Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders

Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).

Comparative study on pharmacokinetics and toxicity of intravitreal and sub-Tenon injection of triamcinolone acetonide in ocular tissues

AIM:To compare the differences in kinetics,distribution,and toxicity of triamcinolone acetonide(TA)between the injection methods,sub-Tenon and intravitreal injections in rabbit ocular tissues.METHODS:TA was injected into the vitreous or the sub-Tenon in rabbits.For pharmacokinetic study,rabbits were sacrificed periodically and then TA in blood and ocular tissues(retina/choroids,vitreous,and aqueous humor)were measured over 91 d.For toxicological study,clinical signs,slit-lamp microscopic examination,ophthalmological test were performed.The eyeballs and surrounding tissues were collected and fixed with glutaraldehyde-formalin solution,and then paraffin embedded for histological investigation.RESULTS:Higher levels of TA were distributed in the intraocular tissues when injected into the vitreous compared to the sub-Tenon.Conversely,TA level was remarkably lower in the rabbits which received intravitreal TA injections than those treated with sub-Tenon injection throughout the study period in plasma.Optical discharge probably caused by systemic circulation of TA was observed by receiving sub-Tenon TA injection.Meanwhile,technicassociated toxicological ocular symptoms and findings were more frequently observed in intravitreal injection than in sub-Tenon injection.CONCLUSION:There are significant differences in kinetics and distribution of TA in vitreous body,aqueous humor and plasma,between the two injection methods.Although further study is needed to explain the species difference between human and rabbit,it is assumed that the difference in the frequency of intraocular pressure elevation and cataract formation by TA between the two injection methods are directly related to the TA concentrations in aqueous humor and vitreous body in each injection methods.Systemic toxicity and technic-associated toxicity are also closely related to kinetics of TA in plasma and each injection method itself,respectively.

Comparative Study of Urosepsis-Associated Escherichia coli in Tertiary Care University Hospital in the Central Region of Japan from 2008 to 2011

Escherichia coli infection is important cause of morbidity and mortality. Urosepsis is most commonly caused by Escherichia coli. It is generally reported to have low mortality rates and favorable outcomes compared with sepsis induced in other organ/ system or tissues. This study was conducted to find out the clinical characteristics of urosepsis-associated Escherichia coli isolates at tertiary care university hospital in the central region of Japan from 2008 to 2011. Escherichia coli was identified by standard laboratory procedure. Antimicrobial susceptibility testing was performed by micro dilution assay according to CLSI recommendation. We analyzed the relationship between medical records appended to clinical species and bacterial data by using a statistical method. Of one hundred five Escherichia coli, fifty-three were from urosepsis and fifty-two were from other disease. The ratio of male to female from urosepsis tended to be lower than that from others. Forty-two isolates were from outpatient and sixty-three were from inpatient. The ratio of inpatient to outpatient from urosepsis was significant lower than that from others. With respect to age, the numbers of elder patients were higher than those of others. Most of the Escherichia coli isolates were from the emergency room followed by urology, and general medicine. The ratio of urosepsis to no urosepsis at urology department was significant higher than that at other departments. With respect to antimicrobial susceptible pattern, the ratio of urosepsis to no urosepsis about only aztreonam resistant was significant higher than that about other antibiotics. We need enough attention to be paid to urosepsis, especially female and elder patients.

Efficacy of tolvaptan in an infant with syndrome of inappropriate antidiuretic hormone secretion associated with holoprosencephaly:A case report

BACKGROUND Holoprosencephaly(HPE)is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain.Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported,HPE with the syndrome of inappropriate antidiuretic hormone secretion(SIADH)is very rare.Tolvaptan,a vasopressin V2 receptor antagonist,is effective in adults with SIADH.However,there is no report of its efficacy in infants with SIADH.The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.CASE SUMMARY A 2414-g female infant was born at 38 wk by normal vaginal delivery.Facial anomalies and head magnetic resonance imaging indicated semilobar HPE.After birth,she had hyponatremia due to SIADH and was treated using water and sodium restriction.However,she developed an exaggerated response to the fluid restrictions,resulting in large fluctuations in serum sodium levels.Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration.Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life.There were no side effects,such as hypernatremia or liver dysfunction,during the administration of tolvaptan.CONCLUSION This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

疑似胸腺瘤的前纵隔肿物胸部CT报告标准

临床医生和放射诊断科医生对影像学的格式化报告和标准术语的要求正在不断增加。一项研究[1]发现，CT报告在对肺结节边缘和钙化表述上不统一。另一项研究[2]比较了Fleischner Society Glossary中列举的影像术语和它们常用医学词典中的一致性，包括国际疾病分类、标准参考医学术语和统一医学语言系统等，发现Fleischner术语应用率低，仅为3%-36%[3]。另一方面，研究提示对特殊疾病的标准影像学报告，如乳腺癌筛查报告可以改善患者治疗结果。因此希望对疑似胸腺瘤的前纵隔肿瘤制定标准的描述术语和提高这些术语的应用率，达到能促进临床医生和放射科医生之间的交流的目的，最终给患者治疗带来获益。除了制定统一的术语，报告中还应包含相关疾病知识，使之具有疾病特异性。美国放射医师协会制定了乳腺影像报告和数据系统，描述在钼靶和超声影像发现的乳腺病灶，发现影像报告结果与组织学结果具有相关性[4]。乳腺影像报告和数据系统提供一个对应各种病理类型的百分概率，并在临床上得到广泛应用[5]。一个相似的系统应用于甲状腺结节的超声评估，将这些结节分为高度恶性可能和低度恶性可能，指导适当的临床治疗，这个系统被称为甲状腺影像报告数据系统[6]。

Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.

Role of microRNAs in gastric cancer

Although gastric cancer(GC)is one of the leading causes of cancer-related death,major therapeutic advances have not been made,and patients with GC still face poor outcomes.The prognosis of GC also remains poor because the molecular mechanisms of GC progression are incompletely understood.MicroRNAs(miRNAs)are noncoding RNAs that are associated with gastric carcinogenesis.Studies investigating the regulation of gene expression by miRNAs have made considerable progress in recent years,and abnormalities in miRNA expression have been shown to be associated with the occurrence and progression of GC.miRNAs contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors,affecting cell proliferation,apoptosis,motility,and invasion.Moreover,a number of miRNAs have been shown to be associated with tumor type,tumor stage,and patient survival and therefore may be developed as novel diagnostic or prognostic markers.In this review,we discuss the involvement of miRNAs in GC and the mechanisms through which they regulate gene expression and biological functions.Then,we review recent research on the involvement of miRNAs in GC prognosis,their potential use in chemotherapy,and their effects on Helicobacter pylori infections in GC.A greater understanding of the roles of miRNAs in gastric carcinogenesis could provide insights into the mechanisms of tumor development and could help to identify novel therapeutic targets.

Strategies for gastric cancer in the modern era

Gastric cancer is one of the most common neoplasms in Japan, and it is also the second leading cause of cancer-related deaths worldwide. Nowadays, infection with Helicobacter pylori (H. pylori) is a known risk factor for the development of gastric cancer. Therefore, gastric cancer should be considered as an infectious disease, and in fact, prophylactic eradication of H. pylori may prevent the development of metachronous gastric carcinoma. Before the role of H. pylori was understood, a different approach was used. Recently even after the cancer has developed, some newer therapeutic approaches have been pursued. These newer treatments have been summarized as "minimally invasive therapies" and use endoscopic or laparoscopic techniques. In addition, robotic approaches are being developed that seem to hold a great potential to change the surgical approach. Since basic understanding and treatment of the disease have both changed signif icantly over the last decade, we present a review of current advances in gastric cancer research and therapy.

Inflammatory bowel disease of primary sclerosing cholangitis:A distinct entity?

This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD.IBDassociated with PSC(PSC-IBD)shows an increased incidence of pancolitis,mild symptoms,and colorectal malignancy.Although an increased incidence of pancolitis is a characteristic finding,some cases are endoscopically diagnosed as right-sided ulcerative colitis.Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon.The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition.The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)are similar to those of PSC.The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.

Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells

AIM： To examine whether antithrombin （AT） could prevent hepatic ischemia/reperfusion （I/R）-induced hepatic metastasis by inhibiting tumor necrosis factor （TNF）-α-induced expression of E-selectin in rats. METHODS： Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS： AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION： AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.

Use of barbed suture for peritoneal closure in transabdominal preperitoneal hernia repair

AIM:To investigate the use of the V-Loc wound closure device for transabdominal preperitoneal hernia repair. METHODS:We performed conventional transabdominal preperitoneal hernia repair in 19 patients, including one single incisional case using V-Loc. Except for the use of V-Loc for peritoneal closure, the procedures were the same as those used in conventional techniques. RESULTS:Although the operators included 2 residents who have no experience in laparoscopic herniorrhaphy and intracorporeal suture, the operations were completed. We believe that V-Loc is especially suitable for inexperienced surgeons and the use of V-Loc reduces the operative time by a small amount but reduces operator stress significantly. CONCLUSION:We conclude that V-Loc is the ideal peritoneal closure device for transabdominal preperitoneal hernia repair.

Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt

AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis(UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α) and interleukin-2, and the cellsurface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues(azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody(vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin(ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease(IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.

Association between TNF-a and IL-1β genotypes vs Helicobacter pylori infection in Indonesia

AIM:To investigate the correlation between the Helicobacter pylori(H.pylori)infection and host genetic background of healthy populations in Indonesia.METHODS:In March 2007,epidemiological studies were undertaken on the general population of a city in Indonesia(Mataram,Lombok).The participants included 107 men and 187 women,whose ages ranged from6 to 74 years old,with an average age of 34.0(±14.4)(±SD).The H.pylori of subject by UBT method determination,and through the polymerase chain reaction with confronting two-pair primers(PCR-CTPP)method parsing the single nucleotide polymorphism of interleukin(IL)-8,IL-4,IL-1β,CD14,tumor necrosis factor(TNF-a)and tyrosine-protein phosphates non-receptor type 11(PTPN11)genotypes.The experimental data were analyzed by the statistical software SAS.RESULTS:The H.pylori infection rates in the healthy Indonesian population studied were 8.4%for men and12.8%for women;no obvious differences were noted for H.pylori infection rates by sex or age.TC genotypes of IL-4,TC and CC genotypes of TNF-a,and GA genotypes of PTPN11,were higher in frequency.Both CC and TC genotype of TNF-a T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of(OR=1.99;95%CI:0.67-5.89)and(OR=1.66;95%CI:0.73-3.76),respectively.C allele of IL-1βT-31C gene locus was at a higher risk(OR=1.11;95%CI:0.70-1.73)of H.pylori infection,but no statistical significance was found in our study.CONCLUSION:We reveal that the association between the TNF-a and IL-1βgenotypes may be the susceptibility of H.pylori in the studied population.

Potential significance of CX3CR1 dynamics in stress resilience against neuronal disorders

Recent findings have implicated inflammatory responses in the central nervous system in a variety of neuropsychiatric and neurodegenerative diseases,and the understanding and control of immunological responses could be a major factor of future therapeutic strategies for neurological disorders.Microglia,derived from myelogenous cells,respond to a number of stimuli and make immune responses,resulting in a prominent role as cells that act on inflammation in the central nervous system.Fractalkine(FKN or CX3CL1)signaling is an important factor that influences the inflammatory response of microglia.The receptor for FKN,CX3CR1,is usually expressed in microglia in the brain,and therefore the inflammatory response of microglia is modified by FKN.Reportedly,FKN often suppresses inflammatory responses in microglia and activation of its receptor may be effective in the treatment of inflammatory neurological disorders.However,it has also been suggested that inflammatory responses facilitated by FKN signaling aggravate neurological disorders.Thus,further studies are still required to resolve the conflicting interpretation of the protective or deleterious contribution of microglial FKN signaling.Yet notably,regulation of FKN signaling has recently been shown to be beneficial in the treatment of human diseases,although not neurological diseases.In addition,a CX3CR1 inhibitor has been developed and successfully tested in animal models,and it is expected to be in human clinical trials in the future.In this review,I describe the potential therapeutic consideration of microglial CX3CR1 dynamics through altered FKN signaling.

Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life

MIM： To investigate the different impact of genotypes E and C on the development of liver cirrhosis （LC） among different age groups of patients with chronic hepatitis （CH-B）.METHODS： We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS： In patients 〈 30 years old, there were no significant predictors for development of LC. However, in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12 patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis （7 patients were positive for HBeAg）. In the genotype B group, 4 of 8 patients who developed LC were ≥50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION： The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at 〈 30 years old. However, CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.

Hybrid natural orifice transluminal endoscopic surgery for ileocecal resection

Although laparoscopic colectomy is commonly performed around the world,an operative wound formed during the surgery is large but not sufficient enough to convert for the majority of open surgery.Thus,a certain sized skin incision is required to remove the resected colon.Here we report the case of a pure laparoscopic ileocecal resection which involves transanal specimen extraction.We present a case characterized by a laterally spreading type of tumor of the cecum.We performed a pure laparoscopic ileocecal resection and the resected specimen was removed transanally using colonoscopy.Intracorporeal functional anastomosis was then performed using a flexible linear stapling device under supporting barbed suture traction.The patient was discharged without complications on postoperative day 4.Laparoscopic colectomy performed with minimal incision could essentially increase the usage of this surgical technique.Although our method is restricted to flat or small lesions,we think it is a feasible and realistic solution for minimization of operative invasion because it involves specimen extraction through a natural orifice.

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of thepresent study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii.METHODS: Genotyping of HBV among 61 multi-ethnicc arriers in Hawaii was performed by genetic methods.Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly.RESULTS: HBV genotype distribution among the 61 carderswas 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian,Southeast Asian, and various Asian and Micronesian,respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858).However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C1858 clustered with two isolates from Polynesia with T-1858.In addition, two strains from Asian ethnidties were clustered with known isolates in carriers from Southeast Asia.CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HOV MONITOR test v2.0 (microwell version). METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes. RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test. CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype.METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing.RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E.The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic divers ity (nucleotide homology 96.7-99.2%).Based on the sequences in the basic core promoter (BCP)to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E.CONCLUSION: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics,is observed in HBV/E.