Skip to main content
Egyptian Liver Journal
Download PDF
  • Original Research Article
  • Open access
  • Published:

Effect of achieving sustained virological response with direct-acting antiviral agents on glycemic control in diabetic patients with chronic hepatitis C infection

Egyptian Liver Journal volume 12, Article number: 25 (2022) Cite this article

Abstract

Background

Hepatitis C virus (HCV) is a significant cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. Liver disease is not the only problem caused by chronic HCV infection; many extrahepatic complications, such as insulin resistance, can be associated with HCV infection. The aim of this study was to assess the effect of achieving a sustained virological response after treatment with directly acting antiviral drugs on insulin resistance in patients with chronic HCV infection.

Results

This prospective study was conducted on 46 HCV patients with type 2 diabetes mellitus who received directly acting antiviral drugs for HCV infections. Fasting insulin, fasting blood glucose, and lipid profiles were assessed in all patients at three time points: before treatment, at the end of treatment, and 12 weeks after the end of treatment. Despite using three different directly acting antiviral drug regimens, all patients achieved a sustained viral response, regardless of the regimen used. the Homeostatic Model Assessment for Insulin Resistance decreased significantly at the end of treatment; however, when recalculated at week 12 after end of treatment, the reduction of the Homeostatic Model Assessment for Insulin Resistance was not significant compared to the baseline levels. Total cholesterol and low-density lipoproteins increased at the end of treatment and continued to increase for 12 weeks after the end of treatment.

Conclusions

Improvements in insulin resistance and glycemic control were noted in HCV patients at the end of treatment with directly acting antiviral drugs; this effect was also apparent after 12 weeks. An increase in the levels of total cholesterol and low-density lipoprotein can be expected after treatment with directly acting antiviral drugs.

Background

Infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) [1]. Liver disease is not the only problem caused by chronic HCV infection; many extrahepatic complications, such as insulin resistance (IR), are associated with HCV infection [2]. Some reports have suggested that chronic HCV patients have a high prevalence of metabolic disorders [3]. Modifications to these disorders can be expected after viral eradication [4]. As a result of these metabolic imbalances, HCV increases the incidence of type 2 diabetes mellitus (T2DM) in susceptible individuals, mainly through the development of IR [5]. Although HCV is primarily a hepatic infection, insulin sensitivity is compromised in chronic HCV patients in the absence of metabolic syndrome [6]. One possible explanation for this phenomenon is that infected hepatocytes might release mediators that provoke endocrine effects at extrahepatic locations, such as skeletal muscle. The interaction between the metabolic effects of HCV and host-related genetic and environmental factors can result in worsening of IR, ending in the development of T2DM [4, 7]. Once it has developed, T2DM hastens the development of liver injury, leading to an upsurge in HCC risk, and worsening the response to antiviral treatments [5]. The risk of cardiovascular disease increases because of factors including possible direct viral effects, the presence of existing systemic chronic inflammatory conditions, and possible interactions with metabolic disorders [8].

There have been significant changes in HCV management following the discovery of the oral, interferon-free, direct-acting antivirals (DAAs) that replaced the previous interferon-based standard of care therapy [9, 10]. Because of the association between HCV and the development of IR and T2DM, it was postulated that the clearance of HCV may cause a decrease in T2DM incidence. Successful HCV treatment should also improve clinical outcomes in T2DM patients [11]. Studies are needed to investigate the impact on insulin signaling pathways of treating HCV with DAAs and the possibility of improvement of glucose metabolism.

Methods

In the period between December 2017 and December 2018, 46 patients with confirmed chronic HCV infection and IR were enrolled in the study. Those patients were recruited from the New Cairo Viral Hepatitis Treatment unit, one of the specialized viral hepatitis treatment facilities affiliated to the Egyptian National Committee for Control of Viral Hepatitis (NCCVH) [12]. They were eligible to receive HCV antiviral therapy according to the standardized protocol issued by NCCVH [13, 14]. The main criteria for inclusion were: age between 18 and 75, HCV RNA positivity, and having IR (HOMA test) > 2.5 [15]. Criteria for exclusion included total serum bilirubin > 3 mg/dl, serum albumin < 2.8 g/dl, INR ≥ 1.7, hemoglobin < 10 g/dl, platelets < 50,000/mm3, HCC or extrahepatic malignancy, pregnancy, and the presence of other liver diseases such as HBV or autoimmune hepatitis.

Patients had a complete history taken, and had a thorough clinical examination and anthropometric evaluation, including measurement of weight and height, and calculation of body mass index (BMI). Laboratory investigations included fasting blood sugar (FBS), fasting insulin (FI), and the calculation of the homeostatic model assessment of IR (HOMA-IR = (FPI × FPG)/22.5) [16]. Lipid profiles, hepatitis markers (HCV antibody, HBsAg, and HCV RNA quantitative PCR), kidney function tests, and alpha-fetoprotein were also assessed. Abdominal ultrasound examinations were performed for all patients. These investigations were performed at three time points: at baseline, at the end of treatment (EOT), and 12 weeks after the EOT.

Statistical analysis

The SPSS statistical package was used for data analysis. Data were expressed as mean ± SD for parametric data, and median ± interquartile range for non-parametric data. Means were compared using paired t tests and repeated measure ANOVA tests, while for non-parametric values, Wilcoxon rank, and Friedman tests were used. P values less than 0.05 were considered to be statistically significant, and P < = 0.01 was considered highly significant.

Results

The mean age of the study patients was 55.89 years, and 27 of them (59%) were females. Most of the study subjects were overweight or had early obesity, however there were no significant changes in the mean BMI during the phases of the study. Ten patients (22%) were hypertensive, and two patients (0.04%) had hypothyroidism and were receiving thyroxin. Regarding DM management, most of the included patients did not use insulin (about 61%) but 39% of patient needed insulin in their DM management. Also, insulin sensitizers were not used in DM management.

Patients were assigned to groups receiving one of three different DAA regimens, according to the treatment availability and the protocol used. The combination of sofosbuvir/daclatasvir (SOF/DAC) with or without ribavirin (RBV) was the most frequently used regimen (63% of patients). The other two groups received a fixed-dose combination of ombitasvir/paritaprevir-ritonavir (OMB/PAR/RIT) with RBV (30%), or sofosbuvir/ledipasvir (SOF/LED) (7%).

An indicator of insulin resistance, HOMA-IR, was significantly decreased at the EOT compared to baseline levels [HOMA-IR: 5.25 (3.35–7.65) vs. 3.74 (2.59–5.45), P = 0.001]. However, when baseline HOMA-IR levels were compared to those reported 24 weeks post-treatment, there was a tendency toward a decrease, but the difference was not statistically significant [HOMA-IR: 5.25 (3.35–7.65) vs. 4.83 (3.72–6.66), P = 0.114]. FI levels decreased significantly directly after treatment [14.75 (9.50–22.60) vs.10.35 (8.60–16.00); P = 0.000]. The FI level 12 weeks after treatment was lower than the starting level, but was not statistically significant [10.35 (8.60–16.00) vs. 13.75 (9.00–18.20); P = 0.045]. When comparing HbA1c levels at baseline with those at the EOT, a significant decrease was noticed (7.56 ± 1.01 vs. 7.00 ± 1.52 2; P = 0.013), reflecting the effect of IR on the control of plasma glucose level (Fig. 1). However, when comparing the level at the EOT to that at 12 weeks after the EOT, a significant increase was reported (7.00 ± 1.52 vs. 7.57 ± 1.17; P = 0.000). Lipid metabolism was significantly influenced by HCV treatment (Fig. 2). Serum cholesterol and low-density lipoproteins (LDL) levels increased significantly after the EOT (156.98 ± 43.41 vs. 172.37 ± 36.64; P = 0.002, and 91.97 ± 36.09 vs. 105.73 ± 30.64; P = 0.007, respectively), and this effect persisted at 12 weeks after EOT (156.98 ± 43.41 vs. 173.89 ± 42.62; i= 0.003, and 91.97 ± 36.09 vs. 110.19 ± 33.50; P = 0.000, respectively). The detailed changes in the studied parameters throughout the study checkpoints are listed in Table 1.

Fig. 1
figure 1

Changes in HbA1c over the course of the study

Full size image
Fig. 2
figure 2

Changes in serum LDL over the course of the study

Full size image
Table 1 Change of parameters throughout the study checkpoints
Full size table

Discussion

HCV infection can be associated with extrahepatic manifestations, such as IR [17, 18]. The pathophysiology of IR associated with HCV infection is controversial. Advanced fibrosis and liver cirrhosis can lead to metabolic derangements, which, in turn, result in IR [19]. IR is associated with specific HCV genotypes, G1 and G4, in which there is a direct correlation between viremia and IR levels, and the development of type II DM [20]. This finding was one of the main drivers behind conducting this study, as G4 HCV is widespread in Egypt [13].

In the current study, HOMA-IR levels were significantly decreased at the EOT compared to baseline levels; however, this was not the case when baseline levels were compared with those reported at 24 weeks post-treatment. In the latter situation, there was a tendency toward a decrease, but the decrease was not statistically significant. This phenomenon has previously been reported in a previous research where obesity did not affect the results [21] and could be partly explained by the tight control of diet, and hence better glycemic control, taken by patients with diabetes during the HCV treatment period. The finding of improved IR after HCV treatment was common in most reports discussing the subject, with only a few studies reporting different results. When DAAs are first used, some reports suggested that the SOF/LED combination could worsen IR. raising the risk of hyperglycemia [22, 23]. However, later studies confirmed the acceptable safety margins of DAAS [24]. In a study that involved non-diabetic Egyptian patients who received DAAs, the mean FBS improved at the EOT, indicating better glycemic control; however, HOMA-IR was significantly increased at the EOT, indicating an increase in insulin resistance [25]. In contrast to previous findings, several studies produced results very similar to those of the present study with respect to the effect of treatment with DAAs on IR. Adinolfi et al. reported a reduction in HOMA-IR, increased insulin sensitivity, decreased insulin secretion, and reduction of serum glucose and insulin levels after treatment with DAAs in non-diabetic patients with HCV G1 and advanced liver fibrosis (F3-4) [26].

HOMA-IR was significantly lower at the end of DAAs treatment with SIM/SOF in an Egyptian cohort of non-diabetic naïve patients with different grades of fibrosis and G4 HCV infection [27]. In another study from Egypt, pretreatment HOMA did not differ in responders and non-responders to DAAs (P = 0.098), while IR decreased significantly in responders compared to those who did not achieve a sustained virologic response (SVR) (P < 0.0001), and HOMA improved significantly in patients with SVR than in non-responders (P = 0.001) [28]. These results indicate that the improvement of IR after viral eradication could be reflected in the blood glucose levels, and a parallel improvement in glycemic control can be anticipated. It is also possible that the hypoglycemic agents used should be adjusted to avoid fluctuations in the plasma glucose levels of patients following successful antiviral therapy.

In our study, HbA1c levels showed a significant decrease at EOT compared to pretreatment levels. Reductions in FBS and HbA1c have also been noted after DAA therapy in many studies [21, 29, 30]. This observation suggests a need for close monitoring for a possible reduction in anti-diabetic drugs, especially insulin and sulfonylurea, to avoid hypoglycemic events. This approach has also been suggested by other studies [31]. The need for escalating anti-diabetic therapy during HCV treatment has been reported by other studies [32]. Similar improvements in glycemic control were demonstrated, even before the era of DAAs; however, these studies were confounded by treatment-induced weight loss, a common side effect of interferon [33, 34].

Previous studies have suggested that patients with chronic HCV infection had significantly lower total cholesterol and triglyceride levels compared with healthy controls matched for age, sex, and BMI [35,36,37]. In the present study, both total cholesterol and LDL levels increased significantly after the EOT compared to baseline levels, while HDL levels did not show a significant change. Some studies have suggested a need for repeated measurements of serum lipid levels in patients who responded to antiviral therapy, as viral elimination may uncover some patients with previously undervalued cardiac risk [38]. An increase in serum LDL early in the course of antiviral therapy (SOF/RBV) was noted in patients who cleared the virus [3]. Similarly, an interferon-free antiviral treatment study showed a rapid increase in total LDL and HDL cholesterol levels after 4 weeks, with a rapid decline in patients who did not achieve a SVR [39]. This observation was confirmed by an Egyptian study showing a significant elevation of serum cholesterol and LDL levels after the end of a course of SOF/SIM treatment [27].

Data from literature explained these alterations in the lipid profile after HVC treatment by the fact that HCV affects the expression of some proteins involved in the lipid metabolism. It was shown that HCV increases the expression of LDL receptors on the membrane of the hepatocytes allowing more LDL molecules to enter. On the other hand, it decreases the expression of the enzyme proprotein convertase subtilin/Kexin type 9 (PCSK9) which is responsible for LDL receptor degradation. Consequently, these effects can be reversed causing an increase in plasma LDL after successful treatment of HCV [40].

Conclusions

Improvements in IR and glycemic control were noted in HCV patients at the EOT with DAAs; however, this effect was not observed 12 weeks after the commencement of treatment. An increase in the levels of total cholesterol and LDL can be expected after treatment with DAAs.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

DAAs:

Direct-acting antivirals

DAC:

Daclatasvir

HCV:

Hepatitis C virus

HBV:

Hepatitis B virus

IR:

Insulin resistance

MELD:

Model for end-stage liver disease

OMB/PAR/RIT:

Ombitasvir/paritaprevir-ritonavir

SOF:

Sofosbuvir

RBV:

Ribavirin

T2DM:

Type 2 diabetes mellitus

References

  1. Seeff LB (2002) Natural history of chronic hepatitis C. Hepatology 36(Suppl. 1):S35–S46PMID: 12407575. https://doi.org/10.1053/jhep.2002.36806

    Article  PubMed  Google Scholar 

  2. Gumber SC, Chopra S (1995) Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Int Med 123:615–620 [PMID: 7677303. https://doi.org/10.7326/0003-4819-123-8-199510150-00008

    Article  CAS  PubMed  Google Scholar 

  3. Meissner EG, Lee YJ, Osinusi A, Sims Z, Qin J, Sturdevant D et al (2015) Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology 61:790–801 [PMID: 25203718. https://doi.org/10.1002/hep.27424

    Article  CAS  PubMed  Google Scholar 

  4. Hamed AE, Elwan N, Naguib M et al (2019) Diabetes association with liver diseases: an overview for clinicians. Endocr Metab Immune Disord Drug Targets 19(3):274–280 [PMID: 30444204. https://doi.org/10.2174/1871530318666181116111945

    Article  CAS  PubMed  Google Scholar 

  5. Hamed AE, Elwan N, Naguib M, Elwakil R, Esmat G, El Kassas M et al (2018) Managing diabetes and liver disease association. Arab J Gastroenterol 19(4):166–179 [PMID: 30420265. https://doi.org/10.1016/j.ajg.2018.08.003

    Article  PubMed  Google Scholar 

  6. Milner KL, van der Poorten D, Trenell M, Jenkins AB, Xu A, Smythe G et al (2010) Chronic hepatitis C is associated with peripheral rather than hepatic insulin resistance. Gastroenterology 138:932–941 [PMID: 19962985. https://doi.org/10.1053/j.gastro.2009.11.050

    Article  PubMed  Google Scholar 

  7. Lemoine M, Chevaliez S, Bastard JP, Fartoux L, Chazouillères O, Capeau J et al (2015) Association between IL28Bpolymorphism, TNF _ and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance. J Viral Hepatitis 22:890–896 [PMID: 25818002. https://doi.org/10.1111/jvh.12408

    Article  CAS  Google Scholar 

  8. Cua IH, Hui JM, Kench JG, George J (2008) Genotype-specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C. Hepatology 48:723–731 [PMID: 18688878. https://doi.org/10.1002/hep.22392

    Article  PubMed  Google Scholar 

  9. Esmat G, El Kassas M, Hassany M, Gamil M, El Raziky M (2014) Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues. Liver Int 34(Suppl 1):24–28 [PMID: 24373075. https://doi.org/10.1111/liv.12397

    Article  CAS  PubMed  Google Scholar 

  10. Elbaz T, El-Kassas M, Esmat G (2015) New era for management of chronic hepatitis C virus using direct antiviral agents: a review. J Adv Res 6(3):301–310 [PMID: 26257927. https://doi.org/10.1016/j.jare.2014.11.004

    Article  CAS  PubMed  Google Scholar 

  11. Vanni E, Bugianesi E, Saracco G (2016) Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C : myth or reality ? Digest Liver Dis 48(2):105–111 [PMID: 26614641. https://doi.org/10.1016/j.dld.2015.10.016

    Article  CAS  Google Scholar 

  12. El Kassas M, Alboraie M, Omran D, Salaheldin M, Wifi MN, ElBadry M et al (2018) An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens. Expert Rev Gastroenterol Hepatol 24:1–8 [PMID: 29757684. https://doi.org/10.1080/17474124.2018.1476137

    Article  CAS  Google Scholar 

  13. El Kassas M, Elbaz T, Elsharkawy A, Omar H, Esmat G (2018) HCV in Egypt, prevention, treatment and key barriers to elimination. Expert Rev Anti Infect Ther 16(4):345–350 [PMID: 29506418. https://doi.org/10.1080/14787210.2018

    Article  PubMed  Google Scholar 

  14. El-Akel W, El-Sayed MH, El Kassas M, El-Serafy M, Khairy M, Elsaeed K et al (2017) National treatment programme of hepatitis C in Egypt: hepatitis C virus model of care. J Viral Hepat 24(4):262–267 [PMID: 28145032. https://doi.org/10.1111/jvh.12668

    Article  CAS  PubMed  Google Scholar 

  15. Andrade MI, Oliveira JS, Leal VS, Lima NM, Costa EC, Aquino NB et al (2016) Identification of cutoff points for homeostatic model assessment for insulin resistance index in adolescents: systematic review. Rev Paul Pediatr 34(2):234–242 [PMID: 26559605. https://doi.org/10.1016/j.rpped.2015.08.006

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27(6):1487–1495 [PMID: 15161807. https://doi.org/10.2337/diacare.27.6.1487

    Article  PubMed  Google Scholar 

  17. WHO (2018) Guidelines for the Care and Treatment of Persons Diagnosed with Chronic Hepatitis c Virus Infection. World Health Organization, Geneva PMID: 30307724

    Google Scholar 

  18. Kuna L, Jakab J, Smolic R, Wu GY, Smolic M (2019) HCV extrahepatic manifestations. J Clin Transl Hepatol 7(2):172 [PMID: 31293918. https://doi.org/10.14218/JCTH.2018.00049

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lim TR, Hazlehurst JM, Oprescu AI, Armstrong MJ, Abdullah SF, Davies NP et al (2019) Hepatitis C virus infection is associated with hepatic and adipose tissue insulin resistance that improves after viral cure. Clin Endocrinol 90(3):440–448 [PMID: 30586166. https://doi.org/10.1111/cen.13924

    Article  CAS  Google Scholar 

  20. Moucari R, Asselah T, Cazal-Shatem D, Voitot H, Boyer N, Ripault MP et al (2008) Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology 134(2):416–423 [PMID: 18164296. https://doi.org/10.1053/j.gastro.2007.11.010

    Article  CAS  PubMed  Google Scholar 

  21. Alzahaby A (2018) Effect of Direct Acting Anti-viral Agents on Insulin Resistance in Chronic HCV Patients’. Egypt J Hospital Med 72(4):4413–4419. https://doi.org/10.12816/ejhm.2018.9452

    Article  Google Scholar 

  22. Premji R, Roopnarinesingh N, Qazi N, Nylen ES (2015) New-onset diabetes mellitus with exposure to ledipasvir and sofosbuvir. J Invest Med High Impact Case Rep 3(4):2324709615623300 [PMID: 26788529. https://doi.org/10.1177/2324709615623300

    Article  Google Scholar 

  23. Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ et al (2015) Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. New Engl J Med 373(8):705–713 [PMID: 26196665. https://doi.org/10.1056/NEJMoa1501315

    Article  CAS  PubMed  Google Scholar 

  24. El Kassas M, Elbaz T, Hafez E, Esmat G (2016) Safety of direct antiviral agents in the management of hepatitis C. Expert Opin Drug Saf 15(12):1643–1652 [PMID: 27661100. https://doi.org/10.1080/14740338.2017.1240781

    Article  CAS  PubMed  Google Scholar 

  25. Shehab Eldin W, Nada A, Abdulla A et al (2017) The effect of hepatitis C virus eradication with new direct acting antivirals on glucose homeostasis in non-diabetic Egyptian patients. J Diabetes Metab 8(10). https://doi.org/10.4172/2155-6156.1000766

  26. Dinolfi LE, Nevola R, Guerrera B, D'Alterio G, Marrone A, Giordano M et al (2018) Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J Gastroenterol Hepatol 33(7):1379–1382 [PMID: 29228501. https://doi.org/10.1111/jgh.14067

    Article  CAS  Google Scholar 

  27. El Sagheer G, Soliman E, Ahmad A, Hamdy L (2018) Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs. Libyan J Med 13(1) PMID: 29451090. https://doi.org/10.1080/19932820.2018

  28. Elhelbawy M, Abdel-Razek W, Alsebaey A, Hashim M, Elshenawy H, Waked I (2019) Insulin resistance does not impair response of chronic hepatitis C virus to direct-acting antivirals, and improves with the treatment. Eur J Gastroenterol Hepatol 31(1):16–23 [PMID: 30024489. https://doi.org/10.1097/MEG.0000000000001215

    Article  CAS  PubMed  Google Scholar 

  29. Pavone P, Tieghi T, d'Ettorre G, Lichtner M, Marocco R, Mezzaroma I et al (2016) Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents. Clin Microbiol Infect 22(5):462–471 [PMID: 26812446. https://doi.org/10.1016/j.cmi.2015.12.030

    Article  CAS  PubMed  Google Scholar 

  30. Ciancio A, Bosio R, Bo S, Pellegrini M, Sacco M, Vogliotti E et al (2018) Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 90(2):320–327 [PMID: 28960353. https://doi.org/10.1002/jmv.24954

    Article  CAS  PubMed  Google Scholar 

  31. Dawood AA, Nooh MZ, Elgamal AA (2017) Factors associated with improved glycemic control by direct-acting antiviral agent treatment in Egyptian type 2 diabetes mellitus patients with chronic hepatitis C genotype 4. Diabetes Metab J 41(4):316–321 [PMID: 28868829. https://doi.org/10.4093/dmj.2017.41.4.316

    Article  PubMed  PubMed Central  Google Scholar 

  32. Stine JG, Wynter JA, Niccum B, Kelly V, Caldwell SH, Shah NL (2017) Effect of treatment with direct acting antiviral on glycemic control in patients with diabetes mellitus and chronic hepatitis C. Ann Hepatol 16(2):215–220 [PMID: 31153414. https://doi.org/10.5604/16652681.1231581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Arase Y, Suzuki F, Suzuki Y, Akuta N, Kobayashi M, Kawamura Y et al (2009) Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology 49(3):739–744 [PMID: 19127513. https://doi.org/10.1002/hep.22703

    Article  CAS  PubMed  Google Scholar 

  34. Romero-Gómez M, Diago M, Andrade RJ, Calleja JL, Salmerón J, Fernández-Rodríguez CM et al (2009) Treatment of insulin resistance with metformin in naïve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin. Hepatology 50(6):1702–1708 [PMID: 19845037. https://doi.org/10.1002/hep.23206

    Article  PubMed  Google Scholar 

  35. Bassendine MF, Sheridan DA, Bridge SH et al (2013) Lipids and HCV. Sem Immunopathol 35(1):87–100[PMID: 23111699. https://doi.org/10.1007/s00281-012-0356-2

    Article  CAS  Google Scholar 

  36. Kuo YH, Chuang TW, Hung CH, Chen CH, Wang JH, Hu TH et al (2011) Reversal of hypolipidemia in chronic hepatitis C patients after successful antiviral therapy. J Formosan Med Assoc 110(6):363–371 [PMID: 21741004. https://doi.org/10.1016/S0929-6646(11)60054-5

    Article  CAS  PubMed  Google Scholar 

  37. Marzouk D, Sass J, Bakr I, El Hosseiny M, Abdel-Hamid M, Rekacewicz C et al (2007) Metabolic and cardiovascular risk profiles and hepatitis C virus infection in rural Egypt. Gut 56(8):1105–1110 [PMID: 16956918. https://doi.org/10.1136/gut.2006.091983

    Article  CAS  PubMed  Google Scholar 

  38. Corey KE, Kane E, Munroe C, Barlow LL, Zheng H, Chung RT (2009) Hepatitis C virus infection and its clearance alter circulating lipids: implications for long-term follow-up. Hepatology 50(4):1030–1037 [PMID: 19787818. https://doi.org/10.1002/hep.23219

    Article  CAS  PubMed  Google Scholar 

  39. Chida T, Kawata K, Ohta K, Matsunaga E, Ito J, Shimoyama S et al (2018) Rapid changes in serum lipid profiles during combination therapy with daclatasvir and asunaprevir in patients infected with hepatitis C virus genotype 1b. Gut Liver 12(2):201–207 [PMID: 29212314. https://doi.org/10.5009/gnl17179

    Article  CAS  PubMed  Google Scholar 

  40. Villani R, Di Cosimo F, Romano AD, Sangineto M, Serviddio G (2021) Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis. Sci Rep. 11(1):13944. https://doi.org/10.1038/s41598-021-93251-3 PMID: 34230541; PMCID: PMC8260657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the National Committee for Control of Viral Hepatitis in Egypt and the team of the New Cairo hepatitis treatment unit.

Funding

This is a non-funded work.

Author information

Authors and Affiliations

  1. Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt

    Mohamed El-Kassas

  2. Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Runia El-Folly, Mohamed Bahgat & Mostafa Hamed

  3. Department of Endocrinology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Maram Aboromia

  4. Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Heba Aly

Authors
  1. Mohamed El-Kassas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Runia El-Folly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maram Aboromia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heba Aly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed Bahgat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mostafa Hamed
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MH, MA, and MEK conceptualized the idea and study design. MB, MA, and RF were responsible for data acquisition. HA performed the laboratory analysis. All authors shared in drafting the manuscript and approved the final version of the manuscript.

Corresponding author

Correspondence to Mohamed El-Kassas.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in this study involving human participants were following the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by Research Ethics Committee (REC) for human subject research at the Faculty of Medicine, Ain Shams University, in December 2016 (serial: 343/2016). Written informed consent was obtained from all individual participants included in the study.

Consent for publication

All authors agree to the journal rules for publications.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

El-Kassas, M., El-Folly, R., Aboromia, M. et al. Effect of achieving sustained virological response with direct-acting antiviral agents on glycemic control in diabetic patients with chronic hepatitis C infection. Egypt Liver Journal 12, 25 (2022). https://doi.org/10.1186/s43066-022-00190-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43066-022-00190-3

Keywords