Hepatitis G and C Viruses Respond to Interferon-α with Different Virologic Kinetics

The aim of this work was to specify the timecourse of response to interferon (IFN) of hepatitis Gvirus (HGV) and hepatitis C virus (HCV) in coinfectedindividuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C,was screened for the presence of both HGV and HCV RNAsto select seven coinfected patients. Spontaneousrecovery from HGV infection was excluded through the detection of antibodies to the envelope-2protein of HGV and HCV isolates were genotyped. Withinthree months of treatment, we found that HGV RNA wastransiently cleared in 6/7 patients, but the rate of long-term favorable response was very low(1/7). In addition, considering the same individualsseparately, it was shown that HGV and HCV responded toIFN with different kinetics in 5/7 patients. Takentogether, these results underscore the importance of thevirological basis of the resistance to IFNtreatment.     

Liver inflammatory cells, apoptosis, regeneration and stellate cell activation in non-alcohol steatohepatitis

Background, The pathogenesis of non-alcoholic steatohepatitis remains unclear from several points of view. Minimal diagnostic criteria are still not defined. Aim. To gather information useful for diagnosis and to improve the understanding of pathogenic mechanisms.

Patients. A series of 14 patients with non-alcoholic steatohepatitis, identified among liver outpatients, were paired for age, sex and alanine amino transferase values with 14 patients with hepatitis C virus infection without steatosis.

Methods. Clinical, biochemical and immunohistological examination, including characterisation of inflammatory cell population, evaluation of type 111 collagen and tenascin deposition, activation of stellate cells, hepatocellular apoptosis and proliferation.

Results. Patients with non-alcoholic steatohepatitis were more frequently obese, had higher triglyceride concentrations and lower gamma-globulins. T lymphocytes outnumbered polymorphonuclear cells, both in hepatitis C and in steatohepatitis, with a larger number of CD8 lymphocytes in patients with viral hepatitis but a comparable number of granulocytes. This resulted in a higher granulocytes to T cells ratio in steatohepatitis, possibly making these cells more easily detectable in spite of similar absolute numbers. Portal fibrosis and piecemeal necrosis were prevalent in hepatitis C virus infection, pericentral fibrosis was similar. Hepatocellular, apoptosis and proliferation as well as stellate cell activation were less relevant in steatohepatitis than in hepatitis C virus infection in spite of similar alanine amino transferase levels.

Conclusions. These data provide a possible explanation for the relatively low tendency to progression of non-alcoholic steatohepatitis in most patients despite increased alanine amino transferase and suggest that non-death-related release of alanine amino transferase might occur in non-alcoholic steatohepatitis. This makes liver biopsy an essential part of the clinical setting supporting diagnosis, evaluation of severity and possibly definition of the evolutionary trend.     

Different modalities of classification and prognostic significance of ventricular arrhythmias after acute myocardial infarct. Prospective study

In our study we compared the prognostic significance of clinical variables, laboratory results and different classification models of ventricular ectopic beats recorded by means of a pre-discharge 24 hour ambulatory electrocardiographic monitoring, in 210 survivors of acute myocardial infarction. In addition a full multivariate analysis of the factors affecting survival time was carried out using Cox's proportional hazards (multiple) regression model. Multivariate stepwise discriminant analysis identified hypertension, congestive heart failure assessed by Killip class, and the grading system for ventricular arrhythmias as the most important prognostic variables. When Moss grading system for ventricular arrhythmias was used, the relative risk was a superior as heavy Moss grading system (Moss 2 vs Moss 1 and Moss 3-4 vs Moss 1, relative risk = 1.2 and 3.6 total death, respectively). Furthermore, the hazard ratio of Moss grading system was higher utilizing as comparison patients without ventricular ectopic beats (relative risk = 1.7 for Moss 2 and 5.3 for Moss 3-4) than patients with ventricular ectopic beats less than one/hour (relative risk = 1.2 for Moss 2 and 3.7 for Moss 3-4). Thus, in survivors of acute myocardial infarction, a rational and useful ventricular ectopic beats categorization includes both frequency and the presence or absence of malignant characteristics.     

ADARRI: a novel method to detect spurious R-peaks in the electrocardiogram for heart rate variability analysis in the intensive care unit

We developed a simple and fully automated method for detecting artifacts in the R-R interval (RRI) time series of the ECG that is tailored to the intensive care unit (ICU) setting. From ECG recordings of 50 adult ICU-subjects we selected 60 epochs with valid R-peak detections and 60 epochs containing artifacts leading to missed or false positive R-peak detections. Next, we calculated the absolute value of the difference between two adjacent RRIs (adRRI), and obtained the empirical probability distributions of adRRI values for valid R-peaks and artifacts. From these, we calculated an optimal threshold for separating adRRI values arising from artifact versus non-artefactual data. We compared the performance of our method with the methods of Berntson and Clifford on the same data. We identified 257,458 R-peak detections, of which 235,644 (91.5%) were true detections and 21,814 (8.5%) arose from artifacts. Our method showed superior performance for detecting artifacts with sensitivity 100%, specificity 99%, precision 99%, positive likelihood ratio of 100 and negative likelihood ratio <0.001 compared to Berntson’s and Clifford’s method with a sensitivity, specificity, precision and positive and negative likelihood ratio of 99%, 78%, 82%, 4.5, 0.013 for Berntson’s method and 55%, 98%, 96%, 27.5, 0.460 for Clifford’s method, respectively. A novel algorithm using a patient-independent threshold derived from the distribution of adRRI values in ICU ECG data identifies artifacts accurately, and outperforms two other methods in common use. Furthermore, the threshold was calculated based on real data from critically ill patients and the algorithm is easy to implement.     

Stress Fractures of the Calcaneus Diagnosed by Sonography: Report of 8 Cases

We present a retrospective review of 8 patients (6 women and 2 men, with an age range of 46–80 years; mean age, 60.2 years) in whom sonography was used to diagnose a calcaneal stress fracture. Sonography was performed because of a clinical suspicion of soft tissue injuries. Two patients were first assessed by standard radiography; for the remaining patients, sonography was the first imaging technique used. Patients were subsequently examined by magnetic resonance imaging, except for 1 patient in whom the diagnosis was made only on a clinical‐sonographic correlation. On sonography, there was thickening of the periosteum and subcutaneous edema in all patients; a calcified bone callus was evident in none of the 8 patients. Cortical irregularities were found in 6 of 8 patients. Color Doppler imaging showed local hypervascular changes of the periosteum in all patients. Sonography, together with clinical findings, can be used to diagnose a calcaneal stress fracture. We suggest that sonologists should include a calcaneal stress fracture in their differential diagnosis in cases of mechanical hind foot pain. They must also include, as a part of every sonographic examination of the ankle, an examination of the calcaneus and be aware of the sonographic appearance of stress fractures. If the diagnosis is still uncertain after the sonographic examination, magnetic resonance imaging should be prescribed.     

Allergic cholestatic hepatitis and exanthema induced by metamizole: verification by lymphocyte transformation test

We report about a 66-year-old-male patient who was hospitalized with generalized exanthema and increase of liver enzymes after intake of metamizole because of flue-like symptoms. Despite initial high dose steroids, disease activity persisted, and therefore liver biopsy was performed. Histology revealed acute hepatitis with perivenular non-bridging confluent necrosis and granuloma formation consistent with drug-induced hepatitis. A metamizole-induced process was suspected. Lymphocyte transformation test confirmed the sensitization of the patient's lymphocytes to metamizole and three of its four metabolites (4-methylaminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine). Other drugs could be excluded with high probability. In the follow-up, the general condition of the patient improved, and liver enzymes decreased under treatment with steroids. Thus, we conclude that in this patient metamizole has induced an allergic reaction not only of the skin but also of the liver. To our knowledge, an allergic cholestatic hepatitis caused by metamizole has been reported only once in literature.