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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 3  |  Page : 778-782

Hematological and biochemical changes due to anti-hepatitis C virus therapy


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Menoufia Hepatology Center, Menoufia, Egypt

Date of Submission26-Dec-2018
Date of Decision09-Feb-2019
Date of Acceptance12-Feb-2019
Date of Web Publication30-Sep-2020

Correspondence Address:
Baher E Maadawi Radi
Shabas Elshouhada, Dessouq, Kafr Al Sheikh 32717
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_398_18

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  Abstract 


Objective
The aim of the study was to assess the hematological and biochemical changes in patients who have received anti-hepatitis C virus (HCV) therapy before treatment and follow-up after 3 months of treatment as regards the advantages and disadvantages through a follow up of the studied patients.
Background
There is a dramatic improvement in HCV therapy following the introduction of oral medicines that directly inhibit the replication cycle of HCV, so the follow up of patients who are receiving therapy before and 6 months after treatment is mandatory to choose the best drug for each patient with the least side effects.
Patients and methods
This study was done on 200 patients admitted to the Kafr El-Sheikh Hepatology Center diagnosed as HCV-infected patients. Those patients were classified according to the Child classification as Child A score 6. Of them, 100 patients received sofosbuvir + ledipasvir and another 100 patients received sofosbuvir + daclatasvir, respectively. All patients were subjected to the following investigations before and 6 months after treatment: complete blood count, biochemical investigations including serum albumin, alanine transaminase, aspartate transaminase, random blood sugar, blood urea, serum creatinine, total and direct bilirubin, and alkaline phosphatase, thyroid-stimulating hormone level, alpha-fetoprotein, and antinuclear antibody.
Results
All the previous laboratory investigations were done to all 200 patients, recorded and compared before treatment and 6 months after treatment.
Conclusion
Ledipasvir and sofosbuvir for 8 weeks or 12 weeks is a highly effective treatment option for the treatment of hepatitis C-infected patients and give best results more than sofosbuvir and daclatasvir.

Keywords: biochemical investigations, Child score, oral anti-hepatitis C virus therapy


How to cite this article:
Dala AG, Badr MH, Helwa MA, Maadawi Radi BE. Hematological and biochemical changes due to anti-hepatitis C virus therapy. Menoufia Med J 2020;33:778-82

How to cite this URL:
Dala AG, Badr MH, Helwa MA, Maadawi Radi BE. Hematological and biochemical changes due to anti-hepatitis C virus therapy. Menoufia Med J [serial online] 2020 [cited 2020 Oct 28];33:778-82. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/778/296686




  Introduction Top


Chronic hepatitis is not a single disease but is a clinical and pathological syndrome of multiple etiologies and is characterized by varying degrees of liver cell necrosis, inflammation, and fibrosis continuing without improvement for at least 6 months [1]. Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The long-term natural history of HCV infection is highly variable. The hepatic injury can range from minimal histological changes to extensive fibrosis and cirrhosis with or without hepatocellular carcinoma [2]. There are ∼71 million chronically infected individuals worldwide, many of whom are unaware of their infection, with important variations according to the geographical area [2]. Clinical care for patients with HCV-related liver disease has advanced considerably during the last two decades, thanks to an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and improvements in therapy and prevention [3]. The primary goal of HCV therapy is to cure the infection or to achieve a sustained virological response (SVR) defined as undetectable HCV RNA 12 weeks after treatment completion. An SVR corresponds to a cure of the HCV infection, with a very low chance of late relapse. An SVR is generally associated with normalization of liver enzymes and improvement or disappearance of liver necroinflammation and fibrosis in patients without cirrhosis [3]. Patients with advanced fibrosis or cirrhosis remain at risk of life-threatening complications. However, hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced after sustained virologic response [4]. Recent data suggest that the risk of hepatocellular carcinoma and liver-related mortality is significantly reduced, but not eliminated, in patients with cirrhosis who clear HCV compared with untreated patients and nonsustained virological responders, especially in the presence of cofactors of liver morbidity, such as the metabolic syndrome, harmful alcohol consumption, and/or concurrent hepatitis B virus infection [5].

The aim of this study was to assess hematological and biochemical changes in patients who have received anti-HCV therapy before and 3 months after treatment.


  Patients and Methods Top


This study was done at Kafr El-Sheikh Hepatology Centre from January 2016 to January 2017 with a follow-up period of an average 6 months. The study was approved by the Ethics committee of Menoufia Faculty of Medicine. All patients gave written informed consent before inclusion into the study. The study included 200 patients classified as Child A score 6, 100 patients receiving sofosbuvir + ledipasvir and 100 patients receiving sofosbuvir and daclatasvir, respectively. The mean age was 40.60 years in patients receiving sofosbuvir + ledipasvir and men represent 70% and women represent 30%. But in patients receiving 'sofosbuvir + daclatasvir,' the mean age was 42.64 years and men represent 74% and women represent 26%, with no significant differences between the two groups of patients regarding age and sex.

All patients were subjected to the following investigations 6 months before and after treatment: complete blood count, biochemical investigations [serum albumin, alanine transaminase (SGPT), aspartate transaminase (SGOT), random blood sugar, blood urea, serum creatinine, total and direct bilirubin and alkaline phosphatase, thyroid-stimulating hormone level, alpha-fetoprotein, and antinuclear antibody].

Blood sample technique

Blood samples were taken from a peripheral vein after sterilization of the skin with betadine to do the laboratory investigations 6 months before and after treatment of HCV infection.

Follow-up

Patient were discharged after first blood sample was taken to receive his anti-HCV medications and were followed up for 3 months and then another blood sample was taken from each patient to do the same previous investigations and to compare between them.

Statistical analysis

All data were collected, tabulated, and statistically analyzed. The descriptive measures were mean value and SD for quantitative data, besides frequency and the percentage for qualitative data were calculated by using Epi-Info, version 6, Division of Health Informatics & Surveillance (DHIS), Center for Surveillance, Epidemiology & Laboratory Services (CSELS) Newyork, USA and SPSS, IBM SPSS Statistics for Windows, version 8 (IBM Corp., Armonk, N.Y., USA). The analytic measures were t test for comparison of two independent quantitative variables that are normally distributed and χ2 test for comparison between two independent qualitative variables that are normally distributed.


  Results Top


Our study was conducted on 200 patients infected with HCV to evaluate the possible hematological and biochemical changes due to anti-HCV therapy. The mean age was 40.60 years in patients receiving sofosbuvir + ledipasvir and men represent 70% and women represent 30%. But in patients receiving 'sofosbuvir + daclatasvir,' the mean age was 42.64 years and men represent 74% and women represent 26%, with no significant differences between the two groups of patients regarding age and sex [Table 1]. Laboratory results of patients receiving sofosbuvir + ledipasvir before treatment and 3 months after treatment were tabulated and compared and there were statistically significant difference between patients receiving sofosbuvir + ledipasvir before and after treatment as regards serum creatinine, SGPT, SGOT, serum albumin, hemoglobin concentration, and platelet concentration [Table 2]. Laboratory results of patients receiving sofosbvir and daclatasvir before treatment and 3 months after treatment were tabulated and there were statistically significant difference between patients receiving 'sofosbuvir + daclatasvir' before and after treatment as regards serum creatinine, SGPT, SGOT, serum albumin, total bilirubin, and hemoglobin concentration [Table 3]. Laboratory results of both patient groups are recorded, tabulated, and compared. There were statistically significant difference between two groups of patients receiving sofosbuvir + ledipasvir and sofosbuvir + daclatasvir after treatment as regards alpha-fetoprotein, serum creatinine, SGPT, SGOT, serum albumin, total bilirubin, hemoglobin concentration, and platelet concentration [Table 4]. There were statically significant difference between patients receiving sofosbuvir + ledipasvir before and 3 months after treatment as regards FIB 4 score and MELD score [Table 5]. There were statically significant differences between patients receiving 'sofosbuvir + daclatasvir' before and 3 months after treatment as regards FIB 4 score and MELD score [Table 6]. There were statically significant differences between two groups of patients receiving sofosbuvir + ledipasvir and sofosbuvir + daclatasvir after 3 months of treatment as regards FIB 4 score and MELD score [Table 7].
Table 1: Comparison between two groups of patients receiving sofosbuvir + ledipasvir and the patients group receiving sofosbuvir + daclatasvir as regards age and sex

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Table 2: Comparison between patients receiving (sofosbuvir + ledipasvir) before and after treatment as regards liver function tests, kidney functions, complete blood count, and biochemical markers

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Table 3: Comparison between patients receiving sofosbuvir + daclatasvir before and after treatment as regards liver function tests, kidney function tests, complete blood count, and biochemical markers

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Table 4: Comparison between two groups of patients receiving sofosbuvir + ledipasvir and sofosbuvir + daclatasvir after treatment as regards liver function tests, kidney function tests, complete blood count, and biochemical markers

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Table 5: Comparison between patients receiving sofosbuvir + ledipasvir before and 3 months after treatment as regards FIB 4 score and MELD score

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Table 6: Comparison between patients receiving sofosbuvir + daclatasvir before and 3 months after treatment as regards FIB 4 score and MELD score

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Table 7: Comparison between two groups of patients receiving sofosbuvir + ledipasvir and sofosbuvir + daclatasvir after 3 months of treatment as regards FIB 4 score and MELD score

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  Discussion Top


A dramatic improvement in HCV therapy followed the introduction of oral medicines that directly inhibit the replication cycle of HCV. These medicines, called direct-acting antivirals (DAAs), target three important regions within the HCV genome: NS3/4 A protease, NS5A, and NS5B RNA-dependent polymerase. These medicines had led to higher SVRs than interferon-based regimens, shorter in treatment duration, orally administered, and had fewer side-effects. Individual DAAs vary in therapeutic efficacy, genotypic efficacy, adverse events, and drug–drug interactions, and must be used in combination with at least one other DAA [6]. The pan-genotypic combination of daclatasvir and sofosbuvir, with or without ribavirin, has achieved high SVR rates. Daclatasvir is an inhibitor of the HCV NS5A replication complex; sofosbuvir is a nucleotide inhibitor of the HCV NS5B polymerase. Both had favorable safety profiles and are dosed once daily, with few clinically significant drug–drug interactions, including a lack of interactions with cyclosporine or tacrolimus [7]. The regimen was effective across all five HCV genotypes enrolled, consistent with the expected pan-genotypic activity of daclatasvir and sofosbuvir. Other oral regimens have thus far been evaluated primarily against HCV genotypes 1 and 4 in transplant recipients or in those with advanced cirrhosis [8]. The fixed-dose combination of ledipasvir, an NS5A inhibitor, and sofosbuvir (ledipasvir + sofosbuvir) for 12 weeks had proven to be highly effective and well tolerated in patients with HCV genotype 1 in phase III studies, with rates of SVR at 12 weeks posttreatment of 94–99% [9]. A published trial in patients with HCV genotype 4 who received 12 weeks of ledipasvir + sofosbuvir. Overall, SVR 12 rates of 93–95% were observed, with slightly lower rates for interferon-experienced patients (91%) [10]. The efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin were evaluated for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with HCV genotype 4, including those who had failed previous treatment with sofosbuvir regimens. Of the 255 patients in the study, 61% were men, 67% were treatment naïve, 21% had cirrhosis, and 80% had IL28B non-CC genotype [11].

Abergel et al. [10] published a trial on patients with HCV genotype 4 who received 12 weeks of ledipasvir–sofosbuvir. Overall, SVR 12 rates of 93–95% were observed, with slightly lower rates for interferon-experienced patients (91%).

Shiha et al. [11] evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with HCV genotype 4, including those who had failed previous treatment with sofosbuvir regimens. Of the 255 patients in the study, 61% were men, 67% were treatment naïve, 21% had cirrhosis, and 80% had IL28B non-CC genotype. In this study, there were statistically significant differences between patients receiving (sofosbuvir + ledipasvir) before and after treatment as regards serum creatinine, SGPT, SGOT, serum albumin, hemoglobin concentration, platelet concentration, FIB 4, and MELD score. Also, there were statistically significant differences between patients receiving 'sofosbuvir + daclatasvir' before and after treatment as regards serum creatinine, SGPT, SGOT, serum albumin, total bilirubin, hemoglobin concentration, and FIB 4. But, there were statistically significant differences between two groups of patients receiving sofosbuvir + ledipasvir and 'sofosbuvir + daclatasvir' after treatment as regards alpha-fetoprotein, serum creatinine, SGPT, SGOT, serum albumin, total bilirubin, hemoglobin concentration, platelet concentration, FIB 4, and MELD score.

Elsharkawy et al. [12] evaluated the effect of various DAA regimens on liver biochemical profile and hematological indices during treatment. They concluded that DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and noncirrhotics. Cirrhotic patients require careful observation, they being more vulnerable to treatment-related complications.

Reddy et al. [13] assessed the efficacy and safety of an interferon-free, sofosbuvir-based regimen to treat HCV RNA-positive kidney transplant recipients and the impact of these drugs on calcineurin inhibitor (CNI) levels. They concluded that sofosbuvir and ribavirin combination therapy is useful and safe to treat HCV infection in the postrenal transplant setting at any level of kidney function. There was a reduction in CNI drug exposure with the use of sofosbuvir therapy. None of the patients required any significant dose modification of CNIs while these patients were being monitored by C0 levels of CNIs.


  Conclusion Top


Ledipasvir + sofosbuvir for 12 weeks was a highly effective treatment option for treatment-naïve HCV patients and give better results than sofosbuvir and daclatasvir, respectively.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Bifano M, Adamczyk R, Hwang C, Kandoussi H, Marion A, Bertz RJ. An open-label investigation into drug–drug interactions between multiple doses of daclatasvir and single-dose cyclosporine or tacrolimus in healthy subjects. Clin Drug Investig 2015; 35:281–289.  Back to cited text no. 8
    
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Reddy S, Sharma RK, Mehrotra S, Prasad N, Gupta A, Kaul A, et al. Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C virus infection after kidney transplantation. Clin Kidney J 2017; 11:429–433.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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