Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). RESULTS: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). CONCLUSION: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

The impact of genetic variations in sofosbuvir metabolizing enzymes and innate immunity mediators on treatment outcome in HCV-infected patients.

Hepatitis C virus (HCV) is the leading cause of liver diseases worldwide. At present, combinations of different classes of direct-acting antiviral agents (DAAs) are used as treatment options for HCV, in which sofosbuvir (SOF) is the common DAA among different therapeutic regimes. In Egypt, SOF plus daclatasvir (DCV) is the widely used anti-HCV treatment protocol. Herein, we aimed to assess the association between 3 single-nucleotide polymorphisms (SNPs) at the genes coding for 2 SOF metabolizing enzymes: histidine triad nucleotide-binding protein 1 (HINT1) rs4696/rs7728773 and nucleoside diphosphate kinase 1 (NME1) rs3760468, together with the most potent anti-HCV innate molecule, i.e., interferon lambda 3 (IFNL3) rs12979860 and the response to SOF/DCV in Egyptian patients chronically infected with genotype 4 (GT4). SNPs were genotyped using real-time PCR in DNA from patients who achieved sustained virological response (SVR) at 12 weeks post-SOF/DCV treatment (i.e., responders; n = 188), patients who failed to achieve SVR12 (i.e., non-responders; n = 109), and healthy controls (n = 62). Our results demonstrated that patients bearing HINT1 rs7728773 CT/TT (odds ratio 2.119, 95% CI 1.263-3.559, p = 0.005) and IFNL3 rs12979860 CC (odds ratio 3.995, 95% CI 2.126-7.740, p = 0.0001) were more likely to achieve SVR12. However, neither HINT1 rs4696 nor NME1 rs3760468 seems to contribute to the responsiveness to SOF/DCV. Binary regression analysis defined 5 predictor factors independently associated with SVR12: age, bilirubin, hemoglobin, early stages of fibrosis, and combined HINT1 rs7728773 and IFNL3 rs12979860 favorable and mixed genotypes (odds ratio 3.134, 95% CI 1.518-6.47, p = 0.002), and that was confirmed by the combined ROC curve for the 5 predictor factors (AUC = 0.91, 95% CI 0.869-0.95, P = 0.0001). In conclusion, these data suggest that the two SNPs have the potential in predicting the response rate to SOF/DCV treatment in patients infected with HCV GT4. This study is the first to investigate the pharmacogenetics of SOF metabolizing enzyme and introduce HINT1 rs7728773 as a novel SNP that predicts the treatment efficacy.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.

Seroprevalence of hepatitis C virus infection in children: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Estimates of paediatric hepatitis C virus (HCV) seroprevalence are needed to aid treatment scaling-up, screening and detection approach in this age range, with the ultimate goal of global HCV eradication. The aim of this study was to gather all of the available information on HCV seroprevalence in children all around the world. METHODS: We searched PubMed, Scopus, Web of Science (WOS), Wiley and EBSCO databases for all studies evaluating HCV seroprevalence in children; however, studies examining seroprevalence in high-risk children or specific groups were excluded. RESULTS: Only 20 articles with 48 963 people met our inclusion criteria, with an overall prevalence of 0.904% and a 95% confidence interval (CI) of 0.543 to 1.355. Seroprevalence was higher in research published prior to 2010 than in those published after 2010 (0.77% vs. 0.53%). CONCLUSION: Few studies were conducted to assess the seroprevalence of HCV in children worldwide. However, the worldwide pooled seroprevalence of HCV in children in these studies is low (less than 1%).

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

Open-label pilot study of ethosuximide as adjunctive therapy for relieving abdominal pain related to Irritable Bowel Syndrome.

WHAT IS KNOWN AND OBJECTIVES: There is clear evidence for an association between irritable bowel syndrome (IBS) and visceral hypersensitivity. This clinical study aimed to assess the adjunct role of ethosuximide, an antiepileptic drug with T-type calcium channel blocking activity, in the relieving of IBS-related abdominal pain. METHODS: This is a prospective, 3-month, randomized and controlled study of parallel groups. Fifty outpatients who met the inclusion criteria participated in the trial. Patients were allocated randomly: 25 received mebeverine 135 mg three times daily (t.i.d), whereas the other 25 received mebeverine 135 mg t.i.d and ethosuximide 500 mg t.i.d. At baseline and 12 weeks after starting the drug, patients were evaluated by a gastroenterologist. Serum tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), faecal myeloperoxidase and faecal neutrophile gelatinase-associated lipocalin (NGAL) levels were tested before and after treatment. The Numeric Pain Rating Scale (NRS) was assessed before and after three months of therapy. RESULTS AND DISCUSSION: After 12 weeks, the ethosuximide group showed a statistically and significantly greater reduction in the serum levels of TNF-α, IL-6, IL-8, faecal myeloperoxidase and faecal NGAL in comparison with the control group after the treatment. Moreover, the ethosuximide group showed a statistically significant decrease in NRS compared with the mebeverine group. WHAT IS NEW AND CONCLUSION: Ethosuximide could be a promising adjunct to antispasmodics in the treatment of IBS patients. Trial registration identifier: NCT04217733.

Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study.

BACKGROUND & AIMS: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study.

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients. This was a randomized open-label controlled study that included 164 patients with COVID-19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin-treated group.

Ramadan fasting and liver diseases: A review with practice advices and recommendations.

Ramadan fasting is obligatory for Muslim healthy adults. However, there are many exemptions from fasting; including patients, whose diseases will be aggravated by fasting. Muslim patients with different liver diseases are frequently seen in the clinics discussing their intent to fast this month with their treating physicians. To answer our patients' inquiries about the expected benefits and/or risks of fasting and delivering them the best care, we carried out this review and we draw advices and recommendations based on the available evidence. A web-based search, combining multiple keywords representing different liver diseases with Ramadan fasting had been carried out. To answer the research question: Do adult Muslim patients with different liver diseases who fast the month of Ramadan have had a deleterious effect on their health in comparison to those who did not fast? Relevant publications were retrieved. No randomized controlled trials were focusing on Ramadan fasting and liver diseases in the filtered databases, eg Cochrane library. Consequently, non-filtered databases, eg PubMed, Google Scholar and Egyptian Knowledge Bank searched and full-text high-quality research articles were carefully analysed to draw recommendations. Other relevant publications with low quality of evidence like case studies and short communications were also reviewed to address practice advices. Although Ramadan fasting was found beneficial for patients with NAFLD, it was found deleterious to patients with Child B and C cirrhosis and patients with peptic ulcer. Patients with chronic hepatitis, Child A cirrhosis and those with non-complicated liver transplant can fast with prefasting assessment and strict follow up.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study.

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.

Clinical evaluation of pregnant women with SARS-COV2 pneumonia: a real-life study from Egypt.

BACKGROUND: Knowledge about the outcome of COVID-19 on pregnant women is so important. The published literature on the outcomes of pregnant women with COVID-19 is confusing. The aim of this study was to report our clinical experience about the effect of COVID-19 on pregnant women and to determine whether it was associated with increased mortality or an increase in the need for mechanical ventilation in this special category of patients. METHODS: This was a cohort study from some isolation hospitals of the Ministry of Health and Population, in eleven governorates, Egypt. The clinical data from the first 64 pregnant women with COVID-19 whose care was managed at some of the Egyptian hospitals from 14 March to 14 June 2020 as well as 114 non-pregnant women with COVID-19 was reviewed. RESULTS: The two groups did not show any significant difference regarding the main outcomes of the disease. Two cases in each group needed mechanical ventilation (p 0.617). Three cases (4.7%) died among the pregnant women and two (1.8%) died among the non-pregnant women (p 0.352). CONCLUSIONS: The main clinical outcomes of COVID-19 were not different between pregnant and non-pregnant women with COVID-19. Based on our findings, pregnancy did not exacerbate the course or mortality of COVID-19 pneumonia.

Immunohistochemical staining with chemokine panel of non-specific colitis predicts future IBD diagnosis.

BACKGROUND & AIMS: There is a possible significant difficulty in differentiating between non-specific colitis (NSC) and early IBD patients with no cardinal endoscopic features. This clarifies the need to find markers with high sensitivity and specificity for distinguishing between both and other forms of specific colitis. The aim of this study to investigate the ability to use a chemokine panel (CCR9, CD146 and Foxp3) among patients with lower gastrointestinal symptoms found to have NSC (but do not have current IBD) to predict which patients progress to/develop future IBD or other diagnoses of specific colitis. METHODS: Colonoscopy was done for 182 patients complaining of chronic diarrhea and or constipation, abdominal distention and pain with negative history for IBD, after Histopathological evaluation; 138 cases showing non-specific inflammation submitted for further immunohistochemical CCR9, CD146 and Foxp3 staining. On follow up patients with persistent symptoms or worsen symptoms recolonoscopy was done followed by Histopathological examination of samples and compared by the earlier results. RESULTS: The studied markers expressed significantly in IBD patients differentiating them from NSC patients (p < 0.001) except for CCR9 expression was statistically insignificant in CD patients (p = 0.528). According to the ROC curves in prediction of progression using studied panel, the use of studied markers in combination was more statistically significant in comparison to each marker alone. Median follow up for studied patients was 12 months. CONCLUSIONS: This panel of markers holds a promising hope for early IBD as predictive markers, discriminating IBD from NSC and as potential therapeutic targets.

High success rates for the use of sofosbuvir/ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir/simeprevir/daclatasvir + ribavirin in retreatment of chronic hepatitis C infection after unsuccessful sofosbuvir/daclatasvir therapy: a real-life experience.

The aim of this work was assessment of the efficacy and tolerability of two different regimens for retreatment of hepatitis C virus (HCV) patients who failed to respond to SOF/DCV-based therapy. This prospective study included 104 HCV patients who failed to respond to SOF/DCV-based therapy. Patients were randomly allocated to two groups. Efficacy and tolerability were assessed. The 12-week sustained virological response (SVR12) rates were 96% and 94.4% in groups B and A, respectively, with no significant difference (p = 1.000). Most adverse events reported were mild to moderate, with no deaths during the study. Multi-target direct-acting antiviral (DAA) combinations are efficient for retreatment of HCV patients after failure of SOF/DCV-based therapy in real-world management.ClinicalTrials.gov identifier: NCT02992457.

MicroRNA signature in hepatocellular carcinoma patients: identification of potential markers.

MicroRNAs (miRNAs) play important roles in liver pathologies and they are potential biomarkers for diagnosis of liver diseases progression. Changes in miRNA sera expression can be used as non-invasive biomarkers for hepatocellular carcinoma (HCC). The aim of the study was to identify the miRNome profiling of HCC and its diagnostic value in distinguishing HCC from healthy individuals. Expression profiles of miRNAs in serum samples of 20 HCC patients and 10 healthy controls were detected. Whole miRNome profiling was done using next generation sequencing. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of the deregulated miRNAs for discriminating HCC cases from healthy controls. MiRNA 142 was highly expressed in HCC (P value = 0.023) while miRNAs 191, 22, and 126 were higher in the controls (P value = 0.005, 0.034, 0.010 respectively). We have identified 5 novel miRNAs and they were highly expressed in HCC than controls. Analysis of ROC curve demonstrated that these deregulated miRNAs can be used as a reliable biomarker for detection of HCC with high diagnostic accuracy (AUC = 0.93). We have detected a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC. The study recommends further research to shed light on a possible role of the newly discovered novel miRNAs in HCC pathogenesis.

Correction to: MicroRNA signature in hepatocellular carcinoma patients: identification of potential markers.

The correct spelling of the 7th authors' name is Mona Watany.

A Randomized Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a reversible spectrum of neuropsychiatric abnormalities associated with liver dysfunction. Lactulose is a nonabsorbable disaccharide presently used to treat HE. Nitazoxanide (NTZ) has a broad-spectrum activity against urease-producing bacteria, so it decreases ammonia production and is therefore expected to reverse the symptoms of HE. A previous pilot study on HE patients given NTZ and lactulose had encouraging results with regard to amelioration of the clinical picture. Patients showed improvement in mental status and the drug was well-tolerated. Results such as these are encouraging larger studies. The aim of this study was to compare the safety and adequacy of NTZ plus lactulose versus lactulose and placebo in management of overt HE. METHODS: In total, 120 cirrhotic patients suffering from overt HE were randomly designated to take either NTZ plus lactulose (n=60) or lactulose and placebo (n=60). The Clinical Hepatic Encephalopathy Staging Scale (CHESS) score was assessed for all patients on inclusion to the study and 1 week from the start of treatment. RESULTS: Both groups evinced an improvement in CHESS score at 1 week, yet the improvement was significantly better in the NTZ group as the score decreased from 4.15±2.09 to 0.00±0.00 compared with 4.96±2.29 to 1.28±0.91 in patients receiving lactulose and placebo (P-value <0.001). CONCLUSIONS: NTZ significantly decreases the CHESS score and improves mental status in the form of patient alertness, orientation, response to stimulation, and ability to talk. NTZ is safe and well-tolerated apart from infrequent epigastric pain.

Endoscopic injection sclerotherapy versus N-Butyl-2 Cyanoacrylate injection in the management of actively bleeding esophageal varices: a randomized controlled trial.

BACKGROUND: The management of acute esophageal variceal bleeding remains a clinical challenge. Band ligation is the main therapeutic option, but it may be technically difficult to perform in active bleeders. This may necessitate an alternative therapy for this group of patients. This study was conducted to assess the safety and efficacy of sclerotherapy versus cyanoacrylate injection for management of actively bleeding esophageal varices in cirrhotic patients. METHODS: This prospective study included 113 cirrhotic patients with actively bleeding esophageal varices. They were randomly treated by endoscopic sclerotherapy or cyanoacrylate injection as banding was not suitable for those patients due to profuse bleeding making unclear endoscopic visual field. Primary outcome was incidence of active bleeding control and secondary outcomes were incidence of six weeks rebleeding, complications, and mortality among the studied patients. RESULTS: Initial bleeding control was significantly higher in cyanoacrylate versus sclerotherapy groups (98.25, 83.93% respectively, P = 0.007). No significant differences between sclerotherapy and cyanoacrylate groups regarding rebleeding (26.79, 19.30% respectively, P = 0.344), complications, hospital stay or mortality rate were observed. CONCLUSIONS: Based on this single-center prospective study, both of these therapies appear to have relatively favorable outcomes, although cyanoacrylate injection may be superior to sclerotherapy for initial control of active bleeding. TRIAL REGISTRATION: [ClinicalTrials.gov Identifier: NCT03388125 ]-Date of registration: January 2, 2018 "Retrospectively registered".