With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI). Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area.

SUMMARY BackgroundHigh intensity exercise improves metabolic status and may potentially mobilise hepatic fat.

SUMMARY BackgroundNon-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the most common cause of primary liver disease. Although recent studies have found that coffee drinking is protective against end stage chronic liver disease, there are scarce caffeine intake data in NAFLD specifically.

This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

The KCTD family includes tetramerization (T1) domain containing proteins with diverse biological effects. We identified a novel member of the KCTD family, BTBD10. A comprehensive analysis of protein-protein interactions (PPIs) allowed us to put forth a number of testable hypotheses concerning the biological functions for individual KCTD proteins. In particular, we predict that KCTD20 participates in the AKT-mTOR-p70 S6k signaling cascade, KCTD5 plays a role in cytokinesis in a NEK6 and ch-TOG-dependent manner, KCTD10 regulates the RhoA/RhoB pathway. Developmental regulator KCTD15 represses AP-2α and contributes to energy homeostasis by suppressing early adipogenesis. TNFAIP1-like KCTD proteins may participate in post-replication DNA repair through PCNA ubiquitination. KCTD12 may suppress the proliferation of gastrointestinal cells through interference with GABAb signaling. KCTD9 deserves experimental attention as the only eukaryotic protein with a DNA-like pentapeptide repeat domain. The value of manual curation of PPIs and analysis of existing high-throughput data should not be underestimated.

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Aliment Pharmacol Ther 2011; 33: 801–814 Summary Background  Polycystic ovary syndrome (PCOS) is a common disorder for women of child‐bearing age and is associated with metabolic syndrome (MS). Aim  To assess the literature for associations between polycystic ovary syndrome and non‐alcholic fatty liver disease (NAFLD). Methods  We performed a systematic review using PubMed‐search for peer‐reviewed articles related to polycystic ovary syndrome and NAFLD. Articles were summarised and grouped according to different sections defining interactions of polycystic ovary syndrome with metabolic syndrome and non‐alcholic fatty liver disease as well as risk factors, pathogenic pathways and treatment options. Results  Obesity is a common factor involved in both polycystic ovary syndrome and non‐alcholic fatty liver disease. Obesity causes non‐alcholic fatty liver disease and aggravates hirsutism and menstrual disorders in polycystic ovary syndrome. Insulin resistance, a hallmark of metabolic syndrome is observed in 50–80% of women with polycystic ovary syndrome and patients with non‐alcholic fatty liver disease. Recent findings suggest that women with polycystic ovary syndrome may be at risk for developing non‐alcholic fatty liver disease and conversely, non‐alcholic fatty liver disease may be a risk for polycystic ovary syndrome. Based on the association of polycystic ovary syndrome and other metabolic abnormalities, such as insulin resistance, hyperandrogenism, obesity and non‐alcholic fatty liver disease, the candidate genes have been speculated for polycystic ovary syndrome. Closer scrutiny of these genes placed most of their proteins at the crossroads of three highly inter‐related conditions: metabolic syndrome, obesity and non‐alcholic fatty liver disease. In most studies, the prevalence of both polycystic ovary syndrome and non‐alcholic fatty liver disease rises proportionally to the degree of insulin resistance and increases in the mass of adipose tissue. Conclusions  Non‐alcholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Similarly, it seems appropriate to consider polycystic ovary syndrome as the ovarian manifestation of metabolic syndrome. Both these conditions can co‐exist and may respond to similar therapeutic strategies.

BackgroundGiven the epidemic proportions of obesity worldwide and the concurrent prevalence of metabolic syndrome, there is an urgent need for better understanding the underlying mechanisms of metabolic syndrome, in particular, the gene expression differences which may participate in obesity, insulin resistance and the associated series of chronic liver conditions. Real-time PCR (qRT-PCR) is the standard method for studying changes in relative gene expression in different tissues and experimental conditions. However, variations in amount of starting material, enzymatic efficiency and presence of inhibitors can lead to quantification errors. Hence the need for accurate data normalization is vital. Among several known strategies for data normalization, the use of reference genes as an internal control is the most common approach. Recent studies have shown that both obesity and presence of insulin resistance influence an expression of commonly used reference genes in omental fat. In this study we validated candidate reference genes suitable for qRT-PCR profiling experiments using visceral adipose samples from obese and lean individuals.ResultsCross-validation of expression stability of eight selected reference genes using three popular algorithms, GeNorm, NormFinder and BestKeeper found ACTB and RPII as most stable reference genes.ConclusionsWe recommend ACTB and RPII as stable reference genes most suitable for gene expression studies of human visceral adipose tissue. The use of these genes as a reference pair may further enhance the robustness of qRT-PCR in this model system.