Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods,Quo Vadis?

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale.     

The entire dural sinus tree is compressed in patients with idiopathic intracranial hypertension: a longitudinal, volumetric magnetic resonance imaging study

Introduction  

The objective of this study was to explore the volumetric alterations of dural sinuses in patients with idiopathic intracranial hypertension (IIH).     

Patient Preferences Versus Physicians’ Judgement: Does it Make a Difference in Healthcare Decision Making?

Clinicians and public health experts make evidence-based decisions for individual patients, patient groups and even whole populations. In addition to the principles of internal and external validity (evidence), patient preferences must also influence decision making. Great Britain, Australia and Germany are currently discussing methods and procedures for valuing patient preferences in regulatory (authorization and pricing) and in health policy decision making. However, many questions remain on how to best balance patient and public preferences with physicians’ judgement in healthcare and health policy decision making. For example, how to define evaluation criteria regarding the perceived value from a patient’s perspective? How do physicians’ fact-based opinions also reflect patients’ preferences based on personal values? Can empirically grounded theories explain differences between patients and experts—and, if so, how? This article aims to identify and compare studies that used different preference elicitation methods and to highlight differences between patient and physician preferences. Therefore, studies comparing patient preferences and physician judgements were analysed in a review. This review shows a limited amount of literature analysing and comparing patient and physician preferences for healthcare interventions and outcomes. Moreover, it shows that methodology used to compare preferences is diverse. A total of 46 studies used the following methods—discrete-choice experiments, conjoint analyses, standard gamble, time trade-offs and paired comparisons—to compare patient preferences with doctor judgements. All studies were published between 1985 and 2011. Most studies reveal a disparity between the preferences of actual patients and those of physicians. For most conditions, physicians underestimated the impact of intervention characteristics on patients’ decision making. Differentiated perceptions may reflect ineffective communication between the provider and the patient. This in turn may keep physicians from fully appreciating the impact of certain medical conditions on patient preferences. Because differences exist between physicians’ judgement and patient preferences, it is important to incorporate the needs and wants of the patient into treatment decisions.     

Glucocorticoids activate TGF-β induced PAI-1 and CTGF expression in rat hepatocytes

Background  

In addition to the activation of hepatic stellate cells TGF-β govern apoptosis and growth control of hepatocytes in liver injury. In non-parenchymal cells, TGF-β induces plasminogen activator inhibitor 1 (PAI-1) and connective tissue growth factor (CTGF) expression, which are involved in extra cellular matrix formation. Both genes were also regulated by glucocorticoids, which in certain cases showed antagonistic effects to the TGF-β-Smad 3 pathway. The purpose of our work was to investigate the influence of TGF-β and dexamethasone on PAI-1 and CTGF expression and secretion in primary hepatocytes.     

Early and sustained haemodynamic improvement with levosimendan compared to intraaortic balloon counterpulsation (IABP) in cardiogenic shock complicating acute myocardial infarction

OBJECTIVE: To investigate the haemodynamic effects of levosimendan in patients with cardiogenic shock (CS) complicating acute myocardial infarction in comparison to the effects of intra-aortic balloon counterpulsation (IABP). METHODS: 10 patients with intractable CS under standard therapy (including the use of PCI, inotropes, and vasopressors) received i.v. infusion of levosimendan (bolus 12 microg/kg i.v., followed by continuous infusion 0.1 microg/kg/min for 24 h). Haemodynamic effects were compared to the effects of IABP-placement added to standard care in 12 patients with CS. RESULTS: Within 24 h, both levosimendan and IABP produced a significant increase in cardiac index (CI) and cardiac power index and a decrease in systemic vascular resistance (SVR) (CI [l/min/m2] baseline 1.97+/-0.15, at 24 h 2.82+/-0.22 for levosimendan; baseline 1.98+/-0.17, at 24 h 2.66+/-0.08 for IABP; SVR [dyn*s*cm-5] baseline 1353+/-106, at 24 h 846+/-69 for levosimendan; baseline 1311+/-214, at 24 h 853+/-63 for IABP, respectively). After 3 h of treatment, CI and SVR had significantly improved in patients treated with levosimendan but not in the IABP-group (CI [l/min/m2] at 3 h 2.72+/-0.28 (+38%) for levosimendan versus 2.18+/-0.15 (+10%) for IABP). CONCLUSION: Infusion of levosimendan in acute CS results in early and sustained haemodynamic improvement. Short-term haemodynamic effects compare favourably with those seen after invasive IABP placement.