Role of the PNPLA3 polymorphism rs738409 on silymarin + vitamin E response in subjects with non-alcoholic fatty liver disease

Background: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. Lifestyle changes are the pillar of the treatment, although a pharmacological approach is sometimes required in the case of a failure to respond/adhere to the diet. Objective: the aim of this study was to evaluate the effect of silymarin and the influence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant on the response to treatment in patients with NAFLD in a pilot study. Methods: a total of 54 patients with a NAFLD proven biopsy were enrolled in an open prospective study and were treated with Eurosil 85(R) (silymarin + vitamin E) for six months. Biochemical parameters and cardiovascular risk factors (diabetes mellitus, dyslipidemia, hypertriglyceridemia, arterial hypertension and HOMA-IR > 2.5) were recorded before and after six months of treatment. Non-invasive indexes (fatty liver index, lipid accumulation product and NAFLD-fibrosis score) were also calculated. The rs738409 PNPLA3 gene polymorphism status was also determined. Results: significant statistical changes from baseline values after six months of treatment were observed in transaminases levels but not in non-invasive index markers. Twenty patients (37.1%) were G allele carriers and had a higher percentage of lobular inflammation and ballooning on the basal liver biopsy. Patients with the G allele had a smaller decrease in transaminases levels after treatment with silymarin + vitamin E than non-G-allele carriers. Conclusions: treatment with silymarin + vitamin E produced a decrease in transaminases after six months of treatment without an accompanying weight loss. PNPLA3 G-allele carriers responded poorly to the treatment

No disponible

Role of the PNPLA3 polymorphism rs738409 on silymarin + vitamin E response in subjects with non-alcoholic fatty liver disease.

BACKGROUND: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries. Lifestyle changes are the pillar of the treatment, although a pharmacological approach is sometimes required in the case of a failure to respond/adhere to the diet. OBJECTIVE: the aim of this study was to evaluate the effect of silymarin and the influence of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant on the response to treatment in patients with NAFLD in a pilot study. METHODS: a total of 54 patients with a NAFLD proven biopsy were enrolled in an open prospective study and were treated with Eurosil 85® (silymarin + vitamin E) for six months. Biochemical parameters and cardiovascular risk factors (diabetes mellitus, dyslipidemia, hypertriglyceridemia, arterial hypertension and HOMA-IR > 2.5) were recorded before and after six months of treatment. Non-invasive indexes (fatty liver index, lipid accumulation product and NAFLD-fibrosis score) were also calculated. The rs738409 PNPLA3 gene polymorphism status was also determined. RESULTS: significant statistical changes from baseline values after six months of treatment were observed in transaminases levels but not in non-invasive index markers. Twenty patients (37.1%) were G allele carriers and had a higher percentage of lobular inflammation and ballooning on the basal liver biopsy. Patients with the G allele had a smaller decrease in transaminases levels after treatment with silymarin + vitamin E than non-G-allele carriers. CONCLUSIONS: treatment with silymarin + vitamin E produced a decrease in transaminases after six months of treatment without an accompanying weight loss. PNPLA3 G-allele carriers responded poorly to the treatment.

Factores analíticos, antropométricos y dietéticos asociados al desarrollo de fibrosis en pacientes con enfermedad por hígado graso no alcohólico / Analytical, anthropometric and dietary factors associated with the development of fibrosis in patients with nonalcoholic fatty liver disease

Antecedentes: la esteatohepatitis no alcohólica (EHNA) mantenida en el tiempo puede conducir a estadios avanzados de enfermedad hepática y al desarrollo de hepatocarcinoma. Objetivos: evaluar los factores analíticos, antropométricos y dietéticos asociados a la presencia de fibrosis hepática, evento que más influye en supervivencia y evolución. Métodos: fueron estudiados setenta y seis pacientes diagnosticados de enfermedad por hígado graso no alcohólica mediante biopsia. Las biopsias fueron clasificadas según el NAS-score (Kleiner). Se obtuvieron parámetros analíticos, antropométricos y dietéticos y se calculó el índice no invasivo NAFLD Fibrosis Score (NFLD-FS). Se determinaron los niveles séricos de leptina, adiponectina, resistina y TNF-alfa. Resultados: cincuenta y seis pacientes eran hombres (73,7%), con una edad media de 44,5 ± 11,3 años (19-68). Pacientes con fibrosis en biopsia: 39 (51,3%) (F1-F2: 84,6%; F3-4: 15,4%). Univariante: 17 mujeres (85%) presentaban fibrosis, frente a 22 hombres (39%) (p = 0,000). Los pacientes con fibrosis avanzada tenían mayor edad, menor recuento de plaquetas, menor albúmina sérica, mayor resistencia a la insulina (homeostatic model assessment insulin resistance, HOMA-IR), menor ingesta de lípidos, mayor nivel de leptina sérica y valores más altos de NAFLD-FS. Este índice presenta para detectar fibrosis avanzada un valor predictivo negativo del 98% y un valor predictivo positivo del 60%. Variables asociadas de forma independiente a la presencia de fibrosis (regresión logística): sexo masculino (factor protector) (0,09, IC 95%, 0,01-0,7; p < 0,05) y HOMA-IR (1,7, IC 95% 1,03-2,79; p < 0,05). Conclusiones: el sexo y el HOMA-IR son los únicos factores independientes que se asociaron a la presencia de fibrosis hepática en biopsia. El NAFLD-FS es un buen marcador no invasivo para descartar la presencia de fibrosis avanzada

Background: a prolonged non-alcoholic steatohepatitis (NASH) condition can lead to advanced stages of liver disease and the development of hepatocellular carcinoma. Aim: to evaluate analytical, anthropometric and dietary factors associated with the presence of fibrosis as this is the factor that most influences survival and evolution. Methods: seventy-six patients with liver biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included. Biopsies were scored considering the NASH criteria of Kleiner. Analytical, anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non-invasive fibrosis index and was assessed for each patient. Leptin, adiponectin, resistin and TNF-alpha serum levels were determined. Results: fifty-six patients were male (73.7%) and the mean age was 44.5 ± 11.3 years of age (19-68). Thirty-nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was statistically significant by univariate analysis (p < 0.01). Patients with advanced fibrosis were older, with lower platelet counts, lower serum albumin, greater homeostatic model assessment insulin resistance (HOMA-IR), lower dietary lipids percentage, higher serum leptin levels and higher NAFLD Fibrosis Score (NAFLD-FS) values. This index had a negative predictive value of 98% and a positive predictive value of 60% for the detection of fibrosis. Variables independently associated with fibrosis (logistic regression) included male gender (protective factor) (0.09, 95% CI 0.01-0.7; p < 0.05) and HOMA-IR (1.7, 95% CI, 1.03-2.79; p < 0.05). Conclusions: gender and HOMA-IR were the only independent factors associated with fibrosis. NAFLD-FS could be considered as an accurate scoring system to rule out advanced fibrosis

Analytical, anthropometric and dietary factors associated with the development of fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND: a prolonged non-alcoholic steatohepatitis (NASH) condition can lead to advanced stages of liver disease and the development of hepatocellular carcinoma. AIM: to evaluate analytical, anthropometric and dietary factors associated with the presence of fibrosis as this is the factor that most influences survival and evolution. METHODS: seventy-six patients with liver biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included. Biopsies were scored considering the NASH criteria of Kleiner. Analytical, anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non-invasive fibrosis index and was assessed for each patient. Leptin, adiponectin, resistin and TNF-alpha serum levels were determined. RESULTS: fifty-six patients were male (73.7%) and the mean age was 44.5 ± 11.3 years of age (19-68). Thirty-nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was statistically significant by univariate analysis (p < 0.01). Patients with advanced fibrosis were older, with lower platelet counts, lower serum albumin, greater homeostatic model assessment insulin resistance (HOMA-IR), lower dietary lipids percentage, higher serum leptin levels and higher NAFLD Fibrosis Score (NAFLD-FS) values. This index had a negative predictive value of 98% and a positive predictive value of 60% for the detection of fibrosis. Variables independently associated with fibrosis (logistic regression) included male gender (protective factor) (0.09, 95% CI 0.01-0.7; p < 0.05) and HOMA-IR (1.7, 95% CI, 1.03-2.79; p < 0.05). CONCLUSIONS: gender and HOMA-IR were the only independent factors associated with fibrosis. NAFLD-FS could be considered as an accurate scoring system to rule out advanced fibrosis.

Tratamiento de la hepatitis crónica B antígeno e positiva con antivirales orales: experiencia y resultados en la práctica clínica / HBeAg-positive chronic hepatitis B treatment with oral antiviral agents: Experience and results in clinical practice

INTRODUCCIÓN: La globalización y los movimientos migratorios hacen que la hepatitis crónica B Age+ (HCBe+) cobre cada día mayor relevancia en nuestro entorno. Objetivo Analizar las características epidemiológicas, evolución y respuesta al tratamiento con antivirales orales (AO) de los pacientes con HCBe+.Material y métodosSe analizaron 436 casos de infección crónica por el virus de la hepatitis B atendidos en el Hospital Universitario Ramón y Cajal desde 1990 hasta junio del 2012.ResultadosSesenta y cinco (14,9%) presentaban HCBe+. Siete pacientes en fase de tolerancia inmune no fueron tratados; los 58 restantes, sí. Fueron excluidos 4: 2 hepatitis agudas graves, una coinfección por VHC y otro por virus Delta. De los 54 restantes, 19 recibieron interferón con o sin AO y 35 solo Dos tratados durante menos de un mes no fueron incluidos en el análisis. Este se realizó finalmente en 33 pacientes. Duración media del tratamiento: 46,81 meses (6-138). Lamivudina fue el fármaco más prescrito (39,39%), seguida de tenofovir (24,24%) y entecavir (21,21%). Edad media: 42,08 ± 14 años; varones 75,75% (25/33). El 57,57% (19/33) seroconvirtió el antígeno e y el 27,27% (9/33) eliminó el antígeno de superficie. No se objetivó la reaparición de este último tras un seguimiento medio de 35,6 meses. Resistencias: 8 casos en 7 pacientes, 7 a lamivudina y uno a adefovir. CONCLUSIONES: El 15% de las HCB en nuestro medio son e+. El tratamiento con AO logra una elevada tasa de seroconversión (57,57%) y un considerable porcentaje de pérdida del antígeno de superficie (27,27%)

INTRODUCTION: Due to globalization and migratory movements, HBeAg+ chronic hepatitis B isbecoming increasingly important in Spain. OBJECTIVE: To analyze the epidemiological features, progression, and treatment response to oral antiviral agents (OA) in HBeAg+ chronic hepatitis B patients in our area. MATERIAL AND METHODS: We analyzed 436 patients with chronic hepatitis B infection followed up at the Ramón y Cajal Hospital from 1990 to June 2012. RESULTS: Sixty-five patients (14.9%) had HBeAg+ chronic hepatitis B. Seven patients in the immunotolerant phase were not treated, while the remaining 58 received treatment. Four patients were excluded: two due to severe acute hepatitis, one due to hepatitis C virus coinfection and another because of a Delta virus coinfection. Of the remaining 54 patients, 19 received interferon with or without OA, and 35 received only OA. Two patients treated for less than 1 month were not included in the analysis. The analysis was finally performed in 33 patients. The mean duration of treatment was 46.81 months (6-138). Lamivudine was the most frequently prescribed drug (39.39%) followed by tenofovir (24.24%) and entecavir (21.21%). The mean age was 42.08 ± 14 years and 75.75% (25/33) of the patients were male. Nineteen of 33 patients (57.57%) achieved seroconversion to anti-HBe, and 27.27% (9/33) showed clearance of HBsAg. There was no evidence of HBsAg reversion after a mean follow-up of 35.6 months. There were 8 cases of resistance in 7 patients: 7 to lamivudine and 1 to adefovir. CONCLUSIONS: Approximately 15% of chronic hepatitis B patients in our area are HBeAg+. Treatment with OA achieves a high seroconversion rate (57.57%) and a considerable percentage of HBsAg clearance (27.27%)

[HBeAg-positive chronic hepatitis B treatment with oral antiviral agents: experience and results in clinical practice]. / Tratamiento de la hepatitis crónica B antígeno e positiva con antivirales orales: experiencia y resultados en la práctica clínica.

INTRODUCTION: Due to globalization and migratory movements, HBeAg+ chronic hepatitis B is becoming increasingly important in Spain. OBJECTIVE: To analyze the epidemiological features, progression, and treatment response to oral antiviral agents (OA) in HBeAg+ chronic hepatitis B patients in our area. MATERIAL AND METHODS: We analyzed 436 patients with chronic hepatitis B infection followed up at the Ramón y Cajal Hospital from 1990 to June 2012. RESULTS: Sixty-five patients (14.9%) had HBeAg+ chronic hepatitis B. Seven patients in the immunotolerant phase were not treated, while the remaining 58 received treatment. Four patients were excluded: two due to severe acute hepatitis, one due to hepatitis C virus coinfection and another because of a Delta virus coinfection. Of the remaining 54 patients, 19 received interferon with or without OA, and 35 received only OA. Two patients treated for less than 1 month were not included in the analysis. The analysis was finally performed in 33 patients. The mean duration of treatment was 46.81 months (6-138). Lamivudine was the most frequently prescribed drug (39.39%) followed by tenofovir (24.24%) and entecavir (21.21%). The mean age was 42.08±14 years and 75.75% (25/33) of the patients were male. Nineteen of 33 patients (57.57%) achieved seroconversion to anti-HBe, and 27.27% (9/33) showed clearance of HBsAg. There was no evidence of HBsAg reversion after a mean follow-up of 35.6 months. There were 8 cases of resistance in 7 patients: 7 to lamivudine and 1 to adefovir. CONCLUSIONS: Approximately 15% of chronic hepatitis B patients in our area are HBeAg+. Treatment with OA achieves a high seroconversion rate (57.57%) and a considerable percentage of HBsAg clearance (27.27%).