Lactulose Therapy Research Articles

Persistence of cognitive impairment after resolution of overt hepatic encephalopathy.

Hepatic encephalopathy (HE) represents a spectrum of neurocognitive impairment seen in cirrhotic patients and is considered to be fully reversible with treatment; however, recent evidence suggests otherwise. This longitudinal study was carried out to evaluate the persistence of cognitive impairment in cirrhotics with prior overt HE (OHE) episode despite treatment. Of the 213 patients screened, 107 patients who met the eligibility criteria were enrolled and 102 patients completed the study (52 patients without prior OHE episode and 50 patients with prior OHE). All patients underwent psychometric hepatic encephalopathy score (PHES) evaluation at three separate visits (day 1, day 3, and between 30 and 60 days). A one-point improvement in PHES between the first and second evaluation was considered as a measure of learning. Patients with a previous OHE episode showed learning impairment in PHES on repetition on day 3 (P=0.084), whereas patients without a previous OHE episode demonstrated learning effect (P<0.0001) irrespective of whether they had minimal HE (MHE) or not. Univariate analysis demonstrated that Child-Turcotte-Pugh score, lactulose and/or rifaximin therapy, the presence of MHE, and a previous OHE episode were associated with learning impairment. Multivariate analysis demonstrated that only the presence of a previous episode of OHE (adjusted odds ratio 38.398; 95% confidence interval 9.192-160.4; P<0.0001) significantly affected learning. This study conclusively demonstrated learning impairment in cirrhotic patients with a previous episode of OHE despite normal mental status. Improvement in PHES on repetition may be a measure of learning.

Reversal of Low-Grade Cerebral Edema in Patients with Cirrhosis and Minimal Hepatic Encephalopathy After Lactulose and Rifaximin Therapy

Reversal of Low-Grade Cerebral Edema in Patients with Cirrhosis and Minimal Hepatic Encephalopathy After Lactulose and Rifaximin Therapy

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy

Background and study aimsMinimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE. Patients and methodsThis is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks. ResultsThe probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. ConclusionBoth probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group.

Su1698 Hospitalizations Outcomes in Portal Hypertension Complications Treated With Rifaximin or Lactulose Therapy

Su1698 Hospitalizations Outcomes in Portal Hypertension Complications Treated With Rifaximin or Lactulose Therapy

Lactulose Is Highly Potential in Prophylaxis of Hepatic Encephalopathy in Patients with Cirrhosis and Upper Gastrointestinal Bleeding: Results of a Controlled Randomized Trial

Background and Aims: Upper gastrointestinal bleeding (UGB) is an important precipitating factor for the development of hepatic encephalopathy (HE) in cirrhotic patients. The aim of this study was to evaluate the efficacy of lactulose in a controlled randomized trial for prophylaxis of HE after UGB. Patients and Methods: 128 cirrhotic patients with UGB were consecutively classified according to Child-Pugh criteria and randomized to receive lactulose (group A, n = 63) or no lactulose (group B, n = 65) treatment after the symptoms of active bleeding disappeared. Curative effects were observed for 6 days. Results: Two patients in group A and 11 in group B had developed HE; the incidence rates were 3.2 and 16.9% (χ² 5.2061, p < 0.05). After treatment, a significant increase in ammonia level and higher number connection test (NCT) in the non-lactulose group, median blood ammonia levels (60.0 vs. 52.0), p < 0.05, and median NCT (43 vs. 38), p < 0.05, were observed. Patients who had developed HE had a significantly higher baseline Child-Turcotte-Pugh score (10.15 ±1.82 vs. 6.35 ± 1.60, p < 0.05), alanine aminotransferase (111.25 ± 91.62 vs. 48.32 ± 47.45, p < 0.05), aspartate aminotransferase (171.42 ± 142.68 vs. 46.33 ± 42.68, p < 0.05), total bilirubin (73.44 ± 47.20 vs. 29.75 ± 22.08, p < 0.05), serum albumin (24.65 ± 5.04 vs. 33.43 ± 6.49, p < 0.05), plasma prothrombin time (22.18 ± 4.60 vs. 17.12 ± 4.62, p < 0.05), and lower hemoglobin level (72.31 ± 15.15 vs. 87.45 ± 19.79, p < 0.05) as compared to patients who did not develop HE. On unconditional logistic regression analysis, patients who had developed HE were significantly associated with a higher baseline Child-Turcotte-Pugh score (OR 9.92, 95% CI 1.94-50.63, p < 0.05) and lactulose therapy (OR 0.02, 95% CI 0-0.74, p < 0.05) but were not associated with other parameters. Conclusions: Lactulose is an effective prophylaxis agent of HE for cirrhotic patients who had developed UGB.

Hyperammonemic Coma in an Adult due to Ornithine Transcarbamylase Deficiency.

Objective. To report an unusual cause of coma in an adult. Design. Case report. Setting. University teaching hospital. Patient. A previously healthy 53-year-old man initially presented with altered mental status and progressed to coma. He was found to be substantially hyperammonemic and did not improve with lactulose therapy and continuous venovenous hemodialysis. Results. Biochemical testing revealed previously undiagnosed ornithine transcarbamylase deficiency, and the patient responded to arginine, sodium phenylacetate, and sodium benzoate. Conclusion. Even in adult patients with no known history, inborn errors of metabolism must be considered in the differential diagnosis of unexplained coma. Defects of the urea cycle can present with an unprovoked hyperammonemic coma.

The Potential Role of Lactulose in the Prevention of Clostridium difficile Diarrhea

Purpose:Clostridium difficile (C. diff), a spore-forming, gram-positive anaerobic bacillus, is a common cause of antibiotic-associated diarrhea in the hospital setting, leading to significant morbidity and mortality. Lactulose, a synthetic disaccharide composed of fructose and galactose, is commonly utilized in the management of constipation and hepatic encephalopathy. The drug's metabolism into organic acids in the colon by fecal flora leads to the acidification of the colonic mileau. By promoting the growth of bifidobacteria, lactulose also acts as a prebiotic. C. diff has previously been shown to be susceptible to changes in acidity, and its growth may be suppressed by the addition of lactulose in vitro, suggesting a potential role for lactulose in preventing C. diff infection. In addition, changes in the bacterial colonic flora by fecal transplant have also been shown to prevent and cure recurrent C. diff infection. The purpose of this study was to determine whether lactulose therapy impacts the rates of C. diff infection in hospitalized patients on antibiotic therapy. Methods: A retrospective chart review was performed by comparing C. diff rates in patients on lactulose and antibiotics to those on antibiotics alone. Included patients were admitted to the medicine and surgery services of a large academic medical center from September 1, 2007 to September 1, 2008. Excluded patients were those who had been treated with metronidazole or oral vancomycin. Results: A total of 103 patients (50 men and 53 women) were included in the antibiotics alone arm and 87 patients (46 men and 41 women) were included in the antibiotics with lactulose arm. There were no significant gender differences between the two groups (p = 0.56). The patients in the antibiotics with lactulose arm were significantly older (mean age 67), compared to those in the antibiotics alone arm (mean age 60, p = 0.02). Analysis of C. diff rates revealed that two out of 87 patients (2.3%) on both lactulose and antibiotics developed C. diff compared to 10 out of 103 patients (9.7%) on antibiotics alone (p = 0.04). Conclusion: These statistically significant results suggest that lactulose therapy may help prevent infection with C. diff in patients on antibiotics. Further research is needed to identify additional clinical factors that may be contributing to observed differences, as well as to elucidate the appropriate dosing, route, and duration of therapy.

Malnutrition in Cirrhotics; Daily Calorie Counts and Nutritional Deficits Uncovered

Purpose: Fatigue is a very common complaint in patients suffering from all stages of cirrhosis. One common fatigue that leads to fatigue in this patient population is sarcopenia (muscle loss). There are several factors that lead to sarcopenia including decreased caloric intake culminating in malnutrition. It is well established that compensated cirrhotics consume only nearly 80% of their daily recommended calories. Thus the loss in daily calories in cirrhotic patients magnifies the decrease in quality of life, enhances sarcopenia and deconditioning thus intensifying fatigue. The purpose of this review is to evaluate daily caloric intake of compensated cirrhotic patients while undergoing subclinical hepatic encephalopathy (SHE) management. Methods: The medical charts were reviewed for non-hospitalized patients with compensated cirrhosis with and without the diagnosis of subclinical encephalopathy. The patients were stratified into three groups; cirrhotic without SHE, cirrhotic with SHE treated with lactulose (LAC), and cirrhotic with SHE treated with rifaximin (RFX). Treated patients received either RFX or LAC therapy for SHE and were given daily calorie logs. All patients were reported to be at baseline Coon score Grade 0-1 HE and employment status was identified. Information collected included; gender, age, ethnicity, weight/height, exercise and employment status, and daily calorie counts for 14 days. Daily caloric intake was registered with food consumption logs by patients and family. Normal caloric intake was considered at 1600 to 2200 calories/day depending upon dietary requirements. The daily caloric totals were done with the Calorie Smart calculator. The RFX dose was 1100 mg/day (550 mg twice per day) or LAC 30cc adjusted according to two to three soft bowel movements each day or no therapy. Results: There were 64 patients involved; 29 females, 35 males, age (range 19-68), ethnicity (81% Caucasian, 8% African American, 8% Hispanic, 3% other), and mean MELD 8.5 points (range 6-13). There were no events of occult HE or hospitalizations throughout the review. Conclusion: The above results demonstrate the challenges with adequate nutritional intake in compensated cirrhotic patients with SHE. Patients taking lactulose suffered from bowel bloating culminating in a sensation of decreased appetite thus a marked decrease in caloric intake. Further investigation is needed to evaluate the overall impact of malnutrition upon sarcopenia as a result of the marked caloric deficits in cirrhotic patients maintained on lactulose. Disclosure: Dr. Guy W. Neff - Consultant, Speaker's Bureau, Grant.Table: Calorie count totals

Lactulose in the treatment of hepatic encephalopathy: New evidence for an old modality

See article in J. Gastroenterol. Hepatol. 2012; 27: 1329–1335.

602 LACTULOSE FOR MINIMAL HEPATIC ENCEPHALOPATHY IN PATIENTS WITH EXTRAHEPATIC PORTAL VEIN OBSTRUCTION: A PILOT STUDY

© 2011, INASL 44 AUTOIMMUNE DISEASE AND NON-CIRRHOTIC PORTAL HYPERTENSION Lactulose for Minimal Hepatic Encephalopathy in Patients with Extrahepatic Portal Vein Obstruction—A Pilot Study P Sharma, A Agrawal, BC Sharma, SR Mishra, SK Sarin Department of Gastroenterology, GB Pant Hospital, New Delhi Background and Aims: Minimal hepatic encephalopathy is common in patients with extrahepatic portal vein obstruction (EHPVO). Lactulose is effective in the treatment of MHE in patients with cirrhosis. There is no study on the treatment of MHE using lactulose in patients with EHPVO. Patients and Methods: Consecutive EHPVO patients were assessed by psychometric (number connection test [NCT-A and B], digit symbol test [DST], serial dot test [SDT], line tracing test [LTT]) and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests and CFF were reassessed after 3 months. Results: Of 70 patients screened prevalence of abnormal psychometric test were NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%) and LTT (44%). Thirty patients (43%) had two or more than two abnormal psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. All patients could do CFF with little training. CFF in patients with MHE (n = 30) was significantly lower than those without MHE (n = 40) (38.1 ± 2.4 vs. 41.5 ± 3.1 Hz, p = 0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose need reduction, 3 (10%) did not like its taste but continued, 2 (6%) developed abdominal bloating sensation. Conclusion: Lactulose is effective in the treatment of MHE in patients with EHPVO Conflict of Interest: None Associated HLA Alleles with Pediatric and Adult AIH in North Indian Population RW Minz*, N Kaur*, S Anand*, R Aggarwal*, B Saikia*, YK Chawla** Department of *Immunopathology, **Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh Background and Aims: Autoimmune hepatitis is an unresolving inflammation of liver characterized by presence of hypergammaglobulinemia, autoantibodies and histology showing interface hepatitis. AIH is a polygenetic disorder in which genetic risk factors affect the occurrence, clinical phenotype, severity and disease outcome. The major contributor to genetic susceptibility is the HLA region. This study aimed to find the associated HLA alleles in pediatric AIH and adult AIH. Methods: Twenty pediatric AIH patients and 35 adult AIH patients were enrolled in the study following IAHG guidelines. One hundred twenty-eight healthy controls were also included in the study. The patients and the controls were typed for HLA-DR DQ by PCR–SSP method (Innotrain, Germany). Results: HLA-DRB1*08 was found to be significantly associated with adult AIH and DRB1*03 and DRB1*04 were found to be associated with pediatric AIH. Conclusion: Like other autoimmune diseases, AIH is also associated with HLA genetic susceptibility. Presence of high susceptibility alleles leads to early manifestation of the disease i.e., in childhood age, whereas presence of other associated alleles leads to disease manifestation later in age. However, there are other genetic regions that need to be studied for genetic susceptibility for the disease. Conflict of Interest: None Clinical Profile of Patients with Liver Disease of Autoimmune Etiology R Kavitha*, TM Ramachandran**, T Varghese*** *DM Trainee and Presenting Author,**Additional Professor, ***Professor Department of Gastroenterology, Govt Medical College, Calicut, Kerala Aim: To determine the incidence, clinical, and biochemical profile of autoimmune hepatitis in a tertiary care institution. Methods: Patients presented with acute or chronic liver disease between January 2009 and January 2011 were evaluated. Data was taken retrospectively from data register. Workup included clinical, biochemical, USG, viral markers, autoimmune markers (ANA, SMA, AntiLKM, AMA, RF, p-ANCA) and liver biopsy if possible. AIH was diagnosed using Czaja criteria. Those patients who presented with features of cirrhosis were included since they were evaluated in the past with liver biopsy. 03_JCEH-Abstract.indd 44 3/18/2011 11:13:06 AM

603 IS THERE ANY EFFECT OF THROMBOPOIETIN ON THE THROMBOCYTOPENIA WHICH RELATED WITH PORTAL HYPERTENSION?

Background and Aims: Minimal hepatic encephalopathy is common in patients with extrahepatic portal vein obstruction (EHPVO). Lactulose is effective in the treatment of MHE in patients with cirrhosis. There is no study on the treatment of MHE using lactulose in patients with EHPVO. Patients and Methods: Consecutive EHPVO patients were assessed by psychometric [(number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)] and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests and CFF were reassessed after 3 months. Results: Of 70 patients screened prevalence of abnormal psychometric test were NCT-A (41%), NCT-B(53%), DST(38%), SDT(40%) and LTT(44%). Thirty patients (43%) had two or more than two abnormal psychometry tests. Lactulose improved MHE in 16/30(53%) of patients after 3 months of treatment. All patients could do CFF with little training.CFF in patients with MHE (n =30) was significantly lower than those without MHE (n =40) (38.1±2.4 vs 41.5±3.1Hz, p = 0.01). CFF was less than 38Hz in 21(70%) of 30 patients before treatment and in 10(33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose need reduction, 3(10%) did not like its taste but still continued, 2(6%) developed abdominal bloating sensation. Conclusions: Lactulose is effective in the treatment of MHE in patients with EHPVO.

The Diagnosis and Treatment of Minimal Hepatic Encephalopathy

The subtype of hepatic encephalopathy (HE) called minimal hepatic encephalopathy (MHE) is highly prevalent (22-74%) among patients with liver dysfunction. MEH is defined as HE without grossly evident neurologic abnormalities, but with cognitive deficits that can be revealed by psychometric testing. This article is based on relevant original publications and reviews in English and German (1970-2011) that were retrieved by a selective key-word-based search in the Medline and PubMed databases. Despite its mild manifestations, MHE impairs patients' quality of life and their ability to work. It impairs driving ability and is associated with a higher rate of motor vehicle accidents. Furthermore, patients with MHE fall more often and are more likely to undergo progression to overt HE. The main pathophysiological mechanism of MHE is hyperammonemia leading to astrocyte dysfunction. Psychometric tests are the standard instruments for establishing the diagnosis; further, supportive diagnostic tools include neurophysiological tests and imaging studies. Recent randomized and controlled trials have revealed that treatment with lactulose or rifaximin therapy improves the quality of life of patients with MHE. Rifaximin was also found to improve driving performance in a simulator. A combination of these two drugs prevents the recurrence of episodic HE over a 6-months follow-up period. Moreover, small-scale trials have revealed that some dietary supplements can improve the cognitive deficits of MHE. Clinical trials have shown that patients with MHE and patients who have had an episode of overt HE in the past can benefit from drug treatment.

Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction

Background/Aims:Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO.Patients and Methods:Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months.Results:Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation.Conclusions:Lactulose is effective in the treatment of MHE in patients with EHPVO.

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

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. 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. 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. Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.

Lactulose a day keeps encephalopathy at bay

Lactulose a day keeps encephalopathy at bay

HYPERAMMONEMIC ENCEPHALOPATHY DUE TO A URINARY DIVERSION: AN UNCOMMON CAUSE OF REVERSIBLE DEMENTIA

To the Editor: Patients with cognitive impairment may have potentially reversible conditions. Metabolic diseases constitute an important group of these nondegenerative etiologies. Urinary diversion has been reported to cause hyperammonemic encephalopathy (HE), even without liver disease. This letter presents the case of a patient with hyperammonemia and history of a Bricker diversion after radical cystectomy for bladder cancer previously misdiagnosed with early-onset dementia. After specific treatment for hyperammonemia, the patient's cognition improved greatly. A 74-year-old man was admitted to the acute geriatric unit of our hospital because of a 3-week history of drowsiness and general stiffness. He had a prior medical history of a Bricker uretero-ileostomy after radical cystectomy for bladder cancer performed 1 year before admission and cognitive impairment, labelled as Alzheimer's disease, detected 3 months before by his general physician, although no specific tests had been performed to evaluate it. Omeprazole and lorazepam were his regular medications. On examination, he was unaware of time and place, and he presented with signs of dehydration. Neurological findings included slurred speech, drowsiness, clumsiness, stiffness, postural instability, and bradykinesia. Symptoms were present and stable all day. Blood tests showed mildly high C-reactive protein (3.5 mg/dL), hypernatremia (156 mEq/L), and leucocytosis (18 × 109/L). Glucose, calcium, magnesium, Vitamin B12, thyroid hormone, and renal and liver function tests were normal. Urine sediment evidenced mild leukocyturia with bacteriuria. Chest radiography was normal. Initial diagnosis was hypernatremia secondary to dehydration and urinary infection, and fluid therapy and antibiotic with ceftriaxone were started. Urinary culture was negative. Natremia normalized progressively, but the patient's symptoms did not improve at all. A cranial computed tomography (CT) scan showed mild diffuse cerebral atrophy, and an electroencephalogram revealed diffuse nonspecific encephalopathy. Despite normal liver function, given the urinary diversion, blood ammonia levels were tested revealing marked hyperammonemia (122 μmol/L). An abdominal–pelvic CT scan did not evidence signs of obstruction or dilatation of the uretero-ileal anastomosis. Specific treatment with dietary protein restriction and lactulose therapy was initiated. In a few days, ammonemia became normal, and the patient quickly showed great improvement in his mental state (Mini-Mental State Examination score 29/30 at 1 month after discharge). The global prevalence of dementia in the elderly population is approximately 5%.1 Alzheimer's disease is the most common disorder, accounting for 60% to 80% of cases, followed by vascular dementia (10–20%).2 The prevalence of a potentially reversible cause (Table 1) ranges from less than 1% to 9%, being higher in younger (<60) than older adults and significantly more common in patients with only subjective symptoms than in patients with established dementia.2–4 The most common reversible causes are depression, drugs, hydrocephalus, and metabolic diseases; thyroid disease and vitamin B12 deficiency are the most frequently detected causes from metabolic diseases.2,3 HE is an uncommon reversible etiology of cognitive impairment. Liver diseases, some drugs, portosystemic shunting, congenital defects of enzymes of the urea cycle, parenteral nutrition, hematological dyscrasia, and urinary diversion have been reported as causes of hyperammonemia.5–7 Nonhepatic hyperammonemia in patients undergoing urinary diversion is due to the prolonged contact of urine and the intestinal epithelium that results in high intestinal uptake of urine-excreted products, which can overload the detoxifying capacity of the liver, leading to the download of ammonia into the blood flow.8 Furthermore, urinary tract infections with urease-producing bacteria may cause urine ammonia concentration to rise. Proteus mirabilis and Pseudomonas aeruginosa are the best-known urea-splitting bacteria.9 There are no standardized guidelines for treating acute nonhepatic hyperammonemia. The reduction of intestinal ammonia levels by limiting protein ingestion to 20 g/d and using nonabsorbable disaccharides such as lactulose and lactitol to increase intestinal ammonia elimination is encouraged. If urinary tract infection is suspected, an antibiotic should also be started.10 In conclusion, unexplained neurological or neuropsychiatric symptoms in a patient with a urinary diversion should include hyperammonemia in the differential diagnosis. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors: diagnosis and care of patients and preparation of manuscript. Sponsor's Role: None.

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.

Profile of hepatic encephalopathy in children with cirrhosis and response to lactulose

Background/Aim:Hepatic encephalopathy (HE) is associated with a poor prognosis. There is paucity of data on the treatment of HE with lactulose in children with cirrhosis.Patients and Methods:Retrospective analysis of consecutive cirrhotic patients (<18 years) with HE was done. HE was defined according to West-Haven criteria. Response was defined as complete if patients recovered completely from HE, partial response was defined as improvement of encephalopathy by one or more grades from admission but not complete recovery, and defined as non response if patient did not show any improvement or deteriorated further even after 10 days of lactulose therapy.Results:A total of 300 patients were admitted with cirrhosis and HE (278 adults and 22 children). Of 22 patients, 16 (73%) patients had complete response to lactulose and six (27%) patients did not [three (13.5%) patients worsened (non response) and three (13.5%) did not recover fully even after 10 days of treatment (partial response)]. Comparing baseline characteristics of patients who had complete response (n=16) versus partial (n=3) and non response (n=3), there was significant difference in mean arterial pressure (78.1±10.7 vs 62.6±5.0 mmHg, P=0.003), serum sodium (131.3±3.2 vs 126.5±5.2, P=0.01) and serum creatinine (0.78±0.3 vs 1.1±0.3 mg/dl, P=0.02). We did not find any difference in baseline characteristics of these patients regarding CTP score (9.6±1.2 vs 10.6±1.2), MELD score (17.6±2.9 vs 17.1±3.4), severity of HE (2.5±0.6 vs 2.6±0.5) and etiology of precipitating factors (P=0.78).Conclusions:Lactulose therapy causes complete recovery from hepatic encephalopathy in 73% of pediatrics patients with cirrhosis.

Rifaximin for the Treatment of Hepatic Encephalopathy

Background Previous studies suggest that rifaximin is efficacious in the treatment of hepatic encephalopathy. Objective To evaluate the efficacy and safety of rifaximin in addition to lactulose in improving hospitalization outcomes in patients with hepatic encephalopathy. Methods Hospital records of patients evaluated for liver transplantation at a single center between January 2006 and May 2008 were reviewed. Hospitalizations for hepatic encephalopathy and other conditions and the incidence of spontaneous bacterial peritonitis and adverse events were analyzed. Results Charts of 65 patients who were treated with rifaximin and lactulose were analyzed. Patients received lactulose (20–120 g/d; lactulose phase) before treatment with rifaximin (400– 1200 mg/d; rifaximin phase). During the rifaximin phase, the risk, number, and duration of hospitalizations for hepatic encephalopathy were reduced compared with the lactulose phase. Treatment, age, and Model for End-Stage Liver Disease score were independent predictors of hospitalizations for hepatic encephalopathy ( P < .05). The rifaximin phase had fewer hospitalizations than the lactulose phase (36 vs 47, respectively) and a smaller percentage of patients with repeated hospitalizations than the lactulose phase (5% vs 14%, respectively; P = .006) for conditions other than hepatic encephalopathy. A smaller percentage of patients had evidence of spontaneous bacterial peritonitis during the rifaximin phase than the lactulose phase (2% vs 12%, respectively; P = .02). Rifaximin was better tolerated than lactulose. Conclusions Addition of rifaximin to lactulose therapy significantly reduced the risk and duration of hospitalizations for hepatic encephalopathy.

Gut instinct

Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. RESULTS: Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P = 0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. CONCLUSIONS: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy.