BACKGROUND: Based on the increased consumption of alcohol in Denmark the aim of this study was to measure prevalence of abnormal liver-derived enzymes in a homogeneous Danish population and possible associations with alcohol consumption, smoking and body mass index (BMI). METHOD: In a representative population sample of 905 people (aged 30-50) from the baseline survey of the Ebeltoft Health Promotion Project in Denmark, we examined prevalence of abnormal liver-derived enzymes and its possible association with self-reported alcohol consumption, smoking and BMI, applying logistic regression analyses. RESULTS: In a significant proportion, 12% (women 8%; men 16%) of the cohort we found raised levels of liver-derived enzymes associated with moderate self-reported alcohol intake adjusted for BMI and smoking. If the intake was higher than moderate, i.e. > 28 units per week (one unit equals 12 g of alcohol), the odds ratio (OR) for raised liver enzymes increased further; S-gamma-glutamyltransferase (GGT) (OR: for women 24.4; men 18.4). S-aspartate-aminotransferase (ASAT) (24.2; 5.8) and S-alanine-aminotransferase (ALAT) (27.2; 3.0). Furthermore, daily smoking increased the risk of raised liver enzymes in women (OR: 3.4-4.2), and obesity (BMI > or = 30 kg/m2) in men showed a positive association with all three enzymes (OR: 3.0-9.0). CONCLUSIONS: The occurrence of raised liver-derived enzymes was frequent in the Danish population sample and associated with moderate self-reported alcohol consumption adjusted for BMI and smoking.
Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C: results of a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment.
Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU TIW. At 6 months, 25 patients with a complete or a partial biochemical response were randomly allocated to either a fixed dose regimen (13 patients) (3 or 6 MU thrice weekly) or an individualized dose regimen (12 patients) tapering interferon dose from 3 or 6 MU by one-third every 2 months if transaminases were persistently normal. The remaining 22 biochemical nonresponders were followed for an additional 6 months without further treatment. After 12 months of treatment, 18 patients (38%) had a virological response, irrespective of regimen, and seven patients (16%) had a sustained virological and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable to that obtained in previous studies among nonhaemophiliacs. However, a sustained virological and biochemical response was seen in only 16% of treatment patients.
Screening of 43 healthy Danish haemophiliacs revealed a significantly lower helper/suppressor (H/S) ratio than in controls. 8 of the haemophiliacs had an H/S ratio less than or equal to 1.0. A significant negative correlation occurred between the total lifetime factor VIII treatment and the H/S ratio. However, high-dose factor VIII treatment given to patients with antibodies against factor VIII was not associated with immunological abnormalities. Children had a significantly higher H/S ratio than the adult haemophiliacs. Patients exclusively treated with Danish cryoprecipitate during the last year had a significantly higher H/S ratio than patients receiving preparations from other sources. This difference might, however, be explained by lower age and lower total lifetime dose in the group receiving Danish preparations. Haemophiliacs treated with American preparations did not differ immunologically from those treated with preparations of other origin. Total serum IgG was increased in 23% of the patients. This parameter was negatively correlated with the H/S ratio. The possible relation of the observed immunological alterations among otherwise healthy haemophiliacs to the acquired immune deficiency syndrome warrants further attention.
The Swedish alcohol ignition interlock program for driving while intoxicated (DWI) offenders, both first-time as well as multiple offenders, was launched as a pilot project in 1999. It is a volunteer program and differs in some respects from other programs: It covers a period of 2 years, it includes very strict medical regulations entailing regular checkups by a physician, it does not require a prior period of hard suspension, and it focuses strongly on changes in alcohol habits. Records from the 5 years prior to the offence showed that DWI offenders are generally in a high-risk category long before their offense, with a four to five times higher accident rate (road accidents reported by the police) and a three to four times higher rate of hospitalization due to a road accident. Only 12% of the eligible DWI offenders took part in the program and, of these, 60% could be diagnosed as alcohol dependent or alcohol abusers. During the program, alcohol consumption is monitored through self-esteem questionnaires (AUDIT) and five different biological markers. Our data show a noticeable reduction in alcohol consumption among the interlock users. This, combined with the high rate of compliance with the regulations, probably accounts for the fact that there was no case of recidivism during the program. Preliminary findings also suggest a reduction in the annual accident rate for interlock users while in the program. It still is too early to draw any conclusions concerning the rate of recidivism after completion of the program due to an insufficient amount of data for analysis. Nevertheless, the preliminary results are so promising that the program will now be expanded to cover all of Sweden as well as to include all driver's license categories.
We examined whether metabolic syndrome (MetS) predicts increased alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in young adults, whether spontaneous recovery from MetS has a favorable effect on liver enzyme activities, and whether these enzymes contribute to the atherogenicity of MetS (assessed by carotid intima-media thickness (IMT)).
The study included 1,553 subjects (base-line age 31.5 ± 5.0 years). ALT and GGT were measured in 2007. MetS was diagnosed by the new Joint Interim Societies definition.
ALT and GGT levels were higher in subjects with MetS compared to those without in 2007. The association was independent of alcohol intake and BMI. In multivariable models adjusted for base-line age, LDL cholesterol, CRP, alcohol intake, and adiponectin, MetS in 2001 predicted increased ALT (ß ± SEM = 0.320 ± 0.062, P
BACKGROUND: Blocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation. METHODS: The orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope. RESULTS: Isotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially. CONCLUSIONS: These results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.
The functional and structural changes in the liver of white rats both low- and high-resistant to hypoxia, have been studied using the biochemical and morphological methods. It has been found that intensity and degree of the liver injury in experimental toxic hepatitis depend on the systemic resistance to hypoxia. The functional and morphological changes in the injured liver have been found to be less pronounced in the high-resistant rats as compared with those in the low-resistant animals.
To assess the performance of a range of biomarkers of alcohol consumption in a heavy-drinking population of working-aged Russian men.
Cross-sectional study of men originally sampled at random from a population register.
Izhevsk, a Russian city with a population of 650?000 people.
A total of 1023 men aged 27-59 years living in Izhevsk who took part in a health check examination in 2008-2009.
Self-reported alcohol consumption, hazardous drinking behaviours, socio-economic position, anthropometric measurements plus blood levels of alcohol biomarkers [carbohydrate-deficient transferrin (CDT, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and mean cell volume of erythrocytes (MCV)] and hepatitis B and C status.
In the year before interview there was a high prevalence of high-risk alcohol consumption indicated by consumption of non-beverage alcohols (5%), problem drinking behaviours (4.4%) and alcohol consumption exceeding an average 40?g per day (12.6%). All biomarkers were associated strongly with total beverage alcohol consumption even after adjustment for confounders. CDT performed best as an alcohol biomarker, with a sensitivity of 67% and specificity of 71% for detecting an average consumption of more than 40?g per day versus less. For all biomarkers sensitivity was considerably lower than specificity. Hazardous drinking patterns per se were not well detected by any of the biomarkers, all with sensitivity below 60%.
In a Russian population with high levels of alcohol consumption, carbohydrate-deficient transferrin (CDT) might be the most sensitive and specific biomarker for detecting ethanol consumption above 40?g/day. A biomarker reflecting hazardous drinking patterns has yet to be established.