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.

Situación actual. Perspectivas y vacunación / Current situation. Perspectives and vaccination

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Mixed cryoglobulinaemia in patients with chronic hepatitis C infection: prevalence, significance and relationship with different viral genotypes.

In order to analyse the prevalence and significance of cryoglobulinaemia in patients with chronic hepatitis C virus (HCV) infection and the possible relationship of cryoglobulinaemia with the genotypes of HCV, we studied 89 patients with chronic HCV infection, 42 healthy controls and 22 patients with alcoholic cirrhosis. The patients with HCV were divided into three different groups according to the presence of cirrhosis and alanine aminotransferase levels. Moreover, in 20 patients with HCV and cryoglobulinaemia, HCV RNA sequences were quantified in serum and in cryoprecipitate. Cryoglobulins were detected more frequently in patients with chronic HCV infection than in healthy controls (42.6% vs. 4.7%; P<0.0001). Cryoglobulins were present in 68.4% of patients with HCV-related cirrhosis, which was nearly twice the figure in noncirrhotic HCV-infected patients and alcoholic cirrhotic patients. There were no differences in age, sex, aminotransferase levels or HCV genotype distribution in HCV-infected patients with or without cryoglobulinaemia. Only 13% of patients with chronic HCV infection and cryoglobulins showed symptoms of cryoglobulinaemia. There was a linear association between HCV RNA concentration in sera and in cryoprecipitates (P<0.0005). Patients with chronic HCV infection had a high prevalence of cryoglobulinaemia, especially in advanced forms of the disease, but clinical findings are few. There was no relationship with the genotype of HCV. The presence of HCV RNA in cryoprecipitates supported the hypothesis on the aetiological role of HCV in mixed cryoglobulinaemia.

Late disappearance of hepatitis C virus RNA from peripheral blood mononuclear cells in patients with chronic hepatitis C in sustained response after alpha-interferon therapy.

OBJECTIVE: We aimed to investigate the modifications of HCV RNA (genomic and antigenomic strands) in peripheral blood mononuclear cells (PBMCs) of long-term responder patients to alpha-interferon therapy, and their usefulness as criteria of definitive HCV eradication. METHODS: We studied 10 patients with chronic hepatitis C with > 1 yr of sustained response after alpha-interferon therapy (normal alanine aminotransferase [ALT] and negative serum HCV RNA). Serum HCV RNA and genotyping were determined. Approximately 2 and 4 yr after completion of treatment we investigated the presence of HCV RNA (genomic and antigenomic strands) in PBMCs. Eight of 10 patients were rebiopsed 2 yr after discontinuation of treatment. RESULTS: The mean follow-up was 46.6 +/- 4.6 months (range, 39-51 months). In this period, all patients remained in sustained response. In the first determination, all patients had HCV RNA genomic strands and two patients had antigenomic strands detectable in PBMCs. Two years later only two patients had genomic and none had antigenomic strands detectable. After 4 yr of sustained response, eight of 10 patients lost HCV RNA from PBMCs. CONCLUSIONS: In the long-term follow-up, the majority of patients with chronic hepatitis C with sustained response after alpha-interferon therapy progressively lost HCV RNA from PBMCs. This determination in PBMCs is not a predictor of response.

[Cholestatic acute hepatitis induced by amoxycillin-clavulanic acid combination. Role of ursodeoxycholic acid in drug-induced cholestasis]. / Hepatitis colestásica aguda secundaria a amoxicilina-ácido clavulánico. Papel del ácido ursodesoxicólico en la colestasis inducida por drogas.

We report two cases of acute hepatotoxicity after treatment with amoxicillin-clavulanic. Viral hepatitis serology and autoantibodies were negative. Biliary tree obstruction and other etiologies were excluded. After discontinuation of the drug the evolution was favorable with clinical improvement and normalization of liver tests. Liver biopsy made in one patient showed cholestasic hepatitis with hepatocellular necrosis and other patient was treated with ursodeoxycholic. Also, we analyse potential utility of ursodeoxycholic acid administration in toxic cholestasis.

Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.

BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C. METHODS: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated. RESULTS: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05). CONCLUSIONS: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

Helicobacter pylori infection: a seroepidemiological study in Gipuzkoa, Basque Country, Spain.

Helicobacter pylori is one of the most common bacterial infections worldwide. To evaluate the prevalence of this infection in Gipuzkoa (Basque Country, Spain) we studied the presence of antibodies against Helicobacter pylori (HPAb) using a second-generation EIA (Cobas Core). The study was performed on two groups of subjects: a middle-class group, 2-78 years-old (n = 1335) and a group of slum dwellers, 2-15 years-old (n = 89). In the middle-class group the prevalence of HPAb in children under 6 was 3.1% (3/96); the prevalence was significantly greater in older compared to younger age groups, reaching 84.3% (102/121) in adults 50-59 years. The geometric mean of the titer in seropositive subjects was also greater in older age groups. By logistic regression analysis the prevalence of HPAb was associated with age, educational level and geographic origin but not with sex, smoking, alcohol consumption, or use of nonsteroid anti-inflammatory drugs. The prevalence of HPAb was much higher in the slum-dwelling group 2-15 years-old (55.5% of children 2-5 years-old). The results indicate that H. pylori infection was more common in adult people from our geographic region than in those from other developed countries and show that socioeconomically deprived children constitute at present a group at high risk of acquiring infection in our region.