Episodes Of Hepatic Encephalopathy Research Articles

Increased rate of enteric bacteria as cause of periprosthetic joint infections in patients with liver cirrhosis

IntroductionPeriprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections.MethodsA cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed.ResultsIntestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5.ConclusionPeriprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI.

Racial and ethnic disparities in rifaximin use and subspecialty referrals for patients with hepatic encephalopathy in the United States

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions. We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management. Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist. In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities. Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes.

Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study (NCT01966419). Adult patients hospitalized with an overt HE episode, cirrhosis, and plasma ammonia above the upper limit of normal (ULN) who failed to improve after 48 hours’ standard care were randomly assigned to continuous intravenous OP (10, 15, or 20 g/day, based on Child–Turcotte–Pugh score) or matching placebo for 5 days. Plasma levels of ornithine and phenylacetic acid (PAA) and plasma/urinary levels of phenylacetylglutamine (PAGN) (primary metabolite of PAA) were regularly assessed; plasma ammonia level was the primary pharmacodynamic variable. PAA demonstrated dose‐dependent pharmacokinetics; ornithine and PAGN levels increased with dose. PAGN urinary excretion represented ~50%–60% of administered PAA across all doses. Mean reduction in plasma ammonia with OP at 3 hours postinfusion was significantly greater versus placebo (p = 0.014); and time to achieve plasma ammonia less than or equal to the ULN was significantly reduced (p = 0.028). Achievement of clinical response based on HE stage was associated with a greater reduction in mean plasma ammonia level (p = 0.009). OP effects on plasma ammonia were consistent with its proposed mechanism of action as a primary ammonia scavenger, with a significant association between reduced plasma ammonia and improvement in HE stage. OP should be further evaluated as a promising treatment for hyperammonemia in patients with overt HE.

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.

Correlation of serum sodium with severity of hepatic encephalopathy in liver cirrhosis patients presenting at Dr. Ruth K.M. Pfau Civil Hospital Karachi.

Introduction: Cirrhotic patients suddenly or insidiously develop hepatic en-cephalopathy. Approximately three-fourth of the patients usually die within 3 years of onset of their first episode of hepatic encephalopathy. Hypo-natremia, a multifactorial phenomenon in cirrhotic patients may lead to cer-ebral edema and astrocytes swelling.Objective: To determine the correlation of serum sodium with severity of hepatic encephalopathy in liver cirrhosis patients presenting at tertiary care hospital, Karachi.Methodology: This prospective cross-sectional study conducted at Depart-ment of Medicine, Civil Hospital, Karachi between October 31, 2019 till April 4,2020. Data collected from 138 patients after taking written consent; pre-sented as was as mean, standard deviation, frequency and percentages. Effect modifiers were controlled through stratification to see the effect of these on the outcome variable taking p-value of ≤0.05 as significant.Results: Among 138 patients 92 (66.7%) were male and 46 (33.3%) were female. Mean age, duration of symptoms, height, weight and serum sodium in our study was 51.14±4.49 years, 12±7.21 hours, 161±6.78 cm, 85.2±8.54 kg and 132.7±6.32 mEq/L. Out of 136 patients, 28 (20.3%), 35 (25.4%), 54 (39.1%) and 21 (15.2%) patients belonged to sodium quartile 1, 2, 3 and 4; while 21 (15.2%), 41 (29.7%), 28 (20.3%) and 48 (34.8%) belonged to hepatic encephalopathy severity grade 1, 2, 3 and 4. Hepatic encephalopathy severi-ty showed correlation with rising sodium levels.Conclusion: Hyponatremia was found with increased frequency in patients with cirrhosis of liver having a correlation with frequency and severity of hepatic encephalopathy.Key words: Encephalopathy, Liver Cirrhosis, Hyponatremia.

Porto-Sinusoidal Vascular Disease and Focal Nodular Hyperplasia-like Nodules in a Patient with Neurofibromatosis and Non-Cirrhotic Portal Hypertension

Abstract Introduction/Objective Non-cirrhotic portal hypertension (NCPH) is uncommon. The underlying pathophysiology appears to lie at the level of intrahepatic portal veins and sinusoids, hence the term “porto-sinusoidal vascular disease” (PSVD). We report a rare case of PSVD with focal nodular hyperplasia (FNH)-like nodules in a patient with neurofibromatosis type 2 (NF2). Methods/Case Report A 57-year-old male with NF2 and type 2 diabetes, presented with a large variceal bleed requiring blood transfusion and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Imaging showed a nodular liver, presumed to be cirrhosis due to non-alcoholic liver disease. Liver biopsy was not done. Thereafter, he had several episodes of hepatic encephalopathy and TIPS was downsized to prevent recurrences. The patient required liver transplantation for intractable portal hypertension and severe hepatic encephalopathy; his liver synthetic function was near normal and MELD was 11. Portal vein was patent. The explanted liver was micronodular, soft and weighed 946 grams. Unencapsulated nodules, a few mm to 1 cm in size, were present. Microscopically, there was diffuse nodularity in the absence of bridging fibrosis. Thin, incomplete curvilinear fibrous septa were present. There were aberrant veins, hypervascular portal tracts, herniated portal veins and rare occluded portal veins. Trichrome and reticulin stains confirmed architectural abnormalities including nodularity, lack of bridging fibrosis and approximation of portal tracts. Immunohistochemistry for glutamine synthetase accentuated architectural distortion and revealed nodules with FNH-like geographic areas of staining. Results (if a Case Study enter NA) NA Conclusion This is a rare case of NCPH due to PSVD in a patient with NF2. Microscopy suggested incomplete septal cirrhosis (ISC), a pattern associated with both PSVD and regression of fibrosis in a cirrhotic liver. Isolated portal hypertension without loss of synthetic function favors primary PSVD over regression of fibrosis. FNH-like nodules are consistent with regenerative changes caused by localized abnormalities of blood flow.

Effects of Albumin on Survival after a Hepatic Encephalopathy Episode: Randomized Double-Blind Trial and Meta-Analysis.

No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient’s data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21–0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient’s survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.

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.

The improvement in body composition including subcutaneous and visceral fat reduces ammonia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

BackgroundSarcopenia and myosteatosis have been associated to a poor prognosis of cirrhosis and to a higher incidence of hepatic encephalopathy (HE). The prognostic implications of visceral and subcutaneous adiposity are less known.AimTo evaluate the modifications of visceral and subcutaneous adipose tissue after TIPS and to investigate their relationships with the modification of muscle mass and with the incidence of post‐TIPS HE.Patients and Methods35 cirrhotic patients submitted to TIPS were retrospectively studied. The modification of skeletal muscle index (SMI), muscle attenuation (myosteatosis), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), assessed by CT‐scan and plasma ammonia were evaluated before and after a mean follow‐up of 19 ± 15 months after TIPS. The number of episodes of overt HE was also recorded.ResultsDuring the follow‐up, the mean SMI and muscle attenuation increased significantly; SATI significantly increased while VATI significantly decreased, although not uniformly in all patients. By comparing the patients with or without improvement in their nutritional status after TIPS, MELD remained stable while the number of episodes of overt HE was significantly lower in the patients with improved SMI and in the patients with improved SATI. Finally, inverse correlation was observed between the variation of ammonia and SATI (r = −.40; P < .05).ConclusionIn addition to muscle mass, adipose tissue is modified after TIPS. The improvement of subcutaneous adipose tissue as well as of sarcopenia and myosteatosis is associated to the amelioration of cognitive impairment independently of liver function. The correlation between adipose tissue and ammonia modification may suggest an active role of the adipose tissue in the inter‐organ ammonia trafficking.

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.

OP-3 LONG-TERM RIFAXIMIN IS SAFE AND ITS RELATED TO LESS FREQUENCY OF COMPLICATIONS LIKE VARICEAL BLEEDING IN CIRRHOTIC PATIENTS

Is well established that rifaximin (RFX) is effective as secondary prophylaxis in patients with a previous episode of hepatic encephalopathy (EH); but recently, some studies have found that RFX is related to a lower frequency of other complications. To evaluate the clinical effect of long-term prescription of RFX (more than 6 months) in cirrhotic patients, and also the possible adverse effects. A case-control study nested in a cohort which included cirrhotic patients taking secondary prophylaxis with RFX because of history of a previous EH episode. From this cohort we abstracted two different groups, cases were those who continue taking RFX for more than 6 months, controls were those who suspended RFX before the first three months because of medical indication or by their own decision and therefore they did not continue the medication for long-term. The two groups were match by age, gender, decompensation of cirrhosis (Child-Pugh B/C), history in the last year of at least an episode of variceal bleeding (VB), infections, EH, ascites, also was considered the previous use of beta-blockers and diuretics in patients with ascites. Adherence to therapy was mandatory, it was evaluated through the simplified medication adherence questionnaire (SMAQ) in all patients. Categorical variables were compared with X2 or Fisher´s exact test, odds ratios and 95% confidence intervals were also calculated. Quantitative variables were compared with Student´s t test. A p<0.05 value was considered significant. Considering the difference in incidence regarding the development of complications between the groups, we also calculate the number needed to treat (NNT) to prevent one event. A total of 139 cirrhotic patients who met the selection criteria were identified, of them, 58 were identified as cases taking long-term RFX (41.7%), and were matched with 81 controls without RFX (58.3%). The median time taking RFX was 8.5 months (range= 6-18). The mean dose identified in the medical prescriptions was 400 mg twice or thrice in day. Basal characteristics were similar in both groups (see Table). Patients taking long-term RFX had significant lower frequency of recurrence of EH (adjusted OR=0.2, 95%CI 0.1-0.4; p=0.003; NNT=3.4); and also regard the development of VB (adjusted OR=0.2, 95%CI= 0.068-0.6; p<0.0001; NNT= 4.8); despite no statistical difference, also there was a tendency to a less frequency of severe bacterial infections: RFX 1.7% vs. without RFX 8.6% (NNT= 14.5). There were no adverse effects related to the RFX prescription, neither multidrug resistant bacterial infections were documented. Long-term use of RFX (more than 6 months) was associated with significant less development of VB, less recurrence of EH, and there was a tendency to a less frequency of severe bacterial infections. Mechanisms that could explain our findings are the modulation of intestinal microbiota, reduction of bacterial translocation, reduction of the inflammatory process and secondary regulation of the portal pressure, all of them possible mediated primarily or secondarily by RFX action.

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.

Rifaximin Vs. Norfloxacin for Spontaneous Bacterial Peritonitis Prophylaxis: A Randomized Controlled Trial

Spontaneous bacterial peritonitis (SBP) heralds increased mortality in cirrhosis, mandating strategies for prophylaxis. Norfloxacin has been the recommended choice for SBP prevention. However, its use has raised concerns about antibiotic resistance. Rifaximin has been suggested as an alternative. We investigated the efficacy of rifaximin against norfloxacin in primary and secondary prophylaxis of SBP. In this open-labeled randomized trial, patients with either advanced cirrhosis having ascitic fluid protein levels (<1.5g/l), Child-Pugh score ≥9 points, serum bilirubin ≥3mg/dl or impaired renal function (primary prophylaxis group), or those with prior SBP (secondary prophylaxis group) received either norfloxacin (400mg once daily) or rifaximin (550mg twice daily). All patients were followed for six months, with the primary endpoint being the development of incident SBP. 142 patients were assessed for eligibility, of which 132 met the enrolment criteria; 12 were lost to follow-up, while 4 discontinued treatment. In patients on primary prophylaxis, occurrence of SBP was similar (14.3% vs. 24.3%, P= 0.5), whereas in secondary prophylaxis SBP recurrence was lower with rifaximin (7% vs. 39% P= 0.004). Rifaximin significantly reduced the odds for SBP development in secondary prophylaxis [OR (95% CI0.14 (0.02-0.73; P= 0.02)]. Patients receiving rifaximin as secondary prophylaxis also had fewer episodes of hepatic encephalopathy (23.1% vs. 51.5%, P= 0.02). 180-day survival between the arms in either group was similar (P= 0.5, P= 0.2). In comparison to norfloxacin, rifaximin significantly reduces incident events of SBP, as well as HE when used as a secondary prophylaxis, whereas for primary prophylaxis both have similar effects(NCT03695705). ClinicalTrials.gov number: NCT03695705.

Hepatic Encephalopathy Mimicking Creutzfeldt-Jakob Disease on Laboratory, Physiological, and Imaging Evaluations

Patient: Female, 84-year-old Final Diagnosis: Hepatic encephalopathy Symptoms: Cognitive impairment Medication:— Clinical Procedure: — Specialty: Neurology Objective: Unusual clinical course Background:Creutzfeldt-Jakob disease (CJD) is an irreversible, neurodegenerative, prion disease presenting with cognitive, behavioral, and motor dysfunction. The clinical presentations or laboratory findings of treatable autoimmune and metabolic processes may mimic those of CJD. Hepatic encephalopathy (HE) is a complication of severe hepatic failure that is characterized by neuropsychiatric manifestations. A case of HE whose laboratory, physiological, and imaging results were similar to that of Creutzfeldt-Jakob disease (CJD) in the process of treatment for HE is presented.Case Report:An 84-year-old woman with hepatic encephalopathy (HE) was admitted to our hospital because of acute consciousness disturbance. She had chronic hepatitis type C, liver cirrhosis, and hepatocellular carcinoma, and had had an episode of HE once. Her severe consciousness disturbance did not improve after treatment for concurrent hyperammonemia, unlike in her previous episode. Diffusion-weighted brain magnetic resonance imaging (MRI) showed widespread hyperintensity of the whole cortex. Her electroencephalogram showed periodic sharp wave complexes (PSWCs). Both total t-tau and 14-3-3 proteins were detected in her cerebrospinal fluid. According to these clinical data, CJD was highly suspected. However, the consciousness disturbance was alleviated by the tenth day of admission, and her general condition was markedly improved, which supported the initial diagnosis of HE.Conclusions:The present results suggest that treatable disorders, such as HE, should be considered before making a final diagnosis of a fatal disease such as CJD, since the spectrum of diseases that CJD mimics is vast. We should also aggressively treat patients with severe conditions from which recovery is possible.

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.

Transjugular Intrahepatic Portosystemic Shunt Creation for the Prevention of Gastric Variceal Rebleeding in Patients with Hepatocellular Carcinoma: A Multicenter Retrospective Study

PurposeTo evaluate the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) creation for the prevention of gastric variceal rebleeding in patients with hepatocellular carcinoma (HCC). Materials and MethodsThis multicenter retrospective study included 126 cirrhotic patients (mean age, 54.1 ± 10.2 years; 110 men) with HCC who underwent TIPS creation for the prevention of gastric variceal rebleeding. Of these, 110 (87.3%) patients had gastroesophageal varices and 16 (12.7%) patients had isolated gastric varices. Thirty-five (27.8%) patients had portal vein tumor thrombus. ResultsTIPS creation was technically successful in 124 (98.4%) patients. Rebleeding occurred in 26 (20.6%) patients during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 98.3% ± 1.2% and 81.2% ± 3.9%, respectively. Forty-nine (38.8%) patients died during the follow-up period. The 6-week and 1-year actuarial probabilities of survival were 98.4 ± 1.1% and 65.6 ± 4.4%, respectively. Two (1.6%) patients had major procedure-related complications, including acute liver failure (n = 1) and intra-abdominal bleeding (n = 1). Thirty-three (26.2%) patients had at least 1 episode of overt hepatic encephalopathy during the follow-up period. Shunt dysfunction occurred in 15 (11.9%) patients after a median follow-up time of 11.4 months (range, 1.4–41.3 months). Lung metastasis occurred in 3 (2.4%) patients, 3.9–32.9 months after TIPS creation. ConclusionsTIPS creation may be effective and safe for the prevention of gastric variceal rebleeding in patients with HCC.

Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis.

We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score. Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group. The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.

Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE)

Background & aims The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were: 1) to describe a large cohort of patients with cirrhosis in terms of neuropsychological/neurophysiological HE indices, and 2) to test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. Method 461 patients with cirrhosis (59±10 years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow up information on mortality/HE-related hospitalization in 134/127, respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow up in 124. Results Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Amongst patients without a history of overt HE, those with worse PHES had higher HE risk. Amongst patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. Conclusions In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. To determine whether rifaximin prevents overt HE after TIPS compared with placebo. Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. French Public Health Ministry.

Clinical, neuropsychological and neurophysiological indices and predictors of hepatic encephalopathy (HE).

The occurrence of overt hepatic encephalopathy (HE) marks a significant progression in the natural history of liver disease. The aims of the present study were to: 1) describe a large cohort of patients with cirrhosis in terms of neuropsychological or neurophysiological HE indices, and 2) test if the severity of liver disease and/or any such indices [Psychometric Hepatic Encephalopathy Score (PHES), Scan test, electroencephalography (EEG)] predicted mortality/HE risk in a subgroup of such cohort. Four hundred and sixty-one patients with cirrhosis (59±10years; 345 males) were included; information on previous overt HE episodes was available in 407. Follow-up information on mortality/HE-related hospitalization in 134/127 respectively. Information on previous overt HE episodes and both mortality and HE-related hospitalization over the follow-up in 124. Patients with a history of overt HE (60%) had poorer liver function, worse neuropsychiatric indices, higher ammonia levels and higher prevalence of portal-systemic shunt. The risk of HE-related hospitalization over the follow-up was higher in patients with higher MELD score and worse Scan performance. Mortality was higher in those with higher MELD. Among patients without a history of overt HE, those with worse PHES had higher HE risk. Among patients with a history, those with higher MELD, better PHES and worse Scan performance had higher HE risk. In patients without previous overt HE episodes, neuropsychological and neurophysiological tests predict HE, while in those with previous overt HE episodes, HE development largely depends on the severity of liver dysfunction.