Béla Lombay

Presence of Anti-Microbial Antibodies in Liver Cirrhosis – A Tell-Tale Sign of Compromised Immunity?

Background Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohns disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. Methodology/Principal Findings Sera of 676 patients with various chronic liver diseases (autoimmune diseases:266, viral hepatitis C:124, and liver cirrhosis of different etiology:286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae(ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p<0.001). Occurrence of these antibodies was more frequent in cases of advanced cirrhosis (according to Child-Pugh and MELD score; p<0.001) or in the presence of ascites (p<0.001). During the median follow-up of 425 days, 81 patients (28.3%) presented with severe bacterial infections. Anti-microbial antibody titers (p = 0.003), as well as multiple seroreactivity (p = 0.036), was associated with infectious events. In logistic regression analysis, the presence of ascites (OR:1.62, 95%CI:1.16–2.25), co-morbidities (OR:2.22, 95%CI:1.27–3.86), and ASCA positivity (OR:1.59, 95%CI:1.07–2.36) were independent risk factors for severe infections. A shorter time period until the first infection was associated with the presence of ASCA (p = 0.03) and multiple seropositivity (p = 0.037) by Kaplan-Meier analysis, and with Child-Pugh stage (p = 0.018, OR:1.85) and co-morbidities (p<0.001, OR:2.02) by Cox-regression analysis. Conclusions/Significance The present study suggests that systemic reactivity to microbial components reflects compromised mucosal immunity in patients with liver cirrhosis, further supporting the possible role of bacterial translocation in the formation of anti-microbial antibodies.

Mannose-binding lectin deficiency confers risk for bacterial infections in a large Hungarian cohort of patients with liver cirrhosis.

BACKGROUND & AIMS Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state. METHODS Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients. RESULTS MBL level and the prevalence of absolute MBL deficiency (<100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03). CONCLUSIONS MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.

The effect of gonadotropin releasing hormone analogue therapy in girls with idiopathic central precocious puberty

UNLABELLED It has been proven for more than two decades that gonadotropin releasing hormone analogue therapy is the only choice of treatment in patients with central precocious puberty. AIMS The aim of the authors was to assess the effect of gonadotropin releasing hormone analogue treatment on final height, body mass index, bone mineral density and ovarian function in girls with idiopathic central precocious puberty. METHODS Predicted adult height, target height and achieved height due to therapy was assessed in 15 girls with idiopathic precocious puberty treated with gonadotropin releasing hormone analogue. At the beginning of the treatment, the age of the girls was 7.0±0.8 years (mean±SD) and at the end of the treatment 12±0.8 years. The duration of gonadotropin-releasing hormone analogue treatment was 4.48±0.8 years. At the time of achieving final height, the age of the patients was 18.2±2.0 years and the height was 160.4±7.1 cm. When final height was reached, the authors evaluated bone mineral density Z-score values, levels of bone markers and the function of the hypothalamic-pituitary-gonadal axis. 15 healthy prepubertal girls, 15 pubertal girls and 15 girls who reached final height matched for chronological age were selected as control groups. RESULTS The majority of the gonadotropin releasing hormone-treated girls reached or almost reached their expected height predicted on the basis of the heights of their parents, but the therapy resulted only in a modest beneficial effect on height gain. Despite the fact that the body weight of patients increased during the treatment, there was no significant difference in their body mass index when they reached their final height as compared to controls. As compared to controls, patients had a decreased bone mineral density at the time when they reached their final height (lumbar spine 2-4 Z score, -0.27±1.2 vs. 0.5±0.7 in controls; p = 0.0377), which could be explained by their overweight that already existed before treatment, lack of exercise and poor calcium uptake. Their menarche occurred 12±4.6 months after discontinuing the treatment. CONCLUSIONS Gonadotropin releasing hormone analogue therapy exerts a modest beneficial effect on final height gain. There are no detrimental effects on body mass index, bone mineral density and ovarian function after treatment. Side-effects are of minor severity and they are tolerable.

M1675 Presence of Anti-Microbial Antibodies is Associated With Increased Risk for Systemic Infections in a Large Hungarian Cohort of Patients With Liver Cirrhosis

DNA fragmentation. Total RNA was isolated and IL-8, CXCL1, CXCL2, CCL2, ICAM, VCAM mRNA expression was determined by real time RT-PCR. NF-kB activation was determined by luciferase assay. Results: Exposure of LX2 cells to palmitate significantly induces IL-8 production and gene expression, as well as TLR4, CXCL1, CXCL2, CCL2, ICAM, VCAM mRNA expression. Palmitate induced IL-8 production can not be blocked by pan-caspase inhibitor. However, palmitate induced MIP-2 (rodent homolog of human IL-8) production was completely abrogated in HSCs from TLR4-mutant (C3H/HeJ) mice, but not from wildtype (C3H/HeOuJ) mice. Palmitate also induces NF-kB activation in a dose-dependent manner. Conclusions: Our data demonstrate that palmitate directly stimulates IL-8 production in HSCs via TLR4 signaling pathway, suggesting that HSCs play an important role in FFAs induced liver inflammation and injury.

[Clinical aspects of hepatitis C in women of child-bearing age].

It is difficult to define the optimal timing of antiviral treatment in women infected with viral hepatitis C, who have child-bearing potential. Antiviral treatment is strictly contraindicated during pregnancy and the breast-feeding period. Data are conflicting about the question of treatment with modern drugs (peginterferon and ribavirin) before or after pregnancy. The risk of vertical transmission from mother to child is estimated about 5%. The mothers viraemia seems to be the main transmission factor. There is a worse prognosis in nulliparous and postmenopausal women in the natural history of viral hepatitis C. Poor outcome in gestational age, maturity and Apgar score were not associated with hepatitis C virus infection. Combined treatment has frequent gynecological and other side effects. The timing of antiviral therapy in women in child-bearing period is recommended individually.

Clinical aspects of hepatitis C virus infection in child-bearing aged women

It is difficult to define the optimal timing of antiviral treatment in women infected with viral hepatitis C, who have child-bearing potential. Antiviral treatment is strictly contraindicated during pregnancy and the breast-feeding period. Data are conflicting about the question of treatment with modern drugs (peginterferon and ribavirin) before or after pregnancy. The risk of vertical transmission from mother to child is estimated about 5%. The mothers viraemia seems to be the main transmission factor. There is a worse prognosis in nulliparous and postmenopausal women in the natural history of viral hepatitis C. Poor outcome in gestational age, maturity and Apgar score were not associated with hepatitis C virus infection. Combined treatment has frequent gynecological and other side effects. The timing of antiviral therapy in women in child-bearing period is recommended individually.

Fertilis korú nok hepatitis C-vírus-fertozésének klinikai vonatkozásai

It is difficult to define the optimal timing of antiviral treatment in women infected with viral hepatitis C, who have child-bearing potential. Antiviral treatment is strictly contraindicated during pregnancy and the breast-feeding period. Data are conflicting about the question of treatment with modern drugs (peginterferon and ribavirin) before or after pregnancy. The risk of vertical transmission from mother to child is estimated about 5%. The mothers viraemia seems to be the main transmission factor. There is a worse prognosis in nulliparous and postmenopausal women in the natural history of viral hepatitis C. Poor outcome in gestational age, maturity and Apgar score were not associated with hepatitis C virus infection. Combined treatment has frequent gynecological and other side effects. The timing of antiviral therapy in women in child-bearing period is recommended individually.

Clinical Aspects of Hepatitis C Virus Infection in Women of Child-Bearing Age

It is difficult to define the optimal timing of the antiviral treatment in women infected with hepatitis C virus, who have child-bearing potential. Antiviral treatment is strictly contraindicated during the pregnancy and breast-feeding period. Data are conflicting about the question of treatment with modern drugs (peginterferon and ribavirin) before or after pregnancy. The risk of vertical transmission from mother to child is estimated about 5%. The mother’s viraemia seems to be the main transmission factor. There is a worse prognosis in nulliparous and postmenopausal women in the natural history of viral hepatitis C. Poor outcome in gestational age, maturity and Apgar score was not associated with hepatitis C virus infection. Combined antiviral treatment has frequent gynecological and other side-effects. The timing of the antiviral therapy in women in the child-bearing period is recommended individually.