Search

Background: Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19. Methods: This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19. Results: Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70-305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12-100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31-299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01-1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02-0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27-19.46], p = 0.021) were associated with the mortality. Conclusion: The ALBI grade 3 and FIB-4 index = 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PTINR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission. [ABSTRACT FROM AUTHOR]

End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections. This review summarises current knowledge of alterations in adaptive immune responsiveness and their underlying mechanisms in ESLD. Understanding these mechanisms is of crucial importance in the identification of potential therapeutic targets and applications of targeted treatments beyond antimicrobials, such as immunotherapy. [ABSTRACT FROM AUTHOR]

Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30–40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy. [ABSTRACT FROM AUTHOR]

Background. Variceal rebleeding is a significant and potentially life-threatening complication of cirrhosis. Unfortunately, currently, there is no reliable method for stratifying high-risk patients. Liver stiffness measurements (LSM) have been shown to have a predictive value in identifying complications associated with portal hypertension, including first-time bleeding. However, there is a lack of evidence to confirm that LSM is reliable in predicting variceal rebleeding. The objective of our study was to evaluate the ability of generating a extreme gradient boosting (XGBoost) algorithm model to improve the prediction of variceal rebleeding. Methods. This retrospective analysis examined a cohort of 284 patients with hepatitis B-related cirrhosis. XGBoost models were developed using laboratory data, LSM, and imaging data to predict the risk of rebleeding in the patients. In addition, we compared the XGBoost models with traditional logistic regression (LR) models. We evaluated and compared the two models using the area under the receiver operating characteristic curve (AUROC) and other model performance parameters. Lastly, we validated the models using nomograms and decision curve analysis (DCA). Results. During a median follow-up of 66.6 weeks, 72 patients experienced rebleeding, including 21 (7.39%) and 61 (21.48%) patients who rebleed within 6 weeks and 1 year, respectively. In brief, the AUC of the LR models in predicting rebleeding at 6 weeks and 1 year was 0.828 (0.759–0.897) and 0.799 (0.738–0.860), respectively. In contrast, the accuracy of the XGBoost model in predicting rebleeding at 6 weeks and 1 year was 0.985 (0.907–0.731) and 0.931 (0.806–0.935), respectively. LSM and high-density lipoprotein (HDL) levels differed significantly between the rebleeding and nonrebleeding groups, with LSM being a reliable predictor in those models. The XGBoost models outperformed the LR models in predicting rebleeding within 6 weeks and 1 year, as demonstrated by the ROC and DCA curves. Conclusion. The XGBoost algorithm model can achieve higher accuracy than the LR model in predicting rebleeding, making it a clinically beneficial tool. This implies that the XGBoost model is better suited for predicting the risk of esophageal variceal rebleeding in patients. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several studies have investigated the management of this group of patients. Identification and treatment of precipitants of decompensation and ACLF play an important role, and management of the respective intra- and extrahepatic organ failures is essential. However, no specific treatment for ACLF has been established to date, and the only curative treatment option currently available for these patients is liver transplantation (LT). It has been shown that ACLF patients are at severe risk of waitlist mortality, and post-LT survival rates are high, making ACLF patients suitable candidates for LT. However, only a limited number of patients are eligible for LT due to related contraindications such as uncontrolled infections. In this case, bridging strategies (e.g., extracorporeal organ support systems) are required. Further therapeutic approaches have recently been developed and evaluated. Thus, this review focuses on current management and potential future treatment options. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To observe baseline characteristics, ACLF (Acute on Chronic Liver Failure) grading and mortality in ACLF patients using EASL CLIF CRITERIA. Study Design: Prospective, Observational study. Setting: Medical unit III, ward 7, Jinnah Postgraduate Medical Centre, Karachi. Period: January 2022 to June 2022. Material & Methods: We prospectively analysed data of hospitalised liver cirrhosis patients at a tertiary care hospital in Karachi, Pakistan. The data was analysed in SPSS version 25. Results: There were a total of 43 ACLF patients, with the median age of IQR of 56(47-62) years, out of which 20 (46.5%) patients were male and 23 (53.5%) were females. The most common etiology of liver cirrhosis was hepatitis C 26(60.5%) followed by other etiologies nine (20.9%) and hepatitis B eight (18.6%). The most common precipitating factor was infection 19(44.2%) and the most frequent organ failure (OF) was renal failure (60.5%), followed by cerebral failure (46.5%) and other OFs. There were 24 patients in ACLF grade one, 13 in grade two and six in grade three ACLF. All six patients of ACLF grade three belonged to CTP C (Child-Turcotte-Pugh score) (100%) with 100% mortality. ACLF grade two had nine (69.2%) and ACLF grade one had eight (33.33%) CTP C patients. The in hospital mortality of ACLF was 23%. The median MELD Na of these patients was 28 (23-31), CLIF Consortium Organ Failure score was 9(8-10) and CLIF C ACLF Score was 45 (38-55). Conclusion: Highest mortality was observed in Child Pugh C and ACLF grade three in our patients. Such patients must be closely monitored and referred early for medical management and liver transplantation. [ABSTRACT FROM AUTHOR]

The article selects relevant data from 283 cities in China from 2000 to 2020 and verifies the impact of the establishment of free trade zones on human capital levels based on the asymptotic PSM-DID model. It is found that the establishment of FTZs can significantly contribute to the improvement of regional human capital levels, but the promotion effect has a certain lag. Finally, the article gives constructive suggestions based on the empirical results. [ABSTRACT FROM AUTHOR]

Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic growth factor playing various roles in the human body including cell growth and development. More functions of TGF-β1 have been discovered, especially its roles in viral infection. TGF-β1 is abundant at the maternal–fetal interface during pregnancy and plays an important function in immune tolerance, an essential key factor for pregnancy success. It plays some critical roles in viral infection in pregnancy, such as its effects on the infection and replication of human cytomegalovirus in syncytiotrophoblasts. Interestingly, its role in the enhancement of Zika virus (ZIKV) infection and replication in first-trimester trophoblasts has recently been reported. The above up-to-date findings have opened one of the promising approaches to studying the mechanisms of viral infection during pregnancy with links to corresponding congenital syndromes. In this article, we review our current and recent advances in understanding the roles of TGF-β1 in viral infection. Our discussion focuses on viral infection during pregnancy, especially in the first trimester. We highlight the mutual roles of viral infection and TGF-β1 in specific contexts and possible functions of the Smad pathway in viral infection, with a special note on ZIKV infection. In addition, we discuss promising approaches to performing further studies on this topic. [ABSTRACT FROM AUTHOR]

Pregnancy does not appear to increase susceptibility to SARS-CoV-2 infection, but some physiological changes, such as the reduction of residual functional volumes, elevation of the diaphragm, and impaired cellular immunity, may increase the risk of severe disease and result in a higher risk of complications. The article's primary objective is to evaluate the factors associated with symptomatic COVID-19 disease in pregnancy. The secondary objective is to describe maternal and neonatal outcomes and cases of vertical transmission of the infection. All pregnant women hospitalized with SARS-CoV2 infection were included in a prospective study in the UOC of Obstetrics and Gynecology, AOOR Villa Sofia—Cervello, Palermo, between May 2020 and April 2021. The patients who requested the termination of the pregnancy according to Law 194/78 were excluded. We included 165 pregnancies with a total number of 134 deliveries. Overall, 88.5% of the patients were asymptomatic at the time of admission and 11.5% were symptomatic. Of them, 1.8% of the patients required hospital admission in the intensive care unit. Symptoms occurrences were positively associated with the increase in maternal BMI (OR 1.17; p = 0.002), the prematurity (OR 4.71; p = 0.022), and at a lower birth weight (OR 0.99; p = 0.007). One infant tested positive for SARS-CoV2 nasopharyngeal swab; 11.4% of newborns had IgG anti SARS-CoV2 at birth; IgM was positive in 2.4% of newborns. There was no difference statistically significant difference in the vertical transmission of the infection among the group of symptomatic pregnant women and that of asymptomatic pregnant women. [ABSTRACT FROM AUTHOR]

Background and Aim. Significantly reduced serum ceruloplasmin (Cp) is the most important clue in the diagnosis of Wilson's disease (WD) and is well known to clinicians. The false increase in Cp in some WD patients, which overlaps with that in non-WD liver disease patients, decreases the diagnostic accuracy. The aims of our study were to understand the factors associated with Cp normalisation in WD patients and identify these WD patients using usual predictors. Methods. We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results. Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥−1, the positive and negative predictive values were both 90.8% for WD. Conclusion. Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients. [ABSTRACT FROM AUTHOR]

Background: Early prediction for short-term prognosis is essential for the management of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). In this study, we aim to establish a noninvasive model for predicting the 90-day mortality in patients with HBV–ACLF received glucocorticoid therapy. Methods: Two hundred and eighty patients with HBV–ACLF were enrolled from July 2010 to June 2022. All patients received routine medicine treatment and 204 of them received additional glucocorticoid treatment. Then, the patients who received glucocorticoid treatment were randomly divided into a training cohort and a validation cohort. An early prediction model for 90-day mortality of HBV–ACLF was established in the training cohort and then validated in the validation cohort. Results: HBV–ACLF patients received glucocorticoid treatment showed significantly better survival that those not (P < 0.01). In the training cohort, a noninvasive model was generated with hepatic encephalopathy grade, INR, total bilirubin, age and SIRS status, which was named HITAS score. It showed significantly better predictive value for 90-day mortality of HBV–ACLF than MELD score and Child–Turcotte–Pugh score in both the training cohort and validation cohort. Using the Kaplan–Meier analysis with cutoff points of 2.5 and 3.47, the HITAS score can classify HBV–ACLF patients into different groups with low, intermediate and high risk of death after glucocorticoid therapy. Conclusions: We proposed a HITAS score, which was an early prediction model for the prognosis of HBV–ACLF. It might be used to identify HBV–ACLF patients with favorable responses to glucocorticoid treatment. [ABSTRACT FROM AUTHOR]

Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome, and patients often have high short-term mortality. It occurs with intense systemic inflammation, often accompanied by a proinflammatory event (such as infection or alcoholic hepatitis), and is closely related to single or multiple organ failure. Liver inflammation begins when innate immune cells (such as Kupffer cells (KCs)) are activated by binding of pathogen-associated molecular patterns (PAMPs) from pathogenic microorganisms or damage-associated molecular patterns (DAMPs) of host origin to their pattern recognition receptors (PRRs). Activated KCs can secrete inflammatory factors as well as chemokines and recruit bone marrow-derived cells such as neutrophils and monocytes to the liver to enhance the inflammatory process. Bacterial translocation may contribute to ACLF when there are no obvious precipitating events. Immunometabolism plays an important role in the process (including mitochondrial dysfunction, amino acid metabolism, and lipid metabolism). The late stage of ACLF is mainly characterized by immunosuppression. In this process, the dysfunction of monocyte and macrophage is reflected in the downregulation of HLA-DR and upregulation of MER tyrosine kinase (MERTK), which weakens the antigen presentation function and reduces the secretion of inflammatory cytokines. We also describe the specific function of bacterial translocation and the gut-liver axis in the process of ACLF. Finally, we also describe the transcriptomics in HBV-ACLF and the recent progress of single-cell RNA sequencing as well as its potential application in the study of ACLF in the future, in order to gain a deeper understanding of ACLF in terms of single-cell gene expression. [ABSTRACT FROM AUTHOR]

Background. Inflammation plays a critical role in the progression of acute-on-chronic liver failure (ACLF). Atg13 is a vital regulatory component of the ULK1 complex, which plays an essential role in the initiation of autophagy. Previously, hepatic stellate cells (HSCs) were considered to be noninflammatory cells that contribute only to hepatic fibrosis. Recently, it has been found that HSCs can secrete inflammatory cytokines and participate in hepatic inflammation. Autophagy and proteasome-mediated degradation constitute two major means of protein turnover in cells. Autophagy has been shown to regulate inflammation, but it is unclear whether ubiquitin (Ub)-proteasome system (UPS) is involved in inflammatory responses in HSCs during ACLF. Methods. Clinical data were collected from ACLF patients, and surgically resected paraffin-embedded human ACLF liver tissue specimens were collected. The expression of Atg13 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Secretion of IL-1β was assessed by ELISA. Atg13 was knocked down by siRNA in LX2 cells. Coimmunoprecipitation assay was used to detect protein binding and polyubiquitination of Atg13. In vitro tests with LX2 cells were performed to explore the effects and regulation of p38 MAPK, Atg13, UPS, autophagy, and inflammation. Results. Serum lipopolysaccharide (LPS) was positively associated with disease severity in ACLF patients, and p38 MAPK was overexpressed in ACLF liver tissue. We evaluated the role of Atg13 in HSC inflammation and explored the possible underlying mechanisms. Inflammatory factors were upregulated via activation of p38 MAPK and inhibition of autophagy in LX-2 cells. Expression of Atg13 was decreased in LPS-incubated LX2 cells. Atg13 knockdown markedly inhibited autophagy and promoted LPS-induced inflammation in LX2 cells. Our in vitro experiments also showed that LPS induced depletion of Atg13 via UPS, and this process was dependent on p38 MAPK. Conclusions. LPS induces proteasomal degradation of Atg13 via p38 MAPK, thereby participating in the aggravation of LPS-induced autophagy inhibition and inflammatory responses in LX2 cells. Atg13 serves as a mediator between autophagy and proteasome. Modulation of Atg13 or proteasome activity might be a novel strategy for treating HSC inflammation. [ABSTRACT FROM AUTHOR]

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is relatively common in China and has complex pathogenesis, difficult clinical treatment, and poor prognosis. Immune status is an important factor affecting ACLF prognosis. Interleukins are a family of secreted lymphocyte factors that interact with a host of cell types including immune cells. These signaling molecules play important roles in transmitting information; regulating immune cells; mediating the activation, proliferation, and differentiation of T and B cells; and modulating inflammatory responses. Many studies have investigated the correlation between interleukin expression and the prognosis of HBV-ACLF. This review focuses on the potential use of interleukins as prognostic biomarkers in HBV-ACLF. References were mainly identified through PubMed and CNKI search, including relevant studies published until December 2021. We have summarized reports of several promising diagnostic interleukin biomarkers that predict susceptibility to HBV-ACLF. The use of biomarkers to understand early prognosis can help devise different therapeutic measures and improve patient survival. Ongoing research on prognostic biomarkers of HBV-ACLF is promising, and future preclinical and clinical studies are warranted. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a public health threat worldwide, and there is no direct treatment yet available. In the event of infection, patients may present liver cirrhosis and cancer, which threaten the patients' health globally, especially in the Asia-Pacific region and China. In 2019, Chinese hepatopathologists updated the 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B as the clinical reference. The other versions formulated by the American Association for the Study of Liver Diseases (2018 AASLD guidelines) (AASLD, 2018), European Association for the Study of the Liver (2017 EASL guidelines) (EASL, 2017), and Asian-Pacific Association for the Study of the Liver (2015 APASL guidelines) (APASL, 2015) also provide clinical guidance. However, there are still some issues that need to be addressed. In the present study, the following aspects will be introduced successively: (1) Who should be treated in the general population according to the guidelines; (2) Treatment of specific populations infected with HBV; (3) Controversial issues in clinical practice; (4) Perspective. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation, organ failures, and high short-term mortality whose main cause in China is the Hepatitis B virus (HBV). Moreover, one of the most important causes of morbidity and mortality in HBV-ACLF patients is bacterial infection. Therefore, we investigate the clinical features, risk factors, prophylaxis and management of infections in patients with HBV-ACLF. Methods: We conducted a retrospective analysis of 539 patients with HBV-ACLF in Wuhan Tongji Hospital from October 2015 to May 2018. Differences among groups were compared with Student's t test, Mann-Whitney U test, 2 test, or Fisher exact test as appropriate. Univariate and Multivariate logistic regression analysis was used for modeling the relationship between infection and clinical characteristics of HBV-ACLF. Results: In total 58.81% (317/539) of patients with HBV-ACLF became complicated with infections, and the most common types were spontaneous bacterial peritonitis, urinary tract infection and pulmonary infection. Additionally, 32.18% (102/317) of patients suffered multi-organ infections, and 95.73% (516/539) of patients received anti-infective therapy. We detected a total of 202 isolates in all infected patients, and Escherichia coli (36.14%, 73/202) was the most common causative organism. Moreover, antibiotic susceptibility test patterns showed that 52.97% (107/202) of pathogens were MDR bacteria and 4.95% (10/202) were XDR bacteria. Univariate analysis indicated that patients with infection had a higher proportion of females, taking alcohol, diuretics, hepatic encephalopathy (HE), hepatorenal syndrome (HS), cirrhosis, a long-time in bed and mechanical ventilation, lower prothrombin activity (PTA), alanine aminotransferase (ALT), albumin, total cholesterol (TC), estimated glomerular filtration rate (eGFR), hemoglobin (Hb) and platelet (PLT) and higher age, model for end-stage liver disease (MELD) scores and ACLF grade than patients without infection. Multivariate logistic regression analysis showed that taking alcohol, HE, HS, cirrhosis, albumin and eGFR were risk factors for the development of infection. Conclusions: Bacterial infections were very common in patients with HBV-ACLF. Taking alcohol, the occurrence of complications (HE, HS and cirrhosis), hypoalbuminemia and poor renal function often predict the higher prevalence of infections in patients with HBV-ACLF. It is important to focus on exploring the early recognition of infection and early intervention of those risk factors in patients with HBV-ACLF. [ABSTRACT FROM AUTHOR]

Despite the presence of hepatitis B virus (HBV) in the human breastmilk of mothers infected with HBV, it has been shown that breastfeeding does not increase the risk of mother-to-child transmission (MTCT) of HBV. We tested the hypothesis that human breastmilk may contain active components that bind to HBV and inhibit the infectivity of HBV. The results show that human whey significantly inhibited the binding of the hepatitis B surface antigen (HBsAg) to its antibodies in competitive inhibition immunoassays. The far-western blotting showed that HBsAg bound to a protein of 80 kD in human whey, which was identified as lactoferrin by mass spectrometry. Competitive inhibition immunoassays further demonstrated that both human lactoferrin and bovine lactoferrin bound to HBsAg. Human whey, human lactoferrin, and bovine lactoferrin each significantly inhibited the infectivity of HBV in vitro. Our results indicate that human breastmilk can bind to HBsAg and inhibit the infectivity of HBV, and the active component is lactoferrin. The findings may explain the reason that breastfeeding has no additional risk for MTCT of HBV, although human breastmilk contains HBV. Our study provides experimental evidence that HBV-infected mothers should be encouraged to breastfeed their infants [ABSTRACT FROM AUTHOR]

Objective. This study aims to investigate the clinical efficacy of plasma exchange in treating acute-on-chronic liver failure (ACLF) through meta-analysis. Method. PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched using a computer for all relevant Chinese and English literature from 2000 to 2021 in each database. At the same time, a large number of related papers and materials were manually consulted. Randomized controlled trials of plasma exchange (PE, control group) and combined double plasma molecular absorption system (DPMAS + PE, observation group) for the treatment of ACLF were collected. Meta-analysis was performed with Stata16.0 software. Result. A total of 474 articles were retrieved, and 11 papers were finally included for research after screening. Meta-analysis results showed that the effective rate of treatment in the experimental group was significantly higher than that in the control group. At the same time, the observation group's prothrombin activity (PTA) level was better than that of the control group after treatment. After treatment, there was no significant difference in prothrombin time (PT) and international normalized ratio (INR) between the two groups. In addition, after treatment, the alanine aminotransferase (ALT) level of the observation group was significantly lower than that of the control group. However, TBIL levels and albumin (ALB) levels did not change significantly between the two groups. Regarding blood routine indexes, there were no significant changes in creatinine (Cr) levels and platelet counts (PLT) in the two groups after treatment, but hemoglobin (HGB) levels in the observation group were significantly lower than those in the control group. Conclusion. DPMAS combined with plasma exchange therapy can improve liver function, coagulation function, and blood routine level of ACLF patients and increase the effective rate of treatment. It is an effective treatment for acute-on-chronic liver failure. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to explore the clinical detection and prognosis of coagulation function in patients with liver failure and sepsis. METHODS: The plasma fibrinogen (FIB), factor II, factor VII, factor V, factor IV, antithrombin III (ATIII), platelet (PLT), mean PLT volume (MPV), D-dimer, prothrombin activity (PTA), and fibrin degradation product (FDP) levels and thromboelastogram values were detected in patients with liver failure complicated with sepsis and compared with those in the liver failure and liver cirrhosis groups. The patients with liver failure complicated with sepsis were analyzed by univariate and multivariate logistic regression, and the regression equation was established. RESULTS: The levels of FIB, factor II, factor VII, factor V, ATIII, PLT, MPV, D-dimer, and FDP in the patients with liver failure complicated with sepsis were compared with those in the control group patients, and the differences were statistically significant (p < 0.05). Among the thromboelastography parameters in the patients with liver failure and sepsis, the differences in the K-value, R-value, angle, maximum amplitude, and coagulation index values compared with those of the control group were statistically significant (p < 0.05). The logistic regression model obtained was as follows: p = 1/(1 + e [–0.128×X1–0.058×X2 + 0.211×X3 + 0.2×X4 + 0.25]). The specificity, sensitivity, and accuracy values of the regression equation in determining the prognosis were 92%, 93.9%, and 92.8%, respectively. Among the 11 factors, factor VII, PLT, FDP, and D-dimer were included in the regression equation. CONCLUSION: Coagulation disorder is exacerbated in patients with liver failure and sepsis. Among the 11 coagulation-related factors, factor VII, PLT, FDP, and D-dimer may be the independent factors influencing the prognosis of patients with acute liver failure and sepsis. [ABSTRACT FROM AUTHOR]

Background: The manifestations and prognoses of acute-on-chronic liver failure (ACLF) with different precipitating events remain heterogeneous. We aimed to investigate the characteristics and prognosis of patients with hepatotropic viral insult (HVI)-induced hepatitis B-related ACLF (HBV-ACLF).Methods: 452 patients with confirmed diagnosis of ACLF were screened in three medical centers in China, and 203 HBV-ACLF patients with definite acute precipitating events were retrospectively analyzed. According to the precipitating events, HBV-ACLF patients induced by HBV reactivation and super-infection with HAV were classified as the hepatotropic viral insult group and those induced by other factors, as the non-virus insult (NVI) group. The clinical characteristics, predictive scoring model, and prognosis of the two groups were compared.Results: Hepatitis B virus reactivation accounted for the largest proportion (39.9%) among all precipitating events. Exacerbation time frame of the HVI group was significantly longer than that of the NVI group (20 days vs. 10 days, P < 0.001). Comparison of intergroup prognosis showed that there was no significant difference in the 28 day mortality (20.9 vs. 13.7%, P = 0.125), while the 90 day and 1 year mortality in the HVI group were higher than those in the NVI group (36.3 vs. 24.4%, P = 0.014; 39.5% vs. 27.5%, P = 0.020, respectively). In the HVI group, the lactic acid-free APASL-ACLF Research Consortium (AARC) had better predictive value for 90 day mortality (0.741).Conclusions: The 90 day and 1 year survival rate was lower in HBV-ACLF patients induced by HVI than by NVI. The lactate-free AARC score was a better predictor of short- and long-term prognosis in patients with HVI-induced HBV-ACLF. [ABSTRACT FROM AUTHOR]

Background. T-helper 17 (Th17) and CD4+CD25+ T-regulatory (Treg) cells play important roles in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This study is aimed at investigating shifts in Treg/Th17 balance in the peripheral blood of HBV-ACLF patients at different disease stages. Methods. Sixty HBV-ACLF patients, admitted to the First Hospital of Hunan University of Chinese Medicine, China, including early-stage (n = 20), middle-stage (n = 20), and late-stage patients (n = 20), were enrolled in the study. In addition, 20 patients with chronic hepatitis B and 20 healthy volunteers were also included in the study as controls. Flow cytometry, cytometric bead array, and quantitative real-time PCR protocols were used to evaluate the expression of Treg and Th17 cells as well as of related cytokines. Results. The levels of Th17 cells and their effectors interleukin- (IL-) 17A, IL-23, and tumor necrosis factor-α increased with disease progression. Similarly, Treg cells and their effector cytokines transforming growth factor-β and IL-10 also increased. Although Treg and Th17 levels were positively correlated, the latter were always at higher numbers. Noteworthy, the Treg/Th17 ratio gradually decreased and was negatively correlated with ACLF severity. FoxP3 levels in the peripheral blood gradually decreased with ACLF progression, whereas ROR-γt gradually increased. Serum c-reactive protein, procalcitonin, and lipopolysaccharide were also upregulated with disease progression and positively correlated with Th17 abundance. Further, Th17, IL-17A, and IL-23 were independent risk factors for ACLF. A prognostic model for HBV-ACLF was established, with a correct prediction rate of 90.00% (54/60). Conclusion. Treg/Th17 imbalance occurs throughout the pathogenic course of HBV-ACLF, with an imbalance shift toward Th17. Hence, the Th17-mediated inflammatory response drives HBV-ACLF-associated inflammation and supports the pathological mechanisms of liver failure. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is a comprehensive syndrome characterized by an acute deterioration of liver function and high short-term mortality rates in patients with chronic liver disease. Whether plasma soluble urokinase plasminogen activator receptor (suPAR) is a suitable biomarker for the prognosis of patients with ACLF remains unknown.Method: A prospective cohort of 282 patients with ACLF from three hospitals in China was included. 88.4% of the group was hepatitis B virus-related ACLF (HBV-related ACLF). Cox regression was used to assess the impact of plasma suPAR and other factors on 30- and 90-day mortality. Reactive oxygen species (ROS) production were detected to explore the role of suPAR in regulating neutrophil function in HBV-related ACLF.Result: There was no difference in plasma suPAR levels between HBV-related and non-HBV-related ACLF. Patients with clinical complications had higher suPAR levels than those without these complications. A significant correlation was also found between suPAR and prognostic scores, infection indicators and inflammatory cytokines. Cox's regression multivariate analysis identified suPAR ≥ 14.7 ng/mL as a predictor for both day 30 and 90 mortality (Area under the ROC curve: 0.751 and 0.742 respectively), independent of the MELD and SOFA scores in patients with ACLF. Moreover, we firstly discovered suPAR enhanced neutrophil ROS production under E.coli stimulation in patients with HBV-related ACLF.Conclusions: suPAR was a useful independent biomarker of short-term outcomes in patients with ACLF and might play a key role in the pathogenesis. Trial registration CNT, NCT02965560. [ABSTRACT FROM AUTHOR]

Background: Although the Asian Pacific Association for the Study of the Liver acute-on-chronic liver failure (ACLF) research consortium (AARC) ACLF score is easy to use in patients with hepatitis b virus-related ACLF (HBV-ACLF), serum lactate is not routinely tested in primary hospitals, and its value may be affected by some interference factors. Neutrophil-to-lymphocyte ratio (NLR) is used to assess the status of bacterial infection (BI) or outcomes in patients with various diseases. We developed an NLR-based AARC ACLF score and compared it with the existing model.Methods: A total of 494 HBV-ACLF patients, enrolled in four tertiary academic hospitals in China with 90-day follow-up, were analysed. Prognostic performance of baseline NLR and lactate were compared between cirrhotic and non-cirrhotic subgroups via the receiver operating curve and Kaplan-Meier analyses. A modified AARC ACLF (mAARC ACLF) score using NLR as a replacement for lactate was developed (n = 290) and validated (n = 204).Results: There were significantly higher baseline values of NLR in non-survivors, patients with admission BI, and those with higher grades of ACLF compared with the control groups. Compared with lactate, NLR better reflected BI status in the cirrhotic subgroup, and was more significantly correlated with CTP, MELD, MELD-Na, and the AARC score. NLR was an independent predictor of 90-day mortality, and was categorized into three risk grades (< 3.10, 3.10-4.78, and > 4.78) with 90-day cumulative mortalities of 8%, 21.2%, and 77.5% in the derivation cohort, respectively. The mAARC ACLF score, using the three grades of NLR instead of corresponding levels of lactate, was superior to the other four scores in predicting 90-day mortality in the derivation (AUROC 0.906, 95% CI 0.872-0.940, average P < 0.001) and validation cohorts (AUROC 0.913, 95% CI 0.876-0.950, average P < 0.01), with a considerable performance in predicting 28-day mortality in the two cohorts.Conclusions: The prognostic value of NLR is superior to that of lactate in predicting short-term mortality risk in cirrhotic and non-cirrhotic patients with HBV-ACLF. NLR can be incorporated into the AARC ACLF scoring system for improving its prognostic accuracy and facilitating the management guidance in patients with HBV-ACLF in primary hospitals. [ABSTRACT FROM AUTHOR]

People infected with chronic hepatitis B virus (HBV) might progress to acute-on-chronic liver failure (ACLF) with a high fatality rate. Long noncoding RNAs (lncRNAs) are involved in human diseases, but it is unknown whether lncRNAs are involved in the progression of chronic HBV infection to ACLF. Hence, this study is aimed at systemically identifying and characterizing the landscape and the molecular mechanism of lncRNAs in the pathogenesis of chronic HBV infection progress to ACLF. RNA sequencing (RNA-Seq) of peripheral blood samples from 5 ACLF and 5 HBV infection patients was performed. We detected 9733 lncRNAs, including 406 annotated lncRNAs and 9327 novel lncRNAs. A total of 407 lncRNAs were found to be significantly dysregulated in the patients with ACLF as compared with those in the chronic HBV infection patients. The flanking protein-coding genes of differentially expressed lncRNAs were enriched with pathways that might contribute to the pathogenesis of ACLF, such as the WNT signaling pathway. Furthermore, 9 selected differentially expressed lncRNAs validated by the qRT-PCR, showing that the expression patterns of these 9 lncRNAs were consistent with the RNA-Seq data. Four selected differentially expressed lncRNAs were also validated in another patient cohort comprising 80 patients with ACLF and 65 patients with chronic HBV infection. Aberrant lncRNAs might be used to develop novel diagnostic biomarkers or drug targets for ACLF. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Advanced Nursing (John Wiley & Sons, Inc.) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims. Acute-on-chronic liver failure (ACLF) is common in patients with end-stage liver disease and chronic hepatitis B (CHB) or hepatitis B virus- (HBV-) related cirrhosis. To date, no uniform definition and management strategy are available for ACLF. Although a considerable number of studies on ACLF has been published, there are few reports on ACLF in pregnant women with CHB. This study retrospectively reviewed five patients who were diagnosed with ACLF during pregnancy in the past 10 years. We aimed at investigating their clinical characteristics, treatment, biochemical test results, and maternal and fetal outcomes. Results. Asthenia, anorexia, and jaundice were the main initial clinical manifestations in these patients during the second or third trimester of pregnancy. All patients received antiviral therapy. None of the pregnant women died after treatment. Patient #4 was treated with an artificial liver support system, and patients #2 and #5 underwent transfusion therapy. The acute insult in all patients was HBV DNA reactivation. Except for patient #3, who chose an actively induced vaginal delivery because of intrauterine fetal demise, the remaining four patients underwent a preterm delivery via a cesarean section. The four neonates were alive, although all were small for gestational age. Conclusion. Asthenia, anorexia, and jaundice during mid-late pregnancy should be immediately investigated. Before and during the pregnancy, hepatologists or obstetricians should actively screen pregnant women with CHB for HBV DNA status and alanine aminotransferase levels. Reactivation of HBV replication in pregnant women with CHB may lead to ACLF, especially in multiparous women. Once ACLF is diagnosed, antiviral therapy should be considered as soon as possible to protect maternal and fetal health. [ABSTRACT FROM AUTHOR]

Patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) exhibit complex hemostatic defects. Thromboelastography (TEG) can be used to reveal global hemostasis in patients with liver disease; however, little is known about the association between TEG and the outcome of patients with HBV-related ACLF. The present study aimed to investigate the value of TEG for predicting 90 day mortality in patients with HBV-related ACLF. A total of 51 patients with HBV-related ACLF, 26 patients with chronic hepatitis B (CHB) and 26 healthy controls (HC) were enrolled in the present study. TEG, standard coagulation tests, routine blood tests, biochemical markers and demographic variables were recorded and assessed for prognostic value. The results indicated that a prolonged reaction and kinetics (K) time, a shortened α angle and a decreased maximum amplitude (MA) and coagulation index (CI) were observed in patients with HBV-related ACLF, compared with CHB and HC subjects. Patients with HBV-related ACLF in the mortality group exhibited a decrease in α angle, MA, lysis at 30 min, CI, fibrinogen and platelet count, and an increase in K time, international normalized ratio (INR) and the model for end-stage liver disease (MELD) score in comparison with the survival group. MA and INR were two independent predictors of 90 day mortality in patients with HBV-related ACLF, with hazard ratios of 0.918 (95% CI, 0.867-0.971; P=0.003) and 3.141 (95% CI, 1.843-5.354; P<0.001) respectively. When predicting 90 day mortality, MA + INR exhibited the highest area under the receiver operating characteristic curve, followed by INR, MELD score and MA. Patients with ACLF and MA ≤51.5 mm exhibited a poorer outcome than those with MA >51.5 mm, as revealed via the Kaplan-Meier analysis. In summary, the findings of the present study suggested that TEG MA was associated with 90 day mortality in patients with HBV-related ACLF, and a combination of MA and INR was superior to MA, INR and MELD score in terms of prognostic value. [ABSTRACT FROM AUTHOR]

Aims. Tenofovir (TDF) is an antiviral drug with potential risk of kidney injury. The study is aimed at comparing the incidence of acute kidney injury (AKI) between TDF and entecavir (ETV) treatment in hepatitis B virus- (HBV-) related acute on chronic liver failure (ACLF). Methods. Treatment-naive patients with HBV-related ACLF were included. Propensity score matching was used to balance the baseline characteristics between ETV and TDF groups. The risk of AKI and the efficacy of TDF and ETV were compared. Results. A total of 95 cases with HBV-related ACLF were included in this study, with 74.74% of male and a mean age of 47.01 ± 14.71 years. The antiviral therapy was initiated within 2 days after admission, with 39 cases on the TDF group and 56 on the ETV group. Patients in the TDF group had higher AST, hemoglobin, and serum sodium levels and lower MELD-Na score. After propensity matching, 39 cases of TDF and 39 of ETV were included in the final analysis. No difference was found in the changes of creatinine and cystatin C from baseline to 4 weeks after treatment between ETV and TDF groups. AKI was developed in 1 (2.56%) patient in the ETV group and 2 (5.13%) in the TDF group within one month (P = 0.556). Survival analysis revealed no significant difference in the 6-month mortality between the two groups (P = 0.813). Cox analysis showed that the type of antiviral drug or the development of AKI was not an independent risk factor for the outcomes. Conclusions. Compared to ETV, TDF did not increase the risk of AKI nor the mortality in patients with HBV-related ACLF in the short time. [ABSTRACT FROM AUTHOR]

Purpose: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure.Methods: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.Results: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain.Conclusions: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes. [ABSTRACT FROM AUTHOR]

Autoimmune hepatitis (AIH) is a severe liver disease that arises in genetically predisposed male and female individuals worldwide. Diagnosis of AIH is made clinically applying diagnostic scores; however, the heterotopic disease phenotype often makes a rapid determination of disease challenging. AIH responds favorably to steroids and pharmacologic immunosuppression, and liver transplantation is only necessary in cases with acute liver failure or end-stage liver cirrhosis. Recurrence or development of de novo AIH after transplantation is possible, and treatment is similar to standard AIH therapy. Current experimental investigations of T cell-mediated autoimmune pathways and analysis of changes within the intestinal microbiome might advance our knowledge on the pathogenesis of AIH and trigger a spark of hope for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Aims. Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods. Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results. Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR>16.26 ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions. Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients. [ABSTRACT FROM AUTHOR]

Background. Hyperkalemia is a serious complication in cirrhotic patients. However, the clinical characteristics, risk factors, and its impact on the outcomes in acute-on-chronic liver failure (ACLF) patients remain unclear. Methods. We retrospectively recruited 650 ACLF patients in this study. The risk factors associated with hyperkalemia and its relationship with 90-day mortality were analyzed using multivariable regression models. Results. Among 650 patients with ACLF, 12.2% (79/650) had hyperkalemia during hospitalization. Higher admission serum potassium levels and the presence of acute kidney injury (AKI) were independent risk factors for hyperkalemia. The prevalence rates of hyperkalemia in patients with and without AKI were 23.6% and 4.6%, respectively (P<0.001). Hyperkalemia was a predictor of mortality in AKI and non-AKI patients. The 90-day mortality rates in non-AKI patients with and without hyperkalemia were 44.4% and 24.7%, respectively (P<0.001), and in AKI patients with and without hyperkalemia were 80.3% and 56.6%, respectively (P<0.001). Hepatic encephalopathy (HE), gastrointestinal bleeding, AKI, hyperkalemia, elevated total bilirubin (TBIL) and international normalized ratio (INR) values, and higher Model for End-Stage Liver Disease (MELD) and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores were independent risk factors for predicting the 90-day mortality in ACLF patients. Conclusions. Hyperkalemia increases the 90-day mortality in ACLF patients; hyperkalemia is associated with AKI. Patients with both AKI and hyperkalemia had the worst outcome. [ABSTRACT FROM AUTHOR]

Background. Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. Methods. A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n=30), UC-MSC group (n=30), PE group (n=30), and UC-MSC + PE group (n=20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). Results. The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P<0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (all P<0.05). Conclusion. UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no. NCT01724398. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by profound disrupted coagulation and fibrinolysis. Fibrinolytic marker D-dimer is increased in critically ill patients with cirrhosis which is associated with poorer prognosis. We aim to determine the potential association of D-dimer with the 28-day mortality in ACLF patients.Methods: In a single center retrospective study performed in China, we collected data of 115 patients with ACLF from October 1, 2012 to December 31, 2016. We investigated correlations between D-dimer and other laboratory tests and prognostic scores. The relationship between D-dimer and 28-day mortality was explored by smoothing plot with an adjustment for potential confounders. Logistic regression analyses with crude and adjusted models were performed to explore the association of D-dimer with 28-day mortality in ACLF patients.Results: In ACLF patients, D-dimer at admission was correlated with all prognostic scores (MELD-Na: r = 0.385, P < 0.001; CLIF-C ADs: r = 0.443, P < 0.001; CLIF-C ACLFs: r = 0.375, P < 0.001). A nonlinear relation between D-dimer and 28-day mortality was found with a turning point at 6.5 mg/L FEU. D-dimer level was independently associated with 28-day mortality with an adjusted odds ratio of [1.4 (1.0-1.9), P = 0.030] as continuous variable and [10.3 (1.3, 81.5), P = 0.028] as a classified variable with the cut-off of 6.5 mg/L FEU. An elevated D-dimer within the following 10 days also tended to be associated with higher risk of 28-day mortality [OR: 27.5 (0.9, 814.9), P = 0.055].Conclusions: Elevated D-dimer levels was associated with increased risk of 28-day mortality in patients with ACLF in China. [ABSTRACT FROM AUTHOR]

Background/Aims: The age-bilirubin-international normalized ratio-creatinine (ABIC) score, which is a predictive model commonly used for alcoholic hepatitis, has not yet been studied in acute-on-chronic hepatitis B liver failure (HBV-ACLF). We aimed to investigate the predictive value of the ABIC score in patients with HBV-ACLF. Methods: This retrospective study involved 398 patients diagnosed with HBV-ACLF, who were divided into a training cohort of 305 patients and a validation cohort of 93 patients. Univariate and multivariate Cox regression models were used to determine risk factors for mortality. Area under the receiver operating characteristic curve (AUC) was calculated to estimate and compare the predictive values of different prognostic scores. Results: The ABIC score was significantly higher in the death group of the training cohort than in its survival group. Independent risk factors for mortality identified by multivariate Cox analysis included blood urea nitrogen, ABIC score, and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score. For predicting 1- and 3-month mortality, AUC was higher for the ABIC score than for the Model for End-stage Liver Diseases (MELD) score (0.732 vs. 0.653, P < 0.05, 0.695 vs. 0.619, P < 0.05, respectively), CLIF-C OF score (0.693, P=0.353, 0.656, P=0.341, respectively), and Child-Pugh score (0.675, P=0.189, 0.656, P=0.300, Respectively). Patients with ABIC score > 9.44 had reduced 1- and 3-month survival rates. Conclusion: ABIC score is superior to MELD score in predicting short-term survival in HBV-ACLF patients. ABIC score > 9.44 predicts high short-term mortality risk in HBV-ACLF patients. [ABSTRACT FROM AUTHOR]

Background: Studies on human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have focused primarily on the immunosuppressed population. Few studies have considered immunocompetent and not severely immunocompromised patients. We determined the infection rates of HCMV and EBV, their risk factors and their influence on liver function in patients with HBV-related acute-on-chronic liver failure (ACLF).Methods: Patients infected with ACLF-based hepatitis B virus (HBV) from 1 December 2016 to 31 May 2018 were enrolled in our study and were divided into infected and uninfected groups. The risk factors for HCMV and EBV infection and their influence on liver function were analysed.Results: A total of 100 hospitalized patients with ACLF due to HBV infection were enrolled in this study. Of these patients, 5% presented HCMV deoxyribonucleic acid (DNA) and 23.0% presented EBV DNA. An HBV DNA count of < 1000 IU/mL increased the occurrence of HCMV infection (P = 0.003). Age, especially older than 60 years, was a risk factor for EBV infection (P = 0.034, P = 0.033). HCMV-infected patients had lower alanine aminotransferase (ALT) levels; albumin levels and Child-Pugh scores in EBV-infected patients were higher than those in uninfected patients.Conclusions: HCMV and EBV were detected in patients with ACLF caused by HBV infection. Lower replication of HBV (HBV DNA < 1000 IU/mL) may increase the probability of HCMV infection; age, especially older than 60 years of age, was a risk factor for EBV infection. HCMV infection may inhibit HBV proliferation and did not increase liver injury, while co-infection with EBV may influence liver function and may result in a poor prognosis. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the relationship between elevated serum procalcitonin (PCT) and renal function in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: HBV-ACLF patients (n = 201) presenting to the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, from January 2013 to November 2016 were categorized into three groups according to serum PCT levels: (i) normal group (n = 74) had PCT of ≤ 0.5 ng/mL; (ii) elevated group (n = 85) had PCT in the range 0.5-1.0 ng/mL; and (iii) highly elevated group (n = 42) had PCT of > 1.0 ng/mL. Thirty-five cases received standard care after admission. Serum PCT levels and renal function were determined during a two-week follow-up. Results: Significant increases in serum creatinine (Cr) were recorded in male and female patients in the elevated group and highly elevated group compared with the normal group (P < 0.05). In addition, serum Cr levels in male and female patients were significantly higher in the highly elevated group than in the elevated group (P < 0.05). The glomerular filtration rate (GFR) was significantly lower in the highly elevated group (P < 0.05) and this group had the highest risk of altered Cr (45.9% in males; 80% in females) and abnormal GFR (37.5%). Serum PCT levels correlated significantly with all renal function parameters including homocysteine (Hcy), GFR, Cr, blood urea nitrogen, uric acid, and cystatin C at baseline and during treatment. Univariate and multivariate analyses indicated that serum PCT was a strong predictor of renal dysfunction. Conclusion: Serum PCT is closely related to renal dysfunction in HBV-ACLF. [ABSTRACT FROM AUTHOR]