Palliative care for end-stage liver disease and acute on chronic liver failure:A systematic review

BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome

AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.

Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

AIM： To identify the risk factors in predicting the out- come of acute-on-chronic hepatitis B liver failure pa- tients. METHODS： We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus （ACLF-HBV） and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy. Their demographic, clinical, and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test, Fisher＇s exact test, and a multiple logistic regres- sion analysis. RESULTS： The study included 113 patients （87 men and 26 women） with a mean age of 49.84 years. Fifty- two patients survived, and 61 patients died. Liver failure （85.2%）, sepsis （34.4%）, and multiple organ failure （39.3%） were the main causes of death. Mul- tivariate analyses showed that Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ scores ≥ 12 [odds ratio （OR） = 7.160, 95% CI： 2.834-18.092, P 〈 0.001] and positive blood culture （OR = 13.520, 95% CI： 2.740-66.721, P = 0.001） on the day of diagnosis and model for end-stage liver disease （MELD） scores 28 （OR = 8.182, 95% CI： 1.884-35.527, P = 0.005） after the first week of treatment were independent predictors of mortality. CONCLUSION： APACHE II scores on the day of diag- nosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF- HBV patients.

Acute-on-chronic liver failure:Pathogenesis,prognostic factors and management

Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure(OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept(Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-onchronic liver failure:a nationwide prospective multicenter study in China

BACKGROUND： Plasma exchange （PE）-centered artificial liver support system reduced the high mortality rate of hepa titis B virus （HBV）-related acute-on-chronic liver failure （ACLF）. But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.

Entecavir vs lamivudine therapy for na?ve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure

AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.

Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review

BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant.Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODS Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were assessed.Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist device.RESULTS Three hundred twenty four records were reviewed,of which 62 studies were found to be duplicates.Of the 262 records screened,211 studies were excluded.Fifty-one articles were assessed for eligibility,for which 7 were excluded.Twenty-nine studies were included for ALF only,and 9 studies for ACLF only.Six studies included both ALF and ACLF patients.A total of 44 publications were included.Of the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case reports.All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange.In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was seen.Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT.Using the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high.Plasma exchange in ACLF improves survival at 30-and 90-d in nontransplanted patients.Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

Prognosis of acute-on-chronic liver failure patients treated with artificial liver support system

AIM: To establish a new model for predicting survival in acute-on-chronic liver failure(ACLF) patients treated with an artificial liver support system. METHODS: One hundred and eighty-one ACLF patients who were admitted to the hospital from January 1, 2012 to December 31, 2014 and were treated with an artificial liver support system were enrolled in this retrospective study, including a derivation cohort(n = 113) and a validation cohort(n = 68). Laboratory parameters at baseline were analyzed and correlatedwith clinical outcome. In addition to standard medical therapy, ACLF patients underwent plasma exchange(PE) or plasma bilirubin adsorption(PBA) combined with plasma exchange. For the derivation cohort, KaplanMeier methods were used to estimate survival curves, and Cox regression was used in survival analysis to generate a prognostic model. The performance of the new model was tested in the validation cohort using a receiver-operator curve.RESULTS: The mean overall survival for the derivation cohort was 441 d(95%CI: 379-504 d), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively. The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 d(95%CI: 455-605 d) and 343 d(95%CI: 254-432 d), respectively, which were significantly different(P = 0.012). When variables with bivariate significance were selected for inclusion into the multivariate Cox regression model, number of complications, age, scores of the model for end-stage liver disease(MELD) and type of artificial liver support system were defined as independent risk factors for survival in ACLF patients. This new prognostic model could accurately discriminate the outcome of patients with different scores in this cohort(P < 0.001). The model also had the ability to assign a predicted survival probability for individual patients. In the validation cohort, the new model remained better than the MELD.CONCLUSION: A novel model was constructed to predict prognosis and accurately discriminate survival in ACLF patients treated with an artificial liver support system.

Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acuteon-chronic liver failure

AIM:To evaluate the safety and efficacy of granulocyte-colony stimulating factor(G-CSF) therapy in patients with hepatitis B virus(HBV)-associated acuteon-chronic liver failure(ACLF).METHODS:Fifty-five patients with HBV-associated ACLF were randomized into two groups:the treatment group and the control group.Twenty-seven patients in the treatment group received G-CSF(5 μg/kg per day,six doses) treatment plus standard therapy,and 28 patients in the control group received standard therapy only.The peripheral CD34 + cell count was measured consecutively by flow cytometry.Circulating white blood cell count,biochemical parameters,and other clinical data of these patients were recorded and analyzed.All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate.RESULTS:The peripheral neutrophil and CD34 + cell counts in the G-CSF group increased on day 3 from the onset of therapy,continued to rise on day 7,and remained elevated on day 15 compared to those of the control group.Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy,compared to that in the controls(P = 0.041).Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7(P = 0.004) and remained high on day 30 from the onset of G-CSF therapy(P < 0.001) compared to that in controls.After 3 mo of follow-up observation,the survival rate in the treatment group(48.1%) was significantly higher than that in the control group(21.4%)(P = 0.0181).CONCLUSION:G-CSF therapy promoted CD34 + cell mobilization in patients with HBV-associated ACLF,and improved the liver function and the survival rate of these patients.

Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P < 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.

The immunological roles in acute-on-chronic liver failure:An update

Background: Acute-on-chronic liver failure (ACLF) refers to the acute deterioration of liver function that occurs in patients with chronic liver disease. ACLF is characterized by acute decompensation, organ failure and high short-term mortality. Numerous studies have been conducted and remarkable progress has been made regarding the pathophysiology and pathogenesis of this disease in the last decade. The present review was to summarize the advances in this field. Data sources: A comprehensive search in PubMed and EMBASE was conducted using the medical subject words “acute-on-chronic liver failure”,“ACLF”,“pathogenesis”,“predictors”, and “immunotherapy” combined with free text terms such as “systemic inflammation” and “immune paralysis”. Relevant papers published before October 31, 2018, were included. Results: ACLF has two marked pathophysiological features, namely, excessive systemic inflammation and susceptibility to infection. The systemic inflammation is mainly manifested by a significant increase in the levels of plasma pro-inflammatory factors, leukocyte count and C-reactive protein. The underlying mechanisms are unclear and may be associated with decreased immune inhibitory cells, abnormal expression of cell surface molecules and intracellular regulatory pathways in immune cells and increased damageassociated molecular patterns in circulation. However, the main cause of susceptibility to infection is immune paralysis. Immunological paralysis is characterized by an attenuated activity of immune cells. The mechanisms are related to elevations of immune inhibitory cells and the concentration of plasma antiinflammatory molecules. Some immune biological indicators, such as soluble CD163, are used to explore the pathogenesis and prognosis of the disease, and some immunotherapies, such as glucocorticoids and granulocyte colony-stimulating factor, are effective on ACLF. Conclusions: Overwhelming systemic inflammation and susceptibility to infection are two key features of ACLF. A better understanding of the state of a patient’s immune system will help to guide immunotherapy for ACLF.

Acute-on-chronic liver failure：recent update

Acute on chronic liver failure（ACLF） was first described in 1995 as a clinical syndrome distinct to classic acute decompensation.Characterized by complications of decompensation,ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between45%and 90%.Despite the clinical relevance of the condition,it still remains largely undefined with continued disagreement regarding its precise etiological factors,clinical course,prognostic criteria and management pathways.It is concerning that,despite our relative lack of understanding of the condition,the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%.This paper highlights our current understanding of ACLF,including its etiology,diagnostic and prognostic criteria and pathophysiology.It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates.The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters,while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.

Acute-on-chronic liver failure in a multi-ethnic Asian city:A comparison of patients identified by Asia-Pacific Association for the Study of the Liver and European Association for the Study of the Liver definitions

AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver(APASL) and European Association for the Study of the Liver(EASL) guidelines for acute-on-chronic liver failure(ACLF) in profiling patients and determining the outcome.METHODS Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients' data(including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome.RESULTS A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients(80.8%) meet the APASL criteria, 64 patients(82.1%) meet the EASL criteria, and 49 patients(62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections(59.0%), hepatitis B flare(29.5%), and variceal bleeding(24.4%). The common aetiologies of the underlying chronic disease included hepatitis B(43.6%), alcoholic(20.5%) and cryptogenic(11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures(as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate. CONCLUSION Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.

Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND In China,hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality.Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality.Bacterial translocation from the intestine,impaired hepatic clearance,and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure.The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes.Active prevention,early diagnosis,and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF.AIM To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF.METHODS Patients with HBV-ACLF hospitalized at Taihe Hospital,Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled.Patient-related information was retrieved from the hospital case database,including general information,blood biochemistry,complications,etc.According to the occurrence of secondary infection or not,the patients were divided into an infection group and a non-infection group.The sites,types,and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed.The risk factors for infections were assessed by unconditional logistic regression.RESULTS There were 174 cases of HBV-ACLF that met the enrollment criteria,of which 114 (65.52%) were diagnosed with infectious complications.Infections occurred in the abdominal cavity (87 cases),respiratory tract (51 cases),urinary tract (18 cases),and biliary tract (10 cases).Patients with infectious complications had a significantly higher 28-d mortality (70.18%,80/114) than those without (40.00%,24/60)(70.18% vs 40.00%,P < 0.05).And patients with infectious complications had a much higher incidence of non-infectious complications (54.39%,62/114)(54.39% vs 15.00%,P < 0.05),leading to an extremely high 28-d mortality of 88.71%(55/62)(P < 0.05).The grade of liver failure,period of hospital stay ≥ 30 d,age ≥ 45 years,and percentage of neutrophils > 70% were identified as risk factors for infectious complications.CONCLUSION The high incidence of infectious complications in patients with HBV-ACLF is associated with severity and deterioration of the disease and may contribute to the extremely high mortality of these patients.

High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid

BACKGROUND： Linezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of throm- bocytopenia in patients with acute-on-chronic liver failure （ACLF） who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocyto- penia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.

Serum levels of mi RNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

Background: Hepatitis B virus(HBV)-associated acute-on-chronic liver failure(HBV-ACLF) is a lifethreatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum mi RNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF.Methods: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to30 chronic asymptomatic HBV carriers as controls. The mi RNAs expressions were measured by real-time quantitative PCR(q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed mi RNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model.Results: Real-time q-PCR indicated that serum miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and mi R-122-3 p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+-1.72 × INR-4.963 × gastrointestinal bleeding(Yes = 0; No = 1)-0.278 ×(mi R-122-3 p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve(AUROC) was 0.847.Conclusions: Expression levels of these mi RNAs(miR-146 a-5 p, mi R-122-3 p and mi R-328-3 p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.