[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.

[Peginterferon alpha-2b in patients with chronic hepatitis C]. / Pegylowany intefeon alpha-62b i rybawiyna w leczen przewlekllego wirusoweg zapalenia watroby typu C.

150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5 microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse events the treatment was interrupted in 7 persons, 4 other persons resigned. Periodical reduction of pegylated interferon doses was necessary in 19% and the reduction of ribavirin in 21% of patients. Six months after the completion of treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus genotype, nor viremia was marked in the study. The negative correlation between the degree of fibrosis in the liver tissue and the results of sustained virological response was stated. Degree of inflammation at liver tissue, sex, age over and less than 40 years did not correlate with the final virological results. The recurrence of infection happened at 7% of the treated persons (negative HCV-RNA directly after the treatment--positive 6 months after the completion). During the treatment period, and comparison with the results obtained before its implementation, statistically significantly decreased: hemoglobin concentration, the number of leukocytes, granulocytes and thrombocytes. They returned to the referential values half a year after the completion of treatment. The activity of enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the first weeks of the treatment till the end and remained significantly lower after 6 months. In both sexes statistically significant reduction of bodyweight was stated, while it increased during the six months after the completion of treatment. Adverse events, which mostly were mild and were not the cause of interruption of treatment, were numerous and occurred at different frequency, in the range from over 50% (flu-like) to 0.7%.

[Detection of HCV-RNA in liver tissue does not correlate with inflammatory process and fibrosis activity in chronic hepatitis C]. / Wykrycie HCV-RNA w tkance watroby nie koreluje z aktywnoscia i wlóknieniem watroby w przebiegu przewleklego zapalenia watroby typu C (wzw-C).

The significance of HCV-RNA presence in the liver tissue in chronic hepatitis C activity or prognosis has not yet been clearly explained. Therefore, we have examined the relationship between the presence of HCV-RNA in the liver and selected parameters of disease activity and liver damage. A group of 48 chronically HCV infected patients (7-63 years old, mean 39 years) was evaluated. In the patients we assessed the activity of transaminases (ALT, AST), gammaglutamyltransferase (GGTP), and alkaline phosphatase (ALP). The patients underwent routine liver biopsies and the liver tissue was examined histopathologically and in order to detect the presence of HCV-RNA, by means of a combined procedure joining a new method of HCV-RNA extraction from the liver tissue and HCV-RNA detection with RT-PCR automatic Cobas Amplicor Hepatitis C ver. 2.0 assay (Roche Diagnostics). At the time of the liver biopsy, 44 of the patients were identified as having detectable serum HCV-RNA (as examined by means of Cobas Amplicor Hepatitis C ver. 2.0 assay), 3 patients were negative, and 1 was not tested. The presence of HCV-RNA in the liver tissues was detected in 39 cases (81.2%). In the parameters examined we have not found any significant differences between currently liver HCV-RNA positive and negative patients. Presence of the detectable HCV-RNA in the liver bioptats from chronic hepatitis C patients does not correlate with disease activity or level of liver damage.

Presence of HCV RNA in hepatic tissue and effectiveness of treatment with interferon and ribavirin.

BACKGROUND: The aim of the study was to assess the prognostic value of HCV RNA detection in hepatic tissue for the response to treatment with interferon alfa (IFN) and ribavirin (RIB) in patients with chronic hepatitis C. PATIENTS AND METHODS: A group of 55 patients infected with HCV was examined before the commencement of treatment with IFN and RIB. In all of them HCV RNA was detected in the serum. The presence of HCV RNA in hepatic tissue was confirmed using a technique combining a new method of HCV RNA extraction from hepatic tissue and detection of HCV RNA with RT-PCR Cobas Amplicor Roche tests. The group of 55 patients received IFN (3-6 MU, 3 times a week) and RIB (800-1200 mg daily) for 6 to 12 months. The response to treatment was assessed 6 months after completion of the therapy. Sustained response (SR) was defined as absence of HCV RNA in the serum and normalization of ALT levels. RESULTS: The presence of HCV RNA in hepatic tissue was confirmed in 48 patients (group A), and in 7 (group B) HCV RNA was not detected in the liver. SR was observed in 17 patients from group A and 6 from group B. Significant correlation (p < 0.05) was found between detection of HCV RNA in hepatic tissue and response to IFN + RIB therapy. CONCLUSIONS: As it follows from our results, the detection of HCV RNA in the hepatic tissue of a patient with chronic hepatitis C may be a negative prognostic factor for the patient's response to IFN + RIB therapy.

Preliminary assessment of utility of radiofrequency ablation technique in treatment of primary hepatocellular carcinoma (HCC) in patients with hepatic cirrhosis.

BACKGROUND: Primary hepatocellular carcinoma very often develops in the cirrhotic liver. Surgical treatment of cirrhotic patients is associated with considerable risk. Even partial resection of the liver carries the risk of liver failure in such patients. Therefore, the thermoablation technique used in patients with liver tumors and cirrhosis, arouses considerable interest. The aim of the study was preliminary assessment of the value of radiofrequency (RFA) ablation in the treatment of HCC in patients with hepatic cirrhosis. MATERIAL/METHODS: From April 2001 to April 2002, 14 patients aged 30-79 with cirrhosis and focal lesions of primary liver tumor type (carcinoma hepatocellulare) were treated with transcutaneous thermoablation. Transcutaneous thermoablation with Cool Tip Equipment probe (Radionics) was performed under local anesthesia induced after intravenous sedation, or under general anesthesia with propofol (TIVA). In case of single lesions up to 3 cm in diameter, the exposure to thermal waves lasted 12 min, in case of larger lesions 2 to 4 sessions were used. The effects of RFA were assessed intraoperatively by means of USG, measuring the coagulation area, and then MRI was performed to confirm complete destruction of the lesions. The response to treatment was assessed by CT after 8 weeks. RESULTS: Among 8 patients with single focal lesions complete remission (CR) was obtained in 4, and partial remission (PR) in the remaining 4 cases. One subject with CR died 5 months later because of hemorrhage from esophageal varices. Among 6 patients with more than one HCC focus subjected to RFA, CR was obtained in 1, PR in 3, and one female patient who underwent the procedure in the period of non-compensated liver function, died 1.5 months later because of hepatic failure. Repeated thermoablation is considered in patients with PR. CONCLUSIONS: 1. Radiofrequency ablation is a safe method of treatment of HCC in patients with cirrhosis. 2. One of the advantages of RFA is that it can be performed repeatedly. 3. RFA can be combined with other methods.

Disturbances of iron metabolism in chronic liver diseases.

BACKGROUND: Systematic biochemical and histopathological studies carried out in patients with diagnosed chronic liver diseases (cirrhosis, hepatocellular carcinoma) confirm the important pathogenetic role of commonly occurring accumulation of iron deposits, and not only in the classic form of hemochromatosis. The reports concern the pathologic role of iron storage in the liver often accompanying metabolic disturbance syndrome including obesity, type II diabetes and hypertension. The aim of the study was preliminary assessment of the incidence of iron metabolism disturbances in the population of patients with chronic liver diseases. MATERIAL/METHODS: Among 351 patients of the Department of Infectious Diseases who had histopathologic investigations of liver bioptates performed in 2000-2001, 99 subjects (28%) with morphological confirmation of iron deposition in the liver were selected. Retrospective analysis based on data from the patients' medical records took into consideration demographic information, results of laboratory tests (blood levels of hemoglobin, ALAT, iron, ferritin) and the ultimate diagnosis. The correlations between iron metabolism disturbances and the observed liver pathology were analyzed. RESULTS: The study group consisted of 99 subjects including 77 males (mean age 42.8 yrs) and 22 females (mean age 47.5 yrs). Most of them had been diagnosed with chronic hepatitis C, (N = 39). Liver damage due to hyperlipidemia was diagnosed in 12, and toxic liver damage in 11 patients. Subjects with chronic renal failure and after antitumor therapy accounted for 14%. In 7 patients, hemochromatosis was diagnosed or suspected. In that group, mean serum ferritin level amounted to 959.3 ng/ml. In 79% of cases, ALT values fell within the 41-500 IU/l range, whereas iron and ferritin levels exceeded the normal limits in 49% and 71% of cases, respectively. The preliminary analysis of pathologic iron accumulation in liver bioptates in relation to biochemical parameters of iron metabolism measured in the blood did not allow unequivocal confirmation of linear correlation between these phenomena. CONCLUSIONS: 1. Over 1/4 of patients diagnosed because of chronic liver diseases demonstrated excessive accumulation of iron in liver bioptates. 2. The analyzed group consisted predominantly of males with chronic hepatitis C. 3. Metabolic or toxic liver damage was diagnosed n 1/3 of cases. 4. No unequivocal confirmation of correlation between pathologic iron accumulation in the liver and values of iron metabolism parameters in blood was obtained.