ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C

Background

Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown.

Methods

Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR).

Results

Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12.

Conclusions

ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.

     

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Purpose

To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years.

Methods

We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r?+?DSV?+?RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12).

Results

Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin <?3.5 g/dL (OR 2.04: 95% CI 1.0–4.2, p?<?0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p?<?0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin <?2 mg/dL (OR 4.9: 95% CI 1.17–20.71, p?=?0.029) as the only variable independently associated with SVR12.

Conclusion

Our findings suggest that OBV/PTV/r?+?DSV?+?RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

     

Twelve-week ribavirin-free direct-acting antivirals for treatment-experienced Chinese with HCV genotype 1b infection including cirrhotic patients

Background

Treatment-experienced chronic hepatitis C (CHC) genotype (GT) 1b represents a major medical burden in China. We evaluate the efficacy, safety and cost-effectiveness of ribavirin (RBV)-free pan-oral direct-acting antivirals (DAAs) in treatment-experienced Chinese with GT1b CHC, including patients with cirrhosis.

Methods

One hundred forty treatment-experienced GT1b CHC Chinese with and without cirrhosis were included in this study. Ninety-four patients were treated with either daclatasvir (DCV, 60 mg)-sofosbuvir (SOF, 400 mg) (group 1, n = 46) or ledipasvir (LDV, 90 mg)-SOF (400 mg) (group 2, n = 48) for 12 weeks. Forty-six patients treated with pegylated interferon and RBV therapy for 72 weeks were enrolled as the control group (group 3). Patients were followed at 4-weekly intervals till 24 weeks after the end of treatment.

Results

All patients in group 1 (46/46, 100 %) and 2 (48/48, 100 %) had achieved sustained virologic response at 24 weeks after the end of treatment (SVR 24), which was significantly higher than that of group 3 (13/46, 28.3 %) (p < 0.001). The SVR 24 rates of cirrhotic patients in group 1 (27/27, 100 %) and 2 (27/27, 100 %) were also significantly higher than that of group 3 (3/25, 12 %) (p < 0.001). Twelve weeks of RBV-free LDV-SOF and DCV-SOF was either cost-saving or cost-effective. Adverse events were significantly lower in group 1 and 2 compared with group 3 (p < 0.001).

Conclusion

Compared with standard therapies, 12 weeks of RBV-free DAA therapies is highly effective, well tolerated and cost-effective in treatment-experienced Chinese with GT1b CHC including patients with cirrhosis.

     

High sustained virological response to pegylated interferon and ribavirin for recurrent genotype 3 hepatitis C infection post-liver transplantation

Introduction

Treatment outcomes of recurrent HCV genotype 3 (GT-3) after liver transplantation (LT) are ill-defined.

Aims

To determine efficacy, predictors, and long-term survival after treatment of recurrent HCV GT-3 infection, post-LT, with a combination of pegylated interferon (PEG) and ribavirin (RBV).

Methods

We studied all LT recipients (LTR) in our program treated with PEG and RBV for recurrent HCV GT-3 between Jan 1st 2002 and Dec 31st 2013. Antiviral therapy (AVT) was started if histology showed recurrent HCV with ≥stage2 fibrosis. Treatment was intended for 24 or 36 weeks, depending on early virologic response, and/or 24 weeks consolidation. Primary endpoint was sustained virological response (SVR). We also studied predictors of SVR and long-term patient survival.

Results

Among 492 LT for HCV-related cirrhosis and/or hepatocellular carcinoma performed during the study period, 110 (22 %) had HCV GT-3 infection. Fifty-two (10.5 %) HCV GT-3 patients had indications for AVT. Six were unable to complete the AVT, three because of clinical decompensation and one each because of metastatic disease involving the brain, lung cancer, and ductopenic rejection. Forty-seven (90 %) patients achieved early virological response (EVR) and 37 (71 %) achieved SVR. Predictors of SVR were EVR (p < 0.001), stage ≤3 fibrosis (p = 0.008), and 36 weeks treatment duration (p < 0.001). Less advanced fibrosis ≤3 was independent predictor of SVR (OR 0.18, 95 % CI 0.05–0.67). SVR patients had actuarial (Kaplan–Meier) 1, 3, and 10 year post-treatment survival of 100, 100, and 95 %, compared with 87, 78, and 20 % for non-SVR patients (p < 0.001, log rank test).

Conclusion

Efficacy of AVT for recurrent HCV GT-3 post-LT is high, and comparable with that for non-transplant patients. Less advanced fibrosis is an independent predictor of SVR. SVR improves long-term survival.

     

Baseline risk factors for relapse in HIV/HCV co-infected patients treated with PEG-IFN/RBV

Purpose

Hepatitis C virus (HCV) viral relapse (VR) after end-of-treatment response (ETR) in human immunodeficiency virus (HIV) co-infected patients is observed in as many as one in three co-infected patients. The aim of the study was to identify baseline risk factors for VR in HIV/HCV co-infected patients treated with pegylated interferon plus ribavirin (PEG-INF/RBV).

Methods

A total of 212 Caucasian HIV-infected patients with chronic hepatitis C naïve for PEG-INF/RBV were followed prospectively. Patients were included in this prospective study if they had completed a full course of therapy with an ETR. We assessed the relationship between VR rate and potential predictors of relapse.

Results

Of the patients followed, 130 (61.3 %) attained ETR and 103 (79.2 %) achieved sustained virological response (SVR). Consequently, 27 (20.8 %) showed VR. Patients who relapsed were more often male (p = 0.036), carried the non-CC rs14158 genotype in the low-density lipoprotein receptor (LDLr) gene (p = 0.039), had higher baseline HCV RNA levels (p = 0.012), body mass index (BMI) ≥25 kg/m² (p = 0.034), significant liver fibrosis (p < 0.001), had been diagnosed with acquired immunodeficiency syndrome (AIDS)-defining criteria in the past (p = 0.001) and bore the HCV genotypes 1/4 (p = 0.046) when compared with SVR patients. The IL28B genotype was not associated with relapse. Multivariate binary logistic regression showed that high baseline HCV RNA, significant liver fibrosis, HCV genotypes 1/4, being overweight and being diagnosed with AIDS-defining criteria in the past were independently associated with relapse.

Conclusions

Our study shows that VR can be accurately predicted in HIV/HCV co-infected patients on the basis of risk factors which can be identified before treatment.     

Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

Purpose

A proportion of patients infected with genotype 2a hepatitis C virus (HCV) cannot achieve a sustained virological response (SVR) to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV) but the reason remains unclear. The present study aimed to clarify the possible correlation between viral sequence variations and final outcome.

Methods

The pretreatment complete open reading frame (ORF) sequences of genotype 2a HCV were determined by direct sequencing for two independent groups of patients (43 patients as test; group 1 and 35 as validation; group 2), and the correlation with the final outcome was explored.

Results

Patients with SVR (n = 58) and with non-SVR (n = 20) differed significantly in pretreatment HCV RNA level (p = 0.002), fibrosis score (p = 0.047), and cumulative RBV dosage (p = 0.003). By comparison of all amino acid positions in the complete HCV ORFs, threonine at amino acid (aa) 110 in the core region was remarkably frequent in SVR (p = 0.01 for group 1, p = 0.004 for group 2, and p = 5E?05 for combined). A sliding window analysis revealed that the total number of amino acid variations within the NS5A aa 2258–2306 region were significantly high in SVR compared to non-SVR patients (p = 0.01 for group 1, p = 0.006 for group 2, and p = 0.0006 for combined). Multivariate analyses revealed that core aa 110 (p = 0.02), NS5A aa 2258–2306 (p = 0.03), and cumulative RBV dosage (p = 0.02) were identified as independent variables associated with the final outcome.

Conclusions

The outcome of PEG-IFN/RBV therapy is significantly influenced by variation in the core and NS5A regions in genotype 2a HCV infection.     

Severe obstructive sleep apnea treatment with oral appliance: the impact on obstructive,central and mixed events

Purpose

The aim of this study is to evaluate the effectiveness of two types of oral appliance (OA) in the treatment of severe obstructive sleep apnea syndrome (OSAS) and their impact on the reduction of obstructive, central and mixed apneas.

Methods

Forty-eight patients suffering from severe OSAS with a history of non-adherence to positive airway pressure therapy were treated with OA (lingual orthosis and combined orthosis). Polysomnography exams were performed before and after treatment. Computed tomography and cephalometric radiography were requested for all patients to evaluate the titrated position of the OA and the airspace obtained. Statistical tests used the Minitab, version 17, program. The level of statistical significance was 5%.

Results

Before treatment, the mean AHI was 56.3 ± 19.1 events/h. It decreased to 8.1 ± 5.2 after the OA titration (p ≤ 0.001). There was a significant reduction in obstructive events from 43.0 ± 20.2 to 7.1 ± 4.6 events/h (p ≤ 0.001). The reduction in central events after OA treatment was also significant (from 5.1 ± 9.3 to 0.8 ± 1.9 events/h; p ≤ 0.001), whereas that in mixed events decreased from 6.4 ± 9.5 to 0.1 ± 0.3 events/h (p ≤ 0.001). The minimum oxygen saturation also showed significant improvement after treatment (p ≤ 0.001). There was no statistically significant difference between both OA with respect to central events (p = 0.22) or mixed events (p = 0.98).

Conclusion

The treatment was effective in reducing obstructive events which were evaluated through the AHI and minimum oxygen saturation. The oral appliances also normalized central and mixed events among patients with severe OSAS.

     

CCL4 is the only predictor for non-responder in GT-1 CHC patients with favorable IL28B genotype when treated with PegIFN/RBV

Background

Chemokines/cytokines play important roles in the pathogenesis of chronic hepatitis C (CHC). However, their clinical characteristics and implications in treatment responses to pegylated interferon plus ribavirin treatment (PegIFN/RBV) have not been fully illustrated yet. In this study, we intended to investigate the possible predictability of serum chemokines/cytokines on the treatment response in Taiwanese of CHC, genotype-1 (GT-1).

Methods

60 Patients with GT-1 CHC infection who had been treated with PegIFN/RBV were enrolled, including 27 (45%) with sustained virological response (SVR), 11 (18%) with relapse after 48 weeks of treatment and 22 (37%) non-response (NR). Clinical parameters, seven chemokines/cytokines, CCL3, CCL4, CXCL9, CXCL10, CXCL11, IL-10 and IFN-γ, and genotypes of rs12979860, the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were analyzed for their relationship to treatment response.

Results

Baseline serum levels of CXCL10, CXCL11, CCL3 and CCL4 were significantly higher in NR group while comparing with non-NR group. (CXCL10: p =?0.001; CXCL11: p <?0.001; CCL3: p =?0.006; CCL4: p =?0.005). However, only rs12979860 CC genotype was the independent factors for NR in GT-1 CHC infection (OR, 8.985; p =?0.008). In addition, baseline serum level of CCL4 was found to be the only independent factor for NR in GT-1 CHC patients with favorable IL28B genotype (OR, 1.134; p =?0.039).

Conclusions

IL28B genotype is the predictor for NR in GT-1 CHC patients treated with PegIFN/RBV, while baseline serum level of CCL4 is the only predictor for NR in GT-1 CHC patients with favorable IL28B genotype.

     

Efficacy and safety of sofosbuvir-based therapy for chronic hepatitis C infection in “real-life” cohort

Background

The safety and efficacy of sofosbuvir-based treatment (sofosbuvir and ribavirin with or without pegylated interferon-α) for hepatitis C virus (HCV) infection has been established in clinical trials. However, there is limited data regarding safety and efficacy of sofosbuvir-based treatment for HCV infection in a “real-life” cohort. We describe our experience with sofosbuvir-based treatment for HCV infection in a real-life cohort.

Methods

This was a prospective, nonrandomized and observational study at a tertiary care centre in Surat, India. The primary end-point was proportion of the study patients who achieved a sustained virological response 12 weeks after cessation of treatment (SVR 12). Secondary end-points of the study include SVR 4, virological relapse and appearance of adverse events.

Results

A total of 107 patients with chronic HCV who received sofosbuvir-based treatment were included in the study. During study period, two patients died due to severity of liver complications. Hence, overall rate of SVR 4 and SVR 12 was 98.1 % (n = 103/105) and 94.3 % (n = 99/105), respectively. Among 67 patients with HCV genotype-3 infection, the SVR 12 rate was 92.5 % (n = 62/67), and among 38 patients with HCV genotype-1 infection, the rate of SVR 12 was 97.4 % (n=37/38). A total of 32 (29.9 %) patients reported adverse events during the course of sofosbuvir-based treatment. None of the patient discontinued treatment due to adverse event.

Conclusions

Sofosbuvir-based treatment is safe and efficacious in clinical practice in Indian patients with HCV genotype-1 and genotype-3 infection.

     

Pegylated Interferon-α Plus Ribavirin Therapy Improves Left Ventricular Diastolic Dysfunction in Patients With Chronic Hepatitis C Attaining Sustained Virological Response

Background

Pegylated interferon (pegIFN) in combination with ribavirin (RBV) has successfully improved the rate of sustained virological response (SVR) in chronic hepatitis C virus (HCV) infected individuals, which reduces the progression of the chronic liver disease. However, the influence of combination therapy (pegIFN/RBV) on cardiac function has yielded ambiguous results. The present study aimed to evaluate the effects of combination therapy with pegIFN/RBV on cardiac function of HCV-infected individuals with SVR.

Correlates of disease-specific knowledge among patients with chronic hepatitis B or hepatitis C infection in India

Background

Patient knowledge about chronic diseases increases health-promoting behaviors and improves clinical outcomes. We assessed this association for patients with chronic viral hepatitis.

Methods

Untreated patients chronically infected with HBV (n = 500) or HCV (n = 500) were enrolled at 19 centers across India. A survey, adapted from the US CDC National Health and Nutrition Examination Survey (NHANES) questionnaire, was administered at a single visit to assess HBV/HCV knowledge, community disease awareness, treatment quality, and healthcare barriers. We developed the India Hepatitis Knowledge Index (IHKI), where a higher IHKI score (range 0–10) indicates increased hepatitis knowledge. Multivariate regression models evaluated demographic and disease factors.

Results

The overall mean IHKI score was 5.6 out of 10, with higher scores among patients with HBV (5.9) than HCV (5.3); p < 0.001. In HBV patients lower IHKI was associated with shorter disease duration, government clinic attendance (p < 0.0001), fewer personal experiences with HBV (p < 0.0001), and residing in northern India. Among HCV patients, lower IHKI was associated with shorter disease duration, community (p < 0.0001) and government clinic attendance (p < 0.0001), and fewer personal experiences with HCV (p < 0.0001). Among HBV patients, IHKI was independently associated with disease severity as assessed by MELD score, albumin, and APRI. This association was strongest for HBV patients with elevated ALT and HBV DNA >2000 IU/ml. Among HCV patients, IHKI results had no significant associations with disease severity.

Conclusions

The association of IHKI with disease underscores the need to understand connections between hepatitis knowledge and progression and may guide efforts to address patient education and awareness of chronic viral hepatitis in India.

     

Favorable adverse event profile of sofosbuvir/ribavirin compared to boceprevir/interferon/ribavirin for treatment of hepatitis C

Background

Triple therapy for the treatment of hepatitis C virus (HCV) with first-generation directly acting antiviral agents, the non-structural serine protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved sustained virologic response (SVR) rates. However, a high incidence of adverse events (AEs), high pill burdens and drug interactions remain significant barriers to successful completion of therapy. The aim of this study was to evaluate the AEs observed with BOC triple therapy in comparison to IFN-free sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1) individuals.

Methods

We retrospectively evaluated HCV monoinfected, treatment-naïve or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR), were measured according to the DAIDS toxicity table (version 1.0).

Results

BOC/IFN/RBV was associated with significantly more AEs, most commonly neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %) patients discontinued treatment early, but none (0 %) were because of AEs, while 60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %) because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV.

Conclusions

SOF/RBV treatment was associated with fewer side effects than BOC-based triple therapy, appearing to be a safer and more tolerable alternative for HCV GT-1 subjects. These results show that emerging IFN-free therapies may enhance patient adherence, allowing treatment of larger number of patients with improved efficacy.     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

Predictors of wound dehiscence and its impact on mortality after abdominoperineal resection: data from the National Surgical Quality Improvement Program

Background

Wound dehiscence is a known complication following abdominoperineal resection (APR) and can have a negative impact on recovery and outcome. The aim of this study was to determine the predictors of post-APR 30-day abdominal and/or perineal wound dehiscence, readmission, and reoperation, and to assess the impact of wound dehiscence on 30-day mortality.

Methods

All patients undergoing APR between 2005 and 2012 were analyzed using the American College of Surgeons National Surgical Quality Improvement Program.

Results

There were 5161 patients [male = 3076 (59.6 %)] with a mean age of 61.9 ± 14.3 years. Mean body mass index was 27.4 ± 6.6 kg/m². The most common indication for surgery was rectal cancer (79.1 %), followed by inflammatory bowel disease (8.2 %). The overall rate of wound dehiscence was 2.7 % (n = 141). Older age (p = 0.013), baseline dyspnea (p = 0.043), smoking history (p = 0.009), and muscle flap creation (p ≤ 0.001) were independently associated with the risk of dehiscence. No association was observed between omental flap creation and dehiscence risk (p = 0.47). The 30-day readmission rate (15.6 vs. 5.6 %, p ≤ 0.001) and need for reoperation (39 vs. 6.6 %, p ≤ 0.001) were significantly higher in patients who experienced dehiscence. Dehiscence was an independent risk factor for 30-day mortality [OR = 2.69 (1.02–7.08), p = 0.045)].

Conclusions

Older age, baseline dyspnea, smoking, and the use of muscle flap were associated with higher risk of wound dehiscence following APR. Patients with wound dehiscence had a higher rate of readmission and need for reoperation, and an increased risk of 30-day mortality.

     

Ritonavir-boosted danoprevir-based regimens in treatment-naive and prior null responders with HCV genotype 1 or 4 and compensated cirrhosis

Background and aim

Effective and safe antiviral treatment regimens are needed for patients with chronic hepatitis C (CHC) and cirrhosis.

Methods

An international open-label trial was conducted in CHC patients with genotype (G)1/4 infection, compensated cirrhosis, HCV RNA ≥ 50,000 IU/mL and body mass index 18–35 kg/m². Treatment-naive patients (Cohort 1) received a triple therapy regimen [danoprevir/r 100/100 mg twice daily (bid), ribavirin 1000/1200 mg/day and peginterferon alfa-2a 180 µg/week] for 24 weeks. Prior null responders (Cohort 2) received a quadruple therapy regimen (danoprevir/r 100/100 mg bid, mericitabine 1000 mg bid and peginterferon alfa-2a/ribavirin). The primary efficacy outcome was sustained virological response (HCV RNA < limit of quantification, target not detected) at end of the 24-week follow-up period (SVR24).

Results

In Cohort 1 (n = 23), 73.9 and 65.2 % of patients had a virological response at Weeks 4 and 24, respectively; 39.1 % achieved SVR24 (G1a = 1/13; G1b = 8/9; G4 = 0/1). In Cohort 2 (n = 20), 100 % achieved virological response at Weeks 4 and 24; 65 % achieved SVR24 (G1a = 4/8; G1b = 7/10; G4 = 2/2). Treatment failure was more common in G1a than G1b-infected patients and less common in patients receiving quadruple therapy. Treatment failure was associated with emergence of resistance to danoprevir, but not mericitabine. The safety profile was typical of that associated with peginterferon alfa-2a/ribavirin. No deaths/episodes of hepatic decompensation occurred.

Conclusions

Treatment with danoprevir/r-based regimens for 24 weeks is safe and well tolerated in CHC patients with compensated cirrhosis. A quadruple therapy regimen (danoprevir/r, mericitabine, peginterferon alfa/ribavirin) produced high SVR24 rates in prior null responders, particularly among G1b patients.

     

Postoperative ileus in an enhanced recovery pathway—a retrospective cohort study

Purpose

Enhanced recovery after surgery (ERAS) protocols advocate no nasogastric tubes after colorectal surgery, but postoperative ileus (POI) remains a challenging clinical reality. The aim of this study was to assess incidence and risk factors of POI.

Methods

This retrospective analysis included all consecutive colorectal surgical procedures since May 2011 until November 2014. Uni- and multivariate risk factors for POI were identified by multiple logistic regression and functional and surgical outcomes assessed.

Results

The study cohort consisted of 513 consecutive colorectal ERAS patients. One hundred twenty-eight patients (24.7%) needed postoperative reinsertion of nasogastric tube at the 3.9 ± 2.9 postoperative day. Multivariate analysis retained the American Society of Anesthesiologists group 3–4 (odds ratio (OR) 1.3; 95% CI 1–1.8, p = 0.043) and duration of surgery of >3 h (OR 1.3; 95% CI 1–1.7, p = 0.047) as independent risk factors for POI. Minimally invasive surgery (OR 0.6; 95% CI 0.5–0.8, p ≤ 0.001) and overall compliance of >70% to the ERAS protocol (OR 0.7; 95% CI 0.6–1, p = 0.031) represented independent protective factors. POI was associated with respiratory (23 vs. 5%, p ≤ 0.001) and cardiovascular (16 vs. 3%, p ≤ 0.001) complications.

Conclusions

POI was frequent in the present study. Overall compliance to the ERAS protocol and minimally invasive surgery helped to prevent POI, which was significantly correlated with medical complications.

     

Obstructive sleep apnea does not impair cardiorespiratory responses to progressive exercise performed until exhaustion in hypertensive elderly

Background

Elderly people have a high prevalence to systemic arterial hypertension (SAH) and obstructive sleep apnea (OSA). Both comorbidities are closely associated and inflict damage on cardiorespiratory capacity.

Methods

In order to assess cardiorespiratory responses to the cardiopulmonary exercise test (CPET) among hypertensive elderly with OSA, we enrolled 28 subjects into two different groups: without OSA (No-OSA: apnea/hypopnea index (AHI) < 5 events/h; n = 15) and with OSA (OSA: AHI ≥ 15 events/h; n = 13). All subjects underwent CPET and polysomnographic assessments. After normality and homogeneity evaluations, independent t test and Pearson’s correlation were performed. The significance level employed was p ≤ 0.05.

Results

Hypertensive elderly with OSA presented lower heart rate recovery (HRR) in the second minute (HRR₂) in relation to the No-OSA group. A negative correlation between AHI and ventilation (VE) (r = ?0.63, p = 0.02) was found in polysomnography and CPET data comparisons, and oxygen saturation (O₂S) levels significantly correlated with VE/VCO_2slope (r = 0.66, p = 0.01); in addition, No-OSA group presented a positive correlation between oxygen consumption and O₂S (r = 0.66, p = 0.01), unlike the OSA group.

Conclusions

OSA does not affect the CPET variables in hypertensive elderly, but it attenuates the HRR₂. The association between O₂S during sleep with ventilatory responses probably occurs due to the adaptations in the oxygen transport system unleashed via mechanical respiratory feedback; thus, it has been identified that OSA compromises the oxygen supply in hypertensive elderly.

     

Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet

Aims/hypothesis

Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy.

Methods

Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy.

Results

Male, but not female offspring of HFSSD-fed founders were heavier than those of control-diet-fed counterparts (p?<?0.05 and p?=?0.066 in males and females, respectively). Both male and female offspring of HFSSD-fed founders were longer compared with control (p?<?0.01 for both sexes). Folate treatment of the pregnant dams abolished the effect of the paternal diet on the offspring’s body length (p ? 0.05). Female offspring of HFSSD-fed founders developed impaired glucose tolerance, which was restored by folate treatment of the dams during pregnancy. The beta cell density per pancreatic islet was decreased in offspring of HFSSD-fed rats (?20% in male and ?15% in female F1 offspring, p ? 0.001 vs controls). Folate treatment significantly increased the beta cell density (4.3% and 3.3% after folate supplementation given to dams and founders, respectively, p ? 0.05 vs the offspring of HFSSD-fed male rats). Changes in liver connective tissue of female offspring of HFSSD-fed founders were ameliorated by treatment of dams with folate (p ? 0.01). Hepatic Ppara gene expression was upregulated in female offspring only (1.51-fold, p ? 0.05) and was restored in the female offspring by folate treatment (p ? 0.05). We observed an increase in hepatic Lcn2 and Tmcc2 expression in female offspring born to male rats exposed to an unhealthy diet during spermatogenesis before mating (p ? 0.05 vs controls). Folate treatment of the corresponding dams during pregnancy abolished this effect (p ? 0.05). Analysis of DNA methylation levels of CpG islands in the Ppara, Lcn2 and Tmcc2 promoter regions revealed that the paternal unhealthy diet induced alterations in the methylation pattern. These patterns were also affected by folate treatment. Total liver DNA methylation was increased by 1.52-fold in female offspring born to male rats on an unhealthy diet prior to mating (p ? 0.05). This effect was abolished by folate treatment during pregnancy (p ? 0.05 vs the offspring of HFSSD-fed male rats).

Conclusions/interpretation

Folate treatment of pregnant dams restores effects on female offspring’s glucose metabolism induced by pre-conception male founder HFSSD.

     

Prevalence of asymptomatic sexually transmitted infections in HIV-positive men who have sex with men in Germany: results of a multicentre cross-sectional study

Purpose

Sexually transmitted infections (STIs) occur frequently in risk populations. Hereby, the role of screening-programmes remains controversial. Our study aimed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men (MSM).

Methods

We enrolled asymptomatic, HIV-MSM in a prospective cross-sectional study from February to August 2016 at seven German HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis-B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed. All subjects were asked to complete a sexual-risk-behaviour-questionnaire.

Results

In total, 296 subjects with a median age of 43.2 (36.2–49.5) years were enrolled; 99.3% were on ART for 5.5 (2.3–11.2) years. HIV RNA was < 50 copies/mL in 93.6%. Active syphilis infection was found in 5.0% of all patients, whereas 55.4% had history of infection. HCV seropositivity was found in 33 patients (13.2%) and positive HCV RNA was available in 39.4%. 66/294 (22.5%) showed negative anti-HBs-antibodies, indicating lack of immunity. Overall, 40/296 (13.5%) had positive CT/NG swabs (CT in 8.8%; 7.3% anorectal, 1.7% oropharyngeal, 1.0% urethral and NG in 6.8%; 4.5% anal, 2.0% oropharyngeal, 1.4% urethral). Time since HIV infection < 7 years (OR 2.6 (1.2–5.5); p = 0.012), the use of inhalative nitrites (“poppers”) (OR 2.8 (1.3–5.9; p = 0.008) and reporting unprotected intercourse with > 20 partners within the last 6 months [OR 3.0 (1.2–7.8); p = 0.003] were significantly associated in multivariate analysis.

Conclusion

We found high numbers of asymptomatic syphilis, hepatitis-C and CT/NG infections in HIV-MSM, remarkably in patients with shorter duration of HIV-infection with more sexual partners within last 6 months.