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Biomedical subjects

J Stránský

Publications and source records attributed to J Stránský.

At least 19 recordsLinked to original sources

[Adefovir dipivoxil is a new drug for treatment of chronic hepatitis B].

Adefovir dipivoxil is a new nucleotide analog derived from adenosin-monophosphate. At the 10 mg/day dose significantly decreases HBV DNA in serum, activity of transaminases, and leads to better histology results in liver assessment of adults with hepatitis B in the phase of active viral replication. Treatment with Adefovir dipivoxil is a long term treatment (48 weeks), it is well tolerated, and side effects are moderate and reversible. It can be administered to HBeAg positive patients, to patients with HBV mutant unable to create HBeAg if positive HBV DNA in serum, and to patients with lamivudine resistant HBV mutant.

Adenine↗

[Why is there a poor response to combined therapy with interferon alfa 2b and ribavirin in patients with chronic hepatitis C?].

BACKGROUND: Patients with chronic hepatitis C are now treated with a combination of interferon alpha (IFN) and ribavirin. Therapy was used in initial treatment, for those who were resistant to interferon and in relapsed patients. The aim of the study was to evaluate our results and to compare them with the already published data. METHODS AND RESULTS: 27 adult patients of the average age 46 years were cured from 1997 through 1999 for the histologically verified chronic hepatitis C with IFN-alpha 2 and ribavirin. 16 patients suffered from the chronic hepatitis with low, medium or high activity, 11 of them had cirrhosis. Serological testing was done using ELISA-3 test HCV RNA in serum was estimated by the polymerase chain reaction and serotype HCV was identified by the Murex kit. Treatment lasted 6 to 12 months. Incidences of side effects to both remedies, complications in therapy, therapeutical responses and possible failures of the combination therapy were analysed. In 20/27 patients the HCV serotype could be identified and always serotype 1 was found. Average score of histological activity was in patients with serious chronic active hepatitis and cirrhosis 10.1, in other patients 5.6. Sustained biochemical and virological response was found in 5 out of 27 patients (18.5%). Their average age was 39 years. 9 patients (33%) of average age 49 years had no biochemical and virological response. Sustained biochemical response without the accompanying virological response was found at the end of therapy in 10 patients (37%). After the end of therapy, 33% of patients had a relapse. The most frequently seen accompanying sign was the flu-like syndrome, in two female patients we found impairment of thyroid gland function, and in another two the breakthrough phenomenon. Treatment with ribavirin was in seven cases (26%) complicated with rather serious haemolytic anaemia and the dose had to be reduced. Toxic-allergic exanthema in 5 patients (18.5%) represented the second serious complication causing the termination of therapy. CONCLUSIONS: Sustained biochemical and virological response to the combination therapy was found only in patients with mild form of chronic hepatitis C. No such response was found in 8 patients with cirrhosis and in one female patients with medium activity of the chronic hepatitis. The age of patients with sustained response was significantly lower than in patients without the response (39 years versus 49 years). The most frequent serotype was HCV 1. The combination therapy was more frequently accompanied with clinically serious complications. To the adverse effects to the combination therapy belonged in our population the liver cirrhosis, age about 50 or more years, and the genotype HCV 1. It is also the answer to the question why the combination therapy of patients with chronic HCV infection has so poor results.

Adult↗

[Serious side-effects of interferon alfa and ribavirin combination therapy in patients with chronic hepatitis C].

At present standard treatment of patients with chronic hepatitis C is combined therapy with interferon-alpha and ribavirin which so far gives the best results. It is recommended in patients with resistance to interferon or a relapse after termination of treatment by interferon alone as well as in hitherto untreated patients. Combined treatment produces, however, not only common side-effects which are caused by interferon as well as ribavirin but rarely also serious side-effects produced by combined treatment which call for premature termination of therapy. The authors present an account on two patients who had serious side-effects during combined treatment: the first one was an intravenous drug addict who developed psychosis during combined treatment, the second one a female patient with cirrhosis and incipient portal hypertension who developed after nine months of combined treatment a severe biochemical relapse with jaundice, and treatment was also terminated. Both serious complications after treatment receded and in the first patient a sustained response to antiviral therapy persists for more than one year.

Adult↗

[Aspartate aminotransferase (AST) more than alanine aminotransferase (ALT) levels predict the progression of liver fibrosis in chronic HCV infection].

The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p < 0.002) than ALT activity (p < 0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p < 0.0008). Steatosis was more frequent in patients with fibrosis (p < 0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.

Adolescent↗

Overt and hidden coinfection with hepatitis B and C viruses in chronic liver disease and porphyria cutanea tarda.

The aim of this study was to assess the rate of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection ("the coinfection") in chronic liver disease (CLD) and to reveal overt and hidden HBV infection in patients with antibodies to HCV (anti-HCV). A total of 209 untreated patients (64 with chronic hepatitis B, 79 with chronic hepatitis C and 66 with porphyria cutanea tarda (PCT)) were screened for serological markers of HBV and HCV infection in serum by third generation enzyme-linked immunosorbent assay (ELISA) methods and for HBV DNA and HCV RNA in serum by polymerase chain reaction (PCR). The rate of the overt coinfection in chronic hepatitis B was very low (2/64, 3%). However, in chronic hepatitis C, the rate of the hidden coinfection with HBV was relatively high (19/79, 24%); these patients had higher alanine transaminase (ALT) and asparagine transaminase (AST) levels in serum and a more advanced liver disease. In PCT patients, the rates of HBV and HCV infections were the same, 21% (14/66). In the PCT patients infected with HBV or HCV, the rate of the coinfection was 33% (7/21). The PCT patients with the coinfection had a high serum ALT level and the worst histological picture in the liver. The hidden HBV infection was more frequent than the overt one. The possibility of the overt or hidden coinfection in CLD renders a detailed analysis of all serum samples for both viruses mandatory. Vaccination against HBV infection should be offered to anti-HCV-positive individuals as well as to PCT patients not showing antibodies to HBV (anti-HBV).

Adolescent↗

[Chronic hepatic porphyria and hepatitis B and C virus infections].

BACKGROUND: It is known that in patients with porphyria cutanea tarda (PCT) there is an increased prevalence of the hepatitis B virus (HBV) and the hepatitis C virus (HCV). The incidence of anti-HCV in PCT in our country is 21.7% in estimations by the second generation method, however, the incidence of HBV in PCT was not assessed so far. METHODS AND RESULTS: In 60 patients with PCT antigens and antibodies against HBV and HCV were assessed (by the anti-HCV third generation ELISA method) and in subjects with signs of HBV or HCV. HBV DNA and HCV RNA were assessed by the method of the polymerase chain reaction. PCT without detectable HBV or HCV infection was found in 45 subjects (68%). HBV infection only was confirmed in seven subjects (10.6%), however none of the patients had positive HBsAg in serum. All had only antibodies against HBV. HCV infection only was detected in seven patients (10.6%) and HBV and HCV co-infection also in seven patients (10.6%). In the group of patients with HBV and HCV co-infection there was not a single HBsAg positive subject. The mean ALT serum activity was significantly higher as compared with subjects with HBV or HCV infection only (p < 0.05) and the histological finding on liver biopsy was more serious. CONCLUSION: HBV (21%) and HCV (21%) infection participates significantly in the clinical picture of PCT. A special subgroup is formed by patients with PCT and HBV and HCV co-infection who have as a rule a higher ALT activity and more severe histological changes in the liver. The incidence of HBV and HCV infection in PCT in the Czech Republic is double as compared with Germany or Great Britain.

Adult↗

[Detection of HCV RNA in anti-HCV positive patients with chronic hepatic porphyria].

BACKGROUND: In 1994 the authors published first results of anti-HCV antibodies in the group of 92 porphyria cutanea tarda patients, tested with ELISA second generation enzymatic method. Positivity, found in 21.7 per cent of them, was significantly higher when compared with the results of healthy blood-donors. Anti-HCV reactivity thus ascertained can be, however, non-specific in some cases and need not necessarily indicate existence of an active replication of hepatitis C-virus. The authors have therefore subsequently tried to verify the above results by the more sensitive polymerase chain reaction (PCR), enabling the proof of viral RNA and thus an assessment of the replication-activity of HCV. This study completes their previous findings for the evidence of viraemia in anti-HCV reactive PCT-patients. METHODS AND RESULTS: 21 of 92 PCT-patients were reactive when examined with the second generation ELISA method (Sanofi, Pasteur). HCV RNA was examined in 20 subjects from the above group (one patient died in the meantime) by means of PCR. Positive HCV RNA was found in 17 patients, i.e. in 85 percent of them. Percutaneous liver biopsy without visual control was performed in 17 anti-HCV reactive and HCV RNA positive patients and in 46 anti-HCV negative porphyrics. The biopsy-findings were significantly worse in the HCV RNA-positive group. Also the average activity of ALT and AST was significantly higher in the patients with positive HCV RNA when compared with anti HCV-negative subjects. CONCLUSIONS: High frequency of HCV-infection (21.7 percent) was found in our group of 92 PCT-patients. Viraemia was present in the vast majority (85 per cent) of them, for they had also positive HCV RNA besides anti-HCV reactivity. These patients had also higher ALT- and AST-activity and more severe histological liver-changes. HCV-infection is the main virological cause of their liver lesion, beside ethylism. Hepatocellular carcinoma is rather exceptional in our porphyria patients in spite of their frequent HCV-infection.

Adult↗

[Clinical significance of IgM anti-HCV determination in chronic hepatitis C].

BACKGROUND: In the majority of patients with acute viral hepatitis C the early antibody IgM anti-HCV in serum is positive. However, a substantial portion of the patients with chronic hepatitis C has also positive IgM anti-HCV as a sign of the continuing replication of the virus. The objective of the work was to assess the presence of IgM anti-HCV in patients with confirmed chronic hepatitis C, in subjects with HBsAg negative chronic hepatitis and in excluded blood donors. Moreover, the authors assessed the relationship between IgM anti-HCV positivity and the activity of serum transaminases and whether the presence of IgM anti-HCV has an impact on the histological finding in the liver. METHODS AND RESULTS: 88 patients were examined (44 women and 44 men), average age 48 years. In 47 subjects histological examinations of the liver were made. IgG anti-HCV were assessed by the Monolisa anti-HCV Sanofi Pasteur test and IgM anti-c22 by an Abbott kit IgM HCV EIA: With regard to the results of the serological examination the patients were divided into three groups which were mutually compared. Group 1 comprised 24 patients with a positive IgG and IgM anti-HCV, group 2 38 patients with a positive IgG anti-HCV only and group 3 26 patients with a negative IgG and IgM anti-HCV. Of 88 examined patients 62 had positive IgG anti-HCV (70%). Of 62 IgG anti-HCV positive subjects 24 (39%) had positive IgM anti-c22. A total of 24 patients had blood transfusions (39%) but only 9 of them had positive IgM anti-c22 (37.5%). The mean ALT serum activity was significantly higher in subjects with positive IgM than in those without IgM (p = 0.006), however, for AST the difference was not significant (p = 0.09). Comparison of patients with a confirmed histological finding in the liver revealed that two-thirds of patients with a positive IgM anti-c22 either suffered from cirrhosis or chronic active hepatitis, while anti-HCV positive patients without IgM anti-c22 had cirrhosis or chronic active hepatitis only in one third of the cases. CONCLUSIONS: The results suggest that in chronic hepatitis C some 40% of the patients have positive IgM anti-c22; these subjects have a significantly higher serum ALT activity and a more advanced histological finding in the liver than subjects without IgM anti-c22. Assessment of IgM anti-c22 is important not only for diagnosis but also for treatment of chronic HCV infection with antiviral drugs.

Chronic Disease↗

[The discovery of hepatitis G virus].

Some 20% of cases of posttransfusion and sporadic hepatitis non-A, non-B are anti-HCV negative. In 1995 it proved possible in collaboration of Genelabs with Boehringer Co. Mannheim to identify a new RNA virus which causes acute and chronic hepatitis in humans and tamarins. The genome of the virus contains some 2900 amino acids, and as to its structure, it resembles flaviviruses. It was described as hepatitis G virus (HGV). It differs from the hepatitis C, virus as it has only a 26% homology of amino acids. It is transmitted through blood during transfusion along with other parenteral routes of infection. Risk groups comprise i.v. drug addicts, blood donors and patients with thalassaemia and repeated blood transfusions. HGV can infect the liver as an independent virus or along with the virus of hepatitis B or C (dual infection). As to clinical aspects, hepatitis G is very mild and not associated with jaundice. Some patients develop chronic hepatitis. About half the patients infected with HGV have only a slightly raised transaminase activity, the remainder have normal liver enzymes. As compared with hepatitis C, the mean transaminase activity is one half. It can be diagnosed by assessment of HGV RNA by means of PCR. In the USA the prevalence of HGV RNA in blood donors with normal ALT activity is 1.7% and in donors with increased ALT activity 1.5%. The virus is sensitive to interferon, after treatment the serum concentration of HGV RNA declines rapidly but after withdrawal of treatment the values return to pre-treatment levels. This is the first report on the newly discovered hepatitis G virus.

Hepatitis Viruses↗

Clinical importance of assessment of anti-HCV IgM antibodies in chronic hepatitis C.

In the majority of patients with acute hepatitis C the anti-HCV IgM antibodies in serum were present, however, some patients with chronic hepatitis C were positive for anti-HCV IgM too. The aim of this study was to assess the presence of anti-c22 IgM in patients with chronic hepatitis C and to determine whether the positivity for anti-c22 IgM has an impact on the histological finding in the liver. A total of 88 patients were examined (44 women, 44 men), mean age 48 years. The first group comprised 24 patients positive for both anti-HCV IgG and anti-c22 IgM, the second group 38 patients positive for anti-HCV IgG only, and the third group 26 patients negative for both anti-HCV IgG and anti-c22 IgM. Of 62 anti-HCV-IgG-positive subjects 24 (39%) were positive also for anti-c22 IgM. Of 24 patients who received a blood transfusion 9 (37.5%) were positive for anti-c22 IgM. The mean serum alanine aminotransferase (ALT) activity was significantly higher in subjects with anti-c22 IgM than that in subjects without them (p = 0.006), however, the difference in aspartate aminotransferase (AST) was not significant (p = 0.09). Histological examination was performed in 46 patients. Two-thirds of the patients with anti-c22 IgM had either cirrhosis or chronic active hepatitis (CAH) while only one third of the anti-HCV-positive patients without anti-c22 IgM had CAH or cirrhosis. The results showed that approximately 40% of the patients with CAH and cirrhosis had anti-c22 IgM, a significantly higher serum ALT activity and more serious histological finding in the liver than anti-HCV-positive patients without anti-c22 IgM.

Adolescent↗

[A relapsing and protracted form of viral hepatitis A: comparison of adults and children].

In recent years in children and adults with acute viral hepatitis A relapses and a protracted course of the disease were described. The authors followed up 37 patients with viral hepatitis A (20 children and 17 adults) and compared the clinical course of the disease, the period of hospitalization, persistence of IgM anti-HAV antibody in serum, the incidence of relapses and protracted forms of the disease. In adults the mean hospitalization period was longer (28 days as compared with 19), the average serum bilirubin value was higher (94 mumol/l as compared with 51 mumol/l), there were more cases with obvious jaundice (59% as compared with 30%) and the early serum antibody IgM anti-HAV persisted longer (19 weeks as compared with 14 weeks). Relapses of the disease were equally frequent (12% vs. 10%), however adults had more often a protracted course of hepatitis (23.5% vs. 10%). The observed differences were not statistically significant. Almost half the cases of hepatitis affected several members of the family. The results suggest that viral hepatitis A in adult age has a more severe course than in children. The authors recommend in cases with an elevated transaminase serum activity more frequent check-up examinations to avoid missing of a relapse, and to examine repeatedly IgM anti-HAV as in protracted forms of hepatitis IgM anti-HAV may persist even when the transaminase activity is normal.

Adolescent↗

[Morphologic findings in liver tissue in chronic active hepatitis B after seroconversion from HBeAg to anti-HBe].

Replication of the virus is in the majority of patients with chronic hepatitis B associated with permanent activity and progression of the inflammatory process. The change of the virus to the latent stage expressed by seroconversion of HBeAg to anti-HBe leads to a significant repression of inflammatory changes and has a favourable impact on the course of the disease. The morphological changes in the hepatic tissue after spontaneous seroconversion or after interferon treatment were investigated in specimens of needle biopsy in 18 patients with active chronic hepatitis B. In 10 of them the diagnosis of chronic hepatitis was confirmed by biopsy in the stage of replication of the virus. During the subsequent time interval after seroconversion of HBeAg, incl. two instances where interferon was administered, in the tissue of 14 HBsAg positive patients regression of inflammatory changes was apparent, in particular a lower incidence of piecemeal necroses. The regular finding of periportal and septal fibrosis in these patients is probably associated with a longer course of chronic active hepatitis and late spontaneous or therapeutically induced seroconversion of HBeAg. In one man, treated with interferon, morphological examination revealed one month after seroconversion of HBeAg an acute exacerbation of the disease. In another three patients, who at the time of the bioptic examination were HBsAg negative, in the hepatic tissue minor silent periportal and septal fibrosis persisted.

Adolescent↗

Causes of acute exacerbations of chronic hepatitis B.

The authors analyzed acute exacerbations of chronic hepatitis B in 24 chronic HBsAg carriers (20 with positive HBeAg, 4 with anti-HBe), more than half of whom were treated with glucocorticoids, by examining specific antigens and antibodies of the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis delta virus (HDV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Of 38 observed exacerbations of the disease they found in 7 (18%) deterioration after discontinuation of glucocorticoids, in 7 (18%) seroconversion of HBeAg to anti-HBe, in 9 (24%) spontaneous exacerbation of chronic hepatitis B, in 11 (29%) chronic activation, reactivation of EBV superinfection, in 3 (8%) CMV reactivation or superinfection and in one (3%) HDV superinfection. In no instance HAV superinfection was observed. Exacerbations were found five times more frequently in subjects in the stage of active viral replication (in HBeAg+ subjects) than in subjects with anti-HBe. In eight patients EBV reactivation was found after glucocorticoids withdrawal: in five patients after an average period of 5 months (range 3-7) and in three patients after an average period of 33 months (range 22-48). The results provide evidence that in addition to already known causes of acute exacerbations of chronic hepatitis B in our geographical area probably an important cause of deterioration of hepatitis is reactivation or superinfection with EBV and CMV in some patients in conjunction with previous glucocorticoid treatment.

Acute Disease↗

[Liver cirrhosis mortality at the Outpatient Clinic in District 8 in Prague 1985-1993].

In 1985-1993 in the out-patient clinic in Prague 8 a total of 59 patients died from cirrhosis of the liver, incl. 30 who were for prolonged periods HBsAg positive and 29 who were HBsAg negative. In the group of cirrhotics with positive HBsAg who died 19 of 29 (66%) were also HBeAg positive which suggested advanced HBV replication during the period of reconstruction of the liver. 43% of those who died and had HBV infection, had glucocorticoid treatment. Only one female patient of 13 had positive anti-HD in serum. In HBsAg negative cirrhotics the main cause of development of cirrhosis was ingestion of alcohol, but at that time it was not possible to assess antibodies against HCV. The most frequent cause of death in cirrhotics was haemorrhage into the digestive tract (25%), hepatic failure (20%) and a malignant tumour (12%). The most frequently encountered malignant tumour was primary carcinoma of the liver (in 8 of 11, 73%). Because in chronic hepatitis the replication activity of HBV is high and can persist also in advanced cirrhosis of the liver, patients with hepatitis B in the stage of active viral replication must be treated in time with interferon to prevent the development of the disease into cirrhosis of the liver and its complications.

Adult↗

[Recent advances in clinical aspects of infectious hepatitis].

A review of recent advances in the diagnosis, clinical course, complications and treatment of hitherto known types of viral hepatitis (VHA, VHB, VHC, VHD and VHE). The most serious complication of hepatitis is fulminant hepatic failure. The only effective drug in some types of viral hepatitis is interferon alpha 2a.

Hepatitis, Viral, Human↗