High Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and &amp;#947;-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study

Amanzada, Ahmad; Goralczyk, Armin D.; Schneider, S.; Moriconi, Federico; Lindhorst, A; Mihm, Sabine; Thiel, David H. Van; Ramadori, Giuliano

doi:10.1159/000339879

Cited by 15 publications

(18 citation statements)

References 81 publications

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“…As to the sensitivity of HCV-1 subtypes to Peg-IFN and RIBA, there has been no consistency among studies in regard to a differential responsiveness of subtype 1a vs 1b on either on-and offtreatment parameters (6)(7)(8)(9)(10)(11)(12)(13). In our investigation, HCV clearance by week 4 and 12 of treatments, and at the end of treatment did not differ between patients carrying one or the other subtype ( Figure 1).…”

Section: Discussionmentioning

confidence: 55%

“…Up to now, genotyping for HCV-1 subtypes will not impact on the day-to-day clinical management of chronic HCV infection, whereas conflicting reports exist on their influence on the outcome following conventional therapy with Peg-IFN and RIBA (6)(7)(8)(9)(10)(11)(12)(13). Recently, several HCV inhibitors appear to have selective activity against HCV 1 subtypes both in vitro and in vivo, with subtype 1a appearing more resistance-prone and less responsive to triple therapy than subtype 1b (25)(26)(27)(28)).…”

Section: Discussionmentioning

confidence: 99%

“…Major clinical trials evaluated treatment response among HCV-1a and 1b patients grouped together and, consequently, were unable to unveil a differential outcome of treatment between the two viral strains. Of available trials (7)(8)(9)(10)(11)(12)(13)(14), only few studies were sufficiently powered to detect an eventual difference, with some reporting a lower efficacy of Peg-IFN and RIBA in HCV-subtype 1a, and other studies unraveling an opposite finding. In addition, the impact of HCV-1 subtypes on the on-treatment response milestones, such as the rapid viral response at treatment week 4 (RVR), has not been extensively investigated.…”

Section: Introductionmentioning

confidence: 99%

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HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Andriulli

Morisco²,

Ippolito

et al. 2014

Hepatol Int

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Short title: HCV subtypes 1a and 1b and treatment outcome after peg-interferon and ribavirin Key words: HCV genotype, HCV subtypes, chronic HCV liver disease, sustained virologic response, peg-interferon and ribavirin. Abstract words count: 254Full text words count: Tables # 2 o3 Figures # 2 Conclusion: in Italy HCV-1 subtype 1a prevails in young, male patients with less advanced liver damage, findings which imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Andriulli

Morisco²,

Ippolito

et al. 2014

Hepatol Int

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“…IL28 rs12979860 genotyping was performed using a Custom TaqMan SNP Genotyping assay as described previously [25]. Genotyping of the dinucleotide polymorphism IFNL4 ss469415590 (refSNP number rs368234815) was performed using the published primer and probes [21].…”

Section: Methodsmentioning

confidence: 99%

Interferon-λ4 (IFNL4) Transcript Expression in Human Liver Tissue Samples

Amanzada¹,

Kopp²,

Spengler

et al. 2013

PLoS ONE

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Eradication of hepatitis C virus (HCV) infection, both spontaneous and treatment-induced, is marked by the wildtype allele C of a single nucleotide polymorphism upstream of the IL28B gene, rs12979860. This favorable allele was recently described to be in linkage disequilibrium with the wildtype allele TT of a dinucleotide polymorphism, ss469415590, located within a new protein-coding gene. While the TT allele introduces a frame-shift and disrupts the open reading frame, only the variant allele, ΔG, creates a novel type III interferon (IFN) protein, IFN-λ4/IFNL4. Absence of IFNL4 is thus supposed to favor resolution of HCV infection. As to date IFNL4 mRNA transcription has only been investigated in polyI:C-stimulated primary human hepatocytes and not yet in HCV infection in vivo, this study analyzed IFNL4 mRNA expression in human liver biopsy specimens. Samples were obtained from patients with a broad panel of disorders including no liver disease, liver diseases of non-viral etiology, chronic hepatitis B and chronic hepatitis C. Hepatic IFNL4 transcripts were detectable exclusively in a subgroup of chronic hepatitis C patients (24/45). Their amounts were positively related to liver HCV RNA copy numbers (p = 0.0023, r = 0.56) suggesting that the hepatic viral load influences IFNL4 transcription irrespective of IFNL4 governing genotype. Both, the IFNL4 creating allele ΔG (p<0.0001) and actual IFNL4 transcription (p = 0.0015) were found to be correlated to the activation of IFN stimulatory genes (ISGs). By contrast, IFNL4 ss469415590 genotypes were not found to be related to IFN-λ2/3/IL28 or IFN-λ1/IL29 gene expression. In conclusion, this study is the first report on intrahepatic transcript levels of the recently discovered IFNL4 gene. Data indicate that HCV infection in particular might activate IFNL4 transcription in the liver. It provides a possible explanation as to why hepatitis C patients show ISG stimulation in their livers in the apparent absence of an induction of other IFN subtypes.

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“…It is important to highlight other predictors of therapeutic response: serum vitamin D (14,25) ; and CC (rs 12979860) Interleukin 28B genotype (1,22,27) . The GGT enzyme catalyzes the degradation of extracellular glutathione (GSH) in the transfer of amino acids and peptides across cell membranes (15,19) , forming a "gamma-glutamyl cycle" (30) .…”

Section: Introductionmentioning

confidence: 99%

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature

Queiroga

Paraná

Filho

et al. 2015

Arq. Gastroenterol.

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-Background -The standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase. Objective -To evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C. Methods -This is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013. Results -A total of 4,785 titles were iden tified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study -six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %). Conclusion -Gamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin. HEADINGS -Gamma glutamyltransferase. Hepatitis C. Sustained virological response. Review.

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High Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and γ-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study

Cited by 15 publications

References 81 publications

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

Interferon-λ4 (IFNL4) Transcript Expression in Human Liver Tissue Samples

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature

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