Exploring lipid and apolipoprotein levels in chronic hepatitis C patients according to their response to antiviral treatment

Lacerda, Gilmar de Souza; Medeiros, Thalia; Rosário, Natalia Fonseca do; Peralta, Regina Helena Saramago; Cabral‐Castro, Mauro Jorge; Esberard, Eliane Bordalo Cathalá; Andrade, Thaís Guaraná de; Xavier, Analúcia Rampazzo; Silva, Andréa Alice

doi:10.1016/j.clinbiochem.2018.07.007

Cited by 17 publications

(16 citation statements)

References 30 publications

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“…Although our results were comparable with some reports that the increases in LDL disappeared after treatment [ 32 , 33 ], other studies suggested the elevated LDL continued to post-treatment 1 year [ 34 – 37 ]. The main reason for the inconsistency was that most of these studies were single-arm studies.…”

Section: Discussionsupporting

confidence: 91%

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

et al. 2021

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Background Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients. Methods A systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL. Results Six studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL. Conclusions For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.

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Section: Discussionsupporting

confidence: 91%

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

et al. 2021

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“…Por otro lado, el VHC es también capaz alterar el metabolismo de los lípidos, ya que varios estudios han documentado hipocolesterolemia e hipolipidemia, particularmente niveles más bajos de colesterol total, LDL y ApoB, el principal componente proteico de LDL y VLDL, en pacientes con infección crónica por VHC (37)(38)(39). Aunque nuestro estudio no fue diseñado para aclarar los efectos del VHC sobre el metabolismo de lípidos, ha demostrado que la eliminación exitosa del VHC resultó en un restablecimiento de los niveles circulantes de colesterol total, LDL y ApoB, de acuerdo con las observaciones en pacientes que lograron una respuesta viral sostenida tras el tratamiento con antivirales de acción directa o con interferón (40,41).…”

Section: Discussionunclassified

Sofosbuvir Treatment Improves Hepatitis C Virus-Induced Insulin Resistance

Rey

Marañón²,

González‐Rodríguez

2021

an.ranf

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Chronic hepatitis C virus (HCV) infection is associated with insulin resistance and type 2 diabetes. The overall aim of this study was to evaluate the effects of sofosbuvir (SOF) on HCV-induced insulin resistance. Clinical parameters were recorded and insulin resistance index (HOMA) calculated from 42 insulin-resistant HCV-patients who underwent SOF-based regimens, at baseline, at the end of treatment (EoT), and at one year after the EoT. Likewise, Huh7 cells expressing full-length HCV replicons were used to elucidate the molecular mechanisms involved in insulin action regulated by SOF. All patients reached a sustained virological response after SOF treatment and, as expected, a significant reduction in liver damage markers and fibrosis stage was observed at the EoT that remained one year later. HOMA significantly improved throughout the study time period. Besides, an increase of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B levels were maintained over time after the EoT. At the molecular level, SOF treatment improved the activation of the insulin signalling cascade after stimulation with the hormone in HCV-hepatocytes and, accordingly, reversed the elevated expression of gluconeogenic genes, the increased glucose production and the impairment of glycogen synthesis induced by HCV. Furthermore, SOF challenge induced an increase of insulin receptor substrate 1 (IRS1) content parallel to a reduction in its serine phosphorylation in HCV-hepatocytes. These results provide novel evidence about the molecular mechanisms involved in the hepatic insulin sensitization induced by SOF treatment involving the recovery of IRS1 protein levels as a hallmark of SOF effects.

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“…With respect to lipid metabolism impairment in patients, unlike the short-term beneficial impact of DAA therapies on glucose metabolism, numerous studies have supported the hypothesis that HCV clearance after therapy is associated with a significant improvement in the lipid profile. A study by Gilmar de Souza Lacerda et al found that the level of serum total cholesterol (P<0.0001), low density lipid protein-C (P<0.0001), VLDL-C (P=0.0003) and triglyceride (P=0.0003) were greatly elevated in patients who had acquired SVR at the end of treatment and 1 year after the end of treatment, while HDL-C levels in serum were not significantly changed, comparing with the baseline level [47]. Similar results were observed in the study by Matt Driedger et al They found out that post-treatment levels of cholesterol (n=36) and triglycerides (n=28) were also evaluated.…”

Section: Recovery Of Metabolic Damagementioning

confidence: 96%

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

Zeng¹,

Li²,

Hou³

et al. 2020

Int. J. Med. Sci.

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Owing to the rapid development and wide clinical application of direct acting antiviral (DAA) drugs in the treatment of hepatitis C virus (HCV) infection, the era of interferon-based therapy has almost come to an end. Cumulative studies show that DAA therapy renders high cure efficiency (>90%) and good safety profile, and may even bring some unexpected benefits to the patients. However, some issues of concern arise, one of which is the resistance mutation of HCV genome leading to failure of treatment. With the aim of providing some meaningful references for the treatment of chronic hepatitis C (CHC), this article summarizes the research progress on benefits of DAA accompanied by viral clearance in the treatment of chronic hepatitis and the drug resistance.

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Exploring lipid and apolipoprotein levels in chronic hepatitis C patients according to their response to antiviral treatment

Cited by 17 publications

References 30 publications

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

Sofosbuvir Treatment Improves Hepatitis C Virus-Induced Insulin Resistance

Direct-acting Antiviral in the Treatment of Chronic Hepatitis C: Bonuses and Challenges

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