COMBINED NS5A & NS5B NUCLEOTIDE INHIBITOR THERAPY FOR PATIENTS WITH CHRONIC HEPATITIS C WITH STAGE 5 CHRONIC KIDNEY DISEASE ON HEMODIALYSIS

Abstract

BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

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.…”

“…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…”

“… 27 2017 Prospective China 7 53 71.4 GT-1b: 57, GT-2a: 29, GT-6: 14 DCV, LDV 400 mg daily 6 (86%) Debnath et al . 25 2017–2018 Prospective India 18 39.4 77.8% GT-1: 66.7, GT-2: 5.5, GT-3: 22.3, GT-5: 5.5 DCV, LDV 400 mg daily 18 (100%) Singh et al . 29 2015–2017 Prospective India 39 39.6 83% GT-1: 68, GT-3: 28, GT-4: 4.3 DCV, LDV 400 mg daily 37 (95%) Mandhwani et al .…”