Proton pump inhibitors: use and misuse in the clinical setting

Introduction: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia

Vonoprazan for treatment of gastroesophageal reflux: pharmacodynamic and pharmacokinetic considerations

This review provides an update on the pharmacokinetic properties of vonoprazan and their correlates with pharmacodynamics; preliminary data on the therapeutic efficacy of vonoprazan as compared to lansoprazole in GERD patients Expert opinion: At variance from all available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing. Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability, as compared with PPIs. Preliminary data in patients with erosive esophagitis (EE) have shown the non-inferiority of vonoprazan to lansoprazole in terms of symptom relief and healing rate. Since these pharmacokinetic advantages, it is expected that it will have a significant favorable impact on GERD management. However, the clinical use of vonoprazan raises also some issues about its efficacy and safety in the long-term that deserve verification and careful investigation

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Complexity and diversity of gastroesophageal reflux disease phenotypes

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome

Drugs for improving esophageal mucosa defense: Where are we now and where are we going?

In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients. In this review we will summarize the existing knowledge of the old and novel compounds able to produce this therapeutic effect, including sucralfate, alginate-based drugs, and a new medical device consisting of hyaluronic acid and chondroitin sulfate dispersed in a bioadhesive carrier, together with the potential indications for their use. It is to be stressed, however, that, although these compounds may represent a real alternative to PPI therapy in GERD, the combination of mucosal protection with acid suppression may help manage many cases with a partial or unsatisfactory response to PPIs alone

The Effect of Hyaluronic Acid and Chondroitin Sulphate-Based Medical Device Combined with Acid Suppression in the Treatment of Atypical Symptoms in Gastroesophageal Reflux Disease

Extraesophageal reflux symptoms are increasingly common in the Western population and their clinical management is still controversial. Although therapy with proton-pump inhibitors (PPIs) represents the gold standard, to date, many patients are refractory to this treatment. The aim of this study was to evaluate, in patients with a recent diagnosis of GERD experiencing extraesophageal symptoms, the efficacy and safety of a 6-week treatment with PPI acid suppression in combination with Gerdoff® (a hyaluronic acid and chondroitin sulphate-based medical device) compared to PPI monotherapy. The trial verified the reduction in symptom frequency and severity by evaluating the proportion of Responders and Non-Responder patients after 6 weeks of treatment, compared to baseline. The effects of Gerdoff® + PPI treatment on extraesophageal symptoms were also evaluated after a 12-week follow up only in Responder patients. The analysis of the change in total Reflux Symptoms Index (RSI) score from baseline to the other time points showed that the extent of the decrease from baseline was higher in the Gerdoff® + PPI group than in the PPI group at any time point. However, the comparison between groups did not show statistically significant differences at any time point. A statistically significant difference, in favor of the Gerdoff® + PPI group, was observed for individual RSI items. Even if the trial showed some limitations, this is the first published study on the efficacy of a medical device containing hyaluronic acid and chondroitin sulphate with antacid in the treatment of extraesophageal reflux symptoms

Epidemiology and natural history of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries, particularly when considering its most classic symptom that is heartburn. This symptom is very frequent in the community and ranges from 10% to more than 30%, according to the various population-based studies. This disease is much more represented in Europe and USA than in Asiatic countries. It has been shown that GERD prevalence increases in parallel with the remarkable growth of obesity, as this condition is able to favor all the pathogenetic mechanisms leading to it. Current information regarding the phenotypic presentation of GERD shows that there are two main phenotypic manifestations, that are erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter includes the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, a pre-malignant lesion potentially leading to esophageal adenocarcinoma. Data from medical literature on the natural history of this disease are scant and mainly retrospective, so the interpretation of them is very difficult. However, they seem to suggest that both NERD and mild esophagitis tend to remain as such overtime and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur only in a small number of cases, ranging from 0% to 30%, 10-22% and 1-13%, respectively. Future studies should help us in elucidating better the real transition from one category to another and to do this, we have to exclude from the world of GERD all the functional conditions that nowadays can be easily recognized by means of impedance-pH monitoring

Could Chronic Idiopatic Intestinal Pseudo-Obstruction Be Related to Viral Infections?

Chronic idiopathic intestinal pseudo-obstruction (CIIPO) is a disease characterized by symptoms and signs of small bowel obstruction in the absence of displayable mechanical obstruction. Due to the known neuropathic capacity of several viruses, and their localization in the intestine, it has been hypothesized that such viruses could be involved in the pathogenesis of CIIPO. The most frequently involved viruses are John Cunningham virus, Herpesviridae, Flaviviruses, Epstein–Barr virus and Citomegalovirus. Therefore, the present narrative review aims to sum up some new perspectives in the etiology and pathophysiology of CIIPO

The appropriate use of proton-pump inhibitors

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety. Accordingly, the role of surgery has been enormously reduced in this field. The main indications for PPI use are universally acknowledged by many scientific societies and are the following: treatment of gastroesophageal reflux disease in its various forms and complications, eradication of H. pylori infection in combination with two or more antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger-Ellison Syndrome. Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both Western and Eastern countries and this phenomenon poses serious queries about the appropriate prescription of these drugs worldwide. In fact, the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features: the progressive and irreversible increase of the costs of therapy with this class of drugs and the greater potential harms for the patients. So, there is the need for a reappraisal of PPI correct indications for both general practitioners and various specialists in order to reestablish a correct use of these effective drugs in daily clinical practice, according to the best evidence-based guidelines