Alcohol consumption in China has substantially increased over the last 3 decades and the number of patients with alcoholic liver disease (ALD) is rising at an alarming rate. However, accurate and ...representative data on time trends in its hospitalization rates are not available. The aim of this study is to assess the current status and burden of ALD in China by analyzing the data from a large tertiary referral hospital, Beijing 302 Hospital.Data were retrospectively recorded from patients diagnosed as ALD in Beijing 302 Hospital from 2002 to 2013. The disease spectrum and biochemical parameters of each patient were collected.The patients with ALD accounted for 3.93% (7422) of all patients (188,902) with liver diseases between 2002 and 2013. The number of patients hospitalized with ALD increased from 110 in 2002 to 1672 in 2013. The ratio of patients hospitalized with ALD to all patients hospitalized with liver diseases was rising almost continuously and increased from 1.68% in 2002 to 4.59% in 2013. Most patients with ALD were male. Age distribution of ALD hospitalization showed that the highest rate was in 40- to 49-year-old group in subjects. Notably, the annual proportion of severe alcoholic hepatitis (SAH) increased 2.43 times from 2002 to 2013. We found the highest levels of mean corpuscular volume, the aspartate aminotransferase/alanine aminotransferase ratio, total bilirubin, international normalized ratio, and alkaline phosphatase in SAH patients, while serum levels of hemoglobin, albumin, and cholinesterase were significantly decreased in SAH group. Among these ALD, the SAH patient population has the worst prognosis. Alcoholic cirrhosis (ALC) is the most common ALD, and annual admissions for ALC increased significantly during the analyzed period.The number of hospitalized patients with ALD and the annual hospitalization rate of ALD were increasing continuously in Beijing 302 Hospital from 2002 to 2013. More attention should be paid to develop population-based effective strategy to control ALD.
Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases,resulting in fatty liver,alcoholic hepatitis,fibrosis/cirrhosis,and hepatocellular ...carcinoma(HCC).Although the pathogenesis of alcoholic liver disease(ALD)involves complex and still unclear biological processes,the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species(ROS)play a preeminent role in the clinical and pathological spectrum of ALD.Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes,leading to fat accumulation,fibrogenesis and activation of innate and adaptive immunity.Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis,decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase(AMPK)-dependent mechanism.AMPK activation by ROS modulates autophagy,which has an important role in removing lipid droplets.Acetaldehyde and aldehydes generated from lipid peroxidation induce collagensynthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells(HSCs).Furthermore,activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD.Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide(LPS)translocation by disrupting tight and adherent junctions in human colonic mucosa.Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration.In addition,alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver.Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells,and consequently alters allogenic antigen presentation.Finally,acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis,and they interfere with methylation,synthesis and repair of DNA,thereby increasing HCC susceptibility.
Background: Alcohol is a common cause of hepatic liver injury with steatosis and fibrosis. Cannabinoid receptors (CB) modulate steatosis, inflammation and fibrogenesis. To investigate the differences ...between CB1 and CB2 in the hepatic response to chronic alcohol intake, we examined CB knockout mice (CB1−/−, CB2−/−).
Methods: Eight‐ to 10‐week‐old CB1−/−, CB2−/− and wild‐type mice received 16% ethanol for 35 weeks. Animals receiving water served as controls. We analysed triglyceride and hydroxyproline contents in liver homogenates. mRNA levels of CBs, pro‐inflammatory cytokines tumour necrosis factor (TNF)‐α, monocyte chemotactic protein (MCP)‐1, interleukin (IL)‐1β and profibrotic factors α‐smooth muscle actin (α‐SMA), procollagen‐Ia, platelet‐derived growth factor β receptor (PDGFβ‐R) were analysed by reverse transcription‐polymerase chain reaction (RT‐PCR). Histology (hemalaun and eosin, oil‐red O, CD3, CD45R, CD45, F4/80, Sirius red) characterized hepatic steatosis, inflammation and fibrosis. Activation of lipogenic pathways, activation and proliferation of hepatic stellate cell (HSC) were assessed by western blot fatty acid synthase (FAS), sterol regulatory element binding protein 1c (SREBP‐1c), α‐SMA, proliferating cell nuclear antigen (PCNA), cathepsin D.
Results: Hepatic mRNA levels of the respective CBs were increased in wild‐type animals and in CB1−/− mice after ethanol intake. Ethanol intake in CB2−/− mice induced much higher steatosis (SREBP‐1c mediated) and inflammation (B‐cell predominant infiltrates) compared with wild‐type animals and CB1−/− mice. HSC activation and collagen production were increased in all groups after forced ethanol intake, being most pronounced in CB2−/− mice and least pronounced in CB1−/− mice.
Discussion: The fact that CB2 receptor knockout mice exhibited the most pronounced liver damage after ethanol challenge indicates a protective role of CB2 receptor expression in chronic ethanol intake. By contrast, in CB1 knockouts, the effect of ethanol was attenuated, suggesting aggravation of fibrogenesis and SREBP‐1c‐mediated steatosis via CB1 receptor expression after ethanol intake.
Background & Aims
Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended in clinical guidelines. In real‐life management, surveillance rates below 20% have been ...reported from the United States. We aimed to determine the use of HCC‐surveillance in patients diagnosed with HCC in a European setting, and to identify the reasons for surveillance failures.
Methods
Age, gender, tumour characteristics, BCLC classification, Child–Pugh stage, pre‐existing liver disease, treatment, survival, frequency of HCC surveillance and reasons for surveillance failures were retrospectively determined in 616 patients diagnosed with HCC at Karolinska University Hospital 2005‐2012.
Results
Hepatitis C, alcoholic liver disease and non‐alcoholic fatty liver disease (NAFLD) were the most common diagnoses. The proportion of HCC patients diagnosed through surveillance was 22%. In 35% of cases, surveillance was missed due to doctor′s failure to order surveillance or to diagnose the underlying liver disease. Diagnosis of NAFLD or alcoholic liver disease increased the risk of not receiving surveillance more than two‐fold. Undiagnosed liver disease was most common in NAFLD patients. Patients who underwent surveillance had smaller tumours, more frequently received curative treatment, and had better survival compared to those in whom surveillance was indicated but missed.
Conclusion
In a European setting, only 22% of HCCs were diagnosed by surveillance, and in more than one‐third of cases, surveillance was indicated but missed. NAFLD and alcoholic liver disease were associated with deficient surveillance. Survival was significantly better in patients who underwent surveillance compared with those in whom surveillance was missed although indicated.
Aguardente,chicha,pulque,vino-no matter whether it's distilled or fermented, alcohol either brings people together or pulls them apart.Alcohol in Latin Americais a sweeping examination of the deep ...reasons why. This book takes an in-depth look at the social and cultural history of alcohol and its connection to larger processes in Latin America. Using a painting depicting a tavern as a metaphor, the authors explore the disparate groups and individuals imbibing as an introduction to their study. In so doing, they reveal how alcohol production, consumption, and regulation have been intertwined with the history of Latin America since the pre-Columbian era.Alcohol in Latin Americais the first interdisciplinary study to examine the historic role of alcohol across Latin America and over a broad time span. Six locations-the Andean region, Argentina, Brazil, Chile, Guatemala, and Mexico-are seen through the disciplines of anthropology, archaeology, art history, ethnohistory, history, and literature. Organized chronologically beginning with the colonial era, it features five chapters on Mesoamerica and five on South America, each focusing on various aspects of a dozen different kinds of beverages.An in-depth look at how alcohol use in Latin America can serve as a lens through which race, class, gender, and state-building, among other topics, can be better understood,Alcohol in Latin Americashows the historic influence of alcohol production and consumption in the region and how it is intimately connected to the larger forces of history.
The perception of wine flavour and aroma is the result of several interactions between a large number of chemical compounds and sensory receptors. Compounds show synergistic (one compound enhances ...the perception of another) and antagonistic (one compound suppresses the perception of another) interactions. The chemical profile of a wine is derived from the entire process, starting from the grapes and continuing through to bottled ageing. At the moment, wine makers are limited as to the range of yeasts that are able to impart some specific aromatic characteristic to a wine, and research focuses on issues such as adjusting the levels of flavour and aroma compounds, in particular esters and alcohols, producing enzymes that will release additional volatile compounds from the grapes, and reducing the amount of alcohol to levels that allow a better perception and release of aroma and flavour compounds. New yeast strains are continuously being developed using traditional breeding techniques, leading to different flavour and aroma profiles in wine. The potential flavour volatiles of wine include, but are not limited, to the following: i) varietal; ii) pre-fermentative volatiles formed by the yeast during fermentation; iii) formed by the yeast directly related to alcoholic fermentation; iv) related to amino acid metabolism; v) formed during malolactic fermentation; vi) formed during ageing (reductive and oxidative pathway) and maturation. This Special Issue, “Flavour Volatiles of Wine”, aims to reach a mechanistic understanding of these pathways, with a focus on the reactions involved in the formation or degradation of key wine odorants, and of the technological factors involved during the winemaking process. It consists of six peer-reviewed papers that cover novel aspects of volatile compounds research in the wine sector.
Non-alcoholic fatty liver disease(NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and ...clinically different nonalcoholic entities; fatty liver(NAFL, steatosis hepatis)and steatohepatitis(NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer.NAFL increasingly affects children(paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus(T2DM),insulin resistance(IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2 DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.
Background & Aims There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and ...created a histologic scoring system to predict short-term (90-day) mortality. Methods We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. Results The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0–3 points), moderate (4–5 points), or high (6–9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71–0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. Conclusions We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.
Alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) represent pathological conditions that include many distinct stages, potentially leading to the final stage of ...cirrhotic liver. To date, liver transplantation is the sole successful treatment with concomitant limitations related to donor organ shortage and the need of life-long immunosuppressive therapy. Recently, cell-based therapies for ALD and NAFLD have been proposed with mesenchymal stem/stromal cells (MSCs) as promising effectors. MSC therapeutic applications offer hepatoprotection, regulation of the inflammatory process and angiogenesis particularly in ALD and NAFLD pre-clinical disease models. Recent studies suggested that hepatospecific MSC-based therapies could benefit liver diseases by restoring liver function and decreasing inflammation and fibrosis. Similarly to solid-organ transplantation, limitations in MSC approaches include donor availability exacerbated by high number of cells and cell trapping into lungs. Herein, based on recent advances, we discuss the use of MSCs as a therapeutic approach for ALD and NAFLD and we provide the available information for the establishment of a framework toward a potential clinical application.
Alcohol and high-fat diet are two major risk factors responsible for metabolic diseases, which are manifested as steatohepatitis and liver cancer in the liver, and chronic pancreatitis and pancreatic ...adenocarcinoma (PDAC) in the pancreas. These metabolic diseases are becoming increasingly prevalent around the globe, and more importantly, their two major etiologies commonly coexist to precipitate the disease processes. To highlight the importance of these metabolic diseases, Japanese Society of Gastroenterology (JSGE) and National Institute on Alcoholism and Alcohol Abuse of National Institute of Health cosponsored the JSGE’s 7th International Forum jointly held with the 12th International Symposium on ALPD and Cirrhosis. Toward the main theme of “Frontiers in ASH, NASH, NBNC-HCC and PDAC”, this platform showcased presentations by 12 invited international and Japanese speakers on brain–gut–liver interactions, emerging mechanisms of ASH and NASH, metabolic reprogramming, and new therapeutic targets for cirrhosis, HCC, and PDAC. This editorial discusses the most recent data on global statistics on how alcohol and obesity impact health and longevity as a prelude to a brief summary of the symposium presentations and discussions, primarily focusing on the first two session themes.
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