Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori

Objective. This study compared the eradication rates of of Helicobacter pylori (HP) infection by a 7-day and 14-day anti-HP regimen. Materials and Methods. An open, randomized, prospective study was performed to evaluate the response to anti-HP treatment in adult HP-positive patients following a 7-day course (Regimen A) of a proton pump inhibitor in association with clarithromycin and amoxicillin compared to a 14-day course (Regimen B). Gastric biopsies were performed at baseline and two months after anti-HP treatment. Results. Seventy-eight patients aged 18–64 years (28 males, 50 females) diagnosed with HP infection were included. Fifty-two (66.7%) patients received Regimen B and 26 (33.3%) Regimen A. The overall eradication rate was 70.5%. Better treatment response (p<0.01) was seen in Regimen B (44/52, 84.2% versus 11/26, 42.3%). Significant improvement in histological features was seen in regimen B. There has been significant overall reduction in endoscopic aspects of gastric and duodenal lesions in both regimens. Younger patients ≤35 years had a better response to Regimen B. Better treatment response was seen in women, urban residents, and those with tertiary level of education in both groups. Conclusion. 14-day anti-HP regimen offered a significant better overall eradication of HP in study population

Clinical Study Mediterranean Spotted Fever in Southeastern Romania

Although cases of Mediterranean spotted fever (MSF) have been reported for decades in southeastern Romania, there are few published data. We retrospectively studied 339 patients, diagnosed with MSF at the National Institute of Infectious Diseases &quot;Prof. Dr. Matei Bals&quot; between 2000 and 2011, in order to raise awareness about MSF in certain regions of Romania. According to the Raoult diagnostic criteria 171 (50.4%) had a score &gt;25 points. Mean age was 52.5 years. One hundred and fifty-five (90.6%) patients were from Bucharest and the surrounding region. Almost all patients presented with fever (99.4%) and rash (98.2%), and 57.9% had evidence of a tick bite. There were no recorded deaths. Serologic diagnosis was made by indirect immunofluorescence assay. Of the 171 patients, serology results for R. conorii were available in 147. One hundred and twenty-three (83.7%) of them had a titer IgG ≥1 : 160 or a fourfold increase in titer in paired samples. MSF is endemic in southeastern Romania and should be considered in patients with fever and rash even in the absence of recognized tick exposure. Since the disease is prevalent in areas highly frequented by tourists, travel-associated MSF should be suspected in patients with characteristic symptoms returning from the endemic area

Mediterranean spotted fever in southeastern Romania.

Although cases of Mediterranean spotted fever (MSF) have been reported for decades in southeastern Romania, there are few published data. We retrospectively studied 339 patients, diagnosed with MSF at the National Institute of Infectious Diseases "Prof. Dr. Matei Bals" between 2000 and 2011, in order to raise awareness about MSF in certain regions of Romania. According to the Raoult diagnostic criteria 171 (50.4%) had a score >25 points. Mean age was 52.5 years. One hundred and fifty-five (90.6%) patients were from Bucharest and the surrounding region. Almost all patients presented with fever (99.4%) and rash (98.2%), and 57.9% had evidence of a tick bite. There were no recorded deaths. Serologic diagnosis was made by indirect immunofluorescence assay. Of the 171 patients, serology results for R. conorii were available in 147. One hundred and twenty-three (83.7%) of them had a titer IgG ≥1:160 or a fourfold increase in titer in paired samples. MSF is endemic in southeastern Romania and should be considered in patients with fever and rash even in the absence of recognized tick exposure. Since the disease is prevalent in areas highly frequented by tourists, travel-associated MSF should be suspected in patients with characteristic symptoms returning from the endemic area

Evaluation of carbohydrate and lipid metabolism dynamics in chronic HCV diabetic patients treated with direct antiviral agents

Although Hepatitis C virus (HCV) infection has become a curable disease, the aftermath of the infection remains an important aspect to be evaluated. HCV infection is well known for its extrahepatic manifestations, mostly the tight relationship between HCV, type 2 diabetes mellitus (T2DM) and dyslipidemia. Not only HCV increases the risk of T2DM, but it also affects its control in diabetic patients, increasing the risk of diabetes related complications. Furthermore, HCV hijacks the lipid metabolism resulting in abnormalities in circulating lipids which can lead to multiple complications, such as increased atherosclerotic risk and hepatic steatosis. Objectives. The aim of this study was to evaluate the dynamics of the parameters of carbohydrate and lipid metabolism in HCV-infected diabetic patients compared to non-diabetic patients after viral eradication. Material and methods. This is a prospective study conducted on 100 patients with chronic HVC infection who obtained viral clearance after interferon-free treatment. 58 patients had type 2 diabetes mellitus and 42 were nondiabetic. We evaluated serum total cholesterol, triglycerides, blood glucose and glycosylated hemoglobin in both groups at treatment initiation and 1 year after. Continuous variables were expressed as mean values ± standard deviation or median, categorical variables were represented as relative or absolute frequencies. Characteristics were compared using the Mann-Whitney method or the two-sample Student's T-test method for continuous variables, Chi-square and Fischer's test for categorical variables. A p value < 0.05 was considered statistically significant. Outcomes. The study analyzed and compared lipid and glycemic profiles of diabetic and non-diabetic HVC patients before and after viral cure. Conclusions. 1 year after treatment initiation the changes in lipid metabolism seem to persist, carbohydrate metabolism seems to remain unchanged, with no differences between diabetic and non-diabetic patients

Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report

<p>Abstract</p> <p>Background</p> <p>Cardio toxicity due to interferon therapy was reported only in small case series or case reports. The most frequent cardiac adverse effects related to interferon are arrhythmias and ischemic manifestations. The cardiomyopathy and pericarditis are rare but can be life threatening. The predisposing factors for interferon cardio toxicity were described only for ischemic manifestations and arrhythmias.</p> <p>Case presentation</p> <p>The authors report a case of pericarditis due to alpha interferon therapy for chronic hepatitis C, in a young woman without previous cardiac pathology. The clinical manifestations started during the 7-th month of interferon treatment. The cessation of interferon was necessary. After interferon discontinuation the patient recovered, with complete resolution of pericarditis. The patient scored 9 points on the Naranjo ADR probability scale, indicating a very probable association between pericarditis and interferon administration.</p> <p>Conclusion</p> <p>If a patient receiving interferon therapy complains of chest pain of sudden onset, a cardiac ultrasound should be performed in order to rule out pericarditis. We point out the possibility of an infrequent but severe adverse effect of interferon therapy.</p

Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

Background & AimsTelaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV.MethodsTreatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12–36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.ResultsThree hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0–1% and 8–11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0–4% and 34–47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV.ConclusionsAmong non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97–99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66–82% with 24–48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in Caenorhabditis elegans

Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3), of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation.Howard Hughes Medical InstituteDamon Runyon Cancer Research FoundationCharles A. King Trus

Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: the MALACHITE-I/II trials

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Rapid loss of HBs antigen in patients with HBV reactivation and high level of transaminases during immunosuppressive therapy - case series

Reactivation of hepatitis B virus (HBV) infection has been described in patients with HBsAg negative and antiHBc positive (occult hepatitis B infection -OBI) receiving immunosuppressive therapy (IST). The lack of proper monitoring of patients with this HBV infection during IST can result in viral reactivations with high level of transaminases, jaundice and even acute liver failure. In these situations, it is mandatory to start antiviral therapy with nucleot(s) ide analogs (NA) which produce a strong viral suppression. We report a series of five cases of OBI patients with severe HBV reactivation during IST. One patient was diagnosed with hematologic malignancy (non-Hodgkin lymphoma), two with rheumatoid arthritis, one with psoriasis and one patient with renal transplant. All the patients were evaluated and treated for the reactivation of HBV in the Prof. Dr. Matei Bals National Institute of Infectious Diseases, a tertiary care hospital from Bucharest, Romania. At the time of HBV reactivation diagnosis, 3 patients were asymptomatic and two developed jaundice. All had acute ALT flares (more than 10 times the upper limit of normal range - ULN), very high HBV viral loads and anti-HBc serum IgM antibodies. All patients were immediately treated with ETV 0.5 mg/day and if it was possible, IST was stopped. In all cases was obtained quickly HBsAg loss under antiviral therapy