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Background and aims: The response rate of interferon-α (IFN-α), recently introduced in the treatment of chronic hepatitis C, is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-α treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. Patients and methods: Twenty chronic hepatitis C patients were studied; 10 received IFN-α therapy for 6 months and 10 for 12 months. Liver biopsy material was taken before and after therapy. Results: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. Conclusions: Twelve-month IFN-α treatment affords a better response in the liver histology grade and serum ALT level, but does not influence the staging; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring. [ABSTRACT FROM AUTHOR]

Introduction and objective: Two-thirds of patients with hepatitis C virus (HCV) infection are unaware of their infection in the European Union. The WHO aims to reduce the number of new cases of chronic hepatitis by 90% by 2030. The proportion of people infected with HCV in prisons can be up to ten times higher compared to the general population. This article is a summary of the results of the HCV screening carried out in the Hungarian prisons between 2007 and 2017. Method: Screening of anti-HCV antibodies has been performed on a voluntary basis followed by HCV PCR and genotyping in positive cases. After obtaining written informed consent from the patients, treatment was started. Treatments were performed under the guidance of hepatologists in collaboration with prison medical staff. Results: HCV screening programs and treatments are in place in 84% of Hungarian prisons. A total of 25 384 patients underwent anti-HCV screening. Anti-HCV positive result was detected in 6.6% and HCV PCR positivity was confirmed in 3.8% of the screened inmates. 55.2% patients from the HCV PCR positive population were put on treatment. Only 143 patients received full treatment, while 162 (42.6%) treatments were terminated prematurely, and the duration of treatment was unknown in 75 patients. Based on the results available on the 24th week after the end of treatment, sustained virologic response rate was 88%. Discussion: Education of patients and collaboration between hepatologists and prison medical staff play an important role in the successful result of treatment. Conclusion: Our experience demonstrates that the test and treat principle is feasible and effective at microeliminating HCV in prisons.

Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue. We confirmed earlier results showing a brain region dependent myelin destructive effect of cuprizone. In addition, high resolution in situ CARS imaging revealed myelin debris forming lipid droplets alongwith myelinated axon fibers. Quantification of lipid debris with custom-made software for segmentation and three dimensional reconstruction revealed brain region dependent accumulation of lipid drops inversely correlated with the thickness of myelin sheaths. Finally, we confirmed that in situ CARS imaging is applicable to living human brain tissue in brain slices derived from a patient. Thus, CARS microscopy is potent tool for quantitative monitoring of myelin degradation in unprecedented spatiotemporal resolution during oligodendrocyte damage. We think that the accumulation of lipid drops around degrading myelin might be instrumental in triggering subsequent inflammatory processes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A phase 3, randomized, double-blind trial was conducted in subjects with diabetic foot infections without osteomyelitis (primary study) or with osteomyelitis (substudy) to determine the efficacy and safety of parenteral (intravenous [iv]) tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem ± vancomycin. Among 944 subjects in the primary study who received ≥1 dose of study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.5% of tigecycline- and 82.5% of ertapenem ± vancomycin-treated subjects were cured. Corresponding rates for the clinical modified intent-to-treat population were 71.4% and 77.9%, respectively. Clinical cure rates in the substudy were low (<36%) for a subset of tigecycline-treated subjects with osteomyelitis. Nausea and vomiting occurred significantly more often after tigecycline treatment (P = 0.003 and P < 0.001, respectively), resulting in significantly higher discontinuation rates in the primary study (nausea P = 0.007, vomiting P < 0.001). In the primary study, tigecycline did not meet criteria for noninferiority compared with ertapenem ± vancomycin in the treatment of subjects with diabetic foot infections., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy. Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice since decades. The reactive hepatitis is not frequent, but known serious side effect of alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity is 2.5-10%. In our case, gestation hypertension developed at the 21st gestation week of a 35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker therapy was introduced. On the 23rd gestation week acute hepatitis developed. During differential diagnosis of hepatitis, the etiology of methyldopa was taken into account. Viral and autoimmune origin was rolled out. No fetal aberration was found during ultrasound examination. The function of drug metabolizing function from blood was measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4 gene expression. With the reduced nifedipine therapy (30 mg daily), blood pressure was successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was based on anamnesis, clinical picture and the results of chemical and radiological examination and confirmed by the level of drug-metabolizing capacity. The gestation hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in pregnancy in their case report. Our case report confirms that monitoring of serum aminotransferase level is still valuable when treating a pregnant woman with alpha-methyldopa.

The use of valeriana was underplayed at the beginning of the 20th century because of its addictive and side effects. The 38-year-old woman, mother of a 20-month-old child from Eastern Europe, was treated with liver insufficiency and vascular, parenchymal decompensated cirrhosis needing plasmapheresis for the first time in our hospital. In case history, abusus of aethyl-alcohol and valeriana was found to be as toxic agent which was treated as the etiologic factor of the liver disease and liver failure. After intensive and conservative treatment her status was stabilised, during the follow-up she had no signs and symptoms, the laboratory results tend to be in normal range. Half year after her hospitalization intensive care treatment was necessary abroad due to gastric bleeding. In the background the histology of gastric biopsy taken during gastroscopic examination showed gastric sigillocellular carcinoma in our hospital. Total gastrectomy, omentectomy, lymphadenectomy were performed, the tumor was removed and she received cytostatic treatment. The use of valeriana and aethyl-alcohol is supposed to have a potential effect on tumorgenesis and on the increase of toxicity.

Background/aims: Hepatitis C virus infection is an important disease with a high chronicity rate (50-80%), leading to end-stage liver cirrhosis and hepatocellular carcinoma. In this study, the characteristic histological findings were compared with the epidemiological features of hepatitis C virus infection in liver biopsy material., Methodology: Liver biopsies were studied from 106 patients (60 males, 46 females, aged 11-81 years, mean: 43) found positive for hepatitis C antibody by a second-generation ELISA method. The histological evaluation was based upon the Desmet classification of chronic hepatitis. Statistical analysis involved the chi 2 test., Results: Minimal, mild chronic, and moderate chronic hepatitis were manifest in 13%, 65% and 22% of the cases, while fibrosis 0/1, fibrosis 2, fibrosis 3 and cirrhosis (fibrosis 4) occurred in 42%, 13%, 35% and 10%, respectively. Regarding the histological features of chronic hepatitis C, the frequency of steatosis, lymphoid follicles and/or aggregates and bile duct lesions showed an increase parallel with the hepatitis grade, the changes being more pronounced in moderate chronic hepatitis., Conclusions: Most chronic hepatitis C patients displayed mild histological lesions with stage 1 fibrosis. Lymphoid follicles and/or aggregates, bile duct damage and steatosis are important diagnostic features that show strong correlation with chronic hepatitis activity. The occurrence of stage 3/4 fibrosis in mild chronic hepatitis alerts the hepatologists for the need of liver biopsy.

Background: More than 100 million people are infected with hepatitis C virus (HCV) worldwide. The prevalence of HCV infection varies from country to country and the natural history of hepatitis C infection is not well understood., Objectives: The prevalence of anti-HCV positive blood donors in South Hungary was determined. Potential risk factors of HCV transmission were investigated and compared to anti-HCV-negative blood donors. Furthermore, the rate of anti-HCV positivity in children who had received one or more blood transfusions prior to the implementation of anti-HCV blood donor screening was evaluated., Study Design: A total of 45719 blood donors and 120 children were tested for the presence of anti-HCV antibodies by second- and third-generation enzyme immunoassays. Positive results were confirmed by a recombinant immunoblot assay. Data on potential sources of HCV transmission were obtained by interviews., Results: Among blood donors, the rate of confirmed HCV antibody-positives was 0.4% (195 of 45719 donors). Previous surgery, transfusion, more than three pregnancies, and tattoos were significantly correlated with confirmed anti-HCV positivity. Two of 120 children (1.7%) were confirmed anti-HCV positives. In both of them, serum HCV RNA could be detected., Conclusions: The prevalence of anti-HCV positive blood donors in South Hungary is low. Nosocomial infections and tattooing were found to be the most important risk factors for transmission of HCV. Because of the low prevalence of anti-HCV positive blood donors, only a small number of children, who received blood transfusions prior to the implementation of anti-HCV blood donor screening, are infected with HCV.

Background/aims: Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. Interferon-alfa therapy may prevent the progression of the disease. The expressions of decorin and alfa-smooth muscle cell actin of the extracellular matrix play a central role in liver fibrosis. We set out to assess the expressions of these proteins in chronic hepatitis C patients, and to evaluate how they can be modified by interferon-alfa therapy., Methods: Twenty chronic hepatitis C patients received interferon-alfa-2b therapy for 6 months (group I) or 12 months (group II). Liver biopsy samples were taken before and after the therapy. The alfa-smooth muscle actin-positive cells were determined with a monoclonal antibody, and decorin expression was detected with a polyclonal antibody. The cells were evaluated with a semiquantitative scoring method. For statistical analysis, non-parametric methods were used., Results: Before the therapy, alfa-smooth muscle actin-labeled cells and marked decorin expression were present throughout all the acinar zones. Interferon-alfa-2b therapy resulted in significant decreases in both the number of alfa-smooth muscle actin-positive cells and the decorin expression. The alfa-smooth muscle actin-positive cells and decorin expression correlated with the histological activity index (R=0.72, p<0.03, R=0.68, p<0.05)., Conclusions: This study demonstrates that a large number of alfa-smooth muscle actin-positive cells and a marked decorin expression are frequent findings in chronic hepatitis C. Treatment with interferon-alfa-2b for 12 months reduced the number of labeled cells and the decorin expression. The results suggest that interferon-alfa-2b is capable of interfering with fibrogenesis in an early and presumably still reversible phase of chronic hepatitis C.

Background/aims: Hepatitis C virus (HCV) infection is one of the most important diseases with high chronicity rate (50-80%) leading to end-stag cirrhosis and hepatocellular carcinoma. Hepatic histology shows a characteristic but not diagnostic picture. The aim of this study was to evaluate the characteristic histological findings in correlation with epidemiological features in our liver biopsy material., Patients/methods: 106 liver biopsies were studid between 1993-1996. All patients (60 males, 46 females, age between 11-81 years, mean age: 43 years) were found to be positive for HCV antibody by a second-generation ELISA method. The biopsy materials were fixed in buffered formalin and having embedded in paraffin, stained with hematoxylin and eosin, periodic acid-Schiff after diastase digestion, Gömöri's reticulin stain and picrosirius red for collagen. The histological evaluation was based upon the new classification of chronic hepatitis proposed by Desmet et al. The statistical analysis was performed by the Chi square test., Results: Minimal chronic hepatitis (HAI: 1-3) was found in 14 (13.2%), mild chronic hepatitis (HAI: 4-8) in 69 (65.09%) and moderate chronic hepatitis (HAI: 9-12) in 23 (21.69%) cases, while assessment of fibrosis (staging) resulted fibrosis 0/1 in 44 (41.5%), fibrosis 2 in 14 (13.2%), fibrosis 3 in 37 (34.9%) and cirrhosis (fibrosis 4) in 11 (10.37%) cases. Among histological features of chronic hepatitis C, the frequency of steatosis (70.75%), lymphoid F/A (63.2%), and bile duct lesions (12.26%) have paralelly increased with activity (grade) of hepatitis and these changes were more pronounced in moderate chronic hepatitis (p < 0.001)., Conclusions: More than half of chronic hepatitis C patients presented mild histological lesions with stage 1 fibrosis. Lymphoid F/A, bile duct damage and steatosis are important diagnostic features that show a strong correlation with the activity of chronic hepatitis. The assessment of fibrosis (stage: 3 and stage: 4) in mild chronic hepatitis cases does alert the hepatologist to perform the liver biopsy to detect the fibrotic changes in chronic hepatitis C.

Background and Aims: Interferon-alfa (IFN-alfa) has recently been introduced for chronic C hepatitis treatment; however, the response rate is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alfa treatment via liver biopsy scores and to evaluate the correlation with the biochemical response., Patients and Methods: 20 chronic C hepatitis patients were studied. 10 patients received IFN-alfa therapy for 6 months, and 10 for 12 months (3 million units three times a week). Liver biopsy material was taken before and after therapy., Results: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) occurred only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups., Conclusions: 12-month IFN-alfa treatment affords a better response in the liver histology grade and serum ALT level, but not the stage; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring the fibrotic changes in chronic C hepatitis.

Generally, toxoplasmosis has mild symptoms, or is asymptomatic, in patients with intact immune system. The infection, however, may have serious consequences in immunodeficient or immunosuppressed patients, as well as in the off-springs of pregnant women. If the mother has acute toxoplasmosis during the pregnancy, the passage of parasites through the placenta may result in the death of the fetus, or, in the severe damage of the fetus or neonate. All these consequences can be prevented by the early detection of the disease followed by the immediate therapy of the mother. Contrary to the most infectious diseases, however, the high specific IgM level has not proved to be a reliable marker of the acute infection in the case of toxoplasmosis. Therefore, in the case of infections discovered in the "plateau" period [i.e. with persistent IgM ("residual" IgM) and/or persistent high level of IgG antibody), the "acute" and the "chronic" phases can be distinguished more reliably by the detection with ELISA of the IgA antibody response to the so called P30 protein of Toxoplasma gondii. The anti-P30 IgA antibody response appears very early and generally disappears in 3-9 months. Thus, it is possible to discriminate the acute phase of the disease from the harmless chronic phase. Between 1987 and 1996, practically all pregnant women in Szeged and its region (altogether 21,952 women), underwent serologic toxoplasma screening. Among them, 124 pregnant women were found highly suspicious for having acute toxoplasmosis. Appropriate counselling, followed by spiramycin therapy during pregnancy and regular ultrasound examination were their antenatal management. No clinically manifested fetal or neonatal infection was observed. The screening and treatment schedule seems to be promising in the prevention of fetal and neonatal toxoplasmosis.

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

Authors investigated the presence of antibody to hepatitis C virus (anti-HCV) at 67,534 blood donations, and alanin-amino-transferase (ALT) levels were analysed at the same time. The prevalence of anti-HCV antibody was 0.73% at 15,864 blood donors. Frequency of positive reactions of anti-HCV antibody increased paralelly with advance of age. Increased or high serum ALT level was found at more than 50% of samples with positive HCV reactivity. At the base of follow-up the blood donors were screened out from blood donation temporarily or definitively. Anti-HCV donors were taken to hepatic care. The treatment with interferon of HCV seropositive donors proved by PCR (polimerase chain reaction) was started. Transfusion and tattou are underlined as risk factors of HCV infection. The data were analysed according to sex and ages.

A placebo controlled clinical trial. Thirty two patients with chronic C hepatitis have been enrolled in a double blinded study to assess the therapeutic effect on an orally given antiviral-immunomodulatory drug, Isoprinosine. Seventeen patients were given Isoprinosine (3 g/day) and fifteen were on placebo. The treatment has been lasted for four months, when patients examined monthly. Clinical signs, liver function tests and side effects were evaluated. At the end of the trial, side effects and elevated serum alanine aminotransferase (ALT/GPT) levels occurred with higher frequency in Isoprinosine-treated patients. The results show that this antiviral drug has no beneficial effect in chronic C hepatitis.

Coxsackie-B antibodies were examined in a study of 118 patients with acute and relapsing chronic pancreatitis. The rise in antibody titers was significant in 40 cases. Fourteen had acute, five relapsing acute, and 21 chronic pancreatitis. Among patients with acute pancreatitis, we detected infectious hepatitis in six cases. Two patients with persisting acute pancreatitis received levamisole as an immune adjuvant, which promoted their recovery. It seems that Coxsackie-B virus can cause acute pancreatitis, and it can also worsen chronic pancreatitis.