Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its ...diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non‐invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies.
Aim
To review non‐invasive diagnostic parameters and tools for NAFLD diagnosis and to formulate a diagnostic and prognostic algorithm for a better classification of patients.
Methods
A literature search was carried out on MEDLINE, EMBASE, Web of Science and Scopus for articles and s in English. The search terms used included ‘NAFLD’, ‘non invasive method and NAFLD’, ‘transient elastography’ and ‘liver fibrosis’. The articles cited were selected based on their relevancy to the objective of the review.
Results
Ultrasonography still represents the first‐line diagnostic tool for simple liver steatosis; its sensitivity could be enhanced by the complex biochemical score SteatoTest. Serum cytokeratin‐18 is a promising and accurate non‐invasive parameter (AUROCs: 0.83; 0.91) for the diagnosis of non‐alcoholic steatohepatitis (NASH). The staging of liver fibrosis still represents the most important prognostic problem: the most accurate estimating methods are FibroMeter, FIB‐4, NAFLD fibrosis score (AUROCs: 0.94; 0.86; 0.82) and transient elastography (AUROC: 0.84–1.00).
Conclusions
Different non‐invasive parameters are available for the accurate diagnosis and prognostic stratification of non‐alcoholic fatty liver disease which, if employed in a sequential algorithm, may lead to a reduced use of invasive methods, i.e. liver biopsy.
Association mapping is a powerful tool for the identification of quantitative trait loci through the exploitation of the differential decay of linkage disequilibrium (LD) between marker loci and ...genes of interest in natural and domesticated populations. Using a sample of 230 tetraploid wheat lines (Triticum turgidum ssp), which included naked and hulled accessions, we analysed the pattern of LD considering 26 simple sequence repeats and 970 mostly mapped diversity array technology loci. In addition, to validate the potential for association mapping in durum wheat, we evaluated the same genotypes for plant height, heading date, protein content, and thousand-kernel weight. Molecular and phenotypic data were used to: (i) investigate the genetic and phenotypic diversity; (ii) study the dynamics of LD across the durum wheat genome, by investigating the patterns of LD decay; and (iii) test the potential of our panel to identify marker-trait associations through the analysis of four quantitative traits of major agronomic importance. Moreover, we compared and validated the association mapping results with outlier detection analysis based on population divergence. Overall, in tetraploid wheat, the pattern of LD is extremely population dependent and is related to the domestication and breeding history of durum wheat. Comparing our data with several other studies in wheat, we confirm the position of many major genes and quantitative trait loci for the traits considered. Finally, the analysis of the selection signature represents a very useful complement to validate marker-trait associations.
Despite the high prevalence and serious clinical implications of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), NAFLD is usually overlooked during routine ...diabetes care. This study explored the proportion of NAFLD cases and increased liver fibrosis (LF), and the association between LF and either chronic kidney disease (CKD) or cardiovascular complications in T2DM patients.
The study included 137 patients with non-insulin-treated T2DM and no known liver disease consecutively attending our diabetes outpatients’ service who underwent liver ultrasonography and liver stiffness measurement (LSM) using vibration-controlled transient elastography (FibroScan®).
The proportion of patients with hepatic steatosis on ultrasonography was 73.7%, and the proportion with significant LF was 17.5% with an LSM cut-off ≥7kPa or 10.2% with an LSM cut-off ≥8.7kPa. The presence of CKD (estimated GFR <60mL/min/1.73m2 and/or abnormal albuminuria) increased significantly across LSM tertiles (from around 15% in tertile 1 to 45% in tertile 3). Cardiovascular complications (previous ischaemic heart disease, ischaemic stroke, permanent atrial fibrillation) also tended to increase across LSM tertiles (from around 15% to 30%). After adjusting for established risk factors and potential confounders, LSM tertile 3 remained significantly associated with an approximately threefold higher risk of prevalent CKD (adjusted OR: 3.28, 95% CI: 1.22–8.90; P=0.019), but not for cardiovascular complications.
These results suggest that NAFLD and significant LF (as assessed by FibroScan®) are very commonly seen in T2DM outpatients with no known liver disease attending a secondary-care diabetes service, and that increased LF is associated with a greater proportion of chronic vascular complications, especially CKD.
Information is lacking on the association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) or circulating bone turnover biomarkers in post-menopausal women with type 2 ...diabetes (T2DM).
We recruited 77 white post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Liver ultrasonography and transient elastography (Fibroscan®) were used for diagnosing and staging NAFLD. A dual energy X-ray absorptiometry, and serum levels of 25-hydroxyvitamin D3 25(OH)D, parathyroid hormone and multiple bone turnover biomarkers (periostin, sclerostin, dickkopf-related protein-1 DKK-1, C-terminal telopeptide of type 1 collagen sCTX, procollagen type 1 N-terminal propeptide P1NP, receptor activator of nuclear factor-kB ligand RANKL) were also measured.
Overall, 10 patients had NAFLD with clinically significant fibrosis (i.e., liver stiffness measurement > 7 kPa), 52 had NAFLD without fibrosis and 15 patients were free from steatosis. Although the three patient groups had comparable values of BMD, after adjustment for age, waist circumference, HOMA-insulin resistance and serum 25(OH)D levels, patients with NAFLD and significant fibrosis had significantly higher sclerostin levels (54.1 ± 16.4 vs. 36.1 ± 11.9 vs. 42.3 ± 14.7 pmol/L) and lower levels of serum DKK-1 (26.6 ± 17.8 vs. 49.0 ± 22.4 vs. 42.9 ± 19.4 pmol/L), RANKL (0.04 ± 0.03 vs. 0.08 ± 0.06 vs. 0.11 ± 0.06 pmol/L) and sCTX (0.16 ± 0.09 vs. 0.29 ± 0.17 vs. 0.40 ± 0.28 ng/mL) compared to other groups. Serum periostin and P1NP levels did not significantly differ between the groups.
In post-menopausal women with T2DM, the presence of NAFLD and clinically significant fibrosis was strongly associated with a low bone turnover, which may reflect the presence of qualitative bone abnormalities.
Summary
Non‐alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide ...spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury‐related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin‐sensitizing agents, anti‐oxidants or cytoprotective drugs may be useful, but there is no evidence‐based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.
Evidence is emerging that PNPLA3 rs738409 polymorphism (the major genetic variant associated with susceptibility to non-alcoholic fatty liver disease NAFLD) is associated with chronic kidney disease ...(CKD) in non-diabetic individuals. Currently, little is known about this association in type 2 diabetic (T2DM) patients with and without NAFLD.
We studied 101 Caucasian post-menopausal women with T2DM, consecutively attending our diabetes outpatient service during a 3-month period. Glomerular filtration rate (eGFRCKD-EPI) was estimated using the CKD-Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured with an immunonephelometric assay on morning spot urine samples. NAFLD was detected either by fatty liver index (FLI ≥ 60, n = 101) or by ultrasonography (n = 77). Genotyping was performed by TaqMan-Based RT-PCR system.
Eight patients had G/G, 41 G/C and 52 C/C PNPLA3 rs738409 genotypes, and 21 (20.8%) patients had CKD (eGFRCKD-EPI < 60 mL/min/1.73 m2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFRCKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m2, P = 0.014) and higher prevalence of CKD (50% vs. 24.4% vs. 13.5%, P = 0.04). After adjustment for age, duration of diabetes, haemoglobin A1c, HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFRCKD-EPI (β coefficient: −15.5, 95% CI −26.0 to −5.0, P = 0.004) and higher risk of CKD (adjusted-odds ratio 8.05, 95% CI 1.26–41.4, P = 0.03). Similar results were found when we adjusted for hepatic steatosis on ultrasography (instead of FLI ≥ 60).
Regardless of the presence of NAFLD and common cardio-renal risk factors, in post-menopausal women with T2DM, the G/G genotype of rs738409 in the PNPLA3 gene was strongly associated with lower eGFRCKD-EPI and higher prevalence of CKD.
Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by ...colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular.
The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases.
Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group.
The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.
Summary
Background
In HCV‐infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) ...by interferon (IFN)‐based or IFN‐free regimens on HCC recurrence remain unclear.
Aim
To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN‐based and by IFN‐free regimens.
Methods
We evaluated 443 patients with HCV‐related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN‐free regimens after HCC cure, and 57 patients had SVR achieved by IFN‐based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications.
Results
TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN‐free (P = 0.02) and by IFN‐based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN‐free or by IFN‐based (P = 0.49) strategies.
Conclusion
In HCV‐infected, successfully treated patients with early HCC, SVR obtained by IFN‐based or IFN‐free regimens significantly reduce tumour recurrence without differences related to the anti‐viral strategy used.
Recently, the interest in improving the content of bioactive compounds for enhancing the nutritional value of cereal-based products has largely increased, and several strategies, both genetic and ...agronomic, were proposed. Here, we report the preliminary results of the effect of two sowing periods (winter and spring) on the accumulation of bioactive compounds (i.e., anthocyanins, carotenoids, minerals) and grain morphology in three pigmented cereal species (barley, bread and durum wheat). The results showed that with delayed sowing time, a significant reduction in yield was observed in all species, less in barley (50.4%) than in wheat (70.3% and 66.5% for bread and durum, respectively). On the contrary, the carotenoids accumulation was favored (increased by 12.2%, 15.7% and 27.8% for barley, bread and durum wheat, respectively), as well as those of anthocyanins although strongly dependent on the genotype (i.e., considering only the purple genotypes, the anthocyanins increase by 4.6%, 35.4% and 72.8% in barley, bread and durum wheat, respectively). For minerals compounds, our study highlighted a strong environmental influence even when the pigmented genotypes accumulated more minerals than commercial ones, while the morphometric seed traits were less influenced by this agronomic practice. Therefore, by exploiting the genetic variability for the accumulation of anthocyanins and carotenoids in the grain and by optimizing the sowing time, it could be possible to increase the nutritional value of the final cereal-based products.
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