New markers of fibrosis in hepatitis C:A step towards the Holy Grail?

In the present issue of the World Journal of Hepatology,Ferrassi et al examine the problem of liver fibrosis staging in chronic hepatitis C.They identify novel biomarkers in an effort to predict accurate fibrosis staging with the aid of the metabolome of Hepatitis C patients.Overall I think Ferrassi et al took a different approach in identifying fibrosis biomarkers,by looking at the patients’metabolome.Their biomarkers clearly separate patients from controls.They can also separate out,patients with minimal fibrosis(F0-F1 stage)and patients with cirrhosis(F4 stage).Obviously,if these biomarkers were to be widely used,tests for all the important metabolites would need to be readily available for use in hospitals or outpatient setting and that may prove difficult and above all,costly.Nevertheless,this step could eventually lead to a metabolomic approach for novel biomarkers of Fibrosis.Obviously,it would need to be validated,but could represent a step towards the Holy Grail of Hepatology.

Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy

Chronic liver diseases are very common worldwide, particularly those linked to viral hepatitis and to alcoholic and non-alcoholic fatty liver. Their natural history is variable and long-term evolution differs in individual patients. Optimised clinical management of compensated chronic liver diseases requires precise definition of the stage of liver fibrosis, the main determinant of prognosis and of most therapeutic decisions. Liver biopsy is the gold standard for assessment of hepatic fibrosis. However, it is invasive with possible complications, costly and prone to sampling errors. Many non-invasive markers of liver fibrosis have been recently proposed and assessed in the clinical setting as surrogates of liver biopsy. Direct markers are based on biochemical parameters directly linked to fibrogenesis while indirect markers use simple or more sophisticated parameters that correlate with liver fibrosis stages. Non-invasive markers of liver fibrosis have been tested in different forms of chronic liver disease and showed variable diagnostic performance, but accuracy rarely was above 75%-80%. Better results were obtained when markers were combined. On this line, we have recently proposed a set of algorithms that combine sequentially indirect non-invasive markers of liver fibrosis, reaching 90%-95% diagnostic accuracy with significant reduction in the need for liver biopsy. Based on available evidence, it can be anticipated that non-invasive markers of liver fibrosis and their combined use will soon become a most useful tool in the clinical management of many forms of chronic liver disease. However, their implementation is expected to reduce, but not to completely eliminate, the need for liver biopsy.

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

AIM: To identify the independent predictors of hepatic fibrosis in 69 children with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver biopsy as a confirmatory test. The following clinical and biochemical variables at baseline were examined as likely predictors of fibrosis at histology: age, body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT), platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85, 95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might have fibrotic deposition in the liver.

Sperm collection in Black-legged Kittiwakes and characterization of sperm velocity and morphology

Background:Collecting and studying live sperm is central to many important fields of biology.Yet,a simple method to collect live sperm is lacking in wild seabird species.Here,we describe a non?invasive method to collect viable sperm samples based on a simple massage technique applied to male Black?legged Kittiwakes(Rissa tridactyla).Methods:We studied a colony breeding at Kongsfjorden,Svalbard and successfully obtained sperm samples from 32 males.With a subset of samples(n = 12 males),we compared the suitability of several extenders(0.9% NaCl,PBS,Earle's balance salt solution,Dulbecco's modified Eagle medium) in maintaining sperm alive long enough for analyses.With another 18 ejaculates,we conducted computer assisted sperm analyses using the CASA plugin for ImageJ.We provide details about the settings to be used for such analyses.Lastly,droplets from 20 ejaculates were smeared on glass slides and preserved with formalin to characterize sperm morphology in terms of total sperm length,sperm head length,midpiece length and flagellum length,and percentage of abnormal sperm.Results:With this method and under field conditions,we were able to obtain sufficient amounts of live sperm to assess traits related to sperm quality(e.g.sperm morphology,percentage of motile sperm,sperm velocity).We found that two extenders,Earle's balanced salt solution and Dulbecco modified Eagle's medium,yielded similarly good results.Additionally,we investigated whether specific behaviours were associated with successful sperm collection and whether sperm collection success depended on how long before laying sperm collection was attempted.Finally,we provide mean values for sperm morphology,sperm swimming ability and percentage of motile sperm,which may prove useful for future comparative analyses,and we report high levels of sperm abnormality and within?ejaculate variation in sperm morphology.Conclusions:We discuss the high percentage of abnormal sperm and high within?ejaculate variation in sperm morphology in light of sperm competition theory and conclude that these figures are likely due to relaxed post?cop?ulatory sexual selection,kittiwakes being strictly monogamous.Finally,we suggest that this method could be applied to other seabird species sharing similar ecology.