Prophylaxis Of Hepatic Encephalopathy Research Articles

Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

Prophylactic Lactulose Therapy in Patients with Cirrhosis and Upper Gastrointestinal Bleeding: A Meta-analysis of Randomized Trials.

Lactulose is the first-line drug for both treatment and secondary prophylaxis for overt hepatic encephalopathy (HE). The use of lactulose for the primary prophylaxis of HE in patients with cirrhosis and acute upper gastrointestinal bleeding (AUGIB) has been debated. Hence, we conducted this meta-analysis to assess the role of lactulose in HE prophylaxis in patients with cirrhosis and AUGIB. A comprehensive search of literature from inception to December 2022 was performed of three databases for randomized studies comparing lactulose and placebo in patients with cirrhosis and AUGIB. Risk ratios (RR) with 95% confidence intervals were calculated for all the dichotomous outcomes. A total of five studies were included in the final analysis, out of which three studies had a low risk of bias, and two had a moderate risk of bias. Lactulose therapy was associated with a significantly lower risk of OHE compared to placebo, with a RR of 0.38 (0.23-0.62) and a number needed to treat of 6. There was no difference in the risk of mortality between the groups, with a RR of 0.71 (0.29-1.76). The pooled incidence rates of overall adverse events (AEs) and diarrhea with the use of lactulose therapy were 53.2% (42.2- 64.2) and 34.7% (17.7-51.7), but a majority did not require drug discontinuation. The certainty of the evidence was moderate to low. Prophylactic lactulose reduces the incidence of HE after AUGIB but has no effect on mortality. Diarrhea and abdominal discomfort are common AEs but do not need drug discontinuation.

Recurrence of Hepatic Encephalopathy after TIPS: Effective Prophylaxis with Combination of Lactulose and Rifaximin.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Rifaximin microbial resistance and its efficacy and safety as a secondary prophylaxis of hepatic encephalopathy in patients with hepatitis C virus-related cirrhosis.

Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400mg rifaximin 3 times/d plus 30-45mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84±6.49weeks (mean±SD) in the intervention group and was significantly longer (P=.002) than that in the control group 14±7.52weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P=.005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836.

Use of Probiotics as a Prophylaxis for Hepatic Encephalopathy: A Review Article

Hepatic Encephalopathy (HE) is a serious complication of liver cirrhosis and manifests as altered sensorium. It is precipitated by several factors but all these factors result in elevated ammonia levels. Minimal HE (MHE) is a mild form of HE and is not always easy to diagnose. It is mostly recognized by history, physical examination, and neurological tests that assess cognitive function. Altered microbiota in the gut is not uncommon in patients with cirrhosis and often leads to complications. Probiotics have been studied recently for possible use for primary and secondary prophylaxis of HE. Hence, in this review article, we aim to study the role of probiotics in HE prophylaxis. After applying the inclusion and exclusion criteria, we found 8 Randomized Controlled Trials (RCTs). Our results demonstrated that probiotics can be used for possible prophylaxis for MHE. They can be as good as rifaximin and lactulose, common agents occasionally used for prophylaxis. Furthermore, they can also be used for secondary prophylaxis of MHE. Having said that, the authors believe that there is a need to plan RCTs, aiming to use probiotics as a possible treatment for HE.

Primary prophylaxis of hepatic encephalopathy in decompensated cirrhosis: Low dose vs. full dose rifaximin

Objective:To compare efficacy of high vs low dose rifaximin for primary prophylaxis of portosystemic encephalopathy (PSE) in decompensated liver cirrhosis.Methods:In a quasi-experimental double blind randomized study at Services Institute of Medical Sciences (SIMS), Lahore from August 2017 to August 2018, patients of decompensated cirrhosis with no previous PSE were randomized to receive twice daily rifaximin 200mg in Group-A and 550mg in Group-B. Patients were followed for 6 months for development of PSE.Results:In 75 included patients, mean age was 53.8(±10.7) years and male/female ratio was 0.97/1(37/38). After randomization, 34 (45.3%) patients were included in Group-A and 41 (54.7%) patients in Group-B. During 6 month follow up 24 (32%) patients developed PSE, 12 (35.2%) in Group-A and 12 (29.2%) in Group-B, difference was not significant (p value 0.57). In 6 months, 13 (17.3%) patient died, 6 (17.6%) in Group-A and 7 (17.07%) patients in Group-B, difference not significant (p value 0.94). Patients who died had higher bilirubin (p < 0.00), higher serum creatinine (p 0.05), high CTP score (p 0.04) and worse MELD score (p 0.004).Conclusion:Rifaximin is not effective for primary prophylaxis of overt hepatic encephalopathy in decompensated cirrhosis patients.

Secondary prophylaxis of hepatic encephalopathy in cirrhosis of liver: a double-blind randomized controlled trial of L-ornithine L-aspartate versus placebo.

Hepatic encephalopathy (HE) is associated with a poor prognosis. There is no study on the prevention of recurrence of encephalopathy with L-ornithine L-aspartate (LOLA). We conducted a double-blind randomized controlled trial at a tertiary center. Consecutive patients with cirrhosis who had recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer-based randomization for 6 months. Patients were assessed by psychometric HE scores using five paper-pencil tests, critical flicker frequency test, arterial ammonia, and sickness impact profile scores at inclusion. Primary end point was development of overt HE. Of 306 patients, 150 patients were enrolled. HE recurred in nine (12.3%) of 73 and in 20 (27.7%) of 72 patients receiving LOLA and placebo, respectively (P=0.02), with hazard ratio of 0.389 (95% confidence interval=0.174-0.870). Mortality was similar in both groups (6.8 vs. 13.8%, P=0.18). At 6 months follow-up, there was a significant change in the psychometric hepatic encephalopathy score (2.53±2.18 vs. -0.01±1.92, P<0.001), ammonia level (-23.58±14.8 vs. 1.41±13.34 μmol/l, P<0.001), CFF (5.85±4.82 vs. 0.58±4.53, P<0.001), and SIP scores (-7.89±5.52 vs. -0.95±4.25, P<0.001) in patients treated with LOLA compared with placebo. On multivariate analysis, only MELD score predicted the recurrence of overt HE, with odds ratio of 2.21 (95% confidence interval: 1.526-3.204, P<0.001). LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in psychometric hepatic encephalopathy score, ammonia level, critical flicker frequency scores, and health-related quality of life.

Management of Hepatic Encephalopathy: A Primer.

To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis All published articles evaluating treatments for HE were considered. Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Management Patterns of Hepatic Encephalopathy: A Nationwide Survey in India

Hepatic encephalopathy (HE) is a common complication of cirrhosis. There is no standard practice for its management. This survey was done to determine the diagnostic and therapeutic practices of physicians treating patients with HE in patients with cirrhosis. We designed a 21-item questionnaire, which was given to physicians working in academic and non-academic institutes and regularly treating patients with HE. Of 500 printed questionnaires, we received 451 questionnaires [323 (72%) general physicians and 128 (28%) gastroenterologists] from academic and non-academic institutes. Commonest precipitating event of HE was upper gastrointestinal bleed (47%), constipation (18%) and spontaneous bacterial peritonitis (12%). Arterial ammonia was always measured at admission by 156 (35%) physicians, never measured by 128 (28%) and sometimes by 167 (37%). Prophylactic antibiotics were used by 54% of physicians on the day of admission irrespective of any precipitating event, and 13% used antibiotics only if cultures were positive while others used antibiotics only if patient needs intubation or had variceal bleed as the cause of precipitation of HE. Disaccharides remained the mainstay of treatment in the management of HE and were always used by 87% (n=391) followed by LOLA (n=297, 66%) and rifaximin (n=276, 61%). Combination of therapy was used by 84% of respondents. Lactulose enema was used in patients with HE by 280 (62%) physicians and was thought to be as good as giving lactulose by mouth or nasogastric tube in the treatment of HE. Regarding the recovery of HE with the present mode of therapy, of 451 responses, only 11% (n=49) got 90-100% response to present therapy for the recovery of HE, while 70-90% response was seen by n=152 (34%) and 50-70% response was seen by n=183 (41%). Lactulose was prescribed as secondary prophylaxis agent more by gastroenterologists than non-gastroenterologists (76% vs 41%, P=0.001). Similarly, rifaximin was more prescribed by gastroenterologists at discharge compared to non-gastroenterologists (32% vs 17%, P=0.001). Non-absorbable disaccharides are the most commonly prescribed treatment for HE and for secondary prophylaxis of HE. Combination of therapy (lactulose and LOLA or lactulose and rifaximin) was commonly used by treating physicians.

Prophylaxis of Hepatic Encephalopathy in Acute Variceal Bleed in Patients with Cirrhosis: An Open Label Randomized Controlled Trial of Lactulose Versus Rifaximin

Prophylaxis of Hepatic Encephalopathy in Acute Variceal Bleed in Patients with Cirrhosis: An Open Label Randomized Controlled Trial of Lactulose Versus Rifaximin

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.

Disaccharides in the treatment of hepatic encephalopathy

Management of hepatic encephalopathy (HE) primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treatment of HE needs further validation in large studies.

A Randomised Double Blind Controlled Trial Comparing Rifaximin Plus Lactulose with Lactulose Alone in Treatment of Overt Hepatic Encephalopathy

Background: Hepatic encephalopathy (HE) is associated with poor prognosis. Probiotics alter gut flora with nonurease producing organism with decrease ammonia production. Present study assessed efficacy of probiotics for primary prophylaxis of HE. Methods: In prospective randomised controlled trial, patients with no history of overt HE were randomised into: group 1 [Probiotics, n=86, one capsule (110 billion CFU) TDS] and group 2 [control, n = 74]. All patients underwent psychometric tests, critical flicker frequency (CFF), glucose hydrogen breath test (GHBT) for small intestinal bacterial overgrowth (SIBO) and lactulose hydrogen breath test (LHBT) for oro-cecal transit time (OCTT). Primary end point was development of overt HE. Results: One hundred and sixty patients (age 48.6 11.1 years, M:F 96:64) were included. 25 (15.6%), 51 (31.9%) and 82 (52.5%) patients were in CTP class A, B and C respectively. Baseline laboratory parameters, CTP score, MELD score, CFF, psychometric hepatic encephalopathy score (PHES) and OCTT were comparable. Forty two patients (48.8%) in group 1 and 33 (44.6%) in group 2 had minimal HE (P=0.88). Mean follow up of Group 1 and Group 2 patients was 38.6 8.80 vs. 40.3 9.8 weeks (P =0.67). Eleven patients (6.9%) were lost during follow up. Six patients (7.5%) in group 1 and 7 (10.1%) in group 2 died (P =0.81). There was significant improvement in arterial ammonia levels, SIBO, OCTT, PHES, CFF andMHE after 3 months of treatment with probiotics. Seven (8.8%) patients in Group 1 and 14 (20.3%) patients in Group 2 developed overt HE (P <0.05, hazard ratio 2.1, 95% CI, 1.31-6.53). MHE, CTP score and SIBO correlated with development of overt HE. Conclusion: Probiotics are effective in primary prophylaxis of HE.

An open label randomised controlled trial of probiotics for primary prophylaxis of hepatic encephalopathy in patients with cirrhosis

Background and Aims: Hepatic encephalopathy (HE) is associated with poor prognosis. Probiotics alter gut flora with non-urease producing organism with decrease ammonia production. Present study assessed efficacy of probiotics for primary prophylaxis of HE.

An Open Label Randomised Controlled Trial of Probiotics for Primary Prophylaxis of Hepatic Encephalopathy in Patients with Cirrhosis

Background: Hepatic encephalopathy (HE) is associated with poor prognosis. Probiotics alter gut flora with non-urease producing organism with decrease ammonia production. Present study assessed efficacy of probiotics for primary prophylaxis of HE.

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

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

Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open-Label, Randomized Controlled Trial of Lactulose, Probiotics, and No Therapy

Lactulose is effective in secondary prophylaxis of hepatic encephalopathy (HE). Probiotics improves minimal hepatic encephalopathy (MHE), which predisposes to HE. No study has been conducted on the secondary prophylaxis of HE using probiotics. Our objective was to study the effects of lactulose and probiotics for secondary prophylaxis of HE. Consecutive cirrhotic patients who had recovered from HE were randomized to receive lactulose (Gp-L, 30 ml three times per day), three capsules of probiotics (Gp-P) per day containing 112.5 billion viable lyophilized bacteria per capsule, or no therapy (Gp-N). All patients were assessed by psychometry (number connection test (NCT-A, B), figure connection test if illiterate (FCT-A, B), digit symbol test (DST), and block design test (BDT)), critical flicker frequency (CFF) test, and arterial ammonia at inclusion. The patients were followed up monthly. The primary end point was development of overt HE according to West Haven criteria or a follow-up of 12 months. Of 360 patients who recovered, 235 (65.2%) met the inclusion criteria (Gp-L, n=80; Gp-P, n=77; and Gp-N, n=78). In all, 38 patients (16.1%) were lost to follow-up and 77 patients developed HE (Gp-L, n=18; Gp-P, n=22; and Gp-N, n=37). There was a significant difference between Gp-L and Gp-N (P=0.001) and between Gp-P and Gp-N (P=0.02) but no difference between the Gp-L and Gp-P groups (P=0.349). The rate of readmission for causes other than HE (Gp-L, Gp-P, and Gp-N, 19:21:28; P=0.134) and deaths (Gp-L:Gp-P:Gp-N=13:11:16; P=0.56) in all three groups were similar. There was a high prevalence of abnormal psychometry test results (NCT-A, 71.5%; NCT-B, 69.2%; DST, 76.9%; and BDT, 85.2%), and FCT-A and -B were abnormal in 35 of 48 patients (72.7%). CFF was <38 Hz in 118 patients (50.2%). Upon multivariate analysis, recurrence of overt HE was significantly associated with two or more abnormal psychometric tests and arterial ammonia after the recovery of an episode of HE. Lactulose and probiotics are effective for secondary prophylaxis of HE in patients with cirrhosis.

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.

Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open Label, Randomized Controlled Trial of Lactulose, Probiotics and No-therapy

Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open Label, Randomized Controlled Trial of Lactulose, Probiotics and No-therapy

Prevention of first overt episode of hepatic encephalopathy after TIPS: No easy task

Background/Aims Hepatic encephalopathy is a frequent event after transjugular-intrahepatic-portosystemic-shunt (TIPS), especially during the first months. Aim of this study was to compare two different treatments (lactitol 60 g/day, rifaximin 1200 mg/day) with no-treatment in the prevention of post-TIPS hepatic encephalopathy. Methods Seventy-five consecutive cirrhotics submitted to TIPS were randomized to receive either one of the above treatments or no-treatment. The main end-point was the occurrence of an episode of overt hepatic encephalopathy during the first month post-TIPS. Before the procedure and weekly thereafter the patients were evaluated by examining their mental status, asterixis, ammonia and trail-making-test Part-A (TMT-A). Results The three groups were comparable for age, sex, etiology, Child-Pugh-score, post-TIPS porto-systemic gradient, previous hepatic encephalopathy, basal values of ammonia and psychometric performance. Twenty-five patients developed hepatic encephalopathy (33%, CI 95%=22-45%). One-month incidence was similar in the three groups (P=0.97). Previous hepatic encephalopathy (Relative Hazard=3.79;1.27-11.31) and basal-TMT-A Z-score1.5 (RH=3.55;1.24-10.2) were predictors of post-TIPS encephalopathy at multivariate analysis. A <5 mmHg porto-systemic gradient was also significantly related to the occurrence of encephalopathy. Conclusions Our data show that treatment with lactitol or rifaximin is not effective in the prophylaxis of hepatic encephalopathy during the first month after a TIPS.