Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: firstname.lastname@example.org.
High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease.
We used data on alcohol consumption at conscription to military service from 43,296 men (18-20?years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied.
During a mean follow-up of 37.8?years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day.
Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39?years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised.
We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40?years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more.
There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.
Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.
Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2?±?12.3, HFHS 153.9?±?19.3, BBE 114.4?±?14.3, CLE 82.5?±?13.0, CRE 152.3?±?24.4, ABE 90.6?±?18.0, LGE 95.4?±?10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l?×?min]: chow 14.3?±?1.4, HFHS 31.4?±?3.1, BBE 27.2?±?4.0, CLE 17.7?±?2.2, CRE 32.6?±?6.3, ABE 22.7?±?18.0, LGE 23.9?±?2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.
Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.
All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).
The Norwegian Armed Forces' shooting ranges contain contamination by metals such as lead (Pb) and copper (Cu) and are often used as grazing pastures for livestock. To determine whether the sheep were at risk from grazing at a shooting range in Nord-Trøndelag (the Leksdalen shooting field), a study was conducted wherein the aim was to determine the amount of soil the sheep were eating, the accumulation of Cu and Pb in the livers of lambs grazing on the shooting ranges, and the accumulation of Pb and Cu in the grass. The grazing behavior of the sheep was mapped using GPS tracking and wildlife cameras. Soil, grass, feces, and liver samples were collected. All the samples were analyzed for Pb, Cu, and molybdenum (Mo), and soil and feces were also analyzed for titanium (Ti). Mean concentrations in grass, soil, feces, and liver was 41-7189, 1.3-29, 4-5, and 0.3 mg/kg Pb, respectively, and 42-580, 4.2-11.9, 19-23, and 273 mg/kg Cu, respectively. The soil ingestion rate was calculated using Ti in feces and soil. From these results, the theoretical dose of Cu and Pb ingested by grazing sheep was calculated. The soil ingestion rate was found to be 0.1-0.4%, significantly lower than the soil ingestion rate of 5-30% usually used for sheep. Little or no accumulation of Cu and Pb in the grass was found. There was no difference between the metal concentrations in the washed and unwashed grass. According to the calculated dose, the sheep were at little or no risk of acute or chronic Pb and Cu poisoning from grazing on the Leksdalen shooting range. The analysis of liver samples showed that lambs grazing on the shooting range did not have higher levels of Cu or Pb than lambs grazing elsewhere. None of the lambs had concentrations of Cu or Pb in their livers indicating poisoning.
Fatty liver disease (FLD) has been identified as constituting cardiometabolic risk. However, evidence on the association of fatty liver index (FLI) with cardiovascular disease (CVD) is largely cross-sectional, with limited evidence on the predictability of incident CVD, and specifically, acute myocardial infarction (AMI). Therefore, we aimed to investigate the prospective associations between fatty liver as estimated by FLI and incident CVD, and specifically AMI, in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort.
Our patients were 1205 middle-aged men free of CVD at baseline. The associations of baseline FLI with incident CVD and incident AMI were analyzed using multivariable-adjusted Cox regression models.
During a median follow-up of 17 years, a total of 690 incident cases of CVD and 269 cases of AMI were recorded through Finnish registries. For incident CVD, for the high (FLI=60) versus the low (=30) FLI category, the hazard ratio (HR) was 1.77 [95% confidence interval (CI): 1.46-2.14] in the minimally adjusted model. With increasing adjustment, the association was attenuated progressively. In the most adjusted model, the HR was 1.41 (95% CI: 1.10-1.79). For incident AMI, for the high FLI category, the HR was 1.65 (95% CI: 1.22-2.23) in the minimally adjusted model, but in most comprehensive models when we included metabolic factors, the HR was not significant (HR=1.136, 95% CI: 0.777-1.662).
FLI can predict incident CVD. However, the predictability of AMI using FLI is subject to interactions of metabolic factors. Individuals with FLI in the moderate to high category should be evaluated and monitored for subclinical or overt cardiovascular (including coronary) disease.
Binge drinking or heavy episodic drinking is increasingly prevalent, but the health effects are incompletely understood. We investigated whether binge drinking increases the risk for liver disease above and beyond the risk due to average alcohol consumption.
6366 subjects without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analysed for liver-related admissions, mortality and liver cancer. Binge drinking (=5 drinks per occasion, standard drink 12 g ethanol) was categorised as weekly, monthly, or as less often or none. Multiple confounders were considered.
Eighty-four subjects developed decompensated liver disease. Binge drinking frequency showed a direct association with liver-disease risk after adjustment for average daily alcohol intake and age. After adjustment, the hazard ratios (HRs) for weekly and monthly binge drinking were 3.45 (P=.001) and 2.26 (P=.007) and were higher after excluding regular heavy drinkers. The HR for weekly binging was 6.82 (P=.02) in women; 2.34 (P=.03) in men; and 4.29 (P=.001) in subjects with the metabolic syndrome. Weekly binge drinking and the metabolic syndrome produced supra-additive increases in the risk of decompensated liver disease. Weekly, and to a lesser extent monthly, binging retained significance in sequential multivariate models that additionally adjusted for beverage preference and lifestyle, metabolic, and socioeconomic factors.
Binge drinking is associated with an increased risk for liver disease independently of average alcohol intake and confounders. The rising prevalence of binge drinking and the metabolic syndrome is particularly concerning.
MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n?=?871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC)?=?1.55, p?=?1.36?*?10-14 and FC?=?1.25, p?=?4.86?*?10-4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR?=?2.07, p?=?1.29?*?10-8 and OR?=?1.41, p?=?0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r?=?-0.143, p?=?1.00?*?10-4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.
Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults.
Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver.
Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002).
Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes.
The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.
Chronic arsenicosis and cadmium exposure in wild snowshoe hares (Lepus americanus) breeding near Yellowknife, Northwest Territories (Canada), part 1: Evaluation of oxidative stress, antioxidant activities and hepatic damage.
Previous gold mining activities and arsenopyrite ore roasting activities at the Giant mine site (1948 to 2004) resulted in the release of high amounts of arsenic and trace metals into the terrestrial and aquatic ecosystems of Yellowknife, Northwest Territories, Canada. While elevated levels of arsenic has been consistently reported in surface soils and vegetation near the vicinity of the Giant mine area and in surrounding locations, systematic studies evaluating the overall health status of terrestrial small mammals endemic to the area are lacking. The purpose of this present study was to evaluate and comparatively assess the biochemical responses and histopathological effects induced by chronic arsenic and cadmium exposure in wild snowshoe hares breeding near the city of Yellowknife, specifically around the vicinity of the abandoned Giant mine site and in reference locations. Analysis included measurement of total arsenic and cadmium concentration in nails, livers, kidneys, bones, stomach content of hares, in addition to histopathological evaluation of hepatic and ocular lesions. Biochemical responses were determined through measurement of lipid peroxidation levels and antioxidant enzymes activities (catalase, superoxide dismutase, glutathione peroxidase, and glutathione disulfide). The results revealed that arsenic concentration was 17.8 to 48.9 times higher in the stomach content, and in the range of 4 to 23 times elevated in the nails of hares from the mine area compared to the reference location. Arsenic and cadmium levels were also noted to be increased in the bones, renal and hepatic tissues of hares captured near the mine area compared to the reference site. Specifically, hares from the mine area showed nail cadmium levels that was 2.3 to 17.6 times higher than those from the reference site. Histopathological examination of the eyes revealed no specific ocular lesions, such as lens opacity (cataracts) or conjunctivitis; however, hares from both locations exhibited hepatic steatosis (fatty liver change). Lipid peroxidation levels were relatively increased and accompanied with reduced antioxidant enzyme activities in hares from the mine area compared to the hares from the reference site. The results of this preliminary study suggest that the snowshoe hares breeding near the vicinity of Yellowknife, including near the Giant mine area have been chronically exposed to elevated levels of arsenic and cadmium, which consequently led to the increased levels of oxidative stress and perturbation of antioxidant defense system in exposed animals. The results of this present study constitute the first observation of chronic arsenicosis in wild small mammal species in Canada.
Cinnamon contains cumarin, which may be toxic to the liver. EU-regulations standardardize the amount of cinnamon in pastry including cinnamon rolls. The aim of the study was to investigate if cinnamon intake from pastry was associated with toxic or alcoholic hepatitis.
We registered 58 patients with toxic hepatitis, 38 (66%) women and 20 (34%) men with a median age of 51 (range: 32-80) and 53 (range: 18-78) years, respectively. A total of 22 patients had primarily cholestasis and 36 had hepatitis biochemically. The duration of toxic liver disease from admission to normalization of liver enzymes was similar in the two groups (3.5 ± 3.5 vs 3.6 ± 3.5 months). Toxic hepatitis was most often caused by drugs e.g. NSAID (n = 15; 26%), antibiotics (n = 9; 16%), alternative medicine (n = 7; 12%) and Antabuse (n = 5; 9%). We registered eight patients admitted with severe alcoholic hepatitis, five men and three women, median age of 60 (range: 34-67) years. Alcoholic hepatitis was associated with high alcohol intake. None of the patients with toxic or alcoholic hepatitis reported of excessive intake of cinnamon rolls and there was no evidence of cinnamon added to alcohol of alternative medicine products.
Intake of cinnamon from cinnamon rolls is not associated with admission for toxic or alcoholic hepatitis. However, for the diagnosis of toxic liver diseases including alcohol it is very important to have patient information regarding any new drugs, alternative medicine and alcohol intake. Further, other causes of liver diseases should be excluded.
Inrtroduction: The epidemiological situation for hepatitis D has changed significantly. Reduced population authors infection due to a sharp decline in hospitalizations from Central Asia regions, the Caucasus and Moldova, which are known to be endemic for hepatitis D. Currently, the incidence of chronic hepatitis D (HGD) in Russia is 1%, while in the countries of Central Asia, and in particular in Turkmenistan, the share of HGD among chronic viral hepatitis is 8%. The aim of research was to establish the clinical features, depending on the activity of the replication of hepatitis viruses B and D.
Materials and Methods: We studied 26 patients with viral hepatitis D with a determined activity replicative virus by PCR (polymerase chain reaction). The age of patients ranged from 28 to 78 years. The patients performed the ELISA (enzyme-linked immunosorbent assay) study for the presence of markers of parenteral viral hepatitis (HBsAg, a-HCV and a-HDV), the standard general clinical biochemical blood tests. of the instrumental methods survey used ultrasonography (ultrasound), EGD (fibrogastroduodenoscopy). Grading the severity of liver cirrhosis established by Child-Pugh (eng. Child-Pugh, Child-Turcotte, Child-Turcotte-Pugh, sometimes Child-Paquet) is designed to assess the severity of cirrhosis. The severity of liver cirrhosis is assessed on a point system, which are calculated from 5 or 6 parameters.
Results: It is established that most HGD more prevalent among young people bodied (69%) and occurs mainly in severe symptoms and portal hypertension leading to the rapid development of liver cirrhosis (53%). It showed that hyperenzymemia reaches high levels of ALT to 1715 U / L. with a high viral DNA load virus (HBV) 2648226,0 ± 953892,7 copies / ml in the presence of an RNA virus D (HDV +).
Conclusion: Thus, the main feature of chronic hepatitis D is its predominant tsirrogennost.