Survival after locoregional treatments for hepatocellular carcinoma: a cohort study in real-world patients.

Evidence of relative effectiveness of local treatments for hepatocellular carcinoma (HCC) is scanty. We investigated, in a retrospective cohort study, whether surgical resection, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial embolization with (TACE) or without (TAE) chemotherapy resulted in different survival in clinical practice. All patients first diagnosed with HCC and treated with any locoregional therapy from 1998 to 2002 in twelve Italian hospitals were eligible. Overall survival (OS) was the unique endpoint. Three main comparisons were planned: RFA versus PEI, surgical resection versus RFA/PEI (combined), TACE/TAE versus RFA/PEI (combined). Propensity score method was used to minimize bias related to non random treatment assignment. Overall 425 subjects were analyzed, with 385 (91%) deaths after a median followup of 7.7 years. OS did not significantly differ between RFA and PEI (HR 1.11, 95% CI 0.79-1.57), between surgery and RFA/PEI (HR 0.95, 95% CI 0.64-1.41) and between TACE/TAE and RFA/PEI (HR 0.88, 95% CI 0.66-1.17). 5-year OS probabilities were 0.14 for RFA, 0.18 for PEI, 0.27 for surgery, and 0.15 for TACE/TAE. No locoregional treatment for HCC was found to be more effective than the comparator. Adequately powered randomized clinical trials are still needed to definitely assess relative effectiveness of locoregional HCC treatment.

Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.

Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.

Pulmonary sarcoidosis during interferon therapy: a rare or underestimated event?

Interferon (IFN)-alpha with or without ribavirin is the treatment of choice for patients with chronic HCV-related hepatitis. Cough and dyspnea during IFN therapy are often regarded as a side effect and not as a possible sign of the onset of a pulmonary interstitial disease. It may therefore be claimed that the likelihood that patients treated with IFN develop sarcoidosis is being underestimated. Although they are not conventionally classified as etiopathologic agents of sarcoidosis, the IFNs have been proven to be capable of triggering macrophages and of promoting the expression of class II HLA antigens. It is therefore possible that IFN-alpha treatment could trigger macrophages and promote the polarization of the immune response towards Th1 in the presence of particular susceptibility conditions, thus starting the series of events that lead to the onset of sarcoidosis. We describe a case of pulmonary sarcoidosis in a 33-year-old patient treated with IFN-alpha2b and ribavirin for chronic HCV-related hepatitis after 6 months of therapy. The case we report here brings forth the issue of a possible underestimation of the real incidence of sarcoidosis during IFN therapy and highlights the need for more attention to and a more careful evaluation of respiratory symptoms manifesting in treated patients.

The efficacy of liver biopsy under ultrasonographic guidance on an outpatient basis.

OBJECTIVE: To evaluate the safety and compliance of outpatient echo-guided liver biopsy (ELB) when compared to those performed on inpatients (IP). METHODS: From June 1996 to November 2000, we carried out 418 ELB on patients with diffuse liver disease: 246 inpatients (IP ELB) and 172 in a Day Hospital setting (DH ELB). The same inclusion and exclusion criteria were followed for both groups of patients, performing the same echo-guided intercostal liver biopsy with free-hand technique and post biopsy assessment with colordoppler examination; post biopsy follow-up consisted of 6-h bed rest and blood pressure and heart rate monitoring up to discharge. DH patients were discharged 8 h after biopsy, if they did not live further than a 30-min trip from the hospital. In both groups, the following data was evaluated: death rate, sample adequacy, number of passages, major and minor complications, pain score. RESULTS: The data analysed in our series show that ELB DH presents no fundamental differences in morbidity and mortality when compared to ELB IP.