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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 2
| Issue : 1 | Page : 22-26 |
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Clinical profile and response to treatment in chronic hepatitis C and renal disease: A prospective study from North India
Aadil Ashraf1, Ahmad Yousuf Wajeed2, Javed Khan3, Altaf Hussain Shah4, Hilal Dar5
1 Department of Medical Gastroenterology, Asian Institute of Gastroenterology Hospitals, Hyderabad, Telangana, India
2 Department of Gastroenterology, Health Services Kashmir, Kashmir, India
3 Department of Internal Medicine, GMC Srinagar, Srinagar, India
4 Department of Medical Gastroenterology, Sher I Kashmir Institute of Medical Sciences, Soura, Srinagar, India
5 Department of Internal Medicine, GMC Baramulla, Baramulla, Jammu and Kashmir, India
| Date of Submission | 15-Mar-2023 |
| Date of Decision | 24-Apr-2023 |
| Date of Acceptance | 05-Jun-2023 |
| Date of Web Publication | 21-Aug-2023 |
Correspondence Address:
Dr. Aadil Ashraf
Department of Medical Gastroenterology, Asian Institute of Gastroenterology Hospitals, Mind Space Road, Gachibowli, Hyderabad 500032, Telangana
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JIMPH.JIMPH_3_23
BACKGROUND AND AIMS: Successful treatment of hepatitis C virus (HCV) infection is associated with improved outcomes in different clinical domains. The treatment of HCV infection in high-risk groups like chronic kidney disease (CKD) is challenging. We conducted a study on the efficacy of the fixed-dose combination of sofosbuvir–velpatasvir in CKD patients. MATERIALS AND METHODS: The study was conducted in our hospital, Sher I Kashmir Institute of Medical Sciences Soura. Patients with HCV infection (detectable RNA levels) with an estimated glomerular filtration rate (eGFR) >15 mL/min were included in the study. All the patients were evaluated for liver disease. Patients with prior exposure to a direct-acting antiviral agent, portal vein thrombosis, or hepatocellular carcinoma were excluded from the study. All the patients received an open-label combination of sofosbuvir and velpatasvir (400/100 mg). The primary endpoint was to assess sustained virological response 12 (SVR12), and the secondary endpoint was to assess the side effect profile of the patients. RESULTS: A total of 33 patients were enrolled in the study, with 17 in Group A (GFR 15–30 mL/min/1.73 m2) and 16 in Group B (GFR >30 mL/min/1.73 m2). In total, 142 (87.6%) achieved viral clearance at 4 weeks of therapy. Sixteen out of 17 (94.1%) in Group A and 13 out of 16 (81.25%) in Group B achieved viral clearance at 4 weeks of therapy [early virological respsone (EVR)]. All patients in both groups achieved end-of-treatment response viral clearance, and the same number of patients maintained viral clearance 12 weeks after stopping the treatment (SVR12). In Group A, no significant improvement was seen in the mean level of any parameters pre and posttreatment. In Group B, there was an improvement in all the parameters except serum creatinine after the completion of treatment. However, the difference was significant between pre and posttreatment values of serum alanine transaminase (U/L) and liver stiffness measurement levels (P value of −0.04 and 0.01, respectively). CONCLUSION: We conclude that treatment with sofosbuvir–velpatasvir is a safe and effective treatment option in HCV infection in CKD. Keywords: CKD, hepatwitis C in CKD, sofosbuvir
How to cite this article:
Ashraf A, Wajeed AY, Khan J, Shah AH, Dar H. Clinical profile and response to treatment in chronic hepatitis C and renal disease: A prospective study from North India. J Integr Med Public Health 2023;2:22-6 |
How to cite this URL:
Ashraf A, Wajeed AY, Khan J, Shah AH, Dar H. Clinical profile and response to treatment in chronic hepatitis C and renal disease: A prospective study from North India. J Integr Med Public Health [serial online] 2023 [cited 2023 Sep 21];2:22-6. Available from: http://www.jimph.org/text.asp?2023/2/1/22/384122 |
| Introduction | |  |
Apart from hepatic manifestations, chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations. Chronic kidney disease (CKD) is one such extrahepatic manifestation of HCV infection.[1] HCV infection also causes cryoglobulinemia and leads to cryoglobulin deposits on vascular endothelium, triggering vasculitis in organs such as the kidneys.[2] Chronic hepatitis C is the most commonly seen viral infection in patients with renal insufficiency.[3] HCV infection in patients with CKD carries a risk of more rapid progression of liver disease and is associated with worsening renal function and increased risk of graft failure after renal transplantation and mortality.[4],[5] Treatment of HCV infection has changed markedly in recent years, with direct-acting antiviral agents (DAAs) replacing pegylated interferon and ribavirin combination as the standard-of-care.[6],[7] In many studies, a fixed-dose combination of sofosbuvir–velpatasvir has proved to be extremely effective in the treatment of the high-risk group of hepatitis C with CKD. We intend to study the effectiveness of a fixed-dose combination of sofosbuvir–velpatasvir in CKD patients.
Aims
- ➣ To assess the efficacy of sofosbuvir–velpatasvir in CKD patients, excluding end-stage renal disease and patients on hemodialysis.
- ➣ To assess the safety and side effect profile during treatment.
| Materials and Methods | | |
The study was conducted with both inpatients and outpatients in collaboration with the Department of Nephrology at Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, from September 1, 2018 to February 2021. Permission was sought from the institutional ethical committee (IEC-SKIMS) vide no. RP 86/2020. Proper informed consent was taken from all patients after explaining the whole study design in the local language.
The patients were diagnosed with CKD as per the chronic kidney disease-epidemiology collaboration equation[8] and were classified into different CKD categories as per the latest kidney diseases improving global outcomes guidelines. All CKD patients were tested for hepatitis C by the enzyme-linked immunosorbent assay method. Patients were divided into two groups based on glomerular filtration rate (GFR):
- Group A: Patients with GFR 15–30 mL/min/1.73 m2.
- Group B: Patients with GFR > 31 mL/min/1.73 m2.
All CKD patients with detectable HCV RNA levels were included in the study. A detailed history regarding the present illness and past significant medical and surgical illness was taken. A detailed note of the performance status of patients was taken. Complete baseline investigations were done with a special focus on hepatobiliary, renal, and cardiovascular status.
All the patients were evaluated for liver function status, and liver cirrhosis was diagnosed if the patient had gastroesophageal varices at endoscopy or ascites with serum-ascites albumin gradient of more than 1.1 g/dl[9] with additional supporting clinical and/or biochemical features. Patients were assessed for fibrosis using liver transient elastography. A cutoff value for the liver stiffness measurement >7.1 kPa F2 denoted significant fibrosis, and >12.5 kPa F4 was regarded as cirrhosis.[10] Patients were included irrespective of the severity of liver disease or prior exposure to non-DAA treatment.
Exclusion criteria
Patients who are not willing to be part of the study.
Patients with end-stage renal disease and on hemodialysis.
Patients with prior exposure to a DAA (irrespective of duration).
The endpoints of the study were:
- 12 weeks of follow-up after treatment completion,
- Discontinuation of anti-HCV treatment, or
- Death or loss to follow-up either during treatment or during the posttreatment follow-up period.
Treatment regimen
All the patients were treated as per standard treatment guidelines for hepatitis C infection in CKD patients. The patients received a full-dose of sofosbuvir and velpatasvir combination (400/100 mg) once a daily tablet for 12 weeks or 24 weeks in case of decompensated liver disease.
Follow-up and assessment
The patients were followed up clinically every 2 weeks with kidney function tests repeated after every month during treatment and every 4 weeks thereafter till 12 weeks after treatment completion. More frequent follow-up was done in those with cirrhosis or if the clinician considered this necessary.
A detailed note of any adverse effects with a special focus on renal, cardiac, and hepatic systems was made.
The virological response was assessed by measuring serum HCV RNA concentration after 4 weeks of treatment (rapid virological response), at the end of the scheduled 12 or 24 weeks of treatment (end-oftreatment response [ETR]), and 12 weeks after stopping treatment (sustained virological response 12 [SVR12]). Intention-to-treat analysis was planned, with any missing data treated as a failure.
Statistical analysis
Statistical testing was conducted with the statistical package for the social science system version SPSS 22.0 (IBM SPSS statistics V22.0). Continuous variables are presented as mean ± SD and categorized into groups, and categorical variables are presented as frequencies and percentages. Nominal categorical data between the groups were compared using the Chi-squared test or Fisher’s exact test as appropriate. The comparison of normally distributed continuous variables between the groups was performed using Student’s t-test. P < 0.05 was considered statistically significant.
| Results | | |
Patients were divided into two groups:
Group A: Patients with GFR 15–30 mL/min/1.73 m2.
Group B: Patients with GFR > 31 mL/min/1.73 m2.
Age
A total of 33 patients belonged to these two groups, with 17 patients belonging to Group A (GFR 15–30 mL/min/1.73 m2) and 16 patients belonging to Group B (GFR > 31 mL/min/1.73 m2). The mean age in Group A was 49.6 years with a standard deviation of 11.80 years, while as mean age in Group B was 61.88 years with a standard deviation of 7.63 years [Table 1].
Sex distribution
Males outnumbered females in both study groups [Table 2].
Renal status
The mean creatinine in this Group A was 2.27 ± 0.49 mg/dl, and in Group B was 1.96 ± 0.24 mg/ dl [Table 3].
Liver disease
Of these studied groups, two patients in Group A had evidence of liver disease, while one patient in Group B had liver disease.
Baseline characteristics
The mean bilirubin in Group A and Group B was 1.32 ± 1.49 mg/dL and 0.93 ± 0.26 mg/ dL, respectively, while as mean alanine transaminase (ALT) in Group A and Group B was 127.4 ± 241.4 U/L and 62.1 ± 41.8 U/L, respectively. The values of other parameters are mentioned below [Table 4].
Treatment and posttreatment
All the patients were given full-dose of sofosbuvir and velpatasvir (400/100mg) once a day.
In Group A, 16 out of 17 (94.1%) patients achieved Viral clearance at 4 weeks of therapy (EVR). 17 (100%) of the patients achieved end-of-treatment viral clearance (ETR), and the same number of patients maintained viral clearance 12 weeks after stopping the treatment (SVR12).
In Group B, 13 out of 16 (81.25%) achieved viral clearance at 4 weeks of therapy (EVR). All 16 patients achieved viral clearance at the end of the treatment duration, and all of them maintained the same at 12 weeks after stopping the treatment (SVR) [Table 5].
The change in the mean level of all significant baseline parameters like serum bilirubin, ALT, albumin, creatinine, and International Normalised Ratio were calculated pre and post (12 weeks after treatment). Amongst the patients diagnosed with liver disease, a change in the mean level of MELD score and liver stiffness was calculated.
In Group A, no significant improvement was seen in the mean level of any parameters pre and posttreatment. Even though bilirubin and ALT showed an improvement posttreatment, however, the difference was not significant. There was a slight increase in serum creatinine posttreatment; however, the difference was not significant [Table 6].
In Group B, there was an improvement in all the parameters except serum creatinine after the completion of treatment. However, the difference was significant between pre and posttreatment values of serum ALT (U/l) and liver stiffness measurement levels. As observed in Group B, serum creatinine showed a slight increase after treatment; however, the difference was not statistically significant [Table 7]. | Table 7: Showing the difference in mean before and after treatment in Group B
Click here to view |
Side effect profile
The most common adverse effects noticed in both groups were dyspepsia (21%), nausea (16%), vomiting (10%), generalized weakness (10%), and headache (7%). None of the patients discontinued medication. Two patients were admitted during the study period (both belonging to Group A), one as meningoencephalitis and the other as urosepsis. The patient who was admitted with urosepsis had worsening renal parameters and needed to be dialyzed during the hospitalization.
| Discussion | | |
HCV infection is a major health concern and a major cause of chronic liver disease, with approximately 71 million chronically infected worldwide. The primary goal of HCV therapy is to cure the infection, i.e., to achieve an SVR defined as undetectable HCV RNA after treatment completion. An SVR corresponds to a cure of the HCV infection, as late relapse occurs in less than 0.2% of cases beyond 6 months of follow-up. The treatment of hepatitis C poses a significant challenge in some population groups, with the CKD population being one such group. Chronic HCV infection is independently associated with the development of renal impairment referred to as CKD and is more prevalent in patients with renal disease, especially if they are on dialysis. Sofosbuvir–velpatasvir, a pan-genotypic drug, is a very good option for the treatment of HCV infection in CKD patients.[11] According to these guidelines, patients with CKD with GFR > 30 mL/min/1.73 m2 can be treated with sofosbuvir-containing regimens. European association for study of liver recommends that patients with GFR < 30 mL/min/1.73 m2 can be treated with a fixed-dose combination of sofosbuvir and velpatasvir for 12 or 24 weeks in case of decompensated liver disease patients.
In Group A, 16 out of 17 (94.1%) patients achieved viral clearance at 4 weeks of therapy (EVR). 17 (100%) of the patients achieved end-of-treatment viral clearance (ETR), and the same number of patients maintained viral clearance 12 weeks after stopping the treatment (SVR12). While as in Group B, 13 out of 16 (81.25%) achieved viral clearance at 4 weeks of therapy (EVR). All 16 patients achieved viral clearance at the end of the treatment duration, and all of them maintained the same at 12 weeks after stopping the treatment (SVR). In the study by Okubo et al.,[12] the rates of SVR were 97.0% in patients with CKD stage 1, 97.1% in patients with CKD stage 2, and 94.7% in patients with CKD stage 3, respectively. In the study by Goel et al.,[13] HCV RNA was undetectable at 4 weeks of treatment, treatment completion, and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%), and 37/41 (90.2%), respectively. None of the patients had a relapse.
| Conclusion | | |
Sofosbuvir–velpatasvir fixed-dose combination is an effective treatment option for patients with CKD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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