Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world, but little is known about its potential association with pregnancy outcomes. We aimed to investigate pregnancy outcomes in NAFLD.
The Swedish Medical Birth Register (MBR) was used to identify births between 1992 and 2011 (N = 1 960 416). By linkage with the National Patient Register, we identified women with a diagnosis of NAFLD. The MBR was then used to identify outcomes: gestational diabetes, pre-eclampsia, Caesarean section, Apgar score
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: email@example.com.
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.
To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis.
Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient's lifetime drinking habits: the lifetime drinking history (LDH) questionnaire. In addition, clinical status, transient elastography and biochemistry values were analysed and registered. Patients were defined as having either significant or non-significant fibrosis. Significant fibrosis was defined as either an elastography value of = 17.3 kPa or the presence of clinical signs of cirrhosis. Patients were divided into two groups depending on their alcohol consumption patterns; no/low alcohol consumption (one drink or unit/d) and moderate/high alcohol consumption (= 1 drink or unit/d). LDH data were calculated to estimate lifetime alcohol intake (LAI), current alcohol intake, drinks per year before and after diagnosis of PSC. We also calculated the number of episodes of binge-drinking (defined as consuming = 5 drinks per occasion) in total, before and after the diagnosis of PSC.
The mean LAI was 3882 units of alcohol, giving a mean intake after onset of alcohol consumption of 2.6 units per week. Only 9% of patients consumed alcohol equal to or more than one unit per day. Current alcohol intake in patients with significant fibrosis (n = 26) was less than in patients without significant fibrosis (n = 70), as shown by lower values of phosphatidylethanol (B-PEth) (0.1 ?mol/L vs 0.33 ?mol/L, respectively, P = 0.002) and carbohydrate-deficient transferrin (CDT) (0.88% vs 1.06%, respectively, P = 0.02). Self-reported LAI was similar between the two groups. Patients with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/year. There were no correlations between elastography values and intake of alcohol (units/year) (r = -0.036).
PSC patients have low alcohol consumption. The lack of correlation between fibrosis and alcohol intake indicates that a low alcohol intake is safe in these patients.
High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.
We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into 'high' (n = 89) and 'normal' (n = 133) ferritin values, using a cut-point of 350 µg/L in males, and 150 µg/L in females, and stratified upon iron overload status. Data on mortality were obtained from a national, population-based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.
The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (P
A high body mass index (BMI) is associated with an increased risk for severe liver disease. It is unclear if this risk differs across BMI categories, and if the association is partially attributed to development of type 2 diabetes mellitus (T2DM).
We used register data from more than 1.2 million Swedish men enlisted for conscription between 1969 and 1996. Data regarding new events of severe liver disease and T2DM during follow-up were obtained by record-linkage of population-based registers. We used Cox regression to estimate adjusted HRs for future inpatient care and mortality in severe liver disease and incidence of hepatocellular carcinoma (HCC) across BMI categories, using BMI of 18.5-22.5 kg/m2 as reference.
During a follow-up of more than 34 million person-years, 5281 cases of severe liver disease including 251 cases of HCC were identified. An association with severe liver disease was found for overweight (HR 1.49, 95% CI 1.35 to 1.64) and for obese men (HR 2.17, 95% CI 1.82 to 2.59). Development of T2DM further increased the risk for severe liver disease across all BMI categories, for instance, men with obesity and T2DM had a higher risk of severe liver disease (HR 3.28, 95% CI 2.27 to 4.74) than men with obesity free of T2DM (HR 1.72, 95% CI 1.72 to 2.54).
A high BMI in late adolescent men was associated with an increased risk of future severe liver disease, including HCC. Development of T2DM during follow-up was associated with a further increased risk of severe liver disease, independent of baseline BMI.
Nonalcoholic fatty liver disease (NAFLD) is a strong risk factor for development of type 2 diabetes, but little is known about how long-term NAFLD or its histologic features affect risk. We aimed to investigate the cumulative incidence of type 2 diabetes in patients with NAFLD and to identify histologic factors that affect risk of diabetes.
We performed a retrospective study of 396 patients in Sweden diagnosed with NAFLD by biopsy analysis from 1971 through 2009 who did not have type 2 diabetes at baseline. Data on development of type 2 diabetes were collected from patient charts and national registers. Patients were categorized into groups with fibrosis stages 0-2 (n = 357) or stages 3-4 (n = 39). Hazard ratios of histologic parameters for type 2 diabetes development were calculated separately in a multivariate Cox regression model adjusted for sex, age, body mass index, and serum levels of triglycerides greater than 150 mg/dL.
During a mean follow-up period of 18.4 years (range, 0-41 years), 132 individuals (33%) developed type 2 diabetes. A significantly higher proportion of patients with fibrosis stages 3-4 (51.2%) developed type 2 diabetes than patients with fibrosis stages 0-2 (31.3%) (P = .02). For patients with fibrosis stages 0-2, fat score associated independently with development of type 2 diabetes (adjusted hazard ratio, 1.34; 95% confidence interval, 1.03-1.74; P = .03). No histologic factors associated with development of diabetes in patients with fibrosis stages 3-4. Presence of nonalcoholic steatohepatitis was not associated with development of type 2 diabetes.
In a retrospective study we found a higher proportion of patients with fibrosis stages 3-4 to develop type 2 diabetes than patients with fibrosis stages 0-2. In patients with fibrosis stages 0-2, fat score associates with risk of type 2 diabetes.
Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD.
We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled.
An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p?=?.017). The lowest risk for fibrosis was found with the lowes`t odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p?=?.006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth =0.3?µmol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p?=?.047).
Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.
New guidelines for NAFLD - a Swedish perspective Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally, with an estimated prevalence of 25%. It is clinically challenging to identify which persons with known or suspected NAFLD that have the highest risk for development of severe liver disease. New guidelines from several European organizations were recently presented. The suggested changes to healthcare practice include screening of high-risk groups in order to identify cases with cirrhosis. These guidelines and suggestions for adjustments to Swedish healthcare are discussed.
Centre for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: firstname.lastname@example.org.
The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.
We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.
During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.
Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.
We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.
Prognostication in hepatocellular carcinoma (HCC) is demanding. Not only tumour extent and performance status are to be considered, but also liver function, which is often limiting for both survival itself and for treatment possibilities. This study was conducted to assess whether patient-reported questionnaires containing general and liver-specific questions could improve prognostication of survival.
185 patients with hepatocellular carcinoma in Norway and Sweden were prospectively included. Patients completed the quality-of-life questionnaires EORTC QLQ C30 and HCC18, and clinical, radiological and laboratory parameters were registered. Multivariate Cox regression and Harrell's C-statistics were used to identify the model that best predicted mortality.
Quality-of-life data were prognostic for overall survival. Fatigue and nutrition scales were prognostic in the multivariable analyses alone and in combination with clinical parameters. The prognostic value of established scoring systems was increased by the addition of QoL data. The best prognostic power was achieved by combining HCC18 nutrition scale with selected background parameters.
Quality-of-life questionnaires can prognosticate mortality in HCC patients. When combined with established scoring systems, both the general cancer questionnaire EORTC QLQ C30, and the additional liver cancer-specific HCC18 increased the prognostic accuracy slightly.