Background Genetic variants of Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have been reported with the development of hepatocellular carcinoma (HCC). This study aims to explore the role of The PNPLA3 rs738409 and TM6SF2 rs58542926 single-nucleotide polymorphisms (SNPs) on the incidence and survival of HCV-induced HCC in Egyptians. Methods and results This case-control study included (120) HCC and (144) hepatitis C virus (HCV) patients. Baseline clinical, laboratory, tumor characteristics data, HCC recurrence, and overall survival were collected. PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphism were detected by TaqMan allelic discrimination assay. We found that HCC patients were significantly older with male predominance. A significant difference between the TT genotypes of TM6SF2 frequency was observed in HCC compared with HCV patients. Moreover, the T allele of TM6SF2 distributions revealed a significant contribution to the different stages of HCC ( p =0.03). Both PNPLA3 rs738409 and TM6SF2 rs58542926 variants showed a significant relation with treatment response according to the modified RECIST criteria. Age and diabetes mellitus were the independent factors associated with the development of HCC by multivariate regression analysis. Conclusions TM6SF2 rs58542926 polymorphism, not PNPLA3 rs738409, could be implicated in the development of HCV-induced HCC and its progression.

Purpose: Pharyngeal airway space (PAS) assessment after orthognathic surgery is crucial due to the possible resultant breathing hazards. This study compared PAS after mandibular set-back surgery and bimaxillary surgery and its consequent effect on the patients’ daytime sleepiness in class III dento-skeletal patients. Patients and methods Twenty-four patients with dento-skeletal class III deformity were divided equally into two groups; group A underwent mandibular set-back surgery while group B had bimaxillary orthognathic surgery through mandibular set-back and maxillary advancement surgeries. PAS area was measured on lateral cephalometric radiographs. Daytime sleepiness was assessed by Epworth sleepiness scale (ESS). All results were recorded pre-surgically, immediate post-surgically and at 6-months post-surgically. Results In group A patients, the PAS value at T0 (mean of 546.72±66.61 mm2) revealed a non-significant decrease after mandibular set-back surgery at T1 to reach a mean of 542.89±68.65 mm2, which appeared to minimally relapse at T2 to a value still less than T0 (544.00±68.62 mm2) with a final decreased PAS value. In group B patients, the PAS value (mean of 555.05±75.04 mm2) revealed a non-significant increase after bimaxillary surgery at T1 reaching a mean of 555.73±79.34 mm2 which re-increased at T2 to a mean value of 557.79±78.23 mm2. Following the pattern of PAS, the ESS recorded non-significant changes in both groups from the preoperative values to values at T1 and T2. Conclusion Despite of the resulted post-surgical different changes, orthognathic surgery appeared to have no significant effect on PAS area nor on daytime sleepiness in a six-month duration.

Objectives: To detect the correlation between the single nucleotide polymorphisms (SNPs) in MBOAT7 and PNPLA3 genes and hepatic fibrosis in hepatitis C virus (HCV) Egyptian patients, and to highlight the additive effect, if any, of MBOAT7 on the correlation of PNPLA3 polymorphism with liver fibrosis in HCV patients from Egypt. Methods: In this cross-sectional study, we recruited treatment-naïve patients with chronic HCV. The rs738409 (PNPLA3) and rs641738 (MBOAT7) polymorphisms were assessed by Real-Time PCR. We utilized the METAVIR‐Score to classify the degree of hepatic fibrosis and necroinflammatory activity. Results: A total of 93 patients (mean age 42.72 ± 10.46; males = 49.5%) were included. Our analysis showed that 10.8% of the patients had GG genotype of the PNPLA3 gene and 46.2% had TT genotype of the MBOAT7 gene. Compared to combined CC and GC genotypes, carriers of GG genotype in PNPLA3 gene were more likely to be males (p =0.041), have higher fibrosis grade (p =0.043), have higher serum creatinine (p < span style="text-decoration: line-through;">=0.036), higher TSH (p =0.017) and higher viral load (p =0.045). Notably, we found a significant association between TT genotype in MBOAT7 and advanced fibrosis only (but not with necroinflammation (p >0.05). Our multivariate analysis showed that the GG genotype in the PNPLA3 gene and TT genotype in the MBOAT7 gene were independent predictors of advanced fibrosis. Conclusion: PNPLA3 GG genotype and MBOAT7 TT genotype are independent predictors for hepatic fibrosis, and thus might be linked to faster disease progression.

Background: Association studies identified genetic polymorphisms as predictive risk factors of rapid fibrosis progression in chronic hepatitis C (CHC). This study aims to assess the impact of IL28B rs8099917 polymorphism on CHC genotype 4 (G4) susceptibility and liver fibrosis progression individually; and in combination with PNPLA3 rs738409. Patients and methods: IL28B rs8099917 and PNPLA3 rs738409 were genotyped in 150 Egyptian CHC patients and 175 healthy controls using real-time PCR. Results: IL28B rs8099917 genotype distribution significantly differs in healthy individuals versus CHC patients (p = .018); and in low versus advanced fibrosis IL28B (p = .013). The haplotype CC -GG (PNPLA3-IL28B) is considered a high-risk signature for susceptibility to CHC infection. Similarly, GG-GG (PNPLA3-IL28B) is considered a high-risk signature for higher degree of fibrosis. Conclusion: IL28B rs8099917 and PNPLA3 rs738409 introduce genetic signature to identify patients at higher risk for CHC susceptibility and fibrosis progression in CHC G4.

Chronic inflammation is a pivotal contributor to the liver damage mediated by hepatitis C virus (HCV). The NOD-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome is activated by HCV in both hepatocytes and Kupffer cells. The aim of our study was to investigate the association of nine single-nucleotide polymorphisms in four inflammasome genes (NLRP3, CARD8, IL-1 β , and IL-18) with the susceptibility to HCV infection and outcome of interferon treatment in 201 Egyptian chronic hepatitis C patients and 95 healthy controls. The genotyping was conducted using TaqMan predesigned SNP assay. In the comparative analysis, the CC genotype of the NLRP3 rs1539019 was found to be associated with the lower risk to chronic HCV infection (OR: 0.33, 95% CI: 0.17-0.62). This association was also found for the CA genotype and the A allele of the NLRP3 rs35829419 (OR: 0.18 and 0.22, respectively), in addition to the GG genotype and G allele of IL-18 rs1946518 (OR: 0.55 and 0.61, respectively). In contrast, the AA genotype of the IL-1 β rs1143629 was significantly more frequent in HCV patients (OR: 1.7, 95% CI: 1-2.86). Notably, the frequency of the AA genotype of NLRP3 rs1539019 was significantly higher in patients with lack of response (NR) to the interferon treatment (OR: 1.95, 95% CI: 1-3.7). A similar association was found for both the CC genotype and C allele of the NLRP3 rs35829419 (OR: 2.78 and 2.73, respectively) and for the TT genotype and T allele of CARD8 rs2043211 (OR: 2.64 and 1.54, respectively). Yet, the IL-1 β (rs1143629, rs1143634) and IL-18 (rs187238, rs1946518) polymorphisms did not show any significant association with response to interferon treatment. In conclusion, this study reports, for the first time, the association of genetic variations in NLRP3 with hepatitis C susceptibility and response to treatment in Egyptian patients. However, further large-scale studies are recommended to confirm our findings.

Background: TM6SF2 and NCAN are genes known to be related to fibrosis and steatosis but are not thoroughly investigated in the case of chronic Hepatitis C (HCV) in Egyptians. Aim: This study is carried to investigate the role of TM6SF2 and NCAN in chronic HCV Egyptian patients. Methods: This retrospective study was carried out on 165 patients with chronic HCV who received treatment for it. Results: TM6SF2 showed statistical significance with viral load with a p-value of 0.02 but no statistical significance with fibrosis or activity. NCAN showed statistical significance with activity with a p-value of 0.011. Conclusion: this is the first work recording the prevalence of TM6SF2 (rs58542926) and NCAN (rs2228603) polymorphism in upper African HCV patients. TM6SF2 is not associated with fibrosis or activity in Egyptian patients infected with chronic hepatitis C but associated with high viral load. On the other side, NCAN is associated with severity of activity in the same studied group but no relation with the viral load. These results explain their additive effect exerted during HCV infection which should be further extensively studied.

Alpha-1antitrypsinisaproteinwith inhibitorycapabilityovertheproteolytic enzymeelastase.Sinceitsfirstdescription in1963,over100differenta1ATalleles havebeendescribed(FolchE.,etal, 2007).Themajorclinicalmanifestationsof a1ATdeficiencyrelatetothefunctionofa 1ATandwhereitismade.A1ATserves asaninhibitorofneutrophilelastase(NE), apowerful,destructiveproteolyticenzyme storedinneutrophils(CarrellR.W,etal., 1982)(JanoffA,.1985).Theliveristhe majorsiteofa1ATgeneexpression, releasing2gofa1ATintothecirculation daily.A1ATdiffusesintomostorgans, whereitprotectsextracellularstructures fromattackbyNEreleasedbyactivatedor disintegratingneutrophils.Thelower respiratorytractisparticularlyvulnerableto deficiencyofa1AT,whichnormally represents>90%oftheanti-NEprotective screenofthealveolarwalls(GadekJ.E.,et al.,1981)(Wewers,M.D.,etal.,1987) .WhenserumaIATlevelsare<11um, thereisinsufficientaIATtoprotectthe lowerrespiratorytractfromitsburdenof NE,permittingprogressivedestructionof thealveoli,whichculminatesin emphysema(Wewers,M.D.,etal.,1987). Thepathogenesisoftheliverdiseaseisless wellunderstood,butrelatestothefactthat hepatocytesarethemajorsiteofalAT synthesis,andthatcertainmutationsofthe a1ATgenecausederangementsinthe intracellularprocessingofaIAT, culminatinginhepatocyteinjury (ErricksonS.,1986).Themostsevereform ofdeficiencyisthehomozygousexpression oftheZalleleorPI*ZZ,whenthis expressionoccurs,itaccountsfor95%of casesofseverea1ATdeficiency.The threeorgansmostcommonlyaffectedbya 1ATarethelungs,liverandskin.a1AT deficiencyisthemostfrequently recognizedgeneticriskfactorforchronic obstructivepulmonarydisease(COPD). Eventhoughitremainsunderdiagnosed,its importancecontinuestogrowinthefieldof solidorgantransplantation,accountingfor 8-9%ofalllungtransplants.A1ATisthe mostcommonmetabolicliverdisease requiringlivertransplantationinchildren. Thepresenceofcirrhosisinalpha-1- antitrypsindeficiencyislow,approximately 2.2/100,000forZZhomozygotes.The male-to-femaleratiowas2to1.Inone- thirdofthepatientsalcoholcouldhave beenaco-adjuvantoraggravatingfactorin theliverdisease(FolchE.,etal,2007). Wedescribeauniquecaseofa27year-old manwitha1AT,presentedwithliver cirrhosisportalveinthrombosis&multiple bonydeformities.

BACKGROUND & AIMS:Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy. METHODS:This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy. RESULTS:Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%). CONCLUSION:Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.

Objectives: Chronic hepatitis C (CHC) or liver inflammation resulting from infection with hepatitis C virus (HCV) is the cause of chronic liver disease and leads to cirrhosis and hepatocellular carcinoma. The burden of chronic HCV-related liver disease in Egypt continues to rise and the interaction of liver inflammation with biomarkers and response to therapy is scarcely discussed. Moreover, serum alanine transaminase (ALT) is considered as a moderately accurate test for indicating liver inflammation. This study aims to evaluate the correlation of liver inflammation with response to therapy and with alpha-fetoprotein (AFP), and to assess the potential efficiency of AFP as a marker for liver inflammation. Methods: The study included 134 consecutive Egyptian chronic HCV patients. Sustained virological response (SVR) was assessed by the detection of HCV by reverse polymerase reaction (PCR). Furthermore, fibrosis and necroinflammation were assessed before treatment. Results: Severe liver inflammation was significantly associated with higher pretreatment levels of ALT, aspartate aminotransferase (AST) and AFP. AFP overcomes ALT as marker of inflammation by ROC curve analysis. Early virologic response (EVR), end-of-treatment response (ETR) and SVR was significantly higher in patients with mild inflammation than those with moderate and severe inflammation. Conclusion: Pretreatment AFP levels should be considered as a surrogate marker in predicting liver inflammation. Mild liver inflammation was more prevalent than moderate and severe inflammation in responders by means of EVR, ETR and SVR. d be considered as a surrogate marker in predicting liver inflammation. The response to therapy is more apparent in mild than moderate and severe liver inflammation by means of EVR, ETR and SVR.

Objectives: To evaluate the validity and reliability of the autogenous transplantation of maxillary or mandibular molars. Methods: Ten patients received either a mandibular or maxillary third molar to replace a non restorable mandibular first or second molar. The clinical parameters were mobility and probing pocket depth. Radiographic assessment of progress of root development, periapical or periodontal radiolucencies, root resorption and ankylosis, was done by using digital panoramic radiographs with1:1 magnification correction. All clinical parameters and panoramic radiographs were taken at 2, 4, 6 and 9 months postoperatively. Results: The pocket depth readings and teeth mobility showed statistical significant decrease throughout the study. Regarding the radiographic results, no root resorption or ankylosis and 80% of patients had root development with no observed radiolucencies. Conclusion: The transplantation of developing molars in growing adults is a viable and reliable treatment option. [Maha Negm, Sameh Seif, Khaled El Hayes, Galal Beheiri. Autogenous Transplantation of Maxillary And Mandibular Molars. Life Sci J 2012;9(4):2804-2812] (ISSN: 1097-8135). http://www.lifesciencesite.com. 412

Aim and background:   To evaluate hepatic expression of the nuclear proliferative marker Ki-67  and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to the advanced stages of liver fibrosis in HCV positive Egyptian  patients.   Material & Methods:   Paraffin-embedded liver biopsy specimens were studied from 21 untreated  patients with chronic HCV infection. All patients were HCV antibody positive, as determined by a commercially available enzyme-linked immunosorbent assay kit. Patients having other etiologies for chronic liver disease including HBV infection were not included in this study. Liver biopsies were obtained percutaneous. All biopsies were fixed in formalin, embedded in paraffin, and sectioned by microtome with a thickness of 5 µm. Routine specimen processing involved staining slides with hematoxylin and eosin (5 levels), Masson's trichrome stain (5 levels), for a total of 10 levels per specimen All levels were screened. All specimens were examined by two pathologists, and classified by consensus for all abnormal histological findings. The histological activity index (or histological grade) was determined using Ishak grading scheme22 expressed as a semiquantitative score for portal inflammation (0-4), lobular activity sporadic lytic foci (0-4) and parenchymal confluent necrosis (0-6), and piecemeal necrosis(0-4). The extent of fibrosis (or histological stage) was determined using Ishak score (0-6). Steatosis was scored according to Keliner et al 2005, from grade 0 to 3; where S0 = no steatosis or less than 5% (low or medium power evaluation) of parenchymal involvement by fatty changes, S1 (mild) = 5%-33%, S2 (moderate) = >33%-66% and S3 (severe) > 66% of the hepatocytes are involved by fatty changes.  Expression of p53 and Ki67 were determined by immunohistochemistry, using avidin-biotin-peroxidase.   Results:   Liver histology: The studied group (n = 21) involved 16 males and 5 females (male to female ratio 3.3:1). The histopathological findings of HCV infection, including portal lymphoid infiltration, periportal piecemeal necrosis, lymphocyte infiltration of the lobules, hepatocellular necrosis, steatosis and fibrosis, were studies. The age ranged from 31 to 59 years old with mean of 44.86 ± 8.74, males 76.2%, females 23.8% .P53 expression was positive in 52.4% and negative in 47.6%. cytoplasmic localization dominated over nuclear expression. Ki 67 was negative in 81% of cases and positive in19% of cases,  all cases in stage 6 were positive for p53 while there were no difference in the other stages of fibrosis, and this relation was statistically significant. There was no relation between the grade of necro-inflammation and the expression of p53, and this result was statistically non significant.There was a relation between the percent of steatosis and the expression of p53 as percent of positivity increases with the increase of the percent of steatosis, and this result was statistically significant using independent sample t test and regression test.All negative cases for P53 have negative Ki67 but this rule is not applied on positive cases for P53, and this relation was  not statistically significant There was no relation between the grade of necro-inflammation and the expression of Ki67, and this result was statistically non significant.   Conclusion:   Hepatic expression of the nuclear proliferative marker Ki-67  and the cell cycle marker p53 oncoprotein in chronic hepatitis C in relation to advanced stages of liver fibrosis in HCV positive patients are expressed in a considerable present of cases which should be cansdidates for follow up for early detection of hepatocellular carcinoma.

Fructus Schizandrae Sinensis bail, a traditional Chinese medicine, has been shown to lower the elevated serum level of liver enzymes of patients suffering from chronic active hepatitis. A synthetic derivative compound of Schisandrian, Dimethyl Diphenyl Bicarboxylate (DDB) is now used widely in clinical fields as a hepatoprotective drug. Thus it is important to know whether DDB has a beneficial effect on damaged liver or not.