Steatosis is frequently encountered in healthy persons and is almost always present in obese persons who drink more than 60 g of alcohol per day. Steatosis is more strongly associated with obesity than with heavy drinking, suggesting a greater role of overweight than alcohol consumption in accumulation of fat in the liver.

Background-The Dionysos Study is a cohort study of the prevalence of chronic liver disease in the general population of two northern Italian communities. It included 6917 subjects, aged 12-65 (69% of the total population). Aims-The aim of this part of the study was to examine the relationship of daily alcohol intake, type of alcoholic beverage consumed, and drinking patterns to the presence of alcohol induced liver damage in an open population. Patients and methods-6534 subjects, free of virus related chronic liver disease and participating in the first cross-sectional part of the study, were fully examined. Each subject underwent: (a) medical history and physical examination, (b) evaluation of alcohol intake using an illustrated dietary questionnaire, and (c) routine blood tests. More invasive diagnostic procedures were performed when indicated. Results-Multivariate analysis showed that the risk threshold for developing either cirrhosis or non-cirrhotic liver damage (NCLD) was ingestion of more than 30 g alcohol per day in both sexes. Using this definition, 1349 individuals (21% of the population studied) were at risk. Of these, only 74 (5.5% of the individuals at risk) showed signs of liver damage. The prevalence of "pure" alcoholic cirrhosis was 0.43% (30 of 6917), representing 2.2% of the individuals at risk, with a ratio of men to women of 9:1, while 44 (3.3% of the individuals at risk) showed persistent signs of NCLD. After 50 years of age, the cumulative risk of developing both NCLD and cirrhosis was significantly higher (p<0.0001) for those individuals who regularly drank alcohol both with and without food than for those who drank only at mealtimes. Conclusions-Our data show that in an open population the risk threshold for developing cirrhosis and NCLD is 30 g ethanol/day, and this risk increases with increasing daily intake. Drinking alcohol outside mealtimes and drinking multiple diVerent alcoholic beverages both increase the risk of developing alcohol induced liver damage. (Gut 1997; 41: 845-850)

To demonstrate that the lipid volume fraction in liver steatosis can be accurately estimated with in vivo hydrogen-1 magnetic resonance (MR) spectroscopy, the authors developed a calibration procedure based on in vitro MR spectroscopy of lipid extracts from steatotic liver specimens. The lipid volume fractions determined with the calibration procedure were compared with the results of histomorphometry and with calibrated computed tomographic (CT) data. The volume fraction of fat determined with MR spectroscopy was in good agreement with the CT results, whereas histomorphometry underestimated the amount of hepatic fat. The results indicate that determination of the fat volume fraction in steatotic liver can be achieved noninvasively with MR spectroscopy.

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38).

No abstract

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Background-Theseverity, clinical course, and risk of hepatitis C virus (HCV) related chronic liver disease are still rather poorly defined. Aims-To investigate the prevalence, risk factors, and severity of HCV related liver disease in the general population, and investigate whether infection with a specific genotype is associated with an increased risk of cirrhosis or hepatocellular carcinoma. Methods-HCV RNA determination by polymerase chain reaction (PCR) and HCV genotyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular carcinoma was established by liver biopsy in all cases. All the data were analysed by univariate and multivariate statistics in all the cohort. To investigate the natural history of HCV infection, anti-HCV positive subjects were followed up every six months for three years with liver function tests and ultrasonograms. Results-The overall prevalence of HCV RNA positivity was 2.3%. Positivity increased progressively with age, and was higher in women (ratio of men to women = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intravenous drug use, blood transfusions received before 1990, history of previous hepatitis among the cohabiting, and history of animal (mainly dogs) bites were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, sex, and alcohol intake, genotype 1b infection, with or without coinfection with other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of follow up, 57 (35%) of the HCV RNA positive subjects had consistently normal alanine aminotransferase and -glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcohol a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year).Conclusions-In the general population of Northern Italy, HCV infection is widespread, but only less than 50% of the anti-HCV positive subjects, particularly those infected with genotype 1b, are associated with a more severe liver disease. Alcohol consumption greater that 30 g a day significantly aggravates the natural course of the disease. (Gut 1999;44:874-880)

Using the general population of the Dionysos Study, we followed up 144 subjects without fatty liver (FL ؊ ) and 336 with fatty liver (FL ؉ ) for a median time of 8.5 years. All subjects had suspected liver disease (SLD) defined as altered liver enzymes, high mean corpuscular volume, or low platelet count in the absence of HBV and HCV infection. Ethanol intake was assessed using a food frequency questionnaire, and FL was diagnosed using ultrasonography. The incidence and remission rates of FL were 18.5 and 55.0 per 1,000 person-years. Progression to cirrhosis or HCC was rare in both cohorts (incidence rate: 1.7 versus 1.1 and 0.8 versus 0.4 per 1,000 person-years for FL ؊ versus FL ؉ ). Multivariable Poisson regression was performed to identify predictors of FL incidence and remission among sex, age, body mass index, ethanol, and liver enzymes. Every increase of 20 g/day of ethanol intake at baseline was associated with a 17% increase in the rate of incident FL (P ‫؍‬ 0.019), a 10% decrease in the rate of remitting FL and SLD (P ‫؍‬ 0.043), a 19% decrease in the rate of remitting FL with persistent SLD (P ‫؍‬ 0.002), and a 10% increase in mortality rate (P ‫؍‬ 0.005) in the FL ؉ cohort. Conclusion: In the general population of the Dionysos Study, FL regressed in nearly 1 of every 2 cases and had a substantially benign course. Ethanol intake was the most important risk factor for FL remission and incidence and a predictor of mortality in subjects with FL. (HEPATOLOGY 2007;46:1387-1391 R ecent studies performed in representative samples of the general population have shown that fatty liver (FL) is highly prevalent and that anthropometric and metabolic indicators are better predictors of FL than ethanol intake. 1-4 Data are still lacking, however, on the incidence and natural course of FL in the general population. 5 The incidence and remission rates of nonalcoholic fatty liver disease (NAFLD) were 10% and 16%, respectively, in a convenience sample of 4,401 Japanese employees followed for a mean time of 1.1 years. 6 The survival of a community-based sample of NAFLD patients was lower than that of the general population (standardized mortality rate [SMR], 1.34; 95% CI, 1.003-1.76) and 5% of them developed cirrhosis after a mean (SD) time of 7.6 (4.0) years. 7 In the largest clinical study performed to date, 5% of a convenience sample of 129 hospitalized NAFLD patients developed end-stage liver disease after a mean follow-up time of 13.7 years. 8 Referral bias may be responsible for the relatively high incidence of cirrhosis observed in community-and hospitalbased cohorts. 5,7,9 Indeed, there is an ongoing controversy as to whether NAFLD should be considered a benign disease. 10,11 Using data from the follow-up of the Dionysos Study, we evaluated the incidence and natural course of FL in a representative sample of the general population. Patients and MethodsStudy Design. The purpose of the Dionysos Study was to assess the prevalence, incidence, and natural course of liver disease in the general population of 2 towns o...