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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 3  |  Page : 1126-1131

Study of serum lipid profile before and after hepatitis C virus treatment


1 Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
2 Department of Tropical Medicine, Shebin El-Kom Fever Hospital, Shebin El-Kom, Egypt

Date of Submission27-Mar-2019
Date of Acceptance07-May-2019
Date of Web Publication17-Oct-2019

Correspondence Address:
Marwa M El-Shiekh
Berket El-Sabae, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_141_19

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  Abstract 

Objective
To study the lipid profile in hepatitis C virus (HCV) patients before and after treatment with daclatasvir (DAV)+sofosbuvir (SOF)±ribavirin (RBV) to determine the effect of virus clearance on the lipid profile.
Background
Chronic HCV infection is associated with lipid and lipid protein metabolism disorders. There is a marked increase in serum low-density lipoprotein-cholesterol (LDL-C) in HCV-infected patients treated with SOF and RBV.
Participants and methods
A total of 100 chronic hepatitis C patients were included in a case–control study from February 2017 to August 2017. Twenty healthy individuals volunteered as a control group. Lipid profile changes were analyzed at baseline, after the end of treatment, and 12 weeks after treatment.
Results
Before treatment, the levels of serum LDL-C, cholesterol and triglycerides (TGs) were significantly lower in patients than the controls. At the end of treatment and 12 weeks after treatment with DCV + SOF + RBV, there was a significant increase in serum LDL-C, high-density lipoprotein-cholesterol, cholesterol, and TGs (P = 0.0001, 0.0001, 0.0001, and 0.007), respectively, and there was also a significant increase in patients treated with DCV + SOF (P = 0.035, 0.036, 0.01, and 0.0001), respectively. 100% of the treated patients achieved a sustained viral response (week 24).
Conclusion
Eradication of HCV was associated with an increase in the serum level of total cholesterol, TGs, LDL-C, and high-density lipoprotein-cholesterol; so follow up of the patient's lipid profile after Hepatitis C virus treatment is very important to avoid hyperlipidemia which is a risk for atherosclerotic heart disease.

Keywords: daclatasvir, hepatitis C virus, lipid profile, ribavirin, sofosbuvir


How to cite this article:
El-Lehleh AM, El-Shiekh MM, El-Hamouly MS. Study of serum lipid profile before and after hepatitis C virus treatment. Menoufia Med J 2019;32:1126-31

How to cite this URL:
El-Lehleh AM, El-Shiekh MM, El-Hamouly MS. Study of serum lipid profile before and after hepatitis C virus treatment. Menoufia Med J [serial online] 2019 [cited 2019 Nov 14];32:1126-31. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/1126/268808




  Introduction Top


Hepatitis C virus (HCV) is a major causative agent of chronic liver diseases including steatosis, cirrhosis, and hepatocellular carcinoma. Worldwide, it has been estimated that there are 170 million patients with chronic liver disease, of whom the majority are infected with HCV [1]. The patients with chronic HCV infection can have fatty liver, hypobetalipoproteinemia, and hypercholesterolemia that may cause lipid and lipid protein metabolism disorders [2]. Research into the HCV life cycle has shown a strong interaction between the virus and intracellular lipids, suggesting that host lipids play an important role in viral replication [3]. Host serum lipids play a role in hepatitis C virion circulation and hepatocyte entry. A proportion of circulating hepatitis C viral particles are complexed with host triacylglycerol-rich lipoproteins, known as lipo-viroparticles [4]. In most countries, treatment of chronic HCV infection was shifted from Interferon-based to IFN-free regimens using direct-acting antiviral drugs (DAAs) [5]. Although the association of baseline metabolic characteristics with treatment outcome has not been fully assessed for DAAs, this group was reported to result in improved rates of sustained virological response (SVR) and to reduce the predictive ability of these factors except for the baseline low-density lipoprotein (LDL) [6]. The highest prevalence of HCV was reported in Egypt, where genotype 4 is responsible for 91% of infections [7] and DAAs represented the main line of treatment in most centers [8]. Although the changes in lipid metabolism after treatment with DAAs were reported for other genotypes [9], these were not studied in genotype 4 infected patients.

The aim of this work was to study the lipid profile in HCV patients before and after treatment with daclatasvir (DCV)+sofosbuvir (SOF)±ribavirin (RBV) to determine the effect of virus clearance on the lipid profile.


  Participants and Methods Top


This study included 100 patients with chronic hepatitis C selected from among patients who attended the Hepatology Unit at Shebin El-Kom Fever Hospital from February 2017 to August 2017; all the patients fulfilled the inclusion criteria for this case–control study. The inclusion criteria were age of at least 18 years, nondiabetic naive patients with compensated Chronic Hepatitis C (CHC) after HCV infection, on the basis of the presence of anti-HCV and detectable serum HCV-RNA for 6 months or more and were being treated with DCV + SOF ± RBV. The exclusion criteria were DM, hypertension, heart diseases, obesity, patients who used lipid-lowering agents, as it could affect lipid metabolism, and patients with coexisting liver disease such as hepatitis B virus, HIV, autoimmune hepatitis, etc. Twenty healthy volunteers, 9 men and 11 women, were selected randomly from among the medical and paramedical staff working in the same hospital after they agreed to participate in the study as control participants. Their age ranged from 21 to 48 years.

Treatment protocol

Twenty-seven patients received dual therapy (one DCV 60 mg capsule and one SOF 400 mg tablet once a day) for 12 weeks and 73 patients received triple therapy (one DCV 60 mg capsule, one SOF 400 mg tablet once a day, and 600–1000 mg RBV) according to tolerance for 12 weeks.

Ethics and informed consent

Informed consent was obtained from all participants before the study. Approval from the local research ethics committee was obtained.

Clinical and laboratory assessment

All participants were subjected to a full assessment of history and a thorough clinical examination, with a special focus on age, sex, route of HCV transmission, and BMI. BMI was calculated as weight divided by the square of the height (kg/m 2). All patients were subjected to laboratory investigations such as complete blood count, liver function tests including alanine transaminase, aspartate transaminase, international normalized ratio, serum albumin and serum bilirubin, serum creatinine, and random blood sugar. Then, after the patients fasted for 12 h, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TGs) were determined using automated procedures.

Assessment of HCV-RNA load and viral kinetics

HCV-RNA levels were assessed at baseline, at the end of treatment (week 12), and at 12 weeks after the completion of treatment (week 24). Undetectable HCV-RNA at end of treatment response was defined as an undetectable HCV-RNA at the completion of HCV therapy. Undetectable HCV-RNA (week 24) was defined as sustained virologic response 12.

Statistical analysis

Symmetrically distributed continuous variables were summarized as a mean ± SD. The median and interquartile ranges were used for skewed continuous variables. The variables were compared between the groups using the Mann–Whitney U-test for continuous variables. The Friedman test was used to test the significance of differences in the lipid profile at baseline, after treatment, and 12 weeks after treatment. The χ2-test was used to determine the association between qualitative variables. Logistic regression analysis was used to model the association between the baseline lipid profile and other covariates to determine the factors associated with changes in LDL-C. P value of up to 0.05 was considered statistically significant. SPSS software for Windows version 20 (SPSS Inc., Chicago, Illinois, USA) was used to carry out all analyses.


  Results Top


This study was carried out on 100 patients with CHC; 73 of these patients were treated with SOF + DCV + RBV and 27 with SOF + DCV.

In this study, 56 (56%) patients were men and 44 (44%) were women. Their ages ranged from 21 to 59 years, with a mean of 40.07 years. Their BMI ranged from 18 to 29.1, with a mean of 23.90. There was no statistically significant difference between the patients and the controls in age, sex, and BMI (P = 0.326, 0.367, and 0.644), respectively [Table 1].
Table 1: Sociodemographic characteristics and BMI of the groups studied

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In this study, there were statistically significant differences between patients and controls in serum LDL-C, cholesterol, and TGs before treatment (P = 0.001, 0.0001, and 0.0001, respectively). The mean ± SD of LDL-C was higher in controls than in patients (128.70 ± 33.67 vs. 118.75 ± 15.76), the mean ± SD of cholesterol was higher in controls than in patients (210.75 ± 19.88 vs. 190.09 ± 16.63), and the mean ± SD of TGs was higher in controls than in patients (100.10 ± 22.69 vs. 81.85 ± 18.21). However, there was no statistically significant difference in HDL-C in both groups (P = 0.323) [Figure 1].
Figure 1: Lipid profile (LDL, HDL, cholesterol, and triglycerides) differences between patients and controls. HDL, high-density lipoprotein; LDL, low-density lipoprotein.

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There were statistically significant differences in LDL, HDL, cholesterol, and TGs in patients treated with SOF + DCV + RBV before treatment, end of treatment (12 weeks), and after 12 weeks (P = 0.0001 and 0.01, respectively). The mean ± SD of LDL was higher at the end of treatment and after 12 weeks than before treatment (131.45 ± 20.22 and 130.71 ± 20.67 vs. 116.16 ± 14.22), the mean ± SD of HDL-C was higher at the end of treatment and after 12 weeks than before treatment (56.00 ± 10.07 and 59.86 ± 10.81 vs. 54.63 ± 7.32), the mean ± SD of cholesterol was higher at the end of treatment and after 12 weeks than before treatment (206.01 ± 26.59 and 209.47 ± 22.64 vs. 186.66 ± 14.88), and the mean ± SD of TGs was higher at the end of treatment and after 12 weeks than before treatment (103.04 ± 46.50 and 94.04 ± 31.57 vs. 80.86 ± 19.93) [Table 2].
Table 2: Changes in the lipid profile before treatment, end of treatment (12 weeks), and after 12 weeks of the studied patients treated with daclatasvir + sofosbuvir + ribavirin

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There were statistically significant differences in LDL-C, HDL-C, cholesterol, and TGs in patients treated with SOF + DCV before treatment, end of treatment (12 weeks), and after 12 weeks (P = 0.035, 0.036, 0.01, and 0.0001), respectively. The mean ± SD of LDL-C was higher at the end of treatment and after 12 weeks than before treatment (132.59 ± 14.22 and 133.67 ± 17.72 vs. 125.74 ± 17.77), the mean ± SD of HDL-C was higher at the end of treatment and after 12 weeks than before treatment (56.67 ± 7.94 and 59.26 ± 7.47 vs. 54.85 ± 7.75), the mean ± SD of cholesterol was higher at the end of treatment and after 12 weeks than before treatment (214.59 ± 21.36 and 214.15 ± 20.63 vs. 199.37 ± 17.82), and the mean ± SD of TGs was higher at the end of treatment and after 12 weeks than before treatment (120.26 ± 36.13 and106.19 ± 31.49 vs. 84.52 ± 12.38) [Figure 2].
Figure 2: Changes in the lipid profile (LDL, HDL, cholesterol, and triglycerides) before treatment, end of treatment, and after 12 weeks of treatment with DCV + SOF. DCV, daclatasvir; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SOF, sofosbuvir.

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Patients were stratified into two groups by their delta (ΔLDL-C) levels. The high-ΔLDL-C group was defined as having a median ΔLDL-C level of at least 10.0 mg/dl and included 47 patients, whereas the low-ΔLDL-C group was defined as having a median ΔLDL-C level less than 10.0 mg/dl and included 53 cases. Our univariate analysis to identify the factors associated with an increase in ΔLDL-C at 12 weeks from the start of therapy and the relation of increased LDL-C with age, sex, BMI, aspartate transaminase, alanine transaminase, albumin, bilirubin, platelets, white blood cell count, α-fetoprotein, log viral load, TC, TGs, and HDL. LDL-C, cholesterol, and total leukocytic count were associated closely with ΔLDL-C [Table 3].
Table 3: Univariate analysis of factors associated with the delta low-density lipoprotein-cholesterol value of the patients studied

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We carried out a multiple logistic regression analysis to identify the factors associated with increase in LDL-C after the end of therapy (12 weeks); LDL-C, TGs, and BMI were associated closely with the ΔLDL-C values odds ratio [95% confidence interval: 1.096 (1.023–1.175), 1.032 (1.005–1.060), and 0.784 (0.637–0.964) respectively] (P > 0.01, 0.020, and 0.021, respectively) [Table 4].
Table 4: Multivariate analysis of the factors associated with the delta low-density lipoprotein-cholesterol value of the patients studied, analyzed by multiple logistic regression analysis

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  Discussion Top


In most countries, treatment of chronic HCV infection was shifted from IFN-based to IFN-free regimens using DAAs. Although the association of baseline metabolic characteristics with treatment outcome has not been fully assessed for DAAs, in this group (DAAs), improved rates of SVR were found and to reduce the predictive ability of these factors except for the baseline LDL [6]. This study was carried out on 100 (56 men and 44 women) patients who were HCV positive and candidates for therapy with DCV + SOF ± RBV. This work was carried out to study the lipid profile in HCV patients before and after treatment to determine the effect of virus clearance on lipid levels in the blood. There were no statistically significant differences between the studied patients and controls in age, sex, and BMI (P < 0.05). We found a significant reduction in serum in cholesterol, TGs, and LDL-C in the patients studied than the control group mean = 190.09 ± 16.63 mg/l, P = 0.0001, 81.85 ± 18.21 mg/l, P = 0.0001, and 118.75 ± 15.76 mg/l, P = 0.001, respectively, but no statistically significant difference in HDL-C in comparison with the control group.

In agreement with these results, Butt et al. [10] reported a progressive decrease in lipid fractions other than HDL more than that in a demographically comparable HCV uninfected group and remained significant after adjusting for BMI and degree of liver fibrosis.

We found a significant increase in serum cholesterol at the end of treatment with DCV and SOF as well as at 12 weeks of follow-up (214.15 ± 20.63 mg/l; P < 0.01). This is in agreement with Younossi et al. [11] and Endo et al. [12], who compared the serum cholesterol in CHC patients treated with DCV/asunaprevir or SOF/ledipasvir (LDV) at the beginning of treatment and at 4 and 12 weeks after treatment. They concluded that serum cholesterol increased significantly during SOF/LDV treatment and HCV elimination was associated with a similar increase in cholesterol after treatment, irrespective of the DAAs regimen. This effect is attributed to a reversal of the impact of HCV replication on hepatic lipid metabolism.

The results of this study showed a significant increase in LDL-C at the end of treatment with DCV and SOF as well as at 12 weeks of follow-up: mean = 132.59 ± 14.22 and 133.67 ± 17.72 mg/l, respectively (P ≤ 0.05). This is in agreement with Meissner et al. [13], who found that LDL increased at the end of treatment and after 4 weeks of follow-up. We also found a significant difference in TGs at the end of treatment with DCV and SOF as well as at 12 weeks of follow-up: mean = 120.26 ± 36.13 and 106.19 ± 31.49 mg/l, respectively (P = 0.0001). This finding is in agreement with the result of Chang et al. [14], who found significant post-therapeutic increases in TC, LDL, HDL, and TGs, but greater increases in HDL in patients with genotype 2.

According to our results, we found a significant difference in TC, LDL, HDL, and TGs at the end of treatment with (DCV+SOF+RBV) regimen as well as at 12 weeks of follow up after treatment and as in our results [TGs, with TC mean ± SD are 186.66 ± 14.88, 206.01 ± 26.59, and 209.47 ± 22.64 mg/l] respectively (P = 0.0001), also [LDL mean ±SD are 116.16 ± 14.22, 131.45 ± 20.22, and 130.71 ± 20.67 mg/l] respectively (P = 0.0001),[HDL mean 54.63 ± 7.32, 56.00 ± 10.07, and 59.86 ± 10.81 mg/l] respectively, (P = 0.0001), and [TGs mean 80.86 ± 19.93, 103.04 ± 46.50 and 94.04 ± 31.57 mg/l] respectively (P = 0.01). This is in agreement with Chang et al. [14], who found significant post-therapeutic increases in TC, LDL, HDL, and TGs, but greater increases in HDL in patients with genotype 2.

The factors that could predict changes in LDL levels were identified in a logistic regression analysis. The main independent predictors for LDL changes in our study with univariate analysis were low levels of LDL, cholesterol and low level of total leukocytic count. However, in multivariate analysis that included age, sex, BMI, total leukocytic count, LDL, cholesterol, TGs, and type of therapy, there was a significant association with low levels of LDL, TGs, and BMI. There was no effect of age, sex, or type of therapy on changes in LDL after treatment. This was in agreement with Endo et al. [12], who found that the factor that positively affected the increase in LDL was baseline TG.

The results of this study showed that low levels of LDL, cholesterol, BMI, and total leukocytic count were independent predictors for changes in cholesterol in a logistic univariate analysis. However, in a multivariate analysis that included age, sex, BMI, LDL, cholesterol, and TGs, there was a significant association with basal levels of cholesterol and TGs. This is in agreement with Mauss et al. [15], who found that there was a negative correlation between baseline TC levels and changes in TC between baseline and post-treatment week 12. There was also no effect of the type of therapy on changes in cholesterol in our study. This is in agreement with Endo et al. [12], who compared the serum cholesterol in CHC patients treated with DCV/asunaprevir or SOF/LDV at the beginning of treatment and at 4 and 12 weeks after treatment. They concluded that serum cholesterol increased significantly during SOF/LDV treatment and HCV elimination was associated with a similar increase in cholesterol after treatment irrespective of the DAAs regimen.


  Conclusion Top


The patients with chronic HCV infection had significantly lower TC, TG, and LDL-C levels compared with age-matched, sex-matched, and BMI-matched healthy individuals. Successful eradication of HCV was associated with an increase in the serum level of TC, TGs, LDL-C, and HDL-C irrespective of the therapy protocol (DCV + SOF ± RBV).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Forner A, Liovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379:1245–1255.  Back to cited text no. 1
    
2.
Felmlee DJ, Hafirassou ML, Lefevre M, Baumert T, Schuster C. Hepatitis C virus, cholesterol and lipoproteins – impact for the viral life cycle and pathogenesis of liver disease. Viruses 2013; 5:1292–1297.  Back to cited text no. 2
    
3.
Vogt DA, Camus G, Herker E, Webster BR, Tsou CL, Greene WC, et al. Lipid droplet-binding protein TIP47 regulates hepatitis C virus RNA replication through interaction with the viral NS5A protein. PLoS Pathog 2013; 9:e1003302.  Back to cited text no. 3
    
4.
Schaefer EA, Chung RT. HCV and host lipids: an intimate connection. Semin Liver Dis 2013; 33:358–368.  Back to cited text no. 4
    
5.
Younossi ZM, Stepanova M, Nader F, Lam B, Hunt S. The patient's journey with chronic hepatitis C from interferon plus ribavirin to interferon- and ribavirin-free regimens: a study of health-related quality of life. Aliment Pharmacol Ther 2015; 42:286–295.  Back to cited text no. 5
    
6.
Grasso A, Malfatti F, Testa R. Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C? World J Gastroenterol 2013; 19:6947–6956.  Back to cited text no. 6
    
7.
Wantuck JM, Ahmed A, Nguyen MH. Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6. Aliment Pharmacol Ther 2014; 39:137–147.  Back to cited text no. 7
    
8.
El Kassas M, Elbaz T, Hafez E, Esmat G. Safety of direct antiviral agents in the management of hepatitis C. Expert Opin Drug Saf 2016; 15:1643–1652.  Back to cited text no. 8
    
9.
Gitto S, Cicero AF, Loggi E, Giovannini M, Conti F, Grandini E, et al. Worsening of serum lipid profile after direct acting antiviral treatment. J Hepatol 2017; 66:740.  Back to cited text no. 9
    
10.
Butt AA, Yan P, Simon TG, Chung RT, Abou-Samra AB, ERCHIVES Study Team. Changes in circulating lipids level over time after acquiring HCV infection. BMC Infect Dis 2015; 15:510.  Back to cited text no. 10
    
11.
Younossi ZM, Stepanova M, Estep M, Negro F, Clark PJ, Hunt S, et al. Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin. J Hepatol 2016; 64:29–36.  Back to cited text no. 11
    
12.
Endo D, Satoh K, Shimada N, Hokari A, Aizawa Y. Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b. World J Gastroenterol 2017; 23:2355–2364.  Back to cited text no. 12
    
13.
Meissner EG, Lee YJ, Osinusi A, Sims Z, Qin J, Sturdevant D, et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology 2015; 61:790–801.  Back to cited text no. 13
    
14.
Chang ML, Tsou YK, Hu TH, Lin CH, Lin WR, Sung CM, et al. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance. PLoS One 2014; 9:e104783.  Back to cited text no. 14
    
15.
Mauss S, Berger F, Wehmeyer MH, Ingiliz P, Hueppe D, Lutz T, et al. Effect of antiviral therapy for HCV on lipid levels. Antivir Ther 2017; 21:81–88.  Back to cited text no. 15
    


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