Aleena Sumrin

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

BackgroundHepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.MethodsWe studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].ResultsAlready established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.ConclusionsThe fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.

A brief review on molecular, genetic and imaging techniques for HCV fibrosis evaluation

BackgroundChronic HCV is one of the major causes of morbidity and mortality in the present day world. The assessment of disease progression not only provides useful information for diagnosis and therapeutic supervision judgment but also for monitoring disease. Different invasive and non invasive methods are applied to diagnose the disease from initial to end stage (mild fibrosis to cirrhosis). Although, liver biopsy is still considered as gold standard to identify liver histological stages, an assessment of the disease development based on non-invasive clinical findings is also emerging and this may replace the need of biopsy in near future. This review gives brief insight on non-invasive methods currently available for predicting liver fibrosis in HCV with their current pros and cons to make easier for a clinician to choose better marker to assess liver fibrosis in HCV infected patients.MethodsMore than 200 studies regarding invasive and noninvasive markers available for HCV liver disease diagnosis were thoroughly reviewed. We examined year wise results of these markers based on their sensitivity, specificity, PPV, NPV and AUROCs.ResultsWe found that in all non-invasive serum markers for HCV, FibroTest, Forns Index, Fibrometer and HepaScore have high five-year predictive value but with low AUROCs (0.60~0.85) and are not comparable to liver biopsy (AUROC = 0.97). Even though from its beginning, Fibroscan is proved to be best with high AUROCs (> 0.90) in all studies, no single noninvasive marker is able to differentiate all fibrosis stages from end stage cirrhosis. Meanwhile, specific genetic markers may not only discriminate fibrotic and cirrhotic liver but also differentiate individual fibrosis stages.ConclusionsThere is a need of marker which accurately determines the stage based on simplest routine laboratory test. Genetic marker in combination of imaging technique may be the better non invasive diagnostic method in future.

Association of laboratory parameters with viral factors in patients with hepatitis C.

Background and AimsHCV infection may lead to hepatic fibrosis. In this study, we tried to determine whether there is any correlation of HCV genotypes and viral load to the clinical parameters such as ALT, AST, ALP, bilirubin, Hb level, patients age and gender; and then correlated this association with disease progression in liver biopsy samples.MethodsIn cross-sectional and observational study, 6048 serum HCV RNA positive patients were chosen. The study consists of 53 months from March 2006 to September 2010. Patients were divided into three cohorts to validate our data. Statistical analysis and correlation of lab parameters with viral factors was determined by using SPSS version 16.ResultsThe most prevalent genotype was 3 (70.9%) followed by 1 (13.3%) and 4 (7.4%), collectively. During Univariate analysis, in all cohorts; serum bilirubin, ALP, ALT and AAR showed significant correlation with genotypes, however multivariate analysis showed that all genotypes except 4a have no association with host biochemical markers. Disease progression was also independent of all genotypes. Serum ALP, ALT, bilirubin and viremea levels were significantly elevated in patients with genotype 4a. Viral load showed negative association with serum bilirubin (r = -0.112, P = 0.000) and ALP levels (r = -0.098, P = 0.000). We observed positive correlation of ALP and bilirubin levels, while negative associations of viral load with HCV liver disease progression.ConclusionDisease progression seems independent of the genotypes. Relationship between ALP and bilirubin with viral load may be an attractive marker to guess disease progression in patients with hepatitis C.

Resistance of polio to its eradication in Pakistan

BackgroundThis study is based on EPI (Expanded Program on Immunization) immunization surveys and surveillance of polio, its challenges in immunization and the way forward to overcome these challenges.MethodsSeveral Government documents, survey reports and unpublished program documents were studied and online search was made to find information on EPI Pakistan. SPSS 16 and Microsoft Excel 2007 were used for the statistical analysis.ResultsImmunization against polio is higher in urban areas as compared to rural areas. Marked variation in vaccination has been observed in different provinces of Pakistan in the last decade. Secondly 10-20% of the children who have received their first dose of trivalent polio vaccine were deprived of their 2nd and 3rd dose because of poor performance of EPI and Lack of information about immunization.ConclusionIn spite of numerous successes, such as the addition of new vaccines and raising immunization to over 100% in some areas, EPI is still struggling to reach its polio eradication goals. Inadequate service delivery, lack of information about immunization and limited number of vaccinators were found to be the key reason for poor performance of immunization and for large number of cases reported each year due to the deficiency of second and third booster dose.

NS4A protein as a marker of HCV history suggests that different HCV genotypes originally evolved from genotype 1b

BackgroundThe 9.6 kb long RNA genome of Hepatitis C virus (HCV) is under the control of RNA dependent RNA polymerase, an error-prone enzyme, for its transcription and replication. A high rate of mutation has been found to be associated with RNA viruses like HCV. Based on genetic variability, HCV has been classified into 6 different major genotypes and 11 different subtypes. However this classification system does not provide significant information about the origin of the virus, primarily due to high mutation rate at nucleotide level. HCV genome codes for a single polyprotein of about 3011 amino acids which is processed into structural and non-structural proteins inside host cell by viral and cellular proteases.ResultsWe have identified a conserved NS4A protein sequence for HCV genotype 3a reported from four different continents of the world i.e. Europe, America, Australia and Asia. We investigated 346 sequences and compared amino acid composition of NS4A protein of different HCV genotypes through Multiple Sequence Alignment and observed amino acid substitutions C22, V29, V30, V38, Q46 and Q47 in NS4A protein of genotype 1b. Furthermore, we observed C22 and V30 as more consistent members of NS4A protein of genotype 1a. Similarly Q46 and Q47 in genotype 5, V29, V30, Q46 and Q47 in genotype 4, C22, Q46 and Q47 in genotype 6, C22, V38, Q46 and Q47 in genotype 3 and C22 in genotype 2 as more consistent members of NS4A protein of these genotypes. So the different amino acids that were introduced as substitutions in NS4A protein of genotype 1 subtype 1b have been retained as consistent members of the NS4A protein of other known genotypes.ConclusionThese observations indicate that NS4A protein of different HCV genotypes originally evolved from NS4A protein of genotype 1 subtype 1b, which in turn indicate that HCV genotype 1 subtype 1b established itself earlier in human population and all other known genotypes evolved later as a result of mutations in HCV genotype 1b. These results were further confirmed through phylogenetic analysis by constructing phylogenetic tree using NS4A protein as a phylogenetic marker.

Exosomes as Biomarker of Cancer

Rapid advances in medicine and biotechnology resulted in the development of non-invasive diagnostic and prognostic biomarkers enabling convenient and accurate detection. Exosomes has recently emerged as non-invasive biomarker for a number of diseases including cancer. Exosomes are the small endosome originated membranous vesicles secreted in a number of biological fluids such as serum, saliva, urine, ascites, cerebrospinal fluid, etc. Exosomes contain microRNA proteins and mRNA which can be used as disease specific biomarkers. Here we reviewed recent advancement in the field of exosomes as diagnostic biomarker for cancer along with a brief overview of their biogenesis, function and isolation.

Developing a deeper insight into reproductive biomarkers

The development of biomarkers of reproductive medicine is still in its infancy because many black boxes are still present in reproductive medicine. Novel approaches to human infertility diagnostics and treatment must be developed because reproductive medicine has lagged behind in the implementation of biomarkers in clinical medicine. Despite the dearth of the available literature, the current rapid pace of publications suggests that this gap will soon be filled therefore; this review is a précis of the research that has been done so far and will provide a basis for the development of biomarkers in reproductive medicine.

Potential biomarkers for the diagnosis of respiratory tract infection and lungs cancer

Major hurdle faced by many physicians in treating various respiratory tract infections and lung carcinomas is their late or mis-diagnosis. In most respiratory tract infections the manner of infection is not completely understood. Similarly, various lung carcinomas are diagnosed at advance stages at which not only the treatment possibilities are narrowed but the chances of survival are also reduced. So, for the sake of better treatment, the quick and improved diagnostic strategies are suggested. Protein biomarkers fully fit the description in this regard as they have shown great potential in specific diagnosis of many respiratory diseases and also have shown capability in timely pin pointing different stages of lung carcinomas. Many serum biomarkers are presently being used for diagnosis but the efficiency for diagnosis of these biomarkers is lower when used alone. So, physicians are suggested to use the combination of different biomarkers. Moreover, genetic biomarkers are also currently studied to indicate the exact stage of disease, the possible damage occurred, the severity of disease and also for the analysis of the possible body response to the therapeutics.

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan.

Abstract Objective: A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. Method: A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q − 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Results: Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q − 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype “AAGTCG” in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). Conclusion: These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.