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.

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.

Antibodies to hepatitis C virus: a cross-sectional study in patients attending a trauma unit or admitted to hospital for elective surgery.

OBJECTIVE: To assess the prevalence of hepatitis C virus (HCV) antibodies in patients attending a trauma unit or admitted to hospital for elective surgery, and to identify risk factors for acquiring HCV infection. DESIGN: A cross-sectional study. SETTING: The emergency room of a Department of Orthopaedic Surgery and a hospital for elective (non-digestive) surgery. PATIENTS: A study population of 1824 subjects (mean age 40.1 +/- 18.1 years) and sera from a control group of 4703 blood donors giving their first donation. INTERVENTIONS: Serum samples were screened for HCV antibodies by second-generation enzyme-linked immunosorbent assays and recombinant immunoblot assays. MAIN OUTCOME MEASURES: HCV serostatus and the relationship between anti-HCV-positivity and age, intravenous drug use, tattoos, blood transfusion, a history of hepatitis and exposure to a contact who had had hepatitis. RESULTS: The overall prevalence of anti-HCV antibodies was 2.85% in the study population and 0.5% among blood donors (chi 2 = 64.5; P < 0.0001). Anti-HCV-positivity was more common in men (3.8 versus 1.9%; P < 0.05) and in subjects with history of hepatitis (13.5 versus 2.0%; P < 0.001), exposure to a contact who had had hepatitis (12.5 versus 1.9%; P < 0.001), blood transfusion (7.8 versus 2.3%; P < 0.001), tattoos (36 versus 2.4%; P < 0.001) and intravenous drug use (85.7 versus 1.9%; P < 0.001). However, one third of subjects had no risk factors for HCV infection. The logistic regression analysis confirmed a statistically significant association (P < 0.05) between anti-HCV-positivity and intravenous drug use, tattoos, blood transfusion, a history of hepatitis and exposure to a contact who had had hepatitis. CONCLUSIONS: These results show almost a five-fold higher prevalence of anti-HCV among patients attending a trauma unit or admitted to hospital for elective surgery than among blood donors.

[Mentally deficient patients and infection caused by hepatitis B virus. Prevalence in our area]. / Los deficientes mentales y la infección por el virus de la hepatitis B. Prevalencia en nuestro medio.

To assess the prevalence of hepatitis B virus (HBV) infection in medium level mentally impaired patients (MIP), 620 MIP were evaluated; 181 of them had Down's syndrome and were active inmated of open institutions. At the time of the study, 28.7% had some positive serum marker of HBV infection, and 5.8% were virus carriers. The highest rate of seropositive individuals (48%) was found in male MIP with Down's syndrome. The rate of seropositive individuals was higher among those MIP who had attended special education centers than in those who had not. The tendency to remain as HBV carrier was higher in males with Down's syndrome. Our results confirm the need for prophylaxis in this population.

[Response to recombinant DNA antihepatitis B vaccine in mentally retarded patients with Down's syndrome. A controlled study]. / Respuesta a la vacuna DNA recombinada antihepatitis B en los deficientes mentales con síndrome de Down. Estudio controlado.

To investigate the response of mentally retarded individuals (MR) with Down's syndrome (Down-MR) to recombinant hepatitis B vaccine, three doses (20 micrograms per dose) were administered on the usual schedule (months 0, 1 and 6) to two groups of MR with mean age of 14.6 years. The first group consisted of 32 MR-Down. The second group consisted of 35 MR other etiologies (non Down-MR). Both had the same sex distribution and similar ages and weight/height index. The post vaccination anti-HBs titers were measured on months 1, 2, 6 and 8. The results could be analysed in 63 MR. Eight months after vaccination, 100% of Down-MR and 91% of non Down-MR developed a response to the vaccine (anti-HBs greater than 10 IU/l). Both groups achieved high antibody titers (geometric mean 4.298 and 6.424, respectively). A significant inverse correlation of anti-HBs with age was found, but not with sex of with the weight-height index. It was concluded that Down-MR in young age have a normal response to recombinant hepatitis B vaccine at the usual dose and schedule. Therefore, the goal to suppress the reservoir of hepatitis B in Down-MR both in institutions for MR and in normal schools should be achieved.

[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.

[Follow-up of chronic hepatitis B carriers. Serological course and risk of reactivation]. / Seguimiento del portador crónico de la hepatitis B. Evolución serológica y riesgo de reactivación.

AIM: To investigate serologic changes and risk of reactivation in hepatitis B chronic carriers. PATIENTS AND METHODS: Two hundred chronic HBs-Ag positive patients were included (follow-up greater than 18 months). According to the HBeAg/Anti-HBe status at the moment of inclusion they were classified in 3 groups: I: 40 patients HBeAg positive, II: 158 anti-HBe positive and III: 2 HBeAg/Anti-HBe negatives. All patients were screened in the follow-up for biochemical test, hepatitis B, C and D virus serology, DNA.HBV by hybridization, alpha fetoprotein and abdominal ultrasound. RESULTS: Mean age was 35 +/- 12 years (14-61), and mean follow-up 71 +/- 35.1 months (18-252). In the follow-up 28 patients in group I seroconverted HBeAg/Anti-HBe, 18 spontaneously (annual rate 10%). In group II four patients out off 158 were DNA HBV positive. Only 3 chronic HBV carriers lost HBsAg and developed Anti-HBs (annual rate 0,25%). Reactivation of viral activity was detected in 13 patients Anti-HBe positive, DNA.HBV negative. HBeAg appeared during reactivation in six, both HBeAg/Anti-HBe were negative in one, and six were unchanged. Reactivation was significantly more frequent in chronic carriers with high GPT activity (13 out off 75, 17.3%) than in patients with normal GPT (0 out off 107, 0%) (p < 0.0005). CONCLUSIONS: Reactivation of HBV activity is frequent in HBsAg chronic carriers Anti-HBe positive, DNA.HBV negative and who are abnormal GPT levels; these patients should be considered at risk of reactivation. The control in the follow-up of HBV chronic carriers with persistently normal GPT, without advanced liver disease, may not be so frequent. The increased infectiousness during reactivation of HBV activity must be taken account for prophylaxis of HBV infection in chronic carriers contacts.

[Somatostatin in the treatment of pancreatic ascites]. / La somatostatina en el tratamiento de la ascitis pancreática.

We present the case of a patient with alcoholic chronic pancreatitis who developed pancreatic ascites. The analysis of ascitic fluid was diagnostic; and ERCP showed one fistula in the pancreatic head to the peritoneal cavity. The patient was treated by continuous somatostatin infusion (250 micrograms/h) for 15 days resulting in the disappearance of the ascites and avoiding the risky surgical therapy.

[Liver abscess caused by Streptococcus anginosus]. / Abscesos hepáticos por Streptococcus anginosus.

Pyogenic liver abscess is a relatively rare disease, often concerning elderly patients in bad general condition and with underlying diseases. We report the case of a 77-year-old female with gastric cancer and liver abscesses by Streptococcus anginosus.