Background and Aims:The impact of the characteristics of extrahepatic organ failure(EHOF)including the onset time,number,type,and sequence on the prognosis of acute-onchronic liver failure(ACLF)patients remains unknow...Background and Aims:The impact of the characteristics of extrahepatic organ failure(EHOF)including the onset time,number,type,and sequence on the prognosis of acute-onchronic liver failure(ACLF)patients remains unknown.This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients.Methods:ACLF subjects enrolled at six hospitals in China were included in the analysis.The risk of mortality based on the characteristics of EHOF was evaluated.Survival of study groups was compared by Kaplan–Meier analysis and log-rank tests.Results:A total of 736 patients with ACLF were included.EHOF was observed in 402 patients(54.6%),of which 295(73.4%)developed single EHOF(SEHOF)and 107(26.6%)developed multiple EHOF(MEHOF).The most commonly observed EHOF was coagulation failure(47.0%),followed by renal(13.0%),brain(4.9%),respiratory(4.3%),and circulatory(2.3%)failure.Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis.However,no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis.Patients were further divided into three risk subgroups by the EHOF characteristics.Kaplan–Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts.Conclusions:The mortality of ACLF patients was determined by the number and type,but not the onset time and sequence of EHOF.Risk stratification applicable to clinical practice was established.展开更多
Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fum...Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.展开更多
This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and co...This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.展开更多
To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society...To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the Chinese Medical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.展开更多
To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030,the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an ex...To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030,the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B(CHB).The current guidelines cover recent advances in basic,clinical,and preventive studies of CHB infection and consider the actual situation in China.These guidelines are intended to provide support for the prevention,diagnosis,and treatment of CHB.展开更多
Liver failure （LF） is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. CHnical presentation of LF typically includes severe jaundice, coagulation diso...Liver failure （LF） is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. CHnical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF （ACLF）, and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.展开更多
Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year...Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.展开更多
Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable ...Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.展开更多
In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in t...In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.展开更多
Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to ...Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.展开更多
Background and Aims:Bilirubin encephalopathy/kernicterus is very rare in adults.This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus.Metho...Background and Aims:Bilirubin encephalopathy/kernicterus is very rare in adults.This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus.Methods:Sanger sequencing analysis was performed to identify UGT1A1 gene mutations in the patients and their families.Bioinformatics analysis was used to predict the potential functional effects of novel missense mutations.Clinical manifestations and biochemical parameters were collected and analyzed.Results:Two patients with Crigler-Najjar syndrome type II(CNS2)developed kernicterus in adulthood.Sanger sequencing identified a compound heterozygous mutation in the UGT1A1 gene in patient 1,which was inherited from his mother(G71R)and his father(c.-3279T>G;S191F).Patient 2 carried three heterozygous mutations,namely G71R,R209W and M391K;among which,the M391K mutation has not been reported before.Multiple prediction software showed that the M391K mutation was pathogenic.Symptoms were relieved in the two patients after phenobarbital and artificial liver support treatment.Patient 1 also underwent liver transplantation.Conclusions:Adults with CNS2 are at risk for kernicterus.Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus.展开更多
In China, the death numbers due to primary liver cancer every year account for more than half of this disease burden worldwide. Hepatocellular carcinoma (HCC) represents the major histological type of primary liver ca...In China, the death numbers due to primary liver cancer every year account for more than half of this disease burden worldwide. Hepatocellular carcinoma (HCC) represents the major histological type of primary liver cancer. In the Chinese population, at least 85% HCC cases are due to chronic infection with hepatitis B virus (HBV), most of which were acquired in the perinatal period or in early life. As of January 1992, HBV immunization of newborns was introduced to the national Expended Program of Immunization of China. Prior to this program, the Qidong County in China conducted an hepatitis B intervention study, which was a population-based, cluster randomized, controlled trial of HBV vaccination in neonates. The study demonstrated that among young adults < 30 years old, neonatal HBV immunization decreased around 84% risk of HBV-related liver cancer, and 70% risk of mortality due to severe end-stage chronic liver diseases. More than 72% efficacy of neonatal vaccination against chronic HBV infection in adulthood was achieved;however, when catch-up HBV vaccination was given to children at age 10-14 years, the protection efficacy was only 21%. No difference in mortality of HBV-related liver diseases was observed among the young adults < 30 years who received and those who did not receive the catch-up HBV vaccination. These results highlight the crucial importance of HBV vaccination of neonates in reducing the liver cancer risk beginning at birth in highly HBV endemic regions. Due to large numbers of HBV-infected pregnant women with high viremia in China, clinical studies in which antiviral therapy with the nucleot(s)ide analogues was given to HBV-infected pregnant women have provided important evidence that such therapy can reduce the risk of mother-to-child HBV transmission. These clinical data based on cohort studies, randomized clinical trials, and clinical practices in the Chinese population provide important information on prevention of liver cancer, particularly HCC, by preventing chronic HBV infection starting from birth for other populations.展开更多
To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society ...To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the ChineseMedical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large-scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.展开更多
Background and Aims:Acute-on-chronic liver failure(ACLF)tends to progress rapidly with high short-term mortality.We aimed to create a widely applicable,simple prognostic(WASP)score for ACLF patients.Methods:A retrospe...Background and Aims:Acute-on-chronic liver failure(ACLF)tends to progress rapidly with high short-term mortality.We aimed to create a widely applicable,simple prognostic(WASP)score for ACLF patients.Methods:A retrospective cohort of ACLF cases recruited from three centers in China were divided into training and validation sets to develop the new score.A prospective longitudinal cohort was recruited for further validation.Results:A total of 541 cases were included in the training set,and seven independent ACLF prognostic factors were screened to construct a new quantitative WASP-ACLF table.In the validation set of 671 cases,WASP-ACLF showed better predictive ability for 28-day and 90-day mortality than the currently used prognostic scores at baseline,day 3,week 1,and week 2.The predictive efficacy and clinical validity of the model improved over time.Patients were assigned to low-,intermediate-,and high-risk groups by their WASP-ACLF scores.Compared with the other two groups,intermediate-risk patients had a more uncertain prognosis,with a 90-day mortality of 44.4–50.6%.Sequential assessments at weeks 1 and 2 found the 90-day mortality of intermediate-risk groups was<20%forpatients with a≥2 point decrease in WASP-ACLF and was up to 56%for patients with a≥2 points increase.Similar results were observed in prospective data.Conclusions:The new ACLF prognostic score was simple,widely applicable,and had good predictive efficacy.Continuous assessments and trend of change in WASP-ACLF need to be considered,especially for intermediate-risk patients.展开更多
Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding...Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.展开更多
Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, ...Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, which is rarely investigated. Methods: This study enrolled 236 ma-ternal HBsAg-positive children who were followed up annu-ally until 8 years of age and were hepatitis B surface antigen (HBsAg) negative. Of those 100 received a booster HepB be-tween 1 and 3 years of age (booster group), and 136 were never boosted (non-booster group). Serial follow-up data of children and baseline data of their mothers were collected and between-group differences were analyzed. Results: The incidence of OBI varied dynamically during follow-up, with 37.14% (78/210), 19.09% (42/220), 20.85% (44/211), 31.61% (61/193), 8.65% (18/208) and 12.71% (30/236) at 7 months, 1, 2, 3, 4, and 8 years of age. At 8 years of age, the negative conversion rate of HBV DNA in the booster group was significantly higher than that in non-booster group [57.89% (11/19) vs. 30.51% (18/59), p=0.032]. For chil-dren without OBI at 7 months old, the incidence of OBI in booster group was significantly lower than that in non-boost-er group [25.64% (10/39) vs. 67.74% (63/93), p<0.001]. Conclusions: The incidence of OBI in maternal HBsAg-positive children was high, serum HBV DNA in children with OBI was intermittently positive at low levels, and a booster HepB in infancy reduced the incidence of OBI in children with HBsAg-positive mothers.展开更多
Background and Aims:Hepatitis delta virus(HDV)is a defective virus and causes severe liver disease.Several HDV RNA assays have been developed,however the diagnostic efficacy remains unclear.This systematic review and ...Background and Aims:Hepatitis delta virus(HDV)is a defective virus and causes severe liver disease.Several HDV RNA assays have been developed,however the diagnostic efficacy remains unclear.This systematic review and metaanalysis aims to evaluate the diagnostic accuracy of HDV RNA assays to aid in the diagnosis of active hepatitis D.Methods:The PubMed,Embase,and Cochrane Library databases were systematically searched from the beginning to June 31,2022.Information on the characteristics of the literature and data on sensitivity,specificity,and area under curve(AUC)of the receiver operating characteristic(ROC)were extracted.Stata 14.0 was used for meta-analysis of the combined sensitivity,specificity,positive likelihood ratio,and negative likelihood ratio.Results:A total of 10 studies were included in the meta-analysis.The summary sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and diagnostic odds ratio of HDV RNA assays for HDV diagnosis were 0.92(95%CI:0.87-0.95),0.90(95%CI:0.86-0.93),7.74(95%CI:5.31-11.29),0.10(95%CI:0.06-0.18)and 99.90(95%CI:47.08-211.99),respectively.The AUC of the pooled ROC curve was 0.95(95%CI:0.92-0.96).Conclusions:The results show that HDV RNA assays had high diagnostic performance.However,that is limited by the number and quality of studies.Standard protocols for the development of assays by manufacturers and larger studies on the use of the assays are needed.展开更多
To the Editor:Autoimmune hepatitis(AIH)is a type of liver parenchymal inflammation mediated by the autoimmune response of liver cells.AIH was previously considered to be a chronic liver disease,but recent observers ha...To the Editor:Autoimmune hepatitis(AIH)is a type of liver parenchymal inflammation mediated by the autoimmune response of liver cells.AIH was previously considered to be a chronic liver disease,but recent observers have confirmed that AIH patients can have acute onset or even liver failure(AIH-LF).[1]The incidence of AIH-LF has also increased.Once LF occurs,the mortality rate within 90 days could reach>40%.[2]Therefore,the occurrence of LF has a major impact on the prognosis of AIH.Although AIH-LF has a low incidence and a high mortality rate,some cases can still be cured by treatment.The clinical characteristics that may affect the prognosis of patients with AIH-LF are still unclear.To clarify the factors affecting the prognosis of AIH-LF,we compared the clinical characteristics of two groups of AIH-LF patients with different prognosis.展开更多
Background and Aims:The rapid clearance of hepatitis C virus induced by direct-acting antivirals(DAAs)affects natural killer(NK)cells,but the reported results are not consistent,and the relative mechanism was unclear....Background and Aims:The rapid clearance of hepatitis C virus induced by direct-acting antivirals(DAAs)affects natural killer(NK)cells,but the reported results are not consistent,and the relative mechanism was unclear.This study focused on the dynamic changes of NK cells during and after DAA treatment and analyzed the reasons.Meth-ods:Peripheral blood from 35 chronic hepatitis C patients who were treated with DAAs were collected at baseline and weeks 1,2,4,12,and post-treatment week-12.The fre-quency,subset,and phenotype of NK cells were assayed by flow cytometry.Lactate dehydrogenase assays were used to evaluate the cytotoxicity of NK cells.Cytokine concentra-tions were measured with Luminex kits.Results:All pa-tients achieved a sustained viral response(SVR),and the NK cell frequencies were not changed significantly during DAA therapy.However,the cytotoxicity of NK cells recov-ered significantly early in week 1,and then continuously decreased below normal levels.The changes of genotypes including NKp30+,NKp46+,and NKG2A+NK cells were par-allel to NK function.The subset of CD56dim NK cells con-tinuously increased and did not return to normal even at 12 weeks after treatment.Interleukin(IL)-2,IL10,IL15,interferon-gamma,and tumor necrosis factor-alpha all in-creased after week 4,peaked at the end of therapy,and then exhibited varying degrees of reduction with time.Con-clusions:DAA treatment led to transient functional recov-ery of NK cells in the early stage of treatment,and then continuously decreased to below normal levels.Alterations of NK subsets,phenotypes,and the microenvironment may be involved in the changes.展开更多
End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decom...End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.展开更多
基金supported primarily by research grants from the National 13th 5-Year Plan for Hepatitis Research(No.2017ZX10203201-007).
文摘Background and Aims:The impact of the characteristics of extrahepatic organ failure(EHOF)including the onset time,number,type,and sequence on the prognosis of acute-onchronic liver failure(ACLF)patients remains unknown.This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients.Methods:ACLF subjects enrolled at six hospitals in China were included in the analysis.The risk of mortality based on the characteristics of EHOF was evaluated.Survival of study groups was compared by Kaplan–Meier analysis and log-rank tests.Results:A total of 736 patients with ACLF were included.EHOF was observed in 402 patients(54.6%),of which 295(73.4%)developed single EHOF(SEHOF)and 107(26.6%)developed multiple EHOF(MEHOF).The most commonly observed EHOF was coagulation failure(47.0%),followed by renal(13.0%),brain(4.9%),respiratory(4.3%),and circulatory(2.3%)failure.Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis.However,no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis.Patients were further divided into three risk subgroups by the EHOF characteristics.Kaplan–Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts.Conclusions:The mortality of ACLF patients was determined by the number and type,but not the onset time and sequence of EHOF.Risk stratification applicable to clinical practice was established.
文摘Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
文摘This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.
文摘To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the Chinese Medical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
文摘To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030,the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B(CHB).The current guidelines cover recent advances in basic,clinical,and preventive studies of CHB infection and consider the actual situation in China.These guidelines are intended to provide support for the prevention,diagnosis,and treatment of CHB.
文摘Liver failure （LF） is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. CHnical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF （ACLF）, and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.
基金This study was sponsored by Gilead Sciences,Inc.
文摘Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.
基金Ascletis Pharmaceuticals Co.,Ltd.provided financial support for this study(MANASA)
文摘Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.
文摘In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.
文摘Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.
基金This study was supported by Beijing Municipal Science and Technology Project(No.Z171100002217070)National Key R&D Program of China(No.2017YFA0103000)+5 种基金National Science and Technology Key Project on“Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment”(Nos.2012ZX10002004-006,2017ZX10203201-005,2017ZX10201201,2017ZX10202203-006-001 and 2017ZX 10302201-004-002)“Beijing Municipal Administration of Hospitals”Ascent Plan(No.DFL20151601)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(Nos.ZYLX201806 and ZYLX202125)Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(No.XXZ0503)You An Fund for Liver Diseases and AIDS(No.YNKTTS201801189)Beijing Municipal Natural Science Foun-dation(No.7202068).
文摘Background and Aims:Bilirubin encephalopathy/kernicterus is very rare in adults.This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus.Methods:Sanger sequencing analysis was performed to identify UGT1A1 gene mutations in the patients and their families.Bioinformatics analysis was used to predict the potential functional effects of novel missense mutations.Clinical manifestations and biochemical parameters were collected and analyzed.Results:Two patients with Crigler-Najjar syndrome type II(CNS2)developed kernicterus in adulthood.Sanger sequencing identified a compound heterozygous mutation in the UGT1A1 gene in patient 1,which was inherited from his mother(G71R)and his father(c.-3279T>G;S191F).Patient 2 carried three heterozygous mutations,namely G71R,R209W and M391K;among which,the M391K mutation has not been reported before.Multiple prediction software showed that the M391K mutation was pathogenic.Symptoms were relieved in the two patients after phenobarbital and artificial liver support treatment.Patient 1 also underwent liver transplantation.Conclusions:Adults with CNS2 are at risk for kernicterus.Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus.
文摘In China, the death numbers due to primary liver cancer every year account for more than half of this disease burden worldwide. Hepatocellular carcinoma (HCC) represents the major histological type of primary liver cancer. In the Chinese population, at least 85% HCC cases are due to chronic infection with hepatitis B virus (HBV), most of which were acquired in the perinatal period or in early life. As of January 1992, HBV immunization of newborns was introduced to the national Expended Program of Immunization of China. Prior to this program, the Qidong County in China conducted an hepatitis B intervention study, which was a population-based, cluster randomized, controlled trial of HBV vaccination in neonates. The study demonstrated that among young adults < 30 years old, neonatal HBV immunization decreased around 84% risk of HBV-related liver cancer, and 70% risk of mortality due to severe end-stage chronic liver diseases. More than 72% efficacy of neonatal vaccination against chronic HBV infection in adulthood was achieved;however, when catch-up HBV vaccination was given to children at age 10-14 years, the protection efficacy was only 21%. No difference in mortality of HBV-related liver diseases was observed among the young adults < 30 years who received and those who did not receive the catch-up HBV vaccination. These results highlight the crucial importance of HBV vaccination of neonates in reducing the liver cancer risk beginning at birth in highly HBV endemic regions. Due to large numbers of HBV-infected pregnant women with high viremia in China, clinical studies in which antiviral therapy with the nucleot(s)ide analogues was given to HBV-infected pregnant women have provided important evidence that such therapy can reduce the risk of mother-to-child HBV transmission. These clinical data based on cohort studies, randomized clinical trials, and clinical practices in the Chinese population provide important information on prevention of liver cancer, particularly HCC, by preventing chronic HBV infection starting from birth for other populations.
文摘To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the ChineseMedical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large-scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.
基金supported primarily by research grants from the National 13th 5-Year Plan for Hepatitis Research(No.2017ZX10203201-007)the National Natural Science Foundation of China(No.81870429,82170630)the Natural Science Foundation of Tianjin(No.19JCZDJC36700).
文摘Background and Aims:Acute-on-chronic liver failure(ACLF)tends to progress rapidly with high short-term mortality.We aimed to create a widely applicable,simple prognostic(WASP)score for ACLF patients.Methods:A retrospective cohort of ACLF cases recruited from three centers in China were divided into training and validation sets to develop the new score.A prospective longitudinal cohort was recruited for further validation.Results:A total of 541 cases were included in the training set,and seven independent ACLF prognostic factors were screened to construct a new quantitative WASP-ACLF table.In the validation set of 671 cases,WASP-ACLF showed better predictive ability for 28-day and 90-day mortality than the currently used prognostic scores at baseline,day 3,week 1,and week 2.The predictive efficacy and clinical validity of the model improved over time.Patients were assigned to low-,intermediate-,and high-risk groups by their WASP-ACLF scores.Compared with the other two groups,intermediate-risk patients had a more uncertain prognosis,with a 90-day mortality of 44.4–50.6%.Sequential assessments at weeks 1 and 2 found the 90-day mortality of intermediate-risk groups was<20%forpatients with a≥2 point decrease in WASP-ACLF and was up to 56%for patients with a≥2 points increase.Similar results were observed in prospective data.Conclusions:The new ACLF prognostic score was simple,widely applicable,and had good predictive efficacy.Continuous assessments and trend of change in WASP-ACLF need to be considered,especially for intermediate-risk patients.
文摘Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.
基金National Major Scientific and Technological Special Project during the Thirteenth Five-Year Plan Period(2017ZX10201201003).
文摘Background and Aims: Occult HBV infection (OBI) in chil-dren has proven to be associated with their immune re-sponse to hepatitis B vaccine (HepB). This study aimed to investigate the effect of a booster HepB on OBI, which is rarely investigated. Methods: This study enrolled 236 ma-ternal HBsAg-positive children who were followed up annu-ally until 8 years of age and were hepatitis B surface antigen (HBsAg) negative. Of those 100 received a booster HepB be-tween 1 and 3 years of age (booster group), and 136 were never boosted (non-booster group). Serial follow-up data of children and baseline data of their mothers were collected and between-group differences were analyzed. Results: The incidence of OBI varied dynamically during follow-up, with 37.14% (78/210), 19.09% (42/220), 20.85% (44/211), 31.61% (61/193), 8.65% (18/208) and 12.71% (30/236) at 7 months, 1, 2, 3, 4, and 8 years of age. At 8 years of age, the negative conversion rate of HBV DNA in the booster group was significantly higher than that in non-booster group [57.89% (11/19) vs. 30.51% (18/59), p=0.032]. For chil-dren without OBI at 7 months old, the incidence of OBI in booster group was significantly lower than that in non-boost-er group [25.64% (10/39) vs. 67.74% (63/93), p<0.001]. Conclusions: The incidence of OBI in maternal HBsAg-positive children was high, serum HBV DNA in children with OBI was intermittently positive at low levels, and a booster HepB in infancy reduced the incidence of OBI in children with HBsAg-positive mothers.
基金supported by National Natural Science Foundation of China(grant numbers 81770611,82002243,82100653)Key Projects of the Beijing Municipal Education Commission’s Science and Technology Plan(grant number KZ202010025035)+4 种基金Special Key Research Project of Capital Health Development Scientific Research(grant numbers SF2020-1-1151,SF2021-1G-2181,SF2022-1-2182)Demonstrating Application and Research of Clinical Diagnosis and Treatment Technology in Beijing(grant numbers Z191100006619096,Z191100006619097)Beijing Talents Foundation(grant number 2018000021469G289)Beijing Hospitals Authority Youth Program(grant number QML20201702)Talent Cultivation Plan of“Climbing the Peak”of Beijing Municipal Hospital Administration(grant number DFL20221503).
文摘Background and Aims:Hepatitis delta virus(HDV)is a defective virus and causes severe liver disease.Several HDV RNA assays have been developed,however the diagnostic efficacy remains unclear.This systematic review and metaanalysis aims to evaluate the diagnostic accuracy of HDV RNA assays to aid in the diagnosis of active hepatitis D.Methods:The PubMed,Embase,and Cochrane Library databases were systematically searched from the beginning to June 31,2022.Information on the characteristics of the literature and data on sensitivity,specificity,and area under curve(AUC)of the receiver operating characteristic(ROC)were extracted.Stata 14.0 was used for meta-analysis of the combined sensitivity,specificity,positive likelihood ratio,and negative likelihood ratio.Results:A total of 10 studies were included in the meta-analysis.The summary sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and diagnostic odds ratio of HDV RNA assays for HDV diagnosis were 0.92(95%CI:0.87-0.95),0.90(95%CI:0.86-0.93),7.74(95%CI:5.31-11.29),0.10(95%CI:0.06-0.18)and 99.90(95%CI:47.08-211.99),respectively.The AUC of the pooled ROC curve was 0.95(95%CI:0.92-0.96).Conclusions:The results show that HDV RNA assays had high diagnostic performance.However,that is limited by the number and quality of studies.Standard protocols for the development of assays by manufacturers and larger studies on the use of the assays are needed.
基金supported by grants from the National Key R&D Program of China(No.2017YFA0103000)the National Science and Technology Key Project on"Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment"(Nos.2012ZX10002004-006,2017ZX10203201-005,2017ZX10201201-001-001,2017ZX10201201-002-002,2017ZX10201201-004-002,2017ZX10202203-006-001,2017ZX10302201-004-002)+3 种基金the"Beijing Municipal Administration of Hospitals"Ascent Plan(No.DFL20151601)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.ZYLX201806)the Science and Technology Innovation Service Capacity Building-high-precision Discipline Construction Project(No.11920703)the Open research project of Key Laboratory of Capital Medical University(No.BJYAHKF2017008)。
文摘To the Editor:Autoimmune hepatitis(AIH)is a type of liver parenchymal inflammation mediated by the autoimmune response of liver cells.AIH was previously considered to be a chronic liver disease,but recent observers have confirmed that AIH patients can have acute onset or even liver failure(AIH-LF).[1]The incidence of AIH-LF has also increased.Once LF occurs,the mortality rate within 90 days could reach>40%.[2]Therefore,the occurrence of LF has a major impact on the prognosis of AIH.Although AIH-LF has a low incidence and a high mortality rate,some cases can still be cured by treatment.The clinical characteristics that may affect the prognosis of patients with AIH-LF are still unclear.To clarify the factors affecting the prognosis of AIH-LF,we compared the clinical characteristics of two groups of AIH-LF patients with different prognosis.
基金Beijing Advanced Innova-tion Center for Big Data-based Precision Medicine(No.PXM2021_014226_000026)Special key research pro-ject of capital health development scientific research(No.SF2021-1G-2181)+2 种基金National Natural Science Foundation(No.81500472)Beijing Natural Science Foundation(No.7202070)Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding support(No.ZYLX202125).
文摘Background and Aims:The rapid clearance of hepatitis C virus induced by direct-acting antivirals(DAAs)affects natural killer(NK)cells,but the reported results are not consistent,and the relative mechanism was unclear.This study focused on the dynamic changes of NK cells during and after DAA treatment and analyzed the reasons.Meth-ods:Peripheral blood from 35 chronic hepatitis C patients who were treated with DAAs were collected at baseline and weeks 1,2,4,12,and post-treatment week-12.The fre-quency,subset,and phenotype of NK cells were assayed by flow cytometry.Lactate dehydrogenase assays were used to evaluate the cytotoxicity of NK cells.Cytokine concentra-tions were measured with Luminex kits.Results:All pa-tients achieved a sustained viral response(SVR),and the NK cell frequencies were not changed significantly during DAA therapy.However,the cytotoxicity of NK cells recov-ered significantly early in week 1,and then continuously decreased below normal levels.The changes of genotypes including NKp30+,NKp46+,and NKG2A+NK cells were par-allel to NK function.The subset of CD56dim NK cells con-tinuously increased and did not return to normal even at 12 weeks after treatment.Interleukin(IL)-2,IL10,IL15,interferon-gamma,and tumor necrosis factor-alpha all in-creased after week 4,peaked at the end of therapy,and then exhibited varying degrees of reduction with time.Con-clusions:DAA treatment led to transient functional recov-ery of NK cells in the early stage of treatment,and then continuously decreased to below normal levels.Alterations of NK subsets,phenotypes,and the microenvironment may be involved in the changes.
文摘End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
