Estudio comparativo de eficacia y seguridad de dexrabeprazol versus esomeprazol en el tratamiento de la enfermedad por reflujo gastroesofágico / Efficacy and safety comparative study of dexrabeprazole vs. esomeprazole for the treatment of gastroesophageal reflux disease

Resumen Introducción: Una encuesta nacional en población abierta mostró que la enfermedad por reflujo gastroesofágico (ERGE) tiene alta prevalencia en México. Objetivo: Comparar la eficacia y seguridad de dos isómeros, dexrabeprazol (10 mg) versus esomeprazol (20 mg), en el tratamiento de la ERGE durante cuatro semanas. Métodos: Ensayo clínico fase III, aleatorizado, multicéntrico, prospectivo, doble ciego, en dos grupos que incluyeron 230 pacientes. Resultados: Con ambos tratamientos se observó disminución estadísticamente significativa en la severidad de los síntomas de ERGE (pirosis, regurgitación, dolor epigástrico y disfagia), evaluados mediante una escala visual análoga. La puntuación promedio de dexrabeprazol en el Cuestionario de Carlsson-Dent a los 28 días fue de 2.12 y la de esomeprazol de 3.02. Ambos tratamientos fueron efectivos, sin diferencia estadísticamente significativa (p < 0.05). En el Cuestionario de Salud SF-36 se observó que ambos mejoraron la puntuación en la calidad de vida, sin diferencia significativa. Ambos medicamentos fueron bien tolerados y el perfil de incidencia de eventos adversos fue bajo. Conclusiones: En el tratamiento de ERGE no erosiva, el uso de 10 mg/día de dexrabeprazol es tan efectivo como 20 mg/día de esomeprazol, con la ventaja de que la dosis es menor con un adecuado perfil de seguridad.

Abstract Introduction: A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico. Objective: To compare the efficacy and safety of two isomers, dexrabeprazole (10 mg) vs. esomeprazole (20 mg), in the treatment of GERD for four weeks. Methods: Randomized, multicenter, prospective, double-blind phase III clinical trial in two groups that included 230 patients. Results: A statistically significant decrease in the severity of GERD symptoms (heartburn, regurgitation, epigastric pain and dysphagia), evaluated using a visual analogue scale, was observed with both treatments. Mean score for dexrabeprazole on Carlsson-Dent questionnaire at 28 days was 2.12, and for esomeprazole, 3.02. Both treatments were effective, with no statistically significant difference being recorded (p < 0.05). On SF-36 health questionnaire, both were observed to improve the quality-of-life score, with no significant difference being identified. Both drugs were well tolerated, and the adverse event incidence profile was low. Conclusions: In the treatment of non-erosive GERD, the use of dexrabeprazole at 10 mg/day is as effective as esomeprazole 20 mg/day, with the advantage that the dose is lower with an appropriate safety profile.

Efficacy and safety comparative study of dexrabeprazole vs. esomeprazole for the treatment of gastroesophageal reflux disease.

INTRODUCTION: A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico. OBJECTIVE: To compare the efficacy and safety of two isomers, dexrabeprazole (10 mg) vs. esomeprazole (20 mg), in the treatment of GERD for four weeks. METHODS: Randomized, multicenter, prospective, double-blind phase III clinical trial in two groups that included 230 patients. RESULTS: A statistically significant decrease in the severity of GERD symptoms (heartburn, regurgitation, epigastric pain and dysphagia), evaluated using a visual analogue scale, was observed with both treatments. Mean score for dexrabeprazole on Carlsson-Dent questionnaire at 28 days was 2.12, and for esomeprazole, 3.02. Both treatments were effective, with no statistically significant difference being recorded (p < 0.05). On SF-36 health questionnaire, both were observed to improve the quality-of-life score, with no significant difference being identified. Both drugs were well tolerated, and the adverse event incidence profile was low. CONCLUSIONS: In the treatment of non-erosive GERD, the use of dexrabeprazole at 10 mg/day is as effective as esomeprazole 20 mg/day, with the advantage that the dose is lower with an appropriate safety profile.

INTRODUCCIÓN: Una encuesta nacional en población abierta mostró que la enfermedad por reflujo gastroesofágico (ERGE) tiene alta prevalencia en México. OBJETIVO: Comparar la eficacia y seguridad de dos isómeros, dexrabeprazol (10 mg) versus esomeprazol (20 mg), en el tratamiento de la ERGE durante cuatro semanas. MÉTODOS: Ensayo clínico fase III, aleatorizado, multicéntrico, prospectivo, doble ciego, en dos grupos que incluyeron 230 pacientes. RESULTADOS: Con ambos tratamientos se observó disminución estadísticamente significativa en la severidad de los síntomas de ERGE (pirosis, regurgitación, dolor epigástrico y disfagia), evaluados mediante una escala visual análoga. La puntuación promedio de dexrabeprazol en el Cuestionario de Carlsson-Dent a los 28 días fue de 2.12 y la de esomeprazol de 3.02. Ambos tratamientos fueron efectivos, sin diferencia estadísticamente significativa (p < 0.05). En el Cuestionario de Salud SF-36 se observó que ambos mejoraron la puntuación en la calidad de vida, sin diferencia significativa. Ambos medicamentos fueron bien tolerados y el perfil de incidencia de eventos adversos fue bajo. CONCLUSIONES: En el tratamiento de ERGE no erosiva, el uso de 10 mg/día de dexrabeprazol es tan efectivo como 20 mg/día de esomeprazol, con la ventaja de que la dosis es menor con un adecuado perfil de seguridad.

Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions.

AIM: To investigate the main current etiologies of cirrhosis in Mexico. METHODS: We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period (January 2012-December 2017). RESULTS: A total of 1210 patients were included. The mean age was 62.5 years (SD = 12.1), and the percentages of men and women were similar (52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus (HCV) (36.2%), alcoholic liver disease (ALD) (31.2%), and nonalcoholic steatohepatitis (23.2%), and the least frequent were hepatitis B virus (1.1%), autoimmune disorders (7.3%), and other conditions (1.0%). CONCLUSION: HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease (NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.

Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9-12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1-4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.