Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were prospectively screened for HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. In addition, 137 patients undergoing cardiac surgery (non-HTR) and 537 healthy subjects were studied cross-sectionally. The anti-HEV-IgG seroprevalence was 11% in HTR, 7% in non-HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non-HTR vs. healthy controls p<0.01). Anti-HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV-PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined.

Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration. Because of the low incidence of ALF, however, the molecular mechanisms of liver dysfunction and regeneration are largely unknown. In this study, we investigated the role of apoptosis and caspases in 70 ALF patients using novel biomarkers that allow the detection of caspase activation in serum samples. Compared with healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF revealed a significantly higher activation of caspases than patients that required transplantation or died, although in the latter patients extensive DNA fragmentation and signs of nonapoptotic cell death were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), important cytokines involved in liver regeneration. Conclusion: Our data suggest that caspase activation and apoptosis are involved in ALF of patients with spontaneous recovery, whereas caspase-independent cell death might be more relevant in irreversible forms of liver failure. These findings might be important for therapeutic options of ALF but also suggest that measurement of caspase activation might be of prognostic value to predict the outcome of acute liver failure. (HEPATOLOGY 2008;47:1624-1633

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Patients' perceptions of immunosuppression-related symptom experience impact on quality of life and medication adherence. Using The Modified Transplant Symptom Occurrence and Symptom Distress Scale capturing items on symptom occurrence and symptom distress, 261 heart transplant recipients reported on their symptom experiences. Symptoms occurring with the highest prevalence were tiredness, lack of energy, and nervousness. Men showed erectile dysfunction causing the most distress. Women and younger patients reported significantly higher levels of symptom distress. Distress levels increased with time after transplant. Investigating responses to immunosuppression-related symptom experiences should help develop interventional methods to support long-term outcome.

The safety and efficacy of ivabradine applied in heart transplant (HTx) recipients with permanent sinus tachycardia (PST) has been depicted in previous short-term follow-up studies. We sought to investigate the long-term impact of ivabradine in this patient population. From May to November 2006, 29 HTx recipients with PST, who exhibited either contraindications or intolerance of beta-blocker medication or insufficient heart rate (HR) reduction on beta-blocker treatment, first received oral ivabradine treatment (5 mg bid). Ivabradine treatment was discontinued in three patients due to adverse events within the first week. In the remaining 26 patients, resting HR was significantly lowered from 106.8 ± 9.2 at baseline to 83.2 ± 5.1 bpm after 3 months (p < 0.001). This effect remained stable in the long-term follow-up (82.1 ± 11.8 bpm after 4 years), whilst blood pressure was not affected. Apart from the corrected QT interval (QTc), there were no significant changes in ECG. The elongated QTc at baseline (469.4 ± 29.5 ms) decreased to 444.3 ± 33.1 ms after 3 months ivabradine treatment (p < 0.001). A decrease in QTc until month 9 was observed, followed by a partial increase to the upper limit of the normal value. Neither allograft rejection nor changes in left ventricular ejection fraction were observed over the follow-up period. In conclusion, ivabradine appears to be a safe and feasible long-term therapeutic option for HTx recipients with PST. It reduced the resting HR without impairment of blood pressure, myocardial contractility and cardiac conduction. The prognostic value of normalised QTc following ivabradine administration requires further observation.