Impact of cirrhosis-related complications on posttransplant survival in patients with acute-on-chronic liver failure

Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decompensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4%)patients with ACLF-1,64(30.2%)with ACLF-2,and 73(34.4%)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8%),followed by hepatic encephalopathy(57.1%),bacterial infections(48.1%),hepatorenal syndrome(22.2%)and gastrointestinal bleeding(11.3%).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P<0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P<0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic models(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.

斜仰卧位与截石位在输尿管软镜吸引取石术中的比较

目的比较斜仰卧位与截石位在输尿管软镜吸引取石术中应用的安全性及疗效。方法两组上尿路结石患者共82例,其中斜仰卧位47例,截石位35例,术前两组患者在年龄、性别和合并症等方面比较,差异均无统计学意义(P>0.05),比较两组患者的手术时间、肾盂内压、术后30天清石率、并发症及住院天数。结果 73例手术一期完成,9例留置DJ管2周后成功行软镜手术。与截石位相比,斜仰卧位组患者的结石清除率明显提高,而手术时间明显缩短(P<0.05)。两组的并发症、肾盂内压和住院天数差异无统计学意义(P>0.05)。结论斜仰卧位输尿管软镜吸引取石术与传统体位相比,同样安全且碎石效率更高。

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.

Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients

AIM: To investigate the microbiological characteristics and drug resistance in liver cirrhosis patients with spontaneous peritonitis.METHODS: We analyzed the data of patients with liver cirrhosis and abdominal infection at the First Affiliated Hospital of Zhejiang University between January 2011 and December 2013. Pathogens present in the ascites were identified,and their sensitivity to various antibiotics was determined. RESULTS: We isolated 306 pathogenic bacteria from 288 cases: In 178 cases,the infection was caused by gram-negative strains(58.2%); in 85 cases,grampositive strains(27.8%); in 9 cases,fungi(2.9%); and in 16 cases,more than one pathogen. The main pathogens were Escherichia coli(E. coli)(24.2%),Klebsiella pneumoniae(18.9%),Enterococcus spp.(11.1%),and Staphylococcus aureus(7.5%). Of the 306 isolated pathogens,99 caused nosocomial infections and 207 caused community-acquired andother infections. The E. coli and K. pneumoniae strains produced more extended-spectrum β-lactamases in cases of nosocomial infections than non-nosocomial infections(62.5% vs 38%,P < 0.013; 36.8% vs 12.8%,P < 0.034,respectively). The sensitivity to individual antibiotics differed between nosocomial and non-nosocomial infections: Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections(4% vs 20.8%,P < 0.021). Nitrofurantoin had stronger antibacterial activity against Enterococcus species causing non-nosocomial infections(36.4% vs 86.3%,P < 0.009).CONCLUSION: The majority of pathogens that cause abdominal infection in patients with liver cirrhosis are gram-negative,and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE)in combination with continuous renal replacement therapy(CRRT) (PE+CRRT) for AFLP still needs evaluation.METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT.RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results and they were cured and discharged home after the treatment One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively.CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

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.

Identification of Sphaeroma terebrans via morphology and the mitochondrial cytochrome c oxidase subunit I (COI) gene

Sphaeroma terebrans, a wood-boring isopoda, is distributed worldwide in tropical and subtropical mangroves. The taxonomy of S. terebrans is usually based on morphological characteristics, with its molecular identification still poorly understood. The number of teeth on the uropodal exopod and the length of the propodus of the seventh pereopod are considered as the major morphological characteristics in S. terebrans, which can cause difficulty in regards to accurate identification. In this study, we identified S. terebrans via molecular and morphological data. Furthermore, the validity of the mitochondrial cytochrome c oxidase subunit I （COl） gene as a DNA barcode for the identification of genus Sphaeroma, including species S. terebrans, S. retrolaeve, and S. serratum, was examined. The mitochondrial COl gene sequences of all specimens were sequenced and analysed. The interspecific Kimura 2-parameter distances were higher than intraspecific distances and no intraspecificinterspecific distance overlaps were observed. In addition, genetic distance and nucleotide diversity （TT） exhibited no differences within S. terebrans. Our results revealed that the mitochondrial COl gene can serve as a valid DNA barcode for the identification of S. terebrans. Furthermore, the number of teeth on the uropodal exopod and the length of the propodus of the seventh pereopod were found to be unreliable taxonomic characteristics for S. terebrans.

Risk factors for Clostridium difficile infection in cirrhotic patients

Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. Methods: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization(CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin(TBIL), creatinine(Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor(PPI) on the CDI in cirrhotic patients. Results: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection(NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age > 60 years(OR = 1.689;95% CI: 1.135–3.128), multiple hospitalization(OR = 3.346;95% CI: 1.392–8.043), length of hospital stay > 20 days(OR = 1.564;95% CI: 1.113–2.563), hypoproteinemia(OR = 4.962;95% CI: 2.053–11.996), CDC(OR = 18.410;95% CI: 6.898–49.136), hepatic encephalopathy(OR = 1.357;95% CI: 1.154–2.368), and exposure of antibiotics(OR = 1.865;95% CI: 1.213–2.863) and PPI(OR = 3.125;95% CI: 1.818–7.548) were risk factors of CDI. Conclusions: Age > 60 years, multiple hospitalization, length of hospital stay > 20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.

Accuracy of pipeline blood glucose monitoring in patients with severe liver injury undergoing artificial liver support system treatment

Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, subacute liver failure, acute-on-chronic liver failure, or further worsening of end-stage liver disease [1].

Effects of Salmonella infection on hepatic damage following acute liver injury in rats

BACKGROUND： Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS： Oral supplementation with Salmonella enterica serovar enteritidis（S. enteritidis） was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.RESULTS： The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury（P〈0.01）; The peyer＇s patch CD3＋ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group（P〈0.05）. S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.CONCLUSIONS： Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe.Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

Prediction of Clostridium difficile infection based on gut microbial traits in patients with Clostridium difficile colonization

To the Editor : Cirrhotic patients usually require multiple hospitalizations due to upper gastrointestinal hemorrhage, abdominal infection, and hepatic encephalopathy. These patients need long-term hospital stay, and long-term application of proton pump inhibitors and antibiotics, which may result in Clostridium difficile infection(CDI) [1]. To our best knowledge, Clostridium difficile colonization(CDC) is the major risk factor for the pathogenesis of CDI.

Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues： A Prospective Study

Background： Tenofovir disoproxil （TDF） is a promising salvage therapy for patients with chronic hepatitis B （CHB） who failed regimens of other nucleoside analogues （NAs）. In this study, we aimed to investigate the clinical efficacy and safety ofTDF monotherapy in Chinese CHB patients with genotypic resistance. Methods： A total of 33 CHB patients who had tailed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients＇ demographic data （age, sex, history of hepatitis B virus [HBV] therapy）, laboratory testing results （hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay）, clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 （baseline） and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation. Results： With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability （r = 0.39, P = 0.030）. AET levels were normal in 30 of 33 patients （91%）. HBeAg negative conversion occurred in 7 of 25 patients （28%）, among whom HBeAg seroconversion （12%） and H BeAg seroclearance （16%） occurred. The time of complete virological response was significantly affected by the number of resistance loci （r = 0.36, P = 0.040）. Concerning safety, the study found that no adverse events were observed during the 48 weeks. Conclusion： TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

Identification of micro RNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples

MicroRNAs （miRNAs） are a class of small RNA molecules that are implicated in post-transcriptional reg- ulation of gene expression during development. The discovery and understanding of miRNAs has revolutionized the traditional view of gene expression. Alport syndrome （AS） is an inherited disorder of type IV collagen, which most commonly leads to glomerulonephritis and kidney failure. Patients with AS inevitably reach end-stage renal disease and require renal replacement therapy, starting in young adulthood. In this study, Solexa sequencing was used to identify and quantitatively profile small RNAs from an AS family. We identified 30 known miRNAs that showed a sig- nificant change in expression between two individuals. Nineteen miRNAs were up-regulated and eleven were down-regulated. Forty-nine novel miRNAs showed significantly different levels of expression between two individuals. Gene target predictions for the miRNAs revealed that high ranking target genes were implicated in cell, cell part and cellular process categories. The purine metabolism pathway and mitogen-activated protein kinase （MAPK） signaling pathway were enriched by the largest number of target genes. These results strengthen the notion that miRNAs and their target genes are involved in AS and the data advance our understanding of miRNA function in the patho- genesis of AS.