Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody level: results and possible population-level consequences.

Due to the European measles epidemic and the increased number of imported cases, it can be theorised that the risk of exposure among Hungarian healthcare workers (HCWs) has increased. In 2017, the increased measles circulation in the region led to the emergence of smaller local and hospital epidemics. Therefore, our objective was to determine the herd immunity in the high-risk group of HCWs. A hospital-based study of detecting anti-measles IgG activity was performed in 2017 and included 2167 employees of the Military Medical Centre (Hungary). The screening of HCWs presented a good general seropositivity (90.6%). The highest seroprevalence value (99.1%) was found in the age group of 60 years or older. The lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age group, indicating a significant herd immunity gap between groups. Regarding the Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs, implying that susceptible HCWs may generate healthcare-associated infections. This study suggests that despite the extensive vaccination and high vaccine coverage, it is still important to monitor the level of protective antibodies in HCWs, or in a representative group of the whole population of Hungary, and possibly in other countries as well.

Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Increased total scavenger capacity in rats fed corticosterone and cortisol on lipid-rich diet.

BACKGROUND: In our earlier studies both corticosterone and cortisol had antioxidant effect in vitro. OBJECTIVES: Our aim was to clarify whether corticosterone and cortisol oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo. METHODS: Experimental animals were fed a lipid rich diet and treated with corticosterone or cortisol in the drinking fluid. Control group was fed only lipid rich diet with untreated drinking water. The untreated group was feda normal diet with untreated water. Total scavenger capacity (TSC) was measured before and after 4 weeks of treatment in blood samples using a chemiluminometric assay. RESULTS: Both corticosterone and cortisol treatment caused increased TSC. The control group and the untreated group showed no significant changes in TSC. CONCLUSION: Our results support the hypothesis that corticosterone and cortisol administration can improve the antioxidant status not only in vitro but also in vivo.

Measurement and clinical significance of interleukin 28B in hepatitis C virus-infected liver transplant patients.

One-third of the liver transplantations are performed because of hepatitis C cirrhosis all over the world and also in Hungary. The recurrence rate is practically 100%, influencing graft and patient survivals; within 5 years cirrhosis develops again in 20% to 30% of cases. The therapy is pegylated interferon α-2a and α-2b plus ribavirin as for nontransplanted subjects with the goal to eradicate the virus and maintain graft function. In 25% to 45% of treated patients, it is possible to achieve a sustained virological response (SVR). The response is influenced by viral, donor, and recipient factors. We investigated the genotype of 68 liver recipients transplanted because of hepatitis C virus (HCV) infection between September 1998 and February 2011. We focused on the interleukin (IL) 28B gene locus single nucleotide polymorphism found on chromosome 19; the rs12979860 minor allele (homozygous [wild TT and CC], heterozygous [CT]) in relation to the interferon response. Ten percent of the patients belonged to the CC, 62% to the CT, and 28% to the TT group, and 83% of the CC group became negative or therapy is still ongoing. The CT genotype reached 15.4% SVR with ongoing treatment for most patients. In TT carriers showed a 23.5% SVR. Our patients formed a homogenous group regarding the surgical team, the therapy, and the HCV genotype. Ninety percent belonged to the possible "hard to treat" group. The 10% CC group gave the highest number of SVR and HCV polymerase chain reaction negativity upon antiviral therapy. Regarding our results, one has to take in consideration the small patient number and the fact that the cirrhotic patients were listed for transplantation where they could not be treated or became therapy-resistant. IL28B is just one predictive factor among others for successful posttransplant HCV therapy; further examinations are needed to fully understand its role.

Predictive factors of sustained virological response for recurrent hepatitis C virus after liver transplantation: the hungarian experience.

Recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) occurs consistently. Early initiation of combined antiviral treatment (AVT) has become a standard treatment seeking to achieve sustained virological response (SVR). We evaluated the files of 108 HCV-positive patients between 2003 and 2010. Seventy-two (72) experienced recurrent HCV within 12 months, 31 of whom completed the AVT (43%) but 9 (29%) exhibited SVR. Factors with impacting SVR were male recipient, no fatty changes in the donor liver, short warm ischemia time, cyclosporine-based immunosuppression, neither infective, septic or bleeding complication nor acute rejection episode and a rapid viral response to AVT. De novo diabetes, and unsuccessful AVT prior to OLT were strongly associated with a a failed SVR. The 1- and 3-year cumulative patient survival rates trended to be better in cases of SVR compared with nonresponders (100% and 100% versus 94% and 89%; P = .07).

Relationship between hepatitis C virus recurrence and de novo diabetes after liver transplantation: the Hungarian experience.

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively (P=.011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P=.017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P=.039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P=.019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.

A new approach to drug therapy in non-alcoholic steatohepatitis (NASH).

Liver steatosis is a common human disease, most often caused by long-term alcohol consumption. Non-alcoholic steatohepatitis (NASH) is characterized by similar histopathological features to those observed in alcoholic liver disease, but occurs in the absence of significant alcohol consumption. Several aetiological factors contribute to NASH: obesity, type 2 diabetes mellitus, hyperlipidaemia, pregnancy, different chemical intoxications, parenteral nutrition, jejeuno-ileal bypass, chronic inflammatory bowel disease, nutritional protein deficiency and congenital metabolic disorders. Biochemically, oxidative stress and lipid peroxidation and their ensuing damage are implicated in the pathogenesis of NASH and alcoholic steatohepatitis (probably resulting from free fatty acids in the mitochondria, and induction of the cytochrome P450 isoform CYP2E1 in hepatocytes and Kupffer's cells). This paper deals with the pathomechanisms, clinical findings and currently available therapies for NASH. The potential use of metadoxine in the treatment of NASH is also discussed.

Localization of hepatitis C virus RNA on human erythrocytes by RT in situ PCR technique.

BACKGROUND: Our previous results showed that hepatitis C virus (HCV) is detectable on erythrocytes by RT in situ PCR. The aims of the present study were to compare the sensitivity of this erythrocyte in situ PCR to routine serum solution phase HCV PCR as well as to obtain more data about the binding and cellular localization of HCV in the erythrocyte. METHODS: 105 previously HCV-infected patients and 20 control individuals were studied using RT in situ PCR on erythrocytes and solution phase RT-PCR from serum samples. Binding of HCV to erythrocytes was studied by in vitro inoculation. RT in situ PCR results were evaluated by fluorescence and confocal laser scanning microscopy. RESULTS: From 105 HCV cases, 78 gave positive, while 5-and all control cases-gave negative results by both PCR techniques. In 21 cases, only the in situ technique provided positive results, while in only I case did the solution phase method provide positive results. During in vitro inoculation, an early HCV-erythrocyte binding was detected followed by virus internalization. CONCLUSIONS: Erythrocyte-in situ PCR was found to show higher sensitivity for the detection of HCV compared to the generally applied serum PCR method. In vitro studies suggested a specific binding of HCV to erythrocyte and showed the virus to be capable of internalization.

Oxidative damage in alcoholic liver disease.

OBJECTIVE: The metabolic effects of alcohol are due both to its direct action and to that of its first metabolite, and can also be connected with the changes in redox state. Differences in ethanol distribution, bioavailability and hepatic metabolism can provide insight into the protective and predisposing factors in alcoholism, as well as gender differences of alcohol toxicity. Oxidative stress occurs following various conditions of ethanol consumption. DESIGN: Twenty-six Caucasian patients with alcoholism and 32 healthy, abstinent controls of both sexes were investigated with special regard to reduction-oxidation status and ad hoc free-radical-antioxidant balance. METHOD: Plasma free SH-group concentration, H-donating ability, and reducing power property were measured by simple spectrophotometric methods. Total scavenger capacity was determined by a newly developed chemiluminometric method in plasma and erythrocytes. RESULTS: Alcoholics showed a decrease of free SH-group concentration, hydrogen-donating ability and an increase of reducing power property in plasma. A decreased total scavenger capacity of erythrocytes and plasma of alcoholic patients, combined with gender differences, could be detected. CONCLUSIONS: Alcoholic dependence causes gradual exhaustion of the antioxidant capacity of erythrocytes, therefore this non-invasive measurement may be useful as a follow-up of the evolution of alcoholic liver disease. The results also suggest a gender susceptibility of alcohol toxicity.

[Experience with combined interferon alpha-2b and ribavirin in the therapy of chronic hepatitis C. Experience with one-year therapy of 100 patients. Multicenter study]. / Interferon-alfa-2b és ribavirin kombinált kezelés krónikus C hepatitisben. 100 Beteg egy évig tartó kezelése során szerzett tapasztalatok. Multicentrikus Tanulmány Munkacsoport.

It has been established that the long term interferon therapy in patients with chronic hepatitis C is able to produce sustained remission only in about 20 per cent of the cases. According to the newest data the combined interferon and ribavirin therapy significantly increases the remission of patients in naive, non-responder or relapsed cases. Clinical remission was confirmed by enzyme activity of alaninamino transferase (ALT) and HCV-RNA-PCR tests. In order to get exact data of the remission rate and the symptom free period, a prospective multicenter study has been introduced in Hungary. Ten leading hepatologic units have been involved into the trial. Till now the combined therapy with interferon-alfa-2b (3 MU, three times a week) and ribavirin--(1000-1200 mg daily) for one year has been finished in 100 cases with chronic hepatitis C. The mean value of ALT activity decreased near to the normal level, in 58 patients it was in the normal range. Side effects with mild or moderate grades have been found in 31 cases. The interim report of this multicenter study confirm the efficacy of this combined therapy in chronic hepatitis C.

[Skin diseases associated with chronic hepatitis C]. / Krónikus C hepatitishez társult börbetegségek.

The authors are discussing hepatic and extrahepatic pathologic processes caused by hepatitis C virus (HCV) infection and they focus their interest to the skin disorders appearing in the presence of chronic, active HCV infections. The trigger of the immunologic processes leading to dermatologic manifestations are the activated T cells (CD8 + cytotoxic T lymphocytes), cytokins, and also the expansion of certain B cells. Pathologic immunologic phenomena may initiate various dermatologic manifestations. Immunoglobulins, immuncomplexes generated by the disease itself are manifested as various forms of cutan vasculitis. In the present series of patients (pts), HCV related skin disorders known from the literature were diagnosed in eleven cases and they were representing 7 different disease entities. These were palpable purpura (3 pts), urticaria, prurigo and alopecia areata (2-2 pts), lichen ruber planus, pruritus and vitiligo (1-1 patient respectively). The case reports of 2 pts, one with palpable purpura (vasculitis purpurica), one with prurigo and vitiligo are presented in details.

Oxidative stress in the liver and biliary tract diseases.

Oxidative stress plays an important role in the pathogenesis of toxic liver diseases and of other hepatic alterations. We summarize the pathomechanism of free radical reactions in liver diseases and the results of experimental and clinical observations. Most of the hepatoprotective drugs belong in the group of free-radical scavengers, their mechanism of action involving membrane stabilization, neutralization of free radicals and immunomodulation. We demonstrate the effects of the different drugs used in the therapy of liver diseases in animal experiments and in human clinicopharmacological studies. The scavenger effect of these drugs has been demonstrated in the subcellular fractions of liver cells in animal experiments. In vitro incubation with some hepatoprotective drugs inhibit lectin-induced lymphocyte transformation while others decrease the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. Dihydroquinolin-type antioxidants and silymarin enhanced the superoxide dismutase activity of erythrocytes and lymphocytes. In addition, in a 6-month double-blind clinical trial of patients with chronic alcoholic liver disease, we studied the effects of silymarin therapy on liver function tests, on the parameters characterizing the oxidative stress and immune reaction, on serum procollagen III peptide level, and on liver histology. A wide range of methods was used. The silymarin preparate corrected the altered immune reaction and the decreased superoxide-dismutase activity of erythrocytes and lymphocytes in patients with alcoholic liver cirrhosis. The results indicate that these drugs exert hepatoprotective activity and can improve liver functions in alcoholic patients and in toxic liver diseases. We found a correlation between the bilirubin concentration and lipid peroxidation in cases with toxic liver and biliary tract diseases, and assume that there are two kinds of bilirubin, an antioxidant and a prooxidant form, on the basis of diene conjugates in the bile.

[The role of oxidative stress and the preventive effect of free radical scavengers in arteriosclerosis]. / Az oxidatív stressz szerepe és a szabadgyökfogók preventív hatása arteriosclerosisban.

The role of oxidative stress in the development of arteriosclerosis is well established. This pathogenetic explanation unificates in itself the lipid and thrombotic theories. The authors summarize the most substantial literary data in this relation, they discuss in details those therapic methods, in which the natural and synthetic antioxidants are involved as preventive drugs in the development and consequences of arteriosclerosis. Thus the effects of the dihydroquinoline type antioxidants as well as those of Vitamins A, C and E are discussed partly in experimental, partly in clinical studies. The authors conclude on the basis of own and literary data that the application of antioxidants could decrease the blood vessel alterations produced by arteriosclerosis, as well as the pathological tissue alterations developed in the consequences of ischaemia.

[Possibilities and perspectives of the prevention of viral hepatitis]. / A vírushepatitis megelözésének lehetöségei és perspektívái.

Six district hepatotrop viruses causing viral hepatitis have been identified. Hepatitis A and E viruses are enterically transferred with feco-oral transmission, the others (hepatitis B, C, D and G viruses) produce the infection parenterally with blood, blood products and body fluids. All the hepatitis viruses are able to cause acute hepatitis. Chronic carrier state and chronic hepatitis can develop in case of infections with hepatitis B, C, D, and G viruses. In the prophylaxis the hygienic rules should be applied in all forms of infections. Passive immunisation and active vaccination have been safety developed til now only in hepatitis A and B infections. To prevent the hepatitis C, D, E and G infections the modalities of prophylaxis are in experimental stages.

[Epidemiology and clinical significance of the newly discovered GB,G hepatitis viruses]. / Az újonnan felfedezett hepatitisvírusok--GB,G--epidemiológiája és klinikai jelentósége.

A number of hepatitis viruses have been newly identified belonging to the family hepatitis A-E, by their genome structure. The authors summarize and briefly demonstrate the most important molecular and epidemiological characteristics of te hepatitis GB and G viruses, and they discuss their clinical significance. They discuss the similarities and differences recording the three GB (GB-A, GB-B, GB-C) viruses, and also stress the high rate of similarity between the GB-C and G viruses. All the three GB viruses and G virus have RNA-genome, all of them are transferable with blood and blood preparates, they have been found both in acute and chronic hepatitis. They occur with higher rate in high risk population where the frequency of hepatitis B and C also increased.

[Therapeutic principles after liver transplantation]. / Kezelési elvek májtranszplantációt követóen.

The nontechnical complications following liver transplantation and the main therapeutical principles are summarised. The immunosuppressive therapy against rejection is discussed. The author gives a survey on the prevention of the hepatitis B, C and D virus infection in liver transplant recipients.

[Effect of interferon-alpha2b therapy in chronic hepatitis C]. / Interferon-alpha 2B kezelés hatása chronicus C hepatitisben.

In chronic hepatitis C the interferon treatment given three times a week in a dosage of 3 million units (MU) normalizes the values of alanin-amino-transferase in a part of cases (25-40%), and produces bettering in the subjective complains of patients. In the short term therapy (3-6 months) the activity of ALT increases again after leaving the therapy, and the disease becomes active. The aim of this multicenter study in Hungary was to give newer data in the case of longterm efficacy with alpha-interferon. Ninety-one patients with chronic hepatitis C were selected into the open prospective clinical study in university and hospital departments. Treatment protocol was the following: Patients with chronic hepatitis C diagnosed by clinical and histological methods were treated with interferon-alpha 2B given 3 times a week in a dosage of 3 MU. Treatment period had lasted for one year and afterwards the patient had been on control for an other half a year. In non responder cases after 3 month treatment with interferon the dose of therapy was increased for 3 x 5 MU. In 37 cases (40.6%) out of 91 patients the authors found longterm sustained remission and in other 22 cases (24.2%) they observed a partial remission (among them 5 cases with late relapse). The rate of longterm sustained remission under 40 years was higher, than above 40. Higher rate was found when the treatment was started with a shorter chronicity of the disease. On te basis of the results the authors conclude: Interferon-alpha 2B is a good therapeutic modality for the treatment of patients with chronic hepatitis C. Efficacy of therapy is higher in younger patients and also in earlier application.

[Interferon therapy in chronic active viral hepatitis]. / Interferon kezelés vírus okozta krónikus aktív hepatitisben.

The authors give a short review of the recent data about the types of interferons and their biological activity. The role of interferons in the therapy of B, C and D chronic viral hepatitis is discussed. Interferon treatment means a substantial progress in the therapy of chronic viral hepatitis, however it represents a final recovery from chronic B or C hepatitis only in 25-40 percent or 40-45 percent of the cases, respectively. The authors refer to the combination therapy which seems to be promising in the future.

[Thymostimulin in clinical practice]. / Thymostimulin a klinikai gyakorlatban.

In insufficient function of bone marrow thymostimulin has an important role in the proliferation of haemopoetic cells, take part in the regeneration of lymphocytes, as well as in the normalisation processes of T lymphocytes. Its advantageous effect has been demonstrated in different viral infections, thus in herpes simplex, hepatitis B and C, as well as in AIDS virus induced diseases. It has also an important role in correction of the immunodeficiency of organism in various malignant diseases.