Chemerin, vaspin and insulin resistance in chronic hepatitis C.

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

Visfatin serum levels in chronic hepatitis C patients.

Visfatin is a new adipokine involved in several processes. The data concerning visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum concentration and to study its association with biochemical and morphological features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group 2), similar in age and BMI with normal fasting glucose and lipid profile were included. Visfatin was significantly increased in Group 1 compared with Group 2 (55.6 +/- 23.1 vs 23.7 +/- 3.8 ng/mL; P < 0.001). Visfatin was negatively associated with necro-inflammatory activity grade (r = -0.36; P = 0.007). The lowest levels were found in patients with the most advanced inflammation: grades 3-4 - 46.8 +/- 17.1, grade 2 - 52.6 +/- 18.4 and grade 1 - 75.2 +/- 27.6 ng/mL; P = 0.017. A significant difference was also shown comparing patients with minimal inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver operating characteristic curve analysis for different necro-inflammatory activity - grade 1 vs grades 3-4 with area under the curve 0.81 indicated a good discriminant power for differentiation of moderate/severe inflammation, with the cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive value 0.90, negative predictive value 0.75). Serum visfatin concentration increases significantly in CHC patients. These findings suggest that visfatin is important in the pathogenesis of the inflammatory process in CHC. Visfatin may play a dual role as a pro-inflammatory or/and protective factor. The measurement of visfatin serum concentration may serve as an additional tool in distinguishing more advanced grades of the necro-inflammatory activity.

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.

Disturbances of cell-mediated immunity in ornithosis.

27 cases of ornithosis were observed during an epidemia in 1980 in Kielce and subsequently followed with respect to immunological characteristics of peripheral blood lymphocytes. Blastic transformation of these cells was tested after stimulation in vitro with three different mitogens. Identification of peripheral blood T and B lymphocytes was done using rosette tests (E,EA,EAC) and the occurrence of surface immunoglobulins was determined by the immunofluorescent method with polyvalent anti-immunoglobulin serum. The counts of T and B lymphocytes in the peripheral blood were normal throughout the whole period of the observation, but from the 3rd week on a significant impairment of 3H-thymidine incorporation into the cells stimulated with Con A was observed, and from the 10th week on, this impairment appeared also in cells stimulated with PHA and PWM. These observations revealed considerable disturbances in cell-mediated reactivity in patients with ornithosis and seem to be connected with chronic infection with Chlamydia psittaci.

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. / Efektywnosc leczenia przeciwwirusowego przewleklego zapalenia watroby typu C (wieloosrodkowe badania pòlskie).

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

[Hematologic syndromes in hepatitis C virus infection]. / Zespoly hematologiczne w zakazeniu wirusem zapalenia watroby typu C.

HCV infection may affect not only the liver but also various nonhepatic tissues. This paper presents current information on association between HCV infection and haematological disorders. The pathogenic role of HCV in hepatitis-associated aplastic anaemia development has not been confirmed. The thrombocytopenia has been observed more frequently during chronic hepatitis C than during infections with other hepatotropic viruses. This disorder may be associated with antiplatelet autoantibodies production. However the most common haematological complication of HCV infection is mixed cryoglobulinemia (MC), observed in 40-50% of patients. In some subjects non-Hodgkin B cell lymphoma (B-NHL) may evolve from MC, but it is also reported in acryoglobulinemic HCV infected patients. The frequency of HCV infection in population of patients with B-NHL exceeds 20% in some countries and it is significantly higher than for other lymphoproliferative disorders. There are also data suggesting that HCV may play a role in MALT lymphoma development, too. The observed disorders are explained by HCV lymphotropism and direct or indirect influence of continuous antigenic stimulation by replicating virus on lymphatic system. The paper presents also beneficial results of interferon treatment in patients with HCV-related MC or B-NHL. The authors show that haematological syndromes should be taken under account in diagnostics of hepatitis C patients and interferon treatment should be administered as soon as possible when HCV related cryoglobulinaemia is diagnosed.

Extrahepatic manifestations associated with chronic hepatitis C infections in Poland.

PURPOSE: To assess the prevalence and predictive factors of extrahepatic manifestation (EM) in patients with chronic hepatitis C (CHC) infection in Poland. MATERIAL AND METHODS: 340 consecutive patients (mean age: 42 years) with untreated CHC were studied between 2000 and 2006. The HCV infection was defined by positive serology and serum HCV RNA. The inflammation grade and fibrosis stage were assessed according to Ishak. Demographic, laboratory and liver biopsy data were collected. The patients with liver cirrhosis, concomitant HBV or HIV infection, autoimmune liver diseases and alcohol abusers were excluded from the analysis. RESULTS: 210 patients with CHC (61.7%) presented at least 1 extrahepatic manifestation, including mixed cryoglobulinemia (37.1%), thrombocytopenia (27.6%), thyroid autoimmunity (16.2%), dermatological disorders (4.1%) and type 2 diabetes (4.1%). Other EM such as the sicca syndrome, nephropathy, polyneuropathy and B-cell lymphoma were observed in single cases. In multivariate analysis lower platelet count was found as a predictive factor of EM in patients with CHC. CONCLUSIONS: The majority of patients with CHC, living in Poland, have EM, of which cryoglobulinemia, thrombocytopenia, thyroid autoimmunity, dermatological disorders and type 2 diabetes are most common. Through the multivariate analysis the lower platelet predicts extrahepatic manifestations associated with chronic hepatitis C.

[Clinical pharmacology of ursodeoxycholic acid (UDCA)]. / Farmakologia kliniczna kwasu ursodezoksycholowego (UDCA).

Ursodeoxycholic acid (UDCA) is frequently confused with chenodeoxycholic acid (CDCA), although its pharmacological properties are quite different, clinical indications much broader and it produces practically no side effects. By several mechanisms (including, inter alia, induction of hypercholeresis and formation of liquid crystals with cholesterol) UDCA decreases bile saturation with cholesterol and increases bile metastability. Upon oral administration UDCA, which is hydrophilic, substitutes for and protects hepatocytes against damage by other more hydrophobic and toxic bile acids. In consequence it exerts hepatoprotective and immunocorrective influence. Clinical efficacy of UDCA in gallstone dissolution and prophylaxis, in treatment of biliary dyspepsias, in chronic active hepatitis, in primary biliary cirrhosis and in other cholestatic liver diseases is reviewed. Other therapeutic indications for the drug are also mentioned.

Acute hepatic failure in alcoholic liver disease.

296 patients with first clinical symptoms of alcoholic liver disease were hospitalized in Probationary-Infectious Diseases Department in Kielce, between 1994-2000. In 52 (17.6%) of them, acute hepatic failure was diagnosed by detection of hepatic encephalopathy. Initial laboratory data of those patients who died (6.1%), and those who survived (11.5%) was compared. No statistically significant differences in analyzed parameters were found, except for significantly higher bilirubin concentration in the group of deceased. In both groups of patients, the frequency of hepatic failure complications, present at the admission to the hospital or those developed in the course of the disease, was also analyzed. The following complications were observed significantly more often in deceased: ascites, hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP), and gastrointestinal haemorrhage (GIH), while sepsis was similarly frequent in both groups.

Wilson's disease coexisting with viral hepatitis type C: a case report with histological and ultrastructural studies of the liver.

Histopathological and ultrastructural findings in the liver of a female patient who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are reported. Light and electron microscopy examinations demonstrated a variety of morphological alterations--many of them frequently seen in livers of patients with WD and others that can be found in cases presenting HCV infection. The influence of coexistence of these two diseases on morphological changes is discussed.

Thyroid gland dysfunctions during antiviral therapy of chronic hepatitis C.

BACKGROUND: The aim of this study was assessment of the frequency of thyroid dysfunctions (TD) during antiviral treatment of chronic hepatitis C (CHC). MATERIAL AND METHODS: Data obtained from 120 not treated before patients with CHC, confirmed by the liver biopsy, and with the correct initial thyroid function, was analyzed. 63 patients were treated with IFN-alpha, and 57 with IFN + ribavirin combined therapy. HCV genotype was determined in 80 patients, and alleles HLA DRB1 in 74. Both tests were carried out by the use of commercial assay InnoLipa (Innogenetics, Belgium). All the patients had TSH level regularly monitored every 4 weeks. If any abnormalities were observed, the whole set of tests was applied for diagnosis. Frequency of TD was analyzed according to patients' sex, therapy scheme, HCV genotype and HLA DBR1 alleles. Both groups, with TD and without TD were compared by the initial data, such as: patients' sex, age, ALT activity, and liver biopsy results. RESULTS: TD occurred in 40 patients (33.3%): in 7 (5.8%) signs of hypothyroidism, and in 33 (27.5%) hyperthyroidism. In 14 patients (11.7%) autoimmunological thyroiditis was diagnosed, in 2 (1.7%) subacute thyroiditis, and in the rest of patients only temporary changes in TSH concentration, without any clinical manifestations, were observed. In 4 women, the antiviral treatment was withdrawn, because of thyreotoxicosis, and in 6 patients thyroid hormones supplementation was needed after termination of interferon application. Thyroid complications occurred significantly more often in women than in men. No significant differences according to the age, therapy scheme, ALT activity, fibrosis stage, nor HCV genotype were find in the TD frequency. Among 13 genotyped DRB1 alleles, differences were observed only in DRB*11 allele frequency: in 37.7% of patients with TD, and in 9.1% of patients without TD (p = 0.0093; Pc = 0.12). CONCLUSIONS: Antiviral treatment induces more often latent and transient thyroid dysfunctions as well as autoimmunological, and subacute thyroidis. The last mentioned complication may be the indication for withdrawal of the treatment, or may cause persistent hypothyroidism. Regular monitoring of TSH concentration, in 4-weeks intervals, seems to be essential for early diagnosis of thyroid complications.

Factors influencing natural history of chronic hepatitis C.

The aim of the study was to asses influence of selected epidemiologic and virusologic factors on the course of chronic hepatitis C (CHC). Data obtained from 550 CHC patients was analyzed (F/M: 241/309; age: 14-87, average age: 44.9 +/- 15.6). HbsAg and HIV-positive, as well as patients taking drugs were excluded from the study. Progression of the liver disease was assessed by the maximal ALT activity, presence of clinical or histopathological symptoms of hepatic cirrhosis, and 363 liver biopsy results. Clinical and histological data was analyzed depending on: patients sex, age (= 40, and > 40 years old), portal of infection (history data on transfusion or another source of infection), history of HBV infection (presence or absence of anti-HBc antibodies), and HCV genotype (1b or no-1b group). HCV genotype was determined in 170 patients by the use of commercial InnoLipa kit (Innogenetics). Statistical analysis was based on t-Student test and chi-squared test with or without Yates correction. It was proved that in patients over 40 years old or with history of transfusion inflammatory activity and liver fibrosis activity are significantly higher than in the rest of patients. More advanced age, transfusion and history of HBV infection are risk factors for hepatic cirrhosis development in CHC patients. Neither patient's sex nor HCV genotype were found to have significant influence on the course of CHC.

DRB1 alleles in relation to severity of liver disease in patients with chronic hepatitis C.

The aim of our study was analysis of relation between HLA class II antigens and the liver disease severity in chronic hepatitis C (CHC) patients. The subject of analysis was data obtained from 134 CHC patients with disease confirmed by histopathologic test (F/M: 62/72; age 16-74; average age 41.4 +/- 12.7 yrs), HCV RNA-positive, HbsAg- and HIV-negative with no coexistence of any other liver diseases. Liver biopsy specimens were estimated according to Ishak's criterions (grading 0-18; staging 0-6). HLA DRB1 alleles were determined by a commercial method INNOLiPA DRB (Innogenetics, Belgium). Statistical analysis considered alleles occurring with frequency higher than 10%. The necroinflammatory activity (average grading score) was compared in groups of patients with- and without particular allele. The frequency of each allele's occurrence was analyzed according to patients sex, age and staging score of liver fibrosis. In statistical analysis t-Student test and chi-squared test with or without Yates' correction were applied. Statistically significant correlation was found between occurrence of DRB1*13 and DRB1*07 alleles and necroinflammatory activity intensification, and between occurrence of DRB1*13 allele and progression of liver disease. Mild liver damage, instead, expresses statistically significant relation with DRB1*11 allele.