Elemér Nemesánszky

Association of primary biliary cirrhosis with vitamin D receptor BsmI genotype polymorphism in a Hungarian population

We sought to determine the distribution of vitamin D receptor genotypes defined by the BsmI polymorphism and to investigate their association with bone mineral density in patients with primary biliary cirrhosis. Vitamin D receptor genotype and bone mineral density at the lumbar spine was determined in 31 female Hungarian patients with primary biliary cirrhosis and 51 age-matched healthy female controls. The genotype frequency (BB: 45%, Bb: 32%, bb: 22%) of the patients was significantly different from the control group (P = 0.01) due to an overrepresentation of the BB genotype. There was an apparent trend, not reaching statistical significance, for a lower bone mineral density in both the patient and control groups carrying a B allele. In conclusion, we found a strikingly high frequency of the BB genotype in patients with primary biliary cirrhosis, which raises questions about hormonal influences on the development of primary biliary cirrhosis.

LKM3 autoantibodies in hepatitis C cirrhosis: A further phenomenon of the HCV-induced autoimmunity

Chronic hepatitis C is frequently associated with laboratory markers—including LKM1 autoantibodies—of autoimmunity. A 62-yr-old woman with hepatitis C cirrhosis presented autoantibodies against liver and kidney microsomal proteins. By further evaluation of autoantibodies using ELISA and immunoblotting LKM1 and LKM3 autoantibodies could be revealed. The target antigen of LKM3 autoantibodies proved to be UGT-1.1 isoenzyme. In the absence of chronic hepatitis D infection or autoimmune hepatitis type 2, this is the first case that reports the occurrence of LKM3 autoantibodies in HCV-induced chronic liver disease.

Acquired angioedema associated with chronic hepatitis C

C1-esterase inhibitor (C1-INH) deficiency is known to result in generalized angioedema.1 In addition to its hereditary form, an increasing number of diseases, including tumors and autoimmune disorders, were described in association with C1-INH deficiency (acquired angioedema [AAE]).1 Hepatitis C virus (HCV) has been considered among the most important causes of chronic liver disease, as well as an inducer of autoimmunity.2 The cases of 2 women with chronic hepatitis C are reported herein; both had frequent, severe attacks of angioedema caused by deficiency of C1-INH.

Serum Anti-cholesterol Antibodies in Chronic Hepatitis-C Patients During IFN-α-2b Treatment

Previously we detected more than 3 times higher anti-cholesterol antibody (ACHA) levels in HIV positive patients compared to healthy individuals, however, this level significantly decreased during highly active anti-retroviral therapy (HAART). In our present study we examined whether these findings could also be detected in patients with chronic hepatitis C (CHC). We calculated the correlation between the ACHA levels and the C5b-9 complement activation product. 39 patients with CHC were treated with IFN-alpha-2b (Schering-Plough) 5 MU daily for 6 weeks, followed by 5 MU TIW. Serum levels of ACHA and complement activation products were measured with ELISA. Serum HCV RNA was measured by a highly sensitive branched DNA technique before and 3, 6 and 12 months after the beginning of IFN-alpha-2b therapy. 52 healthy persons served as controls. At the onset of treatment ACHA level was significantly (p = 0.0062) higher in patients (40 (24-69) AU/ml) (median (interquartile range)) than in control sera (26 (20-35) AU/ml). In the 26 responder patients ACHA levels decreased to the normal level during the therapy, but no change was observed in the 13 non-responders. In patients with a sustained response ACHA levels remained low till the end of the 12 months IFN treatment. ACHA levels were significantly (p = 0.0422) higher in the patients with low ( or = 4.0 mmol/l) cholesterol concentrations. The ACHA level before the therapy strongly correlated (r = 0.5499, p = 0.0014) with C5b-9 serum levels. ACHA levels are elevated in CHC, but this elevation is not as high as in HIV. Decrease of viral load by IFN-alpha-2b treatment in the responders results in normalization of ACHA concentration. High ACHA levels in patients with low serum cholesterol concentration suggest that high ACHA levels may contribute to the decrease in cholesterol levels. The correlation between the ACHA and C5b-9 levels indicate, that the ACHA may play a role in the complement activation in CHC.

Effects of interferon treatment on the glucose metabolism of patients with chronic hepatitis C

Background: The authors report on changes in carbohydrate metabolism observed in 32 patients undergoing therapy with interferon-alpha for chronic hepatitis C. Methods: Diabetes had been diagnosed in three patients and impaired glucose tolerance ascertained in one patient before interferon therapy was started. The remaining 28 patients were non-diabetic. Interferon-alpha was administered in 3-MU doses three times per week. Results: Glucose tolerance deteriorated in two of the three diabetics, and eventually these patients had to be switched from oral hypoglycemic agents to insulin. The patient with impaired glucose tolerance at baseline progressed gradually to overt diabetes. Nine of the 28 previously non-diabetic patients developed impaired glucose tolerance during interferon therapy. Conclusion: The deleterious effects of interferon-alpha on carbohydrate metabolism proved to be reversible. Regular monitoring of the glucose level of patients during and after interferon therapy is mandatory.

Lipoprotein(a) concentration and phenotypes in primary biliary cirrhosis

We studied a selected group of 39 female patients suffering from primary biliary cirrhosis (PBC). This disease is characterized by typical lipoprotein alterations and elevated concentrations of serum cholesterol. Despite the increased concentration of atherogenic lipoproteins, enhanced atherogenesis is not characteristic of PBC. Serum total cholesterol, triglycerides, HDL2 and HDL3-cholesterol concentrations were measured by enzymatic methods or in combination with precipitation procedures. Apolipoproteins were determined by using immunonephelometric methods. ELISA sandwich method was used for lipoprotein(a) determinations. Apoprotein(a) phenotyping (isoforms) was performed by Western blotting with specific antibodies. The concentrations of serum lipids, lipoproteins and apoproteins (AI, AII and B) were found in the range of earlier investigations. The serum lipoprotein(a) concentration did not differ between the PBC patients and control subjects (10.0/0.1-54/, median 2.55 vs. 11.5/0-75/, median 5.2 mg/dl). In the advanced stages of PBC we found a higher number of patients with low lipoprotein concentration (lower than 1 mg/dl). In patients with shorter durations and milder histological alterations high HDL2 cholesterol subfractions has been detected (stage I = 0.42 +/- 0.18, stage II = 0.53 +/- 0.29 and stage III = 0.62 +/- 0.41 vs. stage IV = 0.26 +/- 0.15 mmol/l, P < 0.05). Despite the elevation of atherogenic lipoproteins, high HDL2-cholesterol and normal lipoprotein(a) concentrations may be one of the reasons why patients with advanced PBC are not placed at increased risk for atherosclerosis.

Clinical consequences of chronic hepatitis C virus infection, diabetes mellitus and steatosis hepatitis

Subsequent studies have implicated the hepatitis C virus (HCV) core protein in the pathogenesis of hepatic steatosis. Chronic HCV infection may also cause steatosis by impairing fatty acid oxidation. There is relationship between accumulation of fat into the liver and overweight and/or obesity. Another unexpected virus-host interaction is the HCV infection and diabetes. HCV encoded proteins might alter insulin signaling thus explaining impaired insulin sensitivity and the occurrence of glycaemic dysregulation. Some pieces of the puzzle are still not well known; e.g. the factors and the spectrum of disorders associated with insulin resistance, and whether the liver is a trigger or target of metabolic syndrome? In this review article clinical consequence of chronic HCV infection, diabetes mellitus and hepatic steatosis are discussed, as well as their possible effects on antiviral therapy.

Characterization of a Lipoyl Domain-Independent B-Cell Autoepitope on the Human Branched-Chain Acyltransferase in Primary Biliary Cirrhosis and Overlap Syndrome with Autoimmune Hepatitis

Background and aims: Antimitochondrial antibodies (AMA) which recognize pyruvate acetyltransferase (PDC-E2) represent a highly diagnostic feature of primary biliary cirrhosis (PBC). The analysis of immunofluorescence (IF)-AMA-positive sera in PBC patients indicates a conformational epitope located within the lipoyl binding domain of bovine branched-chain acyltransferase (BCKADC-E2) alone or in combination with AMA directed against PDC-E2 the significance of which is presently unclear. In the present study, immunoreactivities and disease associations of AMA against BCKADC-E2 were analyzed. B-cell autoepitopes on BCKADC-E2 were mapped by immunoprecipitation assay. Methods: Sera of 96 IF-AMA-positive patients with serological evidence of anti-BCKADC-E2 alone (n=26), anti-PDC-E2 alone (n=15), and both anti-BCKADC-E2 and anti-PDC-E2 (n=55) were analyzed by Western blot and ELISA in addition to an analysis of B cell autoepitopes on BCKADC-E2 by immunoprecipitation using in vitro translated, unmodified human proteins. Ninety-four patients without IF-AMA [blood donors (n=30), rheumatoid arthritis (n=40), autoimmune hepatitis (AIH) (n=10) and primary sclerosing cholangitis (PSC) (n=14] served as controls. Results: Eighty of 81 (99%) sera positive for BCKADC-E2 recognized the full length, mature protein, while only 2/10 AIH sera and none of the other controls showed reactivity. Of the 68 PBC sera 58 (85%) recognized the N-terminus consisting of aa 1-144 representing the lipoyl domain. Surprisingly, C-terminal sequences (aa 143-421) were recognized by 46 out of 68 sera (68%). Three PBC sera reacted with the C-terminus only. Only 1/7 serum from patients with an “overlap syndrome of PBC and AIH” was reactive with C-terminal sequences. Conclusions: Our analysis of BCKADC-E2-positive PBC sera identified a novel B cell epitope on the C-terminal part of the human protein. Our data indicate that a distinct subset of AMA recognize sequence(s) on BCKADC-E2 which located outside of the lipoyl binding domain. The absence of immunoreactivity against C-terminal sequences may serve as a marker differentiating patients with PBC and overlap syndrome of PBC with AIH.

Unfavourable laboratory results and hepatic disorders in pregnancy: causes and consequences

Graviditas soran proinflammatorikus es prokoagulans status alakul ki, es ennek kovetkezmenyekent valtoznak a laboratoriumi parameterek normalis ertekhatarai is. Barmelyik etiologiaju majbetegseg tarsulhat graviditassal, leggyakrabban a gyogyszer toxikus hatasai, a kronikus virushepatitisek, a metabolikus szindroma, illetve az autoimmun hatterű korfolyamatok fordulnak elő. A terhessegspecifikus hepatologiai korkepek megitelese soran fontos figyelembe venni jelentkezesuk karakterisztikus „időfaktorat” es a klinikai kep progressziojat egyarant. A terhessegi cholestasisra vonatkozo ujabb adatok arra utalnak, hogy a legtobb esetben elkerulhető a korai terminacio. Az egyes korkepek kozotti atfedesek, a tunetek es a koros leletek szeles skalaju variacioi kulonosen a terhesseg masodik es harmadik trimesztereben eszlelhetők. Ilyen esetekben kulonosen fontos a tarsszakmak egyuttműkodese a pontos diagnozis es a terapias lehetősegek sikeres hasznositasa erdekeben. Orv. Hetil., 2013, 154, 1135–1141.