Gastroesophageal reflux disease: key messages for clinicians.

Gastroesophageal reflux disease (GERD) is a chronic common disorder for which patients often refer to specialists. In the last decades, numerous studies helped to clarify the pathophysiology and the natural history of this disease. Currently, in the clinical setting, GERD is defined by the presence of symptoms that, when endoscopic investigation is required, permit to distinguish between cases with or without associated esophageal mucosal injuries. These conditions are called erosive reflux disease and non-erosive reflux disease (NERD), respectively. The latter is the most common manifestation of GERD. Symptoms are defined typical, as heartburn and regurgitation, and atypical (also called extra-esophageal), as coughing and/or wheezing, hoarseness, sore throat, otitis media, and dental manifestations. In this context, it is crucial for clinicians to investigate the presence of features of suspected malignancy, as unexplained weight loss, anemia, dysphagia, persistent vomiting, familiar history of cancer, long history of GERD, and beginning of GERD symptoms after the age of 50 years. The presence of these risk factors should induce to perform an endoscopic examination. Particular attention should be given to functional conditions that can mimic GERD, such as functional heartburn and hypersensitive esophagus as well as, more rarely, eosinophilic esophagitis. The former ones have different pathophysiology and this explains the frequent non-response to proton pump inhibitor drugs. This narrative review provides to clinicians a useful and practical overview of the state-of-the-art on advancements in the knowledge of GERD.

Extra-Esophageal Presentation of Gastroesophageal Reflux Disease: 2020 Update.

Gastroesophageal reflux disease (GERD) is defined by the presence of symptoms induced by the reflux of the stomach contents into the esophagus. Although clinical manifestations of GERD typically involve the esophagus, extra-esophageal manifestations are widespread and less known. In this review, we discuss extra-esophageal manifestations of GERD, focusing on clinical presentations, diagnosis, and treatment. Common extra-esophageal manifestations of GERD include chronic cough, asthma, laryngitis, dental erosions, and gingivitis. Extra-esophageal involvement can be present also when classic GERD symptoms are absent, making the diagnosis more challenging. Although available clinical studies are heterogeneous and frequently of low quality, a trial with proton pump inhibitors can be suggested as a first-line diagnostic strategy in case of suspected extra-esophageal manifestations of GERD.

Dentistry and oral and maxillofacial surgery in the patient with liver disease: key messages for clinical practice.

The recent changes in terms of both epidemiology of chronic liver disease (CLD) and long-term survival of patients with CLD have had a great impact in the field of dentistry and oral and maxillofacial surgery. In this context, compared with the previous decades, today it is more probable to cure patients with CLD also at advanced stage (cirrhosis), that could remain asymptomatic for long, before the appearance of signs of decompensation. Hence, it is crucial to identify the patient with CLD and to define the stage of the latter. The main risks are the viral acquisition on the part of the operator or of the other patients, the risk of bleeding due to the impaired coagulation status or the risk of liver decompensation due to alterations in the metabolism of certain drugs leading to hepatotoxicity. Generally, it is appropriate to treat patients with CLD not yet evolved in cirrhosis or with compensated cirrhosis, in a primary care setting, whilst secondary care management should be reserved to those patients with decompensated cirrhosis (Child-Turcotte-Pugh's grade B or C) or compensated cirrhosis but with signs of thrombocytopenia or previous episodes of decompensation. In the latter case it is mandatory to quantify the perioperative risk. In this updated review the authors describe the practical approach to the patient with CLD.

Incidence of type 2 diabetes mellitus and glucose abnormalities in patients with chronic hepatitis C infection by response to treatment: results of a cohort study.

BACKGROUND: Patients with chronic hepatitis C are at risk of developing type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG), and this risk may increase among hepatitis C virus (HCV) patients not responding to an antiviral therapy. AIM: To compare the incidence of glucose abnormalities (IFG or DM) after an antiviral therapy between HCV+ patients with a long-term virological response (LTR) and nonresponders (NR; persistently positive HCV-RNA). METHODS: All 202 HCV+ patients without the baseline glucose abnormalities enrolled by our center in investigational trials or routinely treated with interferon (IFN)/peginterferon (Peg-IFN) (+/- ribavirin) from 1988 to 2001, with the available baseline sera stored at -80 degrees C, were considered. The baseline data included age, sex, body mass index (BMI), viral load, genotype, liver histologic staging and steatosis, glucose, and cholesterol. The homeostatic assessment of insulin resistance (HOMA-IR) was calculated in the baseline serum. The incidence of IFG or DM at the end of follow-up was compared between patients with LTR and NR. RESULTS: After a median follow-up of 8.0 yr (range 5-16), the cumulative risk of DM (N = 7) or IFG (N = 33) among the 202 HCV+ included patients was 16.9% (95% confidence interval [CI] 11.3-22.5). The 8-yr risk was not significantly lower between LTRs (14.5%) compared to NRs (18.8%) (hazard ratio [HR] 0.60, CI 0.30-1.20, P= 0.16). The HR adjusted for the baseline risk factors for DM and the predictors of a poor response (age, sex, HOMA-IR, BMI, family history of diabetes, HCV genotype 1, high viral load, cirrhosis, and steatosis) was 0.88 (CI 0.38-2.02, P= 0.76). Among other factors, those more associated to IFG-DM were an increasing age (P= 0.017), a higher BMI (P= 0.054), and a family history of DM (P= 0.065). CONCLUSIONS: After adjustment for several baseline risk factors, the incidence of glucose abnormalities was not significantly different between LTRs and NRs. Our data suggest that HCV clearance does not significantly reduce the risk of glucose intolerance.

IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients.

AIM: To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response. METHODS: A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response. RESULTS: Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G)/rs1297860 in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis. CONCLUSION: Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness.

Short duration treatment in genotype 1 chronic hepatitis C patients with rapid virologic response to pegylated interferon plus ribavirin.

BACKGROUND: In patients with chronic hepatitis C, rapid HCV-RNA clearance under treatment might allow shorter treatment duration without modifying the sustained virological response (SVR) rate. This study evaluated the impact of rapid virological response (RVR) in HCV genotype 1b infection management. METHODS: In an open-label trial, 180 patients received standard doses of peginterferon alfa-2a plus ribavirin. Those with undetectable serum HCV-RNA at week 6 (RVR) received 24-week short-course treatment; patients with undetectable HCV-RNA at week 12 (early responders [ER]) received 48-week "standard of care" treatment; patients with positive HCV-RNA at week 12 (non-responders [NR]) stopped the treatment. Study end-point was to determine SVR rate at week 24. RESULTS: The following responses were observed: 24% RVR, 44% ER, 32% NR. Among RVR subjects, HCV-RNA baseline levels and age were significantly lower (P=0.038 and 0.035 respectively) than in non-RVR patients. At follow-up, 91% of RVR and 33% of ER patients achieved SVR. Among those with RVR, patients experiencing post-therapy relapse were older than those who achieved a SVR (P=0.028). CONCLUSIONS: Chronic HCV-1b patients, achieving RVR with a 24-week treatment regimen, attained excellent SVR rates. In a cost-effective therapeutic approach, all HCV-1b patients eligible for therapy may have a short duration therapy on the basis of RVR.

Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures.

BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic challenge. Metal stents occasionally have been used, but results have been disappointing. The present study assessed the safety and the efficacy of temporary placement of the new expandable polyester silicone-covered stent for management of problematic esophageal strictures. METHODS: Fifteen patients with benign esophageal strictures were treated by temporary (6 weeks) placement of an expandable polyester silicone-covered stent. All patients had previously been treated, unsuccessfully, by repetitive endoscopic dilation. RESULTS: Stent placement was successful in all patients. There was no procedure-related complication. Dilation with over-the-guidewire polyvinyl dilators was required before stent placement. With the stent in situ, dysphagia completely resolved in all patients. Six weeks after placement, one stent was found to have migrated into the stomach. In the remaining patients, the stent was easily removed with a foreign body forceps. The pretreatment dysphagia score was 3 (range 2-4); the post-treatment score was 1 (range 0-1) (p < 0.0005). Long-term resolution (mean follow-up 22.7 [2.6] months) of the stricture was achieved in 12 patients (80%). The treatment failed in 3 patients, all of whom continue to require periodic dilation. CONCLUSIONS: In patients with benign esophageal strictures refractory to conventional dilation, temporary placement of a removable expandable polyester silicone-covered stent may lead to long-term relief of dysphagia with minimal morbidity.