Hepatitis: Horváth G

Anonymous00086, Anonymous00087, Gervain J, Horváth G, Hunyady B, Makara M, Pár A, Szalay F, Tornai I, Telegdy L. · No affiliation provided · Orv Hetil. · Pubmed #19087916 No free full text.

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Dalmi L, Gervain J, Horváth G, Hunyady B, Ibrányi E, Makara M, Pár A, Szalay F, Tornai I, Telegdy L, Anonymous00498, Anonymous00499. · No affiliation provided · Orv Hetil. · Pubmed #18194921 No free full text.

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Horváth G, Tolvaj G, Halász T, Stotz G. · IRM Központi Kórház és Intézményei I. Belgyógyászati Osztály Budapest. · Orv Hetil. · Pubmed #17686672 No free full text.

Abstract: The first choice, and the most efficient therapy for chronic hepatitis C is the pegylated interferon + ribavirin treatment. The introduction and application of the STOP rule (pegylated interferon + ribavirin treatment should be stopped in cases without sufficient virological answer for the therapy at the 12th or 24th week of the treatment) is motivated by the very high cost of this treatment. Aims: The greatest problem of the application of the STOP rule is that these patients are not coming in for the proven advantages of one-year interferon treatment (arrest or decrease the inflammation, decrease or prevent the progression to liver cirrhosis, decrease probability or prevent the development of hepatocellular carcinoma), which were observed almost in virologically slow-, partial-, or non-responder patients who received one-year interferon therapy. Based on these data, the official Hungarian treatment protocol allows and recommends the continuation of the antiviral treatment by natural interferon for patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule. Patients and methods: 15 patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule (8 men, 7 women, age: 35-63, mean: 48.8 years, HCV genotype: 1b, HAI mean: 6.7, SD: +/-5.03; stage: mean: 1.75 SD: +/-0.9) treatment was continued with natural IFN for further 16-36 (mean 23.7) weeks. The total treatment duration was 48-52 weeks. The duration of follow-up was at least 6 months. Control group: 18 patients whose pegylated interferon + ribavirin treatment should have been stopped because of the STOP rule (7 men, 11 women, age: 32-63, mean: 48.7 years, HCV genotype: 1b, HAI mean: 10.1, SD: +/-4.8; stage mean: 2.0 SD: +/-0.6). The duration of follow-up was at least 6 months. Results: There is no significant difference between the two groups. The ALT level significantly decreased (73.4 U/l SD: +/-25.5 versus 45.9 U/l SD: +/- 22.1) due to pegylated interferon + ribavirin treatment, and remained at this level during the natural interferon treatment and the follow up (45.7 U/l SD: +/-15.1, and 49.3 U/l SD: +/-19.4 U/l; p < 0.001). The difference is significant. The ALT level decreased (108.5 U/l SD: +/-69.8 versus 86.0 U/l SD: +/-82.8) due to pegylated interferon + ribavirin treatment, but increased after the cessation of the therapy (99.7 U/l SD: +/-60.9) in the control group. The biochemical response (significant reduction of ALT level) which was detected during the pegylated interferon + ribavirin treatment remained permanent during the continuation and after the cessation of the therapy in the natural interferon treated group, while relapse occurred in every case in the control group. The viral load increased at least 1 log 10 after cessation of the therapy in pegylated interferon + ribavirin treatment non-responder patients. The natural interferon treatment was able to control the viral replication (prevent the increasing of the viral load), but after the termination of natural interferon dosage, similar elevation of viral load was observed. The subjective side effects of natural interferon treatment were rarely and milder. Leucopenia and thrombopenia occurs rarely and was milder than that during the pegylated interferon + ribavirin therapy. Conclusions: The patients have no difficulty in the application of natural interferon; probably the positive psychic effect of the fact that they have not been barred from treatment compensated the technical hardness (three injections weekly). A wide range of the application of this therapeutic possibility, and further studies with larger number of patients are suggested.

Halász T, Farkas A, Tolvaj G, Horváth G. · I. Belgyógyászati Osztály, Budapest. · Orv Hetil. · Pubmed #17489160 No free full text.

Abstract: Chronic C hepatitis is a global health problem. Its treatment is still unresolved. Pegylated interferon means substantive breakthrough in therapy. The longer effect, the lasting, steady therapeutic blood level are the pharmacokinetic advances. There is no significant difference in the side effects of pegylated interferon and standard interferon. The most frequent side effects leading to dose reduction or cessation of the treatment are depression and hematologic disorders. Neutropenia is induced more frequently by pegylated interferon, than by the standard form according to the literature. Combined antiviral treatment (pegylated interferon alpha-2a and ribavirin) of a 54 years old woman, who suffered from posttransfusion chronic hepatitis C was started. The dose of the pegylated interferon alpha-2a and ribavirin was reduced at the 8th week due to leucopenia and mild anemia. Fever, cough, sore throat and weakness occurred. Agranulocytosis was detected which was accounted as a side effect of pegylated interferon treatment. Antibiotic, antimycotic therapy and filgastrim was given. Leukocyte number increased, fever stopped after 10 days of therapy. The patient returned 17 days later. She had been having high fever, weakness, sore throat for 4 days. Ciprofloxacin was given by GP before her registration because of the suspicion of urinary infection, then she took sulfamethoxazol + trimethoprim without medical advise. Agranulocytosis was detected again, Staphylococcus sepsis developed. No sign of hematologic disease was found in the bone marrow. Agranulocytosis was considered aftermath of sulfamethoxazol + trimethoprim. Antibiotics, antimycotic and antiviral treatment, and filgastrim were given, sepsis healed, leukocyte number became normal. 274 patients suffering from chronic hepatitis C were treated by standard interferon, and 43 were treated by pegylated interferon. Rapid and significant decrease of leukocyte count was observed in the patients treated by pegylated interferon in the first 4 weeks of the treatment then it remained stable. Cessation of the treatment or dose-reduction was not necessary due to neutropenia among patients treated by standard interferon, while dose reduction was reasonable in two more cases in addition to this one, treated by pegylated interferon. The authors stress the importance of the exact follow-up of patients according to the protocol, which renders the early recognition of side effects, the prevention of complications, and their early and adequate treatment possible. Thus, pegylated interferon--inspite of its marked side effects and more serious suppressive effect on bone marrow--is the most effective drug for the treatment of chronic hepatitis C.

Bálint E, Bakay M, Onody K, Farkas F, Horváth G, Tolvaj G, Dávid K, Horányi M, Béládi I. · Department of Optics and Quantum Electronics, University of Szeged, Hungary. · Acta Microbiol Immunol Hung. · Pubmed #15571075 No free full text.

Abstract: Sera from 86 patients with chronic hepatitis C virus (HCV) infection treated with recombinant interferons-alpha (rIFN-alpha) were screened for IFN-binding and antiviral effect-neutralizing antibodies. Out of the 61 patients treated with rIFN-alpha2b, 46% had binding and 28% had neutralizing antibodies. 44% of the 25 patients treated with rIFN-alpha2a developed binding antibodies and 24% had neutralizing antibodies. Contradictory data were observed concerning the appearance of anti-IFN antibodies and the outcome of IFN therapy. A significantly higher number of the patients with a sustained response to rIFN-alpha2b therapy formed antibodies than the number among the non-responder patients. At the same time, in the patients treated with rIFN-alpha2a, opposite data were found. The activity of the antibodies in some sera was studied against the antiproliferative effect of IFNs on Daudi cells by measuring the [3H]thymidine incorporation. The binding antibodies without neutralization of the antiviral effect of the IFNs inhibited the antiproliferative activity of the rIFNs, similarly to antibodies having both IFN-binding and antiviral effect-neutralizing capacities. At the same time, the antiproliferative effect of the natural IFN was less affected. It is suggested that the antiproliferative assay is more sensitive than the antiviral method for demonstration of the presence of antibodies exerting an inhibitory effect on the biological activities of IFN.

Osztrogonácz H, Stotz G, Horváth G, Tolvaj G, Dávid K. · BM Központi Kórház es Intézményei, I. Belgyógyászati Osztály, Budapest. · Orv Hetil. · Pubmed #15279404 No free full text.

Abstract: INTRODUCTION: 239 anti-HCV seropositive blood donors (132 male, 107 female, age: 19-61, mean: 40.59 y.) and 174 family members of them (74 male, 100 female, age: 4-65, mean: 23.67 y.) were studied for chronic hepatitis C virus infection and chronic liver disease. Detailed virus serology, ultrasonography, and 6 months follow-up and--in patients with HCV RNA--liver biopsy were made. RESULTS: HCV RNA was determined in 165 patients. 70% of them were HCV RNA positive. The ALT level was normal in 95 cases (57%), and lower, than twice of the normal was in 34 cases (20%) among them. Liver biopsy was made in 79 patients; chronic C hepatitis was proven in 75 cases (steatosis in 3 cases, alcoholic liver disease in 1 case was observed). Inflammatory activity was minimal (HAI < 3) in 17, mild (HAI: 3-6) in 41, moderate (HAI: 7-9) in 7, and severe (HAI > 9) in 10 cases. There was no correlation between the serum ALT levels and the severity of the histological activity of chronic C hepatitis. Authors stress the importance of the fact, that 2 patients had normal ALT and 5 patients ALT levels were lower, than the twice of the normal of the 17 patients with significant inflammatory activity (HAI < 6). Chronic C hepatitis need for antiviral therapy was occurred in 45% of patients who known themselves previously healthy. CONCLUSIONS: The necessity of the systematic examination of anti-HCV seropositive patients and of the importance of the liver biopsy in patients with HCV RNA positivity is stressed. 3 anti-HCV seropositive cases of 174 family members of the blood donors were observed, but none of them was HCV RNA positive. It seems to be, family members of the HCV infected patients have no increased risk for HCV infection.

Földes I, Dávid K, Horváth G, Osztrogonácz H, Jankovics K, Tolvaj G. · BM Központi Kórház és Intézményei, Izotóp Osztály, Budapest. · Orv Hetil. · Pubmed #15264588 No free full text.

Abstract: INTRODUCTION: Many studies have explored that thyroid dysfunctions can be induced by cytokine therapy. Most observations were collected in connection with the treatment of viral hepatitis with interferon-alpha. AIM AND METHODS: Frequency and types of thyroid dysfunction developed during and after recombinant interferon-alpha treatment were studied in 138 patients with viral hepatitis C or B. Therapy lasted 12 months or more, subjects having thyroid dysfunction at the start of therapy were excluded from the study. Thyroid parameters (TSH, FT4, FT3 and anti-TPO) were controlled every third month. In patients in whom thyroid dysfunction occurred the measurements were repeated monthly and other tests were also performed (anti-Tg, IL-6, TSH receptor antibody, thyroid scan and 99mTc-pertechnetate uptake). RESULTS: Thyroid function disturbances were found in 30 (21.7%) patients, 12 of them (8.7%) showed persistent hypothyroidism. Hyperthyroidism was transitory in all cases. The clinical course of thyroid dysfunction might be monophasic (hyper- or hypothyroidism), biphasic (hyperthyroidism followed by hypofunction) or triphasic. Immune and non-immune forms can be clearly distinguished. CONCLUSIONS: Every fifth patient with chronic hepatitis showed thyroid dysfunction during interferon-alpha therapy, it is necessary therefore to control the hormonal status and the thyroid antibody titer. Treated patients have to be informed in advance that as a "side effect" persistent hypothyroidism may develop.

Kalabay L, Nemesánszky E, Csepregi A, Pusztay M, Dávid K, Horváth G, Ibrányi E, Telegdy L, Pár A, Bíró A, Fekete B, Gervain J, Horányi M, Ribiczey P, Csöndes M, Kleiber M, Walentin S, Prohászka Z, Füst G. · Third Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Kútvölgyi út 4, 1125 Budapest, Hungary. · Int Immunol. · Pubmed #14688060 links to  free full text

Abstract: 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.

Bíró L, Varga L, Pár A, Nemesánszky E, Telegdy L, Ibrányi E, Dávid K, Horváth G, Szentgyörgyi L, Nagy I, Dalmi L, Abonyi M, Füst G, Horányi M, Csepregi A. · National Institute of Hematology and Immunology, Budapest, Hungary. · Scand J Gastroenterol. · Pubmed #11099064 No free full text.

Abstract: 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.

Bíró L, Varga L, Pár A, Nemesánszky E, Csepregi A, Telegdy L, Ibrányi E, Dávid K, Horváth G, Szentgyörgyi L, Nagy I, Dalmi L, Abonyi M, Füst G, Horányi M. · National Institute of Haematology and Immunology, Budapest, Hungary. · Immunol Lett. · Pubmed #10841940 No free full text.

Abstract: In order to study the effect of interferon alpha on the levels of acute phase complement proteins in vivo, serum concentrations of C9 and C1-inhibitor (C1-INH) were measured in patients with chronic hepatitis C before and 3 months after the beginning of interferon alpha2b therapy. Serum levels of the activation product of terminal complement pathway, C5b-9, HCV RNA and IL-6 were also determined. IFN alpha treatment significantly (P<0.0001) increased the serum concentrations of both complement proteins. C5b-9 levels were found to significantly decrease during the same period of time. When the patients were divided into responders or non-responders (more or less than 50% decrease in plasma HCV RNA concentrations) C9 and C1-INH levels were elevated only in the responder patients. There was no correlation between the changes of IL-6 levels or the amounts of IFN alpha administrated on one hand, and the changes in the complement protein levels on the other. These findings suggest that the marked increase in the serum concentrations of the acute phase complement proteins is a secondary phenomenon due to the IFN alpha-caused diminution of the viral load and the resulting immune complex-induced complement activation.

Osztrogonácz H, Gerevich J, Horváth G, Tolvaj G, Dávid K. · BM Központi Kórház és Intézményei, Budapest. · Orv Hetil. · Pubmed #10803013 No free full text.

Abstract: Authors examined the prevalence of hepatitis B, C and D viral infections in Hungarian drug users. Between January 1995 and October 1998 256 examinations were made (58% intravenous, 42% non intravenous drug user). Hepatitis C virus infection in 27 patients, hepatitis C and B virus infection in 4 patients, hepatitis B virus infection in 17 patients was detected. Every hepatitis B virus positive case was past infection. Hepatitis D virus infection was not detected. Clinically overt liver disease was proved in more than half of the hepatitis C virus infected patients. Because of insufficient collaboration only 11 were followed up. Liver biopsy was made in 5 cases. Interferon therapy was indicated in 3 cases. The 24% of intravenous drug users was anti-HCV seropositive contrary to 1.4% of non intravenous group. Anti-HCV seropositivity was proved in 38% in common needle users, while in disposable needle users only 3%. The prevalence of hepatitis C virus infection in intravenous drug users is rather frequent in Hungary too. The exact diagnosis of liver diseases is very difficult as for insufficient collaboration. The prevalence of hepatitis B virus infection in i.v. and non i.v. drug users is the same as in the normal population. The importance of information, especially to avoid common needle use is stressed.