Direct Acting Antiviral Treatment for Patients with End-Stage Kidney Disease with Acute HCV Infection
Received: February 17, 2019
Accepted: April 12, 2018
Mediterr J Hematol Infect Dis 2019, 11(1): e2019034 DOI 10.4084/MJHID.2019.034
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C virus (HCV) infection is a public health problem. Such an infection
is prevalent and aggressive in patients with end-stage kidney disease
(ESKD). The efficacy and the safety of direct-acting antivirus (DAA) in
patients with acute HCV and ESKD are under investigation. The aim of
this study was to assess the safety and efficacy of
sofosbuvir-containing regimens in this difficult-to-treat population.
The carcinogenesis of HCV is not fully understood. Although it is well known that HCV increases the risk of cancer through a complex molecular pathway that involves an inflammatory process, it is controversial that HCV plays a direct role in the development of liver cancer. Additionally, specific HCV genotypes are associated with a higher risk of hepatocellular carcinoma. In a study conducted in the USA, HCV genotype 3 was shown to be associated with a higher risk of cancer. In addition, a study conducted in Italy showed a significantly higher rate of HCV 1b infection in patients with hepatocellular carcinoma.[4,5]
Risk factors for HCV infections vary from a country to another. Unsafe healthcare practice was the main cause of the spreading of this disease in 2000. The next mode of the transmission in the low and middle-income countries is blood and blood products transfusion due to the lack of blood donor screening. Additionally, the venous injection in drug abusers is a leading cause of the spread of the virus in both developing and developed countries. Patients with ESKD are at higher risk of HCV infection.[1,6] Although the spread of the virus in hemodialysis units is declining, the prevalence of HCV in such patients is still high. Previous studies showed that the prevalence of anti-HCV antibody positivity among subjects with ESKD and on regular hemodialysis ranged from 5% to 60%. In a study conducted in Iraq, 5% of patients who were on dialysis were HCV positive. Acute HCV infection is defined as the occurrence of its manifestation within six months of exposure. It can be defined as the presence of a positive HCV RNA with a concurrent negative anti-HCV antibody level or a positive anti-HCV antibody level after a prior negative anti-HCV antibody within the previous six months,[9,10] With the availability of DAA medications, the mainstream approach of treatment has shifted obtaining a high sustained virologic response. Previously, interferon was used for the treatment of acute HCV in some circumstances with significant side effects. Otherwise, the treatment with DAA is associated with minor side effects and higher cure rates. Studies investigating the effectiveness of DAA in acute HCV are limited and with small sample size. In one study, 20 patients were recruited, and the sustained viral response (SVR) was achieved in all patients. One study was conducted to investigate the effectiveness of DAA in patients with acute HCV and ESKD. Thirty-three patients, who were infected with HCV genotype 1b and 2a were enrolled and were given treatment for 24 weeks. SVR was achieved in all patients without significant side effects. This study aimed to investigate the safety and efficacy of 12 weeks sofosbuvir-containing regimens in patients with ESKD who were infected with acute HCV genotype 1a.
ELISA and Biochemical tests. The HCV-antibody, hepatitis B surface antigen (HBsAg) and hepatitis B core IgG (HBcAb) and HIV Ab&Ag were investigated by ELISA kit (DIA.PRO diagnostic Bioprobes, Italy) following the manufacturer’s instruction. The detection of HCV and HIV was with a sensitivity (100%) and specificity (100%), while the sensitivity and specificity of the test for HBsAg were respectively 100% and 97.5%, according to the manufacturer.
ALT, AST and serum albumin were measured by Cobas chemistry analyzer (Roche). INR was estimated by START4 semiautomated system (STAGO).
HCV quantification and genotyping. In this study, the quantification of HCV was performed using Xpert HCV quantification assay (Cepheid, Sunnyvale, California, the USA). Fresh samples were kept at 4°C and tested within seventy-two hours after the collection. One ml was added to a test cartridge, which was loaded into a GeneXpert instrument. The linear range of the Xpert HCV assay is 10 IU/ml to 108 IU/ml. Results were reported as follows: HCV present (with the associated quantitation reported in IU per milliliter), or HCV was absent. All positive samples were genotyped by reverse hybridization (NLM, Milan, Italy).
|Table 1. Patients characteristics, biochemical test, ultrasound results, and treatment course used for treatment|
Treatment efficacy. The primary end-point of this project was to investigate the proportion of subjects who achieved SVR, which was defined as negative HCV RT-PCR at twelve weeks after treatment. In our study, 17 patients received a half dose of sofosbuvir (200 mg daily) after dialysis and a full dose of daclatasvir (60 mg daily) for 12 weeks. Two patients received sofosbuvir 400mg/ledipasvir 90mg fixed dose. The duration of treatment was for 12 weeks. The viral load became undetected in 16/19 (84.2%) patients after four weeks of treatment (Table 2). Sustained virologic response was achieved in all patients.
|Table 2. Virological response to antiviral treatment|
Safety outcomes. All subjects completed treatment the 12 weeks course and were followed up for the following 12 weeks. The treatment course of acute HCV in ESKD was well tolerated. During the study period, the most frequently reported adverse effects were fatigue, anorexia, headache and dizziness.
DAA medications have revolutionized the treatment of HCV infection. However, no data are available on their effectiveness and safety in treating ESKD patients with acute HCV. Our findings showed that a 12 weeks treatment course with an interferon-free DAA resulted in a sustained virologic response 12 weeks after treatment in all patients with acute HCV genotype 1a plus ESKD patients. The treatment course was not associated with serious side effects related to the medications. The treatment course was associated with rapid decline in the HCV-RNA levels in our patients. In our study, cephid Xpert was used for HCV-RNA detection. In three patients, the level of RNA was detectable but not quantifiable. This was not associated with prior RNA levels. In a previous study recruiting patients with acute HCV and EDKD recruiting patients with HCV genotypes 1b and 2, all patients achieved SVR after receiving a course of treatment for 24 weeks. This is the first study about the treatment of acute HCV in ESKD patients using 12 weeks course. Our findings are important for treatment plan as indicate economic advantage by using half the dose of expensive sofosbuvir, shorter period (12 weeks) and are important for public health as HCV infection can be treated successfully and hence prevent further spread of such an infection. The small sample size must not negate the importance of the study as it showed promising results for the treatment of infection and the prevention of further cases. The main challenge in treating acute HCV is the diagnosis of such cases as the vast majority of cases pass unnoticed. Our study has limitations. We acknowledge that our study was not randomized and the analysis was based upon the per-protocol population. However, we believe that randomized project was considered to be extremely difficult when dealing with such a public health problem.
ConclusionsIn conclusion, DAA containing sofosbuvir were suitable for the treatment of acute HCV infection in patient with ESKD without major adverse events.
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