Treatment of hepatitis C virus infection with direct-acting antivirals plus ribavirin eliminates viral RNA from peripheral blood mononuclear cells and reduces virologic relapse in diverse hepatic parenchymal changes

Alla, Mohamed Darwish Ahmed Abd; Dawood, Reham M.; Rashed, Hassan Abd El-Hafeth; Farrag, Galal; Ammar, Islam Abdel-Mawla; Mahmoud, Mohamed Mahmoud Abdel-Halim; Salum, Ghada M.; Altanbouly, Ahmed Mohamed Abdulhamid; El-Meguid, Mai Abd; Awady, Mostafa K. El

doi:10.1007/s00705-021-04969-4

Cited by 8 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In HCV-related hepatic cirrhosis, hepatocellular carcinoma (HCC) occurs at an annual rate of about 3% [ 30 ]. Orthotropic liver transplantation (OLT) offers a treatment option for end-stage liver disease patients.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

Salum

El-Meguid

Abelhafez

et al. 2021

Journal of Genetic Engineering and Biotechnology

Self Cite

View full text Add to dashboard Cite

Background Orthotropic liver transplantation (OLT) offers a therapeutic choice for hepatocellular carcinoma (HCC) patients. The poor outcome of liver transplantation is HCV recurrence. Several genome-wide associated studies (GWAS) have reported many genetic variants to be associated with HCV recurrence. Seven gene polymorphisms formed a cirrhosis risk score (CRS) signature that could be used to distinguish chronic HCV patients at high risk from those at low risk for cirrhosis in non-transplant patients. This study aims to examine the association of CRS score and other clinical parameters with the probability for HCC emergence and/or the rate of HCV recurrence following liver transplantation. Results Seven gene polymorphisms, forming the CRS, were genotyped by real-time PCR using allelic discrimination protocol in 199 end-stage liver disease patients (79 child A, 43 child B, and 77child C), comprising 106 patients who encountered liver transplantation. Recipient CRS scores were correlated with HCV recurrence (HCV-Rec) at the end of the third year after OLT. Around 81% (39) recipients with low steatosis (LS; < 3.5%) donor percentage revealed no HCV recurrence (non-Rec) (p<0.001). CRS score could distinguish between child A, child B, and child C only at the low-risk group. Among the HCV Rec group 27% (8/30), 40% (12/30), and 33% (10/30) fell into the high, moderate, and low CRS risk groups, respectively. Stepwise logistic regression evinced two features more likely to be seen in HCV-Rec patients: abnormal ALT [OR, 1.1; 95% CI, 1.02–1.2] and donor steatosis >3.5% [OR, 46.07; 95% CI, 1.5–1407.8]. Conclusions Accordingly, the CRS score seems to be less useful to predict HCV recurrence after OLT. ALT and donor steatosis (exceed 3.5%) can significantly promote the HCV recurrence post-OLT. Moreover, the combination of MMF and CNI positively heightens HCV recurrence.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

Salum

El-Meguid

Abelhafez

et al. 2021

Journal of Genetic Engineering and Biotechnology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Neo-angiogenesis may also favor HCC development, and markers of angiogenesis, like VEGF and angiopoietin-2, either increase or persist during or after DAAs administration [122,123] . Another explanation for HCC recurrence and occurrence after DAAs was proposed after the finding that SVR achievement with DAAs was accompanied by a high prevalence of occult HCV persistence in peripheral blood mononuclear cells [124,125] . This occult persistence was not observed when ribavirin was added to the DAAs scheme [126] .…”

Section: An Explanation For Increased Hcc After Daasmentioning

confidence: 99%

Hepatocellular carcinoma after treatment of hepatitis C with direct-acting antivirals: a critical re-appraisal

Tsomidis¹,

Voumvouraki²

2023

Hepatoma Res

View full text Add to dashboard Cite

Soon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, there began a debate over the possibility of hepatocellular carcinoma (HCC) after viral clearance. Although several reports suggested that the question has been answered negatively, other reports suggested the opposite. The present review presents data in favor and against the null hypothesis and analyzes the scientific background of the possible participation of DAAs in HCC development. The reasons for the discrepancy among studies are presented. These include heterogeneity of patient selection, the nature of the studies, and the tumors themselves are responsible for varying results. Exogenous factors like alcohol consumption or metabolic syndrome confound these findings and suggest the need for statistical adjustments. The need for careful attention to the statistical details is exemplified, and the significant points of almost universal agreements are identified. The conclusion is that the definitive study is impossible for ethical and scientific reasons, and the physician should not ignore even simple personal observations and screening of all patients with extensive fibrosis in HCC, irrespective of sustained virologic response, until a robust, reliable prognostic model can be invented.

show abstract

“…The recognized absent hepatic tissue changes, bright liver parenchyma, and coarse hepatic surface by the US are respectively corresponding to normal (up to 5 kPa), up to moderate fibrosis (more than 5 but less than 15 kPa), and cirrhosis (≥ 15 kPa) by Fibroscan [ 9 ]. FIB-4 scoring is a biochemical-dependent scoring system that evaluates hepatic tissue changes and confirms the above-mentioned liver tissue grading by US [ 8 , 10 ]. Sequelae of chronic HCV infection are variable among different hosts; they show no, slow, intermediate, and rapid progress in years or even decades to fibro-cirrhotic changes in liver tissues [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…In chronic naive and post-treatment HCV RNA seropositive patients, evaluation of infection risk factors, as well as the correlation of infection courses with host immune-pathologic changes and treatment outcomes, are convenient tasks [ 5 , 6 ]. On the other hand, diagnosing active chronic HCV infection in the RNA-seronegative population has been a challenge until developing cellular PCR that addressed intra-hepatocytes and intra-PBMCs RNA detection in both cryptogenic and occult viral infection [ 7 , 8 ]. Grading of active hepatic tissues fibro-cirrhotic changes was addressed in chronic HCV infection in viremic patients and in solitary intracellular viral infections (who had negative serum viral RNA PCR) [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Recognition of 7 genes signature (Cirrhosis Risk Score) in the diagnosed non-responders to DAAs therapy by intra-PBMCs nested HCV RNA PCR

Galal,

Dawood,

Awady

et al. 2023

Journal of Genetic Engineering and Biotechnology

Self Cite

View full text Add to dashboard Cite

Background and aims Predictors of chronic HCV response to oral antiviral therapy (OAT) are related to host genetic variations. Single nucleotide polymorphisms (SNP) and alleles variations of host genes in association with hepatic fibro-cirrhotic changes have a distinct role in OAT outcomes. The current research evaluated the association of Cirrhosis-Risk-Scores (CRS) values, based on the correlation of seven genes signature-SNPs, with sonographic liver parenchymal changes in determining OAT outcomes. Methods All study subjects (n = 54) were recruited three months after completing OAT and classified into three groups. Group I (n = 21) had negative HCV PCR, group II (n = 17) showed positive solitary intra-PBMCs HCV infection, and group III(n = 16) was serum HCV RNA PCR-positive. All study-population were subjected to examination by hepatic-ultrasound (US), FIB-4-scoring, and screening for 7 gene-signature that addressed CRS values as low, intermediate, and high depending on gene SNPs identification. Results Group I showed a significant association with low CRS values compared to other groups (P < 0.001). Solitary intra- PBMCs HCV infection in group II was significantly combined with intermediate CRS values in comparison to groups I and III (P < 0.001). The high CRS values were significantly found in group III when compared to groups I and II (P < 0.01). On US imaging, low CRS values were common in normally appeared hepatic parenchyma (P < 0.001) and high CRS values were frequent in coarse-liver (P < 0.001), while bright-liver-tissues appearance was mainly detected in the intermediate CRS category (P = 0.09). On FIB-4 scoring, high CRS value were associated with hepatic fibro-cirrhosis compared to intermediate (P < 0.001) and low (P = 0.08) CRS-categories. Conclusion The current study concluded the association of (a) high CRS values with coarse liver in viral-RNA serologic relapse, (b) low CRS values with normal liver tissues in sustained virologic response (SVR), (c) intermediate CRS values with bright liver in solitary PBMCs relapse.

show abstract

Treatment of hepatitis C virus infection with direct-acting antivirals plus ribavirin eliminates viral RNA from peripheral blood mononuclear cells and reduces virologic relapse in diverse hepatic parenchymal changes

Cited by 8 publications

References 47 publications

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

Evaluation of seven gene signature for predicting HCV recurrence post-liver transplantation

Hepatocellular carcinoma after treatment of hepatitis C with direct-acting antivirals: a critical re-appraisal

Recognition of 7 genes signature (Cirrhosis Risk Score) in the diagnosed non-responders to DAAs therapy by intra-PBMCs nested HCV RNA PCR

Contact Info

Product

Resources

About