Current status and future trends of the global burden of MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease globally, affecting more than a third of the world's adult population. This comprehensive narrative review summarizes the global incidence and prevalence rates of MASLD and its related adverse hepatic and extrahepatic outcomes. We also discuss the substantial economic burden of MASLD on healthcare systems, thus further highlighting the urgent need for global efforts to tackle this common and burdensome liver condition. We emphasize the clinical relevance of early interventions and a holistic approach that includes public health strategies to reduce the global impact of MASLD.

A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most predominant chronic liver disease worldwide. Effect of coffee on NAFLD risk and its potential dose-response patterns were explored in the study. DESIGN: PubMed, Web of Science, MEDLINE, Cochrane and Embase were searched up to 10 April 2018. We performed pair-wise meta-analysis of <1 cup per day vs. 1-2 cups per days or >2 cups per day to pool the relative risks (RRs) and corresponding 95% confidence intervals (CIs). And dose-response analysis was used to estimate relationship of NAFLD occurrence with coffee intake. RESULTS: Seven articles were included with 4825 cases and 49,616 non-cases. Compared with <1 cup, 1-2 cups or >2 cups of coffee consumption per day were not significantly associated with NAFLD occurrence, and RR were 0.97 (95% CI: 0.85-1.11) and 0.88 (95%CI: 0.72-1.06). However, the summary RR of the highest versus lowest coffee consumption was 0.94 (95% CI: 0.92-0.97). Dose-response meta-analysis presented a non-linearity curve relationship of coffee and NAFLD occurrence while coffee consumption >3 cups per day reduced NAFLD significantly. CONCLUSION: Coffee intake level more than 3 cups was observed lower risk of NAFLD than <2 cups per day. Although the risk of NAFLD was inversely associated with coffee consumption, while relevance may not be very close and more observational studies would be needed to verify the relationship of coffee and NAFLD.

Thrombin generation and platelet activation in cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy - A prospective cohort study.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC), indicated for patients with peritoneal metastases from digestive or gynecological malignancies alike, demonstrates a considerable impact on hemostatic metabolism, both on platelet and on coagulation level. The potential hemostatic interference in CRS and HIPEC is phase dependent. The hypothesis of this prospective cohort study is that the procedure exposed an increased thrombotic risk, resulting in a faster and increased thrombin generation and hyper platelet function. METHODS: This study explores the combined use of ROTEM (rotational thromboelastometry), PACT (platelet activation test) and CAT (thrombin generation test) assays during CRS and HIPEC with a follow-up of 7 days postoperative in 27 patients with confirmed histological diagnosis of peritoneal disease. RESULTS: Platelet reactivity (relative to before incision values) to CRP (collagen-related peptide) (p value 0.02) and TRAP (thrombin receptor activator peptide) (p value 0.048) seems to be slightly reduced during CRS and HIPEC with regard to αIIbß3 activation, while P-selectin expression is not affected. During surgery, CAT demonstrates that, the LT (lagtime) (p value 0.0003) and TTP (time-to-thrombin peak) values (p value 0.002) decrease while and the TP (thrombin peak) (p value 0.004) and ETP (endogenous thrombin potential) (p value 0.02) increase. Subsequently, after surgery, the LT and TTP increase and ETP and TP decrease in time. ROTEM EXTEM (extrinsic) MCF (maximum clot firmness) (p value 0.005), INTEM (intrinsic) MCF (p value 0.003) and FIBTEM (fibrinogen) MCF (p value <0.001) decreased during CRS. At day 7 INTEM and FIBTEM MCF values (p values of 0.004 and <0.001) were significantly higher than before surgery. No considerable changes in platelet count and hemoglobin concentration and absence of leukopenia are noticed. CONCLUSION: This approach detects changes in coagulation much earlier than noticed by standard coagulation tests.

Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway.

BACKGROUND AND AIM: Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. METHODS: C57BL/6 mice were employed and divided into three groups - control group (n=8), autoimmune hepatitis group (n=12) and autoimmune hepatitis with treatment of sodium butyrate group (n=12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. RESULTS: The findings revealed that S100/Freund's complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines - interleukin-6 and tumor necrosis factor-a. CONCLUSIONS: Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund's complete adjuvant induced autoimmune hepatitis.

Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced hepatic steatosis and injury.

Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and lipid metabolism in the liver. We sought to determine the role of FGF21 in hepatic steatosis in mice exposed to chronic alcohol treatment and to discern underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were divided into groups that were fed either the Lieber DeCarli diet containing 5% alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12 cells were incubated with metformin or rhFGF21. Hepatic genes and the products involved in in situ lipogenesis and fatty acid ß-oxidation were analyzed. Alcohol exposure increased circulating levels and hepatic expression of FGF21. FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury, which was associated with increased activation of genes involved in lipogenesis mediated by SREBP1c and decreased expression of genes involved in fatty acid ß-oxidation mediated by PGC1α. rhFGF21 administration reduced alcohol-induced hepatic steatosis and inflammation in WT mice. These results reveal that alcohol-induced FGF21 expression is a hepatic adaptive response to lipid dysregulation. Targeting FGF21 signaling could be a novel treatment approach for alcoholic steatohepatitis.

Traditional Chinese medicines benefit to nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Evidences from randomized controlled trials (RCTs) for the efficiency of traditional Chinese medicine (TCM) on the treatment of nonalcoholic fatty liver disease (NAFLD) are conflicting. Here we conducted a systematic review and meta-analysis of RCTs to evaluate the efficiency and safety of TCM in the treatment of NAFLD. Studies were searched on PubMed and China National Knowledge Infrastructure from January 1995 to June 2010. RCTs comparing either TCM formulations alone or in combination with placebo, ursodeoxycholic acid, insulin sensitizers, lipid-lowering drugs, or antioxidants were included. The category of most usually used herbs in the treatment of NAFLD was also calculated. Five thousand nine hundred and four patients from 62 RCTs were included for meta-analysis and 25,661 patients from 419 clinical studies were for TCM formulation analysis. Comparing with western medicines mentioned above, TCM had a better effect on the normalization of alanine aminotransferase and disappearance of radiological steatosis in the treatment of NAFLD. Furthermore, 246 kinds of Chinese herbs were included in our present study, with an average of 10 herbs (range 1-31) in each formulation. Hawthorn Fruit (321 times in 17,670 patients) was the most often used herb in the treatment of NAFLD. In conclusion, TCM is of modest benefit to the treatment of NAFLD.

Traditional Chinese medicine plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma.

OBJECTIVES: To compare the efficacy and safety of Traditional Chinese Medicine (TCM) plus transcatheter arterial chemoembolization (TACE) with that of TACE alone (therapy I versus therapy II, respectively) in treating unresectable hepatocellular carcinoma (UHCC) through a meta-analysis of all available randomized controlled trials. METHODS: Literature retrieval was conducted using the Cochrane Library, MEDLINE, EMBASE, CBMdisk, and CNKI in any language. Meta-analysis was performed on the results of homogeneous studies. Analyses subdivided by TACE frequency (subgroup A, <3 times; subgroup B, > or =3 times) were also performed, but were not done for both therapy I and therapy II. RESULTS: Based on our search criteria, we found 37 trials involving 2653 patients. Our results showed that therapy I, compared with therapy II, improved patient survival, quality of life, alleviation of symptoms, and tumor response, and was thus more therapeutically beneficial. Further analysis showed that subgroup A proved to be better for patients' survival and alleviation of symptoms, while the two subgroups were similar in improved tumor response. No serious adverse events were reported. CONCLUSIONS: Therapy I benefited patients with UHCC. Subgroup A improved the survival of patients and the amelioration of symptoms more than subgroup B. As in some trials, there were flaws in the methodological quality, and the data therefore have a risk of bias and of being insufficient for determining the effects of therapy I and subgroup A. Hence, further large-scale trials are warranted.