Michael JahnMustafa K?z?ürümezSebastian DolffHana Rohn...
788-795页
查看更多>>摘要：Background and objectives: Polymerase chain reaction (PCR) techniques provide rapid detection of pathogens. This pilot study evaluated the diagnostic utility and clini-cal impact of multiplex real-time PCR (mRT-PCR, SeptiFast) vs. conventional microbial culture (CMC) in bile samples of patients with chronic cholestatic liver diseases (cCLDs), endoscopic retrograde cholangio-pancreatography (ERCP), and peri-interventional-antimicrobial-prophylaxis (pAP). Methods: We prospectively collected bile samples from 26 patients for microbiological analysis by CMC and mRT-PCR. Concordance of the results of both methods was determined by Krippendorff's alpha (α) for inter-rater reliability and the Jaccard index of similarity. Results: mRT-PCRbile and CMCbile results were concordant for only Candida albicans (α=0.8406; Jaccard index=0.8181). mRT-PCRbile detected pathogens in 8/8 cases (100％), CMCbile in 7/8 (87.5％), and CMCblood in 5/8 (62.5％) with clinical signs of infection. mRT-PCRbile, CMCbile, and CMCblood had identical detection results in 3/8 (37.5％) with clinical signs of infection (two Klebsiella spp. and one Enterococcus faecium). The total pathogen count was significantly higher with mRT-PCRbile than with CMCbile (62 vs. 31; χ2=30.031, p<0.001). However, patho-gens detected by mRT-PCRbile were more often susceptible to pAP according to the patient infection/colonization his-tory (PI/CH) and surveillance data for antibiotic resistance in our clinic (DARC). Pathogens identified by mRT-PCRbile and resistant to pAP by PI/CH and DARC were likely to be clinically relevant. Conclusions: mRT-PCR in conjunction with CMCs for bile analysis increased diagnostic sensitiv-ity and may benefit infection management in patients with cholestatic diseases. Implementation of mRT-PCR in a bile sample-based diagnostic routine can support more rapid and targeted use of antimicrobial agents in cCLD-patients undergoing ERCP and reduce the rate/length of unneces-sary administration of broad-spectrum antibiotics.
查看更多>>摘要：Background and Aims: There is an unmet need for new bi-omarkers to improve diagnostics and prognostics in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Inter-α-inhibitor heavy chain 4 (ITIH4) is an abun-dant, liver-produced protein, and its synthesis may be al-tered in liver diseases. We investigated whether ITIH4 plas-ma concentrations were affected in PBC and PSC patients. Methods: We developed an immunoassay specific for ITIH4 and determined ITIH4 plasma concentrations in 66 PBC, 126 PSC, 92 autoimmune hepatitis (AIH), 67 chronic hepatitis C (CHC), 33 alcoholic hepatitis (AH) patients and 138 healthy controls (HCs). Hepatic ITIH4 expression was investigated by immunohistochemistry in PBC. Results: The mean plas-ma concentration of ITIH4 was almost doubled in PBC [409 µg/mL (95％ CI: 388–431)] and 35％ higher in PSC [308 µg/mL, (95％ CI: 296–319)] compared with HCs [226 µg/mL (95％ CI: 221–231); p<0.001]. In PBC patients, ITIH4 correlated with IgM (rho=0.49, p<0.001). Responders to ursodeoxycholic acid treatment (UDCA) had lower levels of ITIH4 than incomplete responders [395 µg/mL (95％ CI: 364–425)] vs. 460 µg/mL (95％ CI: 421–498); p=0.02]. Four weeks of UDCA treatment had no effect (p=0.19). In-creased ITIH4 immunohistochemical staining was seen in a liver biopsy from a PBC patient. ITIH4 levels in AIH [224 µg/mL (95％ CI: 208–241)] and HCs were similar (p=0.8). ITIH4 levels were lower in AH [199 µg/mL (95％ CI: 175–223)] and CHC [202 µg/mL (192–212)] patients than in HCs (p<0.05). Conclusions: The plasma concentration of ITIH4 was highly elevated in patients with PBC and PSC, suggesting that ITIH4 should be further investigated as a biomarker in cholestatic liver disease.
查看更多>>摘要：Background and Aims: Acute-on-chronic liver failure (ACLF) is associated with very high mortality. Accurate pre-diction of prognosis is critical in navigating optimal treat-ment decisions to improve patient survival. This study was aimed to develop a new nomogram integrating two-dimen-sional shear wave elastography (2D-SWE) values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes. Methods: A total of 449 consecutive patients with ACLF were recruited and random-ly allocated to a training cohort (n=315) or a test cohort (n=134). 2D-SWE values, conventional ultrasound features, laboratory tests, and other clinical characteristics were in-cluded in univariate and multivariate analysis. Factors with prognostic value were then used to construct a novel prog-nostic nomogram. Receiver operating curves (ROCs) were generated to evaluate and compare the performance of the novel and published models including the Model for End-Stage Liver Disease (MELD), MELD combined with sodium (MELD-Na), and Jin's model. The model was validated in a prospective cohort (n=102). Results: A ACLF prognostic nomogram was developed with independent prognostic fac-tors, including 2D-SWE, age, total bilirubin (TB), neutro-phils (Neu), and the international normalized ratio (INR). The area under the ROC curve (AUC) was 0.849 for the new model in the training cohort and 0.861 in the prospec-tive validation cohort, which were significantly greater than those for MELD (0.758), MELD-Na (0.750), and Jin's model (0.777, all p <0.05). Calibration curve analysis revealed good agreement between the predicted and observed prob-abilities. The new nomogram had superior overall net ben-efit and clinical utility. Conclusions: We established and validated a 2D-SWE-based noninvasive nomogram to pre-dict the prognosis of ACLF patients that was more accurate than other prognostic models.
查看更多>>摘要：Background and Aims: Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) per-formed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associ-ated with recipient survival. Methods: We retrospectively analyzed LDLT recipients and donors from the United Net-work Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and re-gional trends in LDLT, recipient outcomes, and predictors of survival were analyzed. Results: Of the 223,571 candidates listed for an LT, 57.5％ received an organ, of which only 4.2％ were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n=919), while region 1 had the highest proportion (11.1％). Overall, post-LT mortality was 21.4％ among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92％, 87％, and 70％, re-spectively. Interval analysis (2004–2019) showed that pa-tients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95％ confidence interval=0.75–0.88). Conclusions: Following a substan-tial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.
查看更多>>摘要：Background and Aims: Patients with severe fever with thrombocytopenia syndrome (SFTS) commonly show liv-er function impairment. This study aimed to characterize the liver function indices in SFTS patients and investigate their association with mortality. Methods: Clinical infor-mation and laboratory results of 459 laboratory-confirmed SFTS patients, including 78 deceased and 381 surviving patients, were retrospectively analyzed. To explore the in-fectivity of SFTS caused by novel Bunyavirus (SFTSV) in hepatocytes, Huh7 human hepatoma cells were infected with various concentrations of SFTSV in vitro. Results: The proportion of SFTS patients developing liver injury during hospitalization was 73.2％ (336/459); the hepatocellular injury was the predominant type. The median time to oc-currence of liver injury from disease onset was 8 d. Liver injury in the deceased group occurred earlier than that in the surviving group. Alanine aminotransferase (ALT) level between 2–5 times upper limit of normal (ULN) at 4–6 d and between 5–15 ULN at 7–12 d of disease course were independent predictors of mortality. Alkaline phosphatase (ALP) >2 ULN at 7–9 d and elevated ALP at 10–12 days after disease onset were risk factors for death. ALT and aspartate transaminase (AST) levels were correlated with lymphocyte count and platelet-to-lymphocyte ratio (PLR). Total bilirubin (TB), ALT, AST levels showed positive cor-relation with viral load. In the in vitro experiment, SFTSV infected and replicated inside Huh7 cells. Conclusions: Liver injury is common in SFTS patients. ALT and ALP were independent predictors of SFTS-related mortality. Fre-quent monitoring and evaluation of liver function indices are needed for SFTS patients.
查看更多>>摘要：Background and Aims: Previous meta-analyses have shown that aspirin use may reduce the risk of hepatocel-lular carcinoma (HCC). However, the optimal dose, frequen-cy, and duration of aspirin use or the safety and efficacy of aspirin in target populations for HCC prevention remain unclear. The study aim was to investigate the efficacy and safety of aspirin for prevention of HCC. Methods: Publica-tions were retrieved by a comprehensive literature research of several databases. Based on a random-effects model, hazard ratios (HRs) and the corresponding 95％ confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship between aspirin use and HCC risk was assessed with a restricted cubic spline model. Results: Twenty-two studies were included in the meta-analysis. Aspirin use was associated with a reduced risk of HCC (HR=0.64, 95％ CI: 0.56–0.75). The effect was robust across sex and age; however, women and the non-elderly had the greatest benefit from aspirin use. The preventive effect was well reproduced in those with comorbidities. Daily use and long-term use of aspirin appeared to offer greater benefits. Aspirin 100 mg/d was associated with maximum reduction of HCC risk. Aspirin use did slightly in-crease the risk of bleeding (HR=1.14, 95％ CI: 1.02–1.27). Conclusions: Our meta-analysis confirmed that use of as-pirin significantly reduced the incident risk of HCC. Regular and long-term aspirin use offers a greater advantage. As-pirin use was associated with an increased risk of bleeding. We recommend 100 mg/d aspirin as a feasible dose for further research on primary prevention of HCC in a broad at-risk population.
查看更多>>摘要：Background and Aims: The concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increas-ingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic stud-ies. Methods: Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2％ DSS in drinking water; (3) A steatohepa-titis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2％ DSS in drinking water. Results: NASH plus UC had high mortality (58.3％). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was char-acterized by a significantly shorter colon, more colonic con-gestion, and a higher histopathological score (p<0.05). In-flammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic (Bcl2, Bad, Bim, and Bax) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups. Conclusions: Premorbid steatohepati-tis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model.
查看更多>>摘要：Background and Aims: Hepatitis B vaccine is the most ef-fective preventive measure against hepatitis B virus (HBV) infection. However, the risk of HBV breakthrough infection in fully immunized children (neonatal hepatitis B immuniza-tion) who receive immunosuppressive therapy and transfu-sion of blood components is not well characterized. In this real-world study, we aimed to investigate the immune pro-tection conferred by neonatal hepatitis B vaccine in children with acute lymphoblastic leukemia (ALL) who were treated with immunosuppressive therapy and blood component transfusions. Methods: Children with ALL who had received all three doses of neonatal hepatitis B vaccine were included in this study. HBV seromarkers were detected before and after the initiation of immunosuppressive therapy. Results: A total of 1,011 children with ALL who were fully vaccinated against hepatitis B in infancy before the initiation of im-munosuppressive therapy were eligible for inclusion. HBV infection was detected in four of 410 children (0.98％) with an HBsAg test after the initiation of immunosuppressive therapy. The median interval from treatment initiation was 19 months. Conclusions: Three doses of neonatal hepa-titis B vaccine conferred adequate protection. In endemic regions, there is a low risk of HBV breakthrough infection in fully immunized children with immunosuppressive therapy.
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