The fibrogenic process and the unleashing of acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by a rapid deterioration of previously well-compensated chronic liver diseases. One of the main obstacles in ACLF is the lack of knowledge of the pathogenesis and specific broad-spectrum treatments. An excessive systemic inflammatory response has been proposed to explain the pathogenesis of ACLF; this hypothesis involves stellate cells, which are implicated in many liver homeostatic functions that include vitamin A storage, regulation of sinusoidal blood flow, local inflammation, maintenance of the hepatocyte phenotype and extracellular matrix remodeling. However, when there is damage to the liver, these cells are the main target of the inflammatory stimulus, as a result, the secretion of the extracellular matrix is altered. Activated hepatic stellate cells raise the survival of neutrophils by the stimulation of granulocytes colonies and macrophages, which exacerbates liver inflammation and promotes damage to hepatocytes. Elevation of pathogen-associated molecular patterns is related to liver damage by different pathophysiological mechanisms of decompensation, showing ballooning degeneration and cell death with a predominance of cholestatic infection. Moreover, patients with ACLF present a marked elevation of C-reactive protein together with an elevation of the leukocyte count. Chronic liver disease is a complex pathological state with a heterogeneous pathophysiology in which genetic factors of the host and external triggers interact and culminate in hepatic insufficiency. The better understanding of such interactions should lead to a better comprehension of the disease and to the discovery of new treatment targets that will make acute decompensations preventable and even decrease mortality.

Erratum: A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa.

This corrects the article DOI: 10.1038/sdata.2017.63.

A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa.

Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount-results that are comparable to the other datasets.

IL28B polymorphisms predict the response to chronic hepatitis C virus infection treatment in a Mexican population.

INTRODUCTION: The treatment of hepatitis C virus (HCV) genotype 1 with ribavirin (RBV) and pegylated-interferon alpha (peg-IFNα) provides a low-level sustained virological response (SVR). Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene have been identified as SVR predictors. Our aim was to establish an association between three IL28B SNPs (rs8099917, rs12979860, and rs8103142) and the peg-IFNα/RBV treatment response in a Mexican population cohort with chronic HCV. MATERIAL AND METHODS: A cohort study was performed with 83 chronic HCV patients at the Fundación Clínica Médica Sur in Mexico City. All patients were treated with peg-IFNα and RBV. The data were analyzed by logistic regression, with adjustments for age, gender, and viral genotype, to determine any associations between the SNPs and the treatment response. RESULTS: In the study group of 83 HCV patients, the main genotype was genotype 1 (70%, n = 58) and the overall SVR was 32.53% (n = 27). In the HCV-1 group, SVR was 27%, whereas SVR was 44% in the HCV-2 group. We found an association between rs12979860 CC and SVR in a codominant model (OR = 4.83, 95% CI = 1.12-20.8, P = 0.033). There was no statistically significant association between SVR and rs8099917 or rs8103142. rs12979860 polymorphisms of CC, CT, and TT, were present in 24%, 41%, and 35% of patients, respectively. CONCLUSION: A Mexican HCV-1-infected population treated with peg-IFNα and RVB had a low SVR rate, which was associated with the SNP rs12979860 (CC). SVR was not associated with the SNPs rs8099917 or rs8103142.

[Prevalence of NAFLD and metabolic syndrome in asymtomatics subjects]. / Prevalencia de higado graso no alcohólico y síndrome metabólico en población asintomática.

UNLABELLED: Non Alcoholic Fatty Liver Disease (NAFLD) is a frequent entity to progress to liver fibrosis and cirrhosis, and it is associated with several metabolic disturbances. The insulin resistance is often considered the link between metabolic disturbances and NAFLD. The aim of this study was to determine the prevalence of NAFLD in healthy population and the prevalence of metabolic syndrome in this patients. The associated factors to develop liver cirrhosis were identified. METHODS: 2,503 records were reviewed and the presence of steatosis was determined by ultrasonography. A clinical and biochemical examination was carried out and the metabolic criteria were defined according to the ATP III. RESULTS: 427 (17.05%) patients with NAFLD were detected. 359 (14.3%) with NAFLD were included, the mean age was 46.26 +/- 9.85 years. Overweight was present in 46.79% and obesity in 36.49% of patients. The association between DM, HAS, high levels of cholesterol and triglicerides was found in 3.6, 13.6, 63 and 43%, respectively. Steatohepatitis was found in in 34% of patients high levels of AST. AST/ALT ratio > 1 was detected in 76 patients (21.16%). According to the ATP III criteria, the prevalence of metabolic syndrome in patients with NAFLD was 22.8%. CONCLUSIONS: The frequency of NAFLD and metabolic syndrome in this study was 14.3% and 22.8%, respectively. Overweight, obesity and dyslipidemia were the main associated factors to NAFLD.