Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.

Probiotics might reduce gut-derived microbial lipopolysaccharide (LPS) by restoring bowel flora in patients with alcoholic hepatitis (AH). We evaluated the therapeutic effects of probiotics in patients with AH. Between September 2010 and April 2012, 117 patients (probiotics 60 and placebo 57) were prospectively randomized to receive the 7 days of cultured Lactobacillus subtilis/Streptococcus faecium (1500 mg/day) or placebo. All patients were hospitalized and were not permitted to consume alcohol for the 7 days of the study. Liver function test, proinflammatory cytokines, LPS, and colony-forming units by stool culture were examined and compared after therapy. In both groups, the mean levels of aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin, and prothrombin time were significantly improved after 7 days of abstinence. In the probiotics group (baseline and after), albumin (3.5 ± 0.7 and 3.7 ± 0.6 g/dl, P=0.038) and tumor necrosis factor-α (121 ± 244 and 71 ± 123 pg/ml, P=0.047) showed differences. In addition, the number of colony-forming units of Escherichia coli was significantly reduced (435 ± 287 and 168 ± 210, P=0.002). In the placebo group, the level of LPS (1.7 ± 2.8 and 2.0 ± 2.7 EU/ml) was significantly increased. In the intergroup comparison, significant differences in the levels of tumor necrosis factor-α (P=0.042) and LPS (P=0.028) were observed between the groups. Immediate abstinence is the most important treatment for patients with AH. In addition, 7 days of oral supplementation with cultured L. subtilis/S. faecium was associated with restoration of bowel flora and improvement of LPS in patients with AH.

Background: Sarcopenia has been reported as a prognostic factor. We evaluated the impact of sarcopenia to the conventional prognostic factors [Model for End‐Stage Liver Disease (MELD) score, Child–Turcotte–Pugh (CTP) score, hepatic venous pressure gradient (HVPG)] in cirrhosis.Methods: Overall, 452 patients with cirrhosis were stratified by MELD score (low < 15, high ≥ 15), CTP class, and HVPG [non‐clinically significant portal hypertension (CSPH), 6–9 mmHg; CSPH, 10–19 mmHg; extremely severe PH, ≥20 mmHg]. L3 skeletal muscle index as marker of sarcopenia was subdivided into quartiles (47.01–52.25–58.22 cm²/m²).Results: Among the patients, 42% (190/452) presented with sarcopenia. During a median follow‐up period of 21.2 months, sarcopenia was associated with mortality (adjusted hazard ratio = 2.253, P < 0.001) and specifically with compensated and early decompensated stages of cirrhosis, but not with advanced decompensated stages; low (P < 0.001) and high (P = 0.095) MELD scores; CTP classes A (P = 0.034), B (P < 0.001), and C (P = 0.205); and non‐CSPH (P = 0.018), CSPH (P < 0.001), and extremely severe PH (P = 0.846). In quartiles of sarcopenia, MELD score, CTP class, and HVPG were independent predictors of mortality in non‐sarcopenia, but not in severe sarcopenia (MELD, P = 0.182; CTP, P = 0.187; HVPG, P = 0.077).Conclusions: Sarcopenia is associated with mortality in compensated and early decompensated cirrhosis, and existing conventional prognostic factors had limited value in severe sarcopenia. Therefore, incorporating sarcopenia in the conventional prognostic factors had added value, particularly in compensated and early decompensated cirrhosis. Subclassification of prognostic factors according to sarcopenia may help to better assess the prognosis of cirrhosis.

Mechanisms associated with the progression of non-alcoholic fatty liver disease (NAFLD) remain unclear. We attempted to identify the pattern of altered gene expression at different time points in a high fat diet (HFD)-induced NAFLD mouse model. The early up-regulated genes are mainly involved in the innate immune responses, while the late up-regulated genes represent the inflammation processes. Although recent studies have shown that microRNAs play important roles in hepatic metabolic functions, the pivotal role of microRNAs in the progression of NAFLD is not fully understood. We investigated the functions of miR-451, which was identified as a target gene in the inflammatory process in NAFLD. miR-451 expression was significantly decreased in the palmitate (PA)-exposed HepG2 cells and in liver tissues of HFD-induced non-alcoholic steatohepatitis (NASH) mice. Its decreased expressions were also observed in liver specimens of NASH patients. In vitro analysis of the effect of miR-451 on proinflammatory cytokine provided evidence for negative regulation of PA-induced interleukin (IL)-8 and tumor necrosis factor-alpha (TNF-α) production. Furthermore, miR-451 over-expression inhibited translocation of the PA-induced NF-κB p65 subunit into the nucleus. Our result showed that Cab39 is a direct target of miRNA-451 in steatotic cells. Further study showed that AMPK activated through Cab39 inhibits NF-κB transactivation induced in steatotic HepG2 cells. miR-451 over-expression in steatotic cells significantly suppressed PA-induced inflammatory cytokine. These results provide new insights into the negative regulation of miR-451 in fatty acid-induced inflammation via the AMPK/AKT pathway and demonstrate potential therapeutic applications for miR-451 in preventing the progression from simple steatosis to severely advanced liver disease.