Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary measures have achieved mixed results in the management of liver disorders. Although a high energy diet may shorten the course of viral hepatitis by a relatively small amount, dietary restriction is usually of no benefit in compensated cirrhosis. Restriction of sodium intake to 22 to 60 mol/day leads to resolution of cirrhotic ascites in approximately 20% of patients, and reduces the requirement for diuretics in the remainder. In advanced liver disease, diet plays an important role in the avoidance of portal-systemic encephalopathy (PSE), with the tolerance of most nutrients, most importantly protein, being sharply reduced. Despite the frequent presence of carbohydrate intolerance in liver disease, carbohydrate supplementation may be required to ensure adequate utilisation of the reduced dietary protein intake. Zinc supplementation may also be required in liver cirrhosis to compensate for a deficiency. Bed rest is an important component of the management of acute and chronic liver disorders, together with the avoidance of fatigue. Abstinence from alcohol is required in alcoholic liver disease patients, who should receive parenteral thiamine 100 mg and other vitamin and mineral supplementation as required. Agents acting on the ascending loop of Henle [such as furosemide (frusemide)] or the distal tubule (such as spironolactone) are the diuretics most frequently employed to mobilise ascites in cirrhosis, the latter drug being the more effective in nonazotaemic patients. In the absence of oedema, the diuresis should be restricted to a maximum of 750 ml/day; however, patients with oedema may safely undergo a diuresis of less than or equal to 1.5 L/day. Diuretic therapy is often associated with renal complications, such as azotaemia (usually reversible) and severe hyponatraemia in cirrhotic patients with ascites; spironolactone may produce antiandrogenic adverse effects. Lactulose, used in the treatment of acute and chronic PSE, acts by inhibiting gastrointestinal absorption of ammonia and other toxic nitrogenous substances, and by reducing urea degradation. Other pharmacological treatments, such as branched-chain amino acids and benzodiazepine antagonists have a limited role in the management of PSE. Chronic cholestasis has been treated with cholestyramine and fat-soluble vitamins, whereas ursodeoxycholic acid appears to be a promising agent in the treatment of primary biliary cirrhosis. In chronic hepatitis, the prevention of development of cirrhosis is a primary treatment goal which has been attempted with variable success using antifibrotic drugs such as penicillamine and colchicine.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Traditional management of liver disorders. 208 80

Four pathophysiological types of hepatic failure suffered by 59 patients with liver cirrhosis were defined: chronic-recurrent type (Group A), acute exacerbation of chronic (Group B), post-operative type (Group C) and terminal type (Group D). The etiological, clinical and prognostic characteristics of the four types of hepatic failure were examined. More patients of Group C were seen in recent years than former years, but the opposite trend was observed in Group D. Direct causes or precipitating factors of hepatic failure differed depending upon the type of hepatic failure. Mortality rates were higher than 80% in the acute types of hepatic failure (Groups B, C and D), but were 50% in the chronic type (Group A). The association of multiple organ failure was frequently observed in Groups C (67%) and D (39%). Lactulose, nonabsorbable antibiotics and branched-chain amino acid solutions were used in combination for the treatment of patients of Groups A and D, with rates of arousal from encephalopathy of 75% and 29%, respectively. Even though further therapeutic maneuvers for acute hepatic failure were employed in Groups B and C, only low arousal rates of 38% and 27%, respectively, were obtained.
 ...
PMID:Forms of hepatic failure in patients with liver cirrhosis. 320 31

To determine how lactulose and lactulose plus neomycin might alter nitrogen metabolism in the colon we investigated the effect of these agents on the distribution of nitrogen in the bacterial, soluble, and fiber fractions of stool. The alterations in fecal nitrogen excretion were additionally correlated with changes in total body urea synthesis and degradation rates. Six patients with stable cirrhosis received a control diet alone followed by the administration of lactulose (56 +/- 6 gm/day), and eight similar patients received lactulose alone (63 +/- 5 gm/day) followed by the addition of neomycin (4 gm/day). Their feces were partitioned into individual fractions by physical separation. Lactulose administration increased nitrogen excreted in the bacterial fraction by 165% (from 0.52 +/- 0.14 gm/day to 1.38 +/- 0.21 gm/day) and by 135% in the soluble fraction (from 0.58 +/- 0.08 gm/day to 1.36 +/- 0.23 gm/day). When lactulose was supplemented with neomycin, the nitrogen content of the bacterial fraction decreased by 28%. Lactulose caused a 23% reduction in the urea production rate that was mainly accounted for by increase in fecal nitrogen excretion. The addition of neomycin caused a further reduction in urea production that was explained by an inhibition of urea degradation. These results demonstrate that a major effect of lactulose was to augment the incorporation of nitrogen into fecal bacteria although nitrogen in the soluble fraction also increased. The additional nitrogen excreted in the fecal bacterial and soluble fractions caused a reduction in urea synthesis.
 ...
PMID:Nitrogen in fecal bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin. 361 49

The altered plasma amino acid pattern (i.e. increased levels of aromatic amino acids and decreased levels of branched chain amino acids) is a characteristic feature of cirrhotic patients. Recently it has been proved that an increased net degradation of BCAA is positively correlated to the plasma NH3 level, strongly suggesting that these amino acids are molecularly involved in glutamine synthesis to detoxify ammonia in skeletal muscle. Lactulose, a synthetic, nonabsorbable disaccharide, is believed to actively promote excretion of ammonia from the body by causing it to be trapped in the acidified fecal stream and making it unavailable for absorption. Therefore therapy with lactulose could determine an increase of BCAA. The present study was undertaken to examine plasma amino acid pattern of ten patients with liver cirrhosis before and after lactulose therapy. No statistically significant changes of amino acids were observed.
 ...
PMID:[Plasma amino acids in patients with liver cirrhosis treated with lactulose]. 652 9

Lactulose is a poorly absorbed synthetic disaccharide frequently used in the treatment of portasystemic encephalopathy. Because lactulose syrup contains small amounts of absorbable sugars, it may cause hyperglycemia in diabetic individuals, but is usually well tolerated. We report the case of a patient with diet-controlled diabetes and cirrhosis who experienced a marked deterioration in glycemic control, requiring insulin use, when he began using a different brand of lactulose syrup. The hyperglycemia resolved and insulin was discontinued after use of the original brand of lactulose syrup was resumed.
 ...
PMID:Marked deterioration in glycemic control with change in brand of lactulose syrup. 771 10

The term "hepatic encephalopathy" describes the neuropsychiatric signs and symptoms of patients with acute or chronic liver disease, irrespective of the presence or absence of liver cirrhosis. Cerebral edema, the pathophysiology and treatment of which being quite different from hepatic encephalopathy, is the leading cause of death in patients with acute liver failure. Lactulose (orally or as enema) is one of the cornerstones of the treatment of hepatic encephalopathy; most important for the management of patients with cerebral edema is close monitoring (including intracranial pressure monitoring) of the patients and rapid reduction of intracranial pressure (e.g. with mannitol). The pathophysiologic and therapeutic concepts in the care of patients with hepatic encephalopathy and cerebral edema are described.
 ...
PMID:[Hepatic coma]. 791 30

To evaluate the prevalence of latent PSE in unselected ambulatory patients with liver cirrhosis practicing physicians were asked to perform two non instrumental psychometric tests (number connection test and line tracing test) on patients with clinical signs of liver cirrhosis and portal hypertension. Tests were repeated after 8 weeks of treatment with Lactulose in those patients considered to have latent PSE at the initial evaluation. 296 physicians tested a total of 783 patients, 771 of these could be evaluated. 551 patients (71.5%) were considered to have latent PSE. There was a significant correlation between psychometric test results and biochemical parameters related to liver function. Repeat testing after 8 weeks treatment with Lactulose revealed definite improvement of psychometric test results in 88% of the patients. At the final evaluation only about 30% of the patients fulfilled the criteria of latent PSE. There was a statistically significant albeit weak correlation between changes in biochemical parameters and psychometric improvement. Psychometric testing with simple non instrumental tests proved to be practicable in the office setting.
 ...
PMID:Prevalence of latent portasystemic encephalopathy in an unselected population of patients with liver cirrhosis in general practice. 849 2

Lactulose exerts a beneficial effect on hepatic encephalopathy by decreasing toxic short-chain (iC4-nC6) fatty acid (isobutyrate, butyrate, isovalerate, valerate, isocaproate and caproate) production. However, the precise mechanism by which lactulose exerts this effect remains uncertain. This study investigated the effect of lactulose on faecal flora, particularly Clostridium difficile, which produces mostly iC4-nC6 fatty acids. An in-vitro faecal incubation system was used to estimate how lactulose influences production of short-chain (C2-nC6) fatty acids and lactate. Faecal specimens were collected from patients with liver cirrhosis, who carried C. difficile in the colon. Supplementation of lactulose along with blood in faecal specimens decreased iC4-nC6 fatty acids production and increased acetate and lactate production, resulting in increased faecal acidity. These changes were statistically significant when compared with supplementation by blood alone. Quantitative faecal culture demonstrated that lactulose supplementation suppressed the growth of C. difficile and Bacteroides spp. (B. fragilis group), iC4-nC6 fatty acids-producing organisms. These results suggest that decreased faecal levels of iC4-nC6 fatty acids after lactulose supplementation may be related to suppression of iC4-nC6 fatty acids-producing faecal organisms, especially C. difficile.
 ...
PMID:Effect of lactulose on short-chain fatty acids and lactate production and on the growth of faecal flora, with special reference to Clostridium difficile. 900 50

1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in patients with deep encephalopathy should be considered. A nasogastric tube is placed for patients in deep encephalopathy. Avoid sedatives whenever possible. Correction of the precipitating factor is the most important measure. B. SPECIFIC MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day. ii. Lactulose is administered via enema or nasogastric tube in deep encephalopathy. The oral route is optimized by dosing every hour until stool evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil may be used in selected cases of suspected benzodiazepine use. 2. Chronic Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors, including the institution of prophylactic measures. ii. Nutrition. Improve protein intake by feeding dairy products and vegetable-based diets. Oral branched-chain amino acids can be considered for individuals intolerant of all protein. iii. Lactulose. Dosing aims at two to three soft bowel movements per day. Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring. iv. Refer for liver transplantation in appropriate candidates. For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion. In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases. The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60). Although these may impact the ability to perform daily activities, many subjects can compensate for these defects. Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62). In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried. Benzodiazepines should not be used for patients with sleep difficulties.
 ...
PMID:Hepatic Encephalopathy. 1146 22

Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction that is present in the majority of patients with cirrhosis. MHE has a characteristic cognitive profile that cannot be diagnosed clinically. This cognitive dysfunction is independent of sleep dysfunction or problems with overall intelligence. MHE has a significant impact on quality of life, the ability to function in daily life and progression to overt hepatic encephalopathy. Driving ability can be impaired in MHE and this may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored during routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of the care of patients with MHE. The preserved communication skills and lack of specific signs and insight make MHE difficult to diagnose. The predominant strategies for MHE diagnosis are psychometric or neurophysiological testing. These are usually limited by financial, normative or time constraints. Studies into inhibitory control, cognitive drug research and critical flicker frequency tests are encouraging. These tests do not require a psychologist for administration and interpretation. Lactulose and probiotics have been studied for their potential use as therapies for MHE, but these are not standard-of-care practices at this time. Therapy can improve the quality of life in MHE patients but the natural history, specific diagnostic strategies and treatment options are still being investigated.
 ...
PMID:Management options for minimal hepatic encephalopathy. 1909 Jul 38


1 2 Next >>