Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

Non-coding RNA genes modulate PI3K/AKT signaling pathway in polycystic ovary syndrome.

BACKGROUND: The PI3K protein kinase B (PI3K/AKT) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. The purpose of this study is to validate the association of PCOS with PI3K/AKT pathway target genes, miRNA486-5p, and miRNA483-5p as well as to evaluate the outcome of metformin on the pathogenesis of PCOS.  METHODS: This case-controlled study included 3 subject groups: twenty healthy females (control group), twenty PCOS females before treatment, and twenty PCOS females treated with metformin at a dose (500 mg 3 times per day for 3 months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miRNA486-5p, and miRNA483-5p in the whole blood. RESULTS: There was a significant decrease in miRNA486-5p and miRNA483-5p in the PCOS group with a significant negative correlation between miRNA486-5p and PI3K and a significant negative correlation between miRNA483-5p and ERK. Metformin treatment resulted in significant elevation of the studied miRNA, significant downregulation of PI3K/AKT target genes, and significant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression. CONCLUSIONS: miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, influence glucose metabolism, and result in IR in PCOS. Metformin's upregulation of those miRNAs affects glucose metabolism by controlling the expression of GLUT4, ameliorates PCOS-related insulin resistance, and improves PCOS-related hormonal imbalance by controlling the PI3K/AKT signaling pathway.

Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis.

BACKGROUND AND STUDY AIMS: Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. PATIENTS AND METHODS: This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. RESULTS: A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001]. CONCLUSION: Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.

ASSESSING PREDICTORS OF DIRECTLY ACTING ANTIVIRALS' FAILURE AS A FURTHER STEP TOWARDS MORE EFFICIENT HCV ELIMINATION PROGRAMS: IL28B (IFNL4) GENE POLYMORPHISM HAS NO ROLE WHILE HIGHER ESTIMATED CREATININE CLEARANCE IS A FORGOTTEN FACTOR.

BACKGROUND: Sustained virologic response (SVR) rates after directly acting antivirals (DAAs) for hepatitis C virus (HCV) exceed 95%. This encouraged policymakers to put plans to achieve HCV elimination by 2030. The remaining percentage of non-SVR12 can affect HCV eradication strategies in the real-world especially the compliance of large numbers of treated persons to follow up for assessment of virologic response cannot be guaranteed. OBJECTIVE: We aimed to assess predictors of failure to achieve SVR after receiving sofosbuvir plus NS5A inhibitor as an important step towards achieving better HCV eradication strategies. METHODS: During the period from 1st November 2018 to 1st November 2019, 1581 treatment-naive patients received sofosbuvir plus daclatasvir ± ribavirin at our unit and 10 patients were referred to us with HCV relapse after the same regimens. A total of 163 out of the 1581 patients were lost for follow-up before assessment of virologic response and excluded from the analysis. 20 out of the remaining patients failed to achieve SVR12. Data from the 30 patients with non-SVR12 were included in the case-control analysis. RESULTS: Every unit increase in estimated creatinine clearance using modification of diet in renal disease study (MDRD) score, total bilirubin, and INR was associated with 1.03, 13.92, and 80.08 times greater odds of non-SVR12 (P<0.001, P=0.0016, P=0.02) respectively. The presence of liver cirrhosis on ultrasonography increases the odds by 10.03. (P=0.009). CONCLUSION: Higher MDRD score, INR, total bilirubin, and presence of sonographic features of liver cirrhosis are predictors of failure to achieve SVR12 using sofosbuvir plus NS5A inhibitor.

The association between vitamin D levels and oxidative stress markers in Egyptian Behcet's disease patients.

BACKGROUND: Oxidative stress is postulated to have a major role in the pathophysiology of Bechet's Disease (BD). Growing evidence suggests that vitamin D has important roles in enhancing the expression of anti-inflammatory cytokines as well as certain antioxidants. However, there is little evidence currently about the antioxidant properties of vitamin D in BD. OBJECTIVE: To study the relationship between vitamin D levels and the oxidative stress markers in patients with BD in addition to its association with disease activity and severity. METHODS: Sixty BD patients (45 males, 15 females; mean age: 34.2 ± 9.6 years) were enrolled in this study and compared to a sex and age matched control group. Plasma 25-Hydroxy vitamin D (25-OH-D) was measured using Human (25-OH-D) ELISA assay. Plasma malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD) activity, catalase (CAT) activity and total antioxidant capacity (TAC) were determined by spectrophotometric methods in both groups. Plasma calcium (Ca) was measured by ELISA assay. RESULTS: When compared to controls vitamin D, GSH, CAT activity, TAC and Ca were significantly lower in BD patients, while MDA and NO levels were significantly increased in BD patients. Our Results Found that vitamin D was inversely correlated to BD current Activity form (BDCAF), disease severity score, ESR, CRP, MDA and NO, while vitamin D was significantly positively correlated to GSH, SOD, TAC and Ca. CONCLUSION: Our study confirms that a lower level of vitamin D is associated with the oxidative stress state in BD patients as detected by MDA and NO elevation as well as decreased GSH, SOD activity, CAT activity and TAC. Hence, Vitamin D fortified foods and beverages or supplementation may improve disease severity and oxidative stress in BD patients.

Avaliação dos preditores da falha dos antivirais de ação direta como mais um passo para programas de eliminação de VHC mais eficiente: o polimorfismo genético IL28B (IFNL4) não tem destaque, enquanto maior liberação estimada do "clearence" de creatinina é um fator esquecido / Assessing predictors of directly acting antivirals' failure as a further step towards more efficient hcv elimination programs: il28b (ifnl4) gene polymorphism has no role while higher estimated creatinine clearance is a forgotten factor

ABSTRACT Background: Sustained virologic response (SVR) rates after directly acting antivirals (DAAs) for hepatitis C virus (HCV) exceed 95%. This encouraged policymakers to put plans to achieve HCV elimination by 2030. The remaining percentage of non-SVR12 can affect HCV eradication strategies in the real-world especially the compliance of large numbers of treated persons to follow up for assessment of virologic response cannot be guaranteed. Objective: We aimed to assess predictors of failure to achieve SVR after receiving sofosbuvir plus NS5A inhibitor as an important step towards achieving better HCV eradication strategies. Methods: During the period from 1st November 2018 to 1st November 2019, 1581 treatment-naive patients received sofosbuvir plus daclatasvir ± ribavirin at our unit and 10 patients were referred to us with HCV relapse after the same regimens. A total of 163 out of the 1581 patients were lost for follow-up before assessment of virologic response and excluded from the analysis. 20 out of the remaining patients failed to achieve SVR12. Data from the 30 patients with non-SVR12 were included in the case-control analysis. Results: Every unit increase in estimated creatinine clearance using modification of diet in renal disease study (MDRD) score, total bilirubin, and INR was associated with 1.03, 13.92, and 80.08 times greater odds of non-SVR12 (P<0.001, P=0.0016, P=0.02) respectively. The presence of liver cirrhosis on ultrasonography increases the odds by 10.03. (P=0.009). Conclusion: Higher MDRD score, INR, total bilirubin, and presence of sonographic features of liver cirrhosis are predictors of failure to achieve SVR12 using sofosbuvir plus NS5A inhibitor.

RESUMO Contexto: As taxas de resposta virológica sustentada (SVR) após ação direta de antivirais (DAAs) para o vírus da hepatite C (VHC) excedem 95%. Isso encorajou os formuladores de políticas a colocar planos para alcançar a eliminação do VHC até 2030. O percentual remanescente de não-respondedores pode afetar as estratégias de erradicação do VHC no mundo real, especialmente a conformidade de um grande número de pessoas tratadas para acompanhamento para avaliação da resposta virológica não pode ser garantida. Objetivo: Nosso objetivo foi avaliar os preditores de não atingir o SVR após receber o inibidor sofosbuvir mais NS5A como um passo importante para alcançar melhores estratégias de erradicação do VHC. Métodos: No período de 1º de novembro de 2018 a 1º de novembro de 2019, 1581 pacientes receberam sofosbuvir mais daclatasvir ± ribavirin em nossa unidade e 10 pacientes foram encaminhados por recaída do VHC após os mesmos regimes. Um total de 163 dos 1581 pacientes foram perdidos para o acompanhamento antes da avaliação da resposta virológica e excluídos da análise. 20 dos demais pacientes não conseguiram a resposta virológica sustentada (SVR12). Os dados de 30 pacientes com não SVR12 foram incluídos na análise caso-controle. Resultados: Cada unidade aumentada no clearence estimado de creatinina usando o escore do estudo Modificação da Dieta em Doença Renal (MDRD), bilirrubina total e INR foram associadas a 1,03, 13,92 e 80,08 vezes maiores chances de não-SVR12 (P<0,001, P=0,0016, P=0,02) respectivamente. A presença de cirrose hepática na ultrassonografia aumenta as chances em 10,03. (P=0,009). Conclusão: Maior escore de MDRD, INR, bilirrubina total e presença de características sonográficas de cirrose hepática são preditores de falha na realização do SVR12 utilizando o inibidor sofosbuvir mais NS5A.

High success rates for the use of ombitasvir/paritaprevir/ritonavir containing regimens in treatment of naïve and experienced chronic hepatitis C genotype 4: Real world results.

INTRODUCTION AND AIMS: Treatment of hepatitis C virus (HCV) genotype 4 patient with fixed dose combination of ombitasvir-paritaprevir-ritonavir plus ribavirin (OBV/rPTV/RBV) has been proven efficacy and safety in many clinical trials. The current study reports the efficacy and safety of OBV/rPTV/RBV (for treatment-naïve), and OBV/rPTV/RBV/sofosbuvir (SOF) (for treatment-experienced), in chronic HCV genotype 4 patients in real life settings. METHODS: Prospective cohort study including all adult chronic HCV genotype 4 patients who were scheduled to receive OBV/rPTV/RBV ± SOF for 12 or 24 weeks in New Cairo Viral Hepatitis Treatment Center. The primary efficacy endpoint was a virologic response at posttreatment week 12 (SVR12). Changes in hematological parameters, liver biochemical profile and fibrosis-4 index (FIB-4), as well as clinical and laboratory adverse events (AEs) across follow up visits (week 4, end of treatment [EOT], and SVR12), were recorded. RESULTS: Our study included 325 patients (age; 47.63 ± 12.63 years, 55.38% [n = 180] men). Most of the included patients (89.85%, n = 292) were treatment naïve and only 7% (n = 23) had liver cirrhosis. Overall, SVR12 was attained by 98.44% (316 of 321) of the patients; 97.15% (307 of 316) of patients who received 12 weeks of OBV/rPTV/RBV ± SOF and 100% (9 of 9) of patients who received 24 weeks of OBV/rPTV/RBV as assessed by modified intention to treat analysis. There was a significant improvement of baseline alanine aminotransferase, aspartate aminotransferase, hemoglobin, FIB-4 at SVR12 (P < 0.05). The most common reported AEs were anemia (n = 106), fatigue (n = 41) and elevated indirect bilirubin (n = 37). CONCLUSION: OBV/rPTV/RBV (±SOF) is a highly effective therapy for chronic HCV patients in real life settings.

Real-life experience of treating HCV co-infection among HIV-infected population in Egypt: single-center experience.

BACKGROUND: Liver disease has emerged as a leading cause of death among PLHIV coinfected with HCV. METHODS: A retrospective study involving all HCV viremic patients coinfected with HIV who presented to HCV/HIV multidisciplinary clinics located at Embaba fever hospital. Patients were assigned to receive DAAs according to the national treatment guidelines. The primary endpoint was SVR12. RESULTS: Of the 519 patients enrolled, 38.73% LTFU; either not initiated (n = 170) or did not complete the treatment (n = 31). The main identified reasons behind LTFU were schedule conflict (19%) or hospitalization (13%). Among 318 patients who completed their DAAs course, nine patients had a relapse after the end of treatment and 97% had attained SVR12. There were significant differences among different virological response groups in baseline factors including smoking (p = 0.005), history of dental procedure (p = 0.007), CD4 count (p = 0.007), and HIV viral load (p = <0.001). Among responders (n = 309), there was a significant reduction of baseline hemoglobin and significant improvement of baseline platelets (p = 0.005) at on-treatment week 8. Baseline necro-inflammatory markers showed significant improvement across follow-up time points (p < 0.001). CONCLUSIONS: DAAs are an effective and safe choice to treat HCV in PLHIV. Social stigma could be a major cause for lacking adherence to follow-up visits.Abbreviations: ALT: Alanine Aminotransferase; ARV: Antiretroviral treatment; AST: Aspartate Aminotransferase; DAAs: Direct acting antivirals; ARVs: antiretroviral therapy; EMR: Eastern Mediterranean region; HCV: Hepatitis C virus; kPa: Kilopascal; LTFU: Patient lost to follow up; NCCVH: The National Committee for Control of Viral Hepatitis; PWID: People who inject drugs; SVR: Sustained virological response;UNAIDS: The Joint United Nations Programme on HIV/AIDS.

Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis.

BACKGROUND: Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. OBJECTIVE: We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. METHODS: A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. RESULTS: In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. CONCLUSIONS: DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.

Hepatocellular Carcinoma in Oman: An analysis of 284 cases.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the most common type of primary liver tumour worldwide and is increasing in incidence. This study aimed to describe the clinical characteristics of HCC among Omani patients, along with its major risk factors, outcomes and the role of surveillance. METHODS: This retrospective case-series study was conducted between January 2008 and December 2015 at the three main tertiary care hospitals in Oman. All adult Omani patients diagnosed with HCC and visited these hospitals during the study period were included. Relevant data were collected from the patients' electronic medical records. RESULTS: A total of 284 HCC patients were included in the analysis. The mean age was 61.02 ± 11.41 years and 67.6% were male. The majority had liver cirrhosis (79.9%), with the most common aetiologies being chronic hepatitis C (46.5%) and B (43.2%). Only 13.7% of cases were detected by the HCC surveillance programme. Approximately half of the patients (48.5%) had a single liver lesion and 31.9% had a liver tumour of >5 cm in size. Approximately half (49.2%) had alpha-fetoprotein levels of ≥200 ng/mL. The majority (72.5%) were diagnosed using multiphase computed tomography alone. Less than half of the patients (48.9%) were offered one or more HCC treatment modalities. CONCLUSION: The majority of Omani HCC patients were male and had cirrhosis due to viral hepatitis. In addition, few patients were identified by the national surveillance programme and presented with advanced disease precluding therapeutic or even palliative treatment.

Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant.

Kinase D-interacting substrate of 220 kDa (KIDINS220) is a transmembrane protein playing integral role in growth mediating pathways in the nervous and cardiovascular systems. KIDINS220 heterozygous truncating variants that affect the protein's C-terminus have been associated with a phenotype, so far described only in few unrelated children, including spastic paraplegia, intellectual disability, nystagmus, and obesity. More recently, a homozygous, more N-terminal truncating variant in KIDINS220 gene was suggested to be associated with enlarged cerebral ventricles and limb contractures in three fetuses from a consanguineous family. We confirm the latter finding by presenting the first detailed prenatal identification of a fetal phenotype associated with novel homozygous deleterious frameshift variant in KIDINS220 gene in a consanguineous healthy Egyptian couple. History of unexplained seven miscarriages and a similar stillbirth were recorded. Prenatal ultrasonography revealed limb contractions and ventriculomegaly; in addition to previously unreported cerebellar anomalies, cardiac anomalies and hydrops fetalis. These findings represent an expansion of clinical and molecular spectrum associated with KIDINS220 variants and broaden our understanding of genotype-phenotype relationships in lethal congenital contractures syndromes and associated severe abnormal embryological development. More generally, our study adds KIDINS220 to the rare group of genes which may cause disease by either of two distinct mutational mechanisms.

Retreatment of chronic hepatitis C patients who failed previous therapy with directly acting antivirals: A multicenter study.

AIM OF THE STUDY: The current study aimed to evaluate the efficacy of different DAAs regimens in the treatment of chronic hepatitis C (CHC) Egyptian patients who failed to achieve SVR after their treatment with SOF-based regimens. METHODS: This was a retrospective observational multicenter study that included CHC patients that failed to achieve cure on SOF-based regimens who were re-treated using different DAAs regimen and were allocated according to national guidelines for the treatment of hepatitis C. Primary outcome was to assess the SVR12 rate among prior non-responders after retreatment with a second course of DAAs. RESULTS: Our study included 172 patients who failed to achieve SVR after treatment with SOF-based treatment regimen [age: 51.2 ± 11.3, 58.7% men]. Included patients were retreated using SOF/DCV/RBV, SOF/ r/PAR /OMB /RBV, SOF/DCV/SIM, SOF/LDV ± RBV or SIM/SOF. SVR12 was successfully attained in 95.35% (164/172) of the included non-responders. CONCLUSION: The current multicenter study proved the efficacy of various DAAs regimens issued by the National Committee for Control of Viral Hepatitis for retreatment of relapsed CHC Egyptian patients.

Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience.

Background: Liver fibrosis assessment is a key factor for disease management in hepatitis B virus (HBV). Several serum biomarkers have been introduced for noninvasive fibrosis assessment. This study aims to evaluate the validity of simple noninvasive indices, namely Fibrosis-4 score (FIB4), aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), Goteborg University Cirrhosis Index (GUCI), and fibrosis index in evaluation of liver fibrosis in chronic HBV.Methods: 226 patients with chronic HBV genotype D were included. FIB4, APRI, GUCI, and fibrosis index were performed. Receiver operating characteristic (ROC) curves were used to predict ≥F2 fibrosis.Results: The mean age of patients was 39.00 years and 72.27% of patients were treatment naïve. Patients with ≥F2 hepatic fibrosis had significantly higher FIB-4 (1.58 ± 1.46 vs. 1.15 ± 1.09), APRI (0.68 ± 0.71 vs. 0.43 ± 0.37), GUCI score (0.75 ± 0.94 vs. 0.42 ± 0.29) and Fibrosis index (2.18 ± 0.84 vs. 1.84 ± 0.69). All studied indices were able to diagnose ≥F2 fibrosis. APRI had the highest area under the ROC (AUROC) of 0.67. Predictivity of all indices was higher in on-treatment vs naive patients.Conclusion: FIB4, APRI, and GUCI scores are acceptable, noninvasive, and cheap simple indices that can be helpful on treatment follow-up of fibrosis regression in the setting of low socioeconomic conditions compared to the relatively expensive fibroscan modality.

The ability of perfusion index to detect segmental ulnar nerve sparing after supraclavicular nerve block.

Supraclavicular nerve block (SCB) is a commonly used regional block for upper extremity surgery. The most common form of failure of SCB is ulnar segmental sparing. We aimed to evaluate the accuracy of perfusion index (PI) in early detection of segmental sparing of the ulnar component of SCB. A prospective observational study included adult patients scheduled for surgery under ultrasound-guided SCB. PI was simultaneously measured at the index finger and little finger. PI was recorded every minute for the first 10 min after SCB. PI ratio was calculated at every measurement point as PI/baseline PI. The area under the receiver operating characteristic (AUROC) curve was calculated for the ability of PI ratio to detect segmental ulnar sparing with comparison of little finger readings to the index finger readings. Forty-nine patients were available for the final analysis. Nine patients (18%) had segmental ulnar sparing. PI ratio at the little finger showed excellent predictive ability for ulnar sparing starting from the fifth minute (AUROC 0.92 [0.8-0.98], cutoff value ≤ 1.71) and reached the highest value at the seventh minute (AUROC 0.96 [0.86-1], cutoff value ≤ 1.35), whereas PI ratio at the index finger showed poor predictive ability. When using the PI for evaluation of successful SCB, segmental ulnar sparing could be accurately detected when the PI was measured at the little finger and not at the index finger. An increase of 71% in PI at the little finger 5 min after SCB could accurately rule out ulnar sparing.Clinical trial identifier NCT03880201. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03880201?term=NCT03880201&draw=2&rank=1 .

Comparative study between intrathecal dexmedetomidine and intrathecal magnesium sulfate for the prevention of post-spinal anaesthesia shivering in uroscopic surgery; (RCT).

BACKGROUND: Hypothermia and shivering are common complications after spinal anaesthesia, especially after uroscopic procedures in which large amounts of cold intraluminal irrigation fluids are used. Magnesium sulfate and dexmedetomidine are the most effective adjuvants with the least side effects. The aim of this study was to compare the effects of intrathecal dexmedetomidine versus intrathecal magnesium sulfate on the prevention of post-spinal anaesthesia shivering. METHODS: This prospective randomized, double-blinded controlled study included 105 patients who were scheduled for uroscopic surgery at the Kasr El-Aini Hospital. The patients were randomly allocated into three groups. Group C (n = 35) received 2.5 ml of hyperbaric bupivacaine 0.5% (12.5 mg) + 0.5 ml of normal saline, Group M (n = 35) received 2.5 ml of hyperbaric bupivacaine 0.5% (12.5 mg) + 25 mg of magnesium sulfate in 0.5 ml saline, and Group D (n = 35) received 2.5 ml of hyperbaric bupivacaine 0.5% (12.5 mg) + 5 µg of dexmedetomidine in 0.5 ml saline. The primary outcomes were the incidence and intensity of shivering. The secondary outcomes were the incidence of hypothermia, sedation, the use of meperidine to control shivering and complications. RESULTS: Group C had significantly higher proportions of patients who developed shivering (21), developed grade IV shivering (20) and required meperidine (21) to treat shivering than group M (8,5,5) and group D (5,3,6), which were comparable to each other. The time between block administration and meperidine administration was similar among the three groups. Hypothermia did not occur in any of the patients. The three groups were comparable regarding the occurrence of nausea, vomiting, bradycardia and hypotension. All the patients in group C, 32 patients in group M and 33 patients in group D had a sedation score of 2. Three patients in group M and 2 patients in group D had a sedation score of 3. CONCLUSIONS: Intrathecal injections of both dexmedetomidine and magnesium sulfate were effective in reducing the incidence of post-spinal anaesthesia shivering. Therefore, we encourage the use of magnesium sulfate, as it is more physiologically available, more readily available in most operating theatres and much less expensive than dexmedetomidine. TRIAL REGISTRATION: Clinical trial registration ID: Pan African Clinical Trial Registry (PACTR) Trial Number PACTR201801003001727 ; January 2018, "retrospectively registered".

A significant upsurge of body mass index in patients with chronic hepatitis C successfully treated with direct-acting antiviral regimens.

BACKGROUND/AIMS: There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change. MATERIALS AND METHODS: The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity. RESULTS: The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience. CONCLUSION: Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.

Egyptian liver library: An indexed database for liver disease evidence in Egypt.

Liver diseases are among the most challenging health care problems worldwide. In Egypt, we established different care programs to combat liver diseases including schistosomiasis and viral hepatitides. A lot of research work addressing liver diseases in Egypt have been published with special focus on these two major fields. Other liver disease seems to be neglected although present and contributing to the liver disease burden in Egypt. In this report we reviewed the available evidence published from Egypt and elucidate areas of weakness and future research needs. Our search for Egyptian liver disease evidence retrieved 4683 articles, 67% of them were relevant to the topic. Out of the relevant articles; 1646/3265 (50.4%) were discussing clinical science, 1131 (34.7%) were discussing basic science and 488 (14.9%) were discussing both basic and clinical sciences. Cairo university (16.8%, n = 513) and Mansoura university (9.3%, n = 285) had the largest number of publications related to liver disease in Egypt respectively. The most commonly reported diseases were hepatitis C in 719/3361 articles (21.4%), parasitic liver infestations in 663 articles (19.7%), hepatocellular carcinoma in 544 articles (16.2%), liver fibrosis or cirrhosis in 537 articles (16%), and drug induced liver injury in 516 articles (15.4%). Most of the reviewed articles (36%) were discussing treatment of chronic liver diseases (n = 1201) followed by diagnostics (28%, n = 940), pathogenesis and pathophysiology (21%, n = 706). This review will direct attention to areas with less research like hepatitis B related liver disease, HIV/HCV co-infections, and non-alcoholic fatty liver disease (NAFLD) to encourage future research in these topics. In conclusion; our results ring a bell inviting the development of a roadmap for liver research in Egypt targeting to put future policies to cover areas of weakness in liver research with an ultimate goal of tackling liver disease and its overwhelming socioeconomic burden in our developing country.

High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study.

Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.

DAAs therapy associated with improved hepatic fibrosis in HCV-GT4 patients co-infected with HIV.

Background: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV. Patients and methods: In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg. Results: Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively. Conclusion: Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.

Ritonavir-boosted paritaprevir, ombitasvir plus ribavirin could improve eGFR in patients with renal impairment and HCV: an Egyptian cohort.

BACKGROUND: The present study aimed at evaluation of changes in estimated glomerular filtration rate (eGFR) among chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) Stages 3-5 who were treated with 12 weeks of ritonavir-boosted paritaprevir, ombitasvir plus ribavirin. METHODS: Changes in renal functions were compared across follow up time points (baseline, SVR4, and SVR8). Data on on-treatment adverse events (AEs), serious AEs, laboratory abnormalities, treatment discontinuation were collected. RESULTS: 171 patients were included (females 35%, mean age 53 years). 29 patients had liver cirrhosis. The most common etiologies of CKD were diabetes and/or hypertension (n = 67). All included patient reached the end of treatment (EOT) with no treatment discontinuations. The overall EOT response was 100%. 122/122 (100%) patients who reached 4 weeks post-treatment have achieved SVR4, and 80/80 (100%) have achieved SVR12. No reported SAEs. Ribavirin therapy was interrupted in 25% (43/171) of patients due to anemia; 16 patients required blood transfusions. The median eGFR improved from 33.5 (15) mL/min/1.73 m2 at baseline to 35 (36) mL/min/1.73 m2 at SVR8 (p = 0.0003). CONCLUSIONS: The use of ombitasvir, paritaprevir, and ritonavir for treatment of HCV-infected patients with advanced renal disease was safe and effective, moreover, it was associated with significantly improved eGFR.