Generic Sofosbuvir-based Direct-acting Antivirals in Hepatitis C Virus-infected Patients With Chronic Kidney Disease

Manoj Kumar; Suman L. Nayak; Ekta Gupta; Ashish Kataria; Shiv K. Sarin

Disclosures

Liver International. 2018;38(12):2137-2148. 

In This Article

Results

Baseline Characteristics

The demographic and baseline clinical characteristics of patients are shown in Table 1.

Seventy-one patients who fulfilled the inclusion and exclusion criteria were enrolled into the study.

Efficacy Outcomes

End of treatment response (HCV RNA <12 IU/mL at week 24 for sofosbuvir plus ribavirin group; and at 12 weeks for the other 2 groups) and sustained virological response (HCV RNA <12 IU/mL) at 12 weeks after stopping treatment sustained (SVR12) was seen in 100% of the patients in all the 3 groups (Table 2).

At the last follow-up, all 71 patients had completed 24 weeks of follow-up after end of therapy, and at that time 1 patient in sofosbuvir plus ledipasvir group became HCV RNA positive. This patient was not on dialysis after end of therapy and the virus was of the same genotype as pretreatment virus. That patient was treated with sofosbuvir plus valpatasvir for 12 weeks, when that combination became available in India in May 2017 and has achieved end of treatment virological response, SVR 12 weeks and SVR 24 weeks.

At the last follow-up, 67 (94.4%) of 71 had completed 48 weeks of follow-up after end of therapy and at that time 1 more patient became HCV RNA positive (in sofosbuvir plus ribavirin group). This patient was on regular haemodialysis after end of therapy and the virus was of the same genotype as pretreatment virus. This patient was later treated with sofosbuvir and ledipasvir for 12 weeks, when that combination became available in India and achieved end of treatment virological response, SVR 12 weeks, SVR 24 and SVR 48 weeks.

At the last follow-up, 35 (49.3%) had completed 72 weeks of follow-up after end of therapy (including the 2 patients who became HCV RNA positive at 24 and 48 weeks of follow-up after end of therapy). No other patient became HCV RNA positive at this time.

Safety Outcomes

None of the patients had to discontinue treatment because of side effects. Common non-haematological adverse events included fatigue, headache, insomnia, nausea and diarrhoea (Table 3).

In sofosbuvir plus ribavirin group, anaemia developed in 17/26 (65.4%) of patients; ribavirin had to be stopped in 8 (30.8%) of patients. Anaemia development was less in sofosbuvir plus ledipasvir [2/26 (7.7%)] and sofosbuvir plus daclatasvir group [2/19 (10.5%)] and was managed by increase in erythropoietin stimulating drugs dosage and none of the patients required stoppage of therapy.

Overall, 11 (15.5%) of patients were not on maintenance dialysis [5 (19.2%) in sofosbuvir plus ribavirin, 1 (3.8%) in sofosbuvir plus ledipasvir and 5 (26.3%) in sofosbuvir plus daclatasvir group]. Table 4 and Figure 1 show changes in e-GFR among these patients during follow-ups.

Figure 1.

Sequential estimated glomerular filtration rates during and after therapy among patients who were not on maintenance haemodialysis. S+R, sofosbuvir plus ribavirin; S+L, sofosbuvir plus ledipasvir; S+D, sofosbuvir plus daclatasvir

Estimated GFRs were statistically analysed up to 12 weeks after stopping of therapy only, as changes in e-GFRs after 12 weeks of stopping therapy may be because of other factors like natural progression of CKD or any other precipitating events. In 2 patients, there was increase in serum creatinine of >0.3 mg/dL at end of therapy from the baseline (patient 1 and 4, both treated with sofosbuvir and ribavirin for 24 weeks). In 1 patient (Figure 1, patient 3, treated with sofosbuvir and ribavirin), the patient was post liver transplant and developed urinary tract infection and tacrolimus toxicity at 2 weeks before the end of therapy. In the other patient, there was no clear precipitating factor for creatinine increase. Overall there was no significant change in median e-GFR values up to 12 weeks after stopping therapy. Figure 1 shows changes in e-GFR in individual patients till their last follow-up.

There were no serious adverse events or deaths in any of the groups.

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