Gastric myoelectrical activity in patients with primary biliary cirrhosis.

OBJECTIVE: To examine gastric myoelectrical activity in patients with primary biliary cirrhosis (PBC). MATERIALS AND METHODS: The study comprised 11 female PBC patients (average age 53.4 years, range 43-70) and two aged-matched control groups: 11 (53.4 years, range 37-78) healthy women, and 10 female patients with chronic hepatitis C, CHC (53.9 years, range 35-66), who were examined prior to administration of an antiviral therapy. Every subject underwent an electrogastrographic recording comprising a 30-min interdigestive and a 120-min postprandial period. RESULTS: Abnormal electrogastrograms, containing prolonged epochs of tachygastria in the postprandial phase were found in 2 out of 11 (18.2%) patients having both stage IV of the Scheuer's PBC classification, as well as in 1 patient out of 10 (10%) with CHC at stage F2 according to the METAVIR fibrosis score. CONCLUSION: Electrogastrographic abnormalities do not seem to be pathognomonic for the PBC as a disease, but rather would be considered an unspecific sequel of a morbid liver affection.

[Pegylated interferon-alfa 2a with ribavirin in chronic viral hepatitis C (final report)]. / Pegylowany interferon alpha-2a z rybawiryna w leczeniu przewleklego wirusowego zapalenia watroby typu C (raport koncowy z badan).

UNLABELLED: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia). CONCLUSIONS: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

Effect of single-dose administration of recombinant interferon-alpha2b on gastric myoelectrical activity in patients with chronic hepatitis C.

BACKGROUND: Upper abdominal complaints during interferon therapy may result from impaired gastric motility and/or evacuatory function. We examined the effect of acute administration of interferon on gastric myoelectrical activity (GMA) with the use of surface electrogastrography. METHODS: The study population comprised 25 patients with chronic hepatitis C. All of them were naive to interferon. On 2 days, after a 25-min basal GMA registration, in group A (5 men, 7 women, aged 44.3 +/- 2.8 years) placebo or 5 million i.u. recombinant interferon alpha-2b (IFNA) was administered s.c. and the GMA was recorded in the interdigestive state for two periods (2 h and 4 h), separated by a 15-min break. In group B (7 men, 6 women, aged 44.7 +/- 3.9 years) placebo or 5 million i.u. IFNA was injected s.c. after the ingestion of a semiliquid test meal of 364 kcal. Subsequently, the postprandial GMA was recorded for two periods (2 h and 4 h), separated by a 15-min break. RESULTS: A typical flu-like syndrome was observed in 91.7% of patients in group A, and in 92.3% of patients in group B, thus providing evidence of the pharmacodynamic efficiency of the IFNA administration. In the fasted state, IFNA brought about a negligible increase in the rhythmicity and power of the gastric slow waves. IFNA did not elicit any statistically significant effect on gastric slow-wave activity postprandially. CONCLUSIONS: Acute administration of interferon does not involve any deterioration of GMA that could be linked to the previously reported upper abdominal symptoms in patients undergoing treatment with this drug.

[Does long-term erythropoietin therapy influence the prevalence of serum markers of hepatitis B and C in haemodialysed uraemic patients?]. / Czy dlugotrwale leczenie erytropoetyna wplywa na czestosc wystepowania wskazników zakazen wirusami zapalenia watroby typu B i C u hemodializowanych chorych na przewlekla niewydolnosc nerek?

UNLABELLED: Haemodialysed patients are highly exposed to different virus infections namely hepatitis B (HBV) and C (HCV). Recently it was shown, that the use of recombinant human erythropoietin (rHuEPO) in haemodialysed patients with chronic renal failure (CRF) stimulates not only erythropoesis but also increases--in an indirect or direct manner--the humoral and cell--mediated immune defense. The aim of the present study was to determine the prevalence of HBV and HCV infection in haemodialysed patients with CRF and renal anaemia treated either with rHuEPO or with allogenic blood transfusions only. 32 patients with CRF and renal anaemia (haematocrit value below 28%) were included in this study at the early stage of the dialysis therapy (0 to 6 months from the first haemodialysis session). All patients were randomly allocated into two groups. The first one consisted of 15 haemodialysed patients treated with rHuEPO, the second group composed of 17 occasionally treated with blood transfusions (No-EPO group). In patients of both groups the following parameters were examined before (0) and after 3, 6, 9, 12 months of monitoring number of units blood transfused, hemoglobin concentration, serum levels of ferritin. Before the study (0) and after 6 and 12 months presence of antigen HBs (AgHBs), antibodies anti-HBc, anti-HBs, anti-HCV, DNA HBV and RNA HCV were examined. Before the study markers of HBV infection (DNA HBV and/or AgHBs and/or anti-HBc) were found in 46.7% of patients in EPO group and in 52.9% of patients in NO-EPO group respectively (NS). After six months of the study markers of HBV infection were present in 60% of patients in EPO group and in 76.5% of patients in No-EPO group (NS). After 12 months of dialysotherapy HBV infection markers were found in 66.7% patients in EPO group and in 76.5% of patients in No-EPO group (NS). Significantly higher prevalence of HBV infections were found after 6 and 12 months respectively in No-EPO group in comparison to the prestudy period (p < 0.05). At the beginning of the study markers of HCV infection (RNA HCV and/or anti-HCV) were present in 26.7% of patients in EPO group compared to 35.3% of patients in No-EPO group (NS). After 6 months of therapy markers of HCV infection were found in 26.7% of patients in EPO group and in 64.7% of patients in No-EPO group (p < 0.05). After 12 months of treatment markers of HCV infections were present in 40% of patients in EPO group and 76.5% of patients in No-EPO group (p < 0.05).ln patients of No-EPO group significantly higher prevalence of HCV infection ware found after 6 and 12 months of the follow-up compared to the prestudy period (p < 0.05 and p < 0.01 respectively). CONCLUSIONS: Treatment of renal anaemia with rHuEPO contributes to the significant decrease in prevalence of HCV infection. Decrease of prevalence of HCV infection in haemodialysed patients with chronic renal failure treated with rHuEPO seems to be predominantly a result of the complete cessation of allogenic blood transfusion. Blood transfusions seem not to be the main cause of HBV transmission in haemodialysed patients.

Changes in TNF-alpha mRNA levels in the peripheral blood of patients with chronic hepatitis C virus (HCV) infection during alpha-interferon and ribavirin therapy.

HCV virus infections have become a serious epidemiological problem throughout the world. Hepatitis C therapy includes the administration of IFN-alpha and ribavirin, but results in the complete eradication of HCV viremia in only 30% of patients. TNF-alpha is one of the factors involved in hepatitis C pathogenesis and the results of therapy. In this study, we present the results of applying real-time RT-PCR for assessing the TNF-alpha mRNA level in the peripheral blood of patients treated with IFN-alpha and ribavirin. We found the TNF-alpha mRNA level to be higher in HCV-infected patients compared with healthy controls when analyzed after 4 weeks (p = 0.001) and 3 months (p = 0.003) of IFN-alpha/RIBA therapy. The pretreatment level and the level after six months of therapy were not significantly different from the level of healthy controls. There were no significant differences in TNF-alpha mRNA levels between patients who responded to anti-HCV therapy, resulting in a decrease in HCV viremia below detection limit over 6 months and patients whose HCV RNA was not eliminated (p = 0.881). These results indicate that there is a transient increase of TNF-alpha gene expression during anti-HCV therapy. This fact may be connected with the host organism's response to IFN-alpha/RIBA therapy.

Blood serum glutathione alpha s-transferase (alpha GST) activity during antiviral therapy in patients with chronic hepatitis C.

BACKGROUND: Glutathione transferases (GST) belong to enzymes involved primarily in the processes of detoxification of exo- and endogenous substances. Immunohistochemical studies have demonstrated that alpha-GST present in the liver is localized exclusively in hepatocytes. The activity of alpha-GST is reported to reflect interstitial liver damage better than that of aminotransferases, especially in patients with autoimmune hepatitis, and, according to some authors, also in patients with chronic hepatitis C. The GST system has also been proposed to be indirectly involved in hepatocellular damage due to hepatitis C virus (HCV) infection. THE AIM OF THE STUDY: Was to assess the utility of alpha-GST as an accessory marker in monitoring antiviral therapy in patients with chronic hepatitis C. MATERIAL/METHODS: 21 patients (12 males and 9 females) with chronic HCV infections were evaluated. The diagnosis was based on clinical presentation and detection of anti-HCV, as well as the presence of HCV-RNA in blood serum detected by PCR. Fifteen patients (group I) were treated with interferon alpha-2b (IFN alpha-2b) at 3 MU s.c. doses administered three times a week (tiw) and ribavirin at 0.8 do 1.2 g/day doses, whereas 6 remaining patients (Group II) were treated with IFN alpha-2b alone at 5 MU s.c. tiw doses. The activity of alpha GST was determined with ELISA before and after 6 months of treatment, together with assessment of HCV-RNA viremia determining the decision concerning continuation of the therapy. RESULTS: The results are presented in Table 1 as mean values +/- SD. *p, 0.05. CONCLUSIONS: Combined antiviral treatment with IFN alpha-2b and ribavirin, and IFN alpha-2b monotherapy reduce blood serum alpha-GST activity in patients with chronic hepatitis C. alpha-GST is less useful as a liver damage parameter than ALT in monitoring of antiviral treatment.

Hepatitis C virus RNA level changes in sera during different regimens of treatment in patients with chronic hepatitis C.

BACKGROUND: Interferon alfa-2b (IFN) has been shown to be effective for chronic hepatitis C infection, but treatment efficacy is still limited. Sustained response after interferon alfa monotherapy is achieved in about 15-25%. Great efforts are made to identify more effective forms of therapy. Some of them include modifications of dosage of antiviral drugs, duration of the therapy and more optimal selection of patients for the treatment. Several virus- and host-related predictive factors for response to antiviral treatment have been proposed. One of the key predictive factors of sustained response to therapy are the pretreatment levels of viremia as well as the dynamics of initial changes of HCV-RNA levels assessed during antiviral therapy. AIM: The aim of our study was to compare changes of HCV-RNA viremia in patients with chronic hepatitis C during different regimens of antiviral treatment. MATERIAL/METHODS: 21 patients chronically infected with HCV (anti-HCV positive, HCV-RNA positive by PCR) were enrolled in the study. 11 patients (Group I) were treated with interferon alfa-2b (IFN-alpha 2b) at 3 MU tiw doses administered subcutaneously for 12 months. 10 patients (Group II) received 3 MU of IFN-alpha 2b daily during the first month and later the treatment was continued with the same dosage tiw for the next 11 months. The response to the treatment was assessed according to the generally accepted criteria after 6-month follow-up. The initial decline of HCV-RNA after 4 weeks of therapy was assessed. RESULTS: Results are presented in the Table. HCV-RNA expressed in copy/ml. CONCLUSION: The initial decline of HCV-RNA level during the first 4 weeks of antiviral therapy with interferon correlates with the final response to the treatment. The greater decline of viremia was observed in the group of patients treated with the 'induction' variant of treatment.

A multi-center open study to determine the effect of lamivudine on HBV DNA clearance and to assess the safety of the regimen in patients with chronic hepatitis B infection.

BACKGROUND: Patients with on-going HBV viral replication often present with clinical features of active chronic hepatitis. Until the recent introduction of nucleoside analogues, interferon-alpha was the only approved drug for these patients. One of the former drugs, lamivudine, has been shown in clinical trials in the US and Asia to effectively inhibit the viral polymerase of HBV. Our study was undertaken to assess the efficacy and safety of lamivudine therapy in Polish patients with chronic hepatitis B. MATERIAL/METHODS: Forty-five patients with chronic hepatitis B (HBeAg positive, anti-e negative, HBV-DNA positive by hybridization assay) were enrolled in the study. The patients received 100mg of lamivudine orally, once daily for 12 months. They returned for routine clinical and laboratory control every two weeks during the first months of treatment, and later at 3-month intervals while receiving lamivudine. RESULTS: At the end of treatment, serum HBeAg was not detected in 21 patients (48.8%), and anti-HBe appeared in the serum of 19 patients. 37.2% of the patients in the study group showed sustained suppression of serum HBV DNA at the end of treatment. Lamivudine therapy was well tolerated, with the rate of occurrence of adverse events similar to that observed in other clinical studies. CONCLUSIONS: 12-month lamivudine therapy in this Polish population of patients with chronic hepatitis B induced a high rate of HBeAg seroconversion, accompanied by reduction of HBV-DNA and the normalization of alanine aminotransferase activities.

Distribution of hepatitis C virus RNA in whole blood of patients with HCV infection and HBV-HCV coinfection.

BACKGROUND: Although HCV and HBV are essentially hepatoptropic, several lines of evidence suggest that these viruses can infect other cells, also PBMC in most patients with chronic HCV. MATERIAL/METHODS: The presence of HBV DNA and HCV-RNA was determined by a polymerase chain reaction (multiplex PCR and RT-PCR - nested PCR) in a group of patients with chronic liver disease. HCV-RNA was investigated in serum, plasma and peripheral blood mononuclear cells (PBMC) while HBV-DNA only in serum or plasma. RESULTS: Among 374 patients tested, HCV-RNA was detected in the venous blood of 208 patients; HCV RNA alone was detected in 154 patients and 54 patients were co-infected by HCV and HBV. HBV-DNA was found in 128 of 374 patients, while infection by HBV only was found in 74 patients. It was also shown that in the presence of HBV the replication ability of HCV is lower (p=0.085, Goodman-Kruskal Gamma = 0.561 and YuleQ = 0.5610). CONCLUSIONS: Since coexistence of HBV and HCV is not a rare case, diagnostics of hepatitis cannot be limited to detection of one type of the virus only. Misinterpretation of the virus type that caused the infection may lead to serious complications, especially in those cases when interferone is used for treatment.

[Lung function tests and bronchoalveolar lavage (BAL) findings in patients with primary biliary cirrhosis]. / Czynnosc ukladu oddechowego oraz sklad komórkowy popluczyn oskrzelowo-pecherzykowych (BAL) u chorych na pierwotna zólciowa marskosc watroby.

Primary biliary cirrhosis (PBC) is a rare cholestatic liver disease with an autoimmune etiology. The present study was done to estimate the frequency of occurrence of pulmonary disturbances and to analyse the results of bronchoalveolar lavage (BAL) findings in patients with PBC. Thirteen patients (only women) aged 50.4 with histologically proved PBC were investigated. Mean values of lung function tests in the study group were within normal range. In 38% of patients the impairment of DICO was observed. Only in one patient decrease of lung compliance (Cdyn) was observed. BAL findings showed the increase of lymphocytes ratio (> 15%) in 5 patients (38%). The disturbances in lung function and BAL were observed in patients with different stage of PBC and without clinical symptoms of lung disease.