Noninvasive Criteria Research Articles

Impact of sustained virological response with DAAs on gastroesophageal varices and Baveno criteria in HCV-cirrhotic patients.

Direct-acting antivirals (DAAs) show high efficacy and safety in HCV-cirrhotic patients, but most maintain clinically significant portal hypertension after sustained virological response (SVR). Non-invasive Baveno and expanded-Baveno criteria can identify patients without high-risk gastroesophageal varices (GEV) whohave no need for endoscopic surveillance. However, data after SVR are scarce. We performed a multicenter study to evaluate SVR effects over GEV and diagnostic accuracy of non-invasive criteria after SVR. HCV-cirrhotic patients receiving DAAs and baseline endoscopic evaluation were included (November 2014-October 2015). GEV were classified as low risk (LR-GEV) (< 5mm) or high risk (HR-GEV) (≥ 5mm or with risk signs). Transient elastography (TE) and endoscopy were performed during follow-up. SVR was achieved in 230 (93.1%) of 247 includedpatients, 151 (65.7%) with endoscopic follow-up. Among 64/151 (42.4%) patients without baseline GEV, 8 (12.5%) developed GEV after SVR. Among 50/151 (33.1%) with baseline LR-GEV, 12 (24%) developed HR-GEV. Patients with GEV progression showed TE ≥ 25kPa before treatment (64.7%) or ≥ 20kPa after SVR (66.7%). Only 6% of patients without GEV and LSM < 25kPa before treatment, and 10% of those with baseline LSM < 25kPa and LSM < 20kPa after SVR showed GEV progression after 36months. The negative predictive value of Baveno and expanded-Baveno criteria to exclude HR-GEV was maintained after SVR (100% and 90.7%, respectively). HCV-cirrhotic patients can develop HR-GEV after SVR. Surveillance is especially recommended in those with GEV before antiviral treatment. Baveno and expanded-Baveno criteria can be safely applied after SVR. https://clinicaltrials.gov: NCT02758509.

Early Ultrasound Signs of Splenomegaly in Neonates

The purpose of the study is to determine early non-invasive (ultrasound) diagnostic criteria of splenomegaly in neonates with a high risk of congenital or postnatal infection.Materials and methods. In the prospective study, 163 newborn infants of the first week of live were included. All neonates included in the study were classified as possessing a high risk of an intra-uterine infection (IUI). Depending on the birth weight, the infants were split into two groups: group «А» — 80 full-term newborns with normal birth weight, and group «В» — 83 full-term newborns with fetal growth restriction (FGR). A comprehensive examination of newborns including spleen ultrasound was carried out.Results. An increased spleen weight coefficient (Km) was found in newborns with high risk of infection development that included congenital oromaxillofacial and gastrointestinal defects, perinatal contacts with various microorganism. The increased spleen weight and Km reflected conditions of the immune system organ of the newborn in response to an adverse exposure including infection.Conclusion. Ultrasound examination of morphometrical characteristics of the spleen in newborns with various medical conditions represents a convenient and simple method of early diagnosis of splenomegaly. The most sensitive index is the spleen weight coefficient (Km), which reflects the immune system organ response to an adverse perinatal exposure including contact with an infectious agent. The mean spleen weight coefficient is within the range of 1.1 to 3.0. When the index exceeds 4, the risk of development of an infectious disease increases. This method can be used as a screening approach for newborns of different gestation age who have been included in the high-risk group based on a congenital or early postnatal infection.

Surveillance and diagnosis of hepatocellular carcinoma: A systematic review.

BACKGROUNDHepatocellular carcinoma (HCC) appears in most of cases in patients with advanced liver disease and is currently the primary cause of death in this population. Surveillance of HCC has been proposed and recommended in clinical guidelines to obtain earlier diagnosis, but it is still controversial and is not accepted worldwide.AIMTo review the actual evidence to support the surveillance programs in patients with cirrhosis as well as the diagnosis procedure.METHODSSystematic review of recent literature of surveillance (tools, interval, cost-benefit, target population) and the role of imaging diagnosis (radiological non-invasive diagnosis, optimal modality and agents) of HCC.RESULTSThe benefits of surveillance of HCC, mainly with ultrasonography, have been assessed in several prospective and retrospective analysis, although the percentage of patients diagnosed in surveillance programs is still low. Surveillance of HCC permits diagnosis in early stages allows better access to curative treatment and increases life expectancy in patients with cirrhosis. HCC is a tumor with special radiological characteristics in computed tomography and magnetic resonance imaging, which allows highly accurate diagnosis without routine biopsy confirmation. The actual recommendation is to perform biopsy only in indeterminate nodules.CONCLUSIONThe evidence supports the recommendation of performing surveillance of HCC in patients with cirrhosis susceptible of treatment, using ultrasonography every 6 mo. The diagnosis evaluation of HCC can be established based on noninvasive imaging criteria in patients with cirrhosis.

Performance of Noninvasive Assessment in the Diagnosis of Right Heart Failure After Left Ventricular Assist Device.

Right heart failure (RHF) after left ventricular assist device (LVAD) is associated with poor outcomes. Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) defines RHF as elevated right atrial pressure (RAP) plus venous congestion. The purpose of this study was to examine the diagnostic performance of the noninvasive Intermacs criteria using RAP as the gold standard. We analyzed 108 patients with LVAD who underwent 341 right heart catheterizations (RHC) between January 1, 2006, and December 31, 2013. Physical exam, echocardiography, and laboratory data at the time of RHC were collected. Conventional two-by-two tables were used and missing data were excluded. The noninvasive Intermacs definition of RHF is 32% sensitive (95% cardiac index (CI), 0.21-0.44) and 97% specific (95% CI, 0.95-0.99) for identifying elevated RAP. Clinical assessment failed to identify two-thirds of LVAD patients with RAP > 16 mm Hg. More than half of patients with elevated RAP did not have venous congestion, which may represent a physiologic opportunity to mitigate the progression of disease before end-organ damage occurs. One-quarter of patients who met the noninvasive definition of RHF did not actually have elevated RAP, potentially exposing patients to unnecessary therapies. In practice, if any component of the Intermacs definition is present or equivocal, our data suggest RHC is warranted to establish the diagnosis.

Diagnostic Value of Different Noninvasive Criteria of Latent Myocarditis in Comparison with Myocardial Biopsy

Purpose: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. Methods: In 100 patients (65 men, 44.7 ± 12.5 years old) with “idiopathic” arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery. Results: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development. Conclusion: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with “idiopathic” arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.

Prospective evaluation of gadoxetic acid magnetic resonance for the diagnosis of hepatocellular carcinoma in newly detected nodules ≤2cm in cirrhosis.

Most of the published studies about the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (EOB-MR) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) have had a retrospective design. Thus, we aimed to prospectively evaluate the diagnostic accuracy of EOB-MR for the non-invasive diagnosis of HCC in nodules ≤2cm detected by screening ultrasound (US) in patients with cirrhosis. Between July 2012 and October 2015, 62 consecutive asymptomatic Child-Pugh A-B cirrhotic patients with newly US-detected solitary nodules between 1 and 2cm were prospectively included in the study. Hepatic extracellular contrast-enhanced MR (ECCE-MR) followed by EOB-MR were obtained in less than 1-month interval. Two independent radiologists blindly reviewed the EOB-MR studies, and the diagnosis of HCC was assigned when the lesion showed arterial enhancement followed by portal venous phase washout and/or hypointensity on the hepatobiliary phase (HBP). The final HCC diagnosis was made by ECCE-MR according to the accepted non-invasive criteria, or by biopsy in lesions with atypical vascular profile. Final diagnoses were as follows: HCC (n=41), intrahepatic cholangiocarcinoma (n=2), colorectal metastases (n=1) and benign conditions (n=18). The sensitivity and specificity of EOB-MR for HCC diagnosis were 56.1% (95% CI: 39.7-71.5) and 90.5% (95% CI: 69.6-98.8), respectively, while sensitivity of ECCE-MR was 63.4% (95% CI: 46.9-77.9). The low rate of hypointense HCCs in the HBP and suboptimal liver uptake of contrast agent justify the low sensitivity of EOB-MR for HCC diagnosis. EOB-MR does not surpass the diagnostic accuracy of ECCE-MR for non-invasive diagnosis of HCC in nodules ≤2cm in cirrhotic patients.

From the Editor’s desk…: June 2019

From the Editor’s desk…: June 2019

HEPATOMA;

Objectives: To determine the frequency of hepatoma in patients with cirrhosis attending tertiary care hospital Karachi. Study Period: Six months July to December 2017. Study Design: Descriptive cross sectional study. Setting: Department of Gastroenterology, Liaquat National postgraduate Medical centre Karachi. Patients and Methods: The clinical history was taken from patients and ultrasound of liver was done to and mass if any and its size was noted. Noninvasive criteria for diagnosing hepatoma were utilized and all information was noted and entered in the proforma and analyzed in statistical software. Results: A total of 213 cases, 15.02% individual hepatitis B and 21.13% subject hepatitis C. Frequency of hepatoma in cirrhotic population detected as 10.33% (22/213). Rate of hepatoma was not significant among different age groups (p=0.202). Rate of hepatoma was also not significant between male and female (p=0.59). Conclusion: Persistent chronic viral hepatitis B and C infection with cirrhosis responsible for acquiring hepatoma.

Noninvasive diagnostic criteria for nonalcoholic steatohepatitis based on gene expression levels in peripheral blood mononuclear cells.

Nonalcoholic fatty liver disease (NAFLD) consists of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); the latter progresses to liver cirrhosis and hepatocellular carcinoma. Discriminating NASH from NAFL typically involves liver biopsy. The mechanism of NASH progression is unclear but may involve immunological pathways. In this study, we examined expression levels of cytokine- and chemokine-encoding genes in peripheral blood mononuclear cells (PBMCs) from NAFLD patients and established immunological criteria for discriminating NASH from NAFL. PBMCs were obtained from 54 patients diagnosed histologically with NAFLD (NAFL, 18; NASH, 36). mRNA was extracted from PBMCs, and expression levels of cytokine- and chemokine-encoding genes were determined by quantitative real-time PCR. Statistical analysis was performed by nonparametric test. Expression levels of interferon (IFN)γ, interleukin (IL)2, IL15, C-C-motif chemokine ligand (CCL)2, IL10, and C-X-C-motif chemokine ligand (CXCL)11 were significantly upregulated in NASH patients compared with NAFL patients. Moreover, their expression levels were positively correlated with the degree of ballooning of hepatocytes but not of steatosis or lobular inflammation. We focused on those encoding IL10, IFNγ, and CCL2, and developed a scoring system to discriminate NASH from NAFL. The discriminatory power of the criteria was validated in an independent cohort. Expression levels of the cytokine- and chemokine-encoding genes in PBMCs were positively correlated with ballooning, suggesting their utility for the diagnosis of NASH. The data indicate that peripheral as well as intrahepatic immunity is involved in the progression of NASH. Our findings afford new insight into immunological mechanisms of NASH and will facilitate its noninvasive diagnosis.

Problematic lesions in cirrhotic liver mimicking hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a unique malignancy that can be diagnosed and treated based on non-invasive imaging criteria without histological confirmation in cirrhotic patients, which opens the possibility, although rare, of false-positive diagnosis of the tumor. This brief review illustrates benign and non-HCC malignant lesions arising in cirrhotic liver that could have been erroneously diagnosed as HCC based on imaging criteria: focal nodular hyperplasia-like nodules, serum amyloid A-positive nodules, dysplastic nodules, spontaneously regressing lesions, combined hepatocellular-cholangiocarcinoma, cholangiocarcinoma, sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, hepatoblastoma, and metastatic adenocarcinoma. To determine the potential differences in clinical courses and post-treatment outcome of HCC diagnosed by imaging alone and those histologically, we suggest the terms HCCi and HCCp to distinguish between lesions that are diagnosed as HCC based on imaging alone from those diagnosed based on pathological examination, respectively.Key Points • Benign lesions, such as focal nodular hyperplasia-like nodules, serum amyloid A-positive nodules, dysplastic nodules, and spontaneously regressing lesions, may show imaging findings that mislead to the diagnosis of HCC. • Non-hepatocellular malignant lesions, such as sarcomatoid carcinoma, lymphoepithelioma-like carcinoma, hepatoblastoma, and metastatic adenocarcinomas, can be erroneously diagnosed as HCC based on imaging findings alone, even in cirrhotic liver.

Design and validation of a noninvasive diagnostic criteria for biliary atresia in infants based on the STROBE compliant

It is difficult for clinicians to distinguish biliary atresia (BA) from other causes of neonatal cholestasis (NC) at an early stage. The aim of this study was to design and validate noninvasive diagnostic criterion for early diagnosis of BA in infants.In this retrospective cohort study, a total of 482 medical records of patients with NC were recruited to design diagnostic criteria. Parameters showing a significant difference between BA (n = 166) and non-BA (n = 316) patients were analyzed by logistic regression to predict the occurrence of BA, and then a nomogram scoring system was designed and validated in another cohort that included 190 cases of NC.A prediction diagnostic criterion with parameters including direct bilirubin, total bilirubin, globulin, albumin, gamma glutamyl transpeptidase, cholesterol, total bile acid, hepatobiliary scintigraphy, birth weight, and stool color was established; the sensitivity and specificity of this diagnostic criterion was 89% and 84%, respectively. The accuracy was 86% and the AUC was 0.91 [95% CI (0.88-0.97)]. The total score ranged from 0 to 402, with a cut-off value of ≥254 discriminating BA from other causes of NC. By applying this score in the validation set with age <60 days, the accuracy was 95.3%, the sensitivity was 93.8% and the specificity was 96.0%, respectively.This prediction diagnostic criterion could facilitate clinicians to distinguish infants with and without BA based on a particular series of parameters, reducing treatment burden and enhancing therapeutic efficiency.

Distinguishing Tumor From Bland Portal Vein Thrombus in Liver Transplant Candidates With Hepatocellular Carcinoma: the A‐VENA Criteria

Differentiating tumor versus bland portal vein thrombosis (PVT) is essential in determining liver transplantation (LT) candidacy for patients with hepatocellular carcinoma (HCC). We aimed to evaluate radiographic and clinical features that could noninvasively distinguish tumor PVT from bland PVT in HCC patients. Of 467 patients with HCC listed for LT from 2004 to 2011, 59 (12.6%) had PVT and 12 of 59 (20.3%) were deemed malignant. When comparing tumor versus bland PVT, thrombus enhancement was seen in 100% versus 8.5%; venous expansion was seen in 91.7% versus 10.6%; neovascularity was seen in 58.3% versus 2.1%; and being adjacent to HCC or prior treatment site was seen in 100% versus 21.3% (all P < 0.001). Combining these 4 imaging characteristics with alpha-fetoprotein (AFP) >1000 ng/dL, the presence of ≥3 criteria best characterized tumor PVT with 100% sensitivity, 93.6% specificity, 80% positive predictive value, and 100% negative predictive value. No LT recipients with presumed bland PVT had macrovascular invasion on explant. There were no differences in post-LT survival or HCC recurrence with bland PVT versus no PVT. In conclusion, we proposed noninvasive criteria that could accurately differentiate tumor PVT from bland PVT called A-VENA, which is based on the presence of ≥3 of the following: AFP >1000 ng/dL; venous expansion; thrombus enhancement; neovascularity; and adjacent to HCC. Use of the A-VENA criteria can assist in standardizing the evaluation of PVT in patients with HCC being considered for LT.

Low specificity of washout to diagnose hepatocellular carcinoma in nodules showing arterial hyperenhancement in patients with Budd-Chiari syndrome

It remains unclear whether the classic imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be applied to chronic vascular liver diseases, such as Budd-Chiari syndrome (BCS). Herein, we aimed to evaluate the diagnostic value of washout for the discrimination between benign and malignant lesions in patients with BCS. This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal lesions on MRI from 2000 to 2016. MRI images were reviewed by 2 radiologists blinded to the nature of the lesions. Patient and lesion characteristics were recorded, with a focus on washout on portal venous and/or delayed phases. Lesions were compared using Chi-square, Fisher's, Student's t or Mann-Whitney U tests. A total of 49 patients (mean age 35 ± 12 years; 34 women [69%] and 15 men [31%]) with 241 benign lesions and 12 HCC lesions were analyzed. Patients with HCC were significantly older (mean age 44 ± 16 vs. 33 ± 9 years, p = 0.005), with higher alpha-fetoprotein (AFP) levels (median 16 vs. 3 ng/ml, p = 0.007). Washout was depicted in 9/12 (75%) HCC, and 69/241 (29%) benign lesions (p <0.001). A total of 52/143 (36%) lesions ≥1 cm with arterial hyperenhancement showed washout (9 HCC and 43 benign lesions). In this subgroup, the specificity of washout for the diagnosis of HCC was 67%. Adding T1-w hypointensity raised the specificity to 100%. A serum AFP >15 ng/ml was associated with 95% specificity. Washout was observed in close to one-third of benign lesions, leading to an unacceptably low specificity for the diagnosis of HCC. The non-invasive diagnostic criteria proposed for cirrhotic patients cannot be extrapolated to patients with BCS. Washout on MRI is depicted in a significant proportion of benign nodules in patients with Budd-Chiari syndrome (BCS), limiting its value for the differentiation between benign and malignant lesions. Criteria proposed for the non-invasive diagnosis of hepatocellular carcinoma in patients with cirrhosis cannot be extrapolated to patients with BCS. Additional imaging findings and patient characteristics, including alpha-fetoprotein serum level, can help determine the probability of a nodule being HCC in patients with BCS.

Value of cardiac biomarkers in the early diagnosis of Takotsubo syndrome

Bedside diagnosis between Takotsubo syndrome (TTS) and ACS remains challenging and requires multimodal examinations. Because invasive procedures portend by themselves a sizeable ischemic and bleeding risk in this frail population, non-invasive criteria are warranted to enable early diagnosis. A total of 1100 patients (TTS n = 314, STEMI n = 452, NSTEMI n = 334) were enrolled in two centers. Baseline clinical and biological characteristics were compared between groups. At admission, cut-off values of BNP/TnI ratio of 54 and 329 distinguished respectively STEMI from NSTEMI, and NSTEMI from TTS. Best differentiation between TTS and ACS was obtained by the use of BNP/TnI ratio at peak (cut of value of 6 discriminated STEMI from NSTEMI, and 115 distinguished NSTEMI from TTS). We developed a score including 5 routinely available parameters (age, gender, history of psychiatric disorders, LVEF and BNP/TnI ratio on admission) enabling good distinction between TTS and STEMI 77% specificity and 92% sensitivity, AUC 0.93 (95% CI 0.92–0.95). For the distinction between TTS and NSTEMI, a second 4 variables score (gender, history of psychiatric disorders, LVEF on admission, BNP on admission) achieved a good diagnostic performance Se 89%, Sp 85%, AUC 0.94 (95% CI 0.92-0.96) ( Table 1 ). A distinctive cardiac biomarker profile exists during TTS enabling at an early stage the differentiation between TTS and various myocardial infarction patterns. Best discrimination between TTS and ACS was obtained using a 4 (NSTEMI) or 5 variables score (STEMI).

Haptoglobin degradation product as a novel serum biomarker for hematopoietic stem cell transplant-associated thrombotic microangiopathy.

Hematopoietic stem cell transplant (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a well-known complication of HSCT and carries high risk of morbidity and mortality. A lack of consistent non-invasive diagnostic criteria can delay diagnosis and lead to irreversible organ damage. Serum samples of 100 patients that underwent HSCT at Cincinnati Children's Hospital were serially collected. Unbiased proteomic profiling by SELDI-TOF-MS was performed on serum from TA-TMA patients at baseline (pre-HSCT), 2weeks before TMA diagnosis (pre-TMA), and at clinical TMA diagnosis. Two proteins with mass to charge ratios of 12-13kDa were consistently elevated at the 2week pre-TMA time point by SELDI-TOF, compared to control samples. Potential peptides were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on the Linear Trap Quadropole (LTQ). A MASCOT search identified haptoglobin fragments in the 12-17-kDa range. Western blot was performed to validate haptoglobin fragments as a potential biomarker. Western blot of TA-TMA patients showed haptoglobin fragments at 12, 14, and 17kDa that varied between baseline, pre-TMA, and TMA time points for each patient. By densitometric analysis, the 17-kDa fragment in the pre-TMA samples differed significantly from TMA diagnosis (p < 0.0001). There was no significant difference in the concentrations of the 12-kDa and 14-kDa fragments. The 17-kDa haptoglobin degradation product may represent a novel early serum biomarker for TA-TMA that could potentially allow for earlier diagnosis and intervention.

Risk assessment in medically treated chronic thromboembolic pulmonary hypertension patients.

Abbreviated versions of the risk stratification strategy of the European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines have been recently validated in patients with pulmonary arterial hypertension. We aimed to investigate their prognostic value in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients from the COMPERA registry, which collects six variables of interest (World Health Organization Functional Class, 6-min walk distance, brain natriuretic peptide, right atrial pressure, cardiac index and mixed venous oxygen saturation).We included patients with at least one follow-up visit, no pulmonary endarterectomy and at least three of the six variables available, and classified the patients into low-, intermediate- and high-risk groups. As a secondary analysis, the number of noninvasive low-risk criteria was counted. The association between risk assessment and survival was evaluated.Data from inclusion and follow-up (median 7 months) visits were available for 561 and 231 patients, respectively. Baseline 1- and 5-year survival estimates were significantly different (p<0.0001) in the baseline low-risk (98.6% and 88.3%, respectively), intermediate-risk (94.9% and 61.8%, respectively) and high-risk (75.5% and 32.9%, respectively) cohorts. Follow-up data were even more discriminative, with 100%, 92% and 69% 1-year survival, respectively. The number of low-risk noninvasive criteria was also associated with survival.These analyses suggest that the ESC/ERS risk assessment may be applicable in patients with medically treated CTEPH.

Non-invasive diagnosis of cardiac amyloidosis due to transthyretin. Case report

Amyloidosis due to deposits of transthyretin (ATTR) is currently considered the most frequent form of cardiac amyloidosis and its incidence is increasing thanks to the advances in diagnostic imaging techniques. Some non-invasive diagnostic criteria have recently been published on this entity that due to the development of new drugs for the specific treatment of cardiac ATTR, have prognostic and therapeutic implications. That is why cardiac ATTR could cease to be a rare disease and become a frequent one, and become potentially treatable instead of incurable. We present the case of an 80-year-old male diagnosed with non-hereditary cardiac ATTR by means of gammagraphy with 99mTc diphosfonate scintigraphy (99mTc-DPD) following the new criteria of non-invasive diagnosis.

A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing. Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or noncardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. The derivation cohort included 414 consecutive patients (267 cases with HFpEF and 147 controls; HFpEF prevalence, 64%). The test cohort included 100 consecutive patients (61 with HFpEF; prevalence, 61%). Obesity, atrial fibrillation, age >60 years, treatment with ≥2 antihypertensives, echocardiographic E/e' ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mm Hg were selected as the final set of predictive variables. A weighted score based on these 6 variables was used to create a composite score (H2FPEF score) ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI, 1.74-2.30; P<0.0001), with an area under the curve of 0.841 ( P<0.0001). The H2FPEF score was superior to a currently used algorithm based on expert consensus (increase in area under the curve of 0.169; 95% CI, 0.120-0.217; P<0.0001). Performance in the independent test cohort was maintained (area under the curve, 0.886; P<0.0001). The H2FPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.

Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis

Baveno VI and expanded Baveno VI criteria can avoid the need for esophagogastroduodenoscopy (EGD) to screen for varices needing treatment (VNT) in a substantial proportion of compensated patients with viral and/or alcoholic cirrhosis. This multicenter, cross-sectional study aims to validate these criteria in patients with compensated cirrhosis due to non-alcoholic fatty liver disease (NAFLD), accounting for possible differences in liver stiffness measurement (LSM) values between M and XL probes. We assessed 790 patients with NAFLD-related compensated cirrhosis who had EGD within six months of a reliable LSM, measured by FibroScan® using M and/or XL probe. Baveno VI and expanded Baveno VI criteria were tested. The main variable used to optimize criteria was the percentage of endoscopies spared, keeping the risk of missing large VNT below a 5% threshold. LSM was measured by both M and XL probes (training set) in 314 patients, while only M or XL probe (validation sets) were used to measure LSM in 338 and 138 patients, respectively. In the training set, use of Baveno VI and expanded Baveno VI criteria reduced the number of EGD by 33.3% and by 58%, with 0.9% and 3.8% of large esophageal varices missed, respectively. The best thresholds to rule-out VNT were identified as platelet count >110,000/mm3 and LSM <30 kPa for M probe, and platelet count >110,000/mm3 and LSM <25 kPa for XL probe (NAFLD cirrhosis criteria). Thus, usage of NAFLD cirrhosis criteria would have led to an absolute reduction in the number of EGD screened patients of 34.7% and 10.5% with respect to Baveno VI and expanded Baveno VI criteria, respectively. The new NAFLD cirrhosis criteria, established for the FibroScan probe, can reduce the use of EGD for screening of VNT in NAFLD cirrhosis by more than half, with a chance of missing VNT below 5%. In non-alcoholic fatty liver disease-related compensated cirrhosis, the expanded Baveno VI criteria work better than the Baveno VI criteria for ruling out the presence of varices needing treatment, sparing unnecessary and invasive screening procedures. New diagnostic criteria for this patient group, based on liver stiffness measurement and platelet count, and optimized for the specific FibroScan® probe used, work better than both Baveno VI and expanded Baveno VI criteria. The accuracy of all non-invasive scoring criteria was lower in non-obese patients.

Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines

One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96–100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions.