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Summary: Background and Aims: The prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD)‐related cirrhosis has been increasing these last decades. There are no data regarding the prevalence of MASLD‐related cirrhosis in intensive care unit (ICU). Methods: Prospective single‐centre study in a cohort of patients hospitalized in the ICU of Hepatology La Pitié‐Salpêtrière Hospital between January 2019 and September 2021. We analysed three groups of patients: MASLD‐cirrhosis (alcohol ≤210 g for men and 140 g weekly for women), ALD (alcohol‐related liver disease, alcohol>140 g weekly for women or >210 g for men)‐cirrhosis alone and MetALD (metabolic and alcohol‐related liver disease)‐cirrhosis. Endpoints were 1‐year transplant‐free survival (TFS), further acute decompensation (AD) and re‐admission. Results: A total of 410 patients were hospitalized, and 315 analysed: 39 in MASLD, 160 in ALD and 116 in MetALD groups. The global prevalence was 10% for MASLD, 41% ALD and 29.7% for MetALD. Patients in the MASLD group were significantly older (65 vs. 57 and 59 years, p < 0.001), and had lower Child‐Pugh (8 vs. 11 vs. 10, p < 0.001) and MELD score (17 vs. 22 vs. 21, p < 0.001). The 1‐year TFS was not different between groups (53% vs. 54% vs. 54%, p = 0.96). Cardiovascular mortality was <5% in all groups. The 1‐year probability of developing hepatic encephalopathy was significantly higher in the MASLD group (73% vs. 27% and 21%, p < 0.001). There was no difference regarding the development of other complications between groups. Conclusion: MASLD or MetALD was responsible for 1/3 of the causes of cirrhosis in the ICU. MASLD‐related cirrhosis is as severe as ALD‐related cirrhosis. Liver transplantation should be rapidly discussed. [ABSTRACT FROM AUTHOR]

Summary: Background/Aims: Although it is well admitted that cirrhotic patients display various causes of neurocognitive impairment (NI) hampering the diagnosis of covert hepatic encephalopathy (CHE), those are almost never investigated per se. The aims of this study were, in cirrhotic patients displaying cognitive complaints explored by a complete multimodal work‐up, to assess: (1) the prevalence of CHE and/or that of other causes of NI and (2) their outcomes, according to the cause of NI. Methods: Prospective cohort of cirrhotic patients referred in a dedicated clinic because of cognitive complaints. Work‐up included a complete neuropsychological assessment, electroencephalogram (EEG) and brain magnetic resonance imaging with spectroscopy. The diagnosis of CHE was made by an adjudication committee involving the physicians/neuropsychologist. Results: One hundred and twenty‐three patients were included (alcohol/MASLD/virus in 63/53/14%, MELD = 11). Sixty‐six per cent of them were diagnosed with CHE; among them, 73% exhibited also other causes of NI, mainly cerebrovascular diseases/psychiatric. Among patients without CHE, 48% and 59% displayed pathological Psychometric Hepatic Encephalopathy Score and animal naming test, respectively. Clinical improvement was observed in 77% of the patients re‐evaluated after specific management. CHE, but not the other causes of NI, was independently associated with OHE occurrence. Conclusion: Other causes of NI than CHE are frequent in patients with cirrhosis, and not ruled‐out by the classical tests dedicated to CHE. Prognosis was influenced by the cause of NI. The management of patients even without CHE led to clinical improvement, underlining the need for a multifaceted approach of cirrhotic patients with cognitive complaints. [ABSTRACT FROM AUTHOR]

Background and objectives: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. Methods: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. Results: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. Conclusions: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusions It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients.An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison.Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p = .049), LDL‐cholesterol (97 mg/dL vs. 76 mg/dL, p = .018), white cell count (7.96 × 109/dL vs. 6.24 × 109/dL, p = .039) and platelets (129 × 109/dL vs. 101 × 109/dL, p = .039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p = .020). Multivariable analysis showed that this risk was significantly higher in non‐recompensated patients (p = .003) but no differences were observed in recompensated compared with compensated patients (p = .816). Similarly, decompensated patients presented lower survival rates (p = .011), while no differences were observed between recompensated and compensated patients (p = .677).Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication. [ABSTRACT FROM AUTHOR]

Purpose: To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices. Materials and methods: Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30–70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage. Results: Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 − 1,224 days). Conclusion: Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage. [ABSTRACT FROM AUTHOR]

Background & Aims: The benefits of prophylactic antibiotics in patients with alcohol‐associated hepatitis (AH) receiving steroids remain unclear. We aimed to assess the clinical impact of prophylactic antibiotics in AH patients receiving steroids. Methods: We systematically reviewed four electronic databases from inception to 30 November 2023. Pooled estimates were analysed using random‐effects models. The primary outcome was 90‐day survival. Secondary outcomes included infection at days 30 and 90 days, hepatorenal syndrome (HRS), acute kidney injury (AKI), hepatic encephalopathy (HE) and drug‐related adverse events (AE). Trial sequential analyses were performed for the primary outcome of 90‐day mortality. Results: We screened 419 articles and included six eligible studies (four RCTs and two matched cohort studies) with a total of 510 patients. Compared to standard medical treatment (SMT), prophylactic antibiotics were associated with a lower risk of infection at 30 days (OR: 0.35, 95%CI: 0.20–0.59, I2 = 0%), infection at 90 days (OR: 0.26, 95%CI: 0.10–0.67, I2 = 0%) and a lower rate of HE (OR: 0.32, 95%CI: 0.12–0.87, I2 = 0%). However, prophylactic antibiotics did not improve 90‐day survival, sepsis‐related mortality, HRS, or AKI. The risks of drug‐related AE and fungal infections were similar in patients with AH who received prophylactic antibiotics or SMT. Using trial sequential analysis, the minimum sample size required to detect a 15% relative risk reduction in 90 days mortality with prophylactic antibiotics was 1171. Conclusions: In hospitalized AH patients receiving steroid therapy, prophylactic antibiotics reduced the risk of infection and HE, but did not improve survival or prevent AKI compared to SMT. [ABSTRACT FROM AUTHOR]

Type‐2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis‐related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long‐term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin‐treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p =.016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long‐term HA administration was associated with better survival and a lower incidence of cirrhosis‐related complications. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is characterized by a systemic inflammatory response, predominantly associated with hepatitis B virus in the Asia-Pacific region, with a high short-term mortality rate. The platelet to high-density lipoprotein ratio (PHR) has been used to predict the prognosis of patients with various inflammatory diseases. We aim to is to use the PHR to predict the short-term prognosis of patients with HBV-ACLF. Method: In this study, we retrospectively analyzed clinical data from 270 HBV-ACLF patients. Using logistic regression, we identified independent risk factors for short-term mortality and developed a prognostic model. This model was then validated, compared, and its clinical utility assessed via decision curve analysis (DCA). Results: Among the 270 HBV-ACLF patients, 98 patients died within 28 days. The deceased group exhibited a higher proportion of severe hepatic encephalopathy and ascites. Additionally, there was a statistically significant difference (P = 0.046) in the novel inflammation scoring system, PHR, between the two groups. Following stringent variable selection, PHR was identified as a predictive factor for short-term mortality in HBV-ACLF patients using logistic regression analysis (OR: 0.835 (0.756–0.999), P = 0.009), and it exhibited a synergistic effect with certain traditional scores. The prognostic model constructed based on PHR demonstrated a superior ability to predict short-term mortality compared to traditional scores such as Child-Turcotte-Pugh (AUC: 0.889). Evaluation using calibration curves and decision curve analysis (DCA) suggested its practical utility. Conclusion: PHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Background: Hepatic encephalopathy (HE) is a neurological disorder resulting from advanced liver injury. HE has a high mortality rate and poor prognosis. The pathogenesis of HE is still unclear, which has led to the lack of a satisfactory specific treatment method. There is increasing evidence that the intestinal flora affects the communication between the gut and the brain in the pathogenesis of HE. Adjusting the intestinal flora has had a beneficial effect on HE in recent studies, and the Qingchang Ligan formula (QCLG) has been shown in previous studies to regulate intestinal flora and metabolites. In this study, we established a thioacetamide-induced HE mouse model to evaluate the protective effect of QCLG on HE and explore its potential mechanism, which also demonstrated that intestinal flora dysbiosis is involved in the pathogenesis of HE. Methods: Mice were intraperitoneally injected with thioacetamide (TAA, 150 mg/kg) to induce HE. Additionally, they were orally administered Qingchang Ligan Formula (QCLG) at a dose of 6.725 g/kg·d for seven days, while control mice received an equal volume of saline via gavage. Subsequently, samples were subjected to 16S ribosomal ribonucleic acid (rRNA) gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS), and RNAsequencing (RNA-seq) analysis. Result: QCLG improved weight loss, cognitive impairment, neurological function scores, blood ammonia, and brain gene expression of interleukin-6 (TNF-a), Interleukin-1b (IL-1b), and interleukin-6 (IL-6) induced by HE. Moreover, QCLG increased the levels of liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum TNF-a, IL-1b, and IL-6. 16S RNA sequencing revealed increased Oscillibacter, Colidextribacter, and Helicobacter in TAA-induced mouse fecal samples. Also, the abundance of Bifidobacterium decreases TAA-induced mouse fecal samples. In contrast, QCLG treatment significantly restored the gut microbial community. Metabolomics indicated significant differences in some metabolites among the normal control, treatment, and model groups, including 5-methoxytryptophan, Daidzein, Stercobilin, and Plumieride (PLU). Conclusion: QCLG can alleviate neuroinflammation and prevent HE caused by liver injury by regulating intestinal flora in mouse models. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a life-threatening disorder characterised by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease. The cause of ALF varies across the world. Common causes of ALF in adults include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis. The cause of liver failure affects the management and prognosis, and therefore extensive investigation for cause is strongly suggested. Sepsis with multiorgan failure and cerebral oedema remain the leading causes of death in patients with ALF and early identification and appropriate management can alter the course of ALF. Liver transplantation is the best current therapy, although the role of artificial liver support systems, particularly therapeutic plasma exchange, can be useful for patients with ALF, especially in non-transplant centres. In this Seminar, we discuss the cause, prognostic models, and management of ALF. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. Method: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. Results: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. Conclusion: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future. [ABSTRACT FROM AUTHOR]

Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of –0·05 (95% CI –0·10 to –0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that develops in patients with severe liver dysfunction and/or portocaval shunting. Despite more than a century of research into the relationship between liver damage and development of encephalopathy, pathogenetic mechanisms of hepatic encephalopathy have not yet been fully elucidated. It is generally recognized, however, that the main trigger of neurologic complications in hepatic encephalopathy is the neurotoxin ammonia/ammonium, concentration of which in the blood increases to toxic levels (hyperammonemia), when detoxification function of the liver is impaired. Freely penetrating into brain cells and affecting NMDA-receptor-mediated signaling, ammonia triggers a pathological cascade leading to the sharp inhibition of aerobic glucose metabolism, oxidative stress, brain hypoperfusion, nerve cell damage, and formation of neurological deficits. Brain hypoperfusion, in turn, could be due to the impaired oxygen transport function of erythrocytes, because of the disturbed energy metabolism that occurs in the membranes and inside erythrocytes and controls affinity of hemoglobin for oxygen, which determines the degree of oxygenation of blood and tissues. In our recent study, this causal relationship was confirmed and novel ammonium-induced pro-oxidant effect mediated by excessive activation of NMDA receptors leading to impaired oxygen transport function of erythrocytes was revealed. For a more complete evaluation of "erythrocytic" factors that diminish brain oxygenation and lead to encephalopathy, in this study, activity of the enzymes and concentration of metabolites of glycolysis and Rapoport–Lubering shunt, as well as morphological characteristics of erythrocytes from the rats with acute hyperammoniemia were determined. To elucidate the role of NMDA receptors in the above processes, MK-801, a non-competitive receptor antagonist, was used. Based on the obtained results it can be concluded that it is necessary to consider ammonium-induced morphofunctional disorders of erythrocytes and hemoglobinemia which can occur as a result of alterations in highly integrated networks of metabolic pathways may act as an additional systemic "erythrocytic" pathogenetic factor to prevent the onset and progression of cerebral hypoperfusion in hepatic encephalopathy accompanied by hyperammonemia. [ABSTRACT FROM AUTHOR]

Purpose: Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. Methods: Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. Results: A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. Conclusion: Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) induces increased energy expenditure and disrupts the metabolism of essential nutrients. Hepatic encephalopathy is a complication of ALF with a poor prognosis and mainly involves the metabolic disturbance of amino acids in its pathogenesis. In this review, we discuss the nutritional management for ALF in consideration of the pathophysiology of ALF with respect to the impairment of hepatocyte function. It is known that enteral nutrition is recommended for patients with ALF, while parenteral nutrition is recommended for patients who cannot tolerate enteral nutrition. As ALF leads to a hypermetabolic state, the energy intake is recommended to cover 1.3 times the resting energy expenditure. Because of the high risk of hypoglycemia associated with disturbances in glucose metabolism, substantial glucose intake is recommended. Along with the deterioration of glucose metabolism, protein metabolism is also disrupted. As patients with ALF have increased systemic protein catabolism together with decreased protein synthesis, appropriate amounts of amino acids or protein under monitoring serum ammonia levels are recommended. In conclusion, nutritional management based on the understanding of nutritional pathophysiology is a pivotal therapeutic approach for patients with ALF. The approach should be individualized in the acute phase, the recovery phase, and the pretransplant phase. [ABSTRACT FROM AUTHOR]

Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective To establish a nomogram prediction model for the development of overt hepatic encephalopathy(OHE) in patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt(TIPS) after esophagogastric variceal bleeding, and to evaluate the predictive ability of the model. Methods This study was conducted among 113 patients with esophagogastric variceal bleeding due to liver cirrhosis who were admitted to The First Affiliated Hospital of Soochow University from January 2020 to December 2022 and underwent TIPS after failed medical or endoscopic therapy. All patients were followed up for 6 months after surgery, and according to the presence or absence of OHE after TIPS, they were divided into OHE group with 32 patients and non-OHE group with 81 patients. Related data were collected from all patients, including clinical data, routine blood test results, serum biochemistry, and coagulation test results. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the independent risk factors for the onset of OHE after TIPS, and then a nomogram prediction model was established. The index of concordance(Cindex) was calculated and the calibration curve was plotted to evaluate the predictive ability of the model, and the clinical decision curve was plotted to analyze the net clinical benefit of the model. The receiver operating characteristic(ROC) curve was used to validate the predictive ability of the model. Results There were significant differences between the OHE group and the non-OHE group in age, diabetes, Child-Pugh class, ascites, main portal vein diameter before surgery, gamma-glutamyl transpeptidase(GGT) level, prothrombin time, and Freiburg index of post-TIPS survival(FIPS) score(all P<0.05). The multivariate Logistic regression analysis showed that Child-Pugh class(odds ratio ［OR］=17.498，95% confidence interval ［CI］：2.561—119.548，P=0.004)，main portal vein diameter before surgery(OR=1.361，95%CI：1.057—1.752，P=0.017), GGT(OR=1.032，95%CI：1.013—1.052，P= 0.001), and FIPS score(OR=2.838，95%CI：1.277—6.311，P=0.010) were independent influencing factors for the development of OHE after TIPS. The nomogram model established based on the above four indicators had a C-index of 0.875, good fitting of the calibration curve, and an area under the ROC curve of 0.875（95%CI：0.799—0.929，P<0.001), and the decision curve analysis showed that the 0.3 — 0.9 threshold probability model had a good net benefit. Conclusion Child-Pugh class, main portal vein diameter before surgery, GGT, and FIPS score have a certain value in predicting the development of OHE after TIPS in patients with esophagogastric variceal bleeding due to liver cirrhosis, and the nomogram model established based on these indicators can be used to individually predict the onset of OHE after TIPS in patients with esophagogastric variceal bleeding due to liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aim: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). Methods: A retrospective review of SBRT‐treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto‐segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. Results: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3‐year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score‐matched cohort, the 3‐year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. Conclusions: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC. [ABSTRACT FROM AUTHOR]

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients. Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48 h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1–5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: • Pediatric acute liver failure is associated with high mortality. • Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described. [ABSTRACT FROM AUTHOR]

Purpose: Prior studies have described complications of radiofrequency ablation (RFA) of liver tumours. The aim of this study was to identify risk factors for hospitalization duration longer than 24 hours following RFA of liver tumours. Methods: This retrospective, single-centre study included patients with liver tumours undergoing RFA between October 2017 and July 2020. Medical records were reviewed to collect patient, tumours, and procedure characteristics for each RFA session. The association between potential risk factors and duration of hospitalization (less than or more than 24 hours) was analyzed using univariate and multivariate logistic regressions. Results: Our study included 291 patients (mean age: 65.2 ± 11.2 [standard deviation]; 201 men) undergoing 324 RFA sessions. Sixty-eight sessions (21.0%) resulted in hospitalization of more than 24 hours. Multivariate analysis identified each additional needle insertion per session (OR 1.4; 95% CI [1.1-1.9]; P =.02), RFA performed in segment V (OR 2.8; 95% CI [1.4-5.7]; P =.004), and use of artificial pneumothorax (OR 14.5; 95% CI [1.4-146.0]; P =.02) as potential risk factors. A history of hepatic encephalopathy (OR 2.6; 95% CI [1.1-6.0]; P =.03) was only significant in univariate analysis. Post-hoc, subgroup analysis of patients with hepatocellular carcinoma (69.8%) did not identify other risk factors. Conclusion: Risk factors for a hospitalization duration longer than 24 hours include a higher number of needle insertions per session, radiofrequency ablation in segment V, and use of an artificial pneumothorax. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) is common in liver cirrhosis and is identified by psychometric tests. The portosystemic hepatic encephalopathy score (PHES) is the most widely used and serves as an inter-study comparator. PHES has not been standardised for use in the Danish population, where German normal values have been applied until now based on the notion that the populations are comparable. This study aimed to evaluate if German PHES normal values can be applied in the Danish population and establish Danish normal values if needed. 200 Danish and 217 German healthy persons underwent Number Connection Test A and B (NCT), Line Tracing Test (LTT), Digit Symbol Test (DST), and Serial Dotting Test (SDT), and based on performance, PHES was calculated. German and Danish PHES performance declined with age in all subtests but more rapidly in Danes. Both German and Danish norms were impacted by gender and education, but to a different extent in the single tests of the test battery. Accordingly, there was a need for specific Danish normal values, which are presented here. Applying the new Danish normal values instead of the German in patients with cirrhosis yielded a lower percentage of out-of-norm performances (58% vs. 66%) and, hence, a lower prevalence of MHE. Danes and Germans perform differently on PHES, and therefore, normal German values cannot be used in Danish patients. Danish normal values are presented here and yield a lower number of 'out of norm' performances. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency with symptoms ranging from slight cognitive changes detectable only by neuropsychiatric testing to coma. Up to 60% of patients with cirrhosis have mild forms of HE and 35% will at some point experience overt HE. Even in its milder forms, HE impacts the patient's daily routines, self-sufficiency, quality of life, and, thereby, socio-economic status. HE is a condition affecting the whole household including formal and informal caregivers, who carry a heavy burden. Early identification, prophylaxis, and treatment of HE are essential for relieving patients and informal caregivers. [ABSTRACT FROM AUTHOR]

Increasing evidences implicate vital role of neuronal damage in the development of hepatic encephalopathy (HE). Neurofilament light chain (NfL) is the main frame component of neurons and is closely related to axonal radial growth and neuronal structural stability. We hypothesized that NfL as a biomarker of axonal injury may contribute to early diagnosis of HE. This study recruited 101 patients with liver cirrhosis, 10 healthy individuals, and 7 patients with Parkinson's disease. Minimal hepatic encephalopathy (MHE) was diagnosed using psychometric hepatic encephalopathy score. Serum NfL levels were measured by the electrochemiluminescence immunoassay. Serum NfL levels in cirrhotic patients with MHE were significantly higher than cirrhotic patients without MHE, and increased accordingly with the aggravation of HE. Serum NfL levels were associated with psychometric hepatic encephalopathy score, Child-Pugh score, model for end-stage liver disease score, and days of hospitalization. Additionally, serum NfL was an independent predictor of MHE (odds ratio of 1.020 (95% CI 1.005–1.034); P = 0.007). The discriminative abilities of serum NfL were high for identifying MHE (AUC of 0.8134 (95% CI 0.7130–0.9219); P ˂ 0.001) and OHE (AUC of 0.8852 (95% CI 0.8117–0.9587); P ˂ 0.001). Elevated serum NfL levels correlated with the presence of MHE and associated with the severity of HE, are expected to be a biomarker in patients with cirrhosis. Our study suggested that neuronal damage may play a critical role in the development of HE. [ABSTRACT FROM AUTHOR]

Purpose Transjugular intrahepatic portosystemic shunt (TIPS) is an established intervention for symptomatic portal hypertension, with many patients experiencing hepatic encephalopathy (HE) as an undesirable side effect. For medically refractory HE, TIPS reduction can decrease the burden of neurotoxic metabolites. This study aimed to evaluate the efficacy of TIPS reduction for the treatment of medically refractory post-TIPS HE. Methods A retrospective search using an institutional database yielded 45 patients who underwent TIPS reduction between 2011 and 2021. Four patients were excluded due to lack of post-TIPS HE, and 41 patients in total were included. The primary endpoint was improvement of HE after TIPS reduction as measured by the West Haven scores. Secondary endpoints included postreduction recurrence of ascites or gastrointestinal bleeding, procedural complications, and 30-day mortality. Results TIPS reduction was performed in all 41 patients with a 30-day mortality rate of 9.8%. No deaths were attributable to the procedure itself. Twenty-seven patients (65.9%) had improvement in HE and 10 patients (24.4%) proceeded to TIPS occlusion due to refractory HE. The average pre- and postreduction West Haven grades were 2.9 ± 0.5 and 1.9 ± 1.2 (p < 0.001), respectively. One patient (2.4%) had spontaneous TIPS thrombosis after reduction and developed arterial gastrointestinal bleeding, 15 patients (36.6%) experienced recurrent ascites, and there were no cases of variceal hemorrhage. Conclusion In this population, TIPS reduction improved medically refractory HE in 65.9% of patients with a 36.6% risk of recurrent ascites, no cases of variceal hemorrhage, and 9.8% 30-day mortality. [ABSTRACT FROM AUTHOR]

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL. [ABSTRACT FROM AUTHOR]