Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in 2001.The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in 2010.Linked to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over time.The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in 2006.Before the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Rocahepevirus ratti: An underrecognised cause of acute hepatitis

Zoonoses are responsible for many of all emerging infectious diseases as well as for those already established.Rocahepevirus ratti is a rat-originated virus related to the hepatitis E virus(Paslahepevirus balayani)but highly divergent genetically from this,with a high cross-species infection potential and zoonotic transmission.It can infect humans,leading to acute hepatitis,and is primarily transmitted through the consumption of contaminated water.Rocahepevirus ratti was first discovered in Germany in 2010.The first human case was described in 2017 in Hong Kong in an immune-compromised patient.The first case of chronic infection with Rocahep-evirus ratti was described in 2023.A meta-analysis based on 38 studies published between 2000 and 2023 identified 21 cases in humans described up to this date and 489 infections in different animals.Raising awareness regarding this virus is essential,as there are probably many cases that remain undiagnosed,and the virus even has the ability to produce chronic infections in selected patients.

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Stromal cell derived factor-1(SDF-1)plays a pivotal role in the recruitment of stem cells to injured livers.However,the changes of SDF-l in patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF)have yet to be elucidated.AIM To study the SDF-1 changes in patients with HBV-related ACLF.METHODS 30 patients with HBV-related ACLF,27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study.The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction.Immunohistochemical staining was performed to illustrate the expression of SDFl,CXC receptor 4(CXCR4)and Ki67.The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays.RESULTS The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients(both P<0.05).The expression of SDF-l,CXCR4 and Ki67 from ACLF were the highest among the three groups(all P<0.01).The serum SDF-l levels in ACLF patients were significantly lower than that in other patients(both P<0.01).Moreover,in ACLF patients,the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio.In addition,the serum SDF-l levels in survival were significantly lower compared with the non-survivals(P<0.05).The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722(P<0.05).CONCLUSION This study provides the SDF-1 changes in patients with HBV-related ACLF.The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

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.

Influence of chronic HBV infection on superimposed acute hepatitis E

AIM:To investigate the influence of chronic hepatitis B virus(HBV)infection[based on the status of hepatitis B e antigen(HBeAg),HBV DNA,and cirrhosis]on superimposed acute hepatitis E.METHODS:A total of 294 patients were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital,Sun Yat-sen University,from January 2003 to January 2012.The patients were classified into two groups:an HBV+hepatitis E virus(HEV)group(a group with chronic HBV infection that was superinfected with acute hepatitis E,n=118)and an HEV group(a group with acute hepatitis E,n=176).We retrospectively analyzed and compared the clinical features of the two groups.Statistical analyses were performed using theχ2test or Fisher’s exact test for categorical variables and the Student’s t test forcontinuous variables.A P value<0.05 was considered statistically significant.RESULTS:The peak values of prothrombin time,serum total bilirubin,and Model for End-Stage Liver Disease scores were significantly higher in the HBV+HEV group.More patients in the HBV+HEV group had complications(39.8%vs 16.5%,P=0.000)and developed liver failure(35.6%vs 8.5%,P=0.000).Additionally,the mortality of the HBV+HEV group was significantly higher(20.3%vs 7.4%,P=0.002).Further analysis of the HBV+HEV group showed that there were no significant differences in complication occurrence,liver failure incidence,or mortality between patients with different HBeAg and HBV DNA statuses.However,in patients with underlying cirrhosis,complication occurrence and liver failure incidence significantly increased.In total,12.7%of the patients in the HBV+HEV group received anti-HBV treatment,but this therapy failed to reduce mortality in patients who developed liver failure.CONCLUSION:The presence of underlying cirrhosis in chronic HBV infection results in more severe clinical outcomes with superimposed acute hepatitis E.AntiHBV treatment cannot improve the prognosis of liver failure caused by HBV-HEV superinfection.

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM: To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis (AIH) with or without centrilobular necrosis (CN). METHODS: Our study comprised 41 patients with biopsy-proven acute presentation (acute exacerbation phase 36, acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009. Elevated serum alanine aminotransferase (ALT) (> 5x upper limit of normal) identified acute presentation of the disease. We compared clinicopathological features of these AIH patients with or without CN. The data used for analysis included patient background (age, sex, type of disease, presence of complications with other autoimmune diseases, human leukocyte antigen, and International Autoimmune Hepatitis Group score), clinical parameters at presentation (ALT, alkaline phosphatase, IgG, anti-nuclear antibodies, and anti-smooth muscle antibodies), histology and therapy. RESULTS: CN was found in 13 (31.7%) patients with acute presentation (acute exacerbation phase 10, acute hepatitis phase 3) of AIH. Serum IgG levels of patients with CN were significantly lower than those of patients without CN (mean: 2307 mg/dL vs 3126 mg/dL, P < 0.05), while antinuclear antibody-negative rates were significantly higher (30.7% vs 3.5%, P < 0.05). However, other clinical features were similar between the two groups. The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN (F0-2: 84.6% vs 35.7%, F3-4: 15.4% vs 64.3%, P < 0.05). Other histological features were similar between the two groups. Although there was no significant difference between groups when evaluated using the revised original score (12 vs 14), the simplified AIH score of patients with CN was significantly lower (6 vs 7, P < 0.05). Frequency of DR4 was similar between patients with and without CN. CONCLUSION: CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH, although AIH with CN often shows clinical features of the genuine acute form.

Autoimmune hepatitis triggered by acute hepatitis A

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on： aspartate aminotransferase （AST）, 1 076 IU/L; alanine aminotransferase （ALT）, 1 400 IU/L; total bilirubin （TB）, 20.9 mg/dL; and prothrombin time rate （PT%）, 46.9%. Acute hepatitis A （HA） was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin （Ig） M HA antibody, but elevation of anti-nuclear antigen （×320） and IgG （3 112 mg/dL） led to suspicion of autoimmune hepatitis （AIH）. Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALl began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

Clinical features and risk factors of acute hepatitis E with severe jaundice

AIM:To compares the clinical features of patients infected with hepatitis E virus(HEV) with or without severe jaundice.In addition,the risk factors for HEV infection with severe jaundice were investigated.METHODS:We enrolled 235 patients with HEV into a cross-sectional study using multi-stage sampling to select the study group.Patients with possible acute hepatitis E showing elevated liver enzyme levels were screened for HEV infection using serologic and molecular tools.HEV infection was documented by HEV antibodies and by the detection of HEV-RNA in serum.We used χ2 analysis,Fisher's exact test,and Student's t test where appropriate in this study.Significant predictors in the univariate analysis were then included in a forward,stepwise multiple logistic regression model.RESULTS:No significant differences in symptoms,alanine aminotransferase,aspartate aminotransferase,al-kaline phosphatase,or hepatitis B virus surface antigen between the two groups were observed.HEV infected patients with severe jaundice had significantly lower peak serum levels of γ-glutamyl-transpeptidase(GGT)(median:170.31 U/L vs 237.96 U/L,P = 0.007),significantly lower ALB levels(33.84 g/L vs 36.89 g/L,P = 0.000),significantly lower acetylcholine esterase(CHE) levels(4500.93 U/L vs 5815.28 U/L,P = 0.000) and significantly higher total bile acid(TBA) levels(275.56 μmol/L vs 147.03 μmol/L,P = 0.000) than those without severe jaundice.The median of the lowest point time tended to be lower in patients with severe jaundice(81.64% vs 96.12%,P = 0.000).HEV infected patients with severe jaundice had a significantly higher viral load(median:134 vs 112,P = 0.025) than those without severe jaundice.HEV infected patients with severe jaundice showed a trend toward longer median hospital stay(38.17 d vs 18.36 d,P = 0.073).Multivariate logistic regression indicated that there were significant differences in age,sex,viral load,GGT,albumin,TBA,CHE,prothrombin index,alcohol overconsumption,and duration of admission between patients infected with acute hepatitis E with and without severe jaundice.CONCLUSION:Acute hepatitis E patients may naturally present with severe jaundice.

SOCS3 Expression Correlates with Severity of Inflammation in Mouse Hepatitis Virus Strain 3-induced Acute Liver Failure and HBV-ACLF

Summary： Recently, suppressor of cytokine signaling-3 （SOCS3） has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription （JAK/STAT） pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure （HBV-ACLF） have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 （MHV-3）-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells （PBMCs） of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immtmohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B （CHB）. Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin （IL）-1 β, IL-6, and tumor necrosis factor （TNF）-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.

N-acetyl cysteine therapy in acute viral hepatitis

AIM: To investigate the effect of N-acetyl cysteine (NAC)on acute viral hepatitis (AVH).METHODS: We administered 200 mg oral NAC three times daily (600 mg/day) to the study group and placebo capsules to the control group. All patients were hospitalized and diagnosed as AVH. Blood total and direct bilirubin, ALT, AST,alkaline phosphatese, albumin and globulin levels of each patient were measured twice weekly until total bilirubin level dropped under 2 mg/dl, ALT level under 100 U/L, follow up was continued and then the patients were discharged.RESULTS: A total of 41(13 female and 28 male) AVH patients were included in our study. The period for normalization of ALT and total bilirubin in the study group was 19.7±6.9 days and 13.7±8.5 days respectively. In the control group it was 20.4±6.5 days and 16.9±7.8 days respectively (P＞0.05).CONCLUSION: NAC administration effected neither the time necessary for normalization of ALT and total bilirubin values nor duration of hospitalization, so we could not suggest NAC for the treatment of icteric AVH cases. However, our results have shown that this drug is not harmful to patients with AVH.

Hepatitis E virus-related acute liver failure associated with pure red cell aplasia

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Prolonged acute hepatitis A mimicking autoimmune hepatitis

AIM: We report a case with a prolonged course of hepatitis A, with alanine aminotransferase (ALT) higher than 500 IU/L for more than 2 mo. METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive anti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out. RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCA proved to be effective.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.

Sustained viral response of a case of acute hepatitis C virus infection via needle-stick injury

A 29-year-old nurse with a hepatitis C virus （HCV） infection caused by needle-stick injury was treated with interferon-beta starting about one year after the onset of acute hepatitis. The patient developed acute hepatitis C with symptoms of general fatigues, jaundice, and ascites 4 wk after the needle-stick injury. When these symptoms were presented, the patient was pregnant by artificial insemination. She hoped to continue her pregnancy. After delivery, biochemical liver enzyme returned to normal levels. Nevertheless, HCV RNA was positive and the pathological finding indicated a progression to chronicity. The genotype was lb with low viral load. Daily intravenous injection of interferon-beta at the dosage of six million units was started and continued for eight weeks. HCV was eradicated without severe adverse effects. In acute hepatitis C, delaying therapy is considered to reduce the efficacy but interferon-beta therapy is one of the useful treatments for hepatitis C infection in chronic phase.

Detection of anti-HAV and anti-HEV IgM in patients with sporadic acute hepatitis in Beijing between 1995-2000

Objective: To investigate the age range, liver functiondamage and prognosis of patients with sporadic acutehepatitis A and E in Beijing.Methods: Enzyme immunoassay (EIA) was used todetect anti-HAV and anti-HEV immunoglobulin M(IgM). Serum samples were collected from the pa-tients with sporadic acute viral hepatitis in Beijingfrom January 1995 to June 2000.Results: The total positive rate for anti-HAV and an-ti-HEV IgM was 55.2% (112)in 203 patients with a-cute hepatitis, of whom 22.2% (45 patients) and33.0% (67) were positive for anti-HAV and anti-HEV respectively. The duration of anti-HEV IgMwas 45-60 days and that of anti-HAV IgM was atleast 2-3 months. The patients with acute hepatitis Aand hepatitis E all experienced jaundice and a risingof liver enzyme, but did not develop chronic hepatitisor died.Conclusion: Acute hepatitis A as well as acute hepatitisE plays an important role in sporadic entericallytransmitted hepatitis in Beijing.

An Analysis of Epidemiological Characteristics and the Clinical Features of 394 Cases of Sporadic Acute Hepatitis E in Southwest China from 2008 to 2010

Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E(AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were reviewed.Results In the 394 cases with sporadic AHE, the ratio of male/female was 1.432∶1, and the mean age was(31.53 ± 18.12) years. Totally, 94(23.86%) patients aged under 18, 271(68.78%) patients aged between 18 and 60, and 29(7.36%) patients aged above 60. The incidence rate was significantly increased in summer(P = 0.000), especially in May(14.72%) and July(13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers(106/394, 26.90%) and Han people(365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients significantly(P < 0.05). The prolonged length of stay, decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age significantly(P < 0.05). The differences in peak values of total bilirubin(TBil), total bile acid(TBA), glutamyltransferase(GGT), cholinesterase(CHE) between AHE group and the groups of AHE accompanied respectively by chronic hepatitis B(CHB), acute alcoholic fatty liver(AFL), nonalcoholic fatty liver disease(NAFLD) were significant(P < 0.05). In addition, no significant difference was found in length of stay and biochemical indexes among anti-HEV-Ig G positive group, anti-HEV-Ig M positive group and antiHEV-Ig M/Ig G both positive group(P > 0.05).Conclusions Four epidemiological characteristics, including aged between 18 and 60, male, summer and migrant laborers, are found to be associated with acute hepatitis E. The prognosis of AHE in the majority of patients was favorable, but aged above 60 years and coexistence with CHB, AFL and NAFLD could be considerede as the factors inducing the infaust prognosis.

Hypermethylation of thymosinβ4 predicts a poor prognosis for patients with acute-on-chronic hepatitis B liver failure

Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.

Early warning and clinical outcome prediction of acute-onchronic hepatitis B liver failure

Hepatitis B virus(HBV) associated acute-on-chronic liver failure(ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B(CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.

Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.

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.