Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

Quantum Glass of Interacting Bosons with Off-Diagonal Disorder.

We study disordered interacting bosons described by the Bose-Hubbard model with Gaussian-distributed random tunneling amplitudes. It is shown that the off-diagonal disorder induces a spin-glass-like ground state, characterized by randomly frozen quantum-mechanical U(1) phases of bosons. To access criticality, we employ the "n-replica trick," as in the spin-glass theory, and the Trotter-Suzuki method for decomposition of the statistical density operator, along with numerical calculations. The interplay between disorder, quantum, and thermal fluctuations leads to phase diagrams exhibiting a glassy state of bosons, which are studied as a function of model parameters. The considered system may be relevant for quantum simulators of optical-lattice bosons, where the randomness can be introduced in a controlled way. The latter is supported by a proposition of experimental realization of the system in question.

The impact of chronic hepatitis C infection on cholesterol metabolism in PBMCs is associated with microRNA-146a expression.

Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs. Blood samples collected from 42 healthy donors and 72 CHC patients were the source of materials. HCV RNA, intracellular cholesterol level and miR-146a expression were determined in PBMCs, as well as HCV genotype and interferon (IFN)α concentration in sera. The influence of miR-146a inhibition on cholesterol expression in PBMCs was analysed in vitro after transient cell transfections with mirVana™ anti-miR-146a Inhibitor. Our data demonstrated an alteration of miR-146a and intracellular cholesterol expression in PBMCs and of IFNα concentration in sera of genotype 1, HCV-infected patients compared to the healthy donors. Also, in cultured PBMCs, miR-146a expression and intracellular cholesterol level were significantly decreased in CHC patients compared to the healthy donors. In vitro blockage of miR-146a expression in PBMCs of CHC patients greatly impaired intracellular cholesterol expression. In these conditions, miR-146a expression was positively correlated with the intracellular cholesterol level. These results suggest that genotype 1 HCV infection may alter miR-146a expression in PBMCs and, consequently, contribute to the observed dysregulation of cholesterol synthesis.

The altered expression of α1 and ß3 subunits of the gamma-aminobutyric acid A receptor is related to the hepatitis C virus infection.

The modulation of the gamma-aminobutyric acid type A (GABA A) receptors activity was observed in several chronic hepatitis failures, including hepatitis C. The expression of GABA A receptor subunits α1 and ß3 was detected in peripheral blood mononuclear cells (PBMCs) originated from healthy donors. The aim of the study was to evaluate if GABA A α1 and ß3 expression can also be observed in PBMCs from chronic hepatitis C (CHC) patients and to evaluate a possible association between their expression and the course of hepatitis C virus (HCV) infection. GABA A α1- and ß3-specific mRNAs presence and a protein expression in PBMCs from healthy donors and CHC patients were screened by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. In patients, HCV RNA was determined in sera and PBMCs. It was shown that GABA A α1 and ß3 expression was significantly different in PBMCs from CHC patients and healthy donors. In comparison to healthy donors, CHC patients were found to present an increase in the expression of GABA A α1 subunit and a decrease in the expression of ß3 subunit in their PBMCs. The modulation of α1 and ß3 GABA A receptors subunits expression in PBMCs may be associated with ongoing or past HCV infection.

Expression of microRNA-155 precursor in peripheral blood mononuclear cells from Hepatitis C patients after antiviral treatment.

Chronic hepatitis caused by Hepatitis C virus (HCV) is the main source of liver cirrhosis, hepatocellular carcinoma, and extra-hepatic diseases. After treatment-induced resolution of hepatitis C, the persistence of HCV RNA in serum and peripheral blood mononuclear cells (PBMCs) is often observed. An expression of the precursor of microRNA-155 (miR-155) called BIC can be the factor responsible for a course of HCV infection. Therefore, we assessed the relationship between BIC expression and HCV RNA status in sera and PBMCs samples of 64 hepatitis C patients treated with interferon alpha(IFN-alpha)+ribavirin. High expression of BIC in PBMCs was determined in 100% of patients that harbored HCV RNA in serum and PBMCs. Further, we found that 83% of PBMCs samples were BIC-positive in a group of patients that eliminated HCV RNA only from serum. The lowest expression of BIC was found in patients that eliminated HCV RNA from both serum and PBMCs.

Azacitidine Use After Allogeneic Stem Cell Transplantation-Results From the Polish Adult Leukemia Group.

BACKGROUND: Relapse of primary hematologic disease constitutes an important reason for failure of allogeneic hematopoietic stem cell transplantation (alloHSCT). There are very few treatment modalities for this indications. Therefore, there is a need for novel effective therapies and even more for the prevention of relapse. There are scarce data that azacitidine can be used for these purposes. METHODS: At the Polish Adult Leukemia Group, we retrospectively analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients, patients with minimal residual disease/mixed chimerism, and patients in complete remission with high risk of relapse were analyzed separately. There were 17 patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8 male, and overall median age of 56 years (range, 15-78); 7 patients received donor lymphocyte infusion (DLI). RESULTS: Patients treated because of relapse received a median of 3 (range, 1-6) cycles of azacitidine, patients receiving preemptive treatment received a median of 4 cycles (range, 2-6), and those on maintenance received a median of 5 cycles (range, 3-5). Toxicity was considerable, especially in relapse-neutropenia (67%), anemia (67%), thrombocytopenia (100%), serious infections (78%)-and preemptive settings. Median overall survival of patients treated for relapse reached 6.8 months (95% confidence interval [CI], 0.7-∞), with better survival observed in patients with temporary disease control (7.7 vs 4.7 mo) and without previous exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75% (95% CI, 13%-96%) for preemptive and 50% (95% CI, 0%-91%) for maintenance treatment. DLI did not aggravate graft-versus-host disease. CONCLUSIONS: Effectiveness of azacitidine in relapsing patients is disappointing. Azacitidine seems to be promising in preemptive and maintenance settings. Toxicity is considerable. Further research is needed.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Early complete donor hematopoietic chimerism in peripheral blood indicates the risk of extensive graft-versus-host disease.

Achievement of complete donor hematopoietic chimerism (CC) is the goal of allogeneic stem cell transplantation (allo-SCT). Persistence of recipient hematopoiesis augments the risk of relapse, which is one of the main reasons for mortality after allo-SCT. Another main reason for morbidity and mortality is severe extensive chronic graft-versus-host disease (cGvHD). We examined chimerism in peripheral blood of 54 allogeneic stem cell recipients using multiplex STR-PCR method and compared it with the timing and severity of cGvHD. In total, 25 patients achieved early CC (by day 100 post transplant) at a median time of 60 days. In total, 21 of them developed extensive cGvHD. In those patients CC uniformly preceded emergence of cGvHD by a mean of 85 days. A total of 26 patients obtained late CC at a median time of 270 days post transplant. Of this group, only eight patients developed extensive disease. Development of cGvHD in those patients preceded achievement of CC in 10 of 13 cases by a mean of 100 days. The difference between early and late CC groups as to the frequency of the extensive cGvHD was statistically significant (P<0.001). Also, there was a significant correlation of the time of CC and time between CC and cGvHD. Additionally, patients with early CC developed significantly more severe cGvHD measured by the need of three-drug treatment to control the disease (P<0.005). It can be concluded that achievement of early complete donor hematopoietic chimerism in peripheral blood is strongly predictive of severe extensive GvHD.

Antagonism by lipophilic quaternary ions of the K+ channel opener, levcromakalim, in vascular smooth muscle.

1. The aim of this study was to characterize the interaction between the K+ channel opener levcromakalim (LKM) and several quaternary ions, in vascular smooth muscle, in vitro. Segments of isolated, thoracic aorta of the rat were suspended in organ baths filled with Krebs solution at 37 degrees C. Cumulative concentration-response curves to LKM were obtained in the absence and in the presence of increasing concentrations of quaternary ions using a number of agents to pre-constrict the vessel. The ions tested were tetraphenylphosphonium (chloride TPP-Cl and bromide TPP-Br salts), tetrapentylammonium (TPeA), tetraethylammonium (TEA), tetraphenylarsonium (TPAs) and tetraphenylboron (TPB). 2. For the compounds which antagonized the vasorelaxation responses of LKM, 'apparent pKB' values were estimated on the basis of a single concentration of antagonist. These were then used to obtain the following order of potency: TPP-Br (7.22 +/- 0.25) = TPAs (7.12 +/- 0.04) = TPP-Cl (7.11 +/- 0.15) > TPeA (6.23 +/- 0.20). TEA and TPB were both found to be inactive at the maximum concentrations used. 3. The interaction between the cationic TPP and anionic TPB was also investigated. The shift in the LKM concentration-response curve constructed in the presence of both of these compounds was compared to that when each agent was present separately. We found that TPB, at concentrations greater than 1 microM, reversed the blockade of the LKM-mediated relaxation induced by TPP (3 microM). 4. Similar experiments were undertaken combining TPB with either alinidine or glibenclamide (both functional antagonists of K+ channel openers). It was found that TPB (10 microM) partially reversed the antagonism induced by alinidine (30 and 100 microM) but had no effect on the action of glibenclamide(3 microM).5. These studies show that lipophilic cations such as TPP and TPAs are potent antagonists of levcromakalim-mediated vasorelaxation responses in the rat thoracic aorta. The mechanism by which these compounds cause their antagonism is not known. However, given the lipophilicity of these compounds, it is possible they may act at a number of sites including the KATP channel itself or possibly via some other intracellular mechanism.

The vascular activity of some isoflavone metabolites: implications for a cardioprotective role.

Legume-derived isoflavones such as genistein, diadzein and equol have been associated with a reduction in risk of cardiovascular disease. In the current study, we explore the vascular activity of several isoflavone metabolites namely dihydrodaidzein, cis and trans-tetrahydrodaidzein and dehydroequol for potential cardioprotective properties. Rat isolated aortic rings were used. 17beta-oestradiol, equol, and all four of the metabolites studied significantly antagonized contractile responses to noradrenaline. The direct vasodilatory action of these compounds were examined and in contrast to 17beta-oestradiol, the vasodilatory effect of which was demonstrated to be endothelium independent, the dilatory action of all four compounds could be inhibited by endothelium denudation. Further, the dilatory action of both dihydrodaidzein and cis-tetrahydrodaidzein were inhibited by the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine (NOLA), by the soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and by 40 mM KCl. Dilatory responses to dehydroequol and trans-tetrahydrodaidzein, on the other hand, were inhibited by 40 mM KCL but not by NOLA nor ODQ. Finally, we examined the protective potential of these compounds in inhibiting endothelium damage by oxidized low density lipoprotein (ox-LDL). Trans-tetrahydrodaidzein was at least 10 fold more potent than 17beta-oestradiol in protecting against ox-LDL induced damage. We conclude that the isoflavone metabolites, dihydrodaidzein, cis- and trans-tetrahydrodaidzein and dehydroequol, may potentially represent a novel series of cardioprotective therapeutics.

Structure-activity relationship of quaternary ion antagonism of levcromakalim-induced relaxation in pig coronary artery.

The aim of this study was to investigate the interaction between the K+ channel opener levcromakalim and several quaternary ions. Cumulative vasorelaxant-response curves to levcromakalim were constructed in the absence and in the presence of the quaternary ions, in the pig coronary artery. The most potent compounds (based on 'apparent pKB' values) were: propyltriphenylphosphonium (7.33), butyltriphenylphosphonium (7.04), tetraphenylarsonium (6.86), tetraphenylphosphonium (6.81), ethyltriphenylphosphonium (6.70), and hexyltriphenylphosphonium (6.63). Tetrabutylphosphonium (6.06), tetrabutylammonium (5.12), methyltriphenylphosphonium (5.25), clofilium (5.66) and guanethidine (5.61) were significantly less potent. Tetrapropylammonium, tetrapentyltin and tetraphenylboron were inactive at the maximum concentrations used (30 microM). Tetraphenylboron (10-100 microM) fully reversed tetraphenylphosphonium, tetraphenylarsonium (both at 3 microM), tetrabutylammonium (30 microM) and clofilium (10 microM) and partially reversed guanethidine (10 microM) antagonism of levcromakalim responses indicating a similarity in the mechanism of action of these chemically distinct compounds. The results show that quaternary ions similar in structure to tetraphenylphosphonium, i.e., containing phosphonium ion centre and phenyl side chains, are the most potent antagonists of levcromakalim, in pig coronary artery. It is also apparent that marked changes can be made in the substitution on the phosphonium ion (ethyl to hexyl) with little or no effect on their potency.

The electrophysiological effects of tetraphenylphosphonium on vascular smooth muscle.

The effect of the lipophilic quaternary ion, tetraphenylphosphonium, on membrane potential of segments of rat small mesenteric artery and on the current in single voltage-clamped smooth muscle cells from rabbit portal vein was studied. In rat small mesenteric artery, tetraphenylphosphonium (1-30 microM) caused membrane depolarization of approximately 23 mV and decreased or abolished the hyperpolarization induced by the KATP channel opener, levcromakalim (0.1-3 microM). In rabbit portal vein K+ currents induced by levcromakalim (10 microM) or pinacidil (10 microM) were completely inhibited by tetraphenylphosphonium (IC50 0.5 microM). The results show that tetraphenylphosphonium antagonizes the KATP current induced by K+ channel openers in vascular smooth muscle possibly by acting on the KATP channel itself.

A case of the subacute brainstem encephalitis.

A case of brainstem encephalitis of undetermined etiology is reported in 66-year-old woman who had a sudden onset of illness with left abducens palsy, nystagmus and ataxia. The symptoms progressed to complete paralysis of eye movements, dysphagia and left hemiparesis with generalized hyperreflexia. Examination of CSF, CT scan and MRI of the brain were normal. The patient died 4 months after onset of disease. Neuropathologic study disclosed in the brainstem numerous perivascular and nodular inflammatory cell infiltrations composed predominantly of lymphocytes T and B. Most intensive inflammation concerned midbrain and pontine tegmentum and to a lesser degree medulla oblongata, pontine nuclei and cerebellar nuclei. Basal ganglia, cerebral and cerebellar cortex were unaffected. Neuropathological finding was reminiscent of brainstem encephalitides related to viral infection or to paraneoplastic syndrome. However, HSV-1, EBV, and CMV antigens were not detected by immunohistochemistry, as well as evidences of malignancy were not present in this case.

School stress, teachers' abusive behaviors, and children's coping strategies.

OBJECTIVE: This paper presents the research study on school stress and the coping strategies children use in public schools in Poland. The main goals were to identify and investigate: (1) school stress components, its frequency and intensity, (2) its psychological and temperamental correlates and consequences, (3) students' coping strategies. METHOD: A field-correlative design was applied to test 271 students, between the ages of 13 and 14, using six questionnaires. School stressors and children's coping strategies were identified and analyzed on two separate questionnaires with open-ended questions. School stress scale investigated the frequency of stress components and the intensity of stress. Anxiety level was measured by standardized, Polish version of STAIC. Temperamental characteristics were tested by the standardized questionnaire STI-R/4. RESULTS: The most frequent stressors were teachers' abusive behaviors in the classroom teaching and assessment. Students' coping strategies, and their school results, were determined by the intensity of school stress, anxiety, and temperamental characteristic. CONCLUSIONS: This study demonstrated teachers' psychological abuse as an important component of children's school stress. An over-abundant by the abuse, stress and anxiety subjects regulate their optimal level of stimulation and activation by using survival-coping strategies, destructive for their school achievements, and well-being.

[Reactive manic syndromes]. / Reaktywne zespoly maniakalne.

The paper is an attempt at discussion of reactive manias--one of the least studied issues in psychiatry. The author present its clinical picture, the course of the two distinguished forms of the disorder, factors conductive to its onset (the rple of life stress events). The differences between "true" and situationally conditioned manic episodes are indicated. The paper discusses views of supporters and opponents of pathogenesis of manic psychosis. In modern classifications of mental disorders the pathology described by the author is not recognized as a separate disease. In the literature of the subject, the problem of reactive manias does not receive much attention, hence an attempt at their description for psychiatric theory and practice.

[Prime-MD as a method for the diagnosis of mental disorders in primary health care]. / DZPOP jako metoda diagnozowania zaburzen psychicznych w podstawowej opiece zdrowotnej.

A random sample of 150 people has been assessed. Prime-MD appears to be a useful tool for rapid diagnosing of mental disorders in primary care health and epidemiological research.

Expression of Bax, Bcl-xL and Bcl-2 proteins in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.

AIMS: To determine the expression of regulators of apoptosis in chronic hepatitis C. METHODS AND RESULTS: Expression of Bax, Bcl-xL and Bcl-2 proteins was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of Bax in hepatocytes correlated inversely with grade of inflammation (P < 0.001) and stage of fibrosis (P = 0.011), classified according to the Scheuer score; expression of Bcl-xL in hepatocytes did not correlate with grade of inflammation (P = 0.106) or stage of fibrosis (P = 0.078); maximum Bcl-xL expression was observed in grade 3 inflammation and stage 4 fibrosis. Expression of Bcl-2 protein in hepatocytes was present in only two cases (both with advanced disease); the expression of Bcl-2 protein in interlobular bile duct epithelial cells correlated with the grade of inflammation (P = 0.018), but not with stage of fibrosis (P = 0.154). The expression of Bcl-2 protein in lymphoid cells infiltrating portal zones and lobules did not correlate with grade of inflammation (P = 0.113) or stage of fibrosis (P = 0.815). CONCLUSION: Major differences in expression of studied proteins were observed in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.