Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography

Two-dimensional shear wave elastography(2D-SWE) is a rapid, simple and novel noninvasive method that has been proposed for assessing hepatic fibrosis in patients with chronic liver diseases(CLDs) based on measurements of liver stiffness. 2 D-SWE can be performed easily at the bedside or in an outpatient clinic and yields immediate results with good reproducibility. Furthermore, 2 D-SWE was an efficient method for evaluating liver fibrosis in small to moderately sized clinical trials. However, the quality criteria for the staging of liver fibrosis are not yet well defined. Liver fibrosis is the main pathological basis of liver stiffness and a key step in the progression from CLD to cirrhosis; thus, the management of CLD largely depends on the extent and progression of liver fibrosis. 2 D-SWE appears to be an excellent tool for the early detection of cirrhosis and may have prognostic value in this context. Because 2 D-SWE has high patient acceptance, it could be useful for monitoring fibrosis progression and regression in individual cases. However, multicenter data are needed to support its use. This study reviews the current status and future perspectives of 2 D-SWE for assessments of liver fibrosis and discusses the technical advantages and limitations that impact its effective and rational clinical use.     

Feasibility of transient elastography versus real-time two-dimensional shear wave elastography in difficult-to-scan patients

Background and aims: Transient elastography (TE) is hampered in some patients by failures and unreliable results. We hypothesized that real time two-dimensional shear wave elastography (2D-SWE), the FibroScan XL probe, and repeated TE exams, could be used to obtain reliable liver stiffness measurements in patients with an invalid TE examination.

Methods: We reviewed 1975 patients with 5764 TE exams performed between 2007 and 2014, to identify failures and unreliable exams. Fifty-four patients with an invalid TE at their latest appointment entered a comparative feasibility study of TE vs. 2D-SWE.

Results: The initial TE exam was successful in 93% (1835/1975) of patients. Success rate increased from 89% to 96% when the XL probe became available (OR: 1.07, 95% CI 1.06–1.09). Likewise, re-examining those with a failed or unreliable TE led to a reliable TE in 96% of patients. Combining availability of the XL probe with TE re-examination resulted in a 99.5% success rate on a per-patient level. When comparing the feasibility of TE vs. 2D-SWE, 96% (52/54) of patients obtained a reliable TE, while 2D-SWE was reliable in 63% (34/54, p?Conclusions: Transient elastography can be accomplished in nearly all patients by use of the FibroScan XL probe and repeated examinations. In difficult-to-scan patients, the feasibility of TE is superior to 2D-SWE.     

Assessment of biopsy proven liver fibrosis by two-dimensional shear wave elastography in patients with primary biliary cholangitis

BackgroundTwo-dimensional shear-wave elastography (2D-SWE) is an ultrasound-based technique used to stage liver fibrosis by measuring liver stiffness (LS). The diagnostic performance of 2D-SWE for assessing liver fibrosis in patients with primary biliary cholangitis (PBC) has not been reported before.AimsTo investigate the diagnostic performance of 2D-SWE for staging liver fibrosis in patients with PBC by using histologic analysis as a reference standard.MethodsPatients with PBC who underwent liver biopsy and 2D-SWE were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. Areas under receiver operating characteristic curve (AUROC) was constructed to assess the accuracy of 2D-SWE and serum fibrosis models for staging liver fibrosis.ResultsThe diagnostic performance characteristics were determined for 157 patients with PBC. The AUROCs of LS measured by 2D-SWE for significant fibrosis, severe fibrosis, and cirrhosis were 0.88, 0.97 and 0.99, respectively. The cutoff values of LS measured by 2D-SWE in discriminating significant fibrosis, severe fibrosis, and cirrhosis were 10.7 kPa, 12.2 kPa and 14.1 kPa, respectively. The diagnostic accuracy of 2D-SWE for staging liver fibrosis was 73.9%.Conclusions2D-SWE is an efficient noninvasive method for the assessment of liver fibrosis in patients with PBC.     

Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

Elastography-based liver stiffness measurement(LSM) is a non-invasive tool for estimating liver fibrosis but also provides an estimate for the severity of portal hypertension in patients with advanced chronic liver disease(ACLD). The presence of varices and especially of varices needing treatment(VNT) indicates distinct prognostic stages in patients with compensated ACLD(cACLD). The Baveno VI guidelines suggested a simple algorithm based on LSM < 20 kPa(by transient elastography, TE) and platelet count > 150 G/L for ruling-out VNT in patients with cACLD. These(and other) TE-based LSM cut-offs have been evaluated for VNT screening in different liver disease etiologies. Novel point shear-wave elastography(pSWE) and two-dimensional shear wave elastography(2D-SWE) methodologies for LSM have also been evaluated for their ability to screen for "any" varices and for VNT. Finally, the measurement of spleen stiffness(SSM) by elastography(mainly by pSWE and 2D-SWE) may represent another valuable screening tool for varices. Here, we summarize the current literature on elastography-based prediction of "any" varices and VNT. Finally,we have summarized the published LSM and SSM cut-offs in clinically useful scale cards.     

小剂量肝素预防异基因造血干细胞移植后肝静脉阻塞症

目的探讨小剂量肝素预防以白消安／环磷酰胺（BU／CY）为预处理的异基因造血干细胞移植（allo-HSCT）后肝静脉阻塞症（VOD）的安全性和有效性,以及肝素使用的最佳时间跨度。方法1997年4月至2005年12月,134例患者在本院进行了allo—HSCT。所有患者均接受标准BU／CY或以此为基础的预处理方案,以肝素100IU·kg^-1·d^-1持续24h静滴预防VOD。分别比较血缘供者和非血缘供者移植、移植前肝功能正常与否、肝素使用时间不同组的VOD发生率。结果134例患者全部顺利植活,中性粒细胞〉0．5×10^9／L和血小板〉20×10^9／L的中位数时间分别为移植后12（9～28）d和20（6～65）d。其中118例白血病患者中97例（82．2％）于移植后100d无白血病生存。134例患者无一例发生VOD,其中包括47例非亲缘供者移植（骨髓移植34例,外周血干细胞移植8例,脐血5例）和肝功能异常组40例,肝素使用时间不同的两组亦无VOD发生。未有定期检测凝血酶原时间、部分活化凝血活酶时间组与监测组比较,临床出血情况并无明显加重。结论单一小剂量肝素预防以BU／CY为预处理方案的allo-HSCT后VOD安全有效,肝素使用时间跨度缩短为移植前7d至移植后14d并不影响其预防效果。     

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices

BackgroundThe aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE).MethodsBetween January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE.ResultsThe area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701–0.810) and 0.813 (95% CI, 0.763–.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621–0.738) and 0.834 (95% CI, 0.785–0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed.ConclusionsThe diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.     

2D shear wave elastography of the rectus femoris muscle in patients with cirrhosis: Feasibility and clinical findings. A pilot study

Background and aimsFrailty is frequent in cirrhosis and associated with skeletal muscle abnormalities and worse prognosis. 2D shear-wave elastography (2D-SWE) could mirror biomechanical properties of skeletal muscle reflecting muscle quality. However, there is no data on 2D-SWE on skeletal muscle stiffness assessment in cirrhosis and on frailty.MethodsOutpatients with cirrhosis were prospectively included in a single center. Skeletal muscle stiffness was studied at the rectus femoris by 2D-SWE. Ileo-psoas area and index (area/height²), and antero-posterior diameter of rectus femoris (RF) was measured on ultrasound.ResultsWe included 44 patients (24 male, age 59 [IQR 49–66]) with a median liver frailty index (LFI) of 3.7 (IQR 3.2–4.0). Measurement of RF muscle stiffness (RFMS) was feasible in all with high inter-measurement reproducibility. RFMS did not correlate with LFI, liver function and skeletal muscle diameters. Ileo-psoas index was lower in frail patients (1.7 vs 1.0 cm²/m², p = 0.024). RF antero-posterior diameter inversely correlated with LFI (r -0.578: p<0.001).ConclusionRFMS by 2D-SWE is feasible and reproducible in cirrhosis and is independent of liver function and LFI, and warrants further studies in this setting. RF antero-posterior diameter could be reported as an objective parameter mirroring sarcopenia and frailty.     

异基因造血干细胞移植后应用伊曲康唑肝功能异常53例病因分析

目的分析异基因造血干细胞移植(allo-HSCT)后应用伊曲康唑患者肝功能异常的病因及特点。方法回顾性分析北京大学血液病研究所2006年1月至2009年12月53例allo-HSCT患者应用伊曲康唑预防或治疗侵袭性真菌感染(IFI)后肝功能异常指标的动态变化特点及病因。结果 14例(26.4%)肝功能异常与移植物抗宿主病(GVHD)相关,13例(24.5%)与感染相关,11例(20.8%)与预处理毒性相关,8例(15.1%)与药物相关,与血栓性微血管病(TMA)、肝窦阻塞综合征(SOS)相关均为1例(1.9%),另5例(9.4%)病因不能确定。GVHD相关组发生肝酶、胆红素同时升高比例高于感染相关组(P=0.007);与预处理毒性相关组比较,GVHD相关组4级肝功能异常发生率较高(P=0.021)。结论 allo-HSCT后应用伊曲康唑患者肝功能异常常见病因依次是GVHD、感染、预处理毒性、药物及其他。GVHD相关组肝功能异常程度较重。     

How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation

Sinusoidal obstruction syndrome (SOS), also called veno‐occlusive disease of the liver, is one of the most relevant complications of endothelial origin that appears early after haematopoietic cell transplantation (HCT). Despite its relatively low incidence and the fact that most cases of SOS resolve spontaneously, the cases that evolve to multi‐organ failure (MOF; severe SOS) have a mortality rate higher than 80% and represent one of the major clinical problems after HCT. For this reason, transplantation teams must have a pre‐established policy regarding preventive measures in high‐risk patients, strict daily control of weight and fluid balance during HCT, homogeneous diagnostic criteria, appropriate complementary studies for a correct differential diagnosis and measures to prevent and manage hepatorenal syndrome; in addition they must also be ready to start early treatment with defibrotide in patients with a possible severe SOS. Due to the lack of definitive evidence to enable the establishment of general recommendations in the management of SOS, this review analyses all of these aspects based on the author's personal experience.     

Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort

BACKGROUND Non-invasive assessment of non-alcoholic steatohepatitis(NASH)is increasing in desirability due to the invasive nature and costs associated with the current form of assessment;liver biopsy.Quantitative multiparametric magnetic resonance imaging(mpMRI)to measure liver fat(proton density fat fraction)and fibroinflammatory disease[iron-corrected T1(cT1)],as well as elastography techniques[vibration-controlled transient elastography(VCTE)liver stiffness measure],magnetic resonance elastography(MRE)and 2D Shear-Wave elastography(SWE)to measure stiffness and fat(controlled attenuated parameter,CAP)are emerging alternatives which could be utilised as safe surrogates to liver biopsy.AIM To evaluate the agreement of non-invasive imaging modalities with liver biopsy,and their subsequent diagnostic accuracy for identifying NASH patients.METHODS From January 2019 to February 2020,Japanese patients suspected of NASH were recruited onto a prospective,observational study and were screened using noninvasive imaging techniques;mpMRI with LiverMultiScan?,VCTE,MRE and 2DSWE.Patients were subsequently biopsied,and samples were scored by three independent pathologists.The diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve(AUC)with the median of the histology scores as the gold standard diagnoses.Concordance between all three independent pathologists was further explored using Krippendorff’s alpha(a)from weighted kappa statistics.RESULTS N=145 patients with mean age of 60(SD:13 years.),39%females,and 40%with body mass index≥30 kg/m2 were included in the analysis.For identifying patients with NASH,MR liver fat and cT1 were the strongest performing individual measures(AUC:0.80 and 0.75 respectively),and the mpMRI metrics combined(cT1 and MR liver fat)were the overall best non-invasive test(AUC:0.83).For identifying fibrosis≥1,MRE performed best(AUC:0.97),compared to VCTE-liver stiffness measure(AUC:0.94)and 2D-SWE(AUC:0.94).For assessment of steatosis≥1,MR liver fat was the best performing non-invasive test(AUC:0.92),compared to controlled attenuated parameter(AUC:0.75).Assessment of the agreement between pathologists showed that concordance was best for steatosis(a=0.58),moderate for ballooning(a=0.40)and fibrosis(a=0.40),and worst for lobular inflammation(a=0.11).CONCLUSION Quantitative mpMRI is an effective alternative to liver biopsy for diagnosing NASH and non-alcoholic fatty liver,and thus may offer clinical utility in patient management.     

Role of two-dimensional shear wave elastography in chronic liver diseases: A narrative review

Liver biopsy is the gold standard for evaluating the degree of liver fibrosis in patients with chronic liver disease. However, due to the many limitations of liver biopsy, there has been much interest in the use of noninvasive techniques for this purpose. Among these techniques real-time two-dimensional shear wave elastography(2D-SWE) has the advantage of measuring tissue elasticity with the guidance of B-mode images. Recently, many studies have been conducted on the application of 2D-SWE in patients with various liver diseases, and their validity has been confirmed. Here, we briefly discuss the role of 2D-SWE in patients with chronic liver diseases, particularly aspects of the examination techniques and clinical applications.     

伴肺部侵袭性真菌病史的血液病患者行异基因造血干细胞移植的临床分析

目的探讨血液病伴肺部侵袭性真菌病(IFD)病史患者行异基因造血干细胞移植(allo-HSCT)后其肺部IFD的复发、疗效及影响因素。方法2005年3月至2006年10月南方医科大学南方医院14例肺部IFD病史的血液病患者接受allo-HSCT,移植前经抗真菌治疗10例完全缓解(CR),4例部分缓解(PR),移植中均给予预防性抗真菌治疗。调查移植后肺部IFD的复发、疗效,IFD相关病死率,Logistic回归模型分析移植方式、移植前IFD状态、预处理方案、移植物抗宿主病(GVHD)预防方案[含抗胸腺球蛋白(ATG)和不含ATG]、供受关系、急性GVHD(aGVHD)及WBC重建对移植后肺部IFD转归的影响。结果移植后肺部IFD的复发率为71.4%(10/14),移植前10例CR患者6例复发,4例PR患者全部复发;其复发时间分别为移植后3个月内7例,4~6个月内3例;10例复发患者中9例接受抗真菌治疗后4例获CR,2例PR,3例无效(NR),总有效率为6/9;移植后IFD相关病死率为35.7%(5/14);二性霉素B、伊曲康唑及伏立康唑预防肺部IFD的复发率差异无显著性意义(P=0.122);经Logisitic回归分析未发现与移植后肺部IFD复发相关的危险因素及影响其转归的危险因素。结论肺部IFD病史不是allo-HSCT的绝对禁忌证;有肺部IFD病史的患者,其移植后IFD复发率及相关病死率高。     

Reactivation of resolved hepatitis B virus infection after allogeneic haematopoietic stem cell transplantation

Hepatitis B virus (HBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is well known in HBsAg-positive carriers but has only occasionally been reported in patients with resolved HBV infection. We investigated six allo-HSCT recipients with pretransplant anti-HBs and anti-HBc antibodies for serologic markers of HBV infection and for the presence of HBV-DNA in serum. Reverse seroconversion, that is, reappearance of HBsAg after a gradual loss of anti-HBs, but no severe liver damage was observed in three patients at 14, 22 and 12 months after HSCT, respectively. There was an increase in HBV-DNA concentration prior to reverse seroconversion. One patient was repeatedly HBV-DNA positive (10(2)-10(3) copies/ml) without reverse seroconversion. Sequencing of the HBsAg and precore region derived from the four HBV-DNA-positive patients showed no relevant mutations. In conclusion, this study demonstrated a high risk (50%) of reverse seroconversion in allo-HSCT recipients with resolved HBV infection. A highly sensitive HBV-DNA assay (TaqMan-PCR) allowed early identification of the individual patients at risk.     

Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: A retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (2-3 risk factors, 27% incidence), or high risk (> or = 3 risk factors, 72% incidence [P < .001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT.     

异基因造血干细胞移植治疗进展期难治性急性髓系白血病17例分析

目的研究异基因造血干细胞移植(allo-HSCT)治疗进展期难治性急性髓系白血病(AML)的临床疗效。方法收集2002年5月至2011年6月苏州大学附属第一医院血液科收治的17例未缓解期难治性AML患者,采用改良马利兰+环磷酰胺(12例)或全身放疗+环磷酰胺(5例)的清髓性预处理方案行allo-HSCT,采用环孢菌素A(CsA)加短程氨甲蝶呤(MTX)预防移植物抗宿主病(GVHD),部分患者加入霉酚酸酯(MMF)。结果 15例成功获得造血重建,中性粒细胞>1.0×109/L和血小板>20×109/L的中位时间分别为12.5(11～14)d和12.5(10～15)d。急性GVHD发生率为53.3%(8/15),可评估的9例中,5例发生慢性GVHD,均为局限性。移植相关病死率为29.4%(5例),移植后成功获得完全缓解的14例中6例血液学复发,其中2例合并髓外复发,复发率为42.9%。中位随访5(0～71)个月,至今有6例无病生存(DFS),2年DFS为35.3%。结论 Allo-HSCT治疗进展期难治性AML仍不失为一种有效的挽救手段,其中发生慢性GVHD的患者预后较好,而移植相关并发症及移植后复发是影响患者生存的主要因素。     

Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection

Background and aims: Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease‐specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow. Methods: In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast. Results: Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness ≤10 kPa. An increase of at least 1 kPa after food intake was found in 24 out of 43 (56%) patients with initial stiffness ≤10 kPa. Notably, nine out of 23 (39%) patients with normal initial liver stiffness (<6 kPa) had a value of >6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures. Conclusion: Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition.     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

供体CD+4CD+25T细胞及调控基因FOXP3在急性移植物抗宿主病中的作用

目的 探讨供体CD+4CD+25T细胞亚群、FOXP3调控基因的表达与受者移植物抗宿主病(GVHD)的相关性.方法 (1)30例异基因造血干细胞移植(allo-HSCT),采用免疫荧光标记和流式细胞术检测并比较供体粒细胞集落刺激因子(G-CSF)动员前外周血、动员后采集物CD+4CD+25T细胞亚群比例,随访异基因移植后GVHD的发生率和严重程度.(2)应用RT-PCR技术检测供体FOXP3基因表达情况,分析其与GVHD、疾病复发的相关性.结果 (1)所有患者均获造血重建,粒细胞绝对数(ANC)≥0.5×109/L的中位时间为14(12～15)d,PLT≥20×109/L为18(15～25)d.30例allo-HSCT,中位随访时间12.8(8～16)个月,Ⅰ～Ⅳ度急性GVHD分别为3、4、3、5例.慢性GVHD 6例.(2)供体G-CSF动员前外周血、动员后采集物CD+4CD+25T细胞亚群分别为(2.67±0.38)%、(5.01±1.33)%,两者相比差异无统计学意义(P＞0.05).(3)移植后无急性GVHD组、Ⅰ～Ⅱ度急性GVHD组、Ⅲ～Ⅳ度急性GVHD组供体CD+4CD+25T细胞亚群分别为(5.05±1.34)%、(4.17±1.73)%、(1.98±1.10)%.其中Ⅰ～Ⅱ度急性GVHD组与Ⅲ～Ⅳ度急性GVHD组相比差异有统计学意义(P=0.04),无急性GVHD组与Ⅲ～Ⅳ度急性GVHD组相比差异有统计学意义(P=0.002).(4)30例allo-HSCT,7例FOXP3基因表达阳性,5/7例移植后无急性GVHD,其中3例移植后复发,另2/7例移植后Ⅰ度急性GVHD,Ⅱ～Ⅳ度急性GVHD患者FOXP3均不表达.结论 (1)供体CD+4CD+25T细胞亚群比例与受者急性GVHD的发生具有一定的相关性,提高供体CD+4CD+25T细胞数量有望减低移植后急性GVHD发生率.(2)供体移植物FOXP3基因表达阳性,与移植后有无严重急性GVHD发生存在一定相关性.     

Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases

Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.     

Non-invasive assessment of liver fibrosis and prognosis

Over the past decade, several advances have been made in the non-invasive assessment of liver fibrosis. Both serum markers and imaging-based tissue elastography predict the presence of advanced fibrosis compared with liver biopsy. Serum markers may be indirect or direct markers of liver structure and function. Imaging-based techniques measure liver stiffness as a surrogate for fibrosis and include ultrasound and MRI-based methods. Most non-invasive techniques work well at identifying subjects at the extremes of fibrosis but may not accurately discern intermediate stages. In addition to being a diagnostic tool, elastography may have an evolving role in prognosis. Increasing stiffness is associated with higher rates of liver decompensation, need for transplantation, hepatocellular carcinoma, and death. There are special populations of patients where elastography may serve as a non-invasive method to impart useful clinical information, such as patients after liver transplantation, those with congenital heart disease and those being treated for chronic viral hepatitis. The role of non-invasive markers in accurately predicting the presence of fibrosis in obese patients needs to be further refined.