Rifaximin vs. conventional oral therapy for hepatic encephalopathy: a meta-analysis

AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents.METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identified through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients.RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical significance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any significant difference in the above findings.CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profile.     

Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis

Hepatic encephalopathy(HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liverbrain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis.Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.     

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

Minimal hepatic encephalopathy (MHE) corresponds to the earliest stage of hepatic encephalopathy (HE). MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests. MHE may affect daily activities and reduce job performance and quality of life. MHE can increase the risk of accidents and may develop into overt encephalopathy, worsening the prognosis of patients with liver cirrhosis. Despite a lack of consensus on the therapeutic indication, interest in finding novel strategies for prevention or reversion has led to numerous clinical trials; their results are the main objective of this review. Many studies address the treatment of MHE, which is mainly based on the strategies and previous management of overt HE. Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia, and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose, antibiotics such as rifaximin, and administration of different probiotics. This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.     

Rifaximin therapy and hepatic encephalopathy: Pros and cons

Hepatic encephalopathy(HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life.Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy.Non-absorbable antibiotics,such as neomycin and paramomycin,are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects.To overcome these limitations,rifaximin use has been proposed.Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention,with a similar incidence of side-effects.Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern.Following long-term rifaximin therapy,Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients.In addition,selection of resistant mutants of both Gram-negative and-positive bacteria in the gastrointestinal tract cannot be definitely ruled out.Electrolyte alterations(sodium and potassium) have been reported during rifaximin therapy,a warning for its long-term use in cirrhotics.Moreover,a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients.The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides.While waiting for further safety data,caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to nonabsorbable disaccharides.     

Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint",characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined,and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover,in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis(SBP),hepatic encephalopathy(HE),and,portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic,immune-modulating and anti-inflammatory activity,a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE,and also to prevent the development of SBP,to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality,triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.     

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.     

Evidence-based approach to management of hepatic encephalopathy in adults

Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.     

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

BACKGROUND Hepatic encephalopathy(HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin.RESULTS188 patients were included. Median age was 57 years(IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31) and 11(IQR 9-12) respectively. The most common causes of cirrhosis were alcohol(62%), hepatitis C(31%) and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92% patients with infection(43%), GI bleeding(16%), medication non-compliance(15%) and electrolyte imbalance(14%) the most common. During a mean follow up period of 12 ± 13 mo 107(57%) patients died and 32(17%) received orthotopic liver transplantation. Themost common causes of death were decompensated chronic liver disease(57%)and sepsis(19%). The probability of survival was 44% and 35% at 12-and 24-mo respectively. At multivariate analysis a model for end stage liver disease 15 and international normalised ratio reached statistical significance in predicting mortality.CONCLUSION Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.     

Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.     

Effect of a specific Escherichia coli Nissle 1917 strain on minimal/mild hepatic encephalopathy treatment

BACKGROUNDHepatic encephalopathy (HE) can be considered a result of dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by gut-centric therapies, such as the administration of nonabsorbable disaccharides, nonabsorbable antibiotics, probiotics and prebiotics.AIMTo assess the short-term efficacy and safety of the probiotic Escherichia coli Nissle (EcN) 1917 strain compared to lactulose and rifaximin in patients with minimal/mild HE.METHODSFrom January 2017 to March 2020, a total of 45 patients with HE were enrolled in this prospective, single-centre, open-label, randomized study. Participants were randomly assigned at a ratio of 1:1:1 to one of the treatment groups: The EcN group (n = 15), lactulose group (n = 15) or rifaximin group (n = 15) for a 1 mo intervention period. The main primary outcomes of the study were changes in serum ammonia and Stroop test score. The secondary outcomes were markers of a chronic systemic inflammatory response (ІL-6, ІL-8, and IFN-γ) and bacteriology of the stool flora evaluated by specialized nonculture techniques after a 1 mo intervention period.RESULTSPatients who were given rifaximin or EcN showed a more significant reduction in serum ammonia and normalization of Bifidobacteria and Lactobacilli abundance compared to the lactulose group. However, the most pronounced restoration of the symbiotic microflora was associated with EcN administration and characterized by the absence of E. coli with altered properties and pathogenic enterobacteria in patient faeces. In the primary outcome analysis, improvements in the Stroop test parameters in all intervention groups were observed. Moreover, EcN-treated patients performed 15% faster on the Stroop test than the lactulose group patients (P = 0.017). Both EcN and rifaximin produced similar significant reductions in the proinflammatory cytokines INF-γ, IL-6 and IL-8. EcN was more efficient than lactulose in reducing proinflammatory cytokine levels.CONCLUSIONThe use of the probiotic EcN strain was safe and quite efficient for HE treatment. The probiotic reduced the ammonia content and the level of serum proinflammatory cytokines, normalized the gut microbiota composition and improved the cognitive function of patients with HE. The application of the EcN strain was more effective than lactulose treatment.     

Actigraphy： A new diagnostic tool for hepatic encephalopathy

AIM: To assess the actigraphy, an ambulatory and continuous monitoring of wrist motor activity fitted to study sleep/wake patterns in hepatic encephalopathy (HE). METHODS: Twenty-five cirrhotic patients (17 M, 8 F, mean age 56+/-11 years, 24/25 alcoholic, Child-Pugh A , B, C: 2, 6, 17) were included. The patients were classified into 3 groups: stage 0 group (n = 12), stage 1-2 group (n = 6), and stage 3-4 group (n = 7) of encephalopathy. Over three consecutive days, patients had clinical evaluation 3 times a day with psychometric test, venous ammoniemia, flash visually evoked potentials (VEP), electroencephalogram and continuous actigraphic monitoring for 3 d, providing 5 parameters: mesor, amplitude, acrophase, mean duration of activity (MDAI) and inactivity (MDII) intervals. RESULTS: Serum ammonia and VEP did not differ among the 3 groups. Electroencephalography mean dominant frequency (MDF) correlated significantly with clinical stages of HE (r = 0.65, P = 0.003). The best correlation with HE stage was provided by actigraphy especially with MDAI (r = 0.7, P < 10(-4)) and mesor (r = 0.65, P < 10(-4)). MDAI correlated significantly with MDF (r = 0.62, 0.004) and was significantly shorter in case of HE compared to patients without HE (stage 0: 5.33+/-1.6 min; stage 1-2: 3.28+/-1.4 min; stage 3-4: 2.52+/-1.1 min; P < 0.05). Using a threshold of MDAI of less than 4.9 min, sensitivity, specificity, positive predictive value, negative predictive value for HE diagnosis were 85%, 67%, 73% and 80%, respectively. CONCLUSION: Actigraphy may be an objective method to identify HE, especially for early HE detection. Motor activity at the wrist correlates well with clinical stages of HE. MDAI and mesor are the most relevant parameters.     

Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese

BACKGROUND Hepatic encephalopathy(HE) is a complication of liver cirrhosis and can result in neuropsychological and neuromuscular dysfunctions in patients. Rifaximin, an antibiotic, has been reported to decrease the occurrence of overt HE and also improve cognitive function in studies from Europe and the United States of America. There is not enough evidence of the relationship between the long-term use of rifaximin and its clinical effects in the Japanese.AIM To determine the clinical effects of long-term rifaximin therapy in decompensated liver cirrhosis patients, with overt HE or hyperammonemia.METHODS In this single-center retrospective observational cohort study, we reviewed the data of 38 patients who had taken rifaximin at the dose of 1200 mg/d for more than 24 wk. The primary outcome measured was the efficacy of long-term rifaximin use, and secondary outcome measured was the safety of its long-term use as determined by its influence on portosystemic shunts as well as Escherichia coli-related infections. Moreover, we compared the prognosis between the rifaximin group and control cases, matched for hepatic elasticity assessed by magnetic resonance ela-stography, age, and Child-Pugh classification.RESULTS Of the 38 patients included in the study, 12(31.6%) had overt HE, 27(71.1%) had complications of esophageal varices, and 9(23.7%) had hepatocellular carcinoma(HCC). The control group was matched for age, Child-Pugh classification, liver stiffness, and presence of HCC. The median of serum ammonia level before treatment was 104 μg/dL(59-297), and 2 wk after treatment, it significantly decreased to 85 μg/dL(34-153)(P = 0.002). A significantly low value of 80.5μg/dL(44-150) was maintained 24 wk after treatment. The long-term use of rifaximin did not cause a decline in liver function. Diarrhea occurred in 2 patients, who improved with the administration of probiotics, and there were no cases of aborted rifaximin therapy owing to adverse events. In patients with Child C, the survival was short, but there was no significant difference compared with that of the control group.CONCLUSION Rifaximin therapy improves overt HE. The long-term use of rifaximin in the Japanese is effective and safe.     

Simple tools for complex syndromes: A three-level difficulty test for hepatic encephalopathy

Background

Despite the impact of hepatic encephalopathy on quality of life and prognosis, easily administered tests for its diagnosis are still lacking.

Aim

To assess the usefulness of the Scan package, a three-level-difficulty computerised reaction time test, to diagnose varying degrees of hepatic encephalopathy.

Methods

Sixty-one cirrhotic patients underwent clinical evaluation, paper-and-pencil psychometry and the Scan package; 32 healthy controls served as reference.

Results

Twenty-nine patients were classified as unimpaired, 15 as having minimal and 17 as having overt hepatic encephalopathy. All healthy controls were able to complete the Scan package; in contrast, the number of patients who were able to complete three/two/one part decreased in parallel with the degree of encephalopathy (χ² = 17, p = 0.01). Reaction times in all three parts increased significantly with the severity of encephalopathy. However, the profile of increase was different [group: F(3,77) = 26, p < 0.0001; test: F(2,154) = 277, p < 0.0001; group × test: F(6,154) = 7, p < 0.0001], with different parts being more/less sensitive to varying degrees of encephalopathy.

Conclusions

The Scan package seems useful for the diagnosis of hepatic encephalopathy and covers a considerable portion of its spectrum of severity.     

乳果糖预防消化道出血后诱发肝性脑病的疗效观察

目的探讨乳果糖预防肝硬化患者上消化道出血后诱发肝性脑病的疗效。方法收集我科因乙肝肝硬化、丙肝肝硬化及其他原因导致的肝硬化出现消化道出血患者42例,随机分为观察组(n=22)和对照组(n=20)。观察组在无活动性出血后在常规治疗基础上加用乳果糖口服,对照组除不用乳果糖外,其他治疗与观察组相同。1周后观察临床症状,数字连接试验(NCT),血氨等变化以判断疗效。结果观察组2例发生肝性脑病,发生率为9.1%;对照组8例发生肝性脑病,发生率为40%(χ2=3.9450,P0.05)。两组治疗前血氨含量、NCT检测结果相似,治疗后对照组血氨含量上升、NCT延长的程度明显大于观察组。结论乳果糖是预防肝硬化患者上消化道出血诱发肝性脑病的有效方法。     

Diagnosis and treatment of hepatic encephalopathy

Hepatic encephalopathy arises from the combination of hepatocellular dysfunction and portal-systemic shunting. Encephalopathy is more prominent in advanced stages of liver cirrhosis and signals the presence of fulminant hepatic failure in patients with acute liver injury. As important as the extent of shunting is the presence of large spontaneous collaterals. Ammonia continues to be a leading toxin influencing brain function. Endogenous benzodiazepines and cytokines may contribute to one of ammonia's key effects in the brain: astrocyte swelling. The diagnosis of hepatic encephalopathy is a diagnosis of exclusion; the search for a precipitating factor should be started immediately in all cases of encephalopathy. The treatment of hepatic encephalopathy has three aims: decrease the nitrogenous load from the gut, improve the extra-intestinal elimination of ammonia and counteract central abnormalities of neurotransmission. The mainstay of treatment is directed at the colon. Newer approaches targeting the brain, such as flumazenil, have become available.     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

AIM： To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy （HE）, and the effect of Hpylori eradication in cirrhotic patients. METHODS： From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, Hpylori infection, liver impairment, blood ammonia concentration and HE. Patients with Hpylori infection were given I wk therapy with omeprazole plus clarithromycin and tinidazole. ^14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after RESULTS： Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE （SHE） was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative （n = 180） and positive （n = 277） cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 μmol/L, respectively （P 〈 0.01）, which was significantly reduced to 53.5 ± 37.7 μmol/L after bacterium eradication （n = 126） （P 〈 0.01）. Blood ammonia was 97.5 ± 81.0 μmol/L in H pylori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after Hpylori eradication （n = 11）. HE was more frequently observed in patients with H pylori infection than in those without （58.5% vs 30.6%, P 〈 0.01）. HE rate significantly dropped to 34.1% after H pylori eradiation （P 〈 0.01）. H pylori prevalence significantly differed among cirrhotic patients with HE （74.4%）, SHE （69.1%）, and those without HE （53.2%） （P 〈 0.05）. Blood ammonia level was significantly different among cirrhotic patients with HE （94.5 ± 75.6 μmol/L）, SHE （59.9 ± 49.2 μmol/L）, and without HE （47.3 ± 33.5 μmol/L） （P 〈 0.05）. Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nit     

Effect of H pylori infection and its eradication on hyperammo-nemia and hepatic encephalopathy in cirrhotic patients

AIM: To investigate the relationship between H pylori infection, blood ammonia concentration and hepatic encephalopathy (HE), and the effect of H pylori eradication in cirrhotic patients.METHODS: From July 2003 to January 2005, 457 cirrhotic patients in five regions of Zhejiang Province were enrolled. Patients were evaluated for demographics, number connection test, H pylori infection, liver impairment, blood ammonia concentration and HE. Patients with H pylori infection were given 1 wk therapy with omeprazole plus clarithromycin and tinidazole. 14C urea breath test was performed and mental symptoms and blood ammonia level were reassessed after bacterium eradication.RESULTS: Overall H pylori infection rate was 60.6%, and HE occurred in 47.5% of cirrhotic patients. Subclinical HE (SHE) was detected in 55 of 117 cirrhotic patients. Blood ammonia concentration in H pylori negative (n = 180) and positive (n = 277) cirrhotic patients was 53.8 ± 51.4 and 78.4 ± 63.6 nmol/L, respectively (P < 0.01), which was significantly reduced to 53.5 ± 37.7 nmol/L after bacterium eradication (n = 126) (P < 0.01). Blood ammonia was 97.5 ± 81.0 nmol/L in H py/ori-positive cirrhotic patients, and this did not significantly change in those with persistent infection after H pylori eradication (n = 11). HE was more frequently observed in patients with H pylori infection than in those without (58.5% vs 30.6%, P < 0.01). HE rate significantly dropped to 34.1% after H pylori eradiation (P < 0.01). H pylori prevalence significantly differed among cirrhotic patients with HE (74.4%), SHE (69.1%), and those without HE (53.2%) (P < 0.05). Blood ammonia level was significantly different among cirrhotic patients with HE (94.5 ± 75.6 nmol/L), SHE (59.9 ± 49.2 nmol/L), and without HE (47.3 ± 33.5 nmol/L) (P < 0.05). Logistic regression analysis showed that blood ammonia concentration, Child-Pugh stage, upper gastrointestinal bleeding, electrolyte disturbance, and urea nitrogen were risk factors for HE.CONCLUSION: H pylori infection is an important factor for inducing high blood ammonia concentration and HE in cirrhotic patients. H pylori eradication may be helpful for treatment and prevention of HE.     

Effects of L-carnitine in patients with hepatic encephalopathy

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind. RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.     

血清甲状腺激素水平对肝硬化患者C型肝性脑病评估的临床意义

目的探讨血清甲状腺激素水平对肝硬化患者C型肝性脑病(HE)评估的临床意义。方法对60例C型HE和120例无HE的肝硬化患者以及50例健康体检者进行血清总甲状腺素(T4)、血清总三碘甲状腺原氨酸(T3)、血清游离甲状腺素(FT4)、血清游离三碘甲状腺原氨酸(FT3)和促甲状腺素(TSH)检测,比较并分析肝硬化患者与健康体检者间甲状腺功能差异;比较60例C型HE各期(0、Ⅰ、Ⅱ、Ⅲ和Ⅳ期)之间甲状腺功能水平。统计学处理采用t检验、方差分析及x~2检验。结果肝硬化组与健康对照组间甲状腺功能比较,差异有统计学意义(P<.111),并与Child-Pugh分级有密切相关性;HE组与无HE组甲状腺功能有明显差异,TSH分别为(13.65±3.12)μU/mL、(9.26±1.86)μU/mL(P<0.01);T3分别为(0.87±0.12)nmol/L、(1.21±0.33)nmol/L(P<0.01);且在同一Child-Pugh分级,HE组与无HE组甲状腺功能亦有差异。HE不同分期甲状腺功能差异具有统计学意义(P<0.01),Ⅲ、Ⅳ期与Ⅰ、Ⅱ期组比较,差异有统计学意义(P<0.01)。入院时为Ⅲ、Ⅳ期患者与入院时为Ⅰ、Ⅱ期患者的预后差异有统计学意义(P<0.01)。结论甲状腺功能低下可能对HE的发生、发展有一定影响;甲状腺功能亦可能是影响HE预后的重要因素之一。