Acute on Chronic Liver Failure (ACLF) is an unfavorable form of cirrhotic disease progression, distinguished from decompensated cirrhosis by a very high short-term mortality associated with damage to one or more organs. The pathophysiology is based on an intense systemic inflammatory reaction, the triggering factor of which can be identified (infection, toxic agent, etc.) in around two thirds of cases. The analogy with sepsis has enabled us to derive prognostic scores linked to organ damage, and thus to better guide these patients, who most often require close monitoring. Treatment remains limited and relies on support for the affected organs. Given the poor prognosis of these patients, attitude discussions should also be part of early management.
L’Acute on Chronic Liver Failure (ACLF) est une forme d’évolution défavorable de la maladie cirrhotique se distinguant de la cirrhose décompensée par une mortalité à court terme très élevée liée à une atteinte d’un ou plusieurs organes. La physiopathologie repose sur une réaction inflammatoire systémique, dont le facteur déclenchant peut être mis en évidence (infection, toxique, etc.) dans environ deux tiers des cas. L’analogie avec le sepsis a permis d’établir des scores pronostiques liés aux atteintes d’organes et ainsi de mieux orienter ces patients nécessitant le plus souvent une surveillance rapprochée. Le traitement reste limité et repose sur le soutien des organes atteints. Au vu du pronostic sombre de ces patients, des discussions d’attitude devraient également faire partie de la prise en charge précoce.

Acute-on-chronic liver failure (ACLF) is a severe condition characterized by high mortality rates, and macrophage-mediated inflammation plays a critical role in its progression. Our previous research has indicated the involvement of the RNA-binding protein IGF2BP3 in the pathogenesis of ACLF. However, the underlying molecular mechanisms contributing to this damage require further elucidation. Initially, we observed heightened expression of pro-inflammatory cytokines and macrophage activation in both ACLF patients and a mouse model induced by D-GalN/LPS. Subsequent loss-of-function experiments targeting IGF2BP3 revealed that the knockdown of IGF2BP3 potentially confers hepatoprotection by mitigating macrophage-induced inflammation. Further investigation using RNA Immunoprecipitation (RIP) assays and dual luciferase reporter assays confirmed that RORα is a target protein of the RNA-binding protein IGF2BP3. Importantly, depletion of RORα was found to significantly increase liver damage and inflammation by modulating the NF-κB signaling pathway. In conclusion, our findings underscore the crucial role of IGF2BP3 in mediating liver damage induced by activated macrophages in ACLF, which is regulated by the RORα-NF-κB signaling pathway. These discoveries offer novel insights into the pathogenesis and potential therapeutic targets for ACLF.

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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.
METHODS: 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.
CONCLUSIONS: PHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death.

This meta-analysis aims to evaluate the effectiveness of the double plasma molecular adsorption system (DPMAS) in combination with plasma exchange (PE) compared to plasma exchange alone in the treatment of Acute-on-Chronic liver failure (LF) caused by hepatitis B. Until August 31, 2023, a comprehensive search of databases including Embase, Chinese Medical Journal Full-text Database, China Biomedical Literature Database, Wan Fang Medical Network, PubMed, and the Cochrane Library was carried out using keywords like \"liver failure,\" \"acute-on-chronic liver failure,\" \"PE,\" \"DPMAS,\" and related terms. The quality of the included studies was evaluated using QUADS (quality assessment of diagnostic accuracy studies). Software Revman 5.3 was used to examine the data, while Stata 15.1 was used to run Egger\'s test. Following thorough screening, 452 patients who received PE alone and 429 patients who received DPMAS in addition to PE were included. Every study that was included was of a high caliber. When comparing the DPMAS plus PE group to the PE alone group, the total bilirubin reduction was considerably higher (mean difference [MD] = -49.09, 95% confidence interval [CI]: -54.84 to -43.35, p < .00001). Prothrombin activity (PTA; MD = -1.53, 95% CI: -3.29 to -0.22, p = .09), albumin (ALB; MD = -0.58, 95% CI: -1.57 to 0.41, p = .25), prothrombin time (PT; MD = -0.07, 95% CI: -1.47 to 1.34, p = .92), and platelet count (PLT; MD = -0.08, 95% CI: -1.33 to 1.66, p = .90) did not differ significantly. The improvement in international standardized ratio (INR) was significantly greater in the PE group (MD = 0.07, 95% CI (0.03, 0.10), p = .0001). When combined with DPMAS, PE has been shown to be more effective in lowering total bilirubin levels. PE can also lower INR in individuals who have hepatitis B-related ACLF. This therapeutic strategy also lessens the need for plasma transfusions.

BACKGROUND: Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision.
METHODS: We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation.
RESULTS: Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5-1368) days, 58% (119/206) died at a median of 21 (9-124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey\'s (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%).
CONCLUSIONS: Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.

UNASSIGNED: Patients with acute-on-chronic liver failure (ACLF) who take entecavir (ETV) and tenofovir disoproxil fumarate (TDF) experience a reduction in hepatic events and mortality. The effectiveness of tenofovir alafenamide (TAF) was not well investigated. This study was aim to compare the antiviral efficacy and mortality between TAF and ETV in patients with ACLF caused by the hepatitis B virus (HBV).
UNASSIGNED: One hundred and six patients with HBV-ACLF who received TAF (25 mg/day) and ETV (0.5 mg/day) for 12 weeks were analyzed. The primary endpoints were overall mortality and liver transplantation (LT) at week 12. Biochemical responses, virologic responses, mortality, drug safety, and side effects were evaluated.
UNASSIGNED: At 4 and 12 weeks of TAF treatment, patients showed significantly higher HBV-DNA reduction (P < .001), higher HBV-DNA undetectability rates (P < .001), and lower HBV DNA levels (P < .001) in serum. Lower Child-Turcotte-Pugh (CTP) scores (P = .003) were observed at 4 weeks in the TAF group, although the CTP scores showed no difference between TAF group and ETV group at 12 weeks (P = 1.143). Lower alanine aminotransferase (ALT) levels of patients in the TAF group at week 4 and 12 were observed (P = .023 and P < .0001, separately). The mortality of TAF group was lower after 4 weeks of treatment (P = .038); however, the 2 groups had similar mortality rates at week 8 and 12. Among the causes of death in HBV-ACLF patients, we found the same incidence of liver-related problems in both groups (P > .05).
UNASSIGNED: This study showed that ACLF patients with chronic HBV infection treated with TAF had a rapid decline in HBV DNA, a higher rate of ALT reduction and improved CTP scores compared to the ETV group, thereby improving patient survival.

BACKGROUND: Especially in terms of alcohol-related liver cirrhosis, discussions quickly arise in times of scarce resources about the justification for carrying out (prolonged) intensive care measures.
UNASSIGNED: The following review aims to address ethical aspects specifically in patients with liver cirrhosis in the intensive care unit. A possible structured approach is presented.
CONCLUSIONS: A general recommendation is not possible. Ultimately, decisions remain on a case-by-case basis and have to take a wide variety of perspectives into account.
UNASSIGNED: HINTERGRUND: Insbesondere bei der ethyltoxischen Leberzirrhose entbrennen in Zeiten knapper Ressourcen rasch Diskussionen über die Rechtfertigung der Durchführung (prolongierter) intensivmedizinischer Maßnahmen.
UNASSIGNED: Die vorliegende Übersichtsarbeit soll ethische Aspekte speziell bei Patienten mit Leberzirrhose auf der Intensivstation adressieren. Eine mögliche strukturierte Vorgehensweise soll dargestellt werden.
UNASSIGNED: Eine generelle Empfehlung ist nicht möglich. Letztendlich bleiben es Einzelfallentscheidungen, die die unterschiedlichsten Blickwinkel zu berücksichtigen haben.

Bilirubin plays a key role in early diagnosis, prognosis, and prevention of liver diseases. Unconjugated bilirubin (UCB) requires conversion to a water-soluble form through liver glucuronidation, producing monoglucuronide (BMG) or diglucuronide bilirubin (BDG) for bile excretion. This study aimed to assess the roles of bilirubin\'s molecular species-UCB, BMG, and BDG-in diagnosing and understanding the pathogenesis of liver cirrhosis in patients with acute-on-chronic liver failure (ACLF), compensated liver cirrhosis (LC) patients, and healthy individuals. The study included patients with ACLF and compensated LC of diverse etiologies, along with healthy controls. We collected laboratory and clinical data to determine the severity and assess mortality. We extracted bilirubin from serum samples to measure UCB, BMG, and BDG using liquid chromatography-mass spectrometry (LC-MS). The quantification of bilirubin was performed by monitoring the mass charge (m/z) ratio. Of the 74 patients assessed, 45 had ACLF, 11 had LC, and 18 were healthy individuals. Among ACLF patients, the levels of molecular species of bilirubin were UCB 19.69 μmol/L, BMG 47.71 μmol/L, and BDG 2.120 μmol/L. For compensated cirrhosis patients, the levels were UCB 11.29 μmol/L, BMG 1.49 μmol/L, and BDG 0.055 μmol/L, and in healthy individuals, the levels were UCB 6.42 μmol/L, BMG 0.52 μmol/L, and BDG 0.028 μmol/L. The study revealed marked elevations in the bilirubin species in individuals with ACLF compared to those with compensated cirrhosis and healthy controls, underscoring the progression of liver dysfunction. The correlation of BMG and BDG levels with commonly used inflammatory markers suggests a relationship between bilirubin metabolism and systemic inflammation in ACLF.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.
UNASSIGNED: Die Leberzirrhose im Endstadium ist ein lebensbedrohliches klinisches Syndrom, das mit Funktionsstörungen des Immunsystems einhergeht. In dieser Lage neigen Patienten zu Infektionen mit bakteriellen, pilzlichen und viralen Erregern, assoziiert mit einer deutlich erhöhten Morbidität und Mortalität. Am häufigsten sind bei Patienten mit Leberzirrhose im Endstadium bakterielle Infektionen; sie machen einen Anteil von fast 30 % aus. Die wachsende Verbreitung multiresistenter Erreger stellt hinsichtlich der Behandlungsstrategien eine enorme Herausforderung dar. Daher besteht ein dringender Bedarf an Präventionsmaßnahmen, Früherkennungsstrategien und breit verfügbaren Therapieoptionen. All diese Ansätze sind erforderlich, wenn die steigende Inzidenz infektionsassoziierter Komplikationen bei Leberzirrhose im Endstadium bewältigt werden soll.