In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including "lean NAFLD" has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.

Nonalcoholic fatty liver disease: Evolving paradigms

Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents

Uric acid (UA), scavenger of oxygen radical, is a very important antioxidant that help maintains the stability of blood pressure and antioxidant stress. However, an abnormal UA concentration may be connected with many diseases: a higher UA concentration, comings from improper lifestyle such as purine excessive intake and excessive drinking, may reveal hyperuricemia, gout and some cardiovascular diseases; meanwhile, some genetic diseases can result in a low level UA relatively for a long time. Therefore, to develop a rapid and accurate detection method of UA is urgent and important. Recently many detection methods have been developed to measure the level of UA in human serum and urine sample even saliva and nails and tears. This review outlines the importance of UA detection and the history of the development of UA detection methods. UA detection include spectral (ultraviolet absorption, fluorescence), electrochemical (voltammetry, electrochemiluminescence, surface plasmon resonance), chromatography (liquid and gas phase), capillary electrophoresis and isotope dilution mass spectrometry, etc. Most of the above detection methods contain both enzymatic and nonenzymatic strategies. The materials used in mentioned methods above tend to be diversified, hence an overview of materials used in UA detection are also reported.

Recent Progress on Uric Acid Detection: A Review

Herbal drug discovery for the treatment of nonalcoholic fatty liver disease

Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.

/pdf/prevalence-and-profile-of-nonalcoholic-fatty-liver-disease-122lbuvqw8.pdf

Prevalence and Profile of Nonalcoholic Fatty Liver Disease in Lean Adults: Systematic Review and Meta-Analysis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/hepr.12734

Relationship of serum uric acid level with non-alcoholic fatty liver disease and its inflammation progression in non-obese adults.

The aim of the present study was to explore the protective effects of Berberine (BBR) against non-alcoholic steatohepatitis (NASH). Male 4-week-old C57BL/6J Apolipoprotein E-deficient (ApoE-/-) mice were divided into the following three groups, which were given different diets: Normal chow diet (SC group); high-fat high-cholesterol diet (HFHC group); and HFHC diet supplemented with BBR (BBR group). Serum biochemical indicators of hepatic function and histological liver tissue changes were evaluated. The expression of neutrophil elastase (NE) and genes involved in the inflammatory response was measured. ApoE-/- mice fed a HFHC diet for 12 weeks developed NASH, characterized by steatosis and liver inflammation. Body weight, and serum triglyceride and cholesterol levels were markedly reduced by BBR. BBR supplementation significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels in mice with HFHC diet-induced NASH, and significantly downregulated hepatic expression and activity of NE, whereas α1-antitrypsin (α1-AT) expression was significantly recovered by BBR (all P<0.05 vs. the HFHC group). Furthermore, treatment with BBR induced a significant reduction in the expression of key genes, including phospoinositide 3-kinase, nuclear factor-κB and interleukin-8, in the C-X-C chemokine receptor type 4 (CXCR4) signaling pathway (all P<0.05 vs. the HFHC group). These results suggest that BBR alleviates NASH in ApoE-/- mice fed a HFHC diet. Restoration of the balance of NE and α1-AT levels, which in turn facilitate the inhibition of the CXCR4 signaling pathways, may be involved in the hepatoprotective effect of BBR. These results indicate that BBR may be a candidate therapeutic agent for the treatment of NASH.

/pdf/berberine-ameliorates-non-alcoholic-steatohepatitis-in-apoe-58dbocgfzq.pdf

Jing Liu

Papers

Relationship of serum uric acid level with non-alcoholic fatty liver disease and its inflammation progression in non-obese adults.

Berberine ameliorates non-alcoholic steatohepatitis in ApoE-/- mice.