Prevention Of Hepatic Encephalopathy Research Articles

Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis.

There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality ofHE. We evaluated the outcomes by various parameters such as thequality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results alsodemonstrated a significant reduction in ammonia betweenL-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.

S1351 Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis

S1351 Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis

S1267 The Use of Prophylactic Treatment in the Prevention of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt

Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) procedures are indicated in the treatment of refractory ascites or variceal bleeding in patients with end-stage liver disease. Hepatic encephalopathy (HE) is a major complication of the procedure as ammonia is able to bypass the liver. Previous studies have shown prophylactic use of rifaximin to have significant benefit in primary prevention of HE. The purpose of our study was to evaluate how frequently primary HE prophylaxis medications were prescribed and to assess if this led to decreased incidence of HE. Methods: We performed a retrospective chart review of 231 patients who received TIPS over the past 10 years at our institution that also had at least one follow up visit. Patient demographics were recorded including age, race, cirrhosis etiology, cirrhotic decompensations, MELDNa, BMI, pre/post TIPS gradients, and use of HE prophylaxis medications. Diagnosis of hepatic encephalopathy was performed through chart review by reviewing both Hepatology clinic notes and all hospital admissions. Variables were analyzed using Chi-Squared test, two sample T test, and multivariate analysis for incidence of hepatic encephalopathy. Results: Our cohort included 231 patients with 95 females (41.1%) and the majority being elective cases (62.8%). Common indications for TIPS included esophageal varices (51.9%), ascites (35.5%), and hepatic hydrothorax (7.8%). There were 111 patients that were discharged with lactulose, 9 patients discharged with rifaximin, 55 patients discharged with a combination of lactulose and rifaximin, and 57 patients were discharged without HE prophylaxis. Multivariate analysis showed the incidence of HE was significantly reduced in the group of patients discharged with lactulose [Adjusted Odds Ratio (OR): 0.48, 95% CI (0.23-0.99), p=0.049] and a near significant difference in patients discharged with a combination of lactulose and rifaximin [Odds Ratio (OR): 0.48, 95% CI (0.20-1.15), p=0.100]. (Table) Conclusion: Lactulose as prophylaxis following TIPS procedure was associated with significantly decreased likelihood of developing HE. Lactulose provides a cost effective alternative to rifaximin. Table 1. - Variable Unadjusted OR 95% CI p-value Adjusted OR 95% CI p-value Age 1.019 0.993, 1.045 0.1482 1.027 0.997, 1.058 0.0781 BMI 0.994 0.959, 1.030 0.7428 0.998 0.959, 1.038 0.9097 Pre-TIPS Gradient 1.009 0.954, 1.068 0.7515 0.977 0.906, 1.053 0.5428 Post-TIPS Gradient 1.079 0.970, 1.200 0.1616 1.076 0.937, 1.236 0.2967 Gradient Change 1.016 0.953, 1.082 0.6283 NA Gender Female ref ref Male 1.459 0.854, 2.493 0.1664 1.300 0.700, 2.413 0.4066 Ethnicity White ref ref Black 0.491 0.169, 1.426 0.1908 0.373 0.105, , 1.322 0.1265 Other 0.510 0.097, 2.689 0.4274 0.388 0.0622.428 0.3115 TIPS Indication EV ref ref Ascites 0.692 0.388, 1.234 0.2118 0.599 0.285, 1.261 0.1775 Hydrothorax 1.011 0.373, 2.741 0.9823 1.130 0.369, 3.462 0.8301 Volume Overload NC Prior HE No ref ref Yes 0.810 0.4411.489 0.4971 1.380 0.636, 2.992 0.4147 Unknown 0.634 0.1832.190 0.4710 0.804 0.186, 3.469 0.7699 Prior Hep Visit No ref ref Yes 1.103 0.619, 1.966 0.7390 1.064 0.5042.245 0.8701 HE Prophylaxis Meds None ref ref Lactulose 0.491 0.257, 0.939 0.0316 0.484 0.235, 0.996 0.0486 Rifaximin 1.048 0.255, 4.313 0.9478 1.326 0.234, 7.503 0.7495 Both 0.518 0.244, 1.100 0.0871 0.476 0.197, 1.153 0.1000 Surgery Elective ref ref Emergent 1.483 0.867, 2.538 0.1503 1.523 0.729, 3.180 0.2632

Construction of an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing.

To establish an early warning model of hepatic encephalopathy in patients with liver cirrhosis based on psychological testing. Data including patient demographics, number connection test-A (NCT-A), digit symbol test (DST), Model for End-Stage Liver Disease (MELD) scores were collected for patients admitted to a tertiary hospital in Shanghai with liver cirrhosis between January and December 2019. Patients were divided into two groups based on the development of hepatic encephalopathy (the hepatic encephalopathy group and non-hepatic encephalopathy group). Risk factors for hepatic encephalopathy in patients with liver cirrhosis were determined by using the binary logistic regression. We developed a predictive model in accordance with the STARD statement criteria (Supplementary File S1) with a cut-off value determined by receiver operating characteristic (ROC) curve analysis and calculation of the Youden index. A total of 417 patients with liver cirrhosis were included in the present study. Of these, 33 out of 66 patients with abnormal psychological tests had hepatic encephalopathy during hospitalisation. In contrast, 6 out of 317 patients with normal psychological tests had hepatic encephalopathy. Logistic regression analysis identified age, MELD score, and abnormal psychological tests as risk factors for hepatic encephalopathy in patients with liver cirrhosis. The area under the ROC curve for our prediction model for hepatic encephalopathy in patients with liver cirrhosis was 0.950 and the largest calculated Youden index was 0.804, which corresponds to a cut-off value is 0.0307. Greater age, higher MELD score and abnormal psychological tests were significantly associated with increased risk of hepatic encephalopathy indicating early warning systems and identification of abnormal psychological tests are important components of the clinical nursing care process for cirrhotic patients. Our early warning model based on psychological testing can provide a basis for nursing observation and prevention of hepatic encephalopathy. Risk assessments for hepatic encephalopathy according to liver function and psychological tests, in addition to traditional neurological observations and dietary guidance, have utility in decreasing the incidence of hepatic encephalopathy.

The importance of electroencephalography in the diagnosis of hepatic encephalopathy due to cirrhosis – a case report

Introduction and aim. Hepatic encephalopathy (HE) associated with cirrhosis of the liver is a neuropsychiatric syndrome, with symptoms ranging from barely detectable changes to deep coma. It frequently occurs in the form of episodes and relapses and can be triggered by external factors. HE severity is graded according to the West Haven criteria. The aim of the study is to draw attention to the ever-important and often key role of electroencephalography in the diagnosis of hepatic encephalopathy, even in today’s era of increasingly advanced diagnostic methods. Description of the case. A 57-year-old patient, professionally active at the time, was admitted to the hospital’s Neurology Department on an emergency basis due to difficulties with standing and moving, orientation disorders and limb tremor. Conclusion. While HE pathogenesis is multifactorial, the most important factors include increased brain exposure to ammonia, intestinal dysbiosis, and endotoxemia inducing a systemic inflammatory response. Patient observation, blood laboratory tests, neuropsychological tests and neurophysiological tests (EEG and evoked potentials) play an important role in establishing the diagnosis. Treatment and secondary prevention of hepatic encephalopathy include elimination of triggers and reduction of ammonia production and improvement of its metabolism.

S1240 Investigation of the Benefit of Fecal Microbiota Transplantation in Prevention of Hepatic Encephalopathy in Patients With Decompensated Liver Cirrhosis: A Systematic Review and Meta-Analysis of Clinical Trials

Introduction: Patients with decompensated liver cirrhosis are at risk of developing hepatic encephalopathy (HE).The current standard of care (SOC) in HE consists of correcting precipitating factors, nutritional support, and the use of lactulose and rifaximin. Lactulose and rifaximin are thought to alter gut flora thereby reducing ammonia production. Recent studies have investigated the benefit of fecal microbiota transplantation (FMT) in preventing HE in patients with liver cirrhosis. We performed a systematic review and meta-analysis to evaluate the benefit of FMT versus SOC in preventing HE and various outcomes in patients with decompensated liver cirrhosis. Methods: A literature search was performed using Scopus, PubMed/MEDLINE, and Cochrane databases from inception to June 2021. Studies included in our meta-analysis involved adult patients diagnosed with decompensated liver cirrhosis who received prophylactic FMT versus standard of care (SOC). Analysis was conducted using the Mantel-Haenszel model to assess the rate of HE, severe adverse events (SAE), death, variceal bleeding, and infection risk. The results were pooled together using Reviewer Manager 5.4 software, and heterogeneity was quantified using I2 statistics. Results: Five clinical trials involving 129 patients were included in the final analysis. All studies but one were randomized controlled trials. Our findings suggest that FMT provides a significant benefit in preventing HE in patients with decompensated liver cirrhosis (OR 0.12, 95% CI [0.02, 0.58], P=0.009) compared to SOC. The rate of severe adverse events was significantly lower in the FMT group (OR 0.07, P< 0.0001). The rates of death (OR 0.33, P=0.05), variceal bleeding (OR 0.51, P=0.30), and infection (OR 1.01, P=0.98) was similar between both groups. Only one study investigated the rate of spontaneous bacterial peritonitis, as a result, analysis was not performed for this outcome. Conclusion: Prophylactic use of fecal microbiota transplantation demonstrated a significant benefit in preventing hepatic encephalopathy and serious adverse events in patients with decompensated liver cirrhosis as compared to standard of care. There were no differences noted in terms of death rate, variceal bleeding, or the incidence of infection. The major limitation of this systematic review is the scarcity of studies about this topic and the small sample size of the analyzed studies.Figure 1.: Multivariate analysis for risk factors for NAFLDTable 1.: Clinical characteristics of the study population

Alcohol use disorders and the brain.

A diagnosis of alcohol use disorder is associated with a higher risk of dementia, but a dose-response relationship between alcohol intake consumption and cognitive impairment remains unclear. Alcohol is associated with a range of effects on the central nervous system at different doses and acts on a number of receptors. Acute disorders include Wernicke's encephalopathy (WE), traumatic brain injury, blackouts, seizures, stroke and hepatic encephalopathy. The most common manifestations of chronic alcohol consumption are Korsakoff's syndrome (KS) and alcohol-related dementia (ARD). There is limited evidence for benefit from memantine in the treatment of ARD, but stronger evidence for the use of high-dose parenteral thiamine in the progression of neuropsychiatric symptoms for WE. Accumulating evidence exists for pharmacological treatment in the prevention of hepatic encephalopathy. Rehabilitation of people with ARD may take several years, and requires an approach that addresses physical and psychosocial factors.

Current state of knowledge of hepatic encephalopathy (part III): non-absorbable disaccharides.

Nonabsorbable disaccharides have been the mainstay of treatment for hepatic encephalopathy since introduced into clinical practice in 1966. Their beneficial effects reflect their ability to reduce the intestinal production/absorption of ammonia. A recent Cochrane review confirmed the efficacy and safety of nonabsorbable disaccharides for the treatment and prevention of hepatic encephalopathy in patients with cirrhosis. The findings were robust and support the use of nonabsorbable disaccharides as a first line treatment for hepatic encephalopathy, in this patient population, and for its prevention.

Short- and long-term evolution of the endoluminal diameter of underdilated stents in transjugular intrahepatic portosystemic shunt

The purpose of this study was to evaluate the short- and long-term evolution of endoluminal diameter of covered metallic stents that were underdilated at the time of transjugular intrahepatic portosystemic shunt (TIPS) creation. Sixteen patients (13 men, 3 women) with a mean age of 57.6years±7.9 (SD) were retrospectively included. All patients had had TIPS creation using a 10-mm diameter covered stent (VIATORR®) that was underdilated (i.e., 8mm) at the time of stent placement. Measurements of the mean circulating diameter of the stents were retrospectively performed on angiographic examinations every 6months up to 2years. The endoluminal stent diameter early enlarged from 8.96mm±1.12 (SD) to 10mm±1.45 (SD) after 6months (P=0.04) with no further significant changes over time after 12months (10.28mm±1.9mm), 18months (9.93±1.51mm) and 24months (9.92±0.9mm). Our results demonstrate a passive expansion of initially underdilated covered stents during the six months following TIPS creation. This should be taken into account regarding hepatic encephalopathy prevention during TIPS placement.

Clinical outcome prediction in aneurysmal subarachnoid hemorrhage - Alterations in brain-body interface.

Background:Brain–body associations are essential in influencing outcome in patients with ruptured brain aneurysms. Thus far, there is scarce literature on such important relationships.Methods:The multicenter Tirilazad database (3551 patients) was used to create this clinical outcome prediction model in order to elucidate significant brain–body associations. Traditional binary logistic regression models were used.Results:Binary logistic regression main effects model included four statistically significant single prognostic variables, namely, neurological grade, age, stroke, and time to surgery. Logistic regression models demonstrated the significance of hypertension and liver disease in development of brain swelling, as well as the negative consequences of seizures in patients with a history of myocardial infarction and post-admission fever worsening neurological outcome.Conclusions:Using the aforementioned results generated from binary logistic regression models, we can identify potential patients who are in the high risk group of neurological deterioration. Specific therapies can be tailored to prevent these detriments, including treatment of hypertension, seizures, early detection and treatment of myocardial infarction, and prevention of hepatic encephalopathy.

PH-sensitive microemulsion-based gels for removal of colonic ammonia: a novel preventative oral preparation for hepatic encephalopathy in rats.

Microemulsions with limited stability in mimetic gastrointestinal environments have previously demonstrated potential for the effective removal of ammonia from artificial colonic fluid. Specialized pH‑sensitive microemulsion‑based gels for the removal of colonic ammonia (MBG‑RCA), however, possess relative stability in the gastrointestinal (GI) tract of normal rats, indicating potential use in in vivo applications. An investigation of the effects of oral MBG‑RCA was conducted in order to evaluate the reduction of intestinal ammonia and the prevention of hepatic encephalopathy (HE) in rat models. Eighty rats were allocated into eight 4‑day treatment groups: The HE model (intraperitoneal injection of thioacetamide) group; the high‑, medium‑ and low‑dose MBG‑RCA therapeutic groups (15, 10 and 5 ml/kg MBG‑RCA, respectively); and the normal, blank, lactulose and acetic acid control groups, each of which received daily treatment administration. Oral MBG‑RCA effects were identified using behavioral monitoring observed by an infrared night vision supervisory control system, electroencephalograms, blood ammonia levels, intestinal ammonia levels, liver functionality and pathological observation. High‑ and medium‑dose oral administrations of MBG‑RCA significantly decreased the blood and intestinal ammonia levels (P<0.05), improved liver functionality and reduced the clinical manifestations of HE in rats. MBG‑RCA demonstrated high clearance of rat colonic ammonia while maintaining sufficient stability in the GI tract, indicating the potential for the development of new clinically relevant oral preparations for the prevention of HE. Additionally, such preparations are advantageous in that ammonia is eliminated without the production of potentially harmful metabolic byproducts.

Protein Recommendations for Older Adults with Cirrhosis: A Review

Protein intake has a key role in liver cirrhosis in older adults. However, types and amounts of protein intake in cirrhosis have been controversial. The aim of this paper is to investigate the optimal protein intake for management of cirrhosis and prevention of hepatic encephalopathy in older adults. Protein restriction of 0.6 g/kg/d has traditionally been used as medical nutrition therapy in liver cirrhosis. However, recent evidence has shown that protein restrictions have many negative consequences for older adults with cirrhosis. Current research indicates protein intakes of 1.2-1.5 g/kg/d in liver cirrhosis; however, many older adults do not consume this amount. Strategies to help increase protein intake and manage cirrhosis include ensuring adequate protein at every meal through either regular intake or supplementation, protein supplementation prior to bedtime or overnight, and supplementation with branched-chain amino acids. An emphasis on vegetable protein versus animal protein is probably not an advantageous treatment option because of lack of conclusive evidence regarding benefits and potential negative side effects.

Probiotics for Secondary Prevention of Hepatic Encephalopathy

Previous nonblinded studies suggest that probiotics plus lactulose may be effective in preventing recurrent hepatic encephalopathy (HE; NEJM JW

Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy.

Spontaneous portosystemic shunt (SPSS) is a frequent cause of recurrent hepatic encephalopathy (HE) in patients with cirrhosis. To assess the effectiveness and optimal candidate selection for embolisation of SPSS, for the treatment of recurrent HE in patients with cirrhosis. This retrospective cohort study compared 17 patients with recurrent HE who achieved complete occlusion of SPSS by angiographic embolisation and 17 control patients. Most baseline characteristics were similar in the two groups. The 2-year HE recurrence rate was significantly lower in the embolisation than in the control group (39.9% vs. 79.9%, P = 0.02), whereas their 2-year overall survival rates were similar (64.7% vs. 53.4%, P = 0.98). Model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) score were significant predictors of 2-year patient mortality in the embolisation group. Analysis of patients with MELD <15 in the absence of hepatocellular carcinoma (HCC) showed that 2-year overall survival rate was significantly higher in the embolisation group than in the control group (100% vs. 60%, P = 0.03). The median changes in MELD (-1.6 vs. 2.5, P < 0.01), CTP score (-3 vs. 0, P < 0.01), and liver volume (61 mL vs. -117 mL; P = 0.046) at 1 year significantly favoured the embolisation group. Serious clinical complications after embolisation occurred only in patients who had MELD ≥15 and/or HCC at baseline, with all six dying within 1 year. Embolisation of a large spontaneous portosystemic shunt may be associated with improved survival and liver function, as well as prevention of hepatic encephalopathy in cirrhotic patients with recurrent hepatic encephalopathy and modestly preserved liver function.

Role of the heme oxygenase/carbon monoxide pathway in the pathogenesis and prevention of hepatic encephalopathy

Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis and its pathogenesis has yet to be fully elucidated. Previous studies have demonstrated that heme oxygenase-1 (HO-1) is important in the induction of liver cirrhosis. The present study aimed to investigate the role of HO-1 in the pathogenesis of HE. Rats were divided into 5treatment groups; sham, bile duct ligation (BDL), HE, zinc protoporphyrin (ZnPP) and cobalt protoporphyrin (CoPP). The levels of HO-1 were examined by western blotting and quantitative real-time PCR (qRT-PCR). Serum levels of carboxyhemoglobin (COHb), ammonia levels in the plasma and brain, brain water content and portal vein pressure (PVP) were also quantified. Aquaporin-4 expression levels were measured by immunohistochemistry and qRT-PCR. The results demonstrated that the levels of HO-1 in the brain and the serum levels of COHb were significantly increased in the HE group compared with the BDL group. Brain water content, PVP and ammonia levels in the plasma and brain were increased in the HE and CoPP groups; however, these were reduced following the treatment with ZnPP. The levels of AQP-4 expression and oxidative stress in the brain were reduced following treatment with ZnPP and increased following treatment with CoPP. In conclusion, following the inhibition of HO-1 expression, treatment with ZnPP improved HE due to reducing the expression levels of AQP-4 and oxidative stress. Therefore, ZnPP treatment may represent a novel therapeutic approach for HE.

Combination Therapy for the Treatment and Prevention of Hepatic Encephalopathy

To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE). A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English. Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and/or probiotics. Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose/neomycin versus placebo or rifaximin/lactulose, 1 assessed the use of rifaximin/lactulose without a control group, and the fourth found no significant difference between lactulose/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics. The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.

Lactulose a day keeps encephalopathy at bay

Lactulose a day keeps encephalopathy at bay

Hyponatremia in cirrhosis: clinical features and management

The presence of dilutional hyponatremia has a poor prognosis for survival in patients with cirrhosis and ascites. Effective and safe treatments are needed to improve prognosis in patients with cirrhosis and dilutional hyponatremia. The initial approach to management includes fluid restriction, low sodium diet, and minimizing the use of diuretics. In addition, the use of hypertonic saline should be avoided in patients with cirrhosis and dilutional hyponatremia. Furthermore, patients should be placed on the top of the list for liver transplantation if they are appropriate candidates. Although V2 arginine vasopressin receptor antagonists that selectively enhance solute-free water excretion in patients with cirrhosis seem very promising, two points must be considered in relation to the available data. First, although the results of phase-2 studies are encouraging, the efficacy and safety of these compounds should be further evaluated. Second, the clinical utility of these agents in cirrhosis has only been assessed in short-term studies. The long-term effects of these drugs remain unknown. Future research with these compounds should not only focus on the effects on serum sodium, but also on treatment and prevention of recurrence of ascites. In addition, the possible beneficial effects of these drugs in the prevention of hepatic encephalopathy would be worth studying.

220 Randomised controlled trial for the prevention of hepatic encephalopathy after transjugular intrahepatic porto-systemic shunt (TIPS): Comparison between lactitol, rifaximin and no treatment

220 Randomised controlled trial for the prevention of hepatic encephalopathy after transjugular intrahepatic porto-systemic shunt (TIPS): Comparison between lactitol, rifaximin and no treatment

Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis.

Hepatic encephalopathy is one of the major complications in decompensated liver cirrhosis. The current study was conducted to clarify the mechanisms of zinc deficiency in liver cirrhosis and its involvement in hepatic encephalopathy via ammonia metabolism. Ten patients each with compensated or decompensated liver cirrhosis and 11 healthy volunteers were enrolled in the study. Serum zinc levels and its daily urinary excretion were measured, an oral zinc-tolerance test was performed to examine zinc malabsorption, and the effects of diuretics on zinc excretion and of zinc supplementation on ammonia metabolism in the skeletal muscle were studied. The mean serum zinc levels in patients with decompensated liver cirrhosis were found to be significantly lower than the levels in controls and patients with compensated liver cirrhosis. The serum zinc levels were inversely correlated with blood ammonia in the fasting state. In the oral zinc-tolerance test, the percent increase in serum zinc levels 120 and 180 min after ingestion was less in cirrhotic patients than in controls. A diuretic administration resulted in a significant reduction in serum zinc levels. An increased uptake of ammonia by and an increased release of glutamine from leg skeletal muscle after oral supplementation of zinc sulfate were evident. Taken together, zinc deficiency in decompensated cirrhotic patients appears to be due to low absorption and to high urinary excretion, for which excessive diuretic administration is, in part, responsible, and zinc supplementation might play an important role in the prevention of hepatic encephalopathy by activating glutamine synthetase.