HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma.

The allelic discrimination of IFNL3-(rs12979860 C > T) polymorphism reveals ambiguous associations with the effectiveness of oral HCV treatment. Solitary intra peripheral-blood-mononuclear-cells (PBMCs) HCV-RNA antisense-strands are independently detected in naïve and experienced cases regardless of viremia or hepatic-parenchymal alterations. We examined the frequencies of IFNL3-genetic variants with chronic-HCV-induced liver changes during the sustained virologic response (SVR) by evaluating the PBMCs- HCV-PCR after oral antiviral therapy. Methods: Twelve weeks after finishing oral antiviral therapy, the effects of IFNL3-genetic variants were evaluated in three groups of patients: Group-I (n = 25) showed HCV-RNA negativity in both serum and PBMCs-, group II (n = 52) showed positivity of HCV-RNA in PBMCs, and group-III (n = 25) had positive HCV-RNA in serum. The genetic variants of the IFNL3-gene were estimated for all the enrolled cases and correlated with their hepatic image changes. Results: IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: a) high frequency of CC-genotype and C-allele in group I compared to group II (P < 0.005) and group III(P ≤ 0.05) when hepatic-parenchyma looks normal by ultrasound b) frequent CT-genotype and T-allele in group II compared with I(P < 0.01) and III(P < 0.05) when liver tissues are bright (early cirrhotic-changes) c) frequent TT-genotype and T-allele in group III relative to I (P < 0.05) and II (P ≤ 0.08) when liver-tissues appear coarse by ultrasound. Conclusion: Outcomes of HCV treatment depend on host IFNL3-gene polymorphism and hepatic-parenchymal changes. A high frequency of wild-CC-genotype and C-allele is observed in patients with normal hepatic parenchyma and that achieved SVR. Solitary relapse in PBMCs occurs on increasing CT-genotype frequency when liver tissues are bright. Serologic relapse is detected when TT-genotype and T-allele are dominant in association with the cirrhotic liver. Therefore, IFNL3-gene-SNP analysis as a genetic predictor in relation to ultra-sonographic hepatic-parenchymal changes could be valuable for selecting the patients with the highest priority for treatment.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS: Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS: The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION: Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.

Evaluation of factors affecting patients' refusal of HCV treatment in a cohort of Egyptian patients.

BACKGROUND: Treatment refusal, defined as active refusal of a patient to receive treatment despite physician recommendations, has not been extensively evaluated before in hepatitis C virus in the era of direct acting antivirals. OBJECTIVE: To investigate the reasons for refusal to receive hepatitis C virus treatment in Egypt. METHODS: an observational study conducted between July 2018 and November 2019 in Egypt. Enrollment was done to all patients who refused to get hepatitis C virus treatment during the national screening and treatment campaign. Reasons for their refusal were identified using a questionnaire as an instrument for data collection. RESULTS: Out of the 220 280 Egyptian hepatitis C virus patients who did not show up to start treatment and were contacted to get therapy, only 84 patients (0.038%) refused to receive treatment. The main reason for their refusal was having concerns about treatment (82.14%) and their main concern was the fear of adverse events (85.5%). Other causes of refusal were non-satisfactory experience at treatment centers (13.09%) and patients preferred to receive complementary and alternative medicines (4.7%). Most patients (65.4%) trusted the efficacy of directly acting antivirals for hepatitis C. None of the study participants was found to suffer from any psychiatric morbidity and the average score of the GHQ-12 was 10.7155. CONCLUSION: Proper health education and awareness regarding hepatitis C virus treatment safety and efficacy is needed to increase treatment acceptance rates.

Nationwide hepatitis C virus screening and treatment of adolescents in Egyptian schools.

Until 2018, Egypt had the highest prevalence of hepatitis C virus (HCV) infection globally, affecting approximately 7% of the population. Despite efforts in diagnosis and treatment since 2006, nearly 2 million individuals with chronic HCV infection had yet to be diagnosed as of early 2018. In December, 2018, a mass HCV screening campaign for adolescents aged 15-18 years was initiated. Among 3 024 325 adolescents screened, the HCV antibody seroprevalence was 11 477 (0·38%), of whom 8187 (78·7%) were HCV RNA-positive. Sustained virological response 12 weeks after completion of treatment (SVR12) was attained by 7327 (99·6%) adolescents with a fixed-dose combination of generic ledipasvir 90 mg plus sofosbuvir 400 mg. Although mass screening in this age group might not be regularly adopted by many health systems and its cost-effectiveness might be lower than the screening of adults and high-risk groups (eg, patients on haemodialysis, people who inject drugs), breaking the chain of transmission in younger populations should lead to a reduction in HCV incidence and complications, and hasten the elimination of the disease.

Pregnancy outcome of anti-HCV direct-acting antivirals: Real-life data from an Egyptian cohort.

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.

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.

Elimination of hepatitis C virus (HCV) may fail, leading to a non-response outcome because of inappropriate testing for viral RNA in peripheral blood mononuclear cells (PBMCs). Sequelae of HCV genotype 4 therapy with sofosbuvir and daclatasvir ± ribavirin were assessed in our study at the 12th week after end of treatment (EOT) by screening for viral genomic RNA in serum and PBMCs with correlation to hepatic parenchymal changes. We recruited 102 out of 2165 patients who had received sofosbuvir/daclatasvir, either alone (n = 1573) or together with ribavirin (n = 592). Subjects were classified into three groups based on testing by single-step reverse transcription PCR: group I, HCV negative in both serum and PBMCs (n = 25); group II, HCV positive in PBMCs only (n = 52); and group III, HCV positive in both serum and PBMCs (n = 25). Groups I and II (n = 77) were selected out of 2102 (every 27th subject), while group III (n = 25) were selected from every second or third serologic relapse (n = 63). The pre-sampling population (n = 2165) showed sustained virologic response (SVR) in 33.21%; serologic relapse in 2.91%; HCV RNA only in PBMCs (66.79%) compared to serologic relapses and potential cure (P < 0.0001); higher serologic (38 out of 63, P = 0.03210) and cellular (36 out of 52, P = 0.0002) relapses in dual therapy than in triple therapy. The post-sampling population (n = 102) showed more HCV relapses in dual (50 out of 60) than in triple (27 out of 42) therapy (P = 0.0351); increased HCV antisense RNA strand in relapses compared to positive-sense strands alone (P < 0.001); and significant SVR events in undetectable (15 out of 31) compared to early (10 out of 55, P = 0.0058) and cirrhotic liver tissue changes (0 out of 16, P = 0.0006). In summary, HCV treatment with sofosbuvir/daclatasvir is followed by higher rates of serologic and intracellular viral RNA relapse than treatment with sofosbuvir/daclatasvir plus ribavirin. Cellular and serum viral RNA relapses are accompanied by HCV-induced hepatic pathology. An increased SVR with no detectable liver tissue changes was observed after triple therapy due to elimination of HCV RNA from PBMCs.

Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis.

OBJECTIVE: To compare the efficacy and safety of dienogest (DNG) with depot leuprolide acetate (LA) in patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. DESIGN: Prospective randomized trial. SETTING: Zagazig University hospitals, Egypt. PATIENTS: Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. INTERVENTION: Dienogest (2 mg/day, orally) or depot LA (3.75 mg/4 weeks, intramuscularly) for 12 weeks. MAIN OUTCOME MEASURES: A visual analogue scale was used to test the intensity of pain before and after the end of treatment. RESULTS: There was highly significant reduction in pelvic pain, back pain and dyspareunia in both groups with mean of difference in dienogest group (28.7 ± 5.3, 19.0 ± 4.3 and 20.0 ± 3.08 mm, respectively) and in LA group (26.2 ± 3.01, 19.5 ± 3.01 and 17.9 ± 2.9 mm, respectively). The most frequent drug-related adverse effects in dienogest group were vaginal bleeding and weight gain (64.5 and 10.8%, respectively) which were significantly higher than LA group (21.5 and 3.3%, respectively). While the most frequent drug-related adverse effects in LA group were hot flushes and vaginal dryness (46.3 and 15.7%, respectively) which were significantly higher than dienogest group (15.7 and 3.3%, respectively). CONCLUSION: Daily dienogest is as effective as depot LA for relieving endometriosis-associated pelvic pain, low back pain and dyspareunia. In addition, dienogest has acceptable safety, tolerability and lower incidence of hot flushes. Thus, it may offer an effective and well-tolerated treatment in endometriosis.

First-Trimester Uterine Artery Pulsatility Index and Maternal Serum PAPP-A and PlGF in Prediction of Preeclampsia in Primigravida.

BACKGROUND: Preeclampsia is a heterogeneous disorder affecting different body systems and frequently associated with morbidity and mortality. Early preeclampsia prediction will reduce this associated morbidity and mortality as it will give the chance for frequent maternal and fetal surveillance and application of prophylactic procedures. OBJECTIVE: The aim of this work is to evaluate the role of mean pulsatility index (PI) of the uterine arteries and maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF) in early preeclampsia prediction in primigravida. PATIENTS AND METHODS: Three hundred primigravida attending the antenatal care clinic in Zagazig University Hospitals were included in the study. The mean PI of the uterine arteries was calculated. Maternal serum levels of PAPP-A and PIGF were analyzed by specific immunoassay. RESULTS: Three hundred women were included in the final analysis, of them 30 patients (10%) suffered from preeclampsia. There was a significant difference between preeclamptic and normal women as regards the mean PI of the uterine arteries and levels of PAPP-A and PIGF at 11-13 weeks. When combining the cutoff levels of the three methods, mean PI of the uterine arteries ≥1.69, PAPP-A assay <0.96 multiple of median (MoM) and PlGF assay <0.91 MoM, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy were 56.7, 99.3, 89.5, 95.4 and 67%, respectively. CONCLUSION: The combined measurement of maternal serum PAPP-A and PlGF concentrations and mean PI of the uterine arteries at 11-13 weeks of pregnancy may help to predict preeclampsia in primigravida when other parameters of preeclampsia prediction are normal. However, we need more studies on larger and variable populations to evaluate the use of those combined methods in preeclampsia prediction.

Major lymphocyte populations and T-cell expression of ICAM-1 and L-selectin adhesion molecules in Kuwaitis with asthma and rhinitis.

The authors evaluate major immunologic features of asthma and allergies in a Kuwaiti population. They analyzed peripheral venous blood from 17 asthmatic and 17 healthy long-term residents of Kuwait by using two-color flow cytometry for major lymphocyte subpopulations; they also evaluated 10 healthy individuals who had recently arrived in Kuwait. Relative to healthy subjects, asthmatics exhibited increased percentages of T+ NK cells (p < .01), T-helper cells (p < .05), T-cytotoxic and NK cells for both total numbers (p < .01-.001) and percentages (p < .05-.01), and increased percentages of T cells expressing CD54 (ICAM-1; p < .001) and CD62 (L-selectin; p < .01). However, B cells were present at significantly lower levels in asthmatics, both in total numbers (p < .05) and percentages (p < .01). In comparison with healthy individuals who had recently arrived in Kuwait, healthy long-term residents exhibited elevated numbers of pan-T cells (p < .01) and T-helper cells (p < .05). These results help establish immunological parameters for asthma and allergies in Kuwaiti populations.