Introduction:
Hepatitis C virus (HCV) infection incidence is 1.5-3 per 100 patient years and 10% prevalence in dialysis population. In India, prevalence ranges from 4 to 46%. In early days, prevalence of HCV in dialysis units in United states was 25% and 50% in developing countries. Mortality risk is high in HCV infected population on dialysis (Relative Risk -1.34) compared to non-HCV infected population on dialysis. HCV is associated with increase in hepatic disease and cardiovascular related mortality. During interferon era, only 1% of dialysis patients used to receive treatment for HCV infection due to side effects associated with the therapy. Mortality in untreated patients was 21%, compared to 9% in the treated group. Treating the dialysis patients may improve the survival. Extra hepatic manifestations in HCV like glomerulonephritis, proteinuria, cryoglobulinemia, Chronic Kidney Disease (CKD), insulin resistance will increase the morbidity and mortality in these patients. Now a days Sustained Virological Response (SVR) is more than 90% with the use of second generation Directly Acting Antiviral (DAA) in HCV infected population. HCV infection causes accelerated progression to End Stage Renal Disease (ESRD) and treatment with DAA decreases rate of decline in Glomerular Filtration Rate (GFR). The recently approved drugs are pan genotypic which are also safe and effective in dialysis patients. Nephrologist needs to know the optimal timing, dose, and choice of DAA based on GFR status of the transplant and degree of liver disease. In this single-centre observational study, our objective is to evaluate the efficacy and safety of Sofosbuvir+ Daclatasvir (S+D) and Sofosbuvir+ Velpatasvir (S+V) in the treatment of HCV genotype 1a in dialysis patients.
Methods:
It is a single center observational study done in tertiary care center, KIMS Hospital, Kurnool, Andhra Pradesh, India. The study duration was from April 2019 - April 2024 (5 years). All the dialysis patients who were detected to have HCV infection from April 2019 to April 2024, who were on follow up at KIMS hospital were enrolled for this study. HCV PCR negative patients were excluded. During this period 70 patients were included for the study. Depending on availability of drugs, cases were allotted to one of the two groups- 1) S+D (Sofosbuvir 400mg, Daclatasvir 100mg 2) S+V (Sofosbuvir 400mg, Velpatasvir 60mg). Both the regimens were given once daily for 12 weeks. Those patients who had relapse or treatment failure, the alternate regimen was given for 24 weeks. Sustained Virologic response (SVR) at 12 weeks was compared in the 2 groups and these patients were followed up for 5 years. HCV PCR was done once in 6 months for all the patients during follow-up. Ethical committee permission was taken from the hospital. No prior power analysis was performed to determine the target sample size. Baseline demographic details and clinical data was obtained and entered in Microsoft excel sheet in a structured format. The categorical variables were analysed using the Chi-Square test and continuous variables were analysed using the Student T-Test or Mann-Whitney U test as appropriate. The P-value of less than 0.05 was taken as statistically significant. Statistical analysis was performed using SPSS 23 software. No external funding was received for this study.
Results:
This Study enrolled 70 haemodialysis patients with HCV genotype 1a infection from April 2019 to April 2024 were allotted to one of the two groups S+D (group A) and S+V (group B). Out of these, 43(96%) patients in S+D group and 24(96%) patients in S+V group achieved remission. Treatment failure in S+D is 2(4%) and S+V is 1(4%). Need to decrease the dose of sofosbuvir was seen in S+D group only by 17% which is statistically significant. Proton Pump Inhibitor (PPI) usage in both groups were 26 and 16 patients respectively. Anti HCV antibodies was positive in 41(91%) and 19(76%) before starting therapy in group A and group B. After starting treatment, Anti HCV antibody was positive in 36 patients (80%) in group A and 15 patients (60%) group B, respectively. The mean viral load in S+D group is 416184(84621-155000) and S+V group is 261631(6582.75-909981.2). One patient in each group was positive for both HBV& HCV. Total number of deaths in S+D group is 10(22%) and S+V group is 7(28%). The mean duration of treatment completion to death in months is 8(2.5-15.5) in group A and 9(6-12.75) in group B. The mean hemoglobin was 9.4 grams(8.9-to10.6) in S+D group and 9.1 grams (7.5 to 9.85) in S+V group which is statistically significant(p value is 0.04). 20(45%) patients in S+D group and 8(32%) patients in S+V group has hemoglobin drop during treatment. Erythropoietin (EPO) dose requirement before initiating the treatment in both the groups was 8000 units S/C. The EPO dose requirement increased to 12000 units in S+D group and 10,000 units in S+V group after treatment. Mean SGOT levels before treatment was 43(20.5-94) in S+D and 29(20-53.5) in S+V whereas after treatment it is 13(12-16) and 14(11-16.25) respectively. Two patients was on ATT in S+D group. Drugs side effects was evident in both the groups. Compared to various other studies like Goel et al, Sergio et al, Sunil et al and Kalyan et al done on genotype 1a, this study has higher sample size (n=70), better SVR (96%) and lesser relapse rate (4%). Strength of this study is being largest study in India in dialysis patients with HCV Genotype 1a infection with follow up for 5 years. The study design was limitation. In near future, need many more studies especially RCT on HCV infected dialysis patient for protocolising standard care of treatment.
Conclusions:
HCV infected dialysis patient was cured completely (96%) and relapse occurred only in 4% of patients who also got cured with 24 weeks of treatment. Both regimens (S+D) and (S+V) are highly effective and well tolerated in dialysis patients, although S+V regimen had less anemia and there was less needed to reduce Sofosbuvir dose. Treatment should be offered to all dialysis patients to prevent spread of HCV infection and its related complications.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.