Prolonged release pirfenidone pharmacokinetics is modified in cirrhosis GENESIS study.

BACKGROUND: In both clinical and experimental trials, pirfenidone (PFD) showed anti-inflammatory and antifibrogenic effects. Considering the wide variation in hepatic functional reserve in patients with cirrhosis, we decided to learn more about the pharmacokinetics of a new formulation of prolonged release PFD in this population (PR-PFD), focusing on assessing changes on AUC0-∞, AUC0-t, and Cmax. METHODS: In this study, 24 subjects with cirrhosis were included: eight subjects with mild liver impairment (Child-Pugh A) and eight with moderate liver impairment (Child-Pugh B), and a third group of eight age-matched subjects without fibrosis. All participants were under fasting conditions before receiving orally two 600-mg tablets of a prolonged-release formulation of pirfenidone (PR-PFD) and remained in the clinical unit for 36 h after PR-PFD administration. Serial blood samples were collected after dosing (0.5-36 h). A validated high-performance liquid chromatography-mass spectrometry method was used to determine PFD plasma concentrations. RESULTS: The exposure to PR-PFD was 3.6- and 4.4-fold greater in subjects with Child-Pugh A and Child-Pugh B than in subjects without cirrhosis, and Cmax was 1.6- and 1.8-fold greater in subjects with Child-Pugh B and Child-Pugh-A than in patients without cirrhosis, without significant differences between the two cirrhotic groups. PFD was well tolerated. CONCLUSION: The pharmacokinetic parameters of PR-PFD are significantly modified in patients with cirrhosis compared with those in controls, indicating that liver impairment should be considered in clinical practice.

Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty liver disease.

BACKGROUND: The definition of metabolic-dysfunction-associated fatty liver disease (MAFLD) allows identification of metabolically complicated patients. Fibrosis risk scores are related to cardiovascular risk (CVR) scores and could be useful for the identification of patients at risk of systemic complications. AIM: To evaluate the relationship between MAFLD and CVR using the Framingham risk score in a group of Mexican patients. METHODS: Cross-sectional, observational and descriptive study carried out in a cohort of 585 volunteers in the state of Veracruz with MAFLD criteria. The risk of liver fibrosis was calculated with aspartate aminotransferase-to-platelet ratio index, nonalcoholic fatty liver disease score and fibrosis-4, as well as with transient hepatic elastography with Fibroscan®. The CVR was determined by the Framingham system. RESULTS: One hundred and twenty-five participants (21.4%) with MAFLD criteria were evaluated, average age 54.4 years, 63.2% were women, body mass index 32.3 kg/m2. The Framingham CVR was high in 43 patients (33.9%). Transient elastography was performed in 55.2% of volunteers; 39.1% with high CVR and predominance in advanced fibrosis (F3-F4). The logistic regression analysis showed that liver fibrosis, diabetes and hypertension independently increased CVR. CONCLUSION: One of every three patients with MAFLD had a high CVR, and in those with high fibrosis risk, the CVR risk was even greater.

Body composition and phase angle by bioimpedance in patients with MAFLD. / Análisis de la composición corporal y ángulo de fase por bioimpedancia en pacientes con MAFLD.

OBJECTIVE: To describe the characteristics of the body components and phase angle (PhA) of patients with MAFLD according to those different to fibrosis and hepatic steatosis. MATERIAL AND METHODS: Observational and descriptive study in a cohort of 585 volunteers from our center with MAFLD criteria. The risk of liver fibrosis was determined by APRI, NAFLD score and FIB-4; at an indeterminate and high risk of fibrosis, a transient elastography (Fibroscan®) were realized. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. Bioimpedance body composition analysis (SECA®) was performed. Patients with ET and SECA® registry were included. RESULTS: 125 participants (21.4%) were evaluated, age 53.9±13.9 years, 62.1% women, BMI 33.2±5.8kg/m2. The SECA® analysis showed mean fat mass of 42%±7.32 and muscle mass 21.18kg±6.6. The PhA was 5.1±0.69, in women 4.92±0.62 and men 5.41±0.70. PhA in patients without fibrosis was 5.091 vs with fibrosis 5.121 (P=.813). In advanced fibrosis, it reported a low value compared to the rest of the groups (P=.031). The PhA in S3 was higher compared to S1 and S2 (5.3 vs 4.82, 4.81) (P=.027). CONCLUSIONS: In MAFLD, the PhA was lower than the healthy Mexican population. In patients without fibrosis and severe steatosis, PhA rises proportionally to the increase in fat mass and BMI and in advanced liver fibrosis, PhA decreases.

[Liver functional test (LFT) and ultrasound (US) usefulness in the diagnostic of non-alcoholic steato-hepatitis (NASH)]. / Utilidad de las pruebas de funcionamiento hepático (PFH) y del ultrasonido (US) en el diagnóstico de la esteatohepatitis no alcohólica (EHNA).

OBJECTIVE: To investigate the Liver Functional Test (LFT) and hepatic ultrasound (US) usefulness in the diagnostic of NASH. BACKGROUND: NASH is part of NAFLD (non-alcoholic fatty liver disease), this condition can lead to cirrhosis; it is associated with others frequents diseases in Mexico such as type 2 diabetes and obesity. Unfortunately the diagnosis of NASH is not easy, since it must be confirmed by an hepatic biopsy and this requisite can conditionate a subnormal register. Until now, we don't have programs oriented to detect this disease; even though several high risk populations have been identified. METHODS: We compared the results of LFT and hepatic US often patients with NASH and ten healthy volunteers. Both groups where matched; the sensibility (S), specificity (Sp) and predictive values (PV) of each test were established. Student t test was used in the statistic analysis. RESULTS: The tests with the most notable difference were aminotransferases (AST, ALT), indirect billirubin (IB) and the US; with S of 100% to IB and US; Sp 100% to aminotransferases; PV+ 100% to ALT and AST, and 71% to US; and PV- 100% to IB and US. CONCLUSIONS: LFT and US are useful to detect NASH, the periodic testing of subjects with type 2 diabetes and overweight in risk of NASH is proposed as an effective tool of detection for the cases that require a subsequent study by a gastroenterologist.

[Trichobezoar: presentation of three cases, clinical and psychological profile]. / Tricobezoar: presentación de tres casos, perfil clínico y psicológico.

INTRODUCTION: The description of Trichobezoar is very ancient; it is an occasional entity and it mainly affects young women with deep psychopathology. CASES REPORT: Three cases of teenagers with gastric Trichobezoar have been studied; their clinical evolution and diagnostic methods were analyzed. Their psychological profile and familiar environment were particularly studied in our hospital by gastroenterology and psychology. DISCUSSION: Clinical manifestations are unspecified, however long-evolution dyspepsia is predominant and the diagnosis can be suspected for the young age of the patients, most of them females, with certain atypical personality characteristics with a palpable abdominal mass in the epigastrium in advanced stages of the illness; the most useful diagnosis methods are simple abdominal x-rays, UGI x-rays and endoscopy. Psychological evaluation revealed a familiar dysfunction in all of them. We observed a profile of dysfunctional personality in different degrees, including psychomotor retardation in two of them. All of the cases were solved surgically without complications. The last two cases, as well as their parents have received family psychotherapy, and now the evolution is favorable. Control endoscopies were made 6 months after the surgical event and do not show any trace of hair in the stomach.

[Treatment of non-alcoholic steatohepatitis (NASH). A comparative study of ursodeoxycholic acid and alpha-tocopherol. A preliminary report]. / Tratamiento de la esteatohepatitis no alcohólica (EHNA). Estudio comparativo con ácido ursodesoxicólico y alfa-tocoferol. Reporte preliminar.

BACKGROUND: At the present time, there is no accepted treatment for non-alcoholic steatohepatitis (NASH); nevertheles, there are some reports of non-controlled studies with apparently good answer with ursodeoxycholic acid (UDCA) as much with alpha-tocopherol (aTP). OBJECTIVE: To value the clinical, biochemical and hepatic ultrasound (US) response in patients with NASH in treatment for 1 year with UDCA or aTP, as well as to establish tolerance, undesirable effects and fulfillment. METHOD: Three patients received UDCA (250 mg TID) and six aTP (100 mg TID). Changes in hepatic function test and US were analyzed. All patients were women with an average age of 52 years, body mass index of 27, five with diabetes mellitus (DM) type II. RESULTS: Fulfillment of treatment was 95%; undesirable effects were not reported; clinical course was asymptomatic and clinically we did not observe important changes; US showed favorable changes in four patients (44%), two in each group. Alkaline phosphatase was normalized in patient who initially registered it as high. ALT and AST average diminished by 40% and normalization was obtained in five of six patients in treatment with aTP (83%) and in one of the UDCA group (33%). No statistically significant difference was obtained. CONCLUSIONS: The group is small and requires more persons and to be compared with a control group. It is possible that both drugs can be useful in the treatment of NASH; they are well tolerated and allow good fulfillment.

Prevalencia de la esteatohepatitis no alcohólica (EHNA): estudio comparativo con diabéticos / Prevalence of non-alcoholic steatohepatitis: comparative study of patients with diabetes

Antecedentes: la esteatohepatitis no alcohólica es una enfermedad poco conocida, cursa casi asintomática, con cambios mínimos en las pruebas de funcionamiento hepático (PFH); predomina en mujeres obesas con diabetes, con alcoholismo negativo; sin embargo sus biopsias hepáticas muestran daño similar a la enfermedad hepática por alcohol. Puede evolucionar a cirrosis. Objetivo: conocer la prevalencia de la EHNA en derechohabientes del IMSS en Pachuca Hidalgo, México. Método: se estudiaron voluntarios de cada sexo, entre 17 y 75 años, sin hepatopatía conocida, ni consumo de alcohol mayor de 20 g/semana. Se les practicó revisión clínica, exámenes de laboratorio y ultrasonido hepático, a aquellos que mostraron cambios en las PFH y en el ultrasonido se les propuso la biopsia hepática. Resultados: completaron el estudio 97 voluntarios, 70 de ellos no-diabéticos y 27 diabéticos. Se indicó la biopsia en 15 casos, y se confirmó EHNA en 10 (10.3 por ciento); la prevalencia en diabéticos fue de 18.5 por ciento y en no-diabéticos de 7.1 por ciento. Aunque encontramos diferencias en género, edad, y diabetes entre los enfermos con EHNA y los controles, en ningún caso se obtuvo significancia estadística; sin embargo, el sexo femenino y la diabetes se identificaron como factores de riesgo para EHNA. El antecedente de colelitiasis, fue notablemente más frecuente en el grupo de EHNA (p= 0.003). Conclusiones: la prevalencia de EHNA fue 10.3 por ciento en el grupo estudiado, es más frecuente en diabéticos y en mujeres. La obesidad no mostró ser un factor de riesgo adicional a la diabetes.