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Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology., Objective: This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases., Patients and Methods: This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment., Results: Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ± 37.56 vs. 265 ± 36.19 dB/ml) ( P  < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ± 1.53 vs. 4.86 ± 1.28 KPa) ( P  = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P  < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml)., Conclusion: A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Portal hypertension and esophageal varices complicating hepatitis C virus (HCV)-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism (SNP), and serum apelin level in patients with chronic HCV, and their association with liver fibrosis and esophageal varices in 112 patients with HCV-related chronic liver disease (40 with liver cirrhosis [LC]/low-grade varices, 33 with LC/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. The serum apelin level was measured by ELISA. Apelin gene expression was undetectable in the studied samples. The SNP analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with LC/varices (median, 31.6 ng/L) compared with patients without LC/varices (median, 2.9 ng/L; P < 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P < 0.001) and portal hypertension (r = 0.438, P < 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of HCV-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.

Introduction: After hepatocellular carcinoma (HCC) interventional therapies, noninvasive vascular diagnostic imaging [duplex, Color/power Doppler ultrasonography, and triphasic computed tomography (CT)] determines the lesion complete/incomplete ablation. The aim was to analyze the usefulness of duplex, color/power Doppler ultrasonography in HCC ablation after percutaneous ablative therapies (PATs)., Methods: We included 30 patients with 33 HCCs subjected to duplex/Doppler ultrasonography, ultrasound-guided fine-needle aspiration cytology (FNAC), and triphasic CT, all these before and after PATs., Results: One week after treatment ended, out of 21 lesions with pretreatment positive color-Doppler, signals disappeared in 19 (90.5%) lesions. Out of 29 lesions with pretreatment positive power-Doppler, signals disappeared in 24 (82.8%). Out of 13 lesions with pretreatment intralesional power/duplex arterial signals, signals disappeared in eight (61.5%). There was a significant correlation (P < 0.05) between power-Doppler arterial signals and FNAC. Before HCC ablation, power-Doppler demonstrated a sensitivity 40% and specificity 96% in HCC detection in relation to FNAC, it had a sensitivity 60% and specificity 85% in HCC detection compared to triphasic CT. After HCC ablation, power-Doppler had a sensitivity and specificity of 100% in viable malignancy detection in relation to FNAC. Power-Doppler had a sensitivity 89% and specificity 93% in residual malignancy detection in relation to triphasic CT., Conclusion: Power-Doppler is a good positive test as intralesional arterial signals in a cirrhotic liver lesion is highly suggestive of HCC. Power-Doppler was sensitive in HCC ablation assessment in pretreatment positive cases only. Both triphasic CT and duplex/Doppler are complementary and the use of different diagnostic modalities after ablation is mandatory., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transient elastography and acoustic radiation force impulse (ARFI) imaging are noninvasive tools for liver stiffness measurement (LSM), which may be influenced by cholestasis., Aim: The aim of the study was to evaluate the performance of transient elastography and ARFI in extrahepatic cholestasis and correlate changes in LSM with biochemical activity., Materials and Methods: A total of 38 patients with extrahepatic cholestasis prospectively underwent transient elastography and ARFI. Changes in LSM by transient elastography/ARFI were evaluated after 1 week of ERCP and correlated with biochemical parameters. The optimal ARFI cutoffs according to stages of clinical interest were analyzed., Results: Biliary obstruction was calcular in 21 (55.3%) and noncalcular in 17 (44.7%) (benign n = 15, malignant n = 2). After 1 week, adequate biliary drainage reduced total bilirubin from 7.7 to 2.2 mg/dL (P < 0.001) which significantly correlated with reduction of LSM by transient elastography from 12.38 ± 6.68 kPa to 8.08 ± 3.21 kPa (P < 0.001), and by ARFI from 1.73 ± 0.51 m/s to 1.56 ± 0.70 m/s (P = 0.014). The LSM percentage change showed a decrease (nonsignificant, P = 0.843) by 25.83% using transient elastography and a significant decrease (P < 0.001) by 18.42% using ARFI in the improved patients. At initial visit, transient elastography positively correlated with ARFI, bilirubin and platelets, also, transient elastography had a positive correlation with ARFI, bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) in follow-up visit. LSM by ARFI (visit 1) negatively correlated with ALT, while in (visit 2), ARFI positively correlated with bilirubin, ALP, GGT and negatively correlated with albumin., Conclusion: The increased LSM in patients with extrahepatic cholestasis is reduced after adequate biliary drainage, implying that increased values are not solely due to liver fibrosis, but due to biliary congestion leading temporarily to increased elasticity., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: There is a growing need for identification of non-endoscopic, non-invasive methods that can accurately predict esophageal varices (EV). Previous studies found an inconclusive correlation between blood ammonia level and the presence and size of EV., Aim: We aimed at assessing the value of serum ammonia as a non-invasive method for early prediction of EV., Patient and Methods: The study included 204 patients with HCV-related cirrhosis. The selected patients were categorized into two groups: patients with EV and those without, also patients with no or small EV and with large EV group. All patients underwent a complete biochemical workup, ultrasound and upper GI endoscopy. Child-Pugh class, Model of End-Stage Liver Disease (MELD) score and platelet count/splenic diameter ratio, and serum ammonia level., Results: There was a statistical difference between the two groups of patients regarding the following parameters: serum ammonia, international normalized ratio, portal vein diameter, spleen diameter, Child-Pugh class, MELD score, platelet count/splenic diameter ratio, aspartate aminotransferase-to-platelet ratio index, alanine aminotransferase-to-aspartate aminotransferase ratio, Forns index, FIB-4 and King's score. Serum ammonia could predict the presence of EV using a cutoff value of 82 (µmol/L) with a sensitivity of 92.3%, specificity 92%. In addition, a cutoff of 95.5 (µmol/L) could predict large EV with a sensitivity of 92.7% and a specificity of 92.3%. Serum Ammonia in cirrhosis with large EV was 143 ± 39 µmol/L and in cirrhosis with small/without EV was 80.7 ± 9.7 µmol/L (P < 0.0001). Platelet/spleen ratio was 555.9 ± 187.3 in cirrhosis with EV and 694.4 ± 74.2 in cirrhosis without EV (P < 0.0001). Platelet/spleen ratio was 407.7 ± 107.1 in cirrhosis with large EV and 690.4 ± 103.7 in cirrhosis with small/without EV (P < 0.0001)., Conclusion: Serum ammonia can accurately predict the presence and the size of EV in patients with liver cirrhosis with high sensitivity and specificity., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Esophageal varices (EV) are serious complications of hepatitis C virus (HCV) cirrhosis. Endoscopic screening is expensive, invasive, and uncomfortable. Accordingly, noninvasive methods are mandatory to avoid unnecessary endoscopy. Acoustic radiation forced impulse (ARFI) imaging using point shear wave elastography as demonstrated with virtual touch quantification is a possible noninvasive EV predictor. We aimed to validate the reliability of liver stiffness (LS) and spleen stiffness (SS) by an ARFI-based study together with other noninvasive parameters for EV prediction in HCV patients. Also, we aimed to evaluate the diagnostic performance of a new simple prediction model (incorporating SS) using data mining analysis., Patients and Methods: This cross-sectional study included 200 HCV patients with advanced fibrosis. Labs, endoscopic, ultrasonographic, LS, and SS data were collected. Their accuracy in diagnosing EV was assessed and a data mining analysis was carried out., Results: Ninety patients (22/46% of F3/F4 patients) had EV (39/30/18/3 patients had grade I/II/III/IV, respectively). LS and SS by ARFI showed high significance in differentiating not only patients with/without EV (P = 0.000 for both) but also correlated with the grading of varices (R = 0.31 and 0.45, respectively; P = 0.000 for both). Spleen longitudinal diameter (SD), splenic vein diameter (SVD), platelets to spleen diameter ratio, LOK index, and FIB-4 score were the best ultrasonographic and biochemical predictors for the prediction of EV [area under receiver operating characteristic (AUROC) 0.79, 0.76, 0.76, 0.74, and 0.71, respectively]. SS (using ARFI) had better diagnostic performance than LS for the prediction of EV (AUROC = 0.76 and 0.70, respectively). The diagnostic performance increased using data mining to construct a simple prediction model: high probability for EV if [(SD cm) × 0.17 + (SVD mm) × 0.06 + (SS) × 0.97] more than 6.35 with AUROC 0.85., Conclusion: SS by ARFI represents a reliable noninvasive tool for the prediction of EV in HCV patients, especially when incorporated into a new data mining-based prediction model.

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.

Background: We aimed at determination of the usefulness of elastography [acoustic radiation force impulse (ARFI) and FibroScan] for evaluation of nonalcoholic fatty liver disease (NAFLD) patients., Patients and Methods: A prospective cross-sectional study included 60 biopsy-proven NAFLD patients (mean age: 45 years) was carried out. All patients were subjected to lab works, liver biopsy, and measurement of liver stiffness by ARFI and FibroScan and steatosis by controlled attenuation parameter (CAP). CAP measurements were adjusted for the presence of NAFLD and presence or absence of diabetes and according to BMI., Results: Linear regression analysis showed that CAP is an independent predictor for significant hepatic steatosis (P<0.001). No significant difference was found in diagnostic accuracy between adjusted and nonadjusted CAP values for diagnosis of mild (>S1) or significant (>S2) hepatic steatosis (P=0.17 and 0.29 respectively). The median ARFI velocities for F1, F2, F3, and F4 were 0.92, 1.08, 1.07, and 2.58 m/s, respectively. Although there was an overall significant increase in ARFI values across the fibrosis grades (P<0.04), the difference in ARFI values was only significant between fibrosis grades F1 and F4 (P=0.02)., Conclusion: Elastography is a promising noninvasive tool for diagnosis and grading of hepatic steatosis and fibrosis in patients with NAFLD/nonalcoholic steatohepatitis with good sensitivity and specificity, especially in moderate to marked grades.

Background and Aim: Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients., Methods: We conducted a case-control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real-time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood., Results: One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups., Conclusions: The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Although hepatitis B virus (HBV) recurrence after liver transplantation (LTx) has been reduced since the application of the combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs (NUCs), the optimum regimen to prevent HBV recurrence with LTx favorable outcome is still not clear., Aim: The aim was to evaluate the efficacy and safety of NUCs prophylaxis (±HBIG) against HBV recurrence after LTx., Patients and Methods: This was a retrospective cohort-longitudinal study on 44 HBV-related post-LTx patients on anti-HBV prophylactic therapy. They included the entecavir (ETV)-based (n=34, 30 males) and the other NUC-based (n=10, 7 males) groups±HBIG., Results: The median age was 63.5 (60-70) years in ETV and 62.5 (55-65) years in other NUCs groups. The mean follow-up duration was 6.09±1.83 years in ETV-based group and 6.3±1.89 years in other NUCs-based group. The mean ETV duration was 3.47±3.04 years. In ETV+HBIG patients, none of them developed HBV recurrence throughout the ±8 years. In the 14 patients on ETV+other NUC+HBIG, four developed HBsAg positive and then transformed to HbsAb positive at the end of ±8 years without hepatitis or detectable HBV-DNA. Liver graft function showed nonsignificant difference for ETV-based patients, in comparison with other NUC groups (P=0.09). With subdivision, the graft function was maintained significantly better in ETV+HBIG or other NUCs+HBIG (P=0.04) groups. None of our patients reported NUCs-related complications or adverse effects., Conclusion: ETV and other NUCs were effective and safe as a long-term prophylaxis of HBV recurrence after LTx, leading to a good graft function. HBsAg temporally reappeared in a minority of patients, where all showed HBsAb seroconversion without detectable HBV-DNA or clinical hepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients., Aim: The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients., Patients and Methods: Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group., Results: Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001)., Conclusion: Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.

Background/aims: Hepatocellular carcinoma (HCC) has a poor prognosis if managed late. Percutaneous microwave ablation (MWA) emerged as one of the top therapeutic decisions for non-surgical patients. The aim of the present study aim was to evaluate the efficacy, side effects, and survival after MWA of hepatitis C virus (HCV)-related HCC tumors with spectrum sizes up to 5 cm., Materials and Methods: Fifty-nine patients with early HCC were treated in the Hepatology Department using percutaneous MWA. Patients were assessed for side effects and efficacy that includes the rate of complete ablation, primary or de novo recurrence, and survival., Results: Complete ablation was achieved in 57 (96.6%) patients treated by MWA, with a minor complication rate of 3.3% (n=2) including liver abscess formation and abdominal skin burn. The ablation rates in lesions <3 versus 3-5 cm were not different. Of the patients, 3 (5%) had primary recurrence in the treated HCC tumors, de novo lesions (secondary recurrence) developed in 8 (13.5%, 5 of them >3 cm), and 2 (3.3%) had malignant portal vein thrombosis. The survival rates were 95.4% and 69% at 1 and 2 years, respectively., Conclusion: Percutaneous MWA had achieved a safe and effective treatment with good overall survival in patients with HCV-related HCC.

Background: Transient elastography (TE) and acoustic radiation force impulse (ARFI) imaging enable a noninvasive assessment of liver stiffness measurement (LSM) and liver fibrosis/cirrhosis staging. However, their use in cholestatic diseases is still scarce., Aim: The aim of this study was to evaluate the performance of TE and ARFI for the initial assessment of hepatic fibrosis in intrahepatic cholestatic (IHC) diseases and assess LSM changes after 3 months of specific therapy., Patients and Methods: This prospective study was carried out on 50 IHC patients. Assessment at baseline and after 3 months of LSM by TE and ARFI was performed., Results: Overall, 60% of the patients were women (36.5±9.2 years). IHC etiologies were 23 (46%) autoimmune hepatitis, eight (16%) primary sclerosing cholangitis, eight (16%) drug induced, and five (10%) primary biliary cirrhosis. TE could diagnose ≥F2, ≥F3, and F4 stages at cutoffs of at least 6.7, 9.4, and 14.0 kPa, sensitivity/specificity were 100/50% for ≥F2, 88.2/83% for ≥F3, and 90/100% for F4. Moreover, the sensitivity and specificity of ARFI were 93/50% for ≥F2 (cutoff: 1.53 m/s); 71/67% for ≥F3 (cutoff 1.77 m/s); and 90/100% for F4 (cutoff: 2.43 m/s).Follow-up showed a significant decrease in TE and ARFI values by 27 and 22.3% (P<0.001 and <0.001, respectively) and, accordingly, fibrosis stages decreased significantly by both TE and ARFI (P=0.002 and <0.001, respectively)., Conclusion: TE and ARFI represent noninvasive methods with adequate diagnostic performance for the assessment of fibrosis, and monitoring disease progression and treatment response in intrahepatic cholestasis.

Background and Aims: Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens®., Methods: Transient elastography (FibroScan®) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for the detection and quantification of hepatic steatosis/fibrosis, respectively, was assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539 were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: According to BMI (kg/m2), among the patients, 17 (21%) were overweight, 56 (69.1%) obese, and 8 (9.9%) morbidly obese. CAP and FibroScan diagnosed steatosis/fibrosis correlated significantly with liver biopsy. There was a significant association between polymorphisms of rs694539-NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found in 33% NAFLD patients versus 1.2% controls (P<0.001), whereas the wild type (GG-genotype) was present in 21% versus 63.8% controls (P<0.001). Moreover, the AA-genotype significantly correlated with the steatosis degree by CAP but not the fibrosis degree by FibroScan. Multivariate regression analysis of all the independent risk factors showed non-significant correlations with the degree of steatosis on CAP. However, by using a stepwise approach, waist circumference showed significance as an independent predictor of NAFLD., Conclusions: Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk factor for developing NAFLD and NASH (indicating susceptibility for progression and complications). Individuals with wild type (GG-genotype) are at less risk of NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and fibrosis.

Sarcopenia, a complex multifactorial condition, is characterized by loss of muscle mass and function, which increases progressively with age. The existence of different definitions has contributed to the large variation in the prevalence estimates of sarcopenia. We aimed to estimate the prevalence of sarcopenia in the general population using the European Working Group on Sarcopenia in Older People (EWGSOP) proposed definition and compared baseline demographic and clinical characteristics between the nonsarcopenia, presarcopenia, and sarcopenia individuals, with particular emphasis on the overlap with osteoporosis and fracture risk. We studied 5911 subjects at a mean age of 69.2 years (55.8% female) with data on sarcopenia participating in the Rotterdam Study, a prospective population-based cohort study in Rotterdam, the Netherlands. Presarcopenia was defined as having only low muscle mass, whereas sarcopenia was defined based on the presence of low muscle mass, plus either low muscle strength or low physical performance. The prevalence of presarcopenia and sarcopenia was 5.9% and 4.4%, respectively. Individuals with sarcopenia were older, more often males, smokers, with less optimal dietary intake, and more often disabled with lower physical activity. Although the prevalence of fractures was higher in individuals with low lean mass (presarcopenic [16.6%] and sarcopenic [23.5%]) compared with the no sarcopenic group (15.5%), the differences were not present after correcting for age and sex. There were no statistical differences in the prevalence of chronic diseases, with the exception of a higher prevalence of COPD in presarcopenic (29.1%) and sarcopenic (26.9%) individuals compared with nonsarcopenic (13.4%) individuals. Osteoporotic individuals with (odds ratio [OR] = 2.59, 95% confidence interval [CI] 1.41-4.45) and without sarcopenia (OR = 2.75, 95% CI 2.01-3.75) had similar elevated risk of nonvertebral fractures. The presence of sarcopenia appears to be independent of chronic diseases with the exception of COPD and more related to lifestyle factors and disabilities. Sarcopenic individuals in the general population are at no greater risk of fracture than what is determined by their low bone mineral density. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

Zinc is essential for the activation of approximately 300 metallo-enzymes. Serum and hepatic zinc is decreased in chronic liver disease patients, and zinc depletion has been suggested to accelerate liver fibrosis. The study was designed to assess Zinc status in chronic HCV Egyptian patients and its relationship to fibrosis stage diagnosed by FibroScan. This was a cross-sectional study on 297 Egyptian patients with naïve chronic HCV. All patients underwent laboratory tests (including assessment of serum Zinc) and liver stiffness measurement (LSM) by Transient Elastography (FibroScan ® ). The study included 170 (57.2%) females and 127 (42.8%) males with a mean age 52.4 ± 10.2 years. Most of the patients had zinc deficiency as the mean zinc level was 55.5 ± 30.7 μg/dl. The FibroScan scores showed that 97 patients had mild to moderate fibrosis (≤F2), while 200 patients had advanced to severe fibrosis (˃F2). Zinc level was significantly lower in patients with ˃F2 than those with ≤F2 (52 ± 30.7 vs 62.5 ± 29.7, p value: 0.005), as the zinc values decreased with the progression of liver fibrosis. Serum zinc level had a negative significant correlation with INR and negative significant correlation with FibroScan score but no correlation to bilirubin, ALT, AST, or albumin. Most of Egyptian chronic liver disease patients had zinc deficiency. Zinc level gets significantly lower with progression of fibrosis. Zinc supplementation is essential before and during antiviral therapy for HCV.

Introduction and Aim: Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF., Patients and Methods: In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy)., Results: The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and abnormal creatinine and electrolytes (p = 0.002, p < 0.01, respectively). Liver profile and INR (after NAC infusion) differed significantly between the two groups with regard to bilirubin (increased in controls, p = 0.02), AST and INR (decreased in NAC group, p < 0.001 for both), but the ALT decrease showed no statistical significance between the two groups., Conclusions: When administered on admission, intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.

Objectives: To develop a healthy aging score (HAS), to assess age and sex differences in HAS, and to evaluate the association of the HAS with survival., Design: Prospective population-based cohort., Setting: Inhabitants of Ommoord, Rotterdam, The Netherlands., Participants: A total of 1405 men and 2122 women, mean (standard deviation) age 75.9 (6.4) years., Main Measures: We included 7 domains in the total score of HAS: chronic diseases, mental health, cognitive function, physical function, pain, social support, and quality of life; each scored 0, 1, or 2 in each domain. A total score (range 0-14) was constructed and was assessed continuously and in tertiles (13-14: healthy aging, 11-12: intermediate aging, 0-10: poor aging). Sex-specific change in the mean HAS was computed for the age categories of 65-69, 70-74, 75-79, 80-84, and ≥85 years. The association between HAS and mortality was assessed with Cox proportional hazards models., Results: Mean follow-up was 8.6 (3.4) years. Men had poorer scores in the chronic disease domain than women. However, women had poorer mental health, worse physical function, more pain, and lower quality of life compared with men. The prevalence of healthy aging was higher in men (n = 396, 28.2%), than in women (n = 526, 24.8%). The mean (standard deviation) HAS was 11.1 (2.2) in men and 10.7 (2.3) in women. Mean HAS was higher in men than in women for all age categories. The β for change in mean HAS across the 5 increasing age categories was -0.55 (-0.65 to -0.45) in men and -0.65 (-0.73 to -0.57) in women. The age-adjusted hazard ratio per unit increase in HAS with mortality was 0.86 (0.83-0.89) in men, and 0.89 (0.87-0.91) in women., Conclusions: Levels of HAS were lower in women compared with men, in all age categories. The HAS declined with increasing age for both sexes, albeit slightly steeper in women. The HAS was strongly associated with mortality in both sexes. A better understanding of population healthy aging and sex differences in this regard could aid to implement strategies for sustainable healthcare in aging populations., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

SEE BREEN AND LANG DOI101093/AWW321 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: At the time of clinical diagnosis, patients with Parkinson's disease already have a wide range of motor and non-motor features that affect their daily functioning. However, the temporal sequence of occurrence of these features remains largely unknown. We studied trajectories of daily functioning and motor and non-motor features in the 23 years preceding Parkinson's disease diagnosis by performing a nested case-control study within the prospective Rotterdam study. Between 1990 and 2013, we repeatedly performed standardized assessments of daily functioning (Stanford Health Assessment Questionnaire, Lawton Instrumental Activities of Daily Living Scale), potential prediagnostic motor (hypo- and bradykinesia, tremor, rigidity, postural imbalance, postural abnormalities) and non-motor features of Parkinson's disease, including cognition (Mini-Mental State Examination, Stroop Test, Letter-Digit-Substitution Test, Word Fluency Test), mood (Center for Epidemiological Studies-Depression Scale, Hamilton Anxiety and Depression Scale), and autonomic function (blood pressure, laxative use). In addition, the cohort was followed-up for the onset of clinical Parkinson's disease using several overlapping modalities, including repeated in-person examinations, as well as complete access to medical records and specialist letters of study participants. During follow-up, 109 individuals were diagnosed with Parkinson's disease, and each case was matched to 10 controls based on age and sex (total n = 1199). Subsequently, we compared prediagnostic trajectories of daily functioning and other features between Parkinson's disease cases and controls. From 7 years before diagnosis onwards, prediagnostic Parkinson's disease cases more commonly had problems in instrumental activities of daily functioning, and more frequently showed signs of movement poverty and slowness, tremor and subtle cognitive deficits. In the past 5 years, Parkinson's disease cases developed additional motor features (postural imbalance, rigidity, and postural abnormalities) and increasingly reported problems in basic daily activities. Parkinson's disease cases also increasingly reported anxiety symptoms, depressive symptoms, and use of laxatives throughout study follow-up, although differences with controls only became statistically significant in the last years before diagnosis. In conclusion, in patients with prediagnostic Parkinson's disease, impairments in instrumental daily activities, which require both motor and non-motor skills, pre-date difficulties in more physically oriented daily activities.media-1vid110.1093/brain/aww291&#95;video&#95;abstractaww291&#95;video&#95;abstract., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Early identification of individuals at high risk of developing neurodegenerative diseases is essential for timely preventive intervention. However, simple methods that can be used for risk assessment in general practice are lacking., Methods: Within the population-based Rotterdam Study, we used the Purdue Pegboard Test (PPT) to assess manual dexterity in 4,856 persons (median age 70 years, 58% women) free of parkinsonism and dementia between 2000 and 2004. We followed these persons until January 1, 2012 for the onset of neurodegenerative diseases (defined as first diagnosis of parkinsonism or dementia). We determined the association of PPT scores with incident neurodegenerative disease, adjusting for age, sex, study cohort, level of education, smoking, preferred hand, parental history, memory complaints, and Mini-Mental State Examination. Furthermore, we determined the incremental predictive value of PPT, expressed as change in risk classification and discrimination., Results: During follow-up (median 9.2 years), 277 participants were diagnosed with a neurodegenerative disease (227 with dementia and 50 with parkinsonism). Lower PPT scores were associated with higher risk of incident neurodegenerative diseases (hazard ratio [HR] = 1.28, 95% confidence interval [CI]: 1.18-1.41) and improved discrimination of incident neurodegenerative diseases. We also observed significant associations of PPT scores separately with incident dementia (HR = 1.25; 95% CI: 1.14-1.39]) and incident parkinsonism (HR = 1.41; 95% CI: 1.19-1.67)., Conclusions: A rapid, nonlaboratory test of manual dexterity may help to identify persons at high risk for neurodegenerative diseases. This highlights the importance of motor function in the preclinical phase of both dementia and parkinsonism and may aid in selecting individuals for refined screening and neuroprotective trials., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gait is an important health indicator and poor gait is strongly associated with disability and risk of falls. Thyroid dysfunction is suggested as a potential determinant of gait deterioration, but this has not been explored in a population-based study. We therefore investigated the association of thyroid function with gait patterns in 2645 participants from the Rotterdam Study with data available on TSH (thyroid-stimulating hormone), FT4 (free thyroxine) and gait, without known thyroid disease or dementia. The primary outcome was Global gait (standardized Z-score), while secondary outcomes included gait domains (Rhythm, Variability, Phases, Pace, Base of support, Tandem, Turning) and velocity. Gait was assessed by electronic walkway. Multivariable regression models revealed an inverted U-shaped association of TSH (p < 0.001), but no association of FT4 concentrations with Global gait (p = 0.2). TSH levels were positively associated with Base of support (p = 0.01) and followed an inverted U-shaped curve with Tandem (p = 0.002) and velocity (p = 0.02). Clinical and subclinical hypothyroidism were associated with worse Global gait than euthyroidism (β = -0.61; CI = -1.03, -0.18; p = 0.004 and β = -0.13; CI = -0.26, -0.00; p = 0.04, respectively). In euthyroid participants, higher thyroid function was associated with worse gait patterns. In conclusion, both low and high thyroid function are associated with alterations in Global gait, Tandem, Base of support and velocity.

Aim: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4 , CD25 genes., Methods: A prospective study was conducted on 120 subjects divided into 4 groups: Group I ( n = 30) treatment naïve chronic HCV patients; Group II ( n = 30) chronic HCV treated with Peg/Riba; Group III ( n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV ( n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction., Results: Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group., Conclusion: Elevated Tregs cells in chronic HCV patients dampen both CD4 + and CD8 + autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest.

Introduction: We investigated whether a risk score based on genetic risk variants for Parkinson's disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals., Methods: Within the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL., Results: During follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], ΔC = 0.011 [-0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23])., Conclusion: Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

At present, there are no validated methods to identify persons who are at increased risk for Parkinson Disease (PD) from the general population. We investigated the clinical usefulness of a recently proposed non-motor risk score for PD (the PREDICT-PD risk score) in the population-based Rotterdam Study. At baseline (1990), we constructed a weighted risk score based on 10 early nonmotor features and risk factors in 6492 persons free of parkinsonism and dementia. We followed these persons for up to 20 years (median 16.1 years) for the onset of PD until 2011. We studied the association between the PREDICT-PD risk score and incident PD using competing risk regression models with adjustment for age and sex. In addition, we assessed whether the PREDICT-PD risk score improved discrimination (C-statistics) and risk classification (net reclassification improvement) of incident PD beyond age and sex. During follow-up, 110 persons were diagnosed with incident PD. The PREDICT-PD risk score was associated with incident PD (hazard ratio [HR] = 1.30; 95 % confidence interval [1.06; 1.59]) and yielded a small, non-significant improvement in overall discrimination (ΔC-statistic = 0.018[-0.005; 0.041]) and risk classification (net reclassification improvement = 0.172[-0.017; 0.360]) of incident PD. In conclusion, the PREDICT-PD risk score only slightly improves long-term prediction of PD in the community.

Background: Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity., Methods: We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment., Results: IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy., Conclusions: Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it's asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important.

Background: Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients., Methods: A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1(st) group (n=25) was given losartan 50 mg OD for 1 year and the 2(nd) group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study)., Results: In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively)., Conclusions: Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation.

We investigated trends in the incidence of parkinsonism and Parkinson disease (PD) by comparing data from the first 2 subcohorts of the Rotterdam Study, a prospective, population-based cohort study (first subcohort: baseline 1990 with 10 years of follow-up; second subcohort, baseline 2000 with 10 years of follow-up). From the baseline years, we observed differences in the second subcohort that were associated with a lower risk of PD for some but not all baseline risk factors. Participants in both subcohorts were followed for a maximum of 10 years and monitored for the onset of parkinsonism, the onset of dementia, or death, until January 1, 2011. We used Poisson regression models to compare the incidences of parkinsonism, both overall and by cause (PD and secondary causes), and competitive events (incident dementia and death) as well as the mortality of parkinsonism patients in the 2 subcohorts. In the 1990 subcohort, there were 182 cases of parkinsonism (84 of which were PD) during 57,052 person-years. In the 2000 subcohort, we observed 28 cases of parkinsonism (10 with PD) during 22,307 person-years. The overall age- and sex-adjusted incidence of parkinsonism was lower in the 2000 subcohort (incidence rate ratio = 0.55, 95% confidence interval: 0.36, 0.81), and PD incidence declined sharply (incidence rate ratio = 0.39, 95% confidence interval: 0.19, 0.72). Competitive event rates were lower in the 2000 subcohort, and mortality rates among persons with parkinsonism remained stable. These findings suggest that the incidence of parkinsonism in general, and of PD in particular, decreased between 1990 and 2011., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

MicroRNAs (miRNAs) are small noncoding RNAs that serve as key regulators of gene expression. They have been shown to be involved in a wide range of biological processes including neurodegenerative diseases. Genetic variants in miRNAs or miRNA-binding sites on their target genes could affect miRNA function and contribute to disease risk. Here, we investigated the association of miRNA-related genetic variants with Parkinson disease (PD) using data from the largest GWAS on PD. Of 243 miRNA variants, we identified rs897984:T>C in miR-4519 (P value = 1.3×10(-5) and OR = 0.93) and rs11651671:A>G in miR-548at-5p (P value = 1.1×10(-6) and OR = 1.09) to be associated with PD. We showed that the variant's mutant alleles change the secondary structure and decrease expression level of their related miRNAs. Subsequently, we highlighted target genes that might mediate the effects of miR-4519 and miR-548at-5p on PD. Among them, we experimentally showed that NSF is a direct target of miR-4519. Furthermore, among 48,844 miRNA-binding site variants, we found 32 variants (within 13 genes) that are associated with PD. Four of the host genes, CTSB, STX1B, IGSF9B, and HSD3B7, had not previously been reported to be associated with PD. We provide evidence supporting the potential impact of the identified miRNA-binding site variants on miRNA-mediated regulation of their host genes., (© 2015 WILEY PERIODICALS, INC.)

Background: The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated., Objective: We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages., Design: This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles., Results: Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids., Conclusions: Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce., (© 2016 American Society for Nutrition.)

Context: Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it may influence blood lipid levels because it is an essential component of very-low-density lipoproteins., Objective: The aim was to systematically review, using PRISMA guidelines, the literature pertaining to the effects of choline on body composition and on metabolic, cardiovascular, respiratory, and neurological outcomes in different life stages., Data Sources: The MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar databases were searched up to July 2014., Data Extraction: Fifty relevant articles were identified. These comprised trials and cohort, case-control, and cross-sectional studies that assessed blood levels of choline, dietary intake of choline, and supplementation with choline in a population free of diseases at baseline., Data Synthesis: There is some observational evidence that choline during pregnancy may be beneficial for the neurological health of the child. In adults, choline may have beneficial effects on cognition, but high-quality (intervention) studies are lacking. Results on the effects of choline on body composition, blood lipids, and cardiovascular health were inconsistent., Conclusions: Evidence to confirm the suggested effects of choline on health in different stages of life is scarce. Potential effects of choline need to be confirmed by intervention studies. Possible harmful effects on cardiometabolic health need careful evaluation., (© The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence., Methods: From the population-based Rotterdam Study, 4945 participants aged ≥45 years were included in the cross-sectional analysis, and 3069 participants had follow-up brain MRI. Information on coumarin use was obtained from automated pharmacy records. Coumarin users were monitored, and INR values were measured in consecutive visits. Presence and location of microbleeds were rated on brain MRI. We investigated the association of coumarin use with microbleeds using multivariable logistic regression., Results: Overall, 8.6% had used coumarin anticoagulants before the first MRI and 5.9% before follow-up MRI. The prevalence of microbleeds was 19.4%, and the incidence was 6.9% during a mean follow-up of 3.9 years (SD, 0.5). Compared with never users, coumarin users had a higher prevalence of deep or infratentorial microbleeds and a higher incidence of any microbleeds, although statistical significance was not reached in the latter. A higher maximum INR was associated with deep or infratentorial microbleeds. Among coumarin users, a greater variability in INR was associated with a higher prevalence of microbleeds., Conclusions: Coumarin use is associated with microbleeds. Associations were strongest for people with greater variability in INR., (© 2014 American Heart Association, Inc.)

Despite the overwhelming evidence supporting the effectiveness of antihypertensive medication, hypertension remains poorly controlled in low and middle-income countries (LMICs). Lifestyle intervention studies reporting effects on blood pressure published from January 1977 to September 2012 were searched on various databases. From the 6211 references identified, 52 were included in the systematic review (12, 024 participants) and 43 were included in the meta-analysis (in total 6779 participants). We calculated and pooled effect sizes in mmHg with random-effects models. We grouped interventions into behavioral counseling (1831 participants), dietary modification (1831 participants), physical activity (1014 participants) and multiple interventions (2103 participants). Subgroup analysis and meta-regression were used to evaluate origins of heterogeneity. Lifestyle interventions significantly lowered blood pressure levels in LMIC populations, including in total 6779 participants. The changes achieved in SBP (95% confidence interval) were: behavioral counseling -5.4 (-10.7, -0.0) mmHg, for dietary modification -3.5 (-5.4, -1.5) mmHg, for physical activity -11.4 (-16.0, -6.7) mmHg and for multiple interventions -6.0 (-8.9, -3.3) mmHg. The heterogeneity was high across studies and the quality was generally low. Subgroup analyses showed smaller samples reporting larger effect sizes; intervention lasting less than 6 months showed larger effect sizes and intention-to-treat analysis showed smaller effect sizes Lifestyle interventions may be of value in preventing and reducing blood pressure in LMICs. Nevertheless, the overall quality and sample size of the studies included were low. Improvements in the size and quality of studies evaluating lifestyle interventions are required.

Guillain-Barré syndrome (GBS) encompasses a broad spectrum of health-related quality of life (HRQL) determinants, including mobility, fatigue, pain, and depression. We systematically reviewed the literature on functional outcome domains in which GBS patients experience limitations in the short and long terms and evaluated determinants of HRQL in GBS patients. MEDLINE and EMBASE were systematically searched by two independent reviewers for articles covering HRQL data of GBS patients. Of 730 abstracts screened, 17 articles covering data of 14 studies matched the selection criteria. The included articles showed that many GBS patients experienced physical limitations, even years after the acute phase of the disease, while results were inconsistent for perceived levels of pain, fatigue, and general mental well-being. Only three papers covered HRQL assessments at more than one time point, generally showing large improvements in HRQL in the first year after GBS onset, but not thereafter. We appraised the methodological quality of included studies using a 13-item checklist; none of the articles fulfilled all items and only seven articles presented data on correlations between HRQL and determinants. In conclusion, the majority of studies on HRQL in GBS patients are cross-sectional and of low methodological quality. This paper provides guidance for much needed high-quality studies on patterns of patient-perceived recovery after GBS onset., (© 2014 Peripheral Nerve Society.)

Background: Lamivudine monotherapy is effective in suppressing hepatitis B virus (HBV) replication to undetectable levels by PCR, in ameliorating liver disease and to some extent in achieving HBsAg seroconversion. This study aimed at assessing the virological and biochemical responses as well as breakthrough in HBeAg-negative chronic HBV (CHB) Egyptian patients receiving lamivudine therapy., Methods: This retrospective study included 140 CHB patients with positive serum HBV-DNA by quantitative PCR assays and negative HBeAg who had never received prior anti-viral therapy for HBV. According to duration of lamivudine therapy (100 mg/day) patients were grouped into: group I (n=59) who received lamivudine for 1 year, group II (n=50) who received lamivudine for 2 years, and group III (n=31) who received lamivudine for 3 years., Results: In group I, 76.3% patients had virologic response but this was reduced in group II and group III to 72% and 67.7% respectively. None of the patients in group I developed virologic breakthrough, whereas 12% and 25.8% in groups II and III respectively developed breakthrough. In group I, 25% of patients having high pre-treatment viremia showed virologic response compared to 84.6% and 83.3% having mild and moderate viremia respectively (P<0.01). However, in groups II and III, there was no significant relationship between pre-treatment viremia and virologic response. No significant relationship was found between pre-treatment viral load and incidence of breakthrough within each group., Conclusion: Lamivudine remains one of the antiviral therapies for HBeAg negative CHB patients. The rates of maintained virologic and biochemical responses to lamivudine decrease in time due to selection of drug-resistant mutants and, hence, breakthrough.

Background: Biomarkers of hepatocellular carcinoma (HCC) are helpful in screening, diagnosis and follow up of cases. Osteopontin (OPN) is a glycoprotein secreted by osteoblasts, osteoclasts, macrophages and T cells, and is over-expressed in a variety of tumors, including carcinomas of liver, stomach, breast , lung, colon , and prostate. So, the aim of this study was to verify the possibility of using the plasma Osteopontin level as a biomarker for diagnosis of HCC., Methods: The study included 70 subjects divided into three groups: group I had 30 patients with HCC (proved by histopathology or combined spiral CT and elevated alpha-fetoprotein) on top of HCV, group II had 30 patients with HCV infection and group III had 10 healthy subjects serving as control. Osteopontin level was measured in plasma of the studied subjects by ELISA, serum alpha fetoprotein (AFP) level was also measured by EIA., Results: Osteopontin levels were significantly elevated in patients with HCC and in HCV patients in comparison to control group (P: 0.005). There was significant correlation between OPN and AFP levels (P: 0.00). The sensitivity and specificity of OPN for selective detection of HCC group over the non-HCC group (HCV group and healthy control group) were73% and 54%, respectively, at a cut-off value of 128.5 ng/mL. Plasma OPN levels directly correlated with the tumor number but not with the size of the tumor (P: 0.00)., Conclusion: Plasma OPN level appears to be an additional biomarker for HCC detection.

Rationale: Chronic obstructive pulmonary disease (COPD) is a common, complex multisystem disease in the elderly with multiple comorbidities that significantly impact morbidity and mortality. Although cerebral small-vessel disease is an important cause of cognitive decline and age-related disability, it is a poorly investigated potential systemic manifestation of patients with COPD., Objectives: To examine whether COPD relates to the development and location of cerebral microbleeds, a novel marker of cerebral small-vessel disease., Methods: Cross-sectional and longitudinal analyses were part of the Rotterdam Study, a prospective population-based cohort study in subjects aged greater than or equal to 55 years. Diagnosis of COPD was confirmed by spirometry. Cerebral microbleeds were detected using high-resolution magnetic resonance imaging (MRI)., Measurements and Main Results: Subjects with COPD (n = 165) had a higher prevalence of cerebral microbleeds compared with subjects with normal lung function (n = 645) independent of age, sex, smoking status, atherosclerotic macroangiopathy, antithrombotic use, total cholesterol, triglycerides, and serum creatinin (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.15-2.47; P = 0.007). Regarding the specific microbleed location, subjects with COPD had a significantly higher prevalence of microbleeds in deep or infratentorial locations (OR, 3.3; 95% CI, 1.97-5.53; P < 0.001), which increased with severity of airflow limitation and are suggestive of hypertensive or arteriolosclerotic microangiopathy. Furthermore, in longitudinal analysis restricted to subjects without microbleed at baseline, COPD was an independent predictor of incident cerebral microbleeds in deep or infratentorial locations (OR, 7.1; 95% CI, 2.1-24.5; P = 0.002)., Conclusions: Our findings are compatible with COPD causing an increased risk of the development of cerebral microbleeds in deep or infratentorial locations.

Background: Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke., Methods and Results: We performed a cross-sectional analysis using data from the Rotterdam Study, a prospective population-based cohort of persons aged 45 years and older. Among 4408 stroke-free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever-users and 4287 never-users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (> 4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19., Conclusions: In stroke-free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibility of residual confounding in this study.

Unlabelled: BACKGROUND AND RATIONALE FOR THE STUDY: Chronic HCV is a major cause of HCC development. Caspase Recruitment Domains (CARD) is protein modules that regulate apoptosis and play an important role in various carcinogenesis processes, our aim is to assess the possible role of CARD9, CARD10 and Caspase only protein (COP) in progression of liver fibrosis and pathogenesis of HCC in Egyptian chronic HCV patients., Material and Methods: 130 patients were recruited and classified into 4 groups; I: chronic HCV, II: chronic active hepatitis, III: liver cirrhosis, IV: HCV related HCC. Biochemical, virological studies, abdominal ultrasonography and liver biopsy were performed. Quantitative estimation of mRNA of CARD9, CARD10 and COP gene expression was performed by RT- PCR in liver biopsy from all patients., Results: In HCC patients; age, AFP and liver profile were significantly higher, HB and platelets were significantly lower (p value <0.01). The expression levels of mRNA of CARD9, CARD10 and COP in liver biopsies of HCC were significantly higher than other groups with direct correlation with age and no correlation with AFP, viral load, liver fibrosis or necroinflammatory activity. On differentiation between HCC and non HCC patients each CARD was assessed separately and combined, on combing the 3 CARDs, the sensitivity was 100%, specificity was 48%, positive predictive value 47% and negative predictive value 100%., Conclusions: CARD9, CARD10 and COP had no role in liver fibrosis but may be involved in hepatic carcinogenesis and they could be used as markers for HCC diagnosis and candid genes for molecular target therapy.

Background and Study Aim: Large hepatocellular carcinoma (HCC) appears to be a major obstacle for radiofrequency ablation (RFA); therefore, attempts to increase the volume of coagulation by injecting hypertonic saline before and/or during RFA have been made. Transarterial chemoembolization (TACE) combines the effect of targeted chemotherapy with ischemic necrosis and eliminates heat loss if combined with RFA. Our aim was to compare the efficacy of hypertonic saline-enhanced RFA versus TACE sequential RFA in the treatment of medium and large nodular HCC., Patients and Methods: This prospective study was carried out on 40 patients with 40 HCCs between 2008 and 2010 in the Tropical Medicine and Hepatology Department, Faculty of Medicine, Cairo University. They were divided into two groups (20 patients each): the first group received hypertonic saline-enhanced RFA (RFA+HS) and the second group underwent transarterial chemoembolization, followed by RFA (TACE+RFA)., Results: Triphasic computed tomography 1 month after the procedure showed that 17 (85%) patients in each group achieved complete ablation, whereas three (15%) in each group achieved partial ablation. In the RFA+HS group, 12/13 (92%) of medium HCC and 5/7 (71%) of large HCC were successfully ablated. In the TACE+RFA group, 8/8 (100%) medium HCC and 9/12 (75%) of large lesions were successfully ablated. The relation between success rate and lesion diameter was statistically significant only in RFA+HS group. After 6 months, 73.7% of patients in the RFA+HS group and 83.3% of patients in the TACE+RFA group showed maintained ablation (P=0.86)., Conclusion: RFA+HS and TACE+RFA are safe and equally effective treatments for medium to large HCC.

Despite, Egypt is started to be considered as an emerging endemic area for cystic echinococcosis (CE), no enough data in the literature about the exact status of the genotype in both animals and humans. Therefore, the present study aims to characterize the underlying genotypes that could be responsible for the transmission cycle and for the growing infectivity. Animal isolates were collected from 47 camels and 6 pigs. Human isolates are 31 CE cases including; 21 of hepatic cases, 5 of pulmonary cases and 5 multiple-organ affection cases. Hot-Start specific PCR followed by DNA sequencing for mitochondrial 12S rRNA gene, revealed G1 genotype in one (3.2%) of 31 human isolate only. G6 genotype was detected in all the 53 (100%) animal isolates and in 30 out of 31 (96.8%) human isolate. The Egyptian G6 strain nucleotide sequence revealed 100% homology with an Argentinean reference strain 99% homology with the Kenyan G6 strain. It was concluded that G6 genotype is the predominant genotype in Egypt., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Genetic polymorphisms of encoding antigen B2 gene (AgB2) in Echinococcus granulosus were studied using PCR-RFLP and DNA sequencing among 20 Egyptian isolates. Five isolates from different host origins (humans, camels, pigs, and sheep) were collected and used. All examined isolates of each host group gave very similar patterns of PCR-RFLP after restriction enzyme digestion with AluI, with the gene size of approximately 140 bp and 240 bp for sheep and human isolates, and approximately 150 bp and 250 bp for pig and camel isolates. No digestion pattern was obtained after incubation of all studied isolates with EcoRI. These results reveal high intra-group homogeneity. DNA sequence analysis highlighted that human infecting strain showed 100% identity with respect to sheep infecting isolate, 96% and 99% with pig and camel infecting isolates, respectively.