Manuel Hernández-Guerra

Are there Predictive Factors of Severe Liver Fibrosis in Morbidly Obese Patients with Non-alcoholic Steatohepatitis?

Background: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity characterized by the presence of steatosis and lobular and/or portal inflammation with or without fibrosis. Patients with non-alcoholic fatty liver and fibrosis on liver biopsy have increased liver-related deaths. Methods: 181 wedge liver biopsies, taken at the time of bariatric surgery from patients with a mean body mass index (BMI) of 47, were studied. In all cases, the liver biopsy was performed without knowledge of the patients clinical and biochemical data, which were then examined with univariate and multivariate analysis. Results: Diagnosis of NASH was established in 105 patients (91%); 74 patients (70%) showed mild steatosis, 20 (19%) had moderate inflammation and fibrosis, and 11 (10%) had steatosis with severe fibrosis. None of the liver biopsies showed cirrhosis. Age was the only independent predictor of moderate and severe fibrosis (p=0.001). Conclusions: Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.

Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury

BACKGROUND & AIMS Chronic outcome following acute idiosyncratic drug-induced liver injury (DILI) is not yet defined. This prospective, long-term follow-up study aimed to analyze time to liver enzyme resolutions to establish the best definition and risk factors of DILI chronicity. METHODS 298 out of 850 patients in the Spanish DILI registry with no pre-existing disease affecting the liver and follow-up to resolution or ⩾1year were analyzed. Chronicity was defined as abnormal liver biochemistry, imaging test or histology one year after DILI recognition. RESULTS Out of 298 patients enrolled 273 (92%) resolved ⩽1year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR: 1.06, p=0.011], dyslipidemia [OR: 4.26, p=0.04] and severe DILI [OR: 14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 x upper limit of normal (xULN) and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001). Main drug classes involved in chronicity were statins (24%) and anti-infectives (24%). Histological examination in chronic patients demonstrated two cases with ductal lesion and seven with cirrhosis. CONCLUSIONS One year is the best cut-off point to define chronic DILI or prolonged recovery, with risk factors being older age, dyslipidemia and severity of the acute episode. Statins are distinctly related to chronicity. ALP and TB values in the second month could help predict chronicity or very prolonged recovery. LAY SUMMARY Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

Hipertensión portal, recomendaciones para su evaluación y tratamiento

a Unidad de Hepatologia, Hospital Clinic-IDIBAPS, Universidad de Barcelona y CIBERehd, Barcelona, Espana b Servicio de Gastroenterologia, Hospital Universitario Ramon y Cajal, IRYCIS, Universidad de Alcala, CIBERehd, Madrid, Espana c Servicio de Gastroenterologia, Hospital Universitario Arnau de Vilanova, Universidad de Lleida-IRBLieida, Lleida, Espana d Seccion de Hepatologia, Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Universidad Complutense, CIBERehd, Madrid, Espana e Seccion de Abdomen, Centro de Diagnostico por la Imagen, Hospital Clinic-IDIBAPS, Barcelona, Espana f Servicio de Gastroenterologia y Hepatologia, Hospital Universitario Puerta de Hierro, Universidad Autonoma, Madrid, Espana g Servicio de Aparato Digestivo, Hospital Marques de Valdecilla, Cantabria, Espana h Servicio de Medicina Interna-Hepatoligia (GENESCA), Hospital Universitari Vall d’Hebron, Universidad Autonoma de Barcelona y CIBERehd, Barcelona, Espana i Servicio de Aparato Digestivo, Hospital Universitario de Canarias, Tenerife, Espana j Unidad de Hepatologia, CIBERehd, Servicio Aparato Digestivo, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Barcelona, Espana k Servicio de Patologia Digestia, Hospital de St Pau, Barcelona, Espana

Hipertensión portal: recomendaciones para su evaluación y tratamiento: Documento de consenso auspiciado por la AEEH y el CIBERehd

a Unidad de Hepatologia, Hospital Clinic-IDIBAPS, Universidad de Barcelona y CIBERehd, Barcelona, Espana b Servicio de Gastroenterologia, Hospital Universitario Ramon y Cajal, IRYCIS, Universidad de Alcala, CIBERehd, Madrid, Espana c Servicio de Gastroenterologia, Hospital Universitario Arnau de Vilanova, Universidad de Lleida-IRBLieida, Lleida, Espana d Seccion de Hepatologia, Servicio de Medicina de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Universidad Complutense, CIBERehd, Madrid, Espana e Seccion de Abdomen, Centro de Diagnostico por la Imagen, Hospital Clinic-IDIBAPS, Barcelona, Espana f Servicio de Gastroenterologia y Hepatologia, Hospital Universitario Puerta de Hierro, Universidad Autonoma, Madrid, Espana g Servicio de Aparato Digestivo, Hospital Marques de Valdecilla, Cantabria, Espana h Servicio de Medicina Interna-Hepatoligia (GENESCA), Hospital Universitari Vall d’Hebron, Universidad Autonoma de Barcelona y CIBERehd, Barcelona, Espana i Servicio de Aparato Digestivo, Hospital Universitario de Canarias, Tenerife, Espana j Unidad de Hepatologia, CIBERehd, Servicio Aparato Digestivo, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Barcelona, Espana k Servicio de Patologia Digestia, Hospital de St Pau, Barcelona, Espana

Decisiones terapéuticas en el tratamiento del carcinoma hepatocelular y patrones de uso de sorafenib. Resultados del estudio internacional observacional GIDEON en España

INTRODUCTION GIDEON is a non-interventional, prospective, international study that evaluated the safety of sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B patients. OBJECTIVES To analyze data collected in Spain on the safety and efficacy of sorafenib and treatment patterns. METHODS Data were collected during follow-up on demographic and disease characteristics, the initial dose used, treatment-emergent adverse events (AEs) and dose modifications. Overall survival was evaluated, as well as time to disease progression. Efficacy and safety were analyzed according to the Child-Pugh classification and the initial dose. RESULTS We included 143 patients from 19 Spanish hospitals. A total of 24.5% of the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9% of patients. In Child-Pugh A patients, dose modifications occurred more frequently and the treatment duration was longer. The incidence of AEs and drug-related AEs were similar in Child-Pugh A and B patients, although serious AEs were more frequent in Child-Pugh B patients. The most common AEs were diarrhea, fatigue and hand-foot skin reactions. The median overall survival was 384 days and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The median time to disease progression was 177 days, similar in both subgroups. CONCLUSION The safety profile of sorafenib in Spanish patients with unresectable HCC is independent of liver function. Child-Pugh status does not seem to influence the approach to sorafenib dosage or time to progression but does seem to be a strong prognostic factor for survival.

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. Conclusions Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.

CKD staging with cystatin C or creatinine-based formulas: flipping the coin

Background Chronic kidney disease (CKD) affects 10-13% of the population worldwide. CKD classification stratifies patients in five stages of risk for progressive renal disease based on estimated glomerular filtration rate (eGFR) by formulas and albuminuria. However, the reliability of formulas to reflect real renal function is a matter of debate. The effect of the error of formulas in the CKD classification is unclear, particularly for cystatin C-based equations. Methods We evaluated the reliability of a large number of cystatin C and/or creatinine-based formulas in the definition of the stages of CKD in 882 subjects with different clinical situations over a wide range of glomerular filtration rates (GFRs) (4.2-173.7 mL/min). Results Misclassification was a constant for all 61 formulas evaluated and averaged 50% for creatinine-based and 35% for cystatin C-based equations. Most of the cases were misclassified as one stage higher or lower. However, in 10% of the subjects, one stage was skipped and patients were classified two stages above or below their real stage. No clinically relevant improvement was observed with cystatin C-based formulas compared with those based on creatinine. Conclusions The error in the classification of CKD stages by formulas was extremely common. Our study questions the reliability of both cystatin C and creatinine-based formulas to correctly classify CKD stages. Thus the correct classification of CKD stages based on estimated GFR is a matter of chance. This is a strong limitation in evaluating the severity of renal disease, the risk for progression and the evolution of renal dysfunction over time.

Documento de consenso. Manejo de la enfermedad hepática grasa no alcohólica (EHGNA). Guía de práctica clínica

Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver diseases in Spain and the incidence is raising due to the outbreak of type 2 diabetes and obesity. This CPG suggests recommendation about diagnosis, mainly non-invasive biomarkers, and clinical management of this entity. Life-style modifications to achieve weight loss is the main target in the management of NAFLD. Low caloric Mediterranean diet and 200 minutes/week of aerobic exercise are encouraged. In non-responders patients with morbid obesity, bariatric surgery or metabolic endoscopy could be indicated. Pharmacological therapy is indicated in patients with NASH and fibrosis and non-responders to weight loss measures. NAFLD could influence liver transplantation, as a growing indication, the impact of steatosis in the graft viability, de novo NAFLD rate after OLT and a raised cardiovascular risk that modify the management of this entity. The current CPG was the result of the First Spanish NAFLD meeting in Seville.

Effect of season and sunlight on viral kinetics during hepatitis C virus therapy

Background and aims Rapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight is the most important source of vitamin D and shows seasonal variation, we evaluated the effect of season on viral kinetics during peginterferon/ribavirin-based therapy for HCV. Methods Consecutive HCV patients treated with peginterferon/ribavirin and boceprevir/ telaprevir (June 2011–July 2014) were included. Patients were grouped according to season when therapy was initiated (Season A: May–October and Season B: November–April) depending on hours of daily sunlight. Multiple logistic regression analysis included factors known to influence SVR to treatment. The dependent variables were undetectable viral load (VL) or VL ≤15 UI/mL (VL ≤15) at weeks 4, 8 and 12, end of treatment and SVR. Results The study included 930 patients (66.8% men; median 54 years) treated with telaprevir (n=537) or boceprevir, without (n=481) or with lead-in therapy of peginterferon/ribavirin. Baseline characteristics of patients in Season A (45.3%, n=421) and Season B groups were similar. Overall, a higher rate of RVR (23.5% vs 16.1%, p=0.005) and VL ≤15 (51.0% vs 38.6%, p≤0.001) was observed in patients starting treatment during Season A versus Season B. By logistic regression analysis, initiating treatment in Season A proved to be an independent predictor of RVR and VL ≤15. Conclusions In our setting, seasonality affects viral kinetics in HCV genotype 1 patients treated with peginterferon/ribavirin-based therapy. Our findings support the hypothesis that vitamin D influences viral response to peginterferon/ribavirin-based therapy.

Terapia triple en pacientes con fibrosis avanzada y cirróticos: aspectos relevantes en la práctica clínica

Resumen El tratamiento de los pacientes con fibrosis hepatica avanzada y cirrosis por el virus de la hepatitis C en su modalidad de terapia triple con boceprevir/telaprevir e interferon pegilado-ribavirina representa actualmente la primera opcion terapeutica en la mayoria de los pacientes con genotipo 1. Sin embargo, hay cuestiones que pueden constituir una barrera para iniciar el tratamiento o alcanzar la respuesta viral sostenida en este tipo de pacientes. Estas limitaciones van desde la percepcion por parte del medico o paciente sobre la eficacia del tratamiento en la practica clinica habitual, y que pueden desviarnos de la decision de iniciar el tratamiento, grado avanzado de enfermedad con hipertension portal y comorbilidad, hasta su interrupcion por la mala adherencia y los efectos adversos, fundamentalmente la anemia. Por otra parte, actualmente se puede identificar pacientes que se benefician de un regimen terapeutico mas corto, sin detrimento de una similar tasa de curacion. En la presente revision se evaluan estos aspectos y su posible interferencia en el uso de triple terapia.