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1.

Background

Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation.

Aim

To evaluate a real-life experience of the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r plus RIB) in patients with end-stage kidney disease (ESKD).

Patients and methods

Between January 2017 and January 2018, an open-label multicenter prospective study was designed to enroll all consecutive patients with proven CHC genotype 4 infections and concomitant ESKD based on estimated glomerular filtration rate (eGFR) with (HD group) or without hemodialysis (non-HD group). Patients were given a co-formula of OBV/PTV/r (25/150/100?mg) once-daily plus RIB was given for 12?weeks. Sustained virologic response (SVR 12) was the primary endpoint.

Results

A total of 110 patients were enrolled. An overall SVR 12 was reported in 104 (94.5%) patients, and treatment failure were reported in 6 patients [2 patients (1.8%) were relapsed, and 4 patients (3.6%) patients were non-responders]. SVR12 was 96% in HD and 91.4% in non-HD patients (P?=?0.286).There were no reported serious adverse events. Anemia was reported in 66.6% (n?=?50) in HD group and in 31.4% (n?=?11) in non-HD group.

Conclusion

Although it is still challenging, achievement of SVR12 in patients with chronic HCV and concomitant end-stage kidney disease in the era of DAAs became possible with a 12?weeks course of a co-formula of ombitasvir/paritaprevir /ritonavir plus ribavirin.

ClinicalTrials.gov ID

NCT03341988.  相似文献   

2.
3.

Introduction

In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes.

Patients and methods

This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014–2017) were analyzed (n = 20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed.

Results

All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose.

Conclusion

HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.  相似文献   

4.

Background

We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis.

Methods

Cirrhotic patients treated by RFA for HCC within Milan criteria were included. Associations between patient features and events were estimated by the Kaplan–Meier method with the log rank test and using uni/multivariate Cox models.

Results

389 cirrhotic patients (Child–Pugh A 86.6%, 473 tumors) were included. OS was 79.8%, 42.4% and 16%, and overall tumor recurrence 45%, 78% and 88% at 2, 5 and 10 years, respectively. In multivariate analysis, age, Child–Pugh, GGT, HCC near major vessels, esophageal varices, alkaline phosphatase and HBV predicted OS. Gender, ALT, AFP and alcohol intake were associated with tumor recurrence. Multinodular HCC (19.5%) was associated with risk of tumor recurrence outside Milan criteria. HBV patients had longer OS than other patients (P?=?0.0059); negative HBV PCR at RFA was associated with decreased tumor recurrence (P?=?0.0157). Using time-dependent analysis in HCV patients, a sustained virologic response was associated with increased OS (124.5 months) compared to other patients (49.2 months, P?<?0.001).

Conclusion

Virologic response and severity of underlying liver disease were the main determinants of long-term OS after RFA for HCC developing on cirrhosis.  相似文献   

5.

Background

Despite the improvement of medical therapies, nearly half of patients with Crohn’s disease require surgery within 10?years after diagnosis. However, intestinal resection is not curative and recurrence may occur.

Aims

To evaluate post-surgical outcomes for patients with Crohn’s disease in a large monocentric cohort, and to identify variables associated with clinical and surgical relapse.

Methods

Patients with Crohn’s disease who had surgery for ileal and colonic Crohn’s disease between 2004 and 2016 and on at least one-year follow-up following surgery were included.

Results

One hundred ninety-three patients were included in the study. Crohn’s disease recurrence concerned 53% of patients after a median 56-month (6–158) follow-up and 29% of patients required a second surgical intervention. At logistic regression analysis, active smoking and young age at diagnosis were identified as independent risk factor for post-surgical relapse (p?=?0.01), while colonic or ileocolonic resection was recognized as a risk factor for surgical Crohn’s disease relapse (p?=?0.003).

Conclusions

Post-surgery recurrence is frequent for patients with Crohn’s disease. Active smoking and young age at diagnosis are risk factors for Crohn’s disease recurrence. As compared with patients undergoing small-bowel surgery, patients with colonic resection are proner to relapse requiring a second surgical intervention.  相似文献   

6.

Background

Sigmoid volvulus is a common cause of colonic obstruction in old and frail patients. Its standard management includes the endoscopic detorsion of the colonic loop, followed by an elective sigmoidectomy to prevent recurrence. However, these patients are often poor candidates for surgery.

Aim

The aim of this study was to compare death rate between elective sigmoidectomy and conservative management following endoscopic detorsion for sigmoid volvulus.

Methods

The medical records of 83 patients undergoing endoscopic detorsion of a sigmoid volvulus from 2008 to 2014 were retrospectively reviewed. Patients were divided into two groups: ‘elective surgery’ and ‘no surgery’.

Results

Patients in the ‘no surgery’ group (n?=?42) were older and had more loss of autonomy than in the ‘elective surgery’ group. Volvulus endoscopic detorsion was successful in 96% of patients with no complications. The median follow-up was 13 months (1 day-67 months). The death rate was 62% in the ‘no surgery’ group versus 32% in the ‘elective surgery’ group (p?=?0.02). In the ‘no surgery’ group, 23/42 of patients had volvulus recurrence. No recurrence occurred after surgery.

Conclusion

Elective surgery must be planned as soon as possible after the first episode of sigmoid volvulus. In frail patients, other options must be developed.  相似文献   

7.

Background

There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs).

Aim

To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking.

Methods

All subjects aged ≥18?years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014.

Results

The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p?<?0.01) but not in those positive for other HBV markers.

Conclusions

These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.  相似文献   

8.

Background

The growing number of gastric cancers together with improved survival resulted in an increasing population of survivors at risk of multiple primary cancers.

Aims

To estimate the 10-year risk and survival of third primary cancers (TPCs) among gastric first primary cancers (FPCs).

Methods

Gastric FPCs from the Portuguese North Region Cancer Registry, diagnosed in 2000-2006 (n?=?7409), were followed for a TPC (31/12/2012), and for all-cause death (31/12/2017). The cumulative incidence of TPCs was estimated. Patients with a TPC were matched (1:1, by sex, age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC?+?SPC patients without a TPC.

Results

Overall, 25 (0.3% of FPCs and 6.8% of SPCs) TPCs were diagnosed. The most common sites were tobacco-related, mainly including digestive organs. Among all FPCs, 10-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.4% (0.2–0.5%) and among SPCs 7.6% (4.4–10.8%). For TPCs, compared to matched patients, age-adjusted hazard ratio (95%CI) for death was 1.68 (0.77–3.67). The 10-year cumulative mortality of TPCs and matched patients was 92.6% and 67.9%, respectively.

Conclusions

A clustering of tobacco-related cancers was observed in TPCs, with a 10-year cumulative incidence of 0.4% among FPCs. TPCs had worse survival than patients without a TPC.  相似文献   

9.
10.

Aim

The aim of this study is to investigate the role of glypican-3(GPC3)/wnt/β-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin.

Methods

HepG2 cells were treated with various concentrations of curcumin and/or GPC3-targeting siRNA in the presence or absence of 3-MA. Cell proliferation and apoptosis were determined by MTT and TUNEL assay, respectively. Expression of GPC3, β-catenin, c-myc, LC3, and Beclin1 was determined by western blotting. In addition, curcumin was tested in tumor xenografts mice model, Caliper IVIS Lumina II was used to monitor the tumor growth, and GPC3/wnt/β-catenin signaling proteins were determined by western blotting.

Results

Curcumin treatment led to proliferation inhibition and apoptosis induction in HepG2 cells in a concentration-dependent manner, and suppressed HCC tumor growth in vivo. Further analysis showed that curcumin treatment inactivated Wnt/β-catenin signaling and decreased GPC3 expression, silencing of GPC3 expression promoted the effects of curcumin on Wnt/β-catenin signaling. In addition, inhibiting autophagy by 3-MA relieved curcumin-dependent down-regulation of GPC3.

Conclusion

Curcumin suppressed HCC tumor growth through down-regulating GPC3/wnt/β-catenin signaling pathway, which was partially mediated by activation of autophagy.  相似文献   

11.
12.

Purpose

To investigate the effects of angiotensin II (Ang II) and tumor necrosis factor-α (TNF-α) on the biological characteristics of hepatocellular carcinoma (HCC) cells and the associated changes in G protein-coupled receptor kinase 2 (GRK2) expression.

Methods

The mean serum levels of Ang II and TNF-α in normal subjects and patients with benign liver tumors (BLTs) and HCC were evaluated by enzyme-linked immunosorbent assay (ELISA), and liver samples from the patients with HCC and HCC mice were used to assess the protein levels of both cytokines, their major receptors and GRK2. In addition, the dynamics of Bel-7402 cells were determined with cell counting kit-8 (CCK-8) and Transwell experiments, while the levels of the primary cytokine receptors Ang II type-1 receptor (AT1R) and type-2 receptor (AT2R) as well as TNF receptor 1 (TNFR1) were detected by flow cytometry (FCM). The effects of Ang II and TNF-α on the GRK2 levels in Bel-7402 cells and on the dynamics of GRK2-knockdown HCC cells were also investigated.

Results

Both cytokines independently enhanced Bel-7402 cell growth, migration and invasion by decreasing the GRK2 level. In contrast, down-regulating the GRK2 level in Bel-7402 cells suppressed these effects. No synergistic effects were discovered when Ang II and TNF-α were administered together. Furthermore, increased AT1R and TNFR1 levels stimulated HCC initiation and progression, whereas AT2R overexpression produced the opposite effect.

Conclusions

The present results suggested that Ang II and TNF-α promote Bel-7402 cell growth, migration and invasion by down-regulating GRK2 expression, and that the associated receptors AT1R, AT2R and TNFR1 participate in HCC initiation and progression.  相似文献   

13.

Introduction

In iatrogenic or potentially reversible bradyarrhythmia, drug discontinuation or metabolic correction is recommended before permanent cardiac pacemaker (PM) implantation. These patients often have conduction system disease and there are few data on recurrence or the need for a permanent PM.

Objective

To analyze the need for PM implantation in patients with iatrogenic bradyarrhythmia or bradyarrhythmia associated with other potentially reversible causes.

Methods

We assessed consecutive symptomatic patients admitted to the emergency department with a primary diagnosis of bradyarrhythmia (atrioventricular [AV] node disease – complete or second‐degree AV block (AVB) [CAVB: 2nd‐degree AVB – 2:1], sinus bradycardia [SB] and atrial fibrillation [AF] with slow ventricular response [SVR]) in the context of iatrogenic causes or metabolic abnormalities. We determined the percentage of patients who required PM implantation.

Results

We studied 153 patients (47% male) admitted for iatrogenic or potentially reversible bradyarrhythmia. Diagnoses were SB 16%, CAVB 63%, second‐degree AVB 12%, and AF with SVR 10%. Eighty‐five percent of patients were under negative chronotropic therapy, 3% had hyperkalemia and 12% had a combined etiology. After correction of the cause, 55% of patients (n=84) needed a PM. In these patients the most common type of bradyarrhythmia was CAVB, in 77% (n=65) patients.

Conclusion

In a high percentage of patients with bradyarrhythmia associated with a potentially reversible cause, the arrhythmia recurs or does not resolve during follow‐up. Patients with AV node disease constitute a subgroup with a higher risk of recurrence who require greater vigilance during follow‐up and should be considered for PM implantation after the first episode.  相似文献   

14.

Background

To report the results of a phase I/II study of helical IMRT-based stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).

Methods

Eligibility included Child–Turcotte–Pugh class A or B, ≤3 lesions, and cumulative tumor diameter ≤6?cm. Dose was escalated from 36?Gy to 60?Gy delivered in 4 fractions. Grade ≥3 gastrointestinal toxicities (CTCAE v3.0) or radiation-induced liver disease defined dose-limiting toxicity (DLT).

Results

Thirty-two patients were enrolled: seven in dose levels 1–2 (36–44?Gy) and 25 in levels 3–4 (42–60?Gy). Failures included 1 local, 14 outfield intrahepatic, 2 distant, 1 concurrent local and outfield, 1 concurrent outfield and distant, and 1 concurrent local, outfield, and distant. Nine had grade 3 hematologic toxicities and 5 had grade 2 hepatic toxicities; no patient experienced DLT. Two-year local control (LFFS), outfield intrahepatic control (OutFFS), and overall survival (OS) rates were 80.9%, 46.7%, and 81.3%, respectively. Dose levels 3–4 and pre-radiotherapy multi-segment recurrence were independent prognostic factors for LFFS and OutFFS, respectively. Two-year LFFS, OutFFS, and OS were significantly higher for patients who were treated with dose-levels 3/4 for tumor(s) involving single segment compared with the rest of the patients.

Conclusions

Helical IMRT-based SBRT was safe and effective, and patients with multi-segment recurrences prior to SBRT need to be closely followed.  相似文献   

15.
16.

Background

Little is known about the unmet needs of physicians caring for patients with inflammatory bowel disease (IBD).

Aims

This study explored the practical difficulties and needs for professional updating of Italian IBD physicians.

Methods

A questionnaire was distributed to 600 physicians attending IG-IBD meetings.

Results

280 physicians completed the questionnaire (46.7%). On a 5-point Likert scale (from 1, strongly disagree to 5, strongly agree), they identified the most problematic issues in managing IBD patients as increasing bureaucracy (3.9), lack of extra-gastroenterological IBD expertise (3.4), lack of diagnostic techniques (3.1) and budget limitations (2.9). The most lacking techniques, ranked from 1 (greatest need) to 9 (lowest need), were: anti-drug antibody and trough level assays (2.7), device-assisted enteroscopy (3.1), exploration under anaesthesia (3.2), MR enterography (3.2), and bowel ultrasonography (3.3). About professional updating, respondents indicated (on a 5-point Likert scale) that helpful topics were practical medicine (4.3), managing difficult patients (4.1), and guidelines (4.0). The most desired modality for updating was residential courses on clinical practice (4.3).

Conclusion

Several factors potentially limit the best management of IBD patients in Italy. Satisfying these unmet needs could improve care for IBD patients.  相似文献   

17.

Background

Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.

Aims

We investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

Methods

A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings.

Results

For the subgroup of 684 patients without cirrhosis, Kaplan–Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P?=?0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox’s proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR?=?1.9; 95% CI?=?1.05–3.43, P?=?0.03).

Conclusions

Diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.  相似文献   

18.
19.

Background

Knowledge of haematological abnormalities in cirrhosis has greatly improved in recent years.

Aims

To evaluate how Spanish Digestive Disease specialists manage haemostatic alterations and associated disorders in patients with cirrhosis.

Methods

All members of the Spanish Association for the Study of the Liver and Spanish Society of Digestive Pathology were invited to fill in a web-based questionnaire.

Results

135 professionals, 93 hepatologists and 42 non-hepatologists responded to the survey. The concept of rebalanced haemostasis was known by 74.8% of them. Most specialists corrected the INR and thrombocytopenia before invasive procedures with moderate risk of bleeding or major surgery and in severe gastrointestinal bleeding. The threshold of platelets and, especially, INR used to administer blood products varied greatly. Pharmacological prophylaxis of venous thromboembolism prevailed, but it was highly dependent on the INR and platelet figures. Most participants initiated anticoagulation regardless of the degree of portal vein thrombosis, even in patients ineligible for transplantation. In potential candidates, only 56% maintained it indefinitely or until liver transplantation. No major differences between hepatologists and non-hepatologists were found.

Conclusions

A significant variability and certain deviation from current guidelines was observed among Spanish Digestive Disease specialists regarding management of haemostatic alterations and associated disorders in cirrhosis.  相似文献   

20.

Background

In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA).

Aims

To evaluate health-related quality of life (HRQoL) in APPRECIA trial.

Methods

HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52.

Results

Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p?<?0.001 and p?≤?0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p?<?0.001) and EQ-5D (p?<?0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score (Pearson’s r: ?0.768) and with EQ-5D index (r: ?0.644).

Conclusion

HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapy used (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, since improvements in HRQoL were only significant in patients with endoscopic remission at 1 year.  相似文献   

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