Population-based and Personalized Reference Intervals for Liver and Spleen Volumes in Healthy Individuals and Those with Viral Hepatitis.

Background Reference intervals guiding volumetric assessment of the liver and spleen have yet to be established. Purpose To establish population-based and personalized reference intervals for liver volume, spleen volume, and liver-to-spleen volume ratio (LSVR). Materials and Methods This retrospective study consecutively included healthy adult liver donors from 2001 to 2013 (reference group) and from 2014 to 2016 (healthy validation group) and patients with viral hepatitis from 2007 to 2017. Liver volume, spleen volume, and LSVR were measured with CT by using a deep learning algorithm. In the reference group, the reference intervals for the volume indexes were determined by using the population-based (ranges encompassing the central 95% of donors) and personalized (quantile regression modeling of the 2.5th and 97.5th percentiles as a function of age, sex, height, and weight) approaches. The validity of the reference intervals was evaluated in the healthy validation group and the viral hepatitis group. Results The reference and healthy validation groups had 2989 donors (mean age ± standard deviation, 30 years ± 9; 1828 men) and 472 donors (mean age, 30 years ± 9; 334 men), respectively. The viral hepatitis group had 158 patients (mean age, 48 years ± 12; 95 men). The population-based reference intervals were 824.5-1700.0 cm3 for liver volume, 81.1-322.0 cm3 for spleen volume, and 3.96-13.78 for LSVR. Formulae and a web calculator (https://i-pacs.com/calculators) were presented to calculate the personalized reference intervals. In the healthy validation group, both the population-based and personalized reference intervals were used to classify the volume indexes of 94%-96% of the donors as falling within the reference interval. In the viral hepatitis group, when compared with the population-based reference intervals, the personalized reference intervals helped identify more patients with volume indexes outside the reference interval (liver volume, 21.5% [34 of 158] vs 13.3% [21 of 158], P = .01; spleen volume, 29.1% [46 of 158] vs 22.2% [35 of 158], P = .01; LSVR, 35.4% [56 of 158] vs 26.6% [42 of 158], P < .001). Conclusion Reference intervals derived from a deep learning approach in healthy adults may enable evidence-based assessments of liver and spleen volume in clinical practice. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ringl in this issue.

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging-guided risk assessment in living donor liver transplant patients with postoperative complications: a pilot study.

OBJECTIVE: To evaluate whether gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI), the measurements of quantitative and qualitative parameters on hepatobiliary phase images can predict the risk of postoperative complications in patients underwent living donor liver transplantation (LDLT) PATIENTS AND METHODS: We obtained Gd-EOB-DTPA-enhanced 3 Tesla MRI before living donor hepatectomy in donors (donor group; n=30) and after LDLT in their recipients (recipient group; n=30). MRIs were evaluated in terms of quantitative and qualitative variables. Quantitative parameters included relative liver enhancement value, biliary signal intensity value, and muscle signal index value. Qualitative parameters included visual evaluation of the liver and biliary enhancement on hepatobiliary phase images. Patients were followed up for postoperative biliary and vascular complications and divided according to the presence and absence of complications. The relationship between MRI parameters and postoperative complications was statistically analyzed. RESULTS: The mean relative liver enhancement values, mean biliary signal values, and muscle signal index were significantly lower in recipients with postoperative complications than those in donors and recipients without complications (p < 0.001). Visual assessments of liver enhancement and biliary signal were also significantly different in recipients with postoperative complications than that in donors and recipients without complications (p < 0.001). CONCLUSIONS: Quantitative and qualitative MRI parameters obtained by Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase images may potentially become a reliable tool for the assessment of the risk for postoperative complications after LDLT.

An acute viral hepatitis epidemic: does ultrasound help the pediatrician?

OBJECTIVE: Acute viral hepatitis (AVH) caused by hepatitis virus A and hepatitis virus E is one of the many epidemics that plague third world countries like Pakistan. The serological tests required for the diagnosis of acute viral hepatitis may be unavailable or unaffordable to the denizens of a developing country like Pakistan. In such a scenario, the clinical manifestations and the ultrasonographic findings are the only diagnostic criteria usually present and these can be used to support a clinical diagnosis. This study aims to judge the utility of ultrasound in the diagnosis of AVH. RESULTS: Among the forty-seven subjects of this study, gall bladder wall thickening (GWT) was the most common radiological finding seen in 39 (82.9%) patients. Pericholecystic edema was the second most common finding, seen in 31 (65.9%) patients. Starry sky appearance of the liver was observed in 30 (63.8) patients. Hepatomegaly and ascites were seen in 28 (59.5%) and 25 (53.2%) of the patients, respectively. The ultrasonographic findings of GWT, pericholecystic edema, and starry sky appearance of the liver were the most common ultrasonographic findings associated with AVH.

Quantifying steatosis in the liver and pancreas with MRI in patient with chronic liver disease. / Cuantificación por resonancia magnética de esteatosis hepática y pancreática en hepatopatía crónica.

AIM: To compare pancreatic and hepatic steatosis quantified by proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) in patients with chronic liver disease. MATERIAL AND METHODS: This cross-sectional study included 46 adult patients who underwent liver biopsy for chronic viral hepatitis (n=19) or other chronic non-alcoholic liver diseases (NALD) (n=27). Liver biopsy was used as the gold standard for diagnosing and grading hepatic steatosis. All patients underwent clinical evaluation and MRI with a multi-echo chemical shift-encoded (MECSE) gradient-echo sequence for liver and pancreas PDFF quantification. We used Spearman's correlation coefficient to determine the degree of association between hepatic PDFF and steatosis grade, and between pancreatic PDFF and steatosis grade and hepatic PDFF. To compare the chronic viral hepatitis group and the NALD group, we used t-tests for continuous or ordinal variables and chi-square tests for categorical variables. RESULTS: Hepatic PDFF measurements correlated with steatosis grades (RS=0.875, p<0.001). Pancreatic PDFF correlated with hepatic steatosis grades (RS=0.573, p<0.001) and hepatic PDFF measurements (RS=0.536, p<0.001). In the subgroup of patients with chronic NALD, the correlations remained significant between pancreatic PDFF and hepatic PDFF (RS=0.632, p<0.001) and between pancreatic PDFF and liver steatosis (RS=0.608, p<0.001); however, in the subgroup of patients with viral hepatitis these correlations were no longer significant. CONCLUSION: Pancreatic fat deposition correlates with hepatic steatosis in patients with chronic NALD, but not in those with chronic viral hepatitis.

Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions.

Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and limitations of US- and MR-based elastography techniques. Diagnostic performance in the most common etiologies of chronic liver disease will be presented. Reliability, reproducibility, failure rate, and emerging advances will be discussed. © RSNA, 2018 Online supplemental material is available for this article.

Can acoustic radiation force impulse elastography be a substitute for liver biopsy in predicting liver fibrosis?

AIM: To evaluate the clinical feasibility and accuracy of acoustic radiation force impulse (ARFI) elastography for the detection of liver fibrosis in patients with chronic viral hepatitis. MATERIALS AND METHODS: ARFI-based ultrasound elastography was performed in 69 patients with chronic liver disease (CLD) of viral aetiology and 36 healthy volunteers. Fifty-eight patients with CLD also underwent liver biopsy. RESULTS: ARFI was feasible in all 36 healthy volunteers and all 69 CLD patients, while valid measurements were obtained in 65 patients (95.6%) and all healthy volunteers. The mean shear-wave velocity (SWV) in healthy volunteers was 1.12±0.2 m/s. A gradual increase in mean SWV was noted from fibrosis of Grade F0 to F6 (Ishak's score) and a high positive correlation was found between the mean SWV on ARFI and fibrosis scores at liver biopsy (rho=0.789). The difference between the mild (F1 and F2) versus significant fibrosis (F3 and F4) was also statistically significant (p<0.001). The difference in the SWV measurements obtained from consecutive groups (i.e., F1 versus F2, F2 versus F3, and F3 versus F4) was not statistically significant. Using the area under the receiver operating characteristic curve (AUROC), the best calculated cut-off SWVs for the presence of fibrosis (≥F1), significant fibrosis (≥F3), severe fibrosis (≥F4), and cirrhosis (F6) were found to be 1.207, 1.347, 1.513, and 1.92 m/s, respectively. ARFI values were significantly higher in cirrhotic patients than in other patients (p<0.001). CONCLUSIONS: ARFI elastography allows valid non-invasive evaluation of liver stiffness and may help to distinguish between no/mild fibrosis and significant fibrosis and guide management decisions.

MR imaging features of liver involvement by Wilson disease in adult patients.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) presentation of liver involvement in adult patients with Wilson disease (WD) and determine the most indicative appearance of this condition on MRI using a retrospective case-control study. MATERIALS AND METHODS: MRI examinations of 23 adult patients with WD (14 men, 9 women; mean age = 40.4 years) were analyzed by two blinded observers and compared to those obtained in 23 patients with chronic viral hepatitis (14 men, 9 women, mean age = 40.4 years) who were matched for age, gender and severity of chronic liver disease. Images were qualitatively and quantitatively analyzed with respect to imaging presentation. Comparisons were performed using univariate analysis. RESULTS: Honeycomb pattern of hepatic parenchyma was the most discriminating independent variable for the diagnosis of WD (odds ratio, 17.082; 95 % CI 2.092-139.497) (P = 0.0081) but had a sensitivity of 43 % (10/23; 95 % CI 23-66 %). Regular liver contours was the other variable that strongly correlated with the presence of liver involvement by WD (odds ratio, 11.939; 95 % CI 1.503-94.836) (P = 0.0190). CONCLUSION: The honeycomb pattern is the most discriminating independent variable for the diagnosis of liver involvement by WD but has limited sensitivity. Familiarity with this finding may clarify the cause of diffuse hepatic parenchymal abnormalities in patients with unknown WD.

Perihepatic nodes detected by point-of-care ultrasound in acute hepatitis and acute-on-chronic liver disease.

AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography. METHODS: One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P < 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups (P < 0.01), and between acute hepatitis A and non-hepatitis A viral groups (P < 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis (P < 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.

Non-invasive score system for fibrosis in chronic hepatitis: proposal for a model based on biochemical, FibroScan and ultrasound data.

BACKGROUND & AIMS: We elaborate a non-invasive score system for liver fibrosis (NISF), exploring its diagnostic performance and comparing its accuracy to FibroScan in patients with chronic viral hepatitis (CH) and non-alcoholic fatty liver disease (NAFLD). METHODS: Clinical, biochemical, elastographic and ultrasound parameters derived from patients with CH (n = 83) or NAFLD (n = 58), undergoing liver biopsy for fibrosis assessment, were prospectively collected as potential predictors of fibrosis. Each parameter was evaluated for its correlation with the liver biopsy (Gold Standard). Candidate predictors with good interobserver agreement and correlation with histological stages were combined into two algorithms (NISF) to predict fibrosis in chronic viral hepatitis and NAFLD. RESULTS: The CH-NISF included six parameters: bluntness of liver edges, irregularity of left lobe surface, diameter of segment 4, liver stiffness measurement, platelet count and ALT values. The ability of the model to discriminate F3-F4 vs F0-F1 stages and F2 vs F0-F1 was high (AUROC of 0.95 and 0.83 respectively) and better than FibroScan alone, especially in intermediate stages (F2 vs F0-F1), AUROC 0.83 vs 0.57 (P = 0.003). The resulting algorithm is available as mathematical formula, nomogram or free online link. [http://health.mafservizi.it/NISF_Calculator/liver.htm] The NAFLD-NISF included liver stiffness, platelet count and AST levels, had good ability to discriminate F0-F1 vs F2-F3-F4 stages (AUROC 0.86), however, not significantly higher than FibroScan. CONCLUSIONS: CH-NISF can be proposed as preliminary and easily available staging tool, superior to FibroScan alone in predicting histological fibrosis, especially in intermediate stages. Further validations are needed to improve NISF accuracy in NAFLD.

Adenovirus hepatitis presenting as tumoral lesions in an immunocompromised patient.

A 59-year-old man with T-cell prolymphocytic leukemia on alemtuzumab presented with neutropenic fever, intermittent nausea, and multiple ill-defined low attenuation foci in the liver on abdominal computed tomography scan which were suspicious for metastatic disease. Histological examination revealed the diagnosis of adenovirus hepatitis. Patient responded well to cidofovir. Adenovirus hepatitis is a rare but important entity to be considered by the clinicians, radiologists, and pathologists. Timely diagnosis and appropriate management are essential to improve the prognosis of adenovirus hepatitis in immunocompromised patients.

Prediction of portal pressure from intraoperative ultrasonography.

BACKGROUND: Portal hypertension is a major risk factor for hepatic failure or bleeding in patients who have undergone hepatectomy, but it cannot be measured indirectly. We attempted to evaluate the intraoperative ultrasonography parameters that correlate with portal pressure (PP) in patients undergoing hepatectomy. METHODS: We examined 30 patients in whom PP was directly measured during surgery. The background liver conditions included chronic viral liver disease in seven patients, chemotherapy-associated steatohepatitis in four patients, fatty liver in one patient, hepatolithiasis in one patient, obstructive jaundice in one patient, and a normal liver in 16 patients. A multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for PP. RESULTS: The mean PP was 10.4 ± 4.1 mm Hg. The PP tended to be increased in patients with chronic viral hepatitis. A univariate analysis identified the association of the six following parameters with PP: the platelet count and the maximum (max), minimum (min), endo-diastolic, peak-systolic, and mean velocity in the portal vein (PV) flow. Using multiple linear regression analysis, the predictive formula using the PV max and min was as follows: Y (estimated PP) = 18.235-0.120 × (PV max.[m/s])-0.364 × (PV min). The calculated PP (10.44 ± 2.61 mm Hg) was nearly the same as the actual PP (10.43 ± 4.07 mm Hg). However, there was no significant relationship between the calculated PP and the intraoperative blood loss and post hepatectomy morbidity. CONCLUSIONS: This formula, which uses ultrasonographic Doppler flow parameters, appears to be useful for predicting PP.

[Comparison of the M and XL FibroScan(®) probes to estimate liver stiffness by transient elastography]. / Comparación de las sondas M y XL para estimar la rigidez hepática por medio de elastografía de transición.

The FibroScan(®) XL probe has been specifically designed for obese patients to measure liver stiffness by transient elastography, but it has not been well tested in non-obese patients. The aim of this study was to compare the M and XL FibroScan(®) probes in a series of unselected obese (body mass index above 30 kg/m(2)) and non-obese patients with chronic liver disease. Two hundred and fifty-four patients underwent a transient elastography examination with both the M and XL probes. The results obtained with the two probes were compared in the whole series and in obese (n=82) and non-obese (n=167) patients separately. The reliability of the examinations was assessed using the criteria defined by Castéra et al. The proportion of reliable exams was significantly higher when the XL probe was used (83% versus 73%; P=.001). This significance was maintained in the group of obese patients (82% versus 55%; P<.001), but not in the non-obese patients (84% versus 83%). Despite a high correlation between the stiffness values obtained with the two probes (R=.897; P<.001), and a high concordance in the estimation of fibrosis obtained with the two probes (Cronbach's alpha value: 0.932), the liver stiffness values obtained with the XL probe were significantly lower than those obtained with the M probe, both in the whole series (9.5 ± 9.1 kPa versus 11.3 ± 12.6 kPa; P<0.001) and in the obese and non-obese groups. In conclusion, transient elastography with the XL probe allows a higher proportion of reliable examinations in obese patients but not in non-obese patients. Stiffness values were lower with the XL probe than with the M probe.

Utilization of FibroScan in clinical practice.

The evaluation of liver fibrosis is critical, particularly to rule out cirrhosis. Novel non-invasive tests such as transient ultrasound elastography are widely used to stage liver fibrosis as an alternative to liver biopsy, and this technology has recently been approved in the US. In this review, we discuss the performance characteristics of elastography for a variety of liver diseases and highlight practical appropriate suggestions for how to incorporate this technology into clinical practice.

[Noninvasive estimation of fibrosis in chronic viral hepatitis]. / Noninvasiv vurdering af fibrose ved kronisk viral hepatitis.

In chronic viral hepatitis the liver biopsy helps the clinician to decide when to start treatment and plan follow-up. However, the execution of a liver biopsy is associated with discomfort, and sampling error can lead to misinterpretation. Serum markers and transient elastography (TE) are being considered as surrogates to the liver biopsy. The noninvasive tests are considered equal in identifying significant fibrosis, but TE is superior in identifying cirrhosis.

Computed tomography findings for predicting severe acute hepatitis with prolonged cholestasis.

AIM: To evaluate the significance of computed tomography (CT) findings in relation to liver chemistry and the clinical course of acute hepatitis. METHODS: Four hundred and twelve patients with acute hepatitis who underwent enhanced CT scanning were enrolled retrospectively. Imaging findings were analyzed for the following variables: gallbladder wall thickness (GWT), arterial heterogeneity, periportal tracking, number and maximum size of lymph nodes, presence of ascites, and size of spleen. The serum levels of alanine aminotransferase, alkaline phosphatase, bilirubin, albumin, and prothrombin time were measured on the day of admission and CT scan, and laboratory data were evaluated every 2-4 d for all subjects during hospitalization. RESULTS: The mean age of patients was 34.4 years, and the most common cause of hepatitis was hepatitis A virus (77.4%). The mean GWT was 5.2 mm. The number of patients who had findings of arterial heterogeneity, periportal tracking, lymph node enlargement > 7 mm, and ascites was 294 (80.1%), 348 (84.7%), 346 (84.5%), and 56 (13.6%), respectively. On multivariate logistic regression, male gender [odds ratio (OR) = 2.569, 95%CI: 1.477-4.469, P = 0.001], toxic hepatitis (OR = 3.531, 95%CI: 1.444-8.635, P = 0.006), level of albumin (OR = 2.154, 95%CI: 1.279-3.629, P = 0.004), and GWT (OR = 1.061, 95%CI: 1.015-1.110, P = 0.009) were independent predictive factors for severe hepatitis. The level of bilirubin (OR = 1.628, 95%CI: 1.331-1.991, P < 0.001) and GWT (OR = 1.172, 95%CI: 1.024-1.342, P = 0.021) were independent factors for prolonged cholestasis in multivariate analysis. CONCLUSION: In patients with acute hepatitis, GWT on CT scan was an independent predictor of severe hepatitis and prolonged cholestasis.

Are different cut-off values of liver stiffness assessed by transient elastography according to the etiology of liver cirrhosis for predicting significant esophageal varices?

AIM: To determine if liver stiffness (LS) measurements by means of Transient Elastography (TE) vary according to the etiology of the underlying liver cirrhosis and to find if there are different TE cut-off values able to predict the presence of significant EV in alcoholic vs. viral etiology of cirrhosis. METHODS: This retrospective study included patients diagnosed with liver cirrhosis of viral or alcoholic etiology. All patients were evaluated by means of TE (FibroScan) and upper gastrointestinal endoscopy. We performed 10 LS measurements in each patient and a median value expressed in kiloPascals (kPa) was calculated. Only those with a SR >/= 60% and an IQR<30% were considered as reliable MS measurements. According to the presence of EV the patients were divided in two categories: without significant EV and patients with significant EV (at least grade 2). RESULTS: The study included 697 cirrhotic patients with reliable LS measurements. The median LS values assessed by TE were significantly higher in cirrhotic patients with alcoholic etiology as compared with those with viral etiology of liver disease: 41 kPa vs. 21.1 kPa, p<0.0001. In the entire cohort of cirrhotic patients, LS assessed by means of TE for a cut-off value >29.5 kPa, had 77.5% sensitivity and 86.9% specificity for predicting the presence of significant EV (AUROC=0.871). The best LS cut-off value for predicting the presence of significant EV was higher in alcoholic cirrhosis as compared with those with viral etiology of liver cirrhosis: 32.5 kPa (AUROC=0.836) vs. 24.8 kPa (AUROC=0.867). CONCLUSIONS: LS cut-off values assessed by TE for predicting significant EV are significantly higher in patients with alcoholic cirrhosis as compared with patients with liver cirrhosis of viral etiology.