Lactitol vs. lactulose in the treatment of chronic recurrent portal-systemic encephalopathy

To compare the efficacy and patient acceptability of lactitol vs. lactulose in chronic recurrent portal-systemic encephalopathy (PSE), 25 cirrhotic patients with a history of repeated episodes of hepatic encephalopathy who required chronic administration of lactulose were included in a controlled cross-over clinical trial in which patients received, at random, lactitol (at an initial dosage of 10 g/6 h) or lactulose (15 ml/6 h, 66% w/v, containing 10 g of lactulose) during a 3 month period and then crossed-over to the alternative treatment for the following 3 months. Doses were adjusted to obtain two bowel movements per day. During the study period the daily protein intake was 40-60 g. Clinical and analytical data (including ammonia levels) were obtained, an EEG and the number connection test were performed and the PSE index was determined before treatment and monthly until the end of the treatment. No significant differences were found between the effects of lactitol and lactulose on the neurological and biological parameters, suggesting that the two treatments could be considered as equally effective. Lactitol was significantly better tolerated than lactulose (P = 0.02), the taste of which was assessed as being too sweet and provoking nausea. In conclusion, lactitol is a good alternative to lactulose for patients with chronic recurrent PSE, especially in those who do not tolerate the excessive sweetness of lactulose.     

Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil

A patient with portal-systemic encephalopathy refractory to standard therapy (40-g protein diet, oral neomycin and lactulose, supplementation of diet with branched chain amino acids) following extensive liver resection and construction of a portacaval shunt was treated with 25 mg of flumazenil twice daily by mouth. Before treatment with flumazenil she was encephalopathic and experienced 12 attacks of coma within 2 yr. When treated with flumazenil all signs of encephalopathy abated in spite of an unrestricted dietary intake of protein. Two days after discontinuation of flumazenil treatment she became comatose again. She remained chronically encephalopathic and had four further episodes of coma during the subsequent 3 mo. Since reinstitution of flumazenil treatment she has been well for 14 mo during follow-up without any signs of encephalopathy while on an unrestricted protein diet. Furthermore, flumazenil therapy reversed abnormalities of recordings of multimodality evoked potentials that were associated with hepatic encephalopathy. The striking remission of encephalopathy by treatment with flumazenil suggests that this benzodiazepine antagonist may be valuable in the long-term management of portal-systemic encephalopathy.     

Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats

AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA). METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days. Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic) dissolved in 2 ml of normal saline, once a day for 8 d (from the 5th d before the experiment to the 3rd d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin, ammonia, liver function and histological grade of hepatic injury of rats were examined individually. RESULTS: There were no overt HE and rat deaths in 3 groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12), 168.33±15.44 mg/dL and 0.36±0.04 EU/mL, respectively, were significantly higher than those in lactulose group, which were 33.3% (4/12), 110.25±7.39 mg/dL and 0.19±0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58±10.24 mg/dL and 0.13±0.03 EU/mL respectively (P <0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP, and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P>0.05). CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.     

Intermittent neomycin therapy in chronic portal-systemic encephalopathy

Conclusion In view of the inherent dangers and expense of neomycin, it is suggested that total dosage may be reduced considerably in some instances by the administration of short, intermittent courses rather than continuous use when necessary for the control of the neuropsychiatric symptoms of chronic portal-systemic encephalopathy.     

Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized controlled trial of lactulose versus no lactulose

Background and Aims: Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB. Methods: Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group‐L) or no lactulose (Group‐P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization. Results: Seventy patients were randomized into group‐L (Gp‐L, n = 35) and group‐P (Gp‐P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp‐L vs Gp‐P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp‐L and 14 patients (40%) in Gp‐P, P = 0.03. The median grade of HE was 2 (range 2–4) and median time interval of development of HE after randomization was 2 days (range 1–4). Nine patients (13%) died; three (8.5%) patients in Gp‐L and six (17%) patients in Gp‐P, P = 0.23. Patients who developed HE had significantly higher baseline Child‐Turcotte‐Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10 505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE. Conclusions: Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.     

Lactitol,a second-generation disaccharide for treatment of chronic portal-systemic encephalopathy

A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P<0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.     

Lactitol versus lactulose in the treatment of acute portal systemic encephalopathy (PSE): A controlled trial

Preliminary data suggest that lactitol (beta-galactoside-sorbitol), a new synthetic non-absorbable disaccharide, has beneficial effects on chronic portal systemic encephalopathy. To compare the efficacy of lactitol vs. lactulose in the treatment of acute portal systemic encephalopathy (PSE), 40 cirrhotic patients with an acute episode of PSE were randomly allocated to one of two groups: group A (20 patients) received lactulose (30 ml/6 h) and group B (20 patients) lactitol (12 g/6 h). These doses were adjusted daily to obtain two bowel movements per day. The duration of treatment was 5 days. Age, sex, hepatic and renal function, precipitating factors and level of PSE measured by clinical examination, EEG and number connection test were similar in the two groups. A complete clinical resolution of PSE occurred in 11 patients in each group. In 5 patients of the lactulose group and in 6 of the lactitol group there was a moderate improvement of PSE during the study. Finally, 4 patients in the lactulose group and 3 in the lactitol group did not respond to treatment. No side effects attributable to therapy were observed in either group. These results indicate that lactitol is as effective as lactulose in the management of patients with cirrhosis and acute PSE.     

Lactitol vs. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial

Lactitol (beta-galactosido-sorbitol) is a nonabsorbable disaccharide available as a powder which, in open comparison, is as effective as lactulose in the treatment of chronic hepatic encephalopathy, but is better tolerated. Twenty-five cirrhotic patients experiencing 28 episodes of acute hepatic encephalopathy were randomized blindly to treatment with either lactitol (n = 15) or lactulose (n = 13). The sugars were dispensed in solutions identical in appearance, taste and pH and of similar osmolarity, which contained either 66.7 gm per 100 ml lactitol or 66.7 ml (44.5 gm) per 100 ml lactulose syrup. The initial dose of 0.75 ml per kg was adjusted to produce two semisoft stools per day. Patients were assessed every 12 hr for 5 days. There were no significant differences in sex ratio, age, body weight, clinical status, duration and extent of coma, etiology of liver disease or of hepatic encephalopathy between the two groups of patients on entry to the trial. An adequate catharsis was obtained with an equivalent mean (+/- 1 S.D.) daily dose of 26 +/- 5 gm lactitol or 31 +/- 7 ml (21 +/- 5 gm) lactulose syrup. During the trial, significant improvements occurred in clinical status and psychometric performance and in the electroencephalogram mean cycle frequencies in the majority of patients in both groups. At the end of the trial, 67% of the patients in the lactitol group and 69% of the lactulose group were clinically normal. However, patients treated with lactitol responded significantly more quickly than patients treated with lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.     

Long-term results of partial splenic artery embolization as supplemental treatment for portal-systemic encephalopathy

OBJECTIVES: To present long-term results of angiographic partial splenic artery embolization (PSE) as a supplemental treatment of portal-systemic encephalopathy. METHODS: Twenty-five patients with portal-systemic encephalopathy were divided into two groups: 14 patients underwent transportal obliteration and/or balloon-occluded retrograde transvenous obliteration (BRTO) of portal-systemic shunts (PSS), followed by PSE (PSE(+) group), and 11 patients underwent only transportal obliteration and/or BRTO of PSS (PSE(-) group). RESULTS: Portal venous pressures pretreatment was similar to posttreatment in the PSE(+) group, but lower than posttreatment in the PSE(-) group. Serum ammonia levels were higher at pretreatment than at 1 wk posttreatment in both groups, but the levels in the two groups were similar at pretreatment, 1 wk, 3 months, 3 yr, 4 yr, and 5 yr posttreatment. However, serum ammonia levels were lower in the PSE(+) group than in the PSE(-) group 6 months, 9 months, 1 yr, and 2 yr posttreatment. Grades of encephalopathy were higher at pretreatment than at 1 wk posttreatment in both groups, but the levels in the two groups were similar at pretreatment, 1 wk, 2 yr, 3 yr, 4 yr, and 5 yr posttreatment. However, grades of encephalopathy were lower in the PSE(+) group than in the PSE(-) group 3 months, 6 months, 9 months, and 1 yr posttreatment. CONCLUSIONS: Obliteration of PSS followed by PSE benefit patients with portal-systemic encephalopathy.     

An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy

BACKGROUND AND AIM: Minimal hepatic encephalopathy (MHE) is associated with poor quality of life and increased work disability. Treatment with lactulose and probiotics has shown some benefit. We compared lactulose with probiotics and a combination of lactulose plus probiotics in the treatment of MHE. PATIENTS AND METHODS: One hundred and ninety cirrhotic patients without overt encephalopathy [Child's A grade 71 patients (37.4%), Child's B grade 72 patients (37.9%), Child's C grade 47 patients (24.7%)] were evaluated by psychometry (number connection tests A and B or figure connection tests A and B) and P300 auditory event-related potential (P300ERP). MHE was diagnosed by abnormal psychometry and/or P300ERP. Patients were randomized to receive lactulose [group A (n=35): dose 30-60 ml/day], probiotics [group B (n=35): dose 1 capsule three times/day, each capsule contained Streptococcus faecalis 60 million, Clostridium butyricum 4 million, Bacillus mesentricus 2 million, lactic acid bacillus 100 million] and lactulose plus probiotics [group C (n=35)] for 1 month. Response was defined by normalization of the abnormal test parameters. RESULTS: MHE was diagnosed in 105 (55.2%) patients. Of the 105 patients, 75 (71%) had both abnormal psychometry and P300ERP, whereas 90 (86%) had abnormal psychometry alone, and 89 patients (85%) had abnormal P300ERP alone. Significant improvement was seen in abnormal psychometry tests (group A: n=31 vs. n=12, group B: n=29 vs. n=14, group C: n=30 vs. n=10), P300ERP (group A: 376.8+/-22.3 vs. 344.3+/-30.6 ms, group B: 385.4+/-28.5 vs. 355.5+/-27.9 ms, group C: 387.7+/-27.5 vs. 347.7+/-31.5 ms) and venous ammonia levels (group A: 102.3+/-63.1 vs. 69.3+/-33.3 micromol/l, group B: 108.2+/-37.5 vs. 75.7+/-33.0 micromol/l, group C: 96.3+/-27.7 vs. 68.7+/-28.4 micromol/l) in lactulose, probiotics and a combination of lactulose plus probiotics groups after treatment. Normalization of abnormal psychometry and P300ERP was seen in 54.8, 51.6 and 56.6% of patients treated with lactulose, probiotics and lactulose plus probiotics groups, respectively. CONCLUSION: A total of 55% of the patients with cirrhosis had MHE. Lactulose or probiotics or combinations of both are equally effective in the treatment of MHE.     

Effect of dietary protein manipulation in subclinical portal-systemic encephalopathy.

Eight stable cirrhotic patients with mild or subclinical portal-systemic encephalopathy (PSE) were studied after shunt surgery when they were off all antiencephalopathic therapy. Equal amounts of mixed proteins were alternated with animal or vegetable protein in a crossover protocol under metabolic conditions for five consecutive, one week periods. The different dietary periods were not associated with either a change in the neurological impairment score or the Trailmaking Tests, which showed a learning effect. The peak frequencies of the computer analysed EEG (CAEEG) were lower during the animal (6.58 +/- 0.42 Hz) than the vegetable (7.10 +/- 0.44 Hz) diet (p 0.01). Neither arterial ammonia levels nor plasma amino acid ratios changed with the diets, whereas urinary 3-methyl-histidine excretion increased during the animal diet. During the vegetable diet the apparent nitrogen balance tended to be more positive than during either the mixed or animal diets associated with decrease in the urinary nitrogen excretion. The peak frequency of the CAEEG is the most sensitive test to monitor methods of treatment in portal-systemic encephalopathy. A vegetable protein diet, rather than overall protein restriction, should be considered in the management of this disorder, particularly when the nutritional state is poor.     

Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy.

Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial. All 12 patients showed a remarkable clinical improvement after vancomycin treatment. The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001). Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations. Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone.     

Lactitol in the treatment of chronic hepatic encephalopathy: an open comparison with lactulose.

Lactulose is currently the drug of choice for the treatment of hepatic encephalopathy. It is, however, only available as a syrup which is contaminated with other sugars. Consequently patients may express aversion to its excessively sweet taste and many experience nausea because of its hyperosmolarity. Lactitol is a disaccharide analogue of lactulose which can be produced as a pure crystalline powder with a low relative sweetness. Theoretically it should have the same therapeutic effects as lactulose but fewer side effects. Five patients with chronic hepatic encephalopathy on maintenance lactulose were monitored clinically, psychometrically, and by measurement of venous blood ammonia, electroencephalogram mean cycle frequency, and cerebral blood flow during three months treatment with lactulose and a similar period on lactitol. Lactitol was at least as efficacious as lactulose but was more acceptable because its cathartic effect was more predictable, its formulation was more convenient and its less sweet taste preferred. Lactitol is the ideal successor to lactulose for treatment of this condition.