Hepatitis: Pár A

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.

This publication has no abstract.

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.

This publication has no abstract.

Dalmi L, Gervain J, Hunyady B, Ibrányi E, Makara M, Pár A, Szalay F, Tornai I, Telegdy L. · No affiliation provided · Orv Hetil. · Pubmed #17378168 No free full text.

This publication has no abstract.

Pár A. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika Pécs. · Orv Hetil. · Pubmed #19091671 No free full text.

Abstract: As hepatitis B and C virus (HBV, HCV) play a pivotal role in the development of hepatocellular carcinoma (HCC), the prophylaxis and treatment of these infections may mean also the prevention of HCC. The primary prevention of HCC is vaccination against HBV as well as the screening of blood donors for HBV and HCV markers. The means of secondary HCC prevention are as follows: antiviral therapy of HBV and HCV-related hepatitis and cirrhosis, screening ("surveillance") of cirrhotic patients for HCC using alpha-fetoprotein and ultrasound, and adjuvant antiviral treatment of HCC patients following curative tumor resection/ablation. It may be anticipated that the world-wide spread of HBV vaccination, the more effective individual treatment and novel antivirals will lead to the decrease of HCC incidence in the not so distant future.

Pár A. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika, Pécs. · Orv Hetil. · Pubmed #17430792 No free full text.

Abstract: The paper is devoted to overview the pathogenesis, diagnosis and treatment of the three immune-mediated liver diseases, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis.

Gasztonyi B, Antal I, Szendy E, Pár A, Hunyady B. · Pécsi Tudományegyetem Orvostudományi es Egészségtudományi Centrum, Altálanos Orvostudományi Kar, I. Sz. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #16468603 No free full text.

Abstract: INTRODUCTION: Viral hepatitis is a problem of population health. Recent data show an estimated number of 400 million patients infected with hepatitis B and 170 million with hepatitis C virus in the world. The prevalence of HBV infected patients is estimated to 50000, the prevalence of the HCV patients to 70,000 in Hungary. AIMS: The authors report the legal and occupational health aspects of viral hepatitis. The knowledge of these facts could help both the patients and doctors. This paper is on the employment, occupational restrictions of the infected patients, the legal aspects of the discrimination and the vaccination. The authors report the knowledge, rules and restrictions relating to health service employees in a separate subchapter. They call the attention to the occupational health aspects in relation to the infected patients and health service employees from the point of view of the occupational health specialist, the commissioner responsible for safeguarding the patients' interest and the specialist attending the infected patients.

Pár A. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #15384856 No free full text.

Abstract: First the short history of the disease, then its etiopathogenesis, the role of genetic, environmental and immunologic factors are described. In the second part, the questions of diagnosis, differential diagnosis and the immunosuppressive treatment, with new therapeutic modalities and liver transplantation are discussed.

Pár A. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #12501575 No free full text.

Abstract: Therapy of different manifestations of HCV infection is discussed--after 12 years of the discovery of HCV. In acute hepatitis C the antiviral treatment of the early phase is debated, but if 3 months after the onset the HCV viremia persists, interferon (IFN) therapy may be recommended. Asymptomatic HCV carriers with normal alanine aminotransferase (ALT) do not need antivirals. However, their serum ALT, GGT, gammaglobulin values and liver ultrasound findings should be monitored, to disclose an underlying liver disease, and biopsy is considered, if suspicion of hepatitis raises. In patients with chronic hepatitis C biopsy is mandatory, it may prove mild, moderate or severe histological activity (HAI). Moderate or severe active hepatitis C (> 2 x normal ALT, HAI > 7) should be treated. In the first period of the antiviral treatment for HCV, a standard IFN monotherapy (3 x 3 MU s.c. IFN weekly for 6-12 months) has been used, which resulted in 15-20% sustained response (SR) rate. In the second half of nineties, combination of IFN with an oral nucleoside analogue ribavirin increased the SR to 30-30%, by means of decrease in relapse rate. Recently, pegylated IFN (PEG-IFN) in combination with ribavirin can lead to 60% SR. (Genotype HCV1 patients may show SR of about 40%, HCV 2.3 ones about 80%, respectively). Compensated HCV cirrhosis patients may also be treated with this type of combination, which can possibly inhibit progression. Decompensated cirrhosis needs liver transplantation. In the prevention of HCV infection, screening of blood donors, viral inactivation of blood products, disposable needles and education of risk populations are of basic importance, HCV vaccination, however is not on the horizon yet. Thus, antiviral treatment remains of great significance. Searches for new therapeutic modalities, such as multiple antiviral combinations (e.g amantadin + ribavirin + IFN), protease- and helicase inhibitors, ribozymes and cytokines may result further advances.

Mózsik G, Figler M, Gasztonyi B, Karádi O, Losonzy H, Nagy A, Nagy Z, Pár A, Rumi G, Sütó G, Vincze A. · Pécsi Tudományegyetem Altalános Orvostudományi Kar, I. sz. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #12013685 No free full text.

Abstract: Molecular biological examinations have been carried out by the authors from 1995 in patients with different haemostasis, very recently these types of the studies were done in patients with different gastrointestinal (Helicobacter pylori-induced gastritis, hepatitis C infection, ileitis terminalis, ulcerative colitis, colon polyposis and adenocarcinoma in polyps) disorders. AIM, PATIENTS, METHOD: The Leiden mutation was detected by polymerase chain reaction (PCR) in 1354 healthy persons and patients with different GI disorders. RESULTS: The results of Leiden prevalence in patients with different gastrointestinal disorders were compared to those obtained in patients with venous thrombosis and familiar thrombophilia. The authors indicated that the prevalence of heterozygous Leiden positive persons was 5.9% in healthy (n = 87) and blood donors (n = 600). The prevalence of heterozygous Leiden mutation was 27% in patents who under went venous thrombosis (n = 300; P < 0.001), 38% in patients with familial thrombophilia (n = 116; P < 0.001). The prevalence of Leiden mutation was 0 in patients with Helicobacter pylori-induced gastritis (n = 24), 8% in hepatitis C infections (n = 75), 14.28% in Crohn's disease, (n = 49; P < 0.01), 27.5% in ulcerative colitis (n = 35; P < 0.001), 44% in colon polyposis (n = 59; P < 0.001) and 55% in situ adenocarcinomas (in polyposis) (n = 9; P < 0.001). CONCLUSION: The presented results suggest that the Leiden mutation is involved in patients with different inflammatory bowel disease, colon polyposis, as one of the suggested genetic factors.

Pár A, Szalay F, Lakatos PL, Nagy Z, Mózsik G. · Altalános Orvostudományi Kar, I. Belgyógyászati Klinika, Pécsi Tudományegyetem, Pécs. · Orv Hetil. · Pubmed #11816376 No free full text.

Abstract: Genetic factors play a privotal role in the pathogenesis of several liver diseases. A review is devoted to discussing the genetics of autoimmune hepatitis, chronic viral hepatitis B and C, cholestatic and alcoholic liver diseases, UDP-glucuronyl transferase deficiency, alpha, antitripsin deficiency, hereditary haemochromatosis, Wilson's disease and hepatocellular carcinoma.

Pár A. · Pécsi Tudományegyetem Altalános Orvostudományi Kar, I. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #11760453 No free full text.

Abstract: The paper is devoted to the actual questions of gastrointestinal immunology. In the first part, structure and function of gut-associated mucosal tissue (GALT), including the role of secretory immunoglobulins and importance of oral tolerance are shown. In the second part, the pathogenesis of unknown origin gastrointestinal and liver diseases (gluten sensitive enteropathy, inflammatory bowel diseases, autoimmune liver diseases, autoimmune pancreatitis) is described. Then the immunology of some gastrointestinal infections (Helicobacter pylori, hepatitis virus B and C, and HIV) and of alcoholic and drug induced, liver diseases is briefly summarized.

Pár A. · First Department of Medicine, Medical Faculty, University of Pécs Hungary. · Acta Physiol Hung. · Pubmed #11732890 No free full text.

Abstract: Immune mechanisms play a role in autoimmune hepatitis which is considered as "idiopathic" inflammatory liver disease of unknown etiology. However, even chronic viral hepatitis B and C have also features suggesting the importance of immunopathogenesis in their development. This paper discusses the major genetical and immunological factors in the above-mentioned chronic liver diseases and briefly summarizes their therapeutic modalities.

Pár A. · First Department of Medicine, University Medical School Pécs, Pécs, Hungary. · Can J Gastroenterol. · Pubmed #10938512 No free full text.

Abstract: This mini-review is devoted to the main questions of diagnosis, treatment and prevention of chronic hepatitis C (CHC). Diagnosis of CHC is based on virological, biochemical and histological findings. The etiology of CHC should be proven by the presence of antibody to hepatitis C virus (anti-HCV) and detection of viral nucleic acid (HCV RNA), using qualitative and quantitative polymerase chain reaction or branched chain DNA techniques. Serum aminotransferase levels can reflect the biochemical activity of liver disease, while biopsy is very important in the grading and staging of the pathological process. The generally accepted treatment of CHC is interferon (IFN); however, recently, the combination of IFN with the oral nucleoside analogue ribavirin has become the therapy of choice, not only for relapsers but also for naive patients. Prevention of hepatitis C by vaccination is not yet available. Screening blood donors and members of high risk groups, as well as ensuring good public health measures, are imperative to inhibit the spread of HCV.

Pár A. · I. Belgyógyászati Klinika, Pécsi Tudományegyetem, Altalános Orvostudományi Kar. · Orv Hetil. · Pubmed #10817009 No free full text.

Abstract: The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis.

Pár A, Telegdy L, Gógl A, Müller E. · Pécsi Orvostudományi Egyetem I. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #10377733 No free full text.

Abstract: 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.

Gasztonyi B, Pár G, Pár A, Hunyady B. · Pécsi Tudományegyetem, Orvos- es Egészségtudományi Centrum, Altalános Orvostudományi Kar, I. Sz. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #16408382 No free full text.

Abstract: OBJECTIVES: The authors described their experience with the therapy with pegylated interferon and its safety in patients with hepatitis C virus (HCV) induced liver cirrhosis treated at First Department of Medicine, Medical School, University of Pécs and at Tawam Hospital, Al Ain, United Arab Emirates. PATIENTS AND METHODS: Twenty four (12 male, 12 female, average: 55.66 +/- 7. 02 years) anti-HCV and/or HCV-RNA PCR positive cirrhotic patients were examined. Liver cirrhosis was diagnosed by abdominal ultrasound and/or histological examination of liver biopsy. RESULTS: Different genotypes of HCV were detected: genotype 1 in 7 cases, genotype 2 in 1 person, genotype 3 in 3 cases. Genotype 4 was detected in 10 patients, all of them were treated out of Hungary. Thirteen of 24 patients were not treated earlier, 6 persons were non-responders to previous interferon monotherapy, pegylated interferon was administered to 5 patients because of relapse. Biochemical parameters showed improvement in 16 cases (16/24, 66.66%), but did not in 5 patients. Until now, virological response was achieved in 13 patients (13/24, 54.16%), while three patients remained HCV-PCR positive. Temporary dose reduction was needed in 13/24 cases (54.16%). Withdrawal of therapy became necessary in only 2 patients due to severe neutropenia, thrombocytopenia and/or signs of decompensation. CONCLUSIONS: Pegylated interferon treatment is well tolerated by patients with compensated liver cirrhosis (Child-Pough stage A). Frequent side-effects (half of all cases) were usually mild or moderate requiring discontinuation only in 2 of 24 patients. The incidence of neutropenia and thrombocytopenia emphasizes the need of frequent blood cell count tests and patients follow up.

Pár G, Rukavina D, Podack ER, Horányi M, Szekeres-Barthó J, Hegedüs G, Paál M, Szereday L, Mózsik G, Pár A. · Institute of Microbiology and Immunology, University of Pécs, Pécs, Hungary · J Hepatol. · Pubmed #12217606 No free full text.

Abstract: BACKGROUND/AIMS: As chronic hepatitis C virus (HCV) infection is associated with impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and perforin expression of peripheral blood lymphocytes, as well as the effect of interferon-alpha2b (IFN-alpha2b) therapy. METHODS: Thirty-three patients had chronic hepatitis C, and of them 12 had been on IFN-alpha2b treatment. Eleven individuals had been treated earlier with IFN-alpha2b and completely cured, and eight were HCV carriers with persistently normal serum alanine aminotransferase. Three-colour flow cytometry was used to measure the percentage of CD3(+/-)CD8+, CD3+CD4+, gammadeltaTcR+, Vdelta2 TcR+, Vgamma9 TcR+, Vdelta1 TcR+, CD3-CD16+, CD3-CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by single cell cytotoxic and flow cytometric assay. RESULTS: Patients with chronic hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3-negative-CD8dim-positive (NK subtype) and Vgamma9/Vdelta2 TcR+ as well as perforin-positive T lymphocytes, compared to controls and to those who were cured from HCV infection. IFN-alpha2b increased NK cell cytotoxicity and the percentage of perforin-positive lymphocytes. CONCLUSIONS: Our findings suggest that in chronic HCV infection a decreased percentage of CD3(-)CD8+, Vgamma9/Vdelta2 TcR+ and perforin-positive T cells and simultaneous decreased peripheral NK activity may contribute to the impaired cellular immune response and the chronicity of the disease.

Pár A, Roth E, Miseta A, Hegedüs G, Pár G, Hunyady B, Vincze A. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar I. Belgyógyászati Klinika, Pécs. · Orv Hetil. · Pubmed #19103558 No free full text.

Abstract: Since oxidative stress may play a pathogenetic role in chronic hepatitis C, and sustained virological response to antiviral therapy is limited in HCV1 genotype infection, a double blind study was performed in HCV1 patients treated with pegylated interferon + ribavirin, to assess the efficacy of supplementation with the antioxidant flavonoid silymarin. PATIENTS AND METHODS: Thirty-two naive HCV1 positive patients with biopsy proven chronic hepatitis C, to be treated with pegylated interferon + ribavirin, have been randomized: group A): 16 patients have been given the antiviral therapy for 6-12 months plus placebo for the first 3 months; group B): 16 patients have been treated with pegylated interferon + ribavirin for 6-12 months plus silymarin, 2 x 166 mg/day, was given for 3 months. Serum alanine aminotransferase and HCV-RNA levels as well as parameters of oxidative stress such as plasma or red blood cell hemolysate, malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase and myeloperoxidase were determined after 0, 1, 3, 6 and 12 months during the treatment. Sustained virological response as undetectable serum HCV RNA was evaluated 24 weeks after the end of therapy. RESULTS: In the silymarin group, a more rapid decrease in the malondialdehyde level as well as a marked decrease in superoxide dismutase and an increase in myeloperoxidase activity after month 12 were found, alanine aminotransferase normalized in 6/16 (vs control 9/16) cases, and sustained virological response occurred in 3/16 (vs 7/16) patients. DISCUSSION/CONCLUSION: Although silymarin supportation to antiviral therapy improved oxidative stress, it was able to affect favourably neither the alanine aminotransferase nor the sustained virological response. These contradictory findings may be related to randomization bias as patients in study group B had more negative predictors of response: they were older with higher fibrosis score and even with more severe pretreatment baseline oxidative stress. Regarding the recently published in vitro experiments with silybinin on HCV replication as well as the newest convincing clinical observations, we do suggest further studies with more than three times higher doses of silymarin in controlled trials to assess the value of this supplementation in antivirally treated HCV patients.

Nemes B, Sárváry E, Gerlei Z, Fazakas J, Doros A, Németh A, Görög D, Fehérvári I, Máthé Z, Gálffy Z, Pár A, Schuller J, Telegdy L, Fehér J, Lotz G, Schaff Z, Nagy P, Járay J, Lengyel G. · Semmelweis Egyetem, Altalános Orvostudományi Kar, Transzplantációs és Sebészeti Klinika, Budapest, Baross u. 23-25., 1082. · Orv Hetil. · Pubmed #17932003 No free full text.

Abstract: 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.

Pár A, Tornai I, Szalay F. · Pécsi Tudományegyetem, Altalános Orvostudományi Kar I. Belgyógyászati Klinika, Pécs. · Orv Hetil. · Pubmed #17468063 No free full text.

Abstract: INTRODUCTION: In the past decade several multicentre, prospective, randomised trials revealed a significant progress in the therapy for chronic viral hepatitis, but limited and controversial data are available regarding the real value of the antiviral treatment in the everyday routine clinical praxis. AIM: A nation-wide retrospective analysis has been made of the antiviral therapy for patients with hepatitis B and C, who represented the entire patient population necessitating treatment in Hungary during a seven-year period. In addition, results of a prospective study for chronic hepatitis C patients were also presented. PATIENTS AND METHODS: A total of 220 patients with chronic hepatitis B treated with standard interferon alpha (112), pegylated interferon alpha-2a (23), or lamivudine (85) were investigated and assessed for the HBeAg seroconversion and/or undetectable HBV-DNA. Out of 2442 chronic hepatitis C patients, 333 were treated with standard interferon monotherapy, 1122 with standard interferon + ribavirin and 987 with pegylated interferon plus ribavirin combination for 6-12 months. In a prospective study, 69 patients with chronic hepatitis C were enrolled and treated with pegylated interferon alpha-2a plus ribavirin. The rate of sustained virological response, the predictors of outcome and the adverse effects of treatment were evaluated. RESULTS: For HBV patients standard IFN provided 31%, PEG-IFN 30% and lamivudine 31-33% sustained virological response rate, respectively. In chronic hepatitis C, a continuous improvement was noted in sustained virological response, from 13% by interferon monotherapy, to 31% by pegylated interferon plus ribavirin combination, in the nation-wide retrospective study, while even a 48% sustained virological response was achieved in the prospective trial. The most important predictors of outcome were the 4-week "rapid" and the 12-week "early" virological responses, then the female sex, age, BMI and adherence. The most frequent complications of the antiviral treatment were cytopenias, haemolysis and depression, 9% of patients experienced adverse effects. CONCLUSION: The efficacy of antiviral treatment unlike HBV infection, in chronic HCV hepatitis gradually improved in our every-day clinical praxis, but the results are far poorer than those achieved in a prospective study. To manage the growing populations of hard-to-treat patients with chronic viral hepatitis, there is a need for more effective treatment modalities, including optimized, individualized dosing and novel antivirals.

Pár A. · Pécsi Tudományegyetem I. Belgyógyászati Klinika Pécs, Ifjúság u. 13, 7643. · Orv Hetil. · Pubmed #17344161 No free full text.

This publication has no abstract.

Pár G, Berki T, Pálinkás L, Balogh P, Szereday L, Halász M, Szekeres-Barthó J, Miseta A, Hegedus G, Mózsik G, Hunyady B, Pár A. · Pécs Tudományegyetem, Altalános Orvostudományi Kar, I. Belgyógyászati Klinika. · Orv Hetil. · Pubmed #16623441 No free full text.

Abstract: BACKGROUND: The outcome of HCV infection and the response to antiviral treatment depend on both viral and host factors. Host immune response contributes not only to viral control, clinical recovery and protective immunity, but also to chronic hepatitis and liver cirrhosis. Establishing immunological status and identifying pretreatment immunological factors associated with better response to therapy might be of importance in the understanding of the successful immune response and in the future of combination therapy to HCV infection. AIMS: The authors delivered a review on the immunology of HCV infection and characterized the cause of impaired cellular immune response in chronic HCV infection. Natural killer (NK) cell activity, perforin and the inhibitory CD81 HCV co-receptor expression, and Th1/Th2 cytokine production of the monocytes and lymphocytes have been investigated. PATIENTS AND METHODS: 42 patients with chronic hepatitis C, out of them 25 being on interferon (PEG-IFN) + ribavirin (RBV) therapy, 12 sustained virological responders, 26 HCV carriers with normal transaminase values and 22 healthy controls were studied. NK cell activity, perforin and CD81 expression, the IFNgamma, TNFalpha, IL-2 (Th1) and IL-4, IL-6, IL-10 (Th2) production of LPS stimulated monocytes and PMA + ionomycine stimulated lymphocytes were measured by flow-cytometry. RESULTS: In patients with chronic hepatitis C we demonstrated decreased NK cell activity associated with increased CD81 expression. The perforin expression of lymphocytes was also impaired in HCV patients. The pretreatment capacity of the macrophages to produce TNFalpha was predictive for sustained virological response. This increased TNFalpha production of the monocytes counteracted the observed impaired Th1 type cytokine production of the lymphocytes. IL-10 and IL-4 production showed positive correlation with HCV RNA levels, and negative correlation with histological activity index was noted. PEG-IFN + RBV treatment increased NK activity, perforin expression, Th1 type cytokine production of thr lymphocytes and downregulated CD81 expression inducing effective cellular immune response against HCV. The author's results provide further data to understand the causes of impaired cellular immune response in chronic HCV hepatitis and may be useful in the developement of immunotherapy as an adjunctive treatment to cure patients with chronic hepatitis C.

Pál J, Nyárády Z, Marczinovits I, Pár A, Ali YS, Berencsi G, Kvell K, Németh P. · Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Pécs, H-7643, Hungary. · Pathol Oncol Res. · Pubmed #16554914 links to  free full text

Abstract: Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various - biologically active - epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections.

Pál J, Pálinkás L, Nyárády Z, Czömpöly T, Marczinovits I, Lustyik G, Saleh Ali Y, Berencsi G, Chen R, Varró R, Pár A, Németh P. · Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, Szigeti u. 12. Pécs, H-7643, Hungary. · J Immunol Methods. · Pubmed #16194545 No free full text.

Abstract: The hepatitis B virus X protein (HBxAg) is responsible for severe complications of HBV infections including primary hepatocellular carcinoma. A sandwich type ELISA and a flow cytometric microbead assay for quantitative determination of serum levels of Hbx-Ag are introduced. We have previously developed monoclonal antibody families against well-conserved epitopes on HbxAg, characterized by different immunohistochemical and immunoserological techniques. Special selection of the antibody pairs provided highly sensitive and highly specific tools for quantitative immunoassay development. The resulting assays were tested on human sera (208 samples) collected from patients suffering from different clinical forms of HBV infection. The sensitivity range of the sandwich type ELISA was between 4 and 2000 ng/ml as measured on both the recombinant antigen and the sera of chronic hepatitis patients. A further flow cytometric microbead assay was established and tested in parallel with the ELISA. The quantitative results of these two immunoserological techniques were in strong correlation and they were found to be highly specific and sensitive on clinical samples. The HBxAg ELISA technique is applicable for routine clinical laboratory measurements, and our HBxAg microbead technique is recommended for complex multiparametric measurements combined with other markers.

Pár A, Takács M, Brojnás J, Berencsi G, Paál M, Horányi M, Miseta A, Hegedüs G, Mózsik G, Hunyady B. · First Department of Medicine, Medical Faculty, University of Pécs, Ifjúság ut 13, H-7624 Pécs, Hungary. · Acta Microbiol Immunol Hung. · Pubmed #15704332 No free full text.

Abstract: The significance of co-infections with novel hepatitis viruses Hepatitis G (GBV-C, HGV) and TT virus (TTV) in chronic hepatitis C is not clear. We determined the prevalence of HGV RNA and TTV DNA in chronic hepatitis C patients and in asymptomatic hepatitis C virus (HCV) carriers, and assessed the influence of these agents on the course of HCV infection. Seventy-seven patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. Previous HBV infection was detected by testing serum HBsAg and aHBc. HGV RNA and TTV DNA were detected by PCR. In the healthy population, the prevalence of anti-HCV was 0.3%, HGV RNA 8.0% and TTV DNA 18.5%. In chronic hepatitis C HGV RNA occurred in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of HGV RNA was 9.09% and TTV DNA 75.7%. Neither HGV RNA nor TTV DNA had apparent effect on the HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.