Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C

Saraiva, Geórgia Nascimento; Rosário, Natalia Fonseca do; Medeiros, Thalia; Leite, Paulo Emílio Corrêa; Lacerda, Gilmar de Souza; Andrade, Thaís Guaraná de; Azeredo, Elzinandes Leal de; Ancuța, Petronela; Almeida, Jorge Reis; Xavier, Analúcia Rampazzo; Silva, Andréa Alice

doi:10.1155/2018/8578051

Cited by 39 publications

(45 citation statements)

References 40 publications

(48 reference statements)

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“…The observations of rapidly improved ALT and sCD163 values combined with a decrease in liver stiffness within the period of DAA therapy suggest prompt resolution of liver inflammation in parallel with clearance of the hepatitis C virus. This is supported by several studies with similar results regarding inflammatory mediators, sCD163 and liver stiffness during DAA therapy …”

Section: Discussionsupporting

confidence: 84%

“…This is supported by several studies with similar results regarding inflammatory mediators, sCD163 and liver stiffness during DAA therapy. [34][35][36] Next, we examined the long-term effects of DAA therapy on liver fibrosis during one-year follow-up after treatment and found a continued decrease in liver stiffness. Whereas ALT and sCD163 levels had plateaued already at EOT, liver stiffness continued to health.…”

Section: Discussionmentioning

confidence: 99%

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Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C

Laursen

Siggaard

Kazankov

et al. 2019

Journal of Viral Hepatitis

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Sofosbuvir‐based direct‐acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy‐one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir‐based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow‐up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post‐treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one‐year follow‐up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C

Laursen

Siggaard

Kazankov

et al. 2019

Journal of Viral Hepatitis

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“…This was explained as, the eradication of virus by Sofosbuvir treatment regimens lead to restoration of immune response. In contrast to this study which done by Saraiva [40] who stated that serum level of interleukin-6 didn't change after the treatment due to its role in liver repair process.…”

Section: Discussioncontrasting

confidence: 72%

Prediction of sofosbuvir response using interleukin-6 serum level and single nucleotide polymorphism of interferon lambda- 4

Saafan

Abobaker

Abbas

et al. 2020

J Infect Dev Ctries

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Introduction: In Egypt, 15% of the populations are suffering from chronic hepatitis C especially genotype 4. Sofosbuvir was approved by FDA in December 2013 for treatment of HCV genotypes 2 and 3 in combination with Ribavirin, and for genotypes 1 and 4 in combination with Peg-IFN. Recently, polymorphism of different genes and plasma levels of IL-6 were utilized for better prediction of HCV clearance. This study aimed at early prediction of the efficacy of HCV treatment with Sofosbuvir (Sovaldi) and comparing the antiviral efficacy of dual and triple Sovaldi combination therapy. Methodology: Blood samples were collected from 100 HCV positive patients and detected by real time PCR at three time intervals. SNP genotyping of INFL-4 gene was estimated by using real-time PCR with predesigned primers and Taqman probes. IL-6 serum level was estimated before, during and after the end of the treatment using ELISA assay based on human IL-6 KIT. Results: SNP genotyping of INFL-4 gene showed that 13.1% of patients carried ∆G/∆G, 30.4% patients had TT/TT and 56.5% patients possessed heterozygote allele ∆G/TT. Clinical data displayed that 13 patients were got relapsed at SVR 12. Serum level of IL-6 was noticed higher in HCV patients than healthy ones. Noteworthy, it was increased during treatment then decreased to a minimal level than begining of treatment. Conclusion: SNP in INFL-4 gene has displayed no effect in response to Sofosbuvir. Dual therapy had the same effect like triple therapy, so interferon could be withdrawn from the treatment regimen.

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“…Does elevated circulating suPAR cause any liver pathology? As described earlier, circulating suPAR was increased in patients with chronic hepatitis C, yet viral control by direct‐acting antiviral therapy failed to reduce suPAR levels even though liver function was improved and the levels of other inflammatory mediator decreased, suggesting that elevated circulating suPAR may not be the culprit for liver damage in this scenario. In regard to kidney disease, our group has identified suPAR as a causative circulating factor that contributes to the development of glomerular diseases such as focal segmental glomerulosclerosis (FSGS) via activating podocyte αvβ3 integrin and c‐src .…”

Section: Role Of Supar In the Management Of Liver Diseasementioning

confidence: 70%

Soluble Urokinase Receptor and Liver Disease

Wei

Zhu

Reiser

2019

Clinical Liver Disease

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Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C

Cited by 39 publications

References 40 publications

Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C

Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C

Prediction of sofosbuvir response using interleukin-6 serum level and single nucleotide polymorphism of interferon lambda- 4

Soluble Urokinase Receptor and Liver Disease

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