Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

Non-invasive biomarkers for monitoring the fibrogenic process in liver:A short survey

The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.

Non-invasive diagnosis of alcoholic liver disease

Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH.

Chronic hepatitis C virus infection:Serum biomarkers inpredicting liver damage

Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus(HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C(CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are(1) the physical ones based on imaging techniques; and(2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss:(1) class?Ⅰ?serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes;(2) class Ⅱ biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and(3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC.

Evolving strategies for liver fibrosis staging: Non-invasive assessment

Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either noninvasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change- even in the event of fibrosis regression. Therefore, future studies are needed to validate noninvasive methods in predicting the different phases of liver cirrhosis.

Non-invasive genetic analysis indicates low population connectivity in vulnerable Chinese gorals:concerns for segregated population management

Detailed information on the size and genetic structure of wildlife populations is critical for developing effective conservation strategies, especially for those species that have suffered population decline and fragmentation due to anthropogenic activities. In the present study, we used a non-invasive approach combining fecal pellet sampling with mitochondrial DNA and nuclear DNA microsatellite marker analysis to monitor and compare the population structure of the Chinese goral (Naemorhedus griseus) in Beijing and northeast Inner Mongolia in China. Of the 307 fecal samples confirmed to be from N. griseus, 15 individuals (nine females and six males) were found in the Beijing population and 61 individuals (37 females and 24 males) were found in the Inner Mongolian population. Among these 76 individuals, we identified eight haplotypes and 13 nucleotide polymorphic sites from mtDNA and 45 alleles from 10 microsatellite loci. Spatially structured genetic variation and a significant level of genetic differentiation were observed between the two populations. In both populations, the sex ratios were skewed toward females, indicating high reproductive potential, which is crucial for population recovery and conservation of this patchily distributed vulnerable species. We suggest that managing the two populations as evolutionarily significant units with diverse genetic backgrounds could be an effective solution for present population recovery, with the possible relocation of individuals among different groups to help ensure future goral species prosperity.

Use of inflammatory markers as predictor for mechanical ventilation in COVID-19 patients with stagesⅢb-Ⅴchronic kidney disease?

BACKGROUND Studies have shown elevated C-reactive protein(CRP)to predict mechanical ventilation(MV)in patients with coronavirus disease 2019(COVID-19).Its utility is unknown in patients with chronic kidney disease(CKD),who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance.AIM To assess whether an association exists between elevated inflammatory markers and MV rate in patients with stagesⅢb-ⅤCKD and COVID-19.METHODS We conducted a retrospective cohort study on patients with COVID-19 and stagesⅢb-ⅤCKD.The primary outcome was the rate of invasive MV,the rate of noninvasive MV,and the rate of no MV.Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables.Cutoffs for variables were CRP:100 mg/L,ferritin:530 ng/mL,D-dimer:0.5 mg/L,and lactate dehydrogenase(LDH):590 U/L.RESULTS 290 were screened,and 118 met the inclusion criteria.CRP,D-dimer,and ferritin were significantly different among the three groups.On univariate analysis for invasive MV(IMV),CRP had an odds ratio(OR)-5.44;ferritin,OR-2.8;LDH,OR-7.7;D-dimer,OR-3.9,(P<0.05).The admission CRP level had an area under curve-receiver operator characteristic(AUROC):0.747 for the IMV group(sensitivity-80.8%,specificity-50%)and 0.663 for the non-IMV(NIMV)group(area under the curve,sensitivity-69.2%,specificity-53%).CONCLUSION Our results demonstrate a positive correlation between CRP,ferritin,and D-dimer levels and MV and NIMV rates in CKD patients.The AUROC demonstrates a good sensitivity for CRP levels in detecting the need for MV in patients with stagesⅢb-ⅤCKD.This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation and reduced clearance due to CKD alone.

Sex Determination in the Near Threatened Guadalupe Fur Seal: Molecular Markers and Their Potential Applications

The determination of sex by simple observation is often difficult in marine mammals, even in sexually dimorphic species. Moreover, there is often the practical necessity to determine sex in samples that have been collected without handling or observing the subjects. In these cases, a molecular assay for sex determination is required. We adapted an assay that targets the zinc-finger region and is based on a single primer pair, to the Guadalupe fur seal, a near threatened species that has a very limited breeding range. First, we validated the assay with a sample of pups in which we determined the sex by direct observation during handling;second, we compared it to a more recent assay, based on two different primer pairs and, finally, we evaluated the effect of DNA quantity on its reliability. The assay that we tested produced excellent results and was more reliable than the other one based on two primers. Reliable results were also obtained when only remarkably small quantities of DNA were amplified. These results show the potential use of this molecular assay in case of non-invasive sampling, an overly common situation when dealing with species of problematic conservation status.

Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients

BACKGROUND Inflammation is crucial to tumor progression.A traumatic event at a specific site in the brain activates the signaling molecules,which triggers inflammation as the initial response within the tumor and its surroundings.The educated immune cells and secreted proteins then initiate the inflammatory cascade leading to persistent chronic inflammation.Therefore,estimation of the circulating inflammatory indicators kynurenine(KYN),interleukin-6(IL-6),tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase(hTERT)along with neutrophil-lymphocyte ratio(NLR)has prognostic value.AIM To assess the utility of chosen inflammatory marker panel in estimating systemic inflammation.METHODS The chosen markers were quantitatively evaluated in 90 naive,molecularly subtyped plasma samples of glioma.A correlation between the markers and confounders was assessed to establish their prognostication power.Follow-up on the levels of the indicators was done 3-mo post-surgery.To establish the validity of circulating KYN,it was also screened qualitatively by dot-immune-assay and by immunofluorescence-immunohistochemistry in tumor tissues.RESULTS Median values of circulating KYN,IL-6,hTERT,tissue-inhibitor of matrixmetalloproteinase-1 and NLR in isocitrate-dehydrogenase-mutant/wildtype and within the astrocytic sub-groups were estimated,which differed from controls,reaching statistical significance(P<0.0001).All markers negatively correlated with mortality(P<0.0001).Applying combination-statistics,the panel of KYN,IL-6,hTERT and NLR achieved higher sensitivity and specificity(>90%)than standalone markers,to define survival.The inflammatory panel could discriminate between WHO grades,and isocitrate-dehydrogenase-mutant/wildtype and define differential survival between astrocytic isocitrate-dehydrogenase-mutant/wildtype.Therefore,its assessment for precise disease prognosis is indicated.Association of KYN with NLR,IL-6 and hTERT was significant.Cox-regression described KYN,IL-6,NLR,and hTERT as good prognostic markers,independent of confounders.Multivariate linear-regression analysis confirmed the association of KYN and hTERT with inflammation marker IL-6.There was a concomitant significant decrease in their levels in a 3-mo follow-up.CONCLUSION The first evidence-based study of circulating-KYN in molecularly defined gliomas,wherein the tissue expression was found to be concomitant with plasma levels.A non-invasive model for assessing indicators of chronic systemic inflammation is proposed.

Current guidelines for the management of celiac disease:A systematic review with comparative analysis

BACKGROUND Wheat and other gluten-containing grains are widely consumed,providing approximately 50%of the caloric intake in both industrialised and developing countries.The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence.This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media.However,in recent years,the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease(CD)from obscurity to global prominence.These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD.Different scientific societies,mainly from Europe and America,have proposed guidelines based on CD's most recent evidence.AIM To identify the most recent scientific guidelines on CD,aiming to find and critically analyse the main differences.METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language.PubMed was lastly accessed on 1 March 2021.RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions.Differences were noted in the possibility of a no-biopsy diagnosis,HLA testing,follow-up protocols,and procedures.CONCLUSION We found a relatively high concordance between the guidelines for CD.Important modifications have occurred in the last years,especially about the possibility of a no-biopsy diagnosis in children.Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.

Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in patients with chronic hepatitis C

BACKGROUND:The prognosis and clinical management of patients with chronic liver diseases are closely related to the severity of liver fibrosis.Liver biopsy is considered the gold standard for the staging of liver fibrosis.However,it is an invasive test sometimes related to complications.This study aimed to assess the diagnostic value of enhanced liver fibrosis(ELF) test to predict liver fibrosis in patients with chronic hepatitis C.METHODS:This study included 162 patients with liver disease and 67 healthy controls.Hyaluronic acid,tissue inhibitor of matrix metalloproteinase type 1,and amino-terminal propeptide type III procollagen were measured by enzymelinked immunosorbent assay with the ELF test ADVIA Centaur(Siemens Healthcare Diagnostics Inc.).Fibrosis stage was determined using the Metavir scoring system.RESULTS:In our study,for the diagnosis of significant fibrosis(Metavir F≥2) a cut-off value 】7.72 provides a sensitivity of 93.0% and a specificity of 83.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,93.3%,81.0%,93.3%,and 81.0%,respectively(P【0.001).For the diagnosis of cirrhosis(Metavir F=4) a cut-off value 】9.3 provides a sensitivity of 93.0% and a specificity of 86.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,79.1%,90.8%,75.6%,and 92.3%,respectively(P【0.001).CONCLUSIONS:The ELF test is a promising non-invasive method for assessing liver fibrosis in patients with chronic hepatitis C.It is effective in the diagnosis of both fibrosis and cirrhosis.

Determining the role for uric acid in non-alcoholic steatohepatitis development and the utility of urate metabolites in diagnosis:An opinion review

There has long been a recognised association between non-alcoholic fatty liver disease(NAFLD)and the composite aspects of the metabolic syndrome.Part of this association highlighted the supposed co-existence of elevated uric acid levels in those with NAFLD.There is interest in exploitation of this as a putative diagnostic and prognostic biomarker in NAFLD.Given the increased economic and health burden associated with the NAFLD epidemic,improved methods of population-based,minimally-invasive methods and biomarkers are clearly highly sought and necessary.In this opinion review we review the proposed role of uric acid in the pathogenesis of NAFLD and its potential utilisation in the diagnosis and monitoring of the disease process.

Effects of anatomical position on esophageal transit time:A biomagnetic diagnostic technique

AIM： To study the esophageal transit time （ETT） and compare its mean value among three anatomical inclinations of the body; and to analyze the correlation of ETT to body mass index （BMI）. METHODS： A biomagnetic technique was implemented to perform this study： （1） The transit time of a magnetic marker （MM） through the esophagus was measured using two fluxgate sensors placed over the chest of 14 healthy subjects; （2） the EIF was assessed in three anatomical positions （at upright, fowler, and supine positions; 90°, 45° and 0°, respectively）. RESULTS： ANOVA and Tuckey post-hoc tests demonstrated significant differences between E-IT mean of the different positions. The ETT means were 5.2 ± 1.1 s, 6.1 ± 1.5 s, and 23.6 ± 9.2 s for 90°, 45° and 0°, respectively. Pearson correlation results were r = -0.716 and P 〈 0.001 by subjects＇ anatomical position, and r = -0.024 and P 〉 0.05 according the subject＇s BMI. CONCLUSION： We demonstrated that using this biomagnetic technique, it is possible to measure the ETT and the effects of the anatomical position on the ETT.

Diagnostic challenges in alcohol use disorder and alcoholic liver disease

Alcohol use disorders represent a heterogeneous spectrum of clinical manifestations that have been defined by the Diagnostic and Statistical Manual of Mental Disorders-5. Excessive alcohol intake can lead to damage of various organs, including the liver. Alcoholic liver disease includes different injuries ranging from steatosis to cirrhosis and implicates a diagnostic assessment of the liver disease and of its possible complications. There is growing interest in the possible different tools for assessing previous alcohol consumption and for establishing the severity of liver injury, especially by noninvasive methods.

Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.

Effects of Hepatitis B Virus Co-Infection and Antiretroviral Therapy on Disease Progression among HIV Patients Treated at the Buea Regional Hospital, Southwest Region, Cameroon: A Case-Control Study

In the era of “test and treat”, when AIDS-defining events have been drastically reduced, chronic liver disease associated with viral hepatitis and antiretroviral therapy (ART) remains an important cause of non-AIDS morbidity and mortality among HIV-infected patients. Compared to the general population, HIV-infected patients are about 10-times at risk of hepatitis B virus infection. Additionally, several antiretroviral regimens are hepatotoxic. Therefore, effective monitoring and management of ART and HBV co-infection are essential to ending the AIDS epidemic and eliminating viral hepatitis by 2030. This was a hospital-based, matched (age and sex) case-control study. HIV patients (case patients) on ART for at least six months and “healthy” controls aged 18 years and older were enrolled. Blood samples were collected for immuno-hematologic indices and transaminases measurements. Data were presented as counts, percentages, median (IQR) and means (SD), and a p-value 1.5) and mild (0.6 - 1.5) liver fibrosis based on the APRI score was 0.5% and 8%, respectively. Significant fibrosis (>3.25) was 0.9%, while 18.4% had inconclusive fibrosis (1.45 - 3.25) based on the FIB-4 score. HIV/HBV co-infected patients had a higher occurrence of liver fibrosis (APRI: 0.5% vs FIB-4: 0.9%). Co-infections with HBV increase the risk of liver-related morbidity in HIV patients. Therefore, screening for serological markers of chronic HBV infection and hepatic transaminase levels in HIV patients remains crucial in the continuum of care.

The combination of endoglin and FIB-4 increases the accuracy of detection of hepatic fibrosis in chronic hepatitis C patients

Background and aim: In patients infected with chronic hepatitis C virus, liver biopsy is the gold standard method of staging fibrosis. Different combinations of serum markers attempted to correlate with hepatic fibrosis in place of liver biopsy and have shown encouraging results. The aim of our study is to evaluate the diagnostic value of endoglin and FIB-4 as non-invasive markers of hepatic fibrosis in HCV patients. Methods: We estimated serum endoglin & FIB-4 index in 40 infected chronic hepatitis C patients. Histological staging of hepatic fibrosis was done according to the METAVIR scoring system. Results: Both endoglin and FIB-4 index showed positive correlation with age and aspartate transaminase and inverse correlation with albumin. The diagnostic performance determined by AUROCs for early fibrosis (≤F2), was 0.868 for endoglin and 0.887 for FIB-4, at cut off va- lues of 5.5 & 0.98 with sensitivity of 64.3% & 82.1%, and specificity of 100% & 85% respectively. For ad-vanced fibrosis (>F2), the AUROC was 0.98 for endoglin and 0.967 for FIB-4, obtained at cut off values of 6.29 & 1.6, with sensitivity of 100% & 91.7%, and specificity of 89.3% & 92.9%, respectively. Conclusion: Both serum endoglin and FIB-4 index are fairly accurate in differentiating stages of hepatic fibrosis;their combination in a single equation enhanced the accuracy of fibrosis detection in chronic HCV patients.

Genetic analysis for geographic isolation comparison of brown bears living in the periphery of the Western Carpathians Mountains with bears living in other areas

Populations of the European brown bear (Ursus arctos L.) differ substantially in size, degree of geographic isolation and level of genetic diversity. Present patterns result from phylogeographic processes and profound human intervention. We assessed the genetic variability of a subpopulation of brown bears near the periphery of their range in the Western Carpathian Mountains and compared their genetic properties with those of bears in the core of the same population and elsewhere. Samples were collected non-invasively in 2007-2008 and2010 in Strázovské Vrchy Protected Landscape Area (PLA) in Slovakia (included in the NATURA 2000 networking programme). Seven polymorphic microsatellite loci (UaMU26, UaMU64, G10B, G1D, G10L, UaMU50 and UaMU51) were amplified using a nested PCR in order to assess the following parameters: variability, allelic combinations, heterozygosity, number of alleles and inbreeding coefficient. Sufficient brown bear DNA for analysis was obtained from 57 out of 140 samples (41%), among which 45 different genotypes were identified. Loci had a mean of 2.71 ± 0.76 alleles. Average observed heterozygosity was 0.59. The inbreeding coefficient was negative for all but one of the analysed loci (2007-2008). In the year 2010 was negative three of seven loci. These results imply that gene flow with other parts of the population has been maintained in the reduced level and the isolation level of bears in the study area was not so low. Nevertheless, the genetic variability of bears in Strázovské Vrchy PLA was lower than that reported from other localities in the Carpathian Mountains. The results are discussed in the context of behavioural ecology and conservation genetics.