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 Table of Contents  
SHORT COMMUNICATION
Year : 2019  |  Volume : 4  |  Issue : 2  |  Page : 224-226

Use of liver enzymes as a surrogate marker for monitoring treatment of hepatitis C virus disease


1 Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-the Medicity, Gurgaon, Haryana, India
2 Department of Flow Cytometry, Waikato Hospital, Hamilton, New Zealand

Date of Submission15-Jun-2019
Date of Acceptance09-Aug-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Dr. Aseem Kumar Tiwari
Department of Transfusion Medicine, Molecular and Transplant Immunology Laboratory, Medanta-the Medicity, Gurgaon, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_36_19

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  Abstract 

Introduction: Hepatitis C virus infects 3% people globally, that causes significant morbidity and mortality. For diagnosis and monitoring of treatment of HCV infection; biochemical markers and HCV RNA are tested. Aim of the Study: We tried to find out whether there is an association of liver enzymes (AST, ALT) and anti HCV antibody with the HCV viral load in patient's serum. Material and Methods:238 consecutive patients with suspected or confirmed Hepatitis C viral disease were included in this study. All consecutive samples of patients for two years were tested for HCV RNA quantification using real time PCR (viral load). Serum aminotransferase (AST, ALT) and anti-HCV antibody levels were also recorded and compared with the viral load. Correlation coefficient was used to study association between different parameters. Results: Significant positive correlation was found between liver enzymes (AST, ALT) and HCV viral load. Conclusion: There is a significant correlation between liver enzymes and RNA viral load. Therefore, viral load may be substituted with test for liver enzymes during monitoring of treatment, at least partially, and this could result in substantial cost savings.

Keywords: Hepatitis C virus, liver enzymes, viral load


How to cite this article:
Rajvanshi C, Tiwari AK, Dorwal P, Mehra S. Use of liver enzymes as a surrogate marker for monitoring treatment of hepatitis C virus disease. Glob J Transfus Med 2019;4:224-6

How to cite this URL:
Rajvanshi C, Tiwari AK, Dorwal P, Mehra S. Use of liver enzymes as a surrogate marker for monitoring treatment of hepatitis C virus disease. Glob J Transfus Med [serial online] 2019 [cited 2019 Nov 20];4:224-6. Available from: http://www.gjtmonline.com/text.asp?2019/4/2/224/269387




  Introduction Top


Hepatitis C virus (HCV) is the most common cause of liver disease, such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), leads to liver transplantation in many cases.[1],[2],[3] The mortality from HCV is predicted to increase as patients with HCV surviving for a longer duration. This greatly affects public health and leads to economic burden as well. Biochemical and viral markers detect the severity of liver disease and also help to monitor the patient response during treatment. Biochemical markers include aspartate aminotransferase (AST) and alanine aminotransferase (ALT).[4] Viral markers include anti-HCV antibody and HCV-RNA quantification. Hepatocytes contain significant levels of AST and ALT. Elevated level of these enzymes can be determined if the liver is damaged.[5]

Our aim of this study was as follows:

(1) to correlate different biochemical markers and anti-HCV antibody with the value of HCV viral RNA and (2) to provide clinicians with data-based approaches for the diagnosis and management of HCV infection in a resource-constraint country.


  Subjects and Methods Top


Settings

This study was conducted in the molecular and transplant immunology Laboratory of a tertiary care hospital in Gurgaon, Haryana, India, over a period of 2 years from January 2013 to January 2015. The study population comprised all patients suspected or confirmed for HCV disease. Gender and age were noted. For this study, all individuals were categorized into three age groups: ≤25, 26–50, and ≥51 years.

Patients and samples

All consecutive samples of patients with suspected or confirmed hepatitis C disease were included in the study. A total of 238 patients were subjected to HCV viral load detection. Anti-HCV antibody and liver enzymes were tested with plain serum vacuumized containers. Ethylenediaminetetraacetic acid tubes were used to test HCV-RNA. Patients with hepatitis B virus (HBV)/HCV, HIV/HCV, HIV/HBV/HCV coinfection, and other forms of liver disease of nonviral etiology were excluded from the study.

Test methods

Liver enzymes (AST and ALT) were estimated by calorimetric method using VITROS 5600 instrument (Ortho Clinical Diagnostics, NJ, USA). Anti-HCV antibody detection was carried out using 3600 Ortho Immmunodiagnostic System and VITROS ECIQ Immmunodiagnostic System (Ortho Clinical Diagnostics, NJ, USA). HCV viral RNA extraction and quantification were done using Abbott m2000sp and m2000rt (Abbott Molecular Inc., USA) instrument. The RNA was extracted from the plasma using Abbott RNA isolation kit (Abbott Molecular Inc., USA) with a fully automated instrument m2000sp (Abbott Molecular Inc., USA.) which is based on magnetic particle technology. Extracted RNA was transferred to the Abbott m2000rt system (Abbott Molecular Inc., USA) for amplification. The fluorescent signal was detected by the Abbott m2000rt, which is proportional to the log of the HCV-RNA concentration present in the sample.

The reference values of our laboratory are 17–59 IU/L for AST and 21–72 IU/L for ALT. The reference values of anti-HCV antibody levels are 0.00–0.99 for nonreactive and ≥1.00 for reactive. The reference value for HCV-RNA was 12 -100 million IU/ ml.

Confirmation of diagnosis

The World Health Organization (WHO) recommends HCV serology testing of individuals who have a history of sensitization and/or are from the high-prevalence population (for example, patients with a history of jaundice). In seropositive cases, HCV-RNA testing is performed for the confirmation of diagnosis.[6]

Monitoring of response to therapy

There are different levels of virological response that has to be monitored from the time of initiation of therapy: (1) rapid virological response (RVR) is the absence of HCV-RNA at 4 weeks of treatment; (2) early virological response (EVR) defined as the absence of or ≥2 log reduction of HCV-RNA at week 12 of therapy; and (3) sustained virological response (SVR) is the absence of HCV-RNA by week 24 of treatment.[2],[6] Monitoring of response to treatment is required for predicting whether SVR has been achieved or not. SVR, in turn, helps the physician decide the discontinuation of antiviral therapy.

Statistical analysis

The ordinal data obtained were expressed in terms of mean and standard deviation. The analysis was performed using Microsoft Excel and SPSS software (version 24.0; IBM, Bengaluru, Karnataka, India).

Ethical approval

Patient consent was obtained for the diagnosis and treatment to the hospital. This was an observational study, and no additional sample was drawn for this study. All investigation, treatment, and monitoring were according to the current “Standard of Care.”


  Results Top


Demographics

Of 238 patients, 76% were male and 24% were female. The median age of the male patients was 47 ± 14 years and female patients was 48 ± 14 years, as shown in [Figure 1].
Figure 1: Distribution of active hepatitis C virus infection in males and females

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Association between hepatitis C virus viral load and liver enzymes

Significant positive correlation of HCV-RNA viral load was found with AST (P < 0.00001 and r - 0.6227) and ALT (P < 0.0001 and r - 0.4479). We did not found any correlation of HCV viral load with anti-HCV antibody (P < 0.00001 and r = −0.5266) [Table 1].
Table 1: Correlation between hepatitis C virus viral load with aspartate aminotransferase, alanine aminotransferase, and antihepatitis C virus antibody

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  Discussion Top


One hundred and eighty-four million people have chronic HCV infection globally with the majority of them from developing countries.[7] The WHO reports that 75% of HCV-infected individual develop chronic liver disease. Nearly 1.6% of chronic liver disease develop HCC having a mortality rate >80%.[8] Patients with HIV, patients on regular hemodialysis, those receiving multiple blood transfusions, organ transplant, sexually active adults with multiple partners, children with vertical transmission (3%–5%),[9],[10],[11],[12] injection drug users, those with tattooing,[13],[14],[15],[16],[17] and health-care workers are prone to the HCV infection.[4],[5]

In our study, we assessed AST and ALT and found that they significantly relate to HCV viral load in patient samples. Mushtaq et al.[18] also found a significant positive relation between liver aminotransferase (AST and ALT) and viral load in the population of Pakistan. Puoti et al.[19] explained that abnormal levels of ALT were found in patients with HCV infection. Zechini et al.[20] also found a positive correlation between HCV viral load and different aminotransferases (AST and ALT). Ahmad et al. emphasize on a significant relationship of elevated level of liver enzymes with hepatitis C viral load in their study.[21] The association of viral load with liver enzymes has been reported in other countries, but this is possibly the first study reporting this in Indian patients.

It is considered that patients with chronic HCV infection have high HCV-RNA titer and abnormal level of ALT, and this is the basis of starting antiviral therapy and at later point in time, monitoring response to therapy.[22] For this regular, HCV-RNA quantification is usually done.


  Conclusion Top


As India is a resource-constraint country, we are suggesting the use of liver enzymes (cost INR 300), ALT or AST, as a surrogate marker to monitor the response to therapy and predict RVR or EVR, which is otherwise, usually monitored by “viral load” test which is far more expensive (cost INR 6000). This suggestion of using liver enzyme instead of viral load tests, if adopted in the laboratory practice could help patients and bring down the overall cost of treatment. SVR would, however, be decided on the basis of viral load test only.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: A review. Pan Afr Med J 2013;14:44.  Back to cited text no. 1
    
2.
Strader DB, Wright T, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004;39:1147-71.  Back to cited text no. 2
    
3.
National Institutes of Health. National institutes of health consensus development conference statement: Management of hepatitis C: 2002 – June 10-12, 2002. Hepatology 2002;36:S3-20.  Back to cited text no. 3
    
4.
Seeff LB. Natural history of hepatitis C. Hepatology 1997;26:21S-28S.  Back to cited text no. 4
    
5.
Pecker F, Duvaldestin P, Berthelot P, Hanoune J. The adenylate cyclase system in human liver: Characterization, subcellular distribution and hormonal sensitivity in normal or cirrhotic adult, and in foetal liver. Clin Sci (Lond) 1979;57:313-25.  Back to cited text no. 5
    
6.
World Health Organization. Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection. World health Organization; 2014.  Back to cited text no. 6
    
7.
Phelan M, Cook C. A treatment revolution for those who can afford it? Hepatitis C treatment: New medications, profits and patients. BMC Infect Dis 2014;14 Suppl 6:S5.  Back to cited text no. 7
    
8.
Maheshwari A, Thuluvath PJ. Management of acute hepatitis C. Clin Liver Dis 2010;14:169-76.  Back to cited text no. 8
    
9.
Tohme RA, Holmberg SD. Is sexual contact a major mode of hepatitis C virus transmission? Hepatology 2010;52:1497-505.  Back to cited text no. 9
    
10.
Lam NC, Gotsch PB, Langan RC. Caring for pregnant women and newborns with hepatitis B or C. Am Fam Physician 2010;82:1225-9.  Back to cited text no. 10
    
11.
Papanastasiou DA, Spiliopoulou I, Katinakis S, Karana-Ginopoulou A, Repanti M. Lack of transmission of hepatitis C in household contacts of children with homozygous beta-thalassaemia. Acta Haematol 1997;97:168-73.  Back to cited text no. 11
    
12.
Ohto H, Terazawa S, Sasaki N, Sasaki N, Hino K, Ishiwata C, et al. Transmission of hepatitis C virus from mothers to infants. The vertical transmission of hepatitis C virus collaborative study group. N Engl J Med 1994;330:744-50.  Back to cited text no. 12
    
13.
Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001;345:41-52.  Back to cited text no. 13
    
14.
Ghany MG, Strader DB, Thomas DL, Seeff LB. American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: An update. Hepatology 2009;49:1335-74.  Back to cited text no. 14
    
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Huffman MM, Mounsey AL. Hepatitis C for primary care physicians. J Am Board Fam Med 2014;27:284-91.  Back to cited text no. 15
    
16.
Xia X, Luo J, Bai J, Yu R. Epidemiology of hepatitis C virus infection among injection drug users in China: Systematic review and meta-analysis. Public Health 2008;122:990-1003.  Back to cited text no. 16
    
17.
Jafari S, Copes R, Baharlou S, Etminan M, Buxton J. Tattooing and the risk of transmission of hepatitis C: A systematic review and meta-analysis. Int J Infect Dis 2010;14:e928-40.  Back to cited text no. 17
    
18.
Mushtaq A, Tariq MA, Rasheed U, Afroz A, Zeeshan N, Asif AR, et al. Estimation of HCV viral load and liver enzymes among different patients groups of district Gujrat, Pakistan. Adv Biosci Biotechnol 2013;4:866-71.  Back to cited text no. 18
    
19.
Puoti M, Zonaro A, Ravaggi A, Marin MG, Castelnuovo F, Cariani E. Hepatitis C virus RNA and antibody response in the clinical course of acute hepatitis C virus infection. Hepatology 1992;16:877-81.  Back to cited text no. 19
    
20.
Zechini B, Pasquazzi C, Aceti A. Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: The role of serum aspartate transaminase in the evaluation of disease progression. Eur J Gastroenterol Hepatol 2004;16:891-6.  Back to cited text no. 20
    
21.
Ahmad F, Junaid K, Ul Mustafa A. Relationship of liver enzymes with viral load of hepatitis C in HCV infected patients by data analytics (data analytics of HCV and liver profile). Int J Adv Comput Sci Appl 2018;9:502-5.  Back to cited text no. 21
    
22.
Lee YS, Yoon SK, Chung ES, Bae SH, Choi JY, Han JY, et al. The relationship of histologic activity to serum ALT, HCV genotype and HCV RNA titers in chronic hepatitis C. J Korean Med Sci 2001;16:585-91.  Back to cited text no. 22
    


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