A simple index of lipid overaccumulation is a good marker of liver steatosis

<p>Abstract</p> <p>Background</p> <p>Liver steatosis is often found in association with common cardiometabolic disorders, conditions that may all occur in a shared context of abdominal obesity and dyslipidemia. An algorithm for identifying liver steatosis is the fatty liver index (FLI). The lipid accumulation product (LAP) is an index formulated in a representative sample of the US population to identify cardiometabolic disorders. Because FLI and LAP share two components, namely waist circumference and fasting triglycerides, we evaluated the ability of LAP to identify liver steatosis in the same study population from the Northern Italian town where FLI was initially developed.</p> <p>Methods</p> <p>We studied 588 individuals (59% males) aged 21 to 79 years. Liver steatosis was detected by ultrasonography and coded ordinally as none, intermediate and severe. 44% of the individuals had liver steatosis. Using proportional-odds ordinal logistic regression, we evaluated the ability of log-transformed LAP (lnLAP) to identify liver steatosis. We considered the benefits to our model of including terms for sex, age, suspected liver disease and ethanol intake. We calculated the 3-level probability of liver steatosis according to lnLAP and sex, providing tables and nomograms for risk assessment.</p> <p>Results</p> <p>An ordinal proportional-odds model consisting of lnLAP and sex offered a reasonably accurate identification of liver steatosis. The odds of more severe <it>vs. </it>less severe steatosis increased for increasing values of lnLAP (odds ratio [OR] = 4.28, 95%CI 3.28 to 5.58 for each log-unit increment) and was more likely among males (OR = 1.88, 95%CI 1.31 to 2.69).</p> <p>Conclusion</p> <p>In a study sample of adults from Northern Italy, the simple calculation of LAP was a reasonably accurate approach to recognizing individuals with ultrasonographic liver steatosis. LAP may help primary care physicians to select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. A more thorough assessment of LAP's potential for identifying liver steatosis will require its cross-evaluation in external populations.</p

Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

<p>Abstract</p> <p>Background</p> <p>Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-<it>db/db </it>(<it>db/db</it>) obese mice.</p> <p>Methods</p> <p>Male <it>db/db </it>mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks.</p> <p>Results</p> <p>At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of <it>TNF-α </it>and <it>interleukin-6 </it>mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.</p> <p>Conclusions</p> <p>Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals.</p

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes

Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity

Statins in liver disease: a molehill, an iceberg, or neither?

A growing number of chronic liver disease patients, especially those with metabolic syndrome-associated nonalcoholic fatty liver disease or hepatitis C virus-associated dysmetabolic syndrome, will take statins to prevent cardiovascular disease. As a result, clinicians will weigh complex issues raised by the interaction of statins with liver metabolism in these disorders. In this article, we critically review data concerning statins and liver pathophysiology with an emphasis on nonalcoholic fatty liver disease and hepatitis C virus, while also touching on other chronic liver diseases. Basic research interests include statins' mechanism of action and their effects on cholesterol-related cell signaling pathways and angiogenesis. From the clinical standpoint, many chronic liver diseases increase cardiovascular risk and would undeniably benefit from sustained statin use. The false alarms and security accompanying aminotransferase monitoring, however, are disturbing in light of the scarcity of data on statins' long-term effects on liver histology. Although some actions of statins might eventually prove to be particularly useful in nonalcoholic steatohepatitis, hepatitis C virus, or hepatocellular carcinoma, others may prove harmful. The lack of definitive data makes a fully informed decision impossible. Research using histological endpoints is urgently needed to determine the indications and contraindications of this extraordinary class of agents in patients with chronic liver disease