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Background: Available data and our observations suggest that elevated levels of interleukin (IL)-6 and -10 and some complement parameters may be associated with a poor response to IFN alpha. We evaluated how baseline levels of C5b-9, IL-6, and IL-10 influence the outcome of IFN alpha treatment. Methods: Fifty-one patients with established chronic hepatitis C were enrolled and treated with IFN alpha-2b. Before and after a 12-week-IFN-treatment (3 MU or 5 MU tiw) serum levels of IL-6, IL-10, C5b-9 and RNA of hepatitis C virus (HCV) were assessed. Sera of 46 sex- and age-matched, healthy blood donors served as control. Results: While two-thirds of patients was considered 'responder', 14 patients had no significant decrease either in HCV RNA or in ALT levels. In the responder's group lower baseline levels of IL-6 and C5b-9 were found than those in the 'non-responder' group. As a result of IFN therapy HCV RNA and C5b-9 levels significantly decreased. While the serum concentration of IL-6 increased during the follow-up period, regarding IL-10, no change was observed. In patients with 'low' baseline levels of C5b-9 (<2053 ng/ml) IFN alpha resulted in a significantly (P = 0.0005) higher decrease in HCV RNA level. Regarding 'low' IL-6 values (<1.47 pg/ml) similar but somewhat less significant (P = 0.0039) difference was found if the change of HCV RNA was investigated. The odds ratio of patients with low IL-6 and/or C5b-9 to responding to IFN alpha treatment was almost 10 times (CI: 9.1 (1.8-50.9)) higher as compared with patients without 'low' levels of these parameters. Conclusion: Our data suggest that serum level(s) of IL-6 and/or C5b-9 taken prior to the initiation of IFN treatment may serve as surrogate marker(s) in evaluating patients with chronic hepatitis C whether to get IFN alpha in monotherapy or to consider having combination therapy in the form of IFN alpha-ribavirin. [ABSTRACT FROM AUTHOR]

Abstract Background Serum 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. Methods We 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. Results Forty-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). Conclusion Serum 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.

Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. Furthermore, these could from prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity, as a socioeconomic aspect. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antivirals and interferon-free combination therapies have been registered for the treatment of chronic hepatitis C with a potential efficacy over 90% and typically with a short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option.

Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. From a socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and / or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment as well as for on-treatment decisions, accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 1), 3-23.

Diagnosis and treatment of hepatitis B and D virus infections mean that the patient is able to maintain working capacity, increase quality of life, prevent cancer, and prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2015, which is agreed on a consensus meeting of specialists involved in the treatment of the above diseases. The prevalence of hepatitis B virus infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline emphasizes the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2015, 156(Suppl. 1), 25-35.

Diagnosis and treatment of hepatitis B and D virus infections mean that the patient is able to maintain working capacity, increase quality of life, prevent cancer, and prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2014, which is agreed on a consensus meeting of specialists involved in the treatment of the above diseases. The prevalence of hepatitis B virus infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline emphasizes the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection.

Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.

Unlabelled: The main indication of the Hungarian Liver Transplant Program is liver cirrhosis caused by hepatitis C., Aim: Authors present the results of liver transplantations performed due to HCV infection., Method: The data (donor-, recipient-, perioperative characteristics, survival, serum titer of C RNA, histology) of 111 HCV positive recipients were evaluated, that are 37.6% of the 295 patients, who were transplanted since 1995 till the closure of this report., Results: Twenty-two (22) of them (20%) died in the early postoperative period, for other reasons, before the recurrence of the HCV was detectable. Among the 89 HCV-positive patients the recurrence of the HCV is still not detected in 16 cases (18%), and there is a histology-proven recurrence in 73 cases (82%). In 40 cases (56%) the viral recurrence was proven within 1 year after OLT, while in 32 cases (44%) over 1 year. The cumulative 1, 3, 5, and 10 years patient survival is 73%, 67%, 56% and 49%, among HCV-positive patients and 80%, 74%, 70% and 70% among HCV-negatives. The difference is significant. The cumulative graft survival at the same time points is 72%, 66%, 56% and 49% among HCV-positives and 76%, 72%, 68% and 68% among HCV-negatives, which is a non-significant difference. The serum titer of HCV-RNA was significantly higher among those HCV-patients who had an early viral recurrence within 1 year, compared to those who had a late one. In case of an early HCV-recurrence the Knodell-score was significantly higher in the 6 months posttransplant biopsy than that of in case of late viral recurrence, however, less fibrosis was observed in early recurrence., Conclusions: An early HCV recurrence can be expected in case of an older donor, with a marginal or fatty liver graft transplanted with a higher transfusion need and having an acute rejection treated with steroid bolus in the postoperative period. The protocol of the postoperative antiviral treatment differs from the average: the so-called "stop-rule" cannot be applied, since less then 10% of the recipients are expected to turn to HCV-PCR-negative due to the immunosuppression. The combined interferon + ribavirin treatment is maintained in spite of RNA-positive state, further, a second or third course of treatment might also be applied. The prolonged and--in case if necessary--repeated antiviral treatment prevents fibrosis, and therefore rate of retransplantation need. The better is the general state of the patient the results of a secondary liver transplantation are better as well. MELD-score can help to set the exact timing for a re-OLT.

Background: Serum concentration of fetuin A/alpha2HS-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., Methods: We determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrollment and in the 1st, 3rd, 6th, and the 12th month thereafter., Results: Forty-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 microg/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 microg/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 microg/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 > or = 365 microg/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 microg/ml had significantly shortened survival both in groups with MELD < 20 and MELD > or = 20 (p < 0.0001 and p = 0.0014, respectively)., Conclusion: Serum 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.

Introductions: The authors summarize the demographic, morbidity and mortality characteristics of the Hungarian Liver Transplant Program., Aims: They evaluate the changes and development, that has taken place with regard to indications, recipient population and characteristics, operation technique, and peroperative patient management., Method: In order to present the development, data are compared between two time periods (before and after 1999). The results are summarized on Tables and statistical Figures. Categorical variables are evaluated by chi2-test, continuous ones are with Levene Test (for homogeneity of means), Student T test and Mann-Whitney U-test. Cumulative survivals are computed with Kaplan-Meier log rank analysis., Results: 194 primary liver transplantation have been performed. The hepatitis C was the leading indication from the beginning. Ten (10) liver transplantation have been performed in 1995, while 44 in 2004. The mortality within the first 2 months decreased from 24% to 5%. The 1, 3 and 5 year cumulative patient survival increased from 55%, 45% es 39% (1995-1997), to 72%, 64% es 61% (1998-2000). Recently this is 78%, 77% es 77%., Conclusions: Between 1995-1997 conventional liver transplantation became standard, while piggy back turned to be popular from 1998. From 1999 the HCV-PCR monitoring, the combined antiviral treatment, the UW perfusion of the donors took place. From 2003 we introduced the tailored immunosuppression, the steroid-free protocol for viral diseases. Total infused volume was decreased together with the amount of transfusion. The retrograde graft reperfusion (from the caval side) was introduced in 2004 together with the split technique in the liver transplantation and the rebirth of the pediatric program. The overall outcome of the retrospective analysis is, that the program has been developed to European standards with respect to its volume, technical capabilities and results.

Treatment of hepatitis B. Treatment of acute icteric hepatitis B is similar to the principles of treatment of acute hepatitis syndrome. Special care must be given to the possibility of fulminant outcome and to the trend to chronicity. Diagnosis and treatment of chronic hepatitis B serves prevention of liver cirrhosis and hepatocellular carcinoma as well as elimination of the sources of further infections. Interferon-alpha treatment results in sustained clinical and virological response in about half of the patients. Nucleoside analogues as lamivudine, entecavir, adenovir dipivoxil are the alternatives. They are effective also in endstage liver cirrhosis caused by hepatitis B virus and able to prevent reinfection and graft loss after liver transplantation. Evaluation of the benefits and disadvantages of the antiviral agents help to determine the individual, patient-tailored treatment.

Previously we observed elevation of the serum concentration of two acute-phase protein (AFP) complement components (C9 and C1-inhibitor) in patients with chronic hepatitis C who responded (R) to IFN-alpha therapy, but not in non-responders (NR). In the present study we investigated the effect of high-dose IFN-alpha therapy on serum concentrations of two positive [orosomucoid (OROSO) and C-reactive protein (CRP)] and two negative [transferrin (TF) and fetuin/alpha2HS-glycoprotein (AHSG)] AFP in an outpatient setting. We investigated blood samples of 40 patients with chronic hepatitis C at the onset and at the end of a 3-month treatment with high-dose IFN-alpha2b (5 MIU/day for 6 weeks, followed by 5 MIU t.i.w.) and of 52 healthy individuals. Serum concentrations of OROSO, TF and AHSG were measured by radial immunodiffusion; CRP levels were determined by immunotubridimetry. Compared to controls, patients with chronic hepatitis C had significantly lower OROSO and CRP, and higher AHSG levels. By the end of treatment, OROSO concentration increased in R (P = 0.0054), but not in NR patients. In contrast, TF levels decreased in R (P = 0.0040), but did not change in NR patients. Similarly, in R patients, AHSG levels tended to decrease (P = 0.0942) following IFN-alpha treatment. We conclude that the acute-phase reaction is suppressed in patients with chronic hepatitis C that may be potentially related to the responsiveness to IFN-alpha therapy.

Introduction: In addition to interferon, lamivudine is the other widely used antiviral agent in the therapy of chronic hepatitis B. This nucleoside analogue inhibits the RNA-dependent DNA polimerase and the reverse transcription by integrating in the viral DNA, which results in the secondary suppression of viral protein synthesis and replication of HBV. It has numerous advantages such as effective viral inhibition, mild side effects and the possibility of oral administration; on the other hand it poses the problem of time-correlated appearance of lamivudine resistant mutants during therapy., Aims: In the Virusserology Laboratory of the Department I. Internal Medicine, Szent György Hospital, Székesfehérvár, detection and type determination of the therapy resistant mutants in the C and B domains of HBV DNA polimerase gene has been carried out the for one year. In this paper, the authors review the molecular biological background of lamivudine resistance and summarise the applied test methodologies and the early results., Patients: Six-month and/or 12-, 18-month samples of 18 chronic hepatitis B patients (4 women/14 men) treated in seven Hepatology Centres in Hungary were analysed., Methodology: Mutants of codons 528, 552, and 555 in the HBV polimerase gene were determined by nested polimerase chain reaction and reverse hybridisation., Results: M528, V552, I552 and I555 mutants in different variations could be detected in ten out of 18 patients., Conclusions: Nowadays, drug therapy is the only treatment option used for the therapy of early and progressed chronic hepatitis B in Hungary. This new diagnostic technique was introduced to clarify the background of ineffective lamivudine therapy. Therapy resistance can occur due to the lack of reaction or the appearance of the special, therapy resistant mutants of the virus. Detection of these YMDD mutants together with the clinical picture and the biochemical and virological parameters can help in forming a decision about cessation of lamivudine therapy or application of a new drug.

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 (< 4.0 mmol/l) than in those with normal (> 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.

The gastrointestinal mucosa is one of the principal portal of entry in systemic fungal infections. Esophagitis is the most frequent among the fungal infections of the gastrointestinal tract. The etiologic factors of fungal infections are various Candida species, most frequently Candida albicans. Due to the large number of asymptomatic patients, great attention should be paid to the predisposing factors (AIDS, cancer, antibiotic or steroid therapy). The diagnosis is based on the endoscopic picture, microscopic examination and culture of the mucosal brushings, and histological examination of the esophageal mucosa. The treatment is based on azol derivates, mainly fluconazole. In fluconazole resistant cases amphotericin B is the drug of choice. The rare complications are perforation, bleeding and stricture.

Objective: Human fetuin/alpha2HS-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 microg/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.

The authors present a case of an adult with Kawasaki syndrome, who, due to jaundice, enlarged liver and abnormal liver function tests, was admitted the hospital with the suspicion of liver disease. The symptoms of Kawasaki syndrome appeared during the first nine days of the hospital stay. The authors emphasise, that liver function tests are frequently abnormal in adults presenting with this clinical entity, therefore Kawasaki syndrome should be taken into consideration in the differential diagnosis of liver diseases.

Symptoms related to fungal esophagitis were studied in patients with alcoholic liver disease who underwent upper gastrointestinal endoscopy. Data of 517 patients were studied retrospectively (group I) and 100 alcoholic liver disease patients, that were successively admitted to hospital, were enrolled in the prospective part (group II). Out of the 41 cases with fungal esophagitis found in group I, data of 38 could be evaluated. In group II 13 of the 93 evaluable patients had fungal esophagitis; according to Kodsi's grading 10 patients had grade 1., one patient grade 2. and two patients grade 2-3. oesophagitis. There was no case with grade 4. esophagitis. The rate of symptoms among the 51 patients with fungal esophagitis was: anorexia 23 (45.0%), abdominal pain 22 (43.1%), vomiting 17 (33.3%), nausea 15 (29.4%), occult gastrointestinal bleeding 12 (23.5%), weight loss 9 (17.6%), melena 7 (13.7%), bloating 6 (11.7%), acidic regurgitation 3 (5.8%), haematemesis 2 (3.9%), thoracic pain 2 (3.9%), singultus 1 (1.9%), odynophagia 0 and dysphagia 0. In 7 patients (13.7%) none of the studied symptoms could be identified. Despite the relatively high frequency of symptom free fungal esophagitis reported in the literature, the total lack of odynophagia and dysphagia in our patient group was remarkable. In the lack of deglutition disorders the other symptoms do not raise the suspicion of esophagitis. The diagnosis in such cases can be established only by endoscopy.

A 38-year-old, male patient, with end-stage HCV cirrhosis, underwent liver transplantation (OLT). After a sufficient recovery a rapid elevation of ALT and profound jaundice developed 3 months after OLT, together with a 15-fold rise of pre-transplant HCV RNS level. Liver biopsy was carried out, histology excluded rejection and signs of acute hepatitis were observed. Interferon alpha 2b 3 MU TIW and ribavirin 800 mg/day resulted in normalization of ALT, se. bilirubin and decrease of viral load by 90 per cent at the 3rd month of treatment. Improvement of hepatitis and no rejection was shown by control histology. A 6-month combination therapy followed by continuous ribavirin monotherapy maintains a permanent good condition with normal ALT, no icterus, a continuously low HCV RNA level and a mild chronic hepatitis with fibrosis in the liver histology 18 months after OLT. Danger of HCV reactivation after OLT, difficulties of diagnosis, interactions of immunostimulant and immunosuppressive drugs, advantages of combination therapy are discussed.

In Hungary over the past 5 years more than thousand patients with chronic viral hepatitis have been examined and included in a treatment program with interferon (IFN) at 16 major hepatology centers, using unified diagnostic and therapeutical criteria. Authors give an account of their experiences on the clinical features of patients with chronic viral hepatitis and report the results of the treatment with IFN. According to the rules and availability of IFN for patients with chronic viral hepatitis in the country, virtually the entire Hungarian population with this diseases who required IFN therapy have been included. A total of 94 patients suffered from hepatitis B virus (HBV) infection, in addition 11 HBV + hepatitis Delta virus (HDV), 24 HBV + Hepatitis C virus (HCV) related liver disease, and 993 had chronic hepatitis C. IFN therapy for chronic HBV hepatitis consisted of IFN 5 MU thrice weekly for 6 months, and resulted in 33% seroconversion and sustained remission with 14% HBsAg clearance. For chronic hepatitis C treatment protocols (dose of IFN and duration of therapy) have changed with the time (from a weekly dose of 3 x 3 MU IFN for 6 months, to 3 x 3 MU for 12 months), and even a combination with ribavirin has been introduced. Although the therapeutic results showed a gradual improvement form a 13% sustained response over 22% in the first and second periods, respectively, differences were most significant with the advent of the combination therapy, that resulted in 36% remission rate. Only fibrosis in histology and baseline pretreatment HCV-RNA level appeared as predictors of response in chronic hepatitis C. Neither age nor gender did influence the outcome, but longer duration of treatment and higher total dose of IFN resulted moderately higher sustained remission rates. The experiences are in accordance with findings of suboptimal efficacy of IFN monotherapy reported worldwide and emphasize the need of seeking for newer and combination therapeutic modalities for these chronic viral diseases.

Loss of cellular immunity accompanying the progressive HIV/AIDS disease, results in altered clinical picture and outcome of traditional infections as well as severe and often lethal illness caused by facultative pathogens. Unusual infections may call the attention to the underlining HIV disease. Liver disease appears in the great majority of HIV/AIDS patients. The authors review the viral, bacterial, fungal and protozoal infections involving the liver in AIDS. Liver biopsy has a diagnostic value beside the serology and bacteriology and may give therapeutic consequences.

Eighty four patients with viral hepatitis attributed to infection with hepatitis B virus (HBV) (n = 43) or hepatitis C virus (HCV) (n = 41) were included in this study employing the MTH-68/B vaccine, an attenuated variant of Bursal Disease Virus. Twenty of the 43 patients in the HBV group, and 22 of the 41 HCV patients were treated with MTH-68/B. The remaining patients received conventional therapy. Significantly more patients progressed into active chronic hepatitis on conventional therapy (13% of HBV and 26% of HCV cases respectively) than in the vaccine treated groups (0% and 9%). Relapses occurred less frequently in the vaccine treated groups (5% of HBV and 32% of HCV) than in the control groups (9% and 79%), while remissions within one month of treatment were observed more often in the vaccine treated groups (both 50% respectively) than in the control groups (26% of HBV and 21% of HCV patients respectively). The duration of hepatitis was also considerably shortened by MTH-68/B treatment in both HBV (from 7.5 +/- 3.7 to 5.9 +/- 3.0 weeks) and HCV patient groups (from 8.9 +/- 7.4 to 5.3 +/- 4.4 weeks). The data presented suggest that attenuated, non-pathogenic viruses may be of significant benefit for patients with viral hepatitis B and C infections.

The features of chronic hepatitis B virus (HBV) related liver diseases and the aim of their therapy have briefly discussed, then treatment modalities are listed. In Hungary, between 1994 and 1996, a total of 68 patients with chronic hepatitis B have been treated with interferon (IFN). IFN resulted in complete clinical-biochemical remission in 50% of the patients, and in 32% the HBV replication was also eliminated. There are various nucleoside analogues, among them mostly famciclovir and lamivudine have been intensively studied as potentially effective treatment for HBV infection, and controlled clinical trials are in progress with these drugs. Nucleoside analogues in combination with IFN possibly improve treatment results in this disease. Various immunomodulatory agents--such as levamisole, thymosine, interleukin-2, and other cytokines--as well as the prednisolon-withdrawal induced rebound phenomenon have also been tested in HBV infection, but with no generally established benefit. A recombinant HBsAg vaccine is under investigation for therapeutic use. For end-stage HBV liver cirrhosis, liver transplantation is the only treatment, but the problem of reinfection is not still solved for more reasons.

Unlabelled: The health-care workers are known to be at risk of occupational transmission of blood-borne viruses. The goal of the investigation was to determine the prevalence of hepatitis C virus (HCV) antibody and the occupational risk of HCV transmission among personnel at the Central. Hospital for Infectious Diseases, Budapest, Hungary. Serum samples of 409 health-care workers were tested for antibody to HCV with second and third generation ELISA-s and anti-HCV positive samples were confirmed with Western Blot Line EIA. A total of 10 (2.4%) of the health-care workers were confirmed to be anti-HCV positive. The prevalence of anti-HCV increased with advancing age: zero under 20 yr age group (N = 0/15), 0.9% in 21-30 yr age group (N = 1/112), 1.8% in 31-40 yr age group (N = 2/111), 3.1% in 41-50 yr age group (N = 3/96) and 4.0% in above 50 yr age group (N = 3/75). We found anti-HCV positive hospital worker in 9 out of 17 departments. The prevalence of hepatitis C antibody was 7.1-1.9% among the personnel of internal departments, pathology, intensive care unit and pediatric departments. No anti-HCV positive health-care worker was found in the surgery and laboratories. None of the physicians tested was seropositive for HCV. Eight of the nurses, one of the sanitary personnel and one pathological technician were seropositive for HCV. Two nurses developed a chronic C hepatitis after a needlestick accident., Conclusions: 1. The hospital personnel is at risk for HCV infection. 2. The occupational risk of HCV infection increases with age but the risk is considerable lower than that of hepatitis B infection. 3. The occupational risk is highest among the workers of the chronic internal department, pathology and intensive care unit. 4. The nurses are at higher risk of HCV infection than the physicians. 5. The needlestick injury is associated with an increased risk for acquiring HCV infection.

The authors report in this ciency in the majority of the cases was alcohol abuse or article about their experiences, how could they select a small group of patients awaiting liver transplantation since September 1994. The cause of the liver insuffiHCV infection. During 37 weeks 3 liver transplantations were performed and 5 patients died on the waiting list. (15,6% of the patients on the waiting list.)

The aim of the study was to assess the effectiveness of a single-dose fluconazole treatment of fungal esophagitis in patients with alcoholic liver disease. Twenty-two alcoholic liver disease patients with fungal esophagitis were randomly assigned to receive either a single-dose of 150 mg fluconazole or a 7-day treatment of daily 50 mg fluconazole. Control esophagoscopy was performed in both groups on days 9-11. Direct smears and cultures on Sabouraud's medium were performed at both endoscopies. Patients' sera were tested for Candida antigens and for antibodies against Candida albicans on days 1, 8 and 15. Twenty patients (18 C. albicans, 1 C. tropicalis, 1 C. pseudotropicalis) completed the study, there were two drop-outs from the single-dose group. Antibodies against C. albicans were found in four cases, Candida antigens in five. There were no significant differences in the treatment outcome between the two groups, clinical cure was recorded in eight out of nine patients in the single-dose group and nine out of eleven patients in the 7-day group, mycological eradication in four out of nine, and in three out of eleven, respectively. Single-dose fluconazole treatment seems to be an effective therapy of fungal esophagitis in alcoholic liver disease patients.

The diagnostic value of ultrasonography (US) and endoscopic retrograde cholangio-pancreatography (ERCP) was compared, in 66 patients with bile duct obstruction, who underwent subsequent biliary surgery. The level of the blockage was diagnosed by US with a 80%, by ERCP with a 95.4% sensitivity, while the cause of the obstruction was determined with a 50% and a 89% sensitivity, respectively. Predictive value of these examinations is over 90%. Based on the clinical results and on the high diagnostic value of the above mentioned examinations, it is essential to fill up the bile ducts with direct contrast material.