Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.

Non-Invasive Indirect Markers of Liver Fibrosis after Interferon-Free Treatment for Hepatitis C.

The effectiveness of interferon-free therapy during the course of HCV infection has already been confirmed. Liver fibrosis can be assessed in several ways, from biopsies to imaging tests. The present study evaluates the usefulness of non-invasive indirect biomarkers of liver fibrosis (APRI, GAPRI, FORNS, FIB-4, the AP index and HUI score) as markers of the effective treatment of HCV with the 3D regimen. Blood samples were collected from 70 patients suffering from chronic hepatitis C. Patients received the 3D AbbVie regimen for hepatitis C. All patients had HCV genotype 1b. The APRI, GAPRI, FIB-4, FORNS, HUI and AP index (age-platelet score) values were calculated with their respective algorithms. The stage of fibrosis was evaluated on the basis of a liver biopsy and confirmed by FibroScan-based transient elastography. An undetectable level of HCV RNA after 12 weeks of treatment with the 3D regimen indicates 100% eradication of hepatitis C virus. After the treatment, non-invasive indirect markers of liver fibrosis achieved levels below the limit for significant fibrosis, Thus, non-invasive indirect biomarkers of hepatic fibrosis failed to detect the presence of significant fibrosis, which was proved in histopathological examination. However, the eradication of hepatitis C virus by means of the 3D regimen treatment does not mean that patients were completely cured.

The red-light emitting diode irradiation increases proliferation of human bone marrow mesenchymal stem cells preserving their immunophenotype.

PURPOSE: For effective clinical application of human bone marrow mesenchymal stem cells (hBM-MSCs), the enhancement of their proliferation in vitro together with maintaining the expression of their crucial surface antigens and differentiation potential is necessary. The present study aimed to investigate the effect of light-emitting diode (LED) irradiation on hBM-MSCs proliferation after two, five, or nine days post-irradiation. MATERIALS AND METHODS: The hBM-MSCs were exposed to the LED light at 630 nm, 4 J/cm2, and power densities of 7, 17, or 30 mW/cm2. To assess the cell proliferation rate in the sham-irradiated and irradiated samples the cells metabolic activity and DNA content were determined. The number of apoptotic and necrotic cells in the samples was also evaluated. The expression of the crucial surface antigens of the hBM-MSCs up to nine days after irradiation at 4 J/cm2 and 17 mW/cm2 was monitored with flow cytometry. Additionally, the potential of hBM-MSCs for induced differentiation was measured. RESULTS: When the metabolic activity was assayed, the significant increase in the cell proliferation rate by 31 and 50% after the irradiation with 4 J/cm2 and 17 mW/cm2, respectively, was observed at day five and nine when compared to the sham-irradiated cells (p < .05). Similarly, DNA content within the irradiated hBM-MSCs increased by 31 and 41% at day five and nine after the irradiation with 4 J/cm2 and 17 mW/cm2 in comparison to the sham-irradiated cells. LED irradiation did not change the expression of the crucial surface antigens of the hBM-MSCs up to nine days after irradiation at 4 J/cm2 and 17 mW/cm2. At the same experimental conditions, the hBM-MSCs maintain in vitro their capability for multipotential differentiation into osteoblasts, adipocytes, and chondrocytes. CONCLUSION: Therefore, LED irradiation at a wavelength of 630 nm, energy density 4 J/cm2, and power density 17 mW/cm2 can effectively increase the number of viable hBM-MSCs in vitro.

Liver involvement in rheumatic diseases.

Liver involvement in rheumatic diseases may occur as a primary liver disease, primary rheumatic disease with hepatic manifestations or antirheumatic drug-induced liver disease. The aim of our article is to underline the importance of monitoring and control of the level of aminotransferases and cholestatic enzymes in rheumatic disorders. Some of the rheumatic diseases with constantly elevated liver enzymes need to be investigated in consideration of concomitant primary autoimmune liver disease (such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis) or drug hepatotoxicity. Also, we should be aware of hepatitis B reactivation or hepatitis C flare when immunosuppressants are used.

The efficacy of paritaprevir/ritonavir/ombitasvir+dasabuvir and ledipasvir/sofosbuvir is comparable in patients who failed interferon-based treatment with first generation protease inhibitors - a multicenter cohort study.

BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.

Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals?

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

Effectiveness and safety of ledipasvir/sofosbuvir±ribavirin in the treatment of HCV infection: The real-world HARVEST study.

BACKGROUND: To evaluate the effectiveness and safety of ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen in a real-world setting. METHODS: Patients received a fixed-dose combination tablet containing LDV and SOF with or without RBV, for 8, 12 or 24 weeks. Patients were assessed at baseline, end of treatment, and 12 weeks after the end of treatment. The primary effectiveness endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: Of the 86 patients, aged 20-80 years, 82.6% were HCV genotype 1b-infected and 50.0% were cirrhotic. More than half (52.3%) had previously followed pegylated interferon-containing (PEG-IFN) treatment regimens, and 38.5% were null-responders. SVR12 was achieved by 94.2% of patients. All non-responders were cirrhotic: two demonstrated virologic breakthrough and the remaining three relapsed. All patients treated with an 8-week regimen achieved SVR12 despite having high viral load at baseline (HCV RNA of >1 million IU/mL in 8/10 patients, including one with a viral load of >6 million IU/mL). Adverse events were generally mild and transient. Most frequently, fatigue (22.1%), headache (15.1%), and arthralgia (7.0%) were observed. Laboratory abnormalities included anemia and hyperbilirubinemia. CONCLUSIONS: Treatment with LDV/SOF±RBV is an effective and safe option for patients with HCV, including those with advanced liver disease or a history of non-response to PEG-IFN-based therapy.

Still's disease in patient with silicone breast implants: case report.

Still's disease is a systemic manifestation of juvenile arthritis that rarely occurs in adults and therefore is often forgotten in differential diagnosis of fever of unknown origin. The case presented here shows diagnostic difficulties in a patient with silicone breast implants and fever with Still disease. The cause-effect relationship between breast implants and Still disease is not certain, however, this possibility should be considered when a patient with fever resistant to antibiotics and with silicone implants is admitted to the hospital.

[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.