Term Hepatic Encephalopathy Research Articles

Hepatic encephalopathy: Sometimes more portal than hepatic.

Hepatic encephalopathy is a severe complication of both chronic and acute liver diseases. The term hepatic encephalopathy stems from the belief that hepatic insufficiency is its fundamental etiopathogenic factor. However, most clinical cases show liver failure along with mesenteric venous portal hypertension. This portal hypertension would explain the abnormal mechanical forces suffered by the digestive tract in the early stages of the disorder. These forces could regulate some gut biochemical pathological pathways in a process known as mechanotransduction. Thus, portal hypertension would begin with the establishment of a mechanotransduced afferent or sensory inflammatory gut-brain pathway, resulting in functional and structural changes in the central nervous system. In this review, we will revisit the term "hepatic encephalopathy" in light of new results where portal hypertension occurs before liver failure and is accompanied by brain changes. Moreover, we will point out cellular links that can explain the microbiota, immune, gut, and brain axis disturbances found in this disorder.

Brain Magnetic Resonance in Hepatic Encephalopathy

The term hepatic encephalopathy (HE) covers a wide spectrum of neuropsychiatric abnormalities caused by portal-systemic shunting. The diagnosis requires demonstration of liver dysfunction or portal-systemic shunts and exclusion of other neurologic disorders. Most patients with this condition have liver dysfunction caused by cirrhosis, but it also occurs in patients with acute liver failure and less commonly, in patients with portal-systemic shunts that are not associated with hepatocellular disease. Various magnetic resonance (MR) techniques have improved our knowledge about the pathophysiology of HE. Proton MR spectroscopy and T1-weighted imaging can detect and quantify accumulations of brain products that are normally metabolized or eliminated such as glutamine and manganese. Other MR techniques such as T2-weighted and diffusion-weighted imaging can identify white matter abnormalities resulting from disturbances in cell volume homeostasis secondary to brain hyperammonemia. Partial or complete recovery of these abnormalities has been observed with normalization of liver function or after successful liver transplantation. MR studies have undoubtedly improved our understanding of the mechanisms involved in the pathogenesis of HE, and some findings can be considered biomarkers for monitoring the effects of therapeutic measures focused on correcting this condition.

Management of Hepatic Encephalopathy in the Hospital

Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes despite lactulose use benefit from the addition of rifaximin, which decreases the frequency of recurrent HE episodes and related hospitalizations. Last, patients and their families should be counseled about the risk of motor vehicle accidents, which require mandatory reporting to the Department of Motor Vehicles in some states.

Update on Management of Patients With Overt Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a multifactorial neuropsychiatric disease that affects patients with cirrhosis. We review the clinical impact, pathogenesis, evaluation, management, and prevention of overt HE in patients with cirrhosis. Articles published between January 1960 and November 2012 were acquired through a MEDLINE search of different combinations of the terms hepatic encephalopathy, pathophysiology, treatment, prophylaxis, prevention, prognosis, and recurrence. The Healthcare Cost and Utilization Project database was used to obtain prevalence and cost information related to hospitalizations of patients with HE. The literature describes significant morbidity and mortality of HE in patients with cirrhosis. Overt HE develops in 30% to 45% of patients with cirrhosis and is associated with a substantial pharmacoeconomic burden, particularly HE-related hospitalizations. The development of HE in patients with cirrhosis portends a worsened prognosis and is incorporated into the Child-Pugh classification of the severity of liver disease. In the hospitalized patient, the development of HE is associated with precipitating events (eg, gastrointestinal bleeding, dehydration, infection), and in some patients, its course is characterized by frequent and severe relapses. In addition, hospitalized patients with overt HE have a 3.9-fold increased mortality risk. Patient management employs nonabsorbable disaccharides, the nonsystemic antibiotic rifaximin, or both, to treat acute HE episodes and prevent HE relapse. In open-label trials, use of the nonabsorbable disaccharide lactulose reduced the risk of overt HE recurrence in patients compared with no-lactulose control groups for ≤ a median of 14 months. In a randomized, placebo-controlled trial, rifaximin 550 mg twice daily was more effective in maintaining HE remission compared with placebo and was associated with a reduction in HE-related hospitalizations. Recent advances in treatment and preventative therapies may reduce the personal, societal, and economic impact of this disorder.

MR Imaging Findings in Hepatic Encephalopathy

The term hepatic encephalopathy (HE) includes a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction. Most cases are associated with cirrhosis and portal hypertension or portal-systemic shunts, but the condition can also be seen in patients with acute liver failure and, rarely, with portal-systemic bypass and no associated intrinsic hepatocellular disease. Although HE is a clinical condition, several neuroimaging techniques, particularly MR imaging, may eventually be useful for the diagnosis because they can identify and measure the consequences of central nervous system (CNS) increase in substances that under normal circumstances, are efficiently metabolized by the liver. Classic MR imaging abnormalities include high signal intensity in the globus pallidum on T1-weighted images, likely a reflection of increased tissue concentrations of manganese, and an elevated glutamine/glutamate peak coupled with decreased myo-inositol and choline signals on proton MR spectroscopy, representing disturbances in cell-volume homeostasis secondary to brain hyperammonemia. Recent data have shown that white matter abnormalities, also related to increased CNS ammonia concentration, can also be detected with several MR imaging techniques such as magnetization transfer ratio measurements, fast fluid-attenuated inversion recovery sequences, and diffusion-weighted images. All these MR imaging abnormalities, which return to normal with restoration of liver function, probably reflect the presence of mild diffuse brain edema, which seems to play an essential role in the pathogenesis of HE. It is likely that MR imaging will be increasingly used to evaluate the mechanisms involved in the pathogenesis of HE and to assess the effects of therapeutic measures focused on correcting brain edema in these patients.

Management of hepatic encephalopathy in patients with cirrhosis

The term hepatic encephalopathy encompasses a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction. Distinct syndromes are identified in acute liver failure and cirrhosis. Rapid deterioration in consciousness level and increased intracranial pressure that may result in brain herniation and death are a feature of acute liver failure whereas manifestations of hepatic encephalopathy in cirrhosis include psychomotor dysfunction, impaired memory, increased reaction time, sensory abnormalities, poor concentration and in severe forms, coma. In patients with acute-on-chronic liver failure the pathophysiology remains undefined. Ammonia has been considered central to its pathogenesis. In the brain, the astrocyte is the main site for ammonia detoxification, during the conversion of glutamate to glutamine. An increased ammonia level raises the amount of glutamine within astrocytes, causing an osmotic imbalance resulting in cell swelling and ultimately brain oedema. Recent studies suggest that inflammation and it modulators may play a synergistic role with ammonia in the pathogenesis of hepatic encephalopathy. Therapy of hepatic encephalopathy is directed primarily at reducing ammonia generation and increasing its detoxification. The currently accepted regimens to treat hepatic encephalopathy such as lactulose and protein restricted diets need further clinical trials and therefore placebo controlled clinical trials in hepatic encephalopathy are justified. In liver failure, ammonia metabolism involves multiple organs and therefore ammonia reduction will require simultaneous targeting of these organs. The present review describes the pathophysiological basis of hepatic encephalopathy and evaluates the available therapies.

Brain tryptophan perturbation in hepatic encephalopathy: implications for effects by neuropsychoactive drugs in clinical practice.

The syndromes encountered within the term metabolic encephalopathy may be defined as “any metabolic disease that disrupts normal cerebral function” (Conn and Bircher, 1988). In the case of liver dysfunction, the terms hepatic encephalopathy (HE) or portal-systemic encephalopthy (PSE) are frequently used. In the human and clinical situation, these HE/PSE disorders are recognized as acute, chronic or, most commonly, acute-on-chronic events. The central nervous system (CNS) processes accompanying the patient suffering from HE/PSE probably include a mixture of reversible as well as irreversible changes of euronal function (Victor et al. 1965; Victor 1974, 1979; see also Conn and Lieberthal, 1979). Thus, clinical HE/PSE, which almost inexclusively have included previous or even ongoing exposure to e.g. liver affecting agents, like those related to a variety of acute or chronic infectious or immunological processes, as well as intake of liver toxins such as ethanol. Since the chronic abuse of alcohol is not an uncommon major cause for a subsequently appearing liver cirrhosis, in turn related to the etiology chronic PSE in many clinical cases by blood vessel collateral development bypassing the liver parenchyma, it should be kept in mind that this type of abuse will most certainly exert effects of its own on the CNS in patients with chronic PSE involving aspects of acute, chronic as well as acute-on-chronic CNS effects of ethanol concomitantly to the encephalopathy component provided by the “isolated” PSE per se. Of course, in the clinical setting the isolated effects on the brain of chronic PSE is almost impossible to purify in scientific terms whereas, however, this pure type of chronic PSE may be identified in experimental in vivo models available such as most prominently evidenced by the advent of the surgically induced end-to-side portacaval shunt (PCS) in the rat (Lee and Fisher, 1961).KeywordsHepatic EncephalopathyQuinolinic AcidKynurenine PathwayHepatic ComaPortacaval ShuntThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.