László Kalabay

Human fetuin/α2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer

Objective Human fetuin/α2HS-glycoprotein (AHSG) is synthesized by hepatocytes. We intended to determine whether liver dysfunction or acute phase reaction is dominant in the regulation of its serum concentrations and to see if decreased AHGS levels are associated with short-term mortality. Design We determined the serum AHSG levels in patients with acute alcoholic, acute A, B, and Epstein–Barr virus hepatitis, alcoholic cirrhosis, and hepatocellular cancer and correlated them to conventional laboratory parameters of inflammation and liver function. Patients were followed for 1 month. Methods Serum AHSG was determined by radial immunodiffusion. Results Compared to controls, significantly lower AHSG levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin and prothrombin was found. Febrile episodes were not associated with significantly decreased AHSG levels. Concentrations below 300 μg/ml were associated with high mortality rate (52.0%; relative risk, 5.497; 95% confidence interval, 2.472–12.23;P < 0.0001). Of all laboratory parameters studied serum AHSG levels showed the greatest difference between deceased and survived patients with cirrhosis and cancer. Moreover, other acute phase reactants did not differ significantly. The multiple logistic regression analysis indicated that the decrease of serum AHSG is independent of all other variables that were found decreased in deceased patients. Conclusions Decreased serum AHSG concentration is due rather to hepatocellular dysfunction than the acute phase reaction and is an outstanding predictor of short-term mortality in patients with liver cirrhosis and liver cancer.

Association of increased serum heat shock protein 70 and C-reactive protein concentrations and decreased serum α2-HS glycoprotein concentration with the syndrome of hemolysis, elevated liver enzymes, and low platelet count

The primary aim of this study was to determine serum Hsp70 concentrations in HELLP syndrome. We measured also the serum concentrations of three acute phase proteins: C-reactive protein (CRP), alpha(2)-macroglobulin (AMG) and alpha(2)-HS glycoprotein (AHSG). Ten severe preeclamptic patients with HELLP syndrome, 20 severe preeclamptic patients without HELLP syndrome and 20 normotensive, healthy pregnant women were included in this case-control study. Serum concentrations of Hsp70, CRP, AMG and AHSG were measured using an enzyme-linked immunosorbent assay (Hsp70), particle-enhanced immunoturbidimetric assay (CRP) and radial immunodiffusion (AMG, AHSG). The serum Hsp70 and CRP concentrations were significantly higher, whereas the serum AHSG concentration was significantly lower in the HELLP group (H) than the severe preeclamptic (P) and control (C) groups (median (25-75 percentile); Hsp70: 2.02 ng/ml (0.76-2.23) (H) versus 0.54 ng/ml (0.47-0.79) (P), p<0.01, and 0.30 ng/ml (0.27-0.33) (C), p<0.001; CRP: 43.9 mg/l (27.1-84.5) (H) versus 6.5 mg/l (2.7-10.7) (P), p<0.001, and 2.5 mg/l (1.1-6.7) (C), p<0.001; AHSG: 588 microg/ml (492-660) (H) versus 654 microg/ml (576-768) (P), p<0.05, and 738 microg/ml (666-804) (C), p<0.01, respectively). The serum AMG concentration did not differ between the study groups. In the HELLP group, there was a statistically significant negative correlation between serum Hsp70 concentration and platelet count (Spearman R=-0.69, p=0.026). In conclusion, serum Hsp70 and CRP concentrations are increased, whereas serum AHSG concentration is decreased, in HELLP syndrome. The maternal systemic inflammation seems to be more pronounced in HELLP syndrome than preeclampsia without HELLP syndrome, as suggested by the alterations in serum CRP and AHSG levels. However, it requires further investigation to determine whether these changes are causes or consequences of the disease.

Affective temperament, history of suicide attempt and family history of suicide in general practice patients

BACKGROUND Untreated major affective disorders are strongly associated with suicidal behaviour; however, clinical, psychological and psycho-social risk factors also play a contributory role. Personal history and family history of suicide are also important predictors of suicidal behaviours, and are also a powerful marker of current major depressive episode in general practice patients. Affective temperaments, which can be considered the subaffective manifestations of major mood disorders also show a specific pattern of association with suicidal behaviour. In the present study our aim was to investigate the association between affective temperaments, personal history of suicide attempts and family history of completed suicide in primary practice patients. METHODS Five hundred and nine patients from 6 primary care practices completed the TEMPS-A, and were assessed concerning self-reported history of personal or family suicide. RESULTS We found that among those answering questions concerning suicide, 9.1% reported a family history of suicide in first and second degree relatives and 4.8% had at least one prior suicide attempt. Among those giving a positive answer to both questions, those who had a positive family history had significantly more frequent suicide attempts (15.4% vs. 4.0%). Patients with prior suicide attempts had a significantly higher score on the cyclothymic and depressive, and those with positive family history of suicide had on cyclothymic and anxious subscales. LIMITATIONS In the present study, personal and family history of suicide was assessed retrospectively and in a self-report way. The cross-sectional nature of this study and the facts that no current psychiatric morbidity has been investigated and only the documented history of depressive and anxiety disorders have been detected limit the generalisability of this study. DISCUSSION We found a significant relationship between depressive and cyclothymic affective temperament and personal history of suicide attempts, and between cyclothymic and anxious temperament and family history of completed suicide in first and second degree relatives. This is in line with previous findings showing a strong relationship between these affective temperaments and major mood episodes and that these temperaments are overrepresented among suicide attempters. Our findings also suggest that the presence of cyclothymic (and to lesser extent depressive) affective temperament in a patient with family history of completed suicide indicates a very high risk of suicidal behaviour.

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

The purpose of this study was to determine serum α2-HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case–control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mg l−1 (2.76–12.69) vs. 3.38 mg l−1 (1.69–7.27), respectively; AHSG: 660 μg ml−1 (612–768) vs. 744 μg ml−1 (660–816), respectively; P<0.001 for both). In preeclamptic patients, the serum AHSG concentrations showed significant inverse correlations with systolic blood pressure and serum CRP levels. A low serum AHSG level (⩽720 μg ml−1) was significantly associated with preeclampsia (adjusted odds ratio (95% confidence interval): 3.69 (1.82–7.51); P<0.001). According to the receiver operating characteristic curves, the measurement of serum AHSG concentrations was as accurate as that of serum CRP levels to detect preeclampsia. In conclusion, serum AHSG concentration is decreased and reflects—at least partly—systemic inflammation in preeclampsia.

Human serum fetuin A/α2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores

BackgroundSerum concentration of fetuin A/α2HS-glycoprotein (AHSG) is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP) and MELD scores.MethodsWe determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrolment and in the 1st, 3rd, 6th, and the 12th month thereafter.ResultsForty-one patients died during the 1-year follow-up period, 37 of them had liver failure. Data of these patients were analysed further. Deceased patients had lower baseline AHSG levels than the 52 patients who survived (293 ± 77 vs. 490 ± 106 μg/ml, mean ± SD, p < 0.001). Of all laboratory parameters serum AHSG level, CP and MELD scores showed the greatest difference between deceased and survived patients. The cutoff AHSG level 365 μg/ml could differentiate between deceased and survived patients (AUC: 0.937 ± 0.025, p < 0.001, sensitivity: 0.865, specificity: 0.942) better than the MELD score of 20 (AUC: 0.739 ± 0.052, p < 0.001, sensitivity: 0.595, specificity: 0.729). Initial AHSG concentrations < 365 μg/ml were associated with high mortality rate (91.4%, relative risk: 9.874, 95% C.I.: 4.258–22.898, p < 0.001) compared to those with ≥ 365 μg/ml (9.3%). Fourteen out of these 37 fatalities occurred during the first month of observation. During months 1–12 low AHSG concentration proved to be a strong indicator of mortality (relative risk: 9.257, 95% C.I.: 3.945–21.724, p < 0.001). Multiple logistic regression analysis indicated that decrease of serum AHSG concentration was independent of all variables that differed between survived and deceased patients during univariate analysis. Multivariate analysis showed that correlation of low serum AHSG levels with mortality was stronger than that with CP and MELD scores. Patients with AHSG < 365 μg/ml had significantly shortened survival both in groups with MELD < 20 and MELD ≥ 20 (p < 0.0001 and p = 0.0014, respectively).ConclusionSerum AHSG concentration is a reliable and sensitive indicator of 1-year mortality in patients with alcoholic liver cirrhosis that compares well to the predictive value of CP score and may further improve that of MELD score.

Cytokine regulation of the acute-phase protein levels in multiple myeloma

Interleukin (IL) 6 has an important role in the regulation of acute‐phase proteins (APPs) during an acute‐phase response. We studied IL‐6 and other cytokines to determine if they regulate serum APP levels in the same way under the condition of the aberrant, long‐lasting ‘acute‐phase response’ that occurs in patients with chronic inflammation and cancer.

Alpha2-HS glycoprotein: a protein in search of a function

In this issue (pp. 305–310) Jun Ren and Amy J. Davidoff author an article entitled ‘Alpha2‐HS glycoprotein, a putative inhibitor of tyrosine kinase, prevents glucose toxicity associated with cardiomyocyte dysfunction’. The protein responsible for this biological activity has recently come to the forefront of research on the biological activity of plasma proteins. Copyright

Serum α2-HS glycoprotein concentration in patients with hematological malignancies: A follow-up study

SummaryWe observed significantly reduced serum α2-HS glycoprotein concentrations in patients with acute lymphocytic, acute nonlymphocytic, chronic granulocytic and chronic myelomonocytic leukemias, Hodgkins and non-Hodgkins lymphomas, myelofibrosis, and multiple myeloma, but not in patients with chronic lymphocytic leukemia and polycythemia vera, as compared with healthy controls. We followed the serum level of the protein for 18 months. Patients with infectious complications, those receiving cytostatic treatment, and those in the preterminal period had further reduced serum α2-HS glycoprotein levels. The reduction of serum α2-HS glycoprotein concentration was primarily due to decreased production caused by infiltration of the liver, a hepatotoxic effect of cytostatic treatment, and, to a lesser degree, to increased consumption. We found statistically significant negative correlations between serum α2-HS glycoprotein concentration and erythrocyte sedimentation rate, serum aspartate aminotransferase and alkaline phosphatase activities, and IgG and IgM concentrations. The determination of the α2-HS glycoprotein concentration is useful for the assessment and follow-up of the clinical status and therapy of patients with hematological malignancies and also has prognostic significance.

Primary care obesity management in Hungary: evaluation of the knowledge, practice and attitudes of family physicians

BackgroundObesity, a threatening pandemic, has an important public health implication. Before proper medication is available, primary care providers will have a distinguished role in prevention and management. Their performance may be influenced by many factors but their personal motivation is still an under-researched area.MethodsThe knowledge, attitudes and practice were reviewed in this questionnaire study involving a representative sample of 10% of all Hungarian family physicians. In different settings, 521 practitioners (448 GPs and 73 residents/vocational trainees) were questioned using a validated questionnaire.ResultsThe knowledge about multimorbidity, a main consequence of obesity was balanced.Only 51% of the GPs were aware of the diagnostic threshold for obesity; awareness being higher in cities (60%) and the highest among residents (90%). They also considered obesity an illness rather than an aesthetic issue.There were wider differences regarding attitudes and practice, influenced by the the doctors’ age, gender, known BMI, previous qualification, less by working location.GPs with qualification in family medicine alone considered obesity management as higher professional satisfaction, compared to physicians who had previously other board qualification (77% vs 68%). They measured their patients’ waist circumference and waist/hip ratio (72% vs 62%) more frequently, provided the obese with dietary advice more often, while this service was less frequent among capital-based doctors who accepted the self-reported body weight dates by patients more commonly. Similar reduced activity and weight-measurement in outdoor clothing were more typical among older doctors.Diagnosis based on BMI alone was the highest in cities (85%). Consultations were significantly shorter in practices with a higher number of enrolled patients and were longer by female providers who consulted longer with patients about the suspected causes of developing obesity (65% vs 44%) and offered dietary records for patients significantly more frequently (65% vs 52%). Most of the younger doctors agreed that obesity management was a primary care issue.Doctors in the normal BMI range were unanimous that they should be a model for their patients (94% vs 81%).ConclusionMore education of primary care physicians, available practical guidelines and higher community involvement are needed to improve the obesity management in Hungary.

Socio-demographic characteristics, health behaviour, co-morbidity and accidents in snorers: a population survey

ObjectiveWe assessed the socio-demographic correlates of snoring and also the patterns of health behaviour and co-morbidity associated with different types of snoring in the Hungarian population. We wanted to study whether different types of snoring are associated with high-risk health behaviour, chronic illnesses, daytime consequences of poor sleep, and with frequent accidents compared with non-snoring individuals.MethodThis is a cross-sectional study. Interviews were carried out in the homes of 12,643 people. This was the largest nationally representative study in Central Europe about health behaviour. In the Athens Insomnia Scale, questions about snoring and sleep behaviour, life-style factors and health behaviour, as well as questions on their history and current medical treatment were included in the questionnaire.ResultsThirty-seven percent of males and 21% of females reported loud snoring with breathing pauses. We found a significant increasing trend for the consumption of alcohol and coffee as well as smoking among non-snorers, habitual snorers and loud snorers, respectively. In an ordinal regression model male gender, the presence of smoking, the presence of three or more co-morbid conditions and alcohol consumption were independent predictors of snoring (OR [95% CI], 1.99 [1.85–2.1], 1.76 [1.60–1.92], 1.45 [1.30–1.62] and 1.22 [1.04–1.43], respectively, P < 0.001) after controlling for multiple socio-demographic and clinical variables. The frequency of accidents was higher in the loud snoring group than among non-snoring individuals (24% vs 17%, P < 0.0001).ConclusionsSnoring is common in the Hungarian adult population. Snoring, especially loud snoring with breathing pauses, is strongly associated with high-risk health behaviour, higher co-morbidity and a higher frequency of accidents.