[Polish multicenter study on safety and efficacy of adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)]. / Wieloosrodkowe badanie bezpieczenstwa i skutecznosci preparatu dipiwoksyl adefowiru w leczeniu przewleklego wirusowego zapalenia watroby typu B u doroslych z opornoscia na lamiwudyne (HEP 2008).

Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.

[Antiviral treatment of chronic B hepatitis; 2010 - therapeutic recommendations]. / Leczenie przeciwwirusowe przewleklego zapalenia watroby typu B--zalecenia terapeutyczne 2010.

The drugs currently approved for treatment of HBV infections are: interferon alpha2a and alpha2b, pegylated interferon (PeglFN-al-pha2a) natural interferons and nucleos(t)ide analogues (NA): adefovir, entecavir, lamivudine, telbivudine (currently not available in Poland) and tenofovir. The following questions are described: the primary goal of antiviral treatment, criteria in therapeutic decision-making (including extrahepatic manifestations, compensated and decompensated cirrhosis of the liver), treatment failure (including: drug resistance), management of patients with HBV-positive markers, in whom chemotherapy or other immunosuppressive therapy is planned. In treatment-naive patients with chronic hepatitis B the first line therapy should be PeglFN-alpha2a monotherapy, and the first-line should be entecavir or tenofovir (highest potential for HBV replication suppression and high genetic barrier to resistance). In drug resistance the patient should be switched to another, preferably high-potency NA (entecavir or tenofovir) or start PeglFN-alpha2a therapy.

Recommendations of the Polish Group of Experts for HCV for the treatment of hepatitis C in 2020.

The recommendations set out the principles of diagnosis and treatment of hepatitis C virus (HCV) infections according to the most recent knowledge. The main goal of therapy for HCV infection is to eliminate the virus from the body, which consequently leads to arrest of progress or regression of changes in the liver. Current version of the recommendations prioritise pangenotypic regimens and provide guidelines in special populations of patients, such as children, cirrhotics, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfected, those with renal failure, hepatic decompensation and non-responders to previous therapies.

[Interferon alpha, gamma, omega before and during treatment of chronic hepatitis C with pegylated interferon alpha and ribavirin]. / Interferony alfa, gamma i omega przed oraz w trakcie leczenia przewleklego wirusowego zapalenia watroby typu C pegylowanym interferonem alfa z rybawiryna.

AIM OF THE STUDY: assessment of interferon alpha, gamma, omega concentrations in patients with chronic hepatitis C before and during antiviral treatment and comparison of these parameters between chronically infected HCV and healthy individuals (control group). METHODS: IFN alpha, gamma, omega concentrations were measured before and in 2, 12, 48 week during antiviral therapy in patients with chronic HCV infection treated with PegIFN plus ribavirin and in 30 cases of healthy individuals of control group. RESULTS: Statistically significant differences in IFN alpha concentrations at different times of investigation in patients with chronic hepatitis C and in IFN alpha and omega concentrations in comparison to results obtained in control group and in patients before treatment were found. Concentrations of IFN gamma in 48 week and omega in "0" and 2 week of the treatment were higher in patients with GI,G2 than with G3. There were no statistically significant differences in IFN alpha, gamma, omega concentrations between patients with good or bad response to antiviral treatment at EVR, ETR, SVR and between patients with shorter or longer than 10 years of HCV infection. CONCLUSION: 1. IFN alpha was no detected in healthy individuals but was detected in 34% of patients with chronic hepatitis C. 2. IFN omega was present in each case from control group but only in less than 50% of chronically infected with HCV. 3. There was no correlation in IFN alpha, gamma and omega concentrations with efficacy of antiviral treatment.

[Long-term viral response to interferon alpha 2b plus ribavirin in chronic hepatitis C patients during standard therapy]. / Odlegle wyniki leczenia inferferonem alfa 2b i rybawiryna chorych z przewleklym wirusowym zapaleniem watroby typu C w warunkach leczenia standardowego.

UNLABELLED: The aim of study was to evaluate the long-term effect of combination treatment with interferon alpha 2b and ribavirin in patients with chronic hepatitis C during standard therapy. MATERIAL: 210 chronic HCV infected patients (M 134, F 76, mean age 43 +/- 12,3) were treated with interferon alpha 2b TIW and ribavirin (1,0--1,2 g/d) for 48 weeks. None of the patients was infected with HBV or HIV. METHODS: HCV infection was confirmed with presence of HCV-RNA in blood serum. HCV-RNA was evaluated before, after 24 and 48 weeks of therapy. SVR was checked 24 weeks after discontinuation of therapy. LTR durability of HCV-RNA negativity was observed with a follow-up > 12 months after cessation of treatment RESULTS: EVR, ETR and SVR were observed respectively in 56,2%, 40,5% and 37% of patients. Median follow-up was 21,9 months (range 6--63 months after SVR). Recurrence of HCV infection was not observed in any case of SVR patients, who completed follow-up. CONCLUSIONS: EVR and SVR was observed in 56,2% and 37%. EVR, ETR and SVR were higher in treated woman than in men. LTR was achieved in all patients with SVR who were checked in prolonged time.

[Bacterial endocarditis in the course of sepsis in 7th month of treatment with peginterferon alfa and ribavirin in patient with chronic hepatitis C]. / Bakteryjne zapalenie wsierdzia w przebiegu posocznicy w 7 miesiacu leczenia peginterferonem alfa I rybawiryna u pacjenta z przewleklym zapaleniem watroby typu C.

In the study we described severe adverse events such as sepsis and bacterial endocarditis in the patient treated because of chronic hepatitis C (CHC). A case of 57 year old man with CHC, with recurring increased aminotransferases up to 100 IU/l; histological result of liver biopsy--G3, S2, HCV-RNA positive, genotype--HCV1b. The therapy with peginterferon alfa and ribavirin was introduced. The negative result of HCV RNA was obtained in 12th week of treatment. In the 7th month the patient was admitted to the hospital because of sepsis due to Escherichia coli, acute renal insufficiency and right orchitis. In spite of the treatment and general clinical improvement, the patient was still febrile. The bacterial endocarditis was found after number of diagnostic procedures. The treatment of endocarditis lasted 6 weeks in the hospital. During the hospitalization and 6 months after the HCV-RNA were performed with the negative results. The therapy of CHC with peginterteron and ribavirin is save in most cases however requires increased clinical surveillance, especially in the second half-year.

[Adult-onset Still's disease--case report]. / Opis przypadku choroby Stilla rozpoznawanej w wieku dojrzalym.

UNLABELLED: We report diagnostic difficulties in the patient with fever of unknown origin. The patient was diagnosed with adult-onset Still's disease, which is a rare seronegative arthritis. Thirty seven year old patient was admitted to the hospital because of symptoms lasting for 6 weeks: fever, evanescent skin rash, arthritis and sore throat with the suspicion of fever of unknown origin. After exclusion the infectious aetiology, Still's adult-onset disease was recognised based on clinical picture, biochemical, serological and radiography, sonography results and after reumatological consultation. Treatment with nonsteroidal anti-inflammatory drugs was introduced with good clinical effect. CONCLUSIONS: Diagnosis of fever of unknown origin is great challenge for doctors and requires realising careful anamnesis, performing overstandard examinations and good co-operation with consultants of other specialities.

Recommendations for the treatment of hepatitis C in 2017.

The goals of treatment is to eliminate HCV infection, stop or reverse histological changes, reduce the risk of hepatocellular carcinoma development and transmission of the infection to other individuals. According to the recommendation of the Polish Group of Experts for HCV in 2017 all patients with chronic HCV infection should receive treatment, but it is not recommended in patients at high risk of short overall survival. If access to therapy is restricted, priority should be given to patients whose HCV infection can lead to an unfavourable outcome of the disease within a short time frame, particular to individuals with liver cirrhosis, rapidly progressing liver fibrosis, extrahepatic manifestations of HCV infection, chronic kidney diseases, patients before and after organ transplantation. Current recommendations of Polish Group of Experts for HCV provide guidelines to select optimal medication, assessment of liver fibrosis, treatment efficacy, dealing with resistance to direct acting antivirals, monitoring for hepatocellular carcinoma, management of HBV/HCV coinfection and drug interactions. It constains also advice on treatment of special patients populations such as renal failure, liver transplant and hepatic decompensation, as well as retreatment of patients which failed interferon free therapy. Moreover specific recommendations of management patients infected with different genotypes with currently reimbursed regimens or those expected to become available shortly in Poland are also included.

Recommendations for the treatment of hepatitis B in 2017.

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.

Interleukin-2 (IL-2) expression in livers of patients with chronic hepatitis C virus (HCV) infection.

The studies performed till now have pointed to an increased serum levels of interleukin 2 (IL-2) in infection with hepatitis C virus (HCV). The present study was aimed at examining intrahepatic expression of IL-2 in children (n=15) and in adults (n=11) with chronic hepatitis C as well as its correlations with histological lesions and selected clinical data. The immunocytochemical techniques and in situ hybridization method were applied at light and electron microscopy level. Under the light microscope, expression of IL-2 was analysed semiquantitatively. As compared to the control material, in livers of both groups of chronic hepatitis C patients augmented expression of IL-2 was demonstrated. The reaction product was localized mainly in the cytoplasm of hepatocytes which was confirmed by hybridocytochemistry. The mean proportion of cells with positive reaction for IL-2 mRNA was significantly lower than the proportion of cells positive for the respective protein. No correlation was disclosed between IL-2 expression on one hand and grading or staging, alanine aminotransferase (ALT) and HCV RNA levels in serum on the other. At the ultrastructural level, IL-2 in hepatocytes was present mainly in the endoplasmic reticulum and mitochondria. Our studies have confirmed augmented expression of IL-2 in livers of patients with chronic hepatitis C and have demonstrated that hepatocytes represent the principal source of the cytokine in HCV in vivo infection. Moreover, expression of IL-2 in the infection was examined for the first time at the ultrastructural level. Mitochondrial localization of IL-2 suggests a direct involvement of the cytokine in disturbed function of the organelles.

Mutations within protein kinase R-binding domain of NS5A protein of hepatitis C virus (HCV) and specificity of HCV antibodies in pretreatment sera of HCV-chronically infected patients and their effect on the result of treatment.

We analyzed protein kinase R (PKR)-binding domain sequences of hepatitis C virus (HCV) NS5A protein and the profile of HCV-specific antibodies from pretreatment sera of HCV-chronically infected patients. Results were compared with clinical data to verify their influence on the course and result of therapy. Of 9 patients enrolled in a 12-month treatment with pegylated interferon alpha (PEG-IFN-alpha) plus ribavirin (RBV), 6 patients responded to therapy, as assessed by the lack of HCV RNA in their sera, and 3 did not. Among 8 HCV-1b-infected patients, those who responded did not have significantly more mutations in the IFN sensitivity determining region (ISDR) compared to non-responders (P = 0.637). Similarly, in the remaining 26-amino acid region of the PKR-binding domain, behind ISDR, the number of mutations did not differ significantly between the two groups (P = 0.796). A correlation was found between the presence of envelope 2 (E2)-specific antibodies and the result of treatment (P = 0.048). This pilot study indicates that mutations in the PKR-binding domain of HCV genotype 1b do not correlate with outcome of PEG-IFN-alpha/RBV therapy. However, the presence of E2-specific antibodies in the pretreatment sera of HCV-chronically infected individuals could serve as a prognostic marker predicting the result of treatment, before its initiation.

[Optimization of the method of treatment of chronic viral hepatitis C with pegylated interferon-alfa and ribavirin]. / Optymalizacja metod leczenia przewleklego wirusowego zapalenia watroby typu C pegylowanym interferonem-alfa z rybawiryna.

Despite of significant progress in the treatment of chronic hepatitis C after introduction of combination therapy with pegylated form of interferon-a with ribavirin, still overall response rate in HCV genotype-1 infected has been modest. Several teams has been working on modification of therapeutic methods. Optimization of the results is realized by individualization of therapy taking under consideration some known virological and host features. The main trends are following: settlement of optimal period of treatment of infected with HCV genotype-1, applying interferon-induction therapy for non-responders and relapsers at the course of previous treatment, as well as prolongation of therapy-period, and ribavirin-dose increasing. Very important is also looking for optimal predictive-viral parameters in early course of disease.

[Procalcitonin as a diagnostic marker in systemic inflammatory response syndrome (SIRS) and sepsis]. / Prokalcytonina jako marker diagnostyczny Zespolu Uogólnionej Reakcji Zapalnej (SIRS) i posocznicy.

OBJECTIVE: Evaluation the value of procalcitonin as a diagnostic and prognostic marker in septic patients and patients with systemic inflammatory response syndrome (SIRS). MATERIAL AND METHODS: 126 patients were included into the study. The patients were divided into four groups: 1--septic patients with positive blood cultures, 2--septic patients with negative blood cultures, 3--patients with SIRS, 4--patients without sepsis and SIRS. PCT level was measured by imunoluminometric assay (LUMItest) and immunochromatographic assay (PCT-Q). RESULTS: PCT level is higher in patients with sepsis than in patients with SIRS. PCT level is only slightly elevated in patients without sepsis and SIRS. The highest PCT level is found in patients with septic shock. In patients with the clinical improvement the frequency of PCT level increase is approximately twice lower than in patients who died. CONCLUSIONS: Measurement of PCT level on the first, second and third day of hospitalization has no prognostic value. There is no significant difference in PCT level in sepsis caused by Gram positive and Gram negative bacteria. PCT is a useful marker in diagnosis of sepsis but its role in monitoring the severity of sepsis requires more clinical studies.

[Fifteen years of investigations on hepatitis C virus in Poland]. / Piektnascie lat badan nad wirusem C zapalenia watroby w Polsce.

The paper reviews published results of investigations on hepatitis C virus on several fields: epidemiology, virology, pathogenesis, immunology, coinfections, and antiviral-treatment. Articles of Polish investigators, as well as Polish--international research groups were taken into consideration.