Therapy For Hepatic Encephalopathy Research Articles

165 Molecular Adsorbent Recirculating System as Therapy for Hepatic Encephalopathy

165 Molecular Adsorbent Recirculating System as Therapy for Hepatic Encephalopathy

Anti-inflammatory therapy in hepatic encephalopathy: A systematic review and meta-analysis

Anti-inflammatory therapy in hepatic encephalopathy: A systematic review and meta-analysis

Reduction in Gastrointestinal Cancers in Cirrhotic Patients Receiving Rifaximin vs Lactulose Only Therapy for Hepatic Encephalopathy.

Background Rifaximin and/or lactulose therapy is widely used in cirrhotic patients for the prevention and treatment of hepatic encephalopathy. The incidence of gastrointestinal cancers in these patients on lactulose, rifaximin, and/or combination therapy is unknown. We investigated the possible effect of lactulose and rifaximin on cancer risk in patients with cirrhosis using the MarketScan database. Methods A retrospective cohort study was conducted using the Truven Health MarketScan Commercial Claims databases from 2007-2017. An index date was defined for each participant as the earliest date of cirrhosis diagnosis. A baseline period for each participant was defined as the 12 months prior to the first medication date while the study follow-up period represented the period from the initiation of the medication to its cessation. ANOVA was used to compare all continuous measures of age and duration of medication. Wald Chi-square tests were performed to test the associations between the study groups. Results A total of 12,409 patients were included in our study. The rifaximin only cohort had the greatest reduction in risk of developing colon cancer, esophageal cancer, and stomach cancer compared to the other groups. Rifaximin reduced the risk of colon cancer and esophageal cancer by 59.42% and 70.37%, respectively, compared to patients taking lactulose only. Patients in the lactulose plus rifaximin cohort had the highest rate of development of pancreatic cancer (lactulose plus rifaximin vs rifaximin only vs lactulose only, 0.45% vs 0.24% vs 0.21%; P < 0.0001) and liver and intrahepatic bile duct cancers (11.73% vs 5.84% vs 5.49%; P < 0.0001). Conclusion Colon, esophageal, and gastric cancers had a marked incidence reduction in the rifaximin only cohort compared to the other cohorts studied.

Results of using L-ornitin-L-aspartate in the treatment of hepatic encephalopathy in liver transplantation

The aim was to study the results of using various treatment regimens for hepatic encephalopathy for patients with liver cirrhosis before and after liver transplantation and the effect on the incidence and severity of hepatic encephalopathy in the perioperative period, and on the posttransplantation course.Material and methods. Fifty four patients with cirrhosis of various etiologies and the presence of significant hepatic encephalopathy undergoing living donor liver transplantation were included in the study. In the comparison group, patients took lactulose and rifaximin. In the main group, patients took lactulose and rifaximin in combination with L-ornithine-L-aspartate in the preoperative period, and L-ornithine-L-aspartate after liver transplantation for 5 days.Results. The use of L-ornithine-L-aspartate in the complex therapy of hepatic encephalopathy led to significantly reduced time of performing the Number Connection Test, the improvement of cognitive functions in patients by the Montreal Cognitive Assessment, a decreased incidence of stage II–III hepatic encephalopathy and an increased incidence of stage 0-I hepatic encephalopathy in the preoperative period. In the postoperative period, patients of the main group showed a rapid decrease in the severe stages of hepatic encephalopathy (stage II–III) towards less severe forms (stage 0–I) on the 3rd, 5th and 7th days after liver transplantation, and also a faster recovery of cognitive functions, an earlier adequate recovery of consciousness, muscle tone, an earlier possibility of extubation, a shorter length of stay in the intensive care unit, and a decreased postoperative hospital length of stay relatively to the patients of the comparison group.Conclusion. The use of L-ornithine-L-aspartate in the combination therapy for hepatic encephalopathy in the peritransplantation period leads to a significant decrease of the incidence and severity of hepatic encephalopathy, accelerates rehabilitation of patients, reduces postoperative hospital length of stay.

Aktualisierte S2k-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) „Komplikationen der Leberzirrhose“

This guideline provides evidence-based key recommendations for diagnosis and therapy of complications of liver cirrhosis and upgrades the 2011 version. An interdisciplinary team of medical experts and patient support groups developed the guideline following the AWMF recommendations for evidence based consensus guidelines. New chapters concerning diagnosis and therapy of hepatic encephalopathy were added.

Liver: the gut is a key target of therapy in hepatic encephalopathy.

Little progress has been made in the pharmacological management of patients with hepatic encephalopathy, partly because it is difficult to perform clinical trials in this group of patients. A new clinical trial now suggests that polyethylene glycol is more effective than the current standard first-line therapy in these patients.

Issue Highlights

Issue Highlights

Complications and outcomes in chronic liver disease

Chronic liver disease (CLD) causes significant morbidity and mortality, mainly due to complications [hepatic encephalopathy, ascites, hepatorenal syndrome (HRS) and esophageal variceal hemorrhage (EVH)]. Studies of the complications, management and outcomes in patients with CLD over the last 18 months are reviewed. Predictors of response to lactulose therapy in hepatic encephalopathy have been reported, along with the effect of minimal hepatic encephalopathy on driving. Rifaximin was found to lead to better maintenance of remission and decreased readmission rates in patients with cirrhosis and hepatic encephalopathy. Satavaptan (a vasopressin receptor antagonist) was investigated for treatment of refractory ascites and appeared to be effective, but this compound is not currently approved by the US Food and Drug Administration (FDA). Patients with refractory ascites taking propranolol were found to have poorer outcomes than those not taking propranolol. Terlipressin currently appears to be the best medical therapy available for patients with type 1 HRS; the addition with albumin to terlipressin appeared to decrease mortality in patients with type 1 HRS. In primary prophylaxis of EVH, carvedilol was found to reduce the rate of initial bleeding compared with band ligation. Early transjugular intrahepatic portosystemic shunts placed in highly selected patients with acute EVH and a high risk of endoscopic failure decreased long-term mortality. In patients with gastric varices, primary prophylaxis with cyanoacrylate may decrease the probability of gastric variceal hemorrhage compared with nonselective beta-blockers. Refinement in clinical management strategies for patients with cirrhosis and its complications appear to continue to contribute to improved patient outcomes.

OP08 Evidence for early astrocyte activation, cellular stress and compensatory microglial related transforming growth factor-α responses in bile-duct ligated rats

IntroductionInflammation and ammonia are important mediators in the pathogenesis of hepatic encephalopathy and though the mechanisms are unclear astrocytes are thought to have a central role. Recently Microglia, which also...

Prebiotics and probiotics show promise as a therapy for hepatic encephalopathy?

Prebiotics and probiotics show promise as a therapy for hepatic encephalopathy?

Zinc deficiency

Zinc plays an essential role in numerous biochemical pathways. Zinc deficiency affects many organ systems, including the integumentary, gastrointestinal, central nervous system, immune, skeletal, and reproductive systems. This article aims to discuss zinc metabolism and highlights a few of the diseases associated with zinc deficiency. Zinc deficiency results in dysfunction of both humoral and cell-mediated immunity and increases the susceptibility to infection. Supplementation of zinc has been shown to reduce the incidence of infection as well as cellular damage from increased oxidative stress. Zinc deficiency is also associated with acute and chronic liver disease. Zinc supplementation protects against toxin-induced liver damage and is used as a therapy for hepatic encephalopathy in patients refractory to standard treatment. Zinc deficiency has also been implicated in diarrheal disease, and supplementation has been effective in both prophylaxis and treatment of acute diarrhea. This article is not meant to review all of the disease states associated with zinc deficiency. Rather, it is an introduction to the influence of the many roles of zinc in the body, with an extensive discussion of the influence of zinc deficiency in selected diseases. Zinc supplementation may be beneficial as an adjunct to treatment of many disease states.

Dietary and nutritional indications in hepatic encephalopathy

The restriction of dietary protein has long been considered a main stay in the therapy of hepatic encephalopathy. More recently it has been recognized that protein energy malnutrition is frequent in advanced liver disease and may adversely affect the patients'outcome. Moreover studies on inter-organ ammonia exchange in liver cirrhosis have shown that the muscle may have a crucial role in ammonia detoxification. In light of these evidences nutritional guidelines have proposed that protein restriction should be avoided in patients with hepatic encephalopathy as protein requirement is even increased in cirrhotic patients. Survey about the current clinical practice show that protein restriction is still considered advisable in patients with hepatic encephalopathy, however a recent trial evidenced that a low protein diet in patients hospitalized for acute hepatic encephalopathy exacerbates protein breakdown without inducing any specific clinical benefit when compared to a normal protein regimen. The relevance of an adequate protein intake and possible strategies to implement protein tolerance are also discussed.

Non-Hepatic Coma in a Cirrhotic Patient due to Chronic Subdural Hematoma

Hepatic encephalopathy is the most frequent cause of altered mental status and coma in cirrhotic patients. In this report we describe an interesting case of a differential diagnostic pitfall, where a cirrhotic patient with compromised mental status initially supposed to suffer from hepatic encephalopathy turned out to have a non-traumatic chronic subdural hematoma. The major points leading to diagnosis were almost normal ammonia, hypertension and deteriorating overall condition despite targeted therapy of hepatic encephalopathy. In comatose cirrhotic patients with normal ammonia and hypertension intracranial hemorrhage should be excluded.

Hyperammonemic Coma—Barking Up the Wrong Tree

Hepatic encephalopathy and myxedema coma share clinical features: coma, ascites, anemia, impaired liver functions, and a “metabolic” electroencephalogram (EEG). Hyperammonemia, a hallmark of hepatic encephalopathy, has also been described in hypothyroidism. Differentiation between the 2 conditions, recognition of their possible coexistence, and the consequent therapeutic implications are of utmost importance. We describe a case of an 82-year-old woman with a history of mild chronic liver disease who presented with hyperammonemic coma unresponsive to conventional therapy. Further investigation disclosed severe hypothyroidism. Thyroid hormone replacement resulted in gain of consciousness and normalization of hyperammonemia. In patients with an elevated ammonia level, altered mental status, and liver disease, who do not have a clear inciting event for liver disease decompensation, overwhelming evidence of hepatic decompensation, or who do not respond to appropriate therapy for hepatic encephalopathy, hypothyroidism should be considered and evaluated.

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.

Nightly high dose lactulose infusion could be a cost-effective treatment for hepatic encephalopathy, renal insufficiency and heart failure

Lactulose is an established remedy for hepatic encephalopathy and shows efficacy for chronic renal insufficiency, reducing volume overload, uremia and hyperkalemia. Potentially lactulose could also be used for non-diuretic treatment of congestive heart failure. However, use of lactulose is limited by diarrhea and flatulence. Chronic lactulose administration might be tolerable if it was accomplished by nocturnal infusion through a percutaneous duodenostomy tube, also placing a rectal foley each night following a clearing enema so that large volumes of liquid stool could be passed while patients sleep. Each morning the duodenostomy would be clamped and the foley removed. For acute patients without duodenostomies, a temporary dobhoff feeding tube with accompanying rectal foley could be employed. Patients who did not want a rectal foley could elect to have a permanent colostomy. Clinical trials could establish the relationship between lactulose infusion and clearance of water, salt, potassium, hydrogen, urea and other wastes, and compare efficacy, cost and tolerability with that of peritoneal dialysis and ultrafiltration. Lactulose could potentially allow inexpensive home-based therapy for hepatic encephalopathy, chronic renal failure and congestive heart failure, and might be life-saving in countries where renal replacement in any form is currently unavailable.

Dispelling myths in the treatment of hepatic encephalopathy

Guidelines for the treatment of hepatic encephalopathy suggest ammonia reduction as the main focus, based on strategies to reduce ammonia's generation and absorption in the colon by using lactulose and a reduced protein diet. Two studies provide compelling and provocative data questioning the relevance of these interventions. Bodils Als-Nielsen and colleagues, in a systematic review of randomised trials, found insufficient evidence about whether non-absorbable disaccharides are beneficial (BMJ 2004; 328: 1046-50). In a small randomised study, Juan Cordoba and colleagues showed that diets with normal protein content can be administered safely during episodic hepatic encephalopathy due to cirrhosis and that protein restriction does not have any beneficial effect during such episodes (J Hepatol 2004; 41: 38-43). Two approaches to new therapies for hepatic encephalopathy are needed. First, it is important to focus on the interorgan metabolism of ammonia. The small intestine and kidneys might be important producers of ammonia, and muscle is an important organ that can remove ammonia. Novel therapies targeting these organs reduce ammonia. Second, research is needed to explore factors other than ammonia that might be important in hepatic encephalopathy, including the synergistic role of inflammation. The lack of conclusive data about the efficacy of any treatment supports the view that placebo-controlled trials of newer agents are needed and ethical. The emphasis should shift to aggressive management of the precipitating event.

Diagnosis and therapy of hepatic encephalopathy.

The diagnosis of Hepatic Encephalopathy (HE) is basically clinical, and consists in the detection of various degrees of mental impairment along with neuromuscular abnormalities. Three components of mental state may be impaired in HE: the level of consciousness, personality (behavior), and the upper intellectual functions (1). The most common neuromuscular abnormality is the so-called asterixis or flapping tremor, however other signs or symptoms such as impaired handwriting are usually present in the lower degrees of HE, with this being impossible to explore in cases of coma flapping tremor; in this situation muscular rigidity and hyperreflexia are common. In Table 1 the most common classification of HE is described. This classification is clearly useful in cases of acute HE, but in cases of chronic HE the four different stages of HE are less clear. It is important to know the existence of subclinical HE in some patients with chronic liver disease with apparent normal mental status, and this may only be documented by certain psychometric tests (2). These patients may have problems when performing activities requiring a correct degree of mental and neuromuscular status, such as driving cars (3).

Clinical manifestations and therapy of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a functional and generally reversible alteration of the central nervous system that appears in patients with acute and chronic liver disease. The pathogenesis of HE is not well understood (this aspect is deeply discussed in another chapter of this issue) although it has been suggested that the key mechanism is due to the inability of the liver to eliminate endogen and exogen products which are toxic to the brain. These substances reach the systemic blood stream because of the presence of hepatic failure, and the development of portosystemic shunts. Both mechanisms allow the intestinal blood to reach the brain without being cleared by the liver (1).KeywordsHepatic EncephalopathyHepatic ComaAcute Hepatic FailurePortal Systemic EncephalopathyNumber Connection TestThese 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.

Lactulose treatment of chronic hepatoportal encephalopathy. A clinical and electroencephalographic study.

Abstract. Current treatment of chronic hepatoportal encephalopathy with dietary protein restriction is not always sufficient, and long‐term administration of antibiotics may lead to some undesirable side‐effects. The present study of three patients with encephalopathy and surgical portacaval shunt demonstrates the favourable effect of a synthetic disaccharide (lactulose, Duphalac). This study also demonstrates clearly that there is a close interrelation between the EEG and the metabolism of the brain. Thus the EEG analysis can be used as a method for checking the effects of therapy in hepatic encephalopathy.