Outcome of treatment for hepatitis C infection in hemodialysis patients with direct-acting second-generation anti-HCV drugs at Azzawiyah kidney hospital, Libya

Badreddin Shaibani; Khairi Ayad; Marwa Melodi; Sabah Albarasi; Badereddin Annajar; Mahdi Jibani

doi:10.4103/ljms.ljms_39_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 6 | Issue : 2 | Page : 53-57

Outcome of treatment for hepatitis C infection in hemodialysis patients with direct-acting second-generation anti-HCV drugs at Azzawiyah kidney hospital, Libya

Badreddin Shaibani¹, Khairi Ayad², Marwa Melodi³, Sabah Albarasi¹, Badereddin Annajar⁴, Mahdi Jibani⁵
¹ Azzawiyah Kidney Hospital, Zawia, Libya
² Sabratha Teaching Hospital, Sabratah, Libya
³ Hawari Kidney Center, Benghazi, Libya
⁴ Faculty of General Health, University of Tripoli, Libya
⁵ Department of Nephrology, Gwynedd Hospital, Betsi Cadwaladr University Health Board, Bangor, Wales, United Kingdom

Date of Submission	28-Jun-2021
Date of Acceptance	17-Nov-2022
Date of Web Publication	02-Jan-2023

Correspondence Address:
Prof. Badreddin Shaibani
Azzawiyah Kidney Hospital, Zawiya
Libya

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ljms.ljms_39_21

Abstract

Background: Hepatitis C virus infection is the most common viral infection in patients on hemodialysis and is a leading cause of chronic liver disease in end-stage renal disease patients. The main aim of this study was to review the outcome of the treatment of HCV in hemodialysis patients with second-generation anti-HCV drugs at Azzawiyah Kidney Hospital. Patients and Methods: Thirty-two hemodialysis patients with proven HCV infection (HCV-polymerase chain reaction-positive) received antiviral treatment for 12 weeks and followed up for 12 months, with liver function tests and repeated HCV-RNA. The primary outcome was the proportion of patients who achieved sustained virological response at 12 weeks posttreatment (SVR-12). Results: 32 patients (32/280, 11.4%) out of the total number of (280) regular hemodialysis patients were proven to have HCV infection, during the period from December 2016 to December 2019. The median age of the study population was 53.5 ± 12 years, and 55% were females. The median duration of dialysis was 9.6 years (range 3–25 years). The causes of chronic kidney disease were diabetes mellitus at 43.7%, hypertension at 25.5%, adult polycystic kidney disease at 12.5%, and chronic glomerulonephritis at 9.3%. Twenty nine (29/32) patients received antiviral treatment with sofosbuvir/daclatasvir (SOF/DLC) and ( 3/32) patients with elbasvir and grazoprevir (ERB/GZR). 96.9% of SOF/DLC achieved SVR 12 and 100% of EBR/GSR by the end of the treatment, only one patient ( 3.1 %) failed to achieve it. No significant side effects were reported for the treatment drugs. Conclusion: This study confirmed that the treatment of hemodialysis patients with chronic hepatitis C infection with second-generation anti-HCV drugs is safe and has elicited a sustained negative virological response.

Keywords: Antiviral therapy, chronic hepatitis, HCV, hemodialysis, hepatitis C virus, Libya

How to cite this article:
Shaibani B, Ayad K, Melodi M, Albarasi S, Annajar B, Jibani M. Outcome of treatment for hepatitis C infection in hemodialysis patients with direct-acting second-generation anti-HCV drugs at Azzawiyah kidney hospital, Libya. Libyan J Med Sci 2022;6:53-7

How to cite this URL:
Shaibani B, Ayad K, Melodi M, Albarasi S, Annajar B, Jibani M. Outcome of treatment for hepatitis C infection in hemodialysis patients with direct-acting second-generation anti-HCV drugs at Azzawiyah kidney hospital, Libya. Libyan J Med Sci [serial online] 2022 [cited 2023 Mar 29];6:53-7. Available from: https://www.ljmsonline.com/text.asp?2022/6/2/53/366079

Introduction

Patients undergoing dialysis treatment, and in particular hemodialysis (HD), are at increased risk for contracting viral infections. This is due to their underlying impaired cellular immunity, which increases their susceptibility to infection. Moreover, HD patients may require blood transfusion, frequent hospitalizations, and surgery, which increases opportunities for nosocomial infection exposure.^[1]

Hepatitis C virus (HCV) is a positive-strand RNA virus of the genus Hepacivirus within the Flaviviridae family infection. It is a well-known causative agent of a serious, contagious, and inflammatory disease, which affects the normal function of the liver, predominantly as a chronic infection.

At least six major genotypes of HCV have been identified worldwide, each comprising multiple subtypes. Substantial regional differences appear to exist in the distribution of HCV genotypes. Although HCV genotypes 1, 2, and 3 appear to have a worldwide distribution, their relative prevalence varies from one geographic area to another. A previous study conducted in Libya had shown that HCV infection with genotype 1 was more prevalent in the western region, and genotype 4 was the most prevalent genotype in the eastern region of the country.^[2] Another study by Elzuoki et al.^[3] reported the prevalence of genotypes 4 and 1a (66% and 60%, respectively) among the Libyan dialysis population.

Hepatitis C can spread in health-care settings when the standard precautions and other infection control practices are not consistently implemented.^[4] Often, most people with chronic HCV infection are asymptomatic or have nonspecific symptoms; in addition, some people might lack the immune response necessary to develop detectable antibodies within this time range.^[5],[6] In these people, virological testing (e.g., polymerase chain reaction [PCR] for HCV-RNA) is considered.

The prevalence of HCV infection varies greatly among patients on HD from different geographic regions.^[7] Some investigators suggested a decline in HCV prevalence among HD patients in recent years mostly attributable to strict adherence to universal precautions, with^{[8],[9],[10],[11],[12],[13]} or even without^[14],[15] observing isolation measures.

The goal of hepatitis HCV treatment is a cure, and the cure rate depends on several factors, including virus genotypes and the type of treatment given.^[16] Direct-acting antiviral agents (DAAs) are in clinical use in other parts of the world since 2014; a combination of sofosbuvir (SOF)/ledipasvir (LDV), approved by the United States Food and Drug Administration in October 2014 for the treatment of patients with HCV genotype 4 and genotype 1. Combination therapy with pegylated IFN-alpha and ribavirin (Peg-IFN-α/RBV) was the standard of care in Libya for the treatment of HCV infection until DAAs were launched in mid-2017.

DAAs have much better efficacy sustained virological response (SVR) and tolerance than interferon-based regimens. These drugs increase the cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs, the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs.

Patients and Methods

The medical records of 280 patients on the regular HD program at Azzawiyah Kidney Hospital from December 2016 to December 2019, were reviewed. 32 (32/280) patients infected with HCV were enrolled to receive antiviral treatment; 29 patients with a combination of SOF 400 mg tablet/daclatasvir (DLC) 60 mg, tablet at once daily dose, and three patients to receive 50 mg elbasvir and 100 mg grazoprevir single tablet once daily for 12 weeks.

All patients included in the study have their medical history reviewed; demographic data including age, race, sex, cause of kidney disease, and duration on HD (years), were collected. Laboratory tests before. During, and after treatment were done for complete blood count, albumin, total bilirubin, direct bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, glutamyl transpeptidase, international standard ratio (INR), prothrombin time, HBsAg, and anti HCV antibody. HCV-RNA was done before and during treatment, as well as 3, 6, and 12 months after treatment using the real-time HCV assay (Abbott), with the lower limit of quantitation of 15 IU/ml.

The scientific committee of the hospital permitted drugs to use for our patients; the treatment protocol applied in the study is according to the National Center for Disease Control (NCDC) regimen and advice. Written informed consent was obtained from each patient after the explanation of the aim of the study, treatment protocol, and possible drug side effects.

The primary endpoint of the study was drug safety, defined as occurrence of severe side effects or death, while the secondary endpoint is achieving a SVR at 12 weeks (SVR12), defined as an undetectable viral load 12 weeks post-treatment.

Patients with concomitant hepatitis B viral infection, malignancy, or liver cirrhosis were not enrolled in the study.

Statistical analysis

The data were analyzed using IBM SPSS version 22, (SPSS Inc. Chicago Il, USA); Descriptive characteristics of the study participants were calculated as mean ± standard deviation; t-test was used to compare the continuous variables.

Results

Patients' demographic characteristics are shown in [Table 1]. The mean age of the study population was 53.78 ± 13.73 (22–85) years; 56% were female (18/32); the mean duration of dialysis was 9.56 ± 5.69 years (range 3–25 years). The underlying etiology of chronic kidney disease was diabetes mellitus 43.7%, hypertension 25.5%, adult polycystic kidney disease 12.5%, and chronic glomerulonephritis in 9.3%. Hemoglobin level did not drop significantly during treatment [P < 0.05, [Table 2]], and erythropoietin doses were not changed. Laboratory tests were monitored at the start and the end of treatment, as shown in [Table 2]. A statistically significant reduction in the median serum ALT was observed from the baseline and at the end of treatment; (P < 0.05). The mean baseline HCV-RNA load was 4.35 × 10⁶ ± 1.08 IU/mL, which became undetectable (P = 0.962) by the end of treatment in the responded patients.

Table 1: Demographic characteristics of the patients at baseline (n=32)

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Table 2: Comparison of the hematological and biochemical blood profiles tests among the studied patients before and at the end of treatment

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Sustained Virological response (SVR12) ([Table 3]) have shown that; SVR12 was achieved in 28 patients (28/29, 96.6%) and not achieved in only one patient (1/29, 3.4%) of the subgroup of SOF/DLC. Three patients (3/3, 100%) achieved SVR12( of the Zepatier subgroup.

Table 3: Distribution of virological responses in the study participants

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Thirty-one patients (96.9%) had negative HCV-PCR at 3-month posttreatment and had achieved a sustained virologic response with negative HCV-PCR 3 months after treatment ends and at 12 months posttreatment. No significant change in bilirubin and INR was recorded. The study shows that: DAA treatment is effective in treatment of HCV infection in hemodialysis patients as 96.9 % (31/32) of patients with HCV infection have responded to DAA treatment, and only one patient (3.1%) had not responded and considered none responder.

No major or serious side effects were observed [Figure 1]. Eighty-three percent of the patients had not complained of any new complaint; although HD patients usually have many complaints due to their disease, and to dialysis treatment itself, we recorded the following complaints: 6% had gastrointestinal tract upsets and dizziness and 3% had a headache. No patient died during the treatment and observation period. All patients tolerated treatment well without dropout cases.

Figure 1: Distribution of observed side effects

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Discussion

Worldwide, the chronic hepatitis C virus has a prevalence between 5% and 60%, depending on the geographical region.^{[17],[18],[19],[20]} The prevalence of HCV infection in Libya varied widely between HD centers from 0% to 35.9%.^[21]

}Previously published data have demonstrated a partial efficacy of IFN in the treatment of HCV-infected dialysis patients,^{[22],[23],[24]} and concluded that the use of ribavirin in these patients had been absolutely contraindicated because of the high incidence of side effects that mainly include hemolytic anemia.

The DAAs therapy was started when the first-wave, first-generation HCV NS3-4A protease inhibitors, boceprevir and telaprevir, were approved in combination with Peg-IFN-α/RBV for the treatment of chronic HCV genotype 1 infection in 2011.^[25] However, these drugs have been reported to have several drug–drug interactions; then in 2014, successively, the second wave of DAA agents (SOF, DLC, simeprevir, LDV, dasabuvir, ombitasvir, paritaprevir, elbasvir, and grazoprevir) are available for the treatment of chronic hepatitis C infection. In randomized clinical trials with DAAs, different superb rates of SVR 12 been achieved.^{[26 30]} Elhaddad et al. confirmed that the second generation anti HCV drugs (SOF, DLC, and Zepatier) in combination or single have proven to be safe and effective in the treatment of HCV patients in Libya^[31] and approved by the NCDC for such a treatment.

One year later; the non-responder patient have received a combination of 50 mg elbasvir and 100 mg grazoprevir in form of single tablet daily for 12 weeks, and had showed a negative anti HCV antibody, and negative HCV RNA, no viral load detected, and finished the treatment with no side effects.

The genetic barrier to resistance for DAAs is decided by the number and type of base pair mutation(s) needed to produce amino acid substitution(s) that confers resistance to the agent.^{[31],[32],[33]} This may explain the no-response case of that single patient, though resistance profiles of currently available DAAs have not been identified, and there are no established standardized commercial assays for testing for resistance;^[34] antiretroviral drug switching may be required to allow for compatible DAAs.

Conclusion

This study confirmed that the treatment of HD patients with chronic HCV infection by the second-generation anti-HCV for 12 weeks is effective, safe, and has elicited a negative SVR.

Acknowledgments

The authors gratefully acknowledge the support of the Authority of the National Center for Diseases Control, Libya, for their support in providing the drugs and their laboratories allowance for the researchers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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