Ramipril-induced liver injury: case report and review of the literature.

BACKGROUND: Ramipril, an inhibitor of the angiotensin-converting enzyme (ACEI), is a drug commonly used in the therapy of hypertension. ACEI-induced hepatotoxicity is rare, and most of the reported cases are associated with captopril. Here, we present the first case of ramipril-induced liver injury proven by positive rechallenge and a review of the literature including the data from the US Food and Drug Administration adverse event reporting system (FAERS). METHODS: Patient data were collected in the Berlin Case-Control Surveillance Study for adverse drug reactions. PubMed research on ACEI-induced hepatotoxicity included all ACEIs except captopril; analysis of the FAERS database focused on ramipril-induced hepatotoxicity in the period 2009-2011. RESULTS: A 40-year-old male patient presented with acute onset jaundice and highly (>20-fold increase of alanine aminotranferase (ALT)) elevated liver enzymes (LEs). Viral or autoimmune hepatitis and biliary etiology were ruled out. Withdrawal of several medications including ramipril resulted in an immediate decrease in LEs, whereas a subsequent re-exposure with ramipril resulted in a striking increase in LEs (>35-fold increase of ALT). After definitely discontinuing ramipril, a rapid decline in LEs was observed, suggesting a certain causal relationship between drug intake and hepatic damage. Analysis of the FAERS database retrieved 65 cases of ramipril-associated hepatotoxicity, with jaundice being the most frequent hepatic adverse event. PubMed research detected 23 relevant publications, with enalapril being the ACEI most commonly reported as being associated with liver injury. CONCLUSIONS: ACEI-induced hepatotoxicity is rare. Our case confirms a hepatotoxic potential of ramipril, highlighting the need for alertness among physicians regarding this matter.

Ribavirin treatment of acute and chronic hepatitis E: a single-centre experience.

BACKGROUND: The role of ribavirin for treatment of severe acute or chronic hepatitis E virus (HEV) infection is not well defined. AIMS: To investigate the applicability and efficacy of ribavirin therapy in acute and chronic HEV infections within a large single-centre cohort. MATERIALS & METHODS: Clinical courses of forty-four German HEV-infected individuals were analysed. RESULTS: In a prospective case series, we observed spontaneous recovery from acute symptomatic HEV-infection in 10/11 immunocompetent individuals. Ribavirin therapy was initiated in one patient with severe acute HEV-genotype-1e infection who rapidly improved liver function and cleared HEV. Of 15 organ transplant recipients with prolonged HEV viraemia, reduction in immunosuppression led to HEV-clearance in three patients, while ribavirin therapy was initiated in 11 subjects. A rapid response with undetectable HEV-RNA occurred in nine subjects. One patient died after experiencing a virological breakthrough associated with ribavirin dose reduction because of severe anaemia. DISCUSSION: Ribavirin is a safe treatment option for HEV infections. However, the optimal dose of ribavirin for the treatment of chronic hepatitis E remains to be determined as treatment failure may occur.

Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system.

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults. Its established first-line adjuvant treatment is radiotherapy in combination with temozolomide (TZM). Hematotoxicity is listed as a frequent adverse drug reaction in the US prescribing information and hepatotoxicity has been reported infrequently in the postmarketing period. We here present the case of a patient diagnosed with GBM who developed severe sustained cholestatic hepatitis following treatment with TZM. The cholestasis was not reversible after withdrawal of TZM during 6 months before the patient's death. Another 2 published case reports of sustained cholestasis following TZM treatment were identified; however, the sustained nature of cholestasis was not emphasized in these reports. Sixteen cases of cholestatic hepatitis/cholestasis associated with TZM were identified in the FDA spontaneous reporting system between 2007 and 2010. Information on the course of the cholestasis in these cases could not be retrieved. In the literature there are other published reports of hepatotoxicity associated with TZM that have reported reversibility upon withdrawal of the drug. Thus, TZM appears to cause different types of hepatotoxicity. Particular attention should be paid to sustained cholestasis as a very serious type of TZM-associated liver toxicity.

Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study.

Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150). End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively. In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation were 94% and 89%, respectively. A maximum alanine aminotransferase level of more than 500 U/L prior to therapy was the only factor associated with successful treatment. In conclusion, in acute HCV infection, early treatment with peginterferon alpha-2b leads to high virological response rates in individuals who are adherent to treatment. The high number of dropouts underlines the importance of thorough patient selection and close monitoring during therapy. Thus, future studies should identify factors predicting spontaneous viral clearance to avoid unnecessary therapy.