Autoantibodies in Autoimmune Hepatitis.

BACKGROUND: The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. KEY MESSAGES: When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. CONCLUSIONS: Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed.

The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.

Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C. Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy. More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects. Compounds able to target selectively the peripheral CB1 receptors are under evaluation. In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research. Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.

Clinical indications for the albumin use: still a controversial issue.

Human serum albumin (HSA) is the most abundant circulating protein and accounts for about 70% of the plasma colloid osmotic pressure. Beside the well known capacity to act as plasma-expander, HSA is provided of many other properties which are unrelated to the regulation of fluid compartmentalization, including binding and transport of many endogenous and exogenous substances, antioxidant function, immuno-modulation, anti-inflammatory activity, and endothelial stabilization. Treatment (hepatorenal syndrome) or prevention (renal failure after spontaneous bacterial peritonitis and post-paracentesis circulatory dysfunction after large volume paracentesis) of severe clinical complications in patients with cirrhosis and fluid resuscitation in critically ill patients, when crystalloids and non-proteic colloids are not effective or contra-indicated, represents the major evidence-based clinical indications for HSA administration. However, a large proportion of HSA prescription is inappropriate. Despite the existence of solid data against a real benefit, HSA is still given for nutritional interventions or for correcting hypoalbuminemia per se (without hypovolemia). Other clinical uses for HSA administration not supported by definitive scientific evidence are long-term treatment of ascites, nephrotic syndrome, pancreatitis, abdominal surgery, acute distress respiratory syndrome, cerebral ischemia, and enteric diseases. HSA prescription should be not uncritically restricted. Enforcement of clinical practice recommendations has been shown to allow a more liberal use for indications supported by strong scientific data and to avoid the futile administration in settings where there is a lack of clinical evidence of efficacy. As a result, a more appropriate HSA use can be achieved maintaining the health care expenditure under control.

Dorsal acoustic windows may ameliorate liver ultrasound in patients with chronic liver disease and meteorism/obesity/ascites.

PURPOSE: To identify dorsal acoustic windows (DAWs) for the study of the liver and to investigate whether they could improve the visualization of the liver in patients with chronic liver disease and ascites, meteorism, and/or obesity. METHODS: The study was based on a single ultrasound examination and divided into three successive stages. Firstly, we performed a preliminary study involving 10 cirrhotic patients to identify new DAWs. Inter-observer reproducibility of measurements obtained through the DAWs was then assessed in another 29 cirrhotic patients. Finally, in 50 patients with chronic hepatitis/cirrhosis, we employed the DAWs when ascites, meteorism or obesity hampered the conventional ultrasound examination. RESULTS: With patients sitting, we found three new DAWs, by the combined use of which it was possible to explore the liver, spleen, and their vascular structures, and which provided reproducible measurements. In the clinical setting, we found 11 of 50 patients in whom the addition of the new DAWs led to better results in terms of successful visualization/Doppler measurements for portal vein (ratio = 100 % vs 27 %, p = 0.001), hepatic artery (ratio = 90 % vs 27 %, p = 0.004), and hepatic veins (mean number = 2.4 ± 0.2 vs 1.0 ± 0.2, p = 0.01). Among these 11 patients, in one case the addition of DAWs led to visualization of hepatic focal lesions in the right lobe, not previously displayed through conventional ultrasound. CONCLUSION: These DAWs may be an additional tool that improves the accuracy of ultrasound examinations in patients with meteorism, ascites, or obesity.