Hepatotoxicity associated with statin use: analysis of the cases included in the Spanish Hepatotoxicity Registry.

OBJECTIVES: The hepatotoxic potential of statins is controversial. The objectives of this study were to describe the relative frequency of hepatotoxicity caused by statins and the phenotypes found in Spain. PATIENTS AND METHODS: The incidence of hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH) were studied and compared with those attributed to other drugs. RESULTS: Between April 1994 and August 2012, the REH included a total of 858 cases of which 47 (5.5 %) were attributed to statins. Of these, 16 were due to atorvastatin (34 %); 13 to simvastatin (27.7 %); 12 to fluvastatin (25.5 %); 4 to lovastatin (8.5 %) and 2 to pravastatin (4.3 %). Statins represented approximately half of the cardiovascular group which occupied 3rd place (10 %), after anti-infectious agents (37 %) and central nervous system drugs (14 %). The hepatocellular pattern was predominant, especially in the simvastatin group (85%), the cholestatic/mixed pattern was more frequent with fluvastatin (66 %) and had a similar distribution to atorvastatin. Patients with statin-induced toxicity were older (62 years versus 53 years, p < 0.001) and more often demonstrated anautoimmune hepatitis phenotype (8.5 % versus 1.4 %, p < 0.003). CONCLUSIONS: Statins are not a common cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the greatest number of incidents. The liver injury pattern varies among the different statins. The hepatitis phenotype with autoimmune features appears to be a characteristic signature of statin-induced hepatotoxicity.

Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis.

BACKGROUND & AIMS: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. METHODS: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. RESULTS: Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. CONCLUSIONS: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

Eficacia de los programas de cribado de hepatocarcinoma: ¿mejoran las opciones terapéuticas de estos pacientes? / Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options?

Objetivo: determinar si la utilización en nuestro medio delprograma de cribado de HCC establecido –alfa-fetoproteína (AFP)y ecografia semestral– en pacientes con hepatopatía crónica permitedetectar pacientes en estadios precoces de la enfermedad.Material y métodos: Diseño experimental: estudio retrospectivo.Criterios diagnósticos de HCC: 2 o más técnicas de imagencon lesión hipervascular mayor de 2 cm o 1 técnica de imagencon lesión hipervascular mayor de 2 cm asociado a AFPmayor de 400 ng/ml. Pacientes: 85 pacientes diagnosticados deHCC en el Hospital Donostia entre los años 2003 y 2005. Datosanalizados: información demográfica (sexo, edad), factores deriesgo (alcohol, virus de hepatitis, hemocromatosis, otras enfermedadesasociadas), e información clínica (etiología de la hepatopatía,estadio de Child-Pugh, determinación de AFP, hallazgos radiológicos,criterios de resecabilidad, tratamiento recibido,evolución). Se divide la muestra en dos grupos según hubieran seguidoo no un programa de cribado.Resultados: el 70% de los pacientes del grupo de cribado sediagnostican en estadio precoz frente al 26,7% del grupo de nocribado (p < 0,05). Trece pacientes no pueden recibir tratamientocurativo a pesar del diagnóstico en fase precoz (9 en el grupo decribado y 4 en el de no cribado). La sensibilidad global del cribadoen nuestra serie es del 95%.Conclusiones: en nuestro medio, el programa de cribado dehepatocarcinoma es eficaz en términos de aplicación de tratamientoscurativos(AU9

Aim: to evaluate whether the current surveillance programs(ultrasonography and alpha-fetoprotein testing every six months)are successful in detecting patients in the early stages.Material and methods: the health records of all patientsdiagnosed with hepatocellular carcinoma in Donostia Hospitalbetween 2003 and 2005 were reviewed retrospectively. Eightyfivepatients (11 women and 74 men) were included in the studyand demographic data, risk factors and clinical data were obtained.Patients were split into two groups according to whether ornot they had been included in a surveillance program.Results: seventy per cent of patients of the surveillance groupis diagnosed in early stage opposite to 26.7% of patients in nosurveillance group (p < 0.05). Thirteen patients cannot receivecurative treatment in spite of the diagnosis in early stage (9 in thesurveillance group and 4 in the no surveillance group. The globalsensibility of the surveillance program in our series is 95%.Conclusions: current hepatocellular carcinoma surveillanceprograms, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programsresult in the detection of hepatocellular carcinoma in itsearly-stages, when potentially curative treatment may be offered(AU)

Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options.

AIM: to evaluate whether the current surveillance programs (ultrasonography and alpha-fetoprotein testing every six months) are successful in detecting patients in the early stages. MATERIAL AND METHODS: the health records of all patients diagnosed with hepatocellular carcinoma in Donostia Hospital between 2003 and 2005 were reviewed retrospectively. Eighty-five patients (11 women and 74 men) were included in the study and demographic data, risk factors and clinical data were obtained. Patients were split into two groups according to whether or not they had been included in a surveillance program. RESULTS: seventy per cent of patients of the surveillance group is diagnosed in early stage opposite to 26.7% of patients in no surveillance group (p < 0.05). Thirteen patients cannot receive curative treatment in spite of the diagnosis in early stage (9 in the surveillance group and 4 in the no surveillance group. The global sensibility of the surveillance program in our series is 95%. CONCLUSIONS: current hepatocellular carcinoma surveillance programs, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programs result in the detection of hepatocellular carcinoma in its early-stages, when potentially curative treatment may be offered.

Porfiria cutánea tarda: asociación con mutaciones HFE, hepatitis virales, alcohol y otros factores de riesgo en Guipúzcoa, País Vasco / No disponible

Objetivo: estudiar la frecuencia de las mutaciones en el genHFE (C282Y, H63D, S65C) en un grupo de 54 pacientes conporfiria cutánea tarda (PCT) y en un grupo de controles sanos (donantesde sangre) en Guipúzcoa. También analizar su relación conlos virus de la hepatitis B y C (VHB, VHC), alcohol y otros factoresde riesgo reconocidos.Métodos: el análisis de las mutaciones se hizo mediante PCR.Se compararon las frecuencias alélicas y genotípicas. Se determinaronla probabilidad y el test de Chi cuadrado.Resultados: no encontramos asociación entre C282Y y PCT(5,76 vs. 5% controles). Se observó una alta frecuencia alélica enla mutación H63D en PCT (34,25%), pero sin ser estadísticamentesignificativa (controles 29,31%), debido a la alta prevalencia deesta mutación en la población vasca. La mutación S65C fue menoren PCT que en controles. Encontramos una idéntica presenciade H63D en heterocigosis en ambos grupos (38,8 vs. 38,8%).La asociación con el VHC se objetivó en el 35,18% de los pacientesy la infección por VHB en el 7,4%. Un 55,55% de los pacientestenía un hábito alcohólico de más de 60 g etanol día. Todoseran negativos para el virus de la inmunodeficiencia humana (VIH)y 1 de las 5 mujeres con PCT tomaba estrógenos.Conclusión: las mutaciones C282Y y H63D no tienen un papelrelevante en los pacientes con PCT en Guipúzcoa. Los factoresexternos (consumo importante de alcohol y VHC) parecen jugarun papel fundamental en el desarrollo de la PCT en nuestrapoblación

Aim: to study the frequency of HFE gene mutations (C282Y,H63D, S65C) in a group of 54 sporadic PCT patients and in agroup of healthy controls (blood donors) from Guipúzcoa, Spain.We studied the association of PCT with HCV, HBV, alcohol abuse,and other established risk factors.Methods: the analysis of mutations was made by PCR. Allelicand genotypic frequencies were compared. Probability was determinedand a Chi-squared test was performed.Results: no association was observed between C282Y mutationand PCT (5.76 vs. 5% in controls). A high H63D mutationfrequency was observed in PCT (34.25%) but was not statisticallysignificant (controls 29.31%) because of the high prevalence ofthis mutation in the Basque general population. The S65C mutationwas lower in PCT than in controls. There is a similar presencefor H63D heterozygosis in PCT (38.8 vs. 38.8%). HCV associationwas observed in 35.18% of patients with PCT. HBVinfected 7.4% of patients. Heavy alcohol intake (> 60 g/day) waspresent in 55.55% of patients. No HIV-infected patients were detected.The study of other risk factors revealed only one of the fivewomen with PCT taking estrogens.Conclusion: our results found no relevant role for C282Yand H63D mutations. External factors such as HCV and alcoholcould be determinant in the development of PCT in the Basquepopulation

Utilidad de los diferentes métodos no invasivos de predicción de fibrosis hepática en pacientes del País Vasco con hemocromatosis fenotípica / No disponible

Objetivo: determinar si el producto de la edad por la concentraciónde hierro hepático (índice de fibrosis) y los valores de plaquetas,ferritina y transaminasas están relacionados con el riesgode padecer fibrosis avanzada (F >= 3) en hemocromatosis.Métodos: estudio retrospectivo de 32 pacientes con hemocromatosishereditaria con expresión fenotípica. Todos los pacientesfueron biopsiados obteniéndose la concentración de hierrohepático.Resultados: en 7 pacientes se realizó RM (1,5T) con obtenciónde concentración de hierro hepático (protocolo de Alustiza).Biopsia hepática: en 23 pacientes fibrosis 0-2; en 9 fibrosis 3-4.El índice de fibrosis mostró una especificidad del 68%, sensibilidaddel 85,7%, VPP del 42,8% y VPN del 94,4% para fibrosis avanzada.La cifra de plaquetas (< 200.000) reveló un VPN 94,4%,ferritina (> 1.000) VPN 75% y el índice de fibrosis por RMN (puntocorte 480.000) VPN 80%. La combinación de los mismos, elíndice de fibrosis (por biopsia o por RM) con las transaminasas ylas plaquetas con las transaminasas, reveló un VPN del 100%.Conclusiones: el índice de fibrosis (> 480.000) y las plaquetas(< 200.000) tienen la mayor sensibilidad para predecir fibrosisde alto grado. Un resultado negativo en ambos permite descartarfibrosis significativa en el 94% de los casos. La RM permite unabuena predicción de fibrosis

Objective: to determine whether the product of multiplyingage by liver iron concentration (LIC) (fibrosis index; cut-off,480,000), platelets, transaminases, and ferritin values are relatedto the risk of high grade fibrosis.Methods: a retrospective study of 32 patients with hereditaryhemochromatosis (HH) with phenotypic expression. All patientshad a liver biopsy with LIC.Results: in 7 patients a magnetic resonance imaging (MRI)scan (1.5 T) was obtained with LIC following Alustiza’s protocol.Liver biopsy: fibrosis grade (F) 0-2 in 23 patients; F 3-4 in 9. Fibrosisindex (FI) showed a specificity of 68%, sensitivity of 85.7%,positive predictive value (PPV) of 42.8%, and negative predictivevalue (NPV) of 94.4% for high-grade fibrosis. Platelet count(< 200,000) revealed a NPV of 94.7% for F3-4. Aspartatetransaminase (AST) levels above the upper limit of normal showeda NPV of 94.4%; ferritin levels (> 1,000) a NPV of 75%, andMRI-derived LIC x age (> 480,000) a NPV of 80%. The combinationof FI (either by biopsy or MRI) with transaminases, and ofplatelets with transaminases revealed a NPV of 100%.Conclusions: FI > 480,000 and platelets < 200,000 havethe highest sensitivity for high-degree fibrosis prediction. A negativeresult allows to discard significant fibrosis in 94% of cases.MRI allows a good fibrosis prediction

[Utility of various non-invasive methods for fibrosis prediction among Basque Country patients with phenotypic hemochromatosis]. / Utilidad de los diferentes métodos no invasivos de predicción de fibrosis hepática en pacientes del País Vasco con hemocromatosis fenotípica.

OBJECTIVE: To determine whether the product of multiplying age by liver iron concentration (LIC) (fibrosis index; cut-off, 480,000), platelets, transaminases, and ferritin values are related to the risk of high grade fibrosis. METHODS: A retrospective study of 32 patients with hereditary hemochromatosis (HH) with phenotypic expression. All patients had a liver biopsy with LIC. RESULTS: In 7 patients a magnetic resonance imaging (MRI) scan (1.5 T) was obtained with LIC following Alustiza's protocol. Liver biopsy: fibrosis grade (F) 0-2 in 23 patients; F 3-4 in 9. Fibrosis index (FI) showed a specificity of 68%, sensitivity of 85.7%, positive predictive value (PPV) of 42.8%, and negative predictive value (NPV) of 94.4% for high-grade fibrosis. Platelet count ( < 200,000) revealed a NPV of 94.7% for F3-4. Aspartate transaminase (AST) levels above the upper limit of normal showed a NPV of 94.4%; ferritin levels (> 1,000) a NPV of 75%, and MRI-derived LIC x age (> 480,000) a NPV of 80%. The combination of FI (either by biopsy or MRI) with transaminases, and of platelets with transaminases revealed a NPV of 100%. CONCLUSIONS: FI > 480,000 and platelets < 200,000 have the highest sensitivity for high-degree fibrosis prediction. A negative result allows to discard significant fibrosis in 94% of cases. MRI allows a good fibrosis prediction.

[Porphyria cutanea tarda. An analysis of HFE gene mutations, hepatitis viruses, alcohol intake, and other risk factors in 54 patients from Guipúzcoa, Basque Country, Spain]. / Porfiria cutánea tarda: asociación con mutaciones HFE, hepatitis virales, alcohol y otros factores de riesgo en Guipúzcoa, País Vasco.

AIM: To study the frequency of HFE gene mutations (C282Y, H63D, S65C) in a group of 54 sporadic PCT patients and in a group of healthy controls (blood donors) from Guipúzcoa, Spain. We studied the association of PCT with HCV, HBV, alcohol abuse, and other established risk factors. METHODS: The analysis of mutations was made by PCR. Allelic and genotypic frequencies were compared. Probability was determined and a Chi-squared test was performed. RESULTS: No association was observed between C282Y mutation and PCT (5.76 vs. 5% in controls). A high H63D mutation frequency was observed in PCT (34.25%) but was not statistically significant (controls 29.31%) because of the high prevalence of this mutation in the Basque general population. The S65C mutation was lower in PCT than in controls. There is a similar presence for H63D heterozygosis in PCT (38.8 vs. 38.8%). HCV association was observed in 35.18% of patients with PCT. HBV infected 7.4% of patients. Heavy alcohol intake (> 60 g/day) was present in 55.55% of patients. No HIV-infected patients were detected. The study of other risk factors revealed only one of the five women with PCT taking estrogens. CONCLUSION: Our results found no relevant role for C282Y and H63D mutations. External factors such as HCV and alcohol could be determinant in the development of PCT in the Basque population.

Ulceración y estenosis del duodeno como forma de presentación de enfermedad celiaca / No disponible

No disponible

Selective sphincteroplasty of the papilla in cases at risk due to atypical anatomy.

AIM: To analyze the indications, efficacy and safety of sphincteroplasty in our centre. METHODS: A retrospective study of sphincteroplasty in 53 cases of papilla at high risk was performed in 2004-2006. The procedure consisted of duodenoscopy with Olympus TJF 145 Videoduodenoscope, approach to the biliary tract using a catheter with a guidewire, and dilatation of the papilla with a dilatation balloon catheter using a syringe with a manometer for control of the filling pressure. RESULTS: The indications included intradiverticular papilla in 26 patients (49%), stenosis of a previous sphincterotomy in 19 patients (35.8%), small size of the papilla in 4 patients (7.5%), Billroth II gastrectomy in 3 patients (5.6%), and coagulopathy in one patient (1.9%). The efficacy was 97.8%, with all the calculi extracted from the common bile duct in 84.4% of the patients, even though 21 of the patients (39.6%) had calculi with a diameter equal to or greater than 10 mm. Seven patients (13.2%) presented complications: haemorrhage in 1 patient (1.9%) and mild pancreatitis in 6 patients (11.3%). The mean hospital stay in case of complications was of 3 +/- 0.63 d. CONCLUSION: Sphincteroplasty is highly effective, with a complication rate similar to that of sphincterotomy, furthermore, the complications are of low clinical importance. The use of the 10 mm balloon makes it possible to extract calculi with a diameter of over 15 mm and to extract more than 3 calculi without increasing the rate of complications and reduces the need to resort to lithotripsy or rescue sphincterotomy.

Cirrosis biliar primaria y eosinofilia: regresión tras tratamiento con ácido ursodesoxicólico / Primary biliary cirrhosis and eosinophilia: regression after treatment with ursodeoxycholic acid

No disponible

Cirrosis biliar primaria y eosinofilia: regresión tras tratamiento con ácido ursodesoxicólico / Primary biliary cirrhosis and eosinophilia: regression after treatment with ursodeoxycholic acid

No disponible

Hepatitis autoinmunitaria en paciente afectada de uveítis / Autoimmune hepatitis in a patient with uveitis

No disponible