Summary
Background
Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non‐alcoholic fatty liver disease ...(NAFLD).
Aim
To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD.
Methods
We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females.
Results
The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3–F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P < 0.001). After adjusting for confounders, the association of sarcopenia with severe fibrosis was maintained (OR 2.36, CI 1.16–4.77, P = 0.01), together with age > 50 (OR 6.53, CI 2.95–14.4, P < 0.001), IFG/Diabetes (OR 2.14, CI 1.05–4.35, P = 0.03) and NASH (OR 13.3, CI 1.64–108.1, P = 0.01). Similarly, a significant association was found between sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06–3.83, P = 0.03) after adjusting for confounders.
Conclusions
In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression.
Aliment Pharmacol Ther 2011; 34: 757–766
Summary
Background Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric ...acid serum levels and clinical diagnosis of non‐alcoholic fatty liver disease (NAFLD).
Aims We aimed to assess the potential association between uric acid serum levels and histological liver damage in a homogeneous cohort of biopsy‐proven NAFLD patients.
Methods Consecutive NAFLD patients (n = 166), assessed by liver biopsy (Kleiner score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum uric acid assays (Roche Diagnostics GmbH, Mannheim, Germany). Hyperuricemia was diagnosed when uric acid serum levels were >7 mg/dL in men, and >6 mg/dL in women.
Results Mean uric acid serum level was 5.75 mg/dL, and about 20% of patients had hyperuricemia, that was independently associated with younger age (OR 0.951, 95% CI 0.918–0.984, P = 0.004), lobular inflammation (OR 2.144, 95% CI 1.055–4.357, P = 0.03) and steatosis grade (OR 1.859, 95% CI 1.078–3.205, P = 0.02), by multivariate logistic regression analysis. Female gender (OR 2.656, 95% CI 1.190–5.928, P = 0.01), higher HOMA index (OR 1.219, 95% CI 1.043–1.426, P = 0.01), and hyperuricemia (OR 4.906, 95% CI 1.683–14.296, P = 0.004) were linked to NAFLD activity score (NAS) ≥ 5 by multiple logistic regression analysis. Conversely, higher HOMA index (OR 1.140, 95% CI 1.001–1.229, P = 0.04), and NAS (OR1.954, 95% CI 1.442–2.649, P < 0.001) were independently associated with significant fibrosis by logistic regression analysis.
Conclusions In NAFLD patients, hyperuricemia is independently associated with the severity of liver damage, representing, in this setting of patients, together with insulin resistance, a potential new therapeutic target in future intervention trials.
Summary
Background Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its ...performance in patients with non‐alcoholic fatty liver disease (NAFLD) are incompletely understood.
Aim To assess LSM.
Methods Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe.
Results Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut‐off for predicting significant fibrosis at biopsy (AUC 0.794); however, this cut‐off still failed to rule out F2‐F4 fibrosis in 31% (false‐negative rate) or rule in F3‐F4 in 29% (false‐positive rate). Similarly a LSM value >8.75 kPa was the best cut‐off for severe fibrosis (F3‐F4) (AUC 0.870), with a rate of false‐negatives 24% and of false‐positives 2%. Body mass index was the major determinant of these diagnostic errors in predicting significant and severe fibrosis both by overestimating or underestimating the stage of fibrosis.
Conclusions In NAFLD patients, even when liver stiffness measurement is feasible, high BMI values negatively affect the diagnostic reliability. Improved performance of transient elastography could be obtained using specifically designed probes.
Aliment Pharmacol Ther 2012; 35: 238–247
Summary
Background Metabolic factors have been associated with liver damage in patients with non‐alcoholic fatty liver disease (NAFLD).
Aims To test a new ...marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings.
Methods One hundred and forty‐two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL‐6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner).
Results By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003–1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023–2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771–8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231–6.757, P = 0.01) were correlated with significant fibrosis (F2–F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%).
Conclusions In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.
Summary
Lower 25‐hydroxyvitamin D 25(OH)D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome‐wide ...study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D‐binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy‐proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high‐pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.
Summary
Background
The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non‐alcoholic fatty ...liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC).
Aim
To test in genotype 1(G1)‐CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis.
Methods
Four hundred and thirty‐four consecutively biopsied Caucasian G1‐CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients.
Results
The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03–2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00–1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04–4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04–1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non‐obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26–3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05–4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002).
Conclusion
In patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non‐obese subjects.
Summary
Background
It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver.
Aim
To determine whether fibrosis, assessed by collagen ...proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow‐up period.
Methods
We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow‐up of 72 months.
Results
At baseline 38 (32.2%) patients had OV and during the follow‐up (median 72 months, IQR 47–91), 17 patients (14.4%) developed LD. The mean CPA value was different in patients with and without OV (14.8 ± 5.9% vs. 21.6 ± 9.5%, P < 0.001). The best CPA cut‐off for OV by area under the receiver operating characteristic (AUROC) was ≥14% and with multivariate logistic analysis CPA was the only variable associated with OV (OR: 28.32, 95% CI: 6.30–127.28; P < 0.001). By AUROC analysis the best CPA cut‐off to predict LD was 18.0%. By Cox regression multivariate analysis CPA ≥18% (HR: 3.99, 95% CI: 1.04–11.45; P = 0.036), albumin (HR: 0.12, 95% CI: 0.04–0.43; P = 0.001) and presence of OV (HR: 8.15, 95% CI: 2.31–28.78; P = 0.001) were independently associated with LD.
Conclusion
Quantification of fibrosis by collagen proportionate area allows identification of patients with compensated HCV cirrhosis with a higher likelihood of clinically relevant portal hypertension and a higher risk of decompensation.
Abstract Esophageal adenocarcinoma originates from columnar metaplastic epithelium of the distal esophagus. Various steps for this carcinogenetic process are known. Before the onset of high-grade ...dysplasia and adenocarcinoma, endoscopic surveillance is possible. However, because of the high cost of long-term surveillance, predictive factors for cancer are being evaluated to identify subjects with metaplasia who have a higher risk of developing malignancy. Molecular changes seem suitable for this purpose, but could require a high resource expenditure. While trying to identify the best predictive factors for cancer risk, molecular changes and differences in miRNA expression profile between the various steps leading to cancer could help to clarify Barrett's carcinogenesis. In this attempt to find a molecular explanation for the onset of esophageal adenocarcinoma, it is still difficult to understand whether the molecular changes are causes or effects of the neoplastic phenotypic modifications.
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