Suboptimal reliability of FIB-4 and NAFLD-fibrosis scores for staging of liver fibrosis in general population.

Background and Aim: The burden and incidence of liver cirrhosis are increasing worldwide. Early detection of liver fibrosis would help in early interventions and preventing the progression of fibrosis and cirrhosis. The accepted noninvasive markers for liver fibrosis staging, namely fibrosis-4 (FIB-4) and nonalcoholic fatty liver disease fibrosis score (NFS), have shown inconsistent performance for detecting the fibrosis stage. We aimed to evaluate the efficacy of FIB-4 score and NFS for the detection of liver fibrosis in the general population. Methods: From a general population referred from a single, community-based family-physician clinic, we included study participants between the ages of 45 and 65 years, with no knowledge of liver disease and no record of alcohol consumption. Liver fibrosis was evaluated by the FIB-4 score and NFS using shear wave elastography (SWE) or transient elastography (TE) measurements as a reference. Results: A total of 76 participants (aged 61.5 ± 0.37 years, 33% females) were included in the study cohort. We observed a nonsignificant correlation between liver stiffness measurement (LSM) and FIB-4 and NFS (r = 0.1, P = 0.37; r = 0.16, P = 0.15, respectively). Our results showed that only 5.2% with FIB-4 >3.25 and 9.7% with NFS >0.675 had LSM >12 kPa. The compatibility of fibrosis staging was 55% between FIB-4 score and LSM and only 18% between NFS and LSM. Conclusion: We found that FIB-4 and NFS are unreliable tools for liver fibrosis estimation in the general population. There is a need for more reliable noninvasive methods for the early detection of liver fibrosis.

Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.

Methyl-donor deficiency is a risk factor for neurodegenerative diseases. Dietary deficiency of the methyl-donors methionine and choline [methionine-choline-deficient (MCD) diet] is a well-established model of nonalcoholic steatohepatitis (NASH), yet brain metabolism has not been studied in this model. We hypothesized that supplemental betaine would protect both the liver and brain in this model and that any benefit to the brain would be due to improved liver metabolism because betaine is a methyl-donor in liver methylation but is not metabolically active in the brain. We fed male Sprague-Dawley rats a control diet, MCD diet, or betaine-supplemented MCD (MCD+B) diet for 8 wk and collected blood and tissue. As expected, betaine prevented MCD diet-induced NASH. However, contrary to our prediction, it did not appear to do so by stimulating methylation; the MCD+B diet worsened hyperhomocysteinemia and depressed liver methylation potential 8-fold compared with the MCD diet. Instead, it significantly increased the expression of genes involved in ß-oxidation: fibroblast growth factor 21 and peroxisome proliferator-activated receptor α. In contrast to that of the liver, brain methylation potential was unaffected by diet. Nevertheless, several phospholipid (PL) subclasses involved in stabilizing brain membranes were decreased by the MCD diet, and these improved modestly with betaine. The protective effect of betaine is likely due to the stimulation of ß-oxidation in liver and the effects on PL metabolism in brain.-Abu Ahmad, N., Raizman, M., Weizmann, N., Wasek, B., Arning, E., Bottiglieri, T., Tirosh, O., Troen, A. M. Betaine attenuates pathology by stimulating lipid oxidation in liver and regulating phospholipid metabolism in brain of methionine-choline-deficient rats.

l-Carnitine improves cognitive and renal functions in a rat model of chronic kidney disease.

Over the past decade, the prevalence of chronic kidney disease (CKD) has reached epidemic proportions. The search for novel pharmacological treatment for CKD has become an area of intensive clinical research. l-Carnitine, considered as the "gatekeeper" responsible for admitting long chain fatty acids into cell mitochondria. l-Carnitine synthesis and turnover are regulated mainly by the kidney and its levels inversely correlate with serum creatinine of normal subjects and CKD patients. Previous studies showed that l-carnitine administration to elderly people is improving and preserving cognitive function. As yet, there are no clinical intervention studies that investigated the effect of l-carnitine administration on cognitive impairment evidenced in CKD patients. Thus, we aimed to investigate the effects of l-carnitine treatment on renal function and on the cognitive performance in a rat model of progressive CKD. To assess the role of l-carnitine on CKD condition, we estimated the renal function and cognitive abilities in a CKD rat model. We found that all CKD animals exhibited renal function deterioration, as indicated by elevated serum creatinine, BUN, and ample histopathological abnormalities. l-Carnitine treatment of CKD rats significantly reduced serum creatinine and BUN, attenuated renal hypertrophy and decreased renal tissue damage. In addition, in the two way shuttle avoidance learning, CKD animals showed cognitive impairment which recovered by the administration of l-carnitine. We conclude that in a rat model of CKD, l-carnitine administration significantly improved cognitive and renal functions.