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.

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.

[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%).