kPa In Patients Research Articles

Sound Touch Elastography for Noninvasive Assessment of Liver Stiffness in Patients With Chronic Heart Failure

Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction ≤40%, n=45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n=40), and right-sided HF (RHF) groups (n=25); normal groups (n=40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 ± 1.1 kPa in normal subjects and increased slightly to 5.9 ± 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 ± 2.0 kPa and 10.3 ± 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens.

Evaluation of the median nerve by shear wave elastography in patients with Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is characterized by enlargement and stiffness of peripheral nerves due to edema with large numbers of "onion bulbs" in the endoneurium. Ultrasound elastography seems to be an ideal method to detect this condition. The aim of this study was to analyze the shear wave elastography (SWE) features of peripheral nerves in patients with CMT1A. We included 24 CMT1A patients with a mean age of 28 years, along with 24 age- and gender-matched controls. All patients presented with mutations of the PMP22 gene and showed length-dependent polyneuropathy. The motor nerve conduction velocity (MNCV) of the median nerve ranged from 5.2 to 37.4 m/s. SWE and cross-sectional area (CSA) were used to evaluate the bilateral median nerves at predefined sites in both patients and con-trols. The average elastography value (EV) of the median nerve was 73.5±11.7 kPa in patients with CMT1A and 37.5±6.1 kPa in control subjects. The difference between the two groups was statistically significant (P<0.05). In CMT1A pa-tients, the average EV at the proximal and distal parts of the median nerve were 81.4±9.4 kPa and 65.2±8.1 kPa, respectively. The average CSAs at the proximal and distal parts of the median nerve were 0.29±0.06 cm2 and 0.20±0.05 cm2, respectively. The EV on SWE was positively correlated with CSA (p< 0.01) and negatively correlated with MNCV in the median nerve (p< 0.01). Peripheral nerve stiffness dramatically increases in CMT1A and is correlated with the severity of nerve involvement.

The Role of ElastPQ in Assessing Liver Stiffness for Non-Alcoholic Fatty Liver Disease in Patients Treated with Atypical Antipsychotic Drugs.

To evaluate the role of elastography point quantification (ElastPQ) for the quantitative assessment of stiffness in the fatty liver disease in mental disorder patients and to provide a noninvasive detection method for non-alcoholic fatty liver (NAFLD) caused by atypical antipsychotics drugs (AAPDs). A total number of 168 mental disorder patients treated with AAPDs and 58 healthy volunteers were enrolled in this study. All the subjects underwent ultrasound and ElastPQ tests. The basic data of the patients were analyzed. BMI, liver function, and the value of ElastPQ were considerably higher in the patient group than that in the healthy volunteers. The values of liver stiffness obtained by ElastPQ were increased gradually from 3.48(3.14-3.81) kPa in the normal liver to 8.15(6.44-9.88) in the severe fatty liver. The receiver operating characteristic (ROC) for the diagnosis of fatty liver with ElastPQ were 0.85, 0.79, 0.80, and 0.87 for the diagnosis of normal, mild, moderate, and severe steatosis, respectively, with a sensitive/specificity of 79%/76.4%, 85.7%/78.3%, 86.2%/73%, and 81.3%/82.1%, correspondingly. Moreover, ElastPQ in the olanzapine group was higher than those in the risperidone and aripiprazole groups (5.11(3.83-5.61) kPa vs 4.35(3.63-4.98) kPa, P < 0.05; 5.11(3.83-5.61) kPa vs 4.79(4.18-5.24) kPa, P < 0.05). After one-year treatment, the value of ElastPQ was 4.43(3.85-5.22) kPa, but it was 5.81(5.09-7.33) kPa in patients treated for more than three years. This value increased with treatment prolongation (P < 0.05). ElastPQ is a real-time, quantitative method for assessing the stiffness of NAFLD. The liver stiffness value could be varied in the different stages of fatty liver. Olanzapine has a considerable influence on liver stiffness. The long-term use of AAPDs can increase the stiffness value of fatty liver.

Features of Idiopathic Intracranial Hypertension on MRI With MR Elastography: Prospective Comparison With Control Individuals and Assessment of Postintervention Changes.

BACKGROUND. Understanding of dynamic changes of MRI findings in response to intracranial pressure (ICP) changes in idiopathic intracranial hypertension (IIH) is limited. Brain stiffness, as assessed by MR elastography (MRE), may reflect changes in ICP. OBJECTIVE. The purpose of this study was to compare pituitary height, ventricular size, and brain stiffness between patients with IIH and control individuals and to evaluate for changes in these findings in patients with IIH after interventions to reduce ICP. METHODS. This prospective study included 30 patients (28 women, two men; median age, 29.9 years) with IIH and papilledema and 21 control individuals (21 women, 0 men; median age, 29.1 years), recruited from January 2017 to July 2019. All participants underwent 3-T brain MRI with MRE; patients with IIH underwent additional MRI examinations with MRE after acute intervention (lumbar puncture with normal closing pressure; n = 11) and/or chronic intervention (medical management or venous sinus stenting with resolution or substantial reduction in papilledema; n = 12). Pituitary height was measured on sagittal MP-RAGE images. Ventricular volumes were estimated using unified segmentation, and postintervention changes were assessed by tensor-based morphometry. Stiffness pattern score and regional stiffness values were estimated from MRE. RESULTS. In patients with IIH, median pituitary height was smaller than in control individuals (3.1 vs 4.9 mm, p < .001) and was increased after chronic (4.0 mm, p = .05), but not acute (2.3 mm, p = .50), intervention. Ventricular volume was not different between patients with IIH and control individuals (p = .33) and did not change after acute (p = .83) or chronic (p = .97) intervention. In patients with IIH, median stiffness pattern score was greater than in control individuals (0.25 vs 0.15, p < .001) and decreased after chronic (0.23, p = .11) but not acute (0.25, p = .49) intervention. Median occipital lobe stiffness was 3.08 kPa in patients with IIH versus 2.94 kPa in control individuals (p = .07) and did not change after acute (3.24 kPa, p = .73) or chronic (3.10 kPa, p = .83) intervention. CONCLUSION. IIH is associated with a small pituitary and increased brain stiffness pattern score; both findings may respond to chronic interventions to lower ICP. CLINICAL IMPACT. The "partially empty sella" sign and brain stiffness pattern score may serve as dynamic markers of ICP in IIH.

Multiparametric MRI with MR elastography findings in patients with sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy

ObjectiveTo evaluate the magnetic resonance elastography (MRE)-derived liver stiffness measurement (LSM), T1 and T2 relaxation times, and hepatobiliary phase images in patients, who developed sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy.MethodsThirty-four patients (M/F:22/12) who underwent liver MRI-MRE and received oxaliplatin for colorectal, gastric, and pancreas cancer were included in the study. SOS was diagnosed by Gd-EOB-DTPA-enhanced MRI in 18 patients. MRE-LSM and T1–T2 maps were evaluated. Patients with SOS were grouped according to the amount of reticular hypointensity on the hepatobiliary phase images.ResultsThe mean MRE-LSM in the patients with SOS was 3.14 ± 0.45 kPa, and the control group was 2.6 ± 0.5 kPa (p = 0.01). The mean-corrected T1 (cT1) relaxation time was 1181 ± 151 ms in the SOS group and 1032 ± 129 ms in the control group (p = 0.005). The mean T2 relaxation time was 50.29 ± 3.6 ms in the SOS group and 44 ± 3.9 ms in the control group (p = 0.01). Parenchymal stiffness values were 2.8 ± 0.22 kPa, 3 ± 0.33 kPa, and 3.65 ± 0.28 kPa in patients with mild, moderate, and advanced SOS findings, respectively (p = 0.002). Although cT1 and T2 relaxation times increased with increasing SOS severity, no statistical significance was found.ConclusionsWe observed increased MRE-LSM in patients with SOS after chemotherapy compared to control group. T1 and T2 relaxation times were also useful in diagnosing SOS but were found inadequate in determining SOS severity. MRE is effective in diagnosing SOS and determining SOS severity in patients who cannot receive contrast agents, and it may be useful in the follow-up evaluation of these patients.

Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients

BackgroundThe impact of hepatic steatosis on liver stiffness measurement (LSM) in both chronic hepatitis B(CHB) and metabolic-associated fatty liver disease (MAFLD) remains controversial. AimsTo determine whether LSM is affected by hepatic steatosis in CHB-MAFLD. MethodsHepatic steatosis and liver fibrosis were assessed by histological and noninvasively methods. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance of LSM. ResultsThe prevalence of MAFLD in CHB patients (n = 436)was 47.5% (n = 207). For patients with low amounts of fibrosis (F0–1 and F0–2), the median LSM was 8.8 kPa and 9.2 kPa in patients with moderate- severe steatosis,which was significantly higher than that in patients with none-mild steatosis (P < 0.05) . The positive predictive value(PPV) was lower for LSM identifying significant fibrosis (F ≥ 2) as well as severe fibrosis (F ≥ 3) in group which controlled attenuation parameter(CAP) ≥ 268 dB/m than its counterpart(68.2% vs 84.6% and 24.3% vs 45.0%). The AUROC of LSM detected F ≥ 2 was 0.833 at a cutoff of 8.8 kPa and 0.873 at a cutoff of 7.0 kPa in patients with CAP ≥ 268 and CAP < 268, respectively. ConclusionsThe presence of moderate-severe steatosis, detected by histology or CAP, should be taken into account to avoid overestimation of LSM.

Combined alcoholic and non-alcoholic steatohepatitis.

SummaryWhile metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.

Performance of B-mode ratio and 2D shear wave elastography for the detection and quantification of hepatic steatosis and fibrosis after liver transplantation.

To evaluate the diagnostic performance of B-mode ratio and shear wave elastography (SWE) for the assessment of steatosis and liver fibrosis after liver transplantation. Patients hospitalized for a systematic check-up after liver transplantation underwent the same day hepatic ultrasound with B-mode ratio and SWE, followed by liver biopsy and biological examinations. Steatosis was measured using hepatorenal sonographic index of B-mode ratio and liver stiffness using SWE. Liver biopsy, used as gold standard, graded steatosis S0(<5%), S1(5-<33%), S2(33-<66%), or S3(≥66%) and liver fibrosis according to the Metavir score. The results were tested against two external validation cohorts. Fifty-eight patients were included. Mean B-ratio value was significantly higher in patients with steatosis (0.95 ± 0.13 versus 1.39 ± 0.41, P < 0.001). A B-mode ratio cutoff values at least 0.985 was found optimal for steatosis' detection [area under the receiver operating characteristic curve (AUROC) 0.902 ± 0.05, sensitivity 95%, specificity 79%]. A B-mode ratio value below 0.9 ruled out steatosis and above 1.12 ruled in steatosis. Mean SWE value for patients without significant fibrosis (≤F1) was 15.90 ± 9.2 versus 19.27 ± 7.7 kPa for patients with fibrosis (P = 0.185). A 2D-SWE value below 7.85 kPa ruled out significant fibrosis and above 26.35 kPa ruled it in. The B-mode ratio is an efficient and accurate tool for the noninvasive diagnostic of steatosis in postliver transplantation patients. Yet, because liver stiffness is higher in postliver transplantation patients, 2D-SWE is not reliable in the diagnosis of significant fibrosis after liver transplantation.

Effectiveness of Shear Wave Elastography in the diagnosis of acute pancreatitis on admission.

We aimed to investigate the effectiveness of shear wave elastography (SWE) in the diagnosis of acute pancreatitis(AP). The pancreatic parenchyma of 50 patients whose clinical and laboratory findings were indicativeof AP and of 70 healthy, asymptomatic volunteer participants with normal laboratory values was examined using SWE.Computed tomography was performed in all patients with AP on admission. Elastographic measurements were performed bymanually drawing the contours of the pancreatic parenchyma using the free region of interest. The quantitative SWE values(meters/second [m/s], kilopascal [kPa]) of the patients and asymptomatic volunteers group were compared. The meanSWE value of the pancreatic parenchyma was 2.60 ± 1.63 m/s in the asymptomatic volunteers and 3.48 ± 0.52 m/s in patientswith AP, with a statistically significant difference (p<0.001, t=-3.685). The mean SWE value of the pancreatic parenchyma was23.77±6.72 kPa in the asymptomatic volunteers and 45.71 ± 10.72 kPa in patients with AP, indicating a significant difference(p<0.001, t=-3.685). AP can be diagnosed with a sensitivity and specificity of 98.0% when 29.45 kPa was designated as cut-offvalue and with a 96.0% sensitivity and 98.3% specificity when 2.77 m/s was designated as the cut-off value. The superiorityof SWE was found over B-mode US and CECT in the diagnosis of AP on admission.Conclusion: SWE can be used as an effective imaging method with high sensitivity and specificity for the diagnosis ofAP. It may be used as an important imaging method to assist in the diagnosis of AP especially when B-mode US and CECTfindings are normal.

Shear wave elastography for liver fibrosis in chronic hepatitis B: Adapting the cut-offs to alanine aminotransferase levels improves accuracy.

To determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection. Patients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively. The first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all p>0.05). The ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection. • The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis. • ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis. • The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels ≤ 2 × ULN.

Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients.

Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors' preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors' preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2 ) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2 ); and 23% preferred SaO2 . Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.

The Efficacy and Safety of Direct-acting Antiviral Treatment for Chronic Hepatitis C Patients: A Single Center Study.

Direct-acting antiviral (DAA) therapy has been shown to achieve a high rate of sustained virologic response (SVR) and favorable outcomes in chronic hepatitis C (CHC) patients. We investigated the virologic response and its clinical impact in CHC patients. CHC patients with compensated liver function treated with DAAs between 2016 and 2017 were included for retrospective analysis. We analyzed baseline characteristics and virologic and biochemical responses at on-treatment 4 weeks, end of treatment, and post-treatment 12 weeks. Fibrosis was measured as liver stiffness measurement by transient elastography (FibroScan). Adverse events were monitored during the treatment period. A total of 135 patients (61.5% with genotype [GT] 1b and 38.5% with GT 2a) were enrolled 47.4% were male, 79.3% were treatment naive, and 30.4% had cirrhosis. SVR 12 was observed in 97.6% (81/83) in the GT 1b and 98.1% (51/52) in the GT 2a; treatment with daclatasvir+asunaprevir was the most commonly used in GT 1b (55/83), and sofosbuvir+ribavirin was the most commonly used in GT 2a (49/52). The median change of liver stiffness measurement at two time points using the signed rank test was -3.2 kPa in patients who underwent transient elastography before treatment and at SVR 12 (n=25). The most common adverse events were anemia, dyspepsia, and insomnia. One GT 2a patient treated with sofosbuvir+ribavirin stopped the treatment at 8 weeks due to symptomatic bradyarrhythmia; however, he recovered spontaneously and achieved SVR 12. DAA treatment of chronic hepatitis C genotype 1b and 2a resulted in a high rate of sustained virologic response and improvement of liver fibrosis score.

On-treatment changes of liver stiffness at week 26 could predict 2-year clinical outcomes in HBV-related compensated cirrhosis.

It is unclear whether liver stiffness measurement (LSM) dynamic changes after anti-HBV treatment could predict the risk of liver-related events (LREs), particularly in patients with HBV-related compensated cirrhosis. Treatment-naïve patients with HBV-related compensated cirrhosis were enrolled. All patients were under entecavir-based antiviral therapy, and followed up every 26weeks for 2years. The association between LSM and LREs was analysed by Cox proportional hazard model and Harrell C-index analysis. A total of 438 patients were included in the study. At the follow-up of 104weeks, LREs developed in 33/438 (7.8%) patients, including 16 episodes of decompensation, 18 HCC and 3 deaths. The median LSM remained high from 20.9, 18.6, 20.4 to 20.3Kpa at week 0, 26, 52 and 78 among patients with LREs, whereas the LSM decreased from 17.8, 12.3, 10.6 to 10.2Kpa in patients without LREs respectively. Percentage changes of LSM at 26weeks from baseline were significantly associated with LREs (excluding 11 cases occurred within the first 26weeks), with a crude hazard ratio of 2.94 (95% CI: 1.73-5.00) and an albumin-adjusted hazard ratio of 2.47 (95% CI: 1.49-4.11). The Harrell C-index of these 2 models for predicting 2-year LREs were 0.68 (95% CI: 0.56-0.80) and 0.75 (95% CI: 0.65-0.85) respectively. Nomograms were developed to identify individuals at high risk for point-of-care application. Dynamic changes of LSM alone, or combined with baseline albumin, could predict LREs in patients with HBV-related compensated cirrhosis during antiviral therapy.

Tongue strength in patients with subacute myelo-optico-neuropathy

Subacute myelo-optico-neuropathy (SMON) is a neurodegenerative disease that may be caused by overdose or prolonged oral administration of clioquinol. Recently, dysphagia has attracted attention as a complication of SMON. To investigate lingual control in SMON, we examined patients with SMON using assessments of maximum tongue pressure, compared with dysphagia-related diseases, such as sporadic inclusion body myositis (sIBM) and amyotrophic lateral sclerosis (ALS), and healthy volunteer. The mean maximum tongue pressure (Pmax) in patients with SMON was 14.7 ± 5.8 kPa, while it was 33.6 ± 4.4 kPa in the controls. In contrast, the mean Pmax for patients with ALS with or without bulbar involvement was 7.8 ± 2.7 kPa and 34.4 ± 5.7 kPa, respectively, while it was 29.4 ± 8.2 kPa in patients with sIBM. Pmax values correlated with lower limb weakness in SMON patients. Decreases in Pmax may be involved in the development of dysphagia in patients with SMON.

Reproducibility of shear wave elastography (SWE) in patients with chronic liver disease.

The presence of significant fibrosis is an indicator for liver disease staging and prognosis.The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.

Association Between Hepatic Steatosis, Measured by Controlled Attenuation Parameter, and Fibrosis Burden in Chronic Hepatitis B

The interaction between chronic hepatitis B (CHB) and hepatic steatosis is poorly understood. We investigated whether measurement of controlled attenuation parameter (CAP), a non-invasive method to quantify steatosis, can assist in monitoring patients with CHB. We performed transient elastography, to measure liver stiffness, and made CAP measurements in 1606 patients with CHB (898 treated with nucleoside analogues, for a median 75.4 months) in Hong Kong, from January 2015 through September 2016. We also collected information on patients' medical history, current treatment, and smoking and alcohol habits, anthropometric measurements. We obtained and analyzed fasting blood samples. Severe liver fibrosis wasdefined, according to guidelines, as a liver stiffness measurement greater than 9.0 kPa inpatients with normal level of alanine aminotransferase (ALT) or greater than 12.0 kPa in patients with a level of ALT 1-5-fold the upper limit of normal. Steatosis was defined as a CAP measurement of 248 dB/m or more, and severe steatosis as a CAP measurement or 280 dB/m more. We performed multivariate analysis to identify factors associated with severe fibrosis. The prevalence of steatosis, severe steatosis, and severe fibrosis in our cohort were 40.8%, 22.6%, and 14.1%, respectively. A higher proportion of patients with severe steatosis had severe fibrosis (21.4% vs 11.9% in the overall cohort; P < .001). In multivariate analysis, severe steatosis was associated with severe fibrosis in treatment-naïve patients (odds ratio, 3.60, 95% CI, 1.21-10.75) and in patients receiving treatment (odds ratios: 1.95 [1.06-3.61] for 3 or more years of treatment, 2.28 [1.13-4.61] for 5 or more years of treatment, and 2.79 [1.17-6.62] for 7or more years of treatment). With every increase in CAP value of 10 dB/m, the risk of severe fibrosis increased by 15% in treatment-naïve patients and by 7%-8% in patients receiving treatment. Severe steatosis, determined by CAP measurement, is associated with severe fibrosis in treatment-naïve patients with CHB and in patients receiving treatment. Longitudinal studies are required to investigate if steatosis control, in addition to antiviral treatment, can reduce the burden fibrosis in patients with CHB.

Experimental pain sensitivity in women with vestibulodynia: a pilot study

Objective: Investigate pain sensitivity in women with vestibulodynia using two experimental pain assessments outside the vulvar region: intramuscular infusion of an acidic phosphate buffer and pressure pain thresholds (PPTs) of the lower limb. Methods: Three women with a history of vestibulodynia (all 24 years old) participated after providing written informed consent. PPTs of the lower limb were assessed using a hand-held Somedic digital algometer (30 kilopascal (kPa)/sec) at baseline (pre-infusion) and during the intramuscular infusion. The acidic phosphate buffer (pH 5.2) was infused into the anterior tibialis muscle at a rate of 40 ml/hr for 15 min (10 ml total). Peak local (infusion site) and referred (ankle) pain ratings were assessed verbally, as well as vulvar pain at the time of the infusion (0 – 10 Borg Scale). Results: Peak local pain was higher in two of the three subjects (2.5, 4.0, 9.5) than the average pain ratings in 34 healthy age-matched (21 – 27 years old) women from our laboratory, mean 3.0/10 (standard deviation (SD) 2.2; range 0.5 to 10). Peak referred pain was also higher in the same two subjects (0, 4.25, and 7.5) than the average of the controls (mean 1.5; SD 1.8; range 0 – 9.0). Similarly, vulvar pain patients all exhibited greater mechanical pain sensitivity (lower PPT values) than the average of the healthy controls (mean [SD] 246.3 [101.7] kPa in patients vs. 431.3 [109.33] in controls). Conclusion: Preliminary data suggests women with vestibulodynia may exhibit greater generalized pain sensitivity to noxious stimuli than the general population of women.

The development of hepatocarcinoma after long-term antivirus treatment of Chinese patients with chronic hepatitis B virus infection: Incidence, long-term outcomes and predictive factors

Patients with chronic hepatitis B virus (HBV) infection are at high risk for progressing to decompensated cirrhosis and hepatocellular carcinoma (HCC). Although long-term treatment with nucleos(t)ide analogues (NAs) benefits patients with chronic hepatitis B (CHB), many develop HCC. Therefore, the clinical outcomes of patients CHB who undergo long-term treatment with NAs remain to be identified. The aim of this study therefore was to evaluate the risk and predictors of patients with CHB who develop hepatitis B-induced HCC. We investigated 1200 patients with CHB who were treated with NAs for at least four years and evaluated the association of the variables ALT, HBsAg, HBV DNA, age and platelet count with the occurrence of HCC. We used multivariable analysis to identify independent risk factors for the development of HCC. HCC developed in 153 NA-treated patients. Serum HBV DNA levels of 18.17% (218/1200) patients were>2000IU/mL. The median level of liver stiffness measurement (LSM) of all patients was 8.3±6.7kPa vs. 19.8±10.1kPa in patients with HCC. Advanced age, lower platelet counts, positive HBV DNA load, lower ALB concentration and relatively advanced liver disease were associated with an increased risk of developing HCC. Further, TGF-β and IFN-γ levels were higher and lower in patients with HCC or CHB, respectively. Hepato-carcinogenesis occurred more frequently in patients with a positive HBV DNA load and relatively advanced liver disease. Therefore, it is important to administer antiviral therapy to patients with CHB before they develop HBV-related cirrhosis.

Changes in liver stiffness and its associated factors during oral antiviral therapy in Chinese patients with chronic hepatitis B.

The present study aimed to assess improvements in liver stiffness determined by transient elastography and associated factors in Chinese patients with chronic hepatitis B (CHB) during long-term treatment with oral antiviral drugs. A total of 334 consecutive Chinese patients with CHB who underwent oral antiviral therapy and received at least two liver stiffness measurements (LSMs) at the First Hospital of Jilin University (Changchun, China) from December 2012 to February 2015 were enrolled in the present study. The cohort included 201 patients without liver cirrhosis (group 0) and 133 patients with liver cirrhosis (group 1). Each patient was subjected to LSM twice with an interval of 6 months. The mean initial liver stiffness values were 14.01±9.37 and 21.59±10.25 kPa for patients in group 0 and group 1, respectively (P<0.001). Multivariate analysis revealed that higher aspartate aminotransferase and lower alanine aminotransferase levels at baseline as well as higher α-fetoprotein levels at follow-up (24 weeks) were associated with a greater decline of liver stiffness in group 0. Furthermore, a higher liver stiffness at baseline and a longer course of antiviral therapy prior to the initial LSM were significantly correlated with a reduction of liver stiffness, whereas higher total bilirubin levels at follow-up contributed to increased liver stiffness in group 1. In conclusion, LSM at the beginning and the end of a 24-week observation period showed that antiviral drug therapy significantly improved in group 1, while a marked decreasing trend was also observed in group 0. In group 0, the reduction of liver stiffness was correlated with liver inflammation, whereas in group 1, it was correlated with the treatment duration prior to the initial LSM and serum levels of hepatitis B virus DNA. Furthermore, a higher liver stiffness at baseline was associated with a greater reduction of liver stiffness in each group.

The effects of gastrocnemius–soleus muscle forces on ankle biomechanics during triple arthrodesis

This paper presents a finite element model of the ankle, taking into account the effects of muscle forces, determined by a musculoskeletal analysis, to investigate the contact stress distribution in the tibio-talar joint in patients with triple arthrodesis and in normal subjects. Forces of major ankle muscles were simulated and corresponded well with the trend of their EMG signals. These forces were applied to the finite element model to obtain stress distributions for patients with triple arthrodesis and normal subjects in three stages of the gait cycle, i.e. heel strike, midstance, and heel rise. The results demonstrated that the stress distribution patterns of the tibio-talar joint in patients with triple arthrodesis differ from those of normal subjects in investigated gait cycle stages. The mean and standard deviations for maximum stresses in the tibo-talar joint in the stance phase for patients and normal subjects were 9.398e7 ± 1.75e7 and 7.372e7 ± 4.43e6 Pa, respectively. The maximum von Mises stresses of the tibio-talar joint for all subjects in the stance phase found to be on the lateral side of the inferior surface of the joint. The results also indicate that, in patients with triple arthrodesis, increasing gastrocnemius–soleus muscle force reduces the stress on the medial malleolus compared with normal subjects. Most of stresses in this area are between 45 and 109 kPa, and will decrease to almost 32 kPa in patients after increasing of 40% in gastrocnemius–soleus muscle force.