiviral regimens: A comparative study in chronic hepatitis C Egyptian patients

“…This phenomenon was explained by a decrease in mean corpuscular volume, serum iron and serum ferritin levels resulting in iron deficiency . In contrast, results of Gp1 were contrary to those of Sperl et al, who showed no significant changes in blood count in HCV G3 patients after a full course of sofosbuvir/ daclatasvir therapy.…”