|Year : 2017 | Volume
| Issue : 4 | Page : 132-135
Nosocomial hepatitis C infection among hemodialysis patients: a single center study in Assuit University Hospital
Effat A.E. Tony1, Haidi K Allah Ramadan2, Ashraf M Osman2, Magda Sh. Hassan2, Azza M Ezz El Din3
1 Department of Internal Medicine and Nephrology, Assiut University, Assiut, Egypt
2 Department of Tropical Medicine and Gastroenterology, Assiut University, Assiut, Egypt
3 Department of Clinical Pathology, Assiut University, Assiut, Egypt
|Date of Submission||08-Aug-2017|
|Date of Acceptance||29-Sep-2017|
|Date of Web Publication||17-Jan-2018|
Effat A.E. Tony
Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, Assuit University, Assuit 71515
Source of Support: None, Conflict of Interest: None
Background There is an increased risk of acquiring hepatitis C virus (HCV) infection among hemodialysis (HD) patients. HCV prevalence varies considerably among different HD centers throughout the world. In Egypt, the prevalence of HCV in HD patients could reach 50.7%.
Aim The aim of this study were to measure the rate of HCV seroconversion for patients at the HD Unit in Assiut University Hospitals and to assess the diagnostic utility of routine laboratory test of anti-HCV antibodies used in those patients.
Patients and methods This study was performed at the HD Unit, in the Internal Medicine Department, Assiut University Hospital. We included patients on regular HD between 2011 and 2014 who were negative for anti-HCV and hepatitis B surface antigen with normal liver enzyme level. Follow up after 3 and 6 months was done by testing for liver enzymes and anti-HCV using third-generation enzyme-linked immunosorbent assay and cases with positive results had qualitative real-time PCR to confirm the result.
Results We recruited 63 patients, seroconversion for anti-HCV was found in 21 (33.3%) patients; seven patients develop this seroconversion after 3 months follow-up transiently and 14 patients develop it after 6 months follow-up. However, all patients lack HCV viremia as confirmed by testing for HCV RNA using real-time PCR.
Conclusion In our study, seroconversion for anti HCV among the HD patients was found in 33.3% but they lack HCV viremia. Screening in HD units is better to be done using PCR testing to avoid transient anti HCV seroconversion particularly in units with high prevalence of anti HCV.
Keywords: hemodialysis, hepatitis B surface antigen, hepatitis B virus, hepatitis C virus, polymerase chain reaction
|How to cite this article:|
Tony EA, Allah Ramadan HK, Osman AM, Hassan MS, Ezz El Din AM. Nosocomial hepatitis C infection among hemodialysis patients: a single center study in Assuit University Hospital. J Egypt Soc Nephrol Transplant 2017;17:132-5
|How to cite this URL:|
Tony EA, Allah Ramadan HK, Osman AM, Hassan MS, Ezz El Din AM. Nosocomial hepatitis C infection among hemodialysis patients: a single center study in Assuit University Hospital. J Egypt Soc Nephrol Transplant [serial online] 2017 [cited 2018 Aug 19];17:132-5. Available from: http://www.jesnt.eg.net/text.asp?2017/17/4/132/223411
| Introduction|| |
The prevalence of antihepatitis C virus (HCV) antibodies among hemodialysis (HD) patients is consistently higher than in the general population, indicating an increased risk of acquiring HCV infection among HD patients . The prevalence of HCV among HD patients varies greatly by geographic area (between 4 and 59% in different countries) . In Egypt, the prevalence of HCV in HD patients (2015) was 50.7% . In a multicenter Egyptian study conducted in 13 HD Units in Beni-Suef Governorate, the rate of HCV seroconversion was 9.7% (37 out of 380 patients after the start of dialysis) using the routine anti-HCV test . Routine laboratory diagnosis of HCV infection is based on the specific antibodies identified by an immunoenzyme assay [enzyme-linked immunosorbent assay (ELISA)]. All anti-HCV positive results have to be verified by detecting HCV RNA levels (viral load) in the blood, commonly using the PCR technique . False-negative rate of anti-HCV is many times higher among HD patients (≤12%), such nucleic acid testing (NAT) is more justified for the dialysis patients . In a study by Tashkandy et al. , they found that the false positivity of HCVAb by ELISA and recombinant immunoblot assay, when compared with real-time (RT)-PCR, was 3.9%, whereas comparing ELISA with RT-PCR, the false positivity was 5.9%. Thus, for maximum elimination of false positive or false negative results, the screening method is determined depending on the prevalence of HCV infection in the respective dialysis center. Serological tests are recommended in low infection prevalence, whereas nucleic acid amplification tests are to be used in cases with high prevalence of the infection .
| Aim|| |
The aim of this study were to measure the rate of HCV seroconversion for patients at the HD Unit in Assiut University Hospital and to assess the diagnostic utility of routine laboratory test of anti-HCV antibodies used in these patients to diagnose HCV infection.
| Patients and methods|| |
This study was performed at the HD Unit in Assiut University Hospital. Patients on maintenance HD between 2011 and 2014, who were negative for anti-HCV and hepatitis B surface antigen (HBsAg) with normal liver enzyme (alanine transaminase and aspartate transaminase) levels were enrolled in our study. All patients were subjected to full medical history, clinical examination for signs of liver diseases and abdominal ultrasound. Then, they were followed up after 3 and 6 months by testing for anti-HCV antibodies and liver enzymes. Qualitative RT-PCR for HCV RNA was performed only for patients who develop positive anti-HCV antibodies at any follow-up period. Anti-HCV assays were performed on ARCHITECT-1000 (Kit lot number 002130, France) based on chemiluminescent immunoassays method and conventional RT-nested PCR was used for the detection of HCV RNA in the serum sample . This study was conducted in accordance with the provisions of the Declaration of Helsiniki. All participants gave an informed written consent to participate in this study. This study was approved by the ethics committee in Assiut University.
Statistical analysis was performed using SPSS software version 16 (SPSS Inc., Chicago, Illinois, USA). The data in this study are presented as mean±SD and number (percentages) of the patients. The association between categorical variables was tested using the χ2-test. The Student t-test was used for comparison between quantitative variables. A value of P value less than 0.05 was considered statistically significant.
| Results|| |
A total of 262 end stage renal disease patients on regular HD were enrolled at the start of the study. Their mean ages ranged between 16 and 80 years with a mean±SD of 45.56+15.45. Of the participants, 35 (55.6%) patients were from the rural areas whereas 28 (44.4%) patients were from urban areas. Unfortunately, more than half (52.4%) of the studied patients were women.
As shown in [Figure 1], there were 262 end stage renal disease patients on regular HD enrolled at the start of the study. By using routine anti-HCV test and HBsAg to screen for HCV and HBV infections, there were 179 (68.3%) patients who were anti-HCV positive, 19 (7.3%) patients were HBsAg-positive, 63 (24%) patients had negative markers for neither HBsAg or anti-HCV, whereas the coinfection were seen in one (0.4%) patient.
|Figure 1 Percentages of positive and negative cases of hepatitis B virus and hepatitis C virus of hemodialysis patients during the study period.|
Click here to view
As shown in [Table 1], during the first follow-up at 3 months of our studied patients, seven anti-HCV positive patients were negative for the qualitative PCR for HCV. Moreover, during the second follow-up at 6 months, 14 patients who were diagnosed as anti-HCV positive one became also negative PCR for HCV. Surprisingly, the patients who were anti-HCV positive on the first follow-up were negative for anti-HCV and again negative for PCR on the second follow-up.
|Table 1 Number of patients who developed positive result for antihepatitis C virus and real-time PCR during follow-up at 3 and 6 months|
Click here to view
The basic characteristics for both anti-HCV positive and anti-HCV negative studied patients after the follow-up period at 3 and 6 months with no statistical significant differences are shown in [Table 2].
|Table 2 The basic characteristics for both anti HCV positive (+) and anti HCV negative (-) studied patients during their follow up after 3 and 6 months|
Click here to view
The difference between alanine transaminase and aspartate transaminase results for both anti-HCV positive and anti-HCV negative patients at each follow-up after 3 and 6 months with no statistically significant differences are shown in [Table 3].
|Table 3 The mean levels of ALT and AST in studied patients with anti HCV positive (+) and anti HCV negative (-) during their follow up after 3 and 6 months|
Click here to view
| Discussion|| |
In the current study, seroconversion for anti-HCV was reported after 3 and 6 months follow-up. However, all patients lacked HCV viremia as confirmed by testing for HCV RNA using RT-PCR. This transient anti HCV seroconversion could be explained by many mechanisms. Firstly, the immunoenzymatic tests we used may fail to detect patients with active HCV infection. False negative and false positive results still be found even with the use of 3rd generation test . Moreover, in our study, the results of positive anti-HCV were around the cut-off value. Although they had negative PCR results it needs to be confirmed by another immunoassay method. Secondly, samples for HCV-RNA testing in HD patients should be obtained prior to the dialysis procedure as heparin used during the dialysis sessions can interfere with the PCR technique. Thirdly, the dialysis procedure can lower HCV RNA levels by the adsorption of HCV RNA onto the inner surface of dialyzers and destruction of viral particles by the hydraulic pressure exerted by the blood during dialysis . Finally, occult HCV infection should be considered in these patients with discordant results (anti-HCV positive/HCV RNA negative). In occult HCV infection, the virus is detected in the peripheral blood mononuclear cells and/or in hepatocytes but not in the blood . However, there is quite scanty evidence for this form of the disease in HD patients . This could explain why in our study, none of the patients (positive for anti-HCV) were positive for qualitative PCR. Many major risk factors in those patients with anti-HCV seroconversion such as the duration and frequency of dialysis, blood transfusions, fixed dialysis on chair of previous anti-HCV positive patient and the lack of strict adherence to infection control measures by the healthcare workers could be participated in our observations. Our results were in concordance with Komitova et al.  who stated that patients with discordant results (anti-HCV positive/HCV RNA negative) could be due to fluctuating viremia, previous exposure to HCV or could be biologically false positive. Notably, Latt et al.  reported that HCV-antibody enzyme immunoassay followed by confirmation with HCV RNA NAT is recommended for low prevalence regions, but in dialysis centers with a high prevalence of HCV, initial testing with NAT is recommended due to higher false-positive enzyme immunoassay rates. Furthermore, in a recent Egyptian study, out of 60 patients followed up, there was one case of HCV seroconversion giving an incidence rate of 0.676/100 person-years of follow-up (95% confidence interval: 0.017–3.76) .
HCV infection in dialysis patients tends to run an asymptomatic course with mild changes in the laboratory and morphology parameters ,. In our study, there was no statistically significant difference between the level of liver enzymes after 3 and 6 months follow-up in the studied patients. This finding was in agreement with many researchers who reported lower serum levels of aminotransferases in dialysis patients than those with normal renal function. This finding could be probably related to vitamin B6 deficiency and to some uremic toxins ,. Results of our study raise questions as regards the adequacy of using anti-HCV test to screen for chronic HCV infection in patients on HD units without testing for HCV RNA and the possibility of occult infection among this group of patients. This would further impact the choice of patients to receive treatment for HCV and during follow-up of their treatment. Most researchers recommend that a combination of ELISA and PCR to be used as the most highly sensitive diagnostic approach to HCV infection in dialysis patients ,.
Our current study was a single center study with small sample size and lack of confirmation for the HCV viremia by testing for occult HCV infection; therefore, we advise regular screening of all patients in HD units for HCV. This screening is better to be done by using PCR testing to avoid transient anti-HCV seroconversion particularly in units with high prevalence of anti-HCV and screening for occult HCV should be considered to exclude false-negative results.
The authors acknowledge Assiut Medical School Grants Office of Assiut University for its support with funding for this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jasuja S, Gupta AK, Choudhry R, Kher V, Aggarwal DK, Mishra A et al.
Prevalence and associations of hepatitis C viremia in hemodialysis patients at a tertiary care hospital. Indian J Nephrol 2009; 19:62–67.
Prati D. Transmission of hepatitis C virus by blood transfusions and other medical procedures: a global review. J Hepatol 2006; 45:607–616.
Sarhan I, Afifi A, El Sharkawy M, Aboseif K, Mady G, Eltayeb M et al.
Current status of HCV infection in hemodialysis patients in Egypt. Nephrol Dial Transplant 2015; 30:317–318.
Senosy SA, El Shabrawy EM. Hepatitis C virus in patients on regular hemodialysis in Beni-Suef Governorate, Egypt. J Egypt Public Health Assoc 2016; 91:86–89.
Urbánek P. Viral hepatitis infections in chronic kidney disease patients and renal transplant recipients. Kidney Blood Press Res 2012; 35:454–467.
Rahnavardi M, Moghaddam S, Alavian S. Hepatitis C in hemodialysis patients: current global magnitude, natural history, diagnostic difficulties, and preventive measures. Am J Nephrol 2008; 28:628–640.
Tashkandy MA, Khodai YA, Ibrahim AM, Dhafar KO, Gazzaz ZJ, Azab BA. Evaluation of the available anti-HCV antibody detection tests and RT-PCR assay in the diagnosis of hepatitis C virus infection. Saudi J Kidney Dis Transpl 2007; 18:523–531.
] [Full text]
KDIGO. Kdigo Practical Guidelines for the prevention, diagnosis, evaluation and treatment of hepatitis C in chronic kidney disease. Kidney Int 2008; 73:S1–S99.
Cantaloube JF, Laperche S, Gallian P, Bouchardeau F, de Lamballerie X, de Micco P. Analysis of the 5’ noncoding region versus the NS5b region in genotyping hepatitis C virus isolates from blood donors in France. J Clin Microbiol 2006; 44:2051–2056.
Moreira RC, Lemos MF, Longui CA, Granato C. Hepatitis C and hemodialysis: a review. Braz J Infect Dis 2005; 9:269–275.
Martin P, Fabriz F. Hepatitis C virus and kidney disease. J Hepatol 2008; 49:613–624.
Castillo I, Pardo M, Bartolomé J, Ortiz-Movilla N, Rodrguez-Iigo E, de Lucas S et al.
Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown. J Infect Dis 2004; 189:7–14.
Barril G, Castillo I, Carreño V. Evidence of occult hepatitis C virus infection in hemodialysis patients. Am J Am Soc Nephrol 2008; 19:2288–2292.
Komitova RT, Atanasova MV, Pavlova TA, Nyagolov MS, Ivanova AV. Diagnostic dilemmas in hepatitis C virus infection for hemodialysis patients. Folia Med (Plovdiv) 2017; 59:70–77.
15.Latt NL, Araz F, Alachkar N, Durand CM, Gurakar A. Management of hepatitis C infection among patients with renal failure. Minerva Gastroenterol Dietol 2015; 61:39–49.
Kamal AT, Farres MN, Eissa AM, Arafa NA, Abdel-Reheem RS. Incidence of hepatitis C virus seroconversion among hemodialysis patients in the Nile Delta of Egypt: a single-center study. Saudi J Kidney Dis Transpl 2017; 28:107–114.
] [Full text]
Rampino T, Arbustini E, Gregorini M et al.
Hemodialysis prevents liver disease caused by hepatitis C virus: role of hepatocyte growth factor. Kidney Int 1999; 56:2286–2291.
Fabrizi F, Lunghi G, Finazzi S, Colucci P, Pagano A, Ponticelli C, Locatelli F. Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis. Am J Kidney Dis 2001; 38:1009–1015.
Espinosa M, Martin-Malo A, Alvarez de Lara MA, Soriano S, Aljama P. High ALT levels predict viremia in anti-HCVpositive HD patients if a modifi ed normal range of ALT is applied. Clin Nephrol 2000; 54:151–156.
Guh JY, Lai YH, Yang CY, Chen SC, Chuang WL, Hsu TC et al.
Impact of decreased serum transaminase level on the evaluation of viral hepatitis in hemodialysis patients. Nephron 1995; 69:459–465.
Schneeberger PM, Keur I, van der Vliet W, van Hoek K, Boswijk H, van Loon AM et al.
Hepatitis C infection in dialysis centers in The Netherlands: a national survey by serological and molecular methods. J Clin Microbiol 1998; 36:1711–1715.
Bukh J, Wantzin P, Krogsgaard K, Knudsen F, Purcell RH, Miller RH et al.
High prevalence of hepatitis C virus (HCV) RNA in dialysis patients: failure of commercially available antibody tests to identify a signifi cant number of patients with HCV infection. Copenhagen dialysis HCV study group. J Infect Dis 1993; 168:1343–1348.
[Table 1], [Table 2], [Table 3]