Acute-on-chronic Liver Failure Cases Research Articles

Prognostic nutritional index application value for acute-on-chronic liver failure co-infection

Objective: To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF). Methods: 220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ(2) test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results: There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group (P < 0.05). Among the 220 ACLF cases, 158 (71.82%) were infected with the hepatitis B virus (HBV). The incidence rate of infection during hospitalization was 69.09% (152/220). The common sites of infection were intraabdominal (57.07%) and pulmonary infection (29.29%). Pearson correlation analysis showed that PNI and MELD-Na were negatively correlated (r = -0.150, P < 0.05). Multivariate logistic analysis results showed that low PNI score (OR=0.916, 95%CI: 0.865~0.970), ascites (OR=4.243, 95%CI: 2.237~8.047), and hepatorenal syndrome (OR=4.082, 95%CI : 1.106~15.067) were risk factors for ACLF co-infection (P < 0.05). The ROC results showed that the PNI curve area (0.648) was higher than the MELD-Na score curve area (0.610, P < 0.05). The effectiveness of predicting infection risk when PNI was combined with ascites and hepatorenal syndrome complications was raised. Patients with co-infections had a good predictive effect when PNI ≤ 40.625. The sensitivity and specificity were 84.2% and 41.2%, respectively. Conclusion: Low PNI score and ACLF co-infection have a close correlation. Therefore, PNI has a certain appraisal value for ACLF co-infection.

Challenges in Diagnosis and Therapeutic Approach of Acute on Chronic Liver Failure-A Review of Current Evidence.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40-50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264-0.892, p = 0.020; OR = 0.323, 95% CI = 0.107-0.972, p = 0.044; OR = 1.492, 95% CI = 1.111-2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

Hepatitis A: Leading Cause of Paediatric Acute Liver Failure in Bangladesh

Background: Pediatric acute liver failure (PALF) is a multisystem disorder that gives rise to severe liver failure within days or weeks and occurs in children without pre-existing chronic liver disease. The etiology of PALF varies with age group and geographical area.&#x0D; Objectives: This study was aimed to evaluate the etiological factors of PALF in Bangladeshi children.&#x0D; Methods: This observational study was conducted at the Department of Paediatric Gastroenterology &amp; Nutrition, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from 2017 to 2020. Twenty-six PALF patients were included, purposively, excluding the acute-on chronic liver failure cases. Demographic data, vaccination history, and other information regarding etiology and complications were recorded. During hospital stay following investigations were performed: Serum bilirubin, liver enzymes, prothrombin time, serum albumin, serum creatinine and electrolytes. Fisher’s exact test determined the association between etiologies of PALF and past histories along with other descriptive statistics using the open-source PSPP software.&#x0D; Results: The average age of the 26 studied patients was 8.6±3.5 years, and 73.1% belonged to 5-12 years of age group. Half of the patients had a history of taking street food or unsafe water. Only six patients had a history of ingestion of herbal medicine. None of the patients had history of vaccination against Hepatitis A. The etiology of PALF patients varied. About 54% of the studied patients had HAV infection, in 23.1% etiology was not determined. About 71.4% of the study patients with HAV infection had a history of taking street food or unsafe water, and this association was statistically significant.&#x0D; Conclusion: This study found that hepatitis A virus infection is the leading cause of paediatric acute liver failure in Bangladesh. Timely preventive measures may help in lowering fatality from liver diseases in children in Bangladesh.&#x0D; DS (Child) H J 2021; 37(2): 93-97

S3313 Acute Sickle Intrahepatic Cholestasis From Sickle Cell SC Disease Causing Acute on Chronic Liver Failure

Introduction: Acute on Chronic Liver Failure (ACLF) is a disorder that results in grave systemic consequences. The dysregulated inflammatory response caused by an acute liver injury often results in multi-organ dysfunction. And while alcoholic/viral hepatitis or infections are common causes of ACLF, hematologic disorders are unusual. We present a case of ACLF due to sickle cell intrahepatic cholestasis from SC disease. Case Description/Methods: A 61-year-old man with history of HTN, sickle-cell trait, alcoholic cirrhosis presented for altered mental status. Initial labs showed TBili 30.7, DBili >20.0, AST/ALT 308/123, ALP 532 and INR 1.6. Phosphatidylethanol level negative. No new history of medication/herbal use, new sexual contacts, or drug use. Workup negative for hepatitis A/B/C/E. ANA negative, ASMA 26.7, IgG 2742. MRI Abdomen showed no liver mass with patent hepatic vasculature/biliary tree. LDH 531, Haptoglobin < 10, reticulocyte count 11.2, and Coombs test was positive. Hb electrophoresis showed 44.4% Hb C and 49.5% Hb S, consistent with SC disease. Hb was 8.5 (baseline), with no known crises since youth. Liver biopsy findings were consistent with sickle cell hepatopathy (sinusoidal dilation and congestion of sickled cells, ballooning degeneration of hepatocytes, and marked intracanalicular cholestasis). Patient had exchange blood transfusion (EBT) with improvement in Hb to 11.8 and decrease in retic count, LDH. Patient however continued to deteriorate, with increasing aminotransferases into thousands, worsening mental status, AKI, and coagulopathy. Patient made hospice care and eventually expired. Discussion: Hemoglobin SC (HbSC) disease is a less common form of sickle cell disease (SCD). Patients with HbSC disease have milder symptoms than SCD but more severe than sickle cell trait. Acute sickle hepatic crisis occurs in 10% of patients with SCD. Acute sickle intrahepatic cholestasis is the most severe form of sickle hepatopathy, associated with increased mortality. It is usually seen in SCD, but rarely in HbSC. Clinical presentation is more severe, with significant hyperbilirubinemia >15 mg/dL and aminotransferase elevations >1000 IU/L, reflecting ischemic injury. ALF/ACLF can evolve rapidly with multi-organ failure. EBT is considered in these situations. Non-responders have poor prognosis. Clinicians should be aware of the liver complications that can arise in patients with sickle cell-related disorders, including HbSC, particularly in patients with chronic liver disease.

Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in ACLF using human liver samples with the help of single-cell RNA-sequencing (scRNA-seq) technology. Here, ACLF exhibited more severe liver injury and inflammation than cirrhosis, as indicated by significant increases in plasma levels of alanine/aspartate aminotransferases and total bilirubin. Compared with cirrhosis cases, the number of intrahepatic LVs was decreased significantly in ACLF patients. ScRNA-seq revealed that many monocyte/macrophages infiltrated into the liver of ACLF cases. Meanwhile, scRNA-seq revealed a group of apoptotic and dysfunctional LyECs, which were the result of secreted phosphoprotein 1 (SPP1) released from infiltrating monocyte/macrophages. In vitro, SPP1 increased the proportion of dead LyECs significantly and impaired the ability of tube formation of LyECs in a dose- and time-dependent manner. In conclusion, ACLF is associated with less LV and LyEC dysfunction, at least in part mediated by SPP1 released from infiltrating monocyte/macrophages. Hepatic LVs and LyECs can be a novel therapeutic strategy for ACLF.

Development of a Widely Applicable and Simple Prognostic Score for Patients with Acute-on-chronic Liver Failure.

Background and AimsAcute-on-chronic liver failure (ACLF) tends to progress rapidly with high short-term mortality. We aimed to create a widely applicable, simple prognostic (WASP) score for ACLF patients.MethodsA retrospective cohort of ACLF cases recruited from three centers in China were divided into training and validation sets to develop the new score. A prospective longitudinal cohort was recruited for further validation.ResultsA total of 541 cases were included in the training set, and seven independent ACLF prognostic factors were screened to construct a new quantitative WASP-ACLF table. In the validation set of 671 cases, WASP-ACLF showed better predictive ability for 28-day and 90-day mortality than the currently used prognostic scores at baseline, day 3, week 1, and week 2. The predictive efficacy and clinical validity of the model improved over time. Patients were assigned to low-, intermediate-, and high-risk groups by their WASP-ACLF scores. Compared with the other two groups, intermediate-risk patients had a more uncertain prognosis, with a 90-day mortality of 44.4–50.6%. Sequential assessments at weeks 1 and 2 found the 90-day mortality of intermediate-risk groups was <20% for patients with a ≥2 point decrease in WASP-ACLF and was up to 56% for patients with a ≥2 points increase. Similar results were observed in prospective data.ConclusionsThe new ACLF prognostic score was simple, widely applicable, and had good predictive efficacy. Continuous assessments and trend of change in WASP-ACLF need to be considered, especially for intermediate-risk patients.

Tri-typing of hepatitis B-related acute-on-chronic liver failure defined by the World Gastroenterology Organization.

Tri-typing of acute-on-chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. Compared with type-B (n=262, compensated cirrhosis) and type-C (n=129, decompensated cirrhosis) ACLF, type-A patients (n=195, non-cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type-A, while bacterial infections in type-B and type-C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type-A compared with type-B or type-C ACLF patients. Kidney failure was predominantly identified in type-C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type-C ACLF showed the highest 28-day (65.2%) and 90-day (75.3%) mortalities, compared with type-A (48.7% and 54.4%, respectively) and type-B (48.4% and 62.8%, respectively) ACLF cases. Compared with type-A (11.7%) ACLF patients, the increased mortality from 28 to 90days was higher in type-B (31.6%) and type-C (37.5%). Tri-typing of HBV-related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short-term prognosis in ACLF patients.

The Association between Meteorological Factors and the Prevalence of Acute-on-chronic Liver Failure: A Population-based Study, 2007–2016

Background and Aims: The aim of this study was to investigate the effect(s) of meteorological factors on the prevalence of acute-on-chronic liver failure (ACLF) based on 10-years’ worth of population data.Methods: We retrospectively collected ACLF case data from January 2007 to December 2016 from three major hospitals in Fuzhou City, China. Climatic data, including rainfall, mean temperature, differences in temperature (delta temperature) and mean humidity for each month were downloaded from the China Climatic Data Service Center. Following data collection, Poisson regression analysis was used to estimate the effect(s) of climatic factors on the risk of the prevalence of ACLF.Results: The population consisted of a total of 3510 cases, with a mean age of 44.7 ± 14.8 years-old and with 79.8% being male. Upon analyzing the population data, we found a growing trend and seasonal pattern of monthly counts of ACLF-related hospitalization throughout the past decade. Specifically, the primary peak of ACLF prevalence was in January and the secondary peak was in July. Poisson regression showed mean temperature (risk ratio = 0.991, 95%CI = 0.986–0.996) and mean humidity (risk ratio = 1.011, 95%CI = 1.006–1.017) to be independently correlated with the monthly cases of ACLF. The results suggest that every unit increase of mean temperature (1°C) and mean humidity (1%) are associated with 0.991- and 1.011-fold changes of ACLF cases, respectively. Rainfall and delta temperature did not appear to affect the prevalence of this disease.Conclusions: The hospitalization for ACLF peaks in January and July. Low temperature and high humidity appear to function as factors contributing to this seasonal pattern.

Is HBV viral load at admission associated with development of acute-on-chronic liver failure in patients with acute decompensation of chronic hepatitis B related cirrhosis?

BackgroundHepatitis B virus (HBV) reactivation is one of the most common precipitating events associated with acute decompensation (AD) or acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB)-related cirrhotic patients. However, whether their serum HBV deoxyribonucleic acid (DNA) levels are associated with ACLF incidence and short-term mortality rate is still ambiguous.MethodsThe ACLF incidences, 28-day and 90-day liver transplantation (LT)-free mortality rates, previous nucleoside/nucleotide analogues (NUCs) treatments and serum HBV DNA levels at admission (ad-levels) of 111 hospitalized patients with AD of CHB-related cirrhosis were analyzed.Results43 (38.7%) patients developed ACLF. The 28-day and 90-day LT-free mortality rates of the ACLF cases were 15.4 and 40.9%, respectively. Though NUCs inhibited HBV replication effectively, there were no differences in the ACLF incidence between antiviral treatment-naïve patients and NUCs treatment-experienced patients with or without interruptions (37.5, 41.7 and 45.5%, respectively, P>0.05). The serum HBV DNA ad-level was similar between the patients with and without ACLF development (logarithms: 4.50 ± 1.96 vs 4.32 ± 1.99; ≥2000 IU/ml: 67.4% vs 67.6%; both P>0.05), so was between the ACLF patients died or survived in 28 or 90 days (logarithms: 4.31 ± 1.91 vs 5.54 ± 2.53, 4.81 ± 1.76 vs 4.84 ± 2.40, respectively, both P>0.05).ConclusionSerum HBV DNA ad-level and previous NUCs treatment are not associated with incidence of ACLF and short-term mortality rate in the hospitalized patients with AD of CHB-related cirrhosis.

Clinical Presentation and Mortality Determinants of Alcohol-Related Liver Disease: A Single-Center Experience of the Rising Menace from Eastern India

Objectives: Recently,the incidenceof alcohol-related liver disease has been rising alarmingly in India with late presentation and short survival. Better delineation of factors affecting mortality is needed for optimal utilization of constrained resources like liver transplantation. Methods: Baseline data of 395 patients with alcohol-related liver disease including age, clinical presentation, alcohol parameters (amount, duration, type), laboratory parameters for detecting organ failure, and prognostic scores were compared between survivor and deceased groups. Further subgroup analysis of deceased patients was done to identify factors associated with early mortality in acute-on-chronic liver failure (ACLF) and cirrhosis groups by multivariate analysis and receiver operating characteristic (ROC) curves. Only best supportive medical therapy was offered to all. Results: 80 (20.3%) patients had alcoholic hepatitis (without cirrhosis) and recovered completely with abstinence. 315 (79.7%) had evidence of either cirrhosis (n = 182, 46.1%) or ACLF (n = 133, 33.6%) at presentation and all died within the next 2 years of follow-up, earlier in the ACLF cases. All deceased patients had been heavy drinkers for long periods (>85 g/day for >17 years). Higher age, amount of alcohol consumption, number of organ failures and discriminant function score predicted severe disease and early mortality, the latter being the best predictor. The European Foundation for the study of chronic liver failure consortium (CLIF-C) score has good applicability in Indian ACLF cohorts. Serum glutamic pyruvic transaminase was normal in 73.8% of deceased patients compared to only 12.5% of survivors. Abstinence did not result in complete normalization of deranged laboratory parameters in those who died. Conclusion: Alcohol-related liver disease is serious with high short-term mortality, which has early identifiable but mostly irreversible factors. Urgent measures need to be taken to curb this rising menace.

Serum Urea at Admission Is a Predictor of Mortality in Patients With Acute on Chronic Liver Failure

Introduction: Occurrence of acute kidney injury [AKI] in Acute on chronic liver failure (ACLF) negatively impacts their survival. Only elevated serum creatinine is used to assess AKI and predict survival in ACLF. There is little data on impact of serum urea on outcome; serum urea values are ignored for prognostication. We performed a prospective study to evaluate the impact of serum urea on survival in ACLF. Methods: This study was conducted in ACLF patients hospitalised in Gastroenterology Department of SCB Medical College in India from October 2016 to March 2018. Demographic, clinical, laboratory parameters were recorded and outcome compared in patients with special reference to admission serum urea level. Results: Consecutive decompensated cirrhosis (DC) patients (n=439) were screened for ACLF as per The Asian Pacific Association for the Study of the Liver (APASL) criteria. 113 (25.7%) of them had ACLF. Out of the 113 ACLF cases, 78 (69%) had AKI as per AKIN (Acute Kidney Injury Network) criteria. Alcohol was the commonest underlying cause of CLD (74.3%) and continued alcohol intake (61%) was the commonest precipitant of ACLF. On multivariate analysis, admission serum urea (not serum creatinine) was found to be an independent predictor of mortality in ACLF both at 28 days; p=.001, AHR 1.014(1.006-1.023) and 90 days; p<.001, AHR 1.016(1.008-1.024) and also in ACLF patients with AKI, both at 28 days; p=0.002, AHR 1.014 (1.005-1.023) and 90 days; p=.001, AHR 1.016 (1.007-1.025). The discrimination ability between survivors and deceased is higher with serum urea [AUROC 28 days; 0.772 (0.686-0.859), 90 days; 0.780(0.695-0.866); 95% CI] than with serum creatinine [AUROC 28 days; 0.760(0.669-0.850), 90 days; 0.768(0.680-0.856); 95% CI]. Conclusion: In our institution, about one fourth of decompensated cirrhotic patients had ACLF, and more than two thirds of them were associated with AKI. Admission serum urea was found to be a better predictor of mortality than serum creatinine. Hence serum creatinine can be replaced by serum urea as a better predictor of mortality [both 28 and 90 days' mortality] in ACLF patients.

Expanded Diagnostic Approach to Hepatitis E Virus Detection in Patients with Acute-on-Chronic Liver Failure: A Pilot Study

Introduction: Acute decompensation of pre-existing chronic liver disease (CLD), known as acute-on-chronic liver failure (ACLF), is associated with high mortality. Hepatitis E virus (HEV) as a potential cause was studied. Objectives: The objectives of this study are to evaluate the role of HEV in ACLF patients using an IgM anti-HEV antibody enzyme-linked immunosorbent assay (ELISA), HEV antigen ELISA, and a quantitative HEV polymerase chain reaction (PCR). Materials and Methods: In this prospective cross-sectional study, blood samples were collected from 50 ACLF (cases) as defined by the standard guidelines (APASL, 2014) and 50 patients with stable CLD (controls) from January 2015 to August 2016, after obtaining informed consent. Two IgM ELISAs (MP Diagnostics HEV IgM ELISA 3.0, Singapore and Wantai HEV IgM ELISA, Beijing, China) were compared using plasma from cases and controls. In addition, an HEV antigen detection by ELISA (Wantai, Beijing, China) and a real-time PCR for quantification of HEV RNA in plasma and stool were employed. Results: Ethanol was the leading cause of acute insult in ACLF (54%) cases. HEV infection accounted for 20% of cases. Ten ACLF patients (20%) had 1–3 markers of HEV versus two (4%) among controls (P = 0.0138). Among ACLF cases, one had HEV viraemia (403 IU/ml), faecal shedding (2790 IU/ml) and detectable HEV antigenaemia. Agreement between the two anti-HEV IgM ELISAs was 0.638 (kappa value). Conclusion: This study shows that alcohol is a major contributing factor for both underlying CLD and ACLF while HEV is the most common infectious cause for ACLF, suggesting a need for a vaccination in such patients, whenever made available.

A Dynamic Model for Predicting Outcome in Patients with HBV Related Acute-On-Chronic Liver Failure

Introduction and aim. Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA).Material and methods. We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B.Results. The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ACLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01).Conclusion. In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.

A Case of Acute-on-Chronic Liver Failure (ACLF) Due to An Uncommon Acute And Chronic Event

Acute on Chronic Liver Failure (ACLF) is an acute worsening of patients with chronic liver disease resulting in liver failure. Usually these patients have cirrhosis as the underlying liver disease with alcohol being the most common etiology. Common hepatitic illnesses causing acute worsening in Indian patients of ACLF include alcoholic hepatitis, acute viral hepatitis related to hepatitis E virus and acute flare in chronic hepatitis B. We report an adult case of ACLF due acute viral hepatitis related to hepatitis A virus infection superimposed on nonalcoholic steatohepatitis without cirrhosis.

Sorafenib-induced acute-on-chronic liver failure in a patient with hepatocellular carcinoma after transarterial chemoembolization and radiofrequency ablation: A case report.

Comprehensive treatments together with sorafenib provide a survival benefit for patients with advanced hepatocellular carcinoma (HCC). Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct entity; however, only few cases induced by sorafenib have been reported to date. We herein present a rare case of ACLF in a patient under treatment with sorafenib. A 63-year-old woman who suffered from hepatitis B for 10 years was admitted to our hospital. A computed tomography (CT) scan led to a diagnosis of HCC in the V/VIII hepatic segment, with invasion of the middle hepatic and the right portal veins. The patient received multidisciplinary treatment, including transarterial chemoembolization, radiofrequency ablation and sorafenib. Two months after sorafenib treatment, the patient was readmitted due to progressive jaundice and ACLF was diagnosed by liver biopsy shortly thereafter. Although aggressive treatment was administered, the patient succumbed to the disease following rapid deterioration of her clinical condition. The majority of patients with HCC have underlying liver disease and combination therapy with sorafenib should be administered with caution, as it may increase the risk of severe hepatotoxicity. The present case suggests that patients treated with sorafenib may require a dose reduction following interventional treatment.

Changing etiologies and outcome of liver failure in Southwest China.

BackgroundThe prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts.MethodsWe screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis.Results97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three-month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001).ConclusionEtiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female.Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF.The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis.The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously.Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF.

Characterization of acute-on-chronic liver failure and prediction of mortality in Asian patients with active alcoholism.

Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism. A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality. Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P < 0.001), serum sodium level (OR, 0.939; P = 0.029), and neutrophil count (OR, 1.000; P = 0.021). For prediction of mortality at predefined time points (28-day and 90-day) in patients with ACLF, areas under the receiver-operating characteristic were significantly greater for the CLIF-C ACLFs than for Child-Pugh, MELD, and MELD-sodium scores. Infection and systemic inflammatory response syndrome play an important role in the development of alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems.

Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia.

In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.

Acute-On-Chronic Liver Failure (ACLF) in a Tertiary Care Hospital in Resource Constrained Region

Introduction: Acute-On-Chronic Liver Failure (ACLF) is an emerging entity. There is limited data on ACLF in the literature. The present study was undertaken to analyze the clinical profile and natural course of ACLF patients. Methods: ACLF was defined as per modified Asian Pacific Association for the Study of Liver (APASL) consensus criteria 2008. Patients fulfilling the criteria were included and prospectively evaluated for three months to study short term outcome. Results: Out of 159 patients with ACLF (mean age: 46.06±11.64 years; male: female-139:20), 38.36% cases had prior decompensation, whereas 61.63% presented first time as ACLF. Etiologies of cirrhosis were alcohol, cryptogenic and chronic hepatitis B virus infection in 67.29%, 22% and 10.69% cases respectively. Active alcohol drinking within 4 weeks (43%) followed by bacterial infection (37.39%) ware the common acute insults. Only 122 cases could be followed up, out of which 72.13% cases died by 3 months (Early mortality). Most of deaths occurred in alcoholics compared to non alcoholics (80% vs. 55.88%; p=0.007). Early mortality was significantly higher in cases with prior decompensation compared to newly diagnosed ACLF cases (84.78% vs. 64.47%; p=0.01). Early mortality was not significantly different between cases with single and multiple acute predispositions (p=0.13). The mean CTP and MELD score were 12.33±1.27 and 27.64±6.81 respectively. The prognostic markers (MELD, MELD-Na, CTP) were not significantly different between survivors and non-survivors. Conclusion: ACLF patients in our region had high short term mortality with majority of death in alcoholics and in cases with prior decompensation. Alcohol intake and bacterial infections were mainly responsible for acute decompensation in our region.