A look at the hepatic encephalopathy in cirrhosis

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia) produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma) but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE); the West Haven Criteria are most often used to grade Overt HE (OHE), with grade ranging from 0 to 4 (4 corresponding to coma). Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE) to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients' quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE, and death. Management of HE includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, dehydration, hypotension, use of benzodiazepines, psychoactive drugs, and/or alcohol). Current treatment is based principally on reducing intestinal ammonia with nonabsorbable disaccharides (lactulose or lactitol); rifaximin, used solely or in addition, is also becoming a first-line treatment

The use of albumin in the complications of cirrhosis: evidence and future perspectives

The therapeutic use of albumin in cirrhosis dates back to the 50s, when hypoalbuminemia was thought to play a crucial role in the pathophysiology of ascites. Today, while its efficacy in the treatment of ascites is still under investigation, it has been proved that albumin is able to improve patient outcome and survival in some specific complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction and the treatment of spontaneous bacterial peritonitis and hepatorenal syndrome. Beside its oncotic power, albumin carries other biological properties, the so called non-oncotic properties, including transportation and detoxification of several molecules, free radical scavenging, modulation of vascular permeability, activity on the immune system and on the haemostatic balance. Some experimental evidences indicate that not only albumin concentration but also its function is reduced in patients with cirrhosis. However, the clinical implications of such functional abnormalities is still unclear. We here present the available evidence on the use of albumin in cirrhosis and future perspectives

A case of pneumonia and sepsis in cirrhosis as paradigm of the problems in the management of bacterial infections in cirrhosis and of the limitations of current knowledge

Bacterial infections are a major problem in the management of liver cirrhosis. They represent the first precipitating cause of death since patients with cirrhosis carry an increased risk of sepsis, sepsis-induced organ failure and death. Although the clinical presentation is often misleading, the presence of bacterial infection should always be actively searched and ruled out with certainty whenever a cirrhotic patient is admitted to the hospital with an acute clinical deterioration. Major changes in the epidemiology of bacterial infections have also occurred in the last decade making the choice of empirical antibiotic therapy a challenge. We report a paradigmatic case of a 54-year old man with hepatitis C-related cirrhosis admitted to the hospital for worsening of his ascites and onset of hepatic encephalopathy, an excellent example for the difficulties of management of sepsis in cirrhosis and the limits of current knowledge

The use of albumin in the complications of cirrhosis: evidence and future perspectives

The therapeutic use of albumin in cirrhosis dates back to the 50s, when hypoalbuminemia was thought to play a crucial role in the pathophysiology of ascites. Today, while its efficacy in the treatment of ascites is still under investigation, it has been proved that albumin is able to improve patient outcome and survival in some specific complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction and the treatment of spontaneous bacterial peritonitis and hepatorenal syndrome. Beside its oncotic power, albumin carries other biological properties, the so called non-oncotic properties, including transportation and detoxification of several molecules, free radical scavenging, modulation of vascular permeability, activity on the immune system and on the haemostatic balance. Some experimental evidences indicate that not only albumin concentration but also its function is reduced in patients with cirrhosis. However, the clinical implications of such functional abnormalities is still unclear. We here present the available evidence on the use of albumin in cirrhosis and future perspectives

A look at the hepatic encephalopathy in cirrhosis

<span style="font-size: x-small;"><p>Hepatic encephalopathy (HE) is a neuropsychiatric syndrome complicating acute and chronic liver failure and characterized by a wide range of manifestations, in absence of other brain disease. HE is very frequent in course of cirrhosis and even mild forms involve a great additional burden on patients, their families and health</p></span><span style="font-size: x-small;">-care resources. Its onset affects subsequent survival of patients. Historically, pathophysiology of HE was connected to several substances (mostly ammonia) produced in the gut and normally metabolized by the liver, but more recently other factors such as inflammation, bacterial translocation and oxidative stress have shown a crucial role. Symptoms are often overt (confusion, asterixis, disorientation, ataxia or coma) but can also be subtle (sleep disturbances, cognitive impairment, mood alterations, impairment of executive decision-making, and psychomotor speed – Minimal HE); the West Haven Criteria are most often used to grade Overt HE (OHE), with grade ranging from 0 to 4 (4 corresponding to coma). Since both Minimal HE and grade 1 HE cannot be diagnosed by clinical examination and need for specific tests, it results practical to combine these entities and name them "Covert" HE (CHE) to aid clinical use. Diagnosis is based on evidence of neurological impairment in presence of liver cirrhosis, only after the exclusion of other brain diseases. Measurement of serum ammonia and electroencephalography are little specific, while brain magnetic resonance and search for portosystemic shunts are important in complex cases. Diagnosis of OHE is often just clinical, while that of CHE requires dedicated psychometric and neurophysiological tests. Although these tests are difficult to be performed in the clinical practice, detection and treatment of CHE are cost-effective and important; indeed, CHE affects patients’ quality of life, socioeconomic status and driving skills, and increases the risk for falls, car accidents, development of OHE, and death. Management of HE includes early diagnosis and prompt treatment of precipitating factors (infection, gastrointestinal bleeding, electrolyte disturbances, dehydration, hypotension, use of benzodiazepines, psychoactive drugs, and/or alcohol). Current treatment is based principally on reducing intestinal ammonia with nonabsorbable disaccharides (lactulose or lactitol); rifaximin, used solely or in addition, is also becoming a first-line treatment. </span

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

Extrahepatic Feeding of HCC Limits the Use of TACE? Evidences from Literature and Clinical Experience

n/

Autoantibodies in Autoimmune Hepatitis

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.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