Hepatic amyloidosis in a patient with chronic liver failure:A case report

BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells.Cases in which the liver is the primary organ affected by amyloidosis,as in this report,are less common in clinical practice.CASE SUMMARY A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes.His condition persisted,and he developed chronic liver failure,with severe cholestasis in the later stage that was gradually accompanied by renal injury.Ultimately,he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination.CONCLUSION Hepatic amyloidosis rarely occurs in the clinic,and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.

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

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

Major liver resections,perioperative issues and posthepatectomy liver failure:A comprehensive update for the anesthesiologist

Significant advances in surgical techniques and relevant medium-and long-term outcomes over the past two decades have led to a substantial expansion in the indications for major liver resections.To support these outstanding results and to reduce perioperative complications,anesthesiologists must address and master key perioperative issues(preoperative assessment,proactive intraoperative anesthesia strategies,and implementation of the Enhanced Recovery After Surgery approach).Intensive care unit monitoring immediately following liver surgery remains a subject of active and often unresolved debate.Among postoperative complications,posthepatectomy liver failure(PHLF)occurs in different grades of severity(A-C)and frequency(9%-30%),and it is the main cause of 90-d postoperative mortality.PHLF,recently redefined with pragmatic clinical criteria and perioperative scores,can be predicted,prevented,or anticipated.This review highlights:(1)The systemic consequences of surgical manipulations anesthesiologistsmust respond to or prevent,to positively impact PHLF(a proactive approach);and(2)the maximal intensivetreatment of PHLF,including artificial options,mainly based,so far,on Acute Liver Failure treatment(s),to buytime waiting for the recovery of the native liver or,when appropriate and in very selected cases,toward livertransplant.Such a clinical context requires a strong commitment to surgeons,anesthesiologists,and intensivists towork together,for a fruitful collaboration in a mandatory clinical continuum.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease:A retrospective observational study

BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.

Acute-on-chronic liver failure induced by antiviral therapy for chronic hepatitis C: A case report

BACKGROUND There have been no reports of acute-on-chronic liver failure(ACLF)during treatment of chronic hepatitis C(CHC)with direct-acting antivirals(DAAs).CASE SUMMARY We report a 50-year-old male patient with CHC.The patient sought medical attention from the Department of Infectious Diseases at our hospital due to severe yellowing of the skin and sclera,which developed 3 mo previously and attended two consecutive hospitals without finding the cause of liver damage.It was not until 1 mo ago that he was diagnosed with CHC at our hospital.After discharge,he was treated with DAAs.During treatment,ACLF occurred,and timely measures such as liver protection,enzyme lowering,anti-infective treatment,and suppression of inflammatory storms were implemented to control the condition.CONCLUSION DAA drugs significantly improve the cure rate of CHC.However,when patients have factors such as autoimmune attack,coinfection,or unclear hepatitis C virus genotype,close monitoring is required during DAA treatment.

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

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

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

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

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

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity.

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

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

Upregulation of Toll-like Receptor 4 on T Cells in PBMCs Is Associated with Disease Aggravation of HBV-related Acute-on-chronic Liver Failure

Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.

Analyses of prognostic indices of chronic liver failure caused by hepatitis virus

AIM: To analyze the related indices about the prognoses of chronic liver failure caused by hepatitis virus. METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P=1/(1+e^(-y)) (y=1.7262-0.0948X_1+2.9846X_2+0.6992X_3+1.6019X_4+2.0398X_5). (Note: X_1-Prothrombin activity; X_2-digestive tract hemorrhage; X_3-hepatic encephalopathy; A_4-hepatorenal syndrome; X_5-pulmonary infection.). CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

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

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

Advanced therapeutic strategies for HBV-related acute-on-chronic liver failure

Acute-on-chronic liver failure （ACLF） is increasingly recognized as a distinct clinical entity and is as- sociated with a high short-term mortality. The most common cause of ACLF is chronic hepatitis B worldwide. Currently, there is no standardized approach for the management of ACLF and the efficacy and safety of therapeutic modalities are uncertain. DATA SOURCES： PubMed and Web of Science were searched for English-language articles. The search criteria focused on clinical trials and observational studies on the treatment of patients with HBV-related ACLF. RESULTS： Therapeutic approaches for ACLF in patients with chronic hepatitis B included nucleos（t）ide analogues, artificial liver support systems, immune regulatory therapy, stem cell therapy and liver transplantation. All of these therapeutic ap- proaches have shown the potential to improve liver function and increase patients＇ survival rate, but most of the studies were not randomized or controUed. CONCLUSION： Substantial challenges for the treatment of HBV-related ACLF remain and further basic research and ran- domized controlled clinical trials are needed.

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure (ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first Bis either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016 The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4 To were community-acquired,46.4 To were healthcare-associated,and 40.2% belonged to nosocomial BIs.Pneumonia (40.7%),spontaneous bacterial peritonitis (SBP)(34.5%),and bloodstream infection (BSI)(13.4%) were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend (P=0.021).Sixty-one strains of bacteria,including 83.6% Gramnegative bacteria and 29.5% multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli (44.3%) and Klebsiella pneumoniae (23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend (ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P <0.001).The independent predictors of the 28-doutcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio[HR]=1.371),acute kidney injury (HR=2.187),BSI (HR=2.339),prothrombin activity (HR=0.967),and invasive catheterization (HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.

Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μmol/L±270.09μmol/L vs 176.13μmol/L±185.70μmol/L,P=0.014).Serum albumin levels were significantly increased in both the"TQD"group and"TTK"group as compared with the MMC group(31.30 g/L±4.77g/L,30.72 g/L±2.89 g/L vs 28.57 g/L±4.56 g/L,P<0.05).There were no significant differences in levels of alanine transaminase among the three groups(P>0.05).Safety data showed that there was one case of stomachache in the"TQD"group and one case of gastrointestinal side effect in the"TTK"group.CONCLUSION:Treatment with"TTK"improved the survival rates of patients with liver failure due to chronic hepatitis B.Additionally,liver tissue was regenerated and liver function was restored.

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

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

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

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

Changes of IL-1, TNF-Alpha, IL-12 and IL-10 Levels with Chronic Liver Failure

[Aim] To investigate the action of cytokines in patients with chronic liver failure and to explore the roles of cytokines in chronic liver failure. [Methods] Thirty-one patients with chronic liver failure admitted from May 2006 to November 2009 were included. Thirty cases with mild to moderate chronic type B hepatitis admitted concomitantly were regarded as control. IL-1, TNF-alpha, IL-12, IL-10 Levels in serum was the factors to determine at clinical diagnosis and 2-week treatment. We analyzed levels of cytokines action in 31 chronic liver failure patients both at clinical diagnosis and 2-week treatment in comparison with control group. [Results] We analyzed IL-1 level in death group at clinical diagnosis and 2-week treatment were sig- nificant higher than in survival and control groups, furthermore it was also higher in survival group than in control group. At clinical diagnosis, TNF-alpha level in death group was higher than that in control. How- ever, there was no obviously difference between the death group and the survival group in TNF-alpha level. With the progression of the disease, TNF-alpha level was remarkably risen in death group, but decreased in survival group. IL-10 level was dramatically increased in death group, but no changed in survival group. IL-12 level in death group was higher than in survival group, but lower than in control group. [Conclusions] The levels of TNF-alpha, IL-1, IL-10 and IL-12 in patients with chronic liver failure was increased and the increase of IL-10 is secondary to elevation of IL-12.

Defining acute-on-chronic liver failure: East,West or Middle ground?

Acute-on-chronic liver failure(ACLF),a newly recognized clinical entity seen in hospitalized patients with chronic liver disease including cirrhosis,is associated with high short- and medium term morbidity and mortality.Noneof the definitions of ACLF proposed so far have been universally accepted,the two most commonly used being those proposed by the Asia-Pacific Association for the Study of Liver(APASL) and the European Association for the Study of Liver- Chronic Liver Failure(EASL-CLIF) consortium.On paper both definitions and diagnostic criteria appear to be different from each other,reflecting the differences in cut-off values for individual parameters used in diagnosis,the acute insult or precipitating event and the underlying chronic liver disease.Data directly comparing these two criteria are limited,and available studies reveal different outcomes when the two are applied to the same set of patients.However a review of the literature suggests that both definitions do not seem to identify the same set of patients.The definition given by the APASL consortium is easier to apply in day-to-day practice but the EASLCLIF criteria appear to better predict mortality in ACLF.The World Gastroenterology Organization working party have proposed a working definition of ACLF which will identify patients from whom relevant data can be collected so that the similarities and the differences between the two regions,if any,can be clearly defined.