Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C.

BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.

Impact of improved upper endoscopy quality on detection of gastric precancerous lesions.

OBJECTIVE: Intestinal metaplasia (IM) is the point of no return in gastric carcinogenesis, and patients with extensive (antrum plus corpus) IM are at high risk of developing gastric cancer. We evaluated the impact of improved gastroscopy quality on the detection of gastric IM in an Italian area at high risk for gastric cancer. METHODS: Data of consecutive patients with gastric biopsies according to the updated Sydney System observed in 2013, 2016 and 2019 resulting in IM diagnosis were retrieved. In the first period, endoscopy was performed with standard white light instruments. In the second period, preendoscopic gastric preparation was administered, and the examinations lasting at least 7 min with standard endoscopes were performed. In the third period, the latter procedure was followed, with virtual chromoendoscopy equipped instruments. The prevalence of IM in any gastric site and that of extensive IM were compared among the three periods. RESULTS: Data of 3485 patients were available. The detection of IM in at least one gastric site increased from 29.9 to 33.6% and 34.5% (95% CI, 32.1-36.8) in the first, second and third period, respectively. The difference was statistically significant between the first and last (P = 0.02; OR, 1.24; 95% CI, 1.04-1.48) period. When considering extensive IM, the detection increased from 4.28 to 6.1% and 5.44%, although the difference failed to reach statistical significance (P = 0.076). CONCLUSION: Our data showed that implementation of a quality protocol increased the probability to detect IM in the stomach, allowing us to select patients deserving stricter follow-up.

Natural history and outcome of hepatic vascular malformations in a large cohort of patients with hereditary hemorrhagic teleangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality. AIM: This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients. METHODS: We analyzed 16 years of surveillance data from a tertiary hereditary hemorrhagic telangiectasia referral center in Italy. We considered for inclusion in this study 502 consecutive Italian patients at risk of hereditary hemorrhagic telangiectasia who presented at the hereditary hemorrhagic telangiectasia referral center and underwent a multidisciplinary screening protocol for the diagnosis of hereditary hemorrhagic telangiectasia. Of the 502 individuals assessed in the center, 154 had hepatic vascular malformations and were the subject of the study; 198 patients with hereditary hemorrhagic telangiectasia and without hepatic vascular malformations were the controls. Additionally, we report the response to treatment of patients with complicated hepatic vascular malformations. RESULTS: The 154 patients were included and followed for a median period of 44 months (range 12-181); of these, eight (5.2%) died from VM-related complications and 39 (25.3%) experienced complications. The average incidence rates of death and complications were 1.1 and 3.6 per 100 person-years, respectively. The median overall survival and event-free survival after diagnosis were 175 and 90 months, respectively. The rate of complete response to therapy was 63%. CONCLUSIONS: This study shows that substantial morbidity and mortality are associated with liver vascular malformations in hereditary hemorrhagic telangiectasia patients.

Premedication with simethicone and N-acetylcysteine for improving mucosal visibility during upper gastrointestinal endoscopy in a Western population.

Background and study aim Pre-endoscopic use of a preparation with tensioactive and mucolytic agents improved gastric mucosa visualization in Eastern studies. Data on Western population are scanty. Patients and methods This prospective, endoscopist-blinded, randomized study enrolled patients who underwent esophagogastroduodenoscopy in a single center. Before endoscopy patients, were randomized to receive or not receive an oral preparation with simethicone and N-acetylcysteine in water. A pretested score (Crema Stomach Cleaning Score [CSCS]) for gastric mucosa cleaning evaluation was used. In detail, the stomach was divided into the antrum, body, and fundus and a score of 1 to 3 was assigned to each part (the higher the score, the better the preparation), and a total value ≤ 5 was considered as insufficient. Time between endoscope insertion and clean achievement (mouth to clean time) or the end of examination (mouth to mouth time) was recorded. Results A total of 197 patients were enrolled. The mean overall CSCS value and mucosal cleaning in all parts was better in treated patients than in controls. Prevalence total score ≤ 5 was significantly lower in patients treated before endoscopy. Need for water flush occurred less frequently in treated patients ( P  < 0.0001). The mouth to clean time was lower in the treated than in the control group (2.3 ±â€Š1.6 vs 3.8 ±â€Š1.6 min; P  < 0.001), whereas no significant difference in mouth to mouth time emerged. Conclusions Data from this study show that premedication with simethicone and N-acetylcysteine results in significantly better endoscopic visualization of gastric mucosa, and the proposed CSCS could be useful for standardizing this evaluation.

Endoscopic ultrasonography findings in autoimmune pancreatitis: be aware of the ambiguous features and look for the pivotal ones.

Autoimmune pancreatitis is a form of chronic pancreatitis caused by an autoimmune process. The classical appearance of autoimmune pancreatitis in abdominal imaging is diffuse pancreatic enlargement, but the focal form appears as a mass and often involves the pancreatic head; this scenario represents a challenging diagnostic problem because these features also resemble pancreatic cancer. We present the endoscopic ultrasound findings of seven patients with autoimmune pancreatitis in order to highlight the ambiguous features and the features pivotal for the diagnosis.

Dietary iron intake and anemia: food frequency questionnaire in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular disease characterized by a heterogeneous clinical presentation and prognosis. Dietary evaluation is relevant in HHT patients to provide adequate iron and nutrient intake. Additionally, different dietary items have been reported to precipitate epistaxis in this setting. Our primary aim was to investigate the dietary habits of HHT patients through a food-frequency questionnaire (FFQ) to evaluate the presence of precipitants and/or protective factors for epistaxis and the occurrence of possible dietary modifications. The secondary aims were to evaluate the nutritional intake of iron in HHT patients and the self-reported effect of iron treatments on epistaxis. From April 2018 to October 2018, a 138-item FFQ was provided to HHT patients followed up at the HHT Referral Center of Crema Maggiore Hospital. The relationship between food items and epistaxis was ascertained on a separate form. Daily iron intake was calculated to establish the mean iron content of food items reported in the FFQ. RESULTS: One hundred forty-nine questionnaires were evaluated [72 females, median age 54 years (12-76). Overall, 26 (18%) patients reported dietary items that improved epistaxis (mostly blueberries and red fruits, green vegetables and legumes), while 38 (26%) reported some dietary items that exacerbated epistaxis (spices, chocolate, alcohol, strawberries and ginger). Dietary modifications were reported in up to 58% of cases. In HHT patients, the mean daily iron intake was 8.46 ± 2.78 mg, and no differences were observed in the iron intake of patients reporting a diet modification and those who did not. CONCLUSIONS: In the comprehensive management of HHT a healthy and balanced diet, with increased consumption of dietary items with a high iron content, should be encouraged.

High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia.

A vascular pathogenesis of hepatic focal nodular hyperplasia (FNH) has been suggested; this study was aimed to evaluate in families with hereditary hemorrhagic telangiectasia (HHT) the prevalence of FNH, relating it to presence and stage of hepatic vascular malformations (VMs). Fifty-two HHT families underwent a screening program including abdominal Doppler sonography (US) searching for hepatic VMs; we classified them as minimal, moderate and severe, depending on the number and degree of abnormalities found by Doppler US. Presence of focal liver lesions was recorded. Diagnosis of FNH was made if at least two examinations, whether color Doppler US, liver scintigraphy, dynamic computed tomography (CT) or magnetic resonance (MR), showed suggestive findings. FNH was found in five out of 274 subjects (1.8%). All five were affected by HHT. Thus, percentage related to the group of affected patients increased to 2.9; 4/5 presented severe liver VMs. Female-to-male ratio was 4:1. FNH was single in three cases; tumor size ranged between 20 and 90 mm. During follow-up, no lesion showed a reduction in size, three showed an increase. Prevalence of FNH in patients with HHT is far greater than that reported in the general population; Doppler US role in its diagnosis and follow-up is highlighted.

Pancreatic involvement in von Hippel-Lindau disease: report of two cases and review of the literature.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant multicancer syndrome caused by the germline mutation of a tumor suppressor gene. Affected individuals develop benign and malignant tumors of the central nervous system, kidneys, adrenal glands, pancreas, and reproductive system. Although VHL disease is mainly diagnosed after the detection of central nervous system tumors, they may not always be the first presentation. CASE REPORT: We report the case of a patient presenting with pancreatic cysts for whom the final genetic diagnosis of VHL disease was formulated. During management, the use of endoscopic ultrasonography (EUS) proved to be valid in the characterization of the pancreatic lesions. Family screening also revealed the genetic mutation in the patient's son and imaging investigations showed the presence of multiple tumors. The diagnosis allowed us to plan appropriate follow-up for both, thus improving their life expectancy. CONCLUSIONS: Gastroenterologists should be aware of the frequent pancreatic involvement in VHL disease and EUS can be useful in this setting.

Radiofrequency thermal ablation of liver tumors.

Radiofrequency ablation (RFA) of liver tumors was first proposed in 1990. New technologies enable us to produce liver thermal lesions of approximately 3-3.5 cm in diameter; RFA has consequently become an emerging percutaneous therapeutic option both for small hepatocellular carcinoma (HCC) and for non-resectable liver metastases, mainly from colorectal cancer. New devices (for example, triplet of cooled needles, wet needles) and combined therapies (tumor ischemia and RFA) have made it possible to treat large tumors. RFA can be carried out by a percutaneous, laparoscopic or laparotomic approach. Percutaneous RFA can be performed with local anaesthesia and mild sedation; deep sedation or general anaesthesia are also used. The guidance system is generally represented by ultrasound. CT or MR examinations are the more sensitive tests for assessing therapeutic results. The series of patients treated with RFA allow the technique to be considered as effective and safe, achieving a relatively high rate of cure in properly selected cases; it should be classified as curative/effective treatment for HCC, replacing percutaneous ethanol injection. The complication rate of RFA is low but not negligible; key elements in a strategy to minimize them are identified.