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Chronic diffuse liver diseases produce a characteristic ultrasound image called bright liver. On the basis of liver attenuation, two major appearances can be observed: low and high attenuation types. It is proved that high attenuation is associated with fatty liver and subcutaneous fat thickness correlates with attenuation. Cut-off value of attenuation and subcutaneous fat thickness was searched for differentiation of the two attenuation types and that of the normal livers. 441 patients (proved by histology) were examined by ultrasound. 132 normal livers, 176 low and 133 high attenuation type bright livers were found. Cut-off level of attenuation, determined by frequency distribution analysis was defined as 1.1 dB/cm/MHz, between fatty liver and low attenuation type bright liver and normal liver. Cut-off value for subcutaneous fat thickness could not be determined. It is concluded, that above the cut-off point of attenuation, the diagnosis of fatty liver can be established without liver biopsy. Subcutaneous fat thickness values give additive confirmative data.

Unlabelled: 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.

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.

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.

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.

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.

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.

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.

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 have investigated the hepatitis B and D virus antigens in the liver tissue of 30 HBsAg and/or anti-HD seropositive patients (23 males, 7 females, age: 20-65, mean: 44 years) by immunohistochemical method. The immunohistochemical identification of HBsAg, HBcAg and HDAg in 42 liver sample (36 obtained by percutaneous biopsy, 6 from dissection) of 30 patients was performed with Dako and Sorin Biomedica kits. The detailed virus serologic examinations were carried out with Biomedica and Abbott kits by radioimmunoassay and ELISA methods. Examining 36 liver tissue samples of 27 HBsAg seropositive patients, HBsAg could be demonstrated in 31 cases. Each patient suffering of active HBV and/or HDV replication was HBsAg positive by immunohistochemistry, while the tissue samples of patients in integrational phase of HBV infection were positive in only 9 cases of 14. There was no HBsAg tissue positivity in HBsAg seronegative cases. 7 of 16 tissue samples of 12 patients classified to active HBV replication state were HBcAg positive by immunohistochemistry. HBcAg could be detected in the liver tissue of each HBe seropositive patient, while in only 3 of 8 cases with only IgM anti-HBc seropositivity (indicating low level of HBV replication). Tissue HBcAg positivity, indicating active virus replication, was verified in 2 of 11 patients classified to HBV integration state by serology. Authors detected HDAg tissue positivity only in cases with serologically active HDV replication (IgM anti-HD seropositive) and HDAg could also be identified from liver tissue in each IgM anti-HD seropositive case. No HBsAg, HBcAg and HDAg tissue positivity was observed in HBsAg negative cases. Authors emphasise mainly the importance of immunohistochemical detection of HBcAg and HDAg completing the serologic diagnosis of chronic HBV and HDV infections, helping the verification or exclusion of active virus replication being essential for selecting adequate therapy.

The prevalence of spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis admitted to our unit during last two years was studied. Criteria of spontaneous bacterial peritonitis were positive bacteriology and greater than 250/mm3 polymorphonuclear leukocyte count. 84 examinations in 50 patients were made. Spontaneous bacterial peritonitis was diagnosed in 4 cases. E. coli, Klebsiella pneumoniae, alpha haemolyzing Streptococcus were isolated from ascitic fluid in positive cases. Three patients died despite of therapy, one patient recovered. Bacterascites (positive bacteriology without increased polymorphonuclear leukocyte count) was detected in two cases. Culture-negatív neutrocytic ascites (greater than 250/mm3 polymorphonuclear leukocyte count without positive bacteriology) was detected in four cases. The clinical picture of above-mentioned cases was symptomless. Low protein concentration of ascitic fluid (less than 10 g/l) predisposing to spontaneous bacterial peritonitis, was found in 15% of cases. Incidence of spontaneous bacterial peritonitis and equivocal states found by us was similar to the data given by the literature: 15-20%. Because of the high mortality rate and frequent symptomless course in cirrhotics, importance of diagnostic paracentesis is stressed.

The results of 43 interferon treatments of 35 patients (23 male, 12 female) are reported. The duration of the treatment was 6-18 months, the dose of interferon was 3x3-5 MU weekly. Complete response (HCV RNA became negative) was found in 11, relapse was observed in 3 patients. Partial response (transaminase levels became normal, or less than twice normal value, but patients remained HCV RNA positive) occurred in 23 cases, relapse was obeserved in 16. The therapy had no effect in 9 cases. The higher dose and longer term interferon therapy resulted in a higher rate of response to the treatment and a reduction in the number of relapses.

The authors tested hepatitis B (HBsAg, anti-HBs, anti-HBc, IgM anti-HBc, HBe, anti-HBe), C (anti-HCV) and D (anti-HD, IgM anti-HD) virus markers in the sera of 204 patients, who suffered from histologically confirmed chronic liver diseases (age: 18-72, average: 46.8 y) by Sorin Biomedica RIA and Abbott ELISA kits. On the basis of detailed virus serological tests, they obtained data indicating viral etiology in 62% of the cases. 33.3% of the patients were anti-HCV, 52.5% of the patients were HBV marker seropositive and 11.2% of the HBV seropositive cases were anti-HD seropositive. In 2% of the cases seropositivity of all the three viruses was proved. In 26% of the patients seropositivity of two viruses (HBV and HCV, or HBV and HDV) was proved. They observed severe, progressing liver diseases in patients with HBV, HCV and HDV marker seropositivity in a higher ratio than in seronegative patients. In the cases of combined virus marker seropositivity the incidence rate of chronic hepatitis and liver cirrhosis was higher than in only HBV marker seropositive patients, but did not differ significantly from those only anti-HCV seropositive. In the cases of fought-off HBV infection the severity of the liver disease was milder than in the cases of replication and integration stage. Anti-HD seropositivity occurred in all stages of HBV infection, but active HDV infection, in most of the cases, was observed only in cases in the integration stage. Anti-HCV seropositivity was observed mainly in the fought-off HBV infection stage. Their results suggest that HCV infection, like HDV infection, may suppress HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS)

The data on hepatitis delta virus and the liver diseases caused by it are reviewed. The findings of hepatitis B and D virus markers in 118 hepatitis B virus seropositive patients suffering from histologically confirmed chronic liver disease are reported. The prevalence of hepatitis delta virus infection was 13.56% of these cases, while active hepatitis delta virus replication was proved in 6 cases of them. Based on their findings, the role of hepatitis delta virus in the progression of chronic liver diseases is concluded, similarly to data published earlier. The importance of repeated, detailed virus-serological and histological examinations is stressed, especially in the cases in which the progression of liver disease are detected. The authors suggest that HBsAg--IgM complex seropositivity in patients suffering from anti-delta seropositive chronic liver disease supports active hepatitis delta virus infection.

The hepatitis B virus (HBV) markers were studied by Sorin RIA kits in the sera of 390 patients suffered from histologically confirmed chronic liver disease. On the base of HBsAg, anti-HBs, anti-HBc seronegativity the HBV infection was excluded in 235 cases. In most HBV negative cases the diagnosis was fatty liver and alcoholic hepatitis (52%), while chronic active hepatitis and/or liver cirrhosis occurred only in 21.7% of patients. Past or present HBV infection was proved in 155 patients. The diagnosis of 52.9% of cases in this group was chronic active hepatitis and/or liver cirrhosis, while fatty liver and alcoholic hepatitis occurred in 27.7%. The detailed HBV marker analysis was performed in 76 patients. Previous infection without replication (anti-HBs and/or anti-HBc and/or anti-HBe positivity) was proved in 48 cases, 12 patients have active HBV infection (HBsAg, HBe, IgM anti--HBc, positivity), while in 16 cases integrated HBV infection (HBsAg, anti-HBc, anti-HBe positivity) was proved. The HBsAg--IgM complex seropositivity was detected in every case with active HBV replication. Because of therapeutic, prognostic and epidemiologic significances the detailed HBV serology in chronic liver diseases is stressed.

A study of hepatitis B and D virus markers in 118 hepatitis B virus seropositive patients suffering from histologically confirmed chronic liver disease is reported. The prevalence of hepatitis delta infection amounted to 13.6%, whereas active hepatitis delta virus replication was proven in 6 of the cases. On the basis of these findings, conclusions--similar to those published earlier--are drawn about the role of hepatitis delta virus in the progression of chronic liver diseases. It is suggested that HBsAg-IgM complex seropositivity in patients suffering from anti-delta positive chronic liver disease supports active hepatitis delta virus replication.

Hepatitis B virus (HBV) markers were studied with Sorin RIA kits in serum samples from 390 patients suffering from histologically confirmed chronic liver disease. On the basis of negative HBsAg, anti-HBs, anti-HBc tests, HBV infection was excluded in 235 of the cases. The diagnosis was fatty liver and/or alcoholic hepatitis in 52%, while chronic active hepatitis and/or liver cirrhosis only in 21.7%. Part or present HBV infection was proven in 155. In 53% of these cases the diagnosis was chronic active hepatitis and/or liver cirrhosis, whereas fatty liver and alcoholic hepatitis occurred in 27.7%. Detailed HBV marker analysis was performed in 76 patients. Previous infection without replication (positive anti-HBs and/or anti-HBc and/or anti-HBe) was proven in 48 cases, 12 patients had active HBV infection (positive HBsAg, HBe, IgM anti-HBc), while in 16 cases HBV integration (positive HBsAg, anti-HBc, anti-HBe) was proven. HBsAg-IgM complex seropositivity was shown in every case with active HBV replication. Because of therapeutic, prognostic and epidemiologic reasons, the significance of detailed HBV serology in chronic liver diseases is stressed.

Water content in the liver in vivo was determined in 89 patients (33 with normal liver and 56 with chronic liver disease), simultaneously with ultrasonography and histopathological examination. A part of each biopsy specimen was used for this purpose. The difference between wet and dry weights was calculated from the pre- and post-lyophilization weights. According to the attenuation type of ultrasonic images, the patients were divided into two groups, viz., patients of low attenuation type (i.e. patients with type I bright liver) and those of high attenuation type (i.e. with type II bright liver). As to water content, no significant difference was observed between the two groups. No correlation was found between liver water content and histopathology either. It is concluded that knowledge of correlation between numerous parameters is needed to clarify the reason of attenuation differences.