Recurrent 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.

Endoscopic Ultrasound-Guided Transgastric Shunt Obliteration for Recurrent Hepatic Encephalopathy.

Occlusion of spontaneous portosystemic shunts (SPSSs) in patients with cirrhosis may be required in recurrent or refractory hepatic encephalopathy. We describe a novel method for occlusion of SPSS using endoscopic ultrasound (EUS). EUS-guided transgastric shunt obliteration was performed by injecting glue and coils directly into SPSS. EUS-guided transgastric shunt obliteration was performed for 7 patients in 9 sessions. Complete cessation of Doppler flow was achieved in 6/7 cases. Adequate clinical response was observed in 6/7 patients. No procedure-related severe adverse events were seen. This novel technique is a potentially effective and efficient method for shunt obliteration.

Efficacy and Safety of Rifaximin in the Prevention of Recurrent Episodes of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.

Rifaximin is an oral antimicrobial drug with a broad-spectrum effect. It locally regulates the function and structure of intestinal bacteria and decreases intestinal endotoxemia. We aimed to investigate the preventive role of rifaximin in recurrent episodes of hepatic encephalopathy in cases with a history of hepatic diseases. We searched PubMed, Scopus, and Web of Science for the relevant studies using the following search strategy: "(Rifaximin) OR (Xifaxan) AND (cirrhosis) OR (encephalopathy)." We assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: recurrence of hepatic encephalopathy, adverse events, mortality rate, and time to the first episode of hepatic encephalopathy from the time of randomization (days). We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was performed under the random-effects model. We analyzed data obtained from 999 patients from 7 included trials. The overall risk ratio proved that the rifaximin group was associated with a lower recurrence rate than the control group (risk ratio [RR] = 0.61[0.50, 0.73], P = .001). We found no significant variation in both groups regarding adverse events (RR = 1.08 [0.89, 1.32], P = .41), and mortality rates (RR = 0.98 [0.61, 1.57], P = .93). The overall risk of bias results was low. The meta-analysis showed that in patients allocated to the rifaximin group, the incidence rate of hepatic encephalopathy was significantly lower when compared with those in the control group with no difference in both groups regarding adverse events and mortality rates.

EE232 Impact of Updated Mortality Estimates on the Cost-Effectiveness of Rifaximin for the Treatment of Patients with Overt Hepatic Encephalopathy

Rifaximin is the only United States (US) Food and Drug Administration approved therapy for reducing the risk of recurrent overt hepatic encephalopathy (OHE) in adults. A study by Jesudian AB et al. (2020) showed that rifaximin ± lactulose (vs. lactulose monotherapy) is cost-effective (incremental cost-effectiveness ratio [ICER] of $29,161/quality adjusted life years [QALY] gained). The authors used mortality estimates from a single-arm, open-label study. The objectives of the current study were to: 1) identify updated rifaximin-associated OHE mortality estimates for US patients and; 2) conduct scenario analyses to assess the robustness of the original model by measuring the impact of assuming no/updated mortality estimates on the ICER of rifaximin for OHE.

An Economic Analysis of Transjugular Intrahepatic Portosystemic Covered Stent Shunt for Variceal Bleeding and Refractory Ascites in a Spanish Setting.

The primary aim is to estimate the cost-effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in two indications from a Spanish perspective. Firstly, as pre-emptive treatment for patients with acute variceal bleeding (indication1) compared with endoscopic band ligation plus drug therapy. Secondly, to treat refractory ascites (indication2) compared with large volume paracentesis. A two-state (alive and dead) Markov model was developed to capture the costs and health impact for the two indications over a 2-year time horizon with monthly cycles. In the alive state, patients could experience adverse event(s), associated with costs and disutility, such as recurrent variceal bleeding, ascites, and hepatic encephalopathy. Discount rates of 3% for utilities and costs and a cost-effectiveness threshold of €25,000 per QALY were applied. In the base case analysis, TIPSS was estimated to be cost-effective as a pre-emptive treatment for indication1 (incremental cost and QALYs of - €230 and 0.211, respectively). TIPSS also remained cost-effective (€16,819/QALY) in a conservative scenario analysis, conducted with an alternate source for clinical parameters. The key drivers of the outcomes were survival for the comparator arm, mean band ligation outpatient procedures, and TIPSS treatment costs. TIPSS was estimated to dominate the comparator for indication2 (incremental cost and QALYs of - €25,687 and 0.531, respectively). The key drivers of the outcomes were monthly paracentesis sessions and cost per inpatient stay for those undergoing paracentesis. TIPSS is likely to be a cost-effective and a cost-saving treatment in patients with cirrhosis in indications 1 and 2, compared with standard treatments. The analyses estimate clinical benefits along with reduced healthcare costs from avoided downstream resource consumption.

Abstract No. 211 To Assess the Efficacy of Endovascular Embolization of Portosystemic Shunts in Management of Recurrent Hepatic Encephalopathy (HE)

Abstract No. 211 To Assess the Efficacy of Endovascular Embolization of Portosystemic Shunts in Management of Recurrent Hepatic Encephalopathy (HE)

Hepatorenaal syndroom na embolisatie van een splenorenale shunt

Hepatorenal syndrome after embolisation of a splenorenal shunt This article discusses a case of hepatorenal syndrome after therapeutic embolisation of a splenorenal shunt in a patient with recurrent hepatic encephalopathy. The hepatorenal syndrome is a unique form of acute kidney failure in patients with end-stage liver cirrhosis and ascites. In this case, no known triggering factors were found, so it was evaluated if the embolisation of the portosystemic shunt can predispose to the emergence of a hepatorenal syndrome.

Recurrent Hepatic Encephalopathy Complicated with Hepatic Myelopathy after Secondary Resection with Hepatocellular Carcinoma: A Case Report

Hepatocellular carcinoma (HCC) is celerity increasing throughout the world with a high mortality rate. The progression of HCC in patients is induced mainly by cirrhosis and hepatitis. Surgical treatment has played a crucial role for HCC therapy, especially at the very early/early HCC stage. It is widespread for patients to experience a postoperative complication after surgery, including Hepatic encephalopathy/myelopathy. This case report disclosed in details a patient diagnosed and treated in our hospital suffered from recurrent hepatic encephalopathy along with hepatic myelopathy due to the secondary surgical resection of HCC.

Rifaximin stimulates nitrogen detoxification by PXR-independent mechanisms in human small intestinal organoids.

Recurrent hepatic encephalopathy (HE) is characterized by hyperammonaemia in combination with neuropsychiatric abnormalities and is treated with lactulose and rifaximin. Rifaximin is a pregnane X receptor (PXR) agonist with low systemic and high intestinal bioavailability. The mechanisms by which it alleviates HE are unclear. We used human small intestinal (hSI) organoids to study whether rifaximin, via PXR activation, affects the epithelial biotransformation machinery, and to gain understanding of its low systemic availability. We generated PXR knockdown hSI organoids via lentiviral delivery of short hairpin RNAs. Organoids were cultured for 24 h with rifaximin or rifampicin. RNA-sequencing and metabolomics were performed to analyse gene expression and amino acid metabolism. Luminal rifaximin was quantified by photospectrometry. Treatment of wild-type hSI organoids with rifaximin resulted in >twofold differential expression of 131 genes compared to DMSO. These effects were largely PXR independent and related to amino acid metabolism. Rifaximin decreased expression of glutaminase-2 and increased expression of asparagine synthetase and solute carrier 7A11, thereby increasing intracellular glutamine and asparagine concentrations, indicating active ammonia detoxification. Rifaximin was apically excreted into the lumen in an ATP binding cassette B1 (ABCB1)-dependent manner. Rifaximin-after uptake into enterocytes-stimulates intracellular nitrogen detoxification by PXR-independent mechanisms. Active apical excretion of rifaximin by ABCB1 into the intestinal lumen explains its low systemic bioavailability. Our study implies that rifaximin, next to modulation of the microbiome, has direct effects on ammonia scavenging in the human small intestinal epithelium.

Frequency of Recurrence of Hepatic Encephalopathy in Patients of Chronic Liver Disease Treated With Rifaximin

Aim: To determine the frequency of recurrence of hepatic encephalopathy in patients treated with Rifaximin. Study design: Observational cross-sectional study. Setting & duration: Department of Medicine, Services institute of Medical Sciences Lahore for duration of 12 months. Methodology: Hepatic encephalopathy was diagnosed using West-Haven classification in patients of chronic liver disease. Recurrence was considered if a new episode of hepatic encephalopathy occurred within 3 months after initiation of treatment. A total 120 patients of chronic liver disease having had an episode of recent hepatic encephalopathy within the last 3 months, of both genders, above 20 years of age with hepatic encephalopathy were included in the study. The patients were followed for 3 months after initiation of therapy and any episode of recurrence of hepatic encephalopathy was recorded. Results: Mean age was 51.5±12.2 years and 52.3±12.8 years respectively in Rifaximin and Placebo groups. Fourteen (23.3%) patients in Rifaximin group and 17(28.3%) in placebo group were younger than 40 years of age. Thirty-three (55%) patients in Rifaximin group were male versus 29(48.3%) patients in Placebo group. Fifteen (25%) patients in Rifaximin Group developed hepatic encephalopathy by 3 months of follow up as compared to 31(51.7%) patients in Placebo Group Conclusion: Frequency of recurrence of hepatic encephalopathy is significantly lower in Rifaximin treated patients. Keywords: Hepatic Encephalopathy, Recurrence, Rifaximin.

S3082 Novel Approach in the Management of Large Portosystemic Shunt Causing Recurrent Hepatic Encephalopathy

S3082 Novel Approach in the Management of Large Portosystemic Shunt Causing Recurrent Hepatic Encephalopathy

Spontaneous portosystemic shunt embolization in liver transplant recipients with recurrent hepatic encephalopathy

Introduction and objectivesSpontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT). PatientsWe identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected. ResultsAt presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12). ConclusionsSPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients.

Review article: post-TIPSS hepatic encephalopathy-current knowledge and future perspectives.

In light of the global rise in the burden of chronic liver diseases and liver cirrhosis, the number of patients suffering from decompensation events is expected to increase. Transjugular intrahepatic portosystemic shunts (TIPSS) provide effective long-term symptom control and may prolong transplant-free survival in portal hypertension-driven recurrent ascites and variceal bleeding. New-onset or recurrent hepatic encephalopathy (HE) after TIPSS insertion (post-TIPSS HE) represents the most severe post-interventional complication. To provide insight into the epidemiology and risk factors for post-TIPSS HE and scrutinize the current state of the art in treatment and drug therapy options. We conducted a literature search on post-TIPSS HE in patients with liver cirrhosis. Post-TIPSS HE occurs in up to 54.5% of cases and particularly early recurrent HE is associated with a dismal prognosis. In recent years, several risk factors for the development of post-TIPSS HE have been identified. These include not only parameters reflecting liver function (model for end-stage liver disease score/Child-Pugh score) as well as cognitive dysfunction caused by minimal HE but also extrahepatic factors such as sarcopenia and common medications such as proton pump inhibitors. In addition, new data on the benefit of rifaximin and of smaller stent grafts emerged and may improve the prevention of post-TIPSS HE. Careful selection of TIPSS candidates is of utmost importance to reduce the risk of post-TIPSS HE. In this narrative review, we provide a concise overview of the current epidemiology and risk factors of the treatment options for post-TIPSS HE.

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-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial

Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-α (550mg BID) or placebo for 90 days. 50% reduction in neutrophil oxidative burst (OB) at 30 days. changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. Patients were well-matched: median MELD (11 rifaximin-α vs. 10 placebo). Rifaximin-α did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p= 0.48). However, HE grade normalised (p= 0.014) and PHES improved (p= 0.009) after 30 days on rifaximin-α. Rifaximin-α reduced circulating neutrophil TLR-4 expression on day 30 (p= 0.021) and plasma tumour necrosis factor-α (TNF-α) (p <0.001). Rifaximin-α suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-α promoted a TNF-α- and interleukin-17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-α were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). Rifaximin-α led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-α plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis. ClinicalTrials.gov NCT02019784. In this clinical trial, we examined the underlying mechanism of action of an antibiotic called rifaximin-α which has been shown to be an effective treatment for a complication of chronic liver disease which effects the brain (termed encephalopathy). We show that rifaximin-α suppresses gut bacteria that translocate from the mouth to the intestine and cause the intestinal wall to become leaky by breaking down the protective mucus barrier. This suppression resolves encephalopathy and reduces inflammation in the blood, preventing the development of infection.

RIFAXIMIN EFFECTIVENESS IN PREVENTING THE RECURRENCE OF HEPATIC ENCEPHALOPATHY AMONG PATIENTS WITH LIVER CIRRHOSIS

Objective: To determine the effectiveness of rifaximin in reducing the frequency of recurrence of hepatic encephalopathy among patients with liver cirrhosis.&#x0D; Study Design: Descriptive case series.&#x0D; Place and Duration of Study: Outpatient department of Combined Military Hospital Peshawar from Jan to Jun 2017.&#x0D; Methodology: We included one hundred patients of either gender having liver cirrhosis with child Pugh B or C class with at least two previous episodes of hepatic encephalopathy. Patients were followed for six months to have any recurrence of hepatic encephalopathy. Conventional group was defined as having standard regimen including lactulose. Rifaximin treatment was defined as a 550mg BD daily dosing along with standard prescription.&#x0D; Results: Fifty patients were on conventional treatment to prevent recurrence of hepatic encephalopathy while 50 patients were using rifaximin in addition to standard prescription. The average age of 54.8 ± 6.1 years with 58% male patients and 48% in child-pugh B class. Thirty (30%) patients developed hepatic encephalopathy among the study population. 14 patients with recurrence belong to rifaximin group while 16 were on conventional treatment (p-value &gt;0.05) showing a non-significant difference. Post stratification revealed only age as a significant predictor of recurrence of hepatic encephalopathy in our study population (p&lt;0.05).&#x0D; Conclusion: Frequency of hepatic encephalopathy is similar in conventional treatment with Lactulose over six months of follow up as compared with rifaximin.

Role of circadian rhythm and autonomic nervous system in liver function: a hypothetical basis for improving the management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Recurrent hepatic encephalopathy caused by the persistent porto-systemic shunt in liver transplant recipients

Hepatic encephalopathy (HE) caused by porto-systemic shunt is one of the representative complications of liver cirrhosis, but HE is an infrequent condition after the full restoration of portal flow through liver transplantation, despite the persistence of porto-systemic shunts. We report two cases with a normal functioning liver graft and patent portal flow that developed recurrent HE after liver transplantation. We reviewed the medical record the two cases, liver transplant recipient represented HE with stable graft function. The one case received a living donor liver transplantation (LDLT) with inferior vena cava (IVC) replacement because of Budd-Chiari Syndrome. Two months after LDLT, recurrent HE occurred despite of well-functioning liver graft and patent portal vein. An abdominal computed tomography scan (CT) showed large port-systemic collaterals between mesenteric vein and IVC. The other case transferred for the further evaluation of recurrent HE. She received a deceased donor liver transplantation, 9 years ago, and a HE with hyperammonemia was repeated, despite of normal liver function test. Persistent meso-caval collateral veins were identified on CT. After the closure of shunt by the interventional angiographic embolization, hyperammonemia and HE were completely resolved. Persistent porto-systemic shunts in liver transplant recipients with stable graft function may be the cause of HE. Therefore, when liver transplant patient with stable graft function represents HE, a more thorough evaluation is needed to identify the existence of persistent porto-systemic shunts that are very rare condition.

Additional L-Carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin

Background: Data regarding the additional effect on the recurrence of hepatic encephalopathy (HE) after oral L-carnitine administration are scarce. Objective: This study aimed to assess the additional effects of L-carnitine in patients who were receiving rifaximin for HE. Methods: This randomized study comprised a screening visit and a 12-week treatment period. Patients who fulfilled the eligibility criteria were randomized to either group A (additional rifaximin) or group B (additional L-carnitine and rifaximin). Group A received 1,200 mg/day of rifaximin. Group B received 1,500 mg/day of L-carnitine and rifaximin at 1,200 mg/day. The endpoints were the changes in the portal systemic encephalopathy (PSE) index and the admission rate from the baseline for the duration of the study in both groups. Results: Eighty-three patients were randomized to either group A (n = 42) or group B (n = 41). In group A, the PSE index decreased from 0.35 ± 0.09 at baseline to 0.27 ± 0.11 on the final evaluation day (p = 0.001). In group B, the PSE index decreased from 0.37 ± 0.09 at baseline to 0.24 ± 0.11 on the final evaluation day (p = 0.001). Although there was not a significant reduction in the PSE index in group A compared to that in group B (p = 0.202), the admission rates were 30.9% and 9.8% in groups A and B, respectively. Additional L-carnitine significantly reduced the admission rate (p = 0.028). Conclusion: L-Carnitine addition reduced the risk of hospitalization for patients who received rifaximin for HE.

Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan.

Background: Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. Methods: We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. Results and Conclusions: 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.