Hepatic Encephalopathy Grade Research Articles

Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study.

Acute liver failure (ALF) is an orphan disease often complicated by acute kidney injury (AKI). We assessed the impact of transient versus persistent AKI on survival in patients with ALF. International multicenter retrospective cohort. U.S. ALF Study Group prospective registry. Patients with greater than or equal to 18 years and ALF in the registry from 1998 to 2016 were included. Patients with less than 3 days of follow-up, without kidney function evaluation on day 3, or with cirrhosis were excluded. AKI was defined by Kidney Disease Improving Global Outcomes guidelines on day 1. Kidney recovery was defined on day 3 as transient AKI, by a return to no-AKI within 48 hours or persistent AKI if no such recovery or renal replacement therapy (RRT) was observed. Primary outcome was transplant-free survival (TFS) at 21 days. Among 1,071 patients with ALF, 339 (31.7%) were males, and median (interquartile range) age was 39 years (29-51 yr). Acetaminophen-related ALF was found in 497 patients (46.4%). On day 1, 485 of 1,071 patients (45.3%) had grade 3-4 hepatic encephalopathy (HE), 500 of 1,070 (46.7%) required invasive mechanical ventilation (IMV), 197 of 1,070 (18.4%) were on vasopressors, and 221 of 1,071 (20.6%) received RRT. On day 1, 673 of 1,071 patients (62.8%) had AKI. On day 3, 72 of 1,071 patients (6.7%) had transient AKI, 601 of 1,071 (56.1%) had persistent AKI, 71 of 1,071 (6.6%) had late onset AKI, and 327 of 1,071 (30.5%) remained without AKI. Following adjustment for confounders (age, sex, race, etiology, HE grade, use of IMV and vasopressors, international normalized ratio, and year), although persistent acute kidney injury (adjusted odds ratio [aOR] [95% CI] 0.62 [0.44-0.88]) or late onset AKI (aOR [95% CI] 0.48 [0.26-0.89]) was associated with lower TFS, transient AKI was not (aOR [95% CI] 1.89 [0.99-3.64]). In a multicenter cohort of patients with ALF, persistent but not transient AKI was independently associated with lower short-term TFS.

Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange

Objective To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). Methods A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. Results Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005–0.768; OR = 1.328, 95%CI: 1.153–1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187–43.796, p < 0.001). Conclusion We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.

CLINICAL PROFILE AND EVALUATION OF SERUM PROLACTIN LEVEL IN CIRRHOSIS OF LIVER WITH SPECIAL REFERENCE TO CHILD PUGH SCORE

Clinical profile and evaluation of serum prolactin level in cirrhosis of liver with special reference to Child Pugh Score. Abstract Background: With the increasing incidence of liver cirrhosis the use of a biomarker such as prolactin, indicates the severity of the disease, its complications and serves as a tool for early intervention. Aim: To study the clinical profile and evaluation of serum Prolactin level in Cirrhosis of Liver with special reference to Child Pugh Score. Materials and Methods: A observational cross sectional study on 70 patients admitted under Department of Medicine, JMCH from July 2020 to June 2021. All the patients are subjected to the routine work up for chronic liver disease including serum prolactin level. Results: A total of 70 Patients analyzed in the study. The mean age is found to be 47 years with SD ±13 years, the male and female ratio is 4:1 with mean prolactin levels among the males, it is 36.9 ng/dl with SD ±15.3 ng/dl and in females it is 42.8 ng/dl with SD ±14.2 ng/dl . Of the 70 patients in this study, 59 (84.3%) of them had serum prolactin levels elevated above 19 ng/ml with various clinical profiles . The various clinical presentations noted in our study included ascites in 69 (98.5%) patients, portal hypertension in 63( 90 %) of the patients , oesophageal varices in 44 (62.85%) with upper GI bleed in 31 (44.3%) patients, hepatic encephalopathy (grades 1-4) in 50 (71.42%) patients. Out of 70 patients 55(78.5%) were of class C in child pugh score and the mean prolactin level is found to be 43.638 ng/ml while normal serum prolactin levels is seen in all patients with Class A of Child Pugh Class with p value &lt; 0.001 . The Spearmen coefficient value i.e. the r-value was 0.830 which is a strong positive correlation between the child pugh scoring system and serum prolactin level. Conclusion: Serum prolactin level correlated with the Child Pugh score in predicting the severity of the disease. Patients with a higher serum prolactin have a greater incidence of complications of cirrhosis like PHTN, HE and Esophageal varices.

Nitrogenous compounds in the saliva and blood of cirrhotic patients: a cross-sectional study.

Serum increase of nitrogenous compounds (NC) in cirrhotic patients has been associated with the development of hepatic encephalopathy (HE). However, the relation between NC in saliva and HE is unclear. The objective of this study is to measure the levels of nitric oxide and urea in the blood and saliva in 38 cirrhotic patients and correlate them with clinical characteristics and presence and grades of HE. Automated enzymatic colourimetric assays were performed to determine the levels of NC. Diagnosis and severity of HE were determined based on the West Haven criteria and by using the inhibitory control test. HE was diagnosed in 89.47% of the patients, with the majority (60.50%) presenting covert HE. With regard to the measurement of NC, although nitric oxide is moderately correlated with its amount in blood and saliva (r = 0.630; P < 0.001), only salivary levels were associated with the presence of ascites and ecchymosis (P = 0.013 and P = 0.030, respectively). In patients with HE, the serum levels of urea were higher (P = 0.013) than those in patients without HE or minimal HE. Nitrogenous compounds in the saliva were correlated with neither the presence nor grades of HE, whereas in the blood, only urea was positively correlated with the severity and presence of HE. Saliva is an excellent fluid for diagnosing several diseases, but it does not seem to be able to collaborate with the identification of HE.

The magnetic resonance imaging assessment of optic nerve sheath diameter in pediatric acute liver failure patients.

To evaluate the diagnostic value of optic nerve sheath diameter (ONSD) using brain MRI in the pretransplantation period in the pediatric acute liver failure patients, and correlate the ONSD with clinical grade of hepatic encephalopathy (HE) and MRI findings. Forty acute liver failure patients and 40 control group patients were retrospectively analyzed. The high signal intensities in T2W (T2-weighted image), FLAIR (Fluid Attenuated Inversion Recovery) and DWI (diffusion-weighted imaging) sequences were evaluated and ONSD was measured. The patients were grouped first into 5 according to their West Haven score, and HE grade 0 and grade 1 were accepted as low grade HE, HE grade 2, 3 and 4 were accepted as high grade HE. The patients were grouped to 2 according to the MRI findings as low grade and high grade MRI group. The mean value of ONSD was 6.0 ± 1.80 and 4.94 ± 1.27 in the all patients and in the control group, respectively. There was statistically significant difference between both the ONSD and the low grade-high grade HE groups (p=0.01), and between the ONSD and the low grade-high grade MRI groups (p<0.001). Although high ONSD values do not make the diagnosis of cerebral edema, it may cause suspicion in the early period. MRI can be helpful in the diagnoses of increased intracranial pressure like ultrasound. Our study is the first study to compare ONSD and MRI findings in addition to HE grades. The widespread use of MRI in children in recent years may help determine the normal range of ONSD values.

Liver volume based prediction model for patients with hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with high short-term mortality. Early and accurate prognosis is significant for clinical decisions, in which liver volume (LV) imparts important information. However, LV has not been considered in current prognostic models for HBV-ACLF. Three hundred and twenty-three patients were recruited to the deriving cohort, while 163 were enrolled to validation cohort. The primary end-point was death within 28days since admission. Estimated liver volume (ELV) was calculated by the formula based on healthy population. Logistic regression was used to develop a prediction model. Accuracy of models were evaluated by receiver operating characteristic (ROC) curves. The ratio of LV to ELV (LV/ELV%) was significantly lower in non-survivors, and LV/ELV% ≤82% indicated poor prognosis. LV/ELV%, Age, prothrombin time (PT), the grade of hepatic encephalopathy (HE), ln-transformed total bilirubin (lnTBil), and log-transformed HBV DNA (Log10 HBV DNA) were identified as independent predictors to develop an LV-based model, LEAP-HBV. The mean area under the ROC (AUC) of LEAP-HBV was 0.906 (95% CI, 0.904-0.908), higher than other non-LV-based models. Liver volume was an independent predictor, and LEAP-HBV, a prediction model based on LV, was developed for the short-term mortality in HBV-ACLF. This study was registered on ClinicalTrails (NCT03977857).

The role of functional magnetic resonance imaging of the brain in the evaluation of hepatic encephalopathy in cirrhotic patients.

Hepatic encephalopathy (HE) is a complication of liver failure, with neurological manifestations ranging from minimal HE (MHE) to deep coma (overt HE). To demonstrate the role of functional magnetic resonance imaging (magnetic resonance spectroscopy [MRS] and apparent diffusion coefficient [ADC] value) in the assessment and grading of HE in cirrhotic patients. A prospective cohort study was conducted on three groups: group I - 20 healthy controls, group II - 25 cirrhotic patients with MHE, and group III - 25 cirrhotic patients with overt HE. Each group was subjected to MRS, diffusion-weighted imaging, and neuropsychological examinations. At 1H-MRS, the glutamate/glutamine complex (Glx), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and creatine (Cr) were determined in the basal ganglia or thalamus. The metabolic ratios and ADC values of Glx/Cr, MI/Cr, Cho/Cr, and NAA/Cr were determined. The brain metabolite Glx increased with a significant correlation to HE grade (p = 0.001). Other brain metabolites, such as Cho and mI, decreased significantly (p = 0.001). Two brain metabolites (NAA and Cr) remained unchanged across all HE grades and the control group (p = 0.47 and 0.38, respectively). There was an increase in the Glx/Cr ratio and a decrease in the mI/Cr and Cho/Cr ratios. In addition, ADC values were significantly higher in cirrhotic patients with HE than in the control group. ADC values and 1H-MRS are imaging modalities that have the potential to detect MHE and grade HE in cirrhotic patients.

Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy.

Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02–1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12–2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18–1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54–1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54–0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.

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.

Clinical characteristics of cirrhosis patients with umbilical vein recanalization: A retrospective analysis.

Umbilical Vein Recanalization (UVR) may occur in patients with long-standing portal hypertension and liver cirrhosis. This study aimed to investigate the clinical significance of UVR.Medical records of a cohort of patients with cirrhosis (n = 247) who were hospitalized at the Digestive Medicine Center of the Second Affiliated Hospital of Nanchang University from January 2012 to October 2015 were accessed. The UVR diagnosis was made by ultrasound examination and was confirmed by computerized tomography scan.The UVR incidence was 20.2% (50/247) in the cohort. The size of UVR was 9.9 ± 4.7 mm (range: 5–26.5 mm) in diameter. The UVR and non-UVR groups showed no difference in grades of hepatic encephalopathy (P = .496), Child-Pugh classification (P = .401), the incidence of moderately severe ascites (26% vs 26%, P = 1), the esophageal variceal bleeding rate (32% vs 39%, P = .402), or portal vein thrombosis (8% vs 12%, P = .580). However, the incidence of cavernous transformation of the portal vein was statistically different, that there was 0 case in the UVR group and 8 cases in the non-UVR group (P < .05).Our results suggested that UVR had little impact on the clinical manifestations of patients with liver cirrhosis, the significance of UVR as an intervention method requires further studies.

P-39 EXPERIENCE IN THE MANAGEMENT OF REFRACTORY HEPATIC ENCEPHALOPATHY THROUGH ENDOVASCULAR THERAPY

Hepatic encephalopathy (HE) is the most common neuropsychiatric syndrome secondary to portal hypertension. It usually responds to medical treatment, but sometimes HE is refractory (RHE) to usual treatment. In some patients it may be important to consider management alternatives. Endovascular therapy (ET) could be a therapeutic option in selected cases that is performed with very low frequency and the evidence is scarce. To present our experience in the management of RHE with ET. The pre and post-procedure clinical characteristics of 10 patients with RHE undergoing splenic vein embolization (n: 5) or porto-systemic bypass embolization (n: 5) between 2009-2019 were retrospectively analyzed. 7/10 were men, average age 67 years (62-79), in 70% the cause of cirrhosis was NASH, the Child Pugh average score was B (8 points), (6-11) and MELD-Na was 13 points, (9-20), in 5 patients the ammonia prior to the procedure was 134 mmol / l (range: 90-180, VN <30), the average degree of HE was 2-3 on the scale of West Haven. One week after the procedure, in all patients the grade of EH decreased to 0-1 and the ammonium to 88 mmol / l. At one month, the grade of HE was 0 in all patients and that of ammonia was 83 mmol / l. There were no complications from the procedure. The results obtained confirm that ET in patients with Child B HE and MELD-Na maximum of 20 is a safe and effective procedure, associated with clinical improvement in RHE.

Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases.

Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear.Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases.Design: We conducted a cohort study of two multicenter prospective cohorts.Setting: China.Participants: Acute-on-chronic liver disease patients with various etiologies.Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale.Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients.Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1–4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1–2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures.Conclusions and Relevance: Hepatic encephalopathy grades 3–4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.

Clinical Profile, Precipitating Factors and Outcome of Hepatic Encephalopathy in Patients with Liver Cirrhosis

Introduction: Hepatic encephalopathy (HE) is characterized by reversible neuropsychological features and is observed with advanced and decompensated cirrhosis of the liver. Patients outcomes and survival depends on clinical presentation, identification of the precipitating factor, early management, and treatment of complications. This study aims to find out the clinical profile of cirrhotic patients with hepatic encephalopathy, their precipitating factors, and clinical outcomes in patients admitted at a tertiary care Teaching Hospital in Gandaki province, Nepal.&#x0D; Materials and Methods: An observational, cross-sectional, hospital-based prospective study comprising of 140 cirrhotic patients with encephalopathy was conducted over a study period of 18 months. Their clinical profile, precipitating factors, and outcomes during hospitalization including mortality were studied. The data analysis was done using SPSS version 20 and a P-value of ≤0.05 was considered significant.&#x0D; Results: Majority (36.5%) of the patients presented with Grade II HE. Upper gastrointestinal (GI) bleeding and spontaneous bacterial peritonitis were the most common precipitating factors. Inpatient mortality was 22.9%. The increased mortality rate was observed in patients with Child class C and with higher grading (Grade III and IV) of hepatic encephalopathy and in presence of more than two precipitating factors&#x0D; Conclusion: Most of the patients presented with Grade II HE. Upper gastrointestinal bleed and infections were the most common precipitating factors. Patients with Hepatic encephalopathy of Grades III and IV, those with CTP Child class C, and in presence of more than two precipitating factors have high mortality.

Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure.

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

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.

Clinical Outcomes of Children Diagnosed Dengue-Associated Acute Liver Failure with or without N-Acetylcysteine Treatment: A Retrospective Cohort Study.

N-acetylcysteine (NAC) has been shown to prevent hepatic damage and improve microcirculatory blood flow and oxygen delivery to the tissue. Previous studies have proposed the benefit of NAC in dengue-associated acute liver failure (ALF). However, most studies are descriptive and lack comparison between groups. We aimed to compare the ALF resolution rate and mortality rate of those who received and did not receive NAC treatment. A retrospective cohort study was conducted among children aged <15 years who were diagnosed with dengue-associated ALF at a tertiary hospital in Thailand, between January 2002 and July 2019. Demographic and clinical information were collected. Main outcomes were ALF resolution and mortality rate. Thirty-three patients were included of which 16 received NAC treatment (48.5%). Mean ages were 8.5 years (SD 3.7) and mean onset of ALF was 6.3 days (SD 1.6) after onset of fever. The grading of hepatic encephalopathy (HE) and organ failure was not significantly different between the two groups. In the NAC group, 13/16 children were prescribed 100 mg/kg/day of NAC until INR <2 without HE or <1.5 with HE. NAC was initiated 1.1 days (SD 0.3) after the ALF diagnosis. The NAC group showed a higher rate of ALF resolution (75% vs. 53% in the non-NAC group, p = 0.34) with a lower mortality rate (31% vs. 53%, p = 0.36). Side effects of NAC were not found. NAC may be beneficial in dengue-associated pediatric ALF. Further well-designed randomized control trials should be carried out.

Critically Ill COVID-19 Patient with Chronic Liver Disease - Insights into a Comprehensive Liver Intensive Care.

The novel coronavirus-related coronavirus disease 2019 (COVID-19) pandemic has been relentless in disrupting and overwhelming healthcare the world over. Clinical outcomes of COVID-19 in patients with chronic comorbidities, especially in those with metabolic syndrome, are well documented. Chronic liver disease and cirrhosis patients are a special sub-group, among whom the management of COVID-19 is challenging. Understanding the pathophysiology of COVID-19 in patients with cirrhosis and portal hypertension improves our identification of at-risk patients for disease progression that will further help compartmentalize generalized and specialized treatment options in this special patient group. In this exhaustive review, we critically review the impact of COVID-19 on the liver and in chronic liver disease and cirrhosis patients. We further discuss common features associated with the pathophysiology of COVID-19 and cirrhosis, based on the renin-angiotensin system and deliberate current literature on guidelines for the treatment of COVID-19 and extrapolate the same to the cirrhosis population to provide a concise and stepwise, evidence-based management for cirrhosis patients with severe and critical COVID-19. There are no specific management guidelines for cirrhosis patients with COVID-19 and current recommendations for treatment are as per guidelines for general population. Nevertheless, specific issues like avoiding corticosteroids in decompensated patients with variceal bleeding, suspected sepsis, high grade hepatic encephalopathy and acute kidney injury, use of early mechanical ventilation strategies in those with severe ascites and hepatopulmonary syndrome, avoidance of remdesivir in advanced liver disease, and application of liver-specific severity scores for prognostication and identification of futility need to be highlighted.

The use of a single pass albumin dialysis for the management of liver failure

Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.

Endoscopic management of acute oesophageal variceal bleeding within 12 hours of admission is superior to 12–24 hours

ABSTRACT Background: Acute oesophageal variceal haemorrhage (AOVH) is a medical emergency. The American Association for the Study of Liver Diseases recommends endoscopy management as soon as possible and not more than 12 hours after presentation. The United Kingdom guidelines recommended endoscopy for unstable patients with severe acute upper gastrointestinal bleeding immediately after resuscitation and within 24 hours of admission. We aimed to evaluate the outcome of endoscopic management of AOVH in less than 12 hours compared to 12–24 hours post admission. Methods: 297 patients with AOVH were divided into groups depending on the timing of the endoscopic management: 180 within 12 h of admission and 117 patients at 12–24 hours of admission. Routine clinical and laboratory data were collected. Results: Compared to patients with endoscopic management at 12–24 hours (mean 16 hours), patients with endoscopic management within 12 hours (mean 8.3 hours) of admission had fewer hospital stay days (P = 0.001), significant reduction of ammonia levels (P < 0.0001) and significant improvement in associated hepatic encephalopathy grade 25 (p = 0.048). There were no major clinical events in the 12-hour group, but 8 events in the 12–24 hour group (p < 0.01). Conclusion: Endoscopic management of acute variceal bleeding within 12 hours of admission is superior to endoscopic management at 12–24 hours of admission regarding reduction of hospital stay, ammonia levels, correction of hepatic encephalopathy, re-bleeding and mortality rate, hence, reducing the cost of treatment benefiting patient satisfaction and improving hospital bed availability.

A Methodology to Generate Longitudinally Updated Acute-On-Chronic Liver Failure Prognostication Scores From Electronic Health Record Data.

Queries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been used in hepatology due to the inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute‐on‐chronic liver failure (ACLF) models. Here, we describe a methodology to use EHR data to calculate rolling ACLF scores. We examined 239 patient admissions with end‐stage liver disease from July 2014 to June 2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses by chart review and calculated sensitivity, specificity, and Cohen’s kappa. Of 239 patient admissions analyzed, 37% were women, 46% were non‐Hispanic white, median age was 60 years, and the median Model for End‐Stage Liver Disease–Na score at admission was 25. Of the 239, 7% were diagnosed with ACLF as defined by the North American Consortium for the Study of End‐Stage Liver Disease (NACSELD) diagnostic criteria at admission, 27% during the hospitalization, and 9% at discharge. Forty percent were diagnosed with ACLF by the European Association for the Study of the Liver– Chronic Liver Failure Consortium (CLIF‐C) diagnostic criteria at admission, 51% during the hospitalization, and 34% at discharge. From the chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1‐4) were 92%‐97% and 76%‐95%, respectively; for severe HE (grades 3‐4), sensitivities and specificities were 100% and 78%‐98%, respectively. Cohen’s kappa between flowsheet and chart review of HE grades ranged from 0.55 to 0.72. Sensitivities and specificities for NACSELD‐ACLF diagnoses were 75%‐100% and 96%‐100%, respectively; for CLIF‐C‐ACLF diagnoses, these were 91%‐100% and 96‐100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission day. Conclusion: We developed an informatics‐based methodology to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such as big data methods, to develop electronic phenotypes for patients with ACLF.