Higher Liver Stiffness Values Research Articles

Age, Sex, and Body Mass Index Should Be Considered When Assessing Spleen Length in Patients with Compensated Advanced Chronic Liver Disease.

We investigated the factors related to spleen length and the diagnostic accuracy of a model using spleen length corrected by related factors, for the prediction of varices needing treatment (VNT). Various prediction models for VNT including spleen length were analyzed in the cohort of compensated advanced chronic liver disease (cACLD), defined as liver stiffness (LS) ≥10 kPa in a recent study. The associated factors for spleen length were identified in healthy subjects to improve the prediction of VNT. Among 1,218 cACLD patients, VNT was noted in 249 patients (20.4%). On multivariate analysis, longer spleen length, lower platelet count, and higher LS value were independent predictors for VNT (all p<0.001). In multivariate analysis of 1,041 healthy subjects, age (β=-0.027), sex (β=0.762), and body mass index (β=0.097) were found to be significant factors for spleen length (all p<0.001). Using the β values, the estimated spleen length was calculated. To improve the prediction of VNT, the ratio of measured and estimated spleen length was calculated. Based on binary regression analysis results, the LS value-spleen ratio to platelet score (LSRPS) was calculated as follows: 0.027×LS value (kPa)+2.690×measured/estimated spleen ratio-0.011×platelet count (cells×109/L)-4.215. The area under the receiver operating characteristic of the LSRPS for VNT was 0.820, which was significantly higher than 0.797 of LS value-spleen diameter to platelet ratio score (LSPS) (p=0.006). Spleen length is influenced by age, sex, and body mass index in the Asian population. The LSRPS using the measured/estimated spleen ratio had higher diagnostic accuracy than LSPS in predicting VNT in patients with cACLD.

S1331 Comparison of Liver Elastography Between Obese and Non-Obese Children: A Systematic Review and Meta-Analysis

Introduction: Non-invasive Liver fibrosis evaluation in suspected NAFLD has been studied in obese adults, but few studies have addressed the utility of Transient and Shear-wave Elastography assessing early-stage fibrosis in pediatric population. We aimed to perform a systematic review and meta-analysis to compare Liver Elastography findings between obese and non-obese children. Methods: PubMed, MEDLINE (OVID), Cochrane Library, Embase, Scopus and Web of Science were searched from inception to January 2022 to identify manuscripts that evaluated Liver steatosis/Liver fibrosis on Elastography (Transient or Shear-wave) in obese children compared to non-obese children. Case series, case reports, editorials, and reviews were excluded. Two independent reviewers extracted data. Disagreements were resolved by a third author. Meta-analyses were performed using a random-effect model with the inverse variance method. We used the Paule-Mandel estimator and Hartung-Knapp-Sidik-Jonkman method for τ2 and 95% confidence intervals calculation. For continuous outcomes we used the Mean Difference (MD). Heterogeneity was assessed by the inconsistency index (I2). Results: Among 3182 articles identified, 17 studies were identified for full text review. Five studies were deemed eligible for inclusion with perfect agreement between investigators (kappa=1.0). A total of 296 obese children and 528 non-obese controls were included in the studies (Table). Three studies used Shear-wave Elastography, four used Transient Elastography and one used both. The female proportion was higher in the non-obese group. ALT and AST values were higher in the obese group in most of the studies. On the non-stratified meta-analysis obese children were found to have higher values of Liver Stiffness Measurement (LSM) measured in kilopascals (kPa) compared with non-obese controls (MD: 1.80, 95% CI: 0.27 - 3.34), however, when stratifying this effect was only significant when using only Transient Elastography (MD: 1.49, 95%: 0.16 - 2.82) (Figure). Conclusion: Our systematic review and meta-analysis demonstrates that obese children present higher values of Liver Stiffness compared to non-obese children. In that sense, this non-invasive testing could be successfully applied as a predictor of NAFLD in the clinical setting. These findings may depend on the elastography type, since it was significant using the Transient Elastography, and more studies are needed to further validate this non-invasive testing.Figure 1.: Forest plot of the effect in Liver stiffness Measurement (kPa) Table 1. - Baseline Characteristics of Included Subjects Study Group Sample size Age (years) Female % ALT AST Total Cholesterol Triglycerides Saglam (2021) Obese 41 11.4 (9.6-13.5) 46.3% 18 (15-22) 21 (19-23) 156 (142-172.75) mg/dl 107.5 (87-135.5) mg/dl Non-obese 25 11.7 (9-13.2) 52% 13 (10.1-16.2) 23 (17.7-25.3) 137.5 (128-149.75) mg/dl 68 (59.25-98.25) mg/dl Zeng Fansen (2020) Obese 67 10.9 (6-17.4) 28.4% 59 (23-101) 32 (21-58) 4.7 (4.3-5.7) mmol/L 1.4 (0.9-1.9) mmol/L Non-obese 139 10.2 (5-17) 41.7% 19 (15-25) 27 (16-34) 3.1 (2.8-3.3) mmol/L 1.1 (0.8-1.3) mmol/L Mărginean (2019) Obese 77 10.4 ± 3.4 33.7% 26.50 ± 43.1 27.33 ± 23.6 NA NA Non-obese 210 11.3 ± 3.83 54.8% 13.64 ± 6.9 22.29 ± 10.9 NA NA Kwon (2019) Obese 59 10.9 ± 2.4 38% 91.27 ± 97.7 57.00 ± 48.5 173.97 ± 37.23 mg/dl NA Non-obese 47 10.1 ± 2.8 40% 16.28 ± 9.8 26.40 ± 11.8 146.65 ± 59.07 mg/dl NA Cho Y (2015) Obese 52 13.0 (3.5-17.6) 26.9% 75 ± 83 48 ± 45 NA 149 ± 73 mg/dl Non-obese 107 11.2 (1.3-17) 49.5% 17 ± 14 24 ± 7 NA 97 ± 65 mg/dl

Combined Liver Stiffness and Α-fetoprotein Further beyond the Sustained Virologic Response Visit as Predictors of Long-Term Liver-Related Events in Patients with Chronic Hepatitis C.

Aims Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5–8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 [1.6–6.4] years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio [aHR] = 3.980, 95% confidence interval [CI] = 2.085–7.597, P < 0.001), and α-fetoprotein (AFP) at Y3PSVR (aHR = 1.017, 95% CI = 1.001–1.034, P=0.034). LS ≥1.45 m/s and AFP ≥3.00 ng/mL for Y3PSVR yielded positive likelihood ratios of 4.24 and 2.62, respectively. Kaplan–Meier analysis revealed that among the stratified subgroups, the subgroup with concurrent LS ≥1.45 m/s and AFP ≥3.00 ng/mL at Y3PSVR exhibited the highest risk of LREs after Y3PSVR (log-rank P < 0.001). Conclusion We recommend the combined use of concurrent LS and AFP in future prediction models for LREs in CHC. Patients with concurrently high LS and AFP values further beyond the SVR visit may require a recall policy involving intense surveillance.

Liver Fibrosis Assessment by Viewing Sinusoidal Capillarization: US Molecular Imaging versus Two-dimensional Shear-Wave Elastography in Rats.

Background US elastography is a first-line assessment of liver fibrosis severity; however, its application is limited by its insufficient sensitivity in early-stage fibrosis detection and its measurements are affected by inflammation. Purpose To assess the sensitivity of US molecular imaging (USMI) in early-stage liver fibrosis detection and to determine whether USMI can specifically distinguish fibrosis regardless of inflammation when compared with two-dimensional (2D) shear-wave elastography (SWE). Materials and methods USMI and 2D SWE were performed prospectively (January to June 2021) in 120 male Sprague-Dawley rats with varying degrees of liver fibrosis and acute hepatitis and control rats. Liver sinusoidal capillarization was viewed at CD34-targeted USMI and quantitatively analyzed by the normalized intensity difference (NID). Data were compared by using a two-sided Student t test or one-way analysis of variance. Linear correlation analyses were used to evaluate the relationships between collagen proportionate area values and NID and liver stiffness measurement (LSM) values. Receiver operating characteristic curves were used to assess the diagnostic performance in detecting liver fibrosis. Results Both NID and LSM values showed good linear correlation with collagen proportionate area values (r = 0.91 and 0.87, respectively). No difference was observed between the areas under the receiver operating characteristic curve in detecting stage F0-F1 between USMI and 2D SWE (0.97 vs 0.91, respectively; P = .20). USMI depicted liver fibrosis at an early stage more accurately than 2D SWE (area under the curve, 0.97 vs 0.82, respectively; P = .01). Rats with hepatitis had higher liver stiffness values than control rats (9.83 kPa ± 0.79 vs 6.55 kPa ± 0.38, respectively; P < .001), with no difference in the NID values between control rats and rats with hepatitis (6.75% ± 1.43 vs 6.74% ± 0.86, respectively; P = .98). Conclusion Sinusoidal capillarization viewed at US molecular imaging helped to detect early-stage liver fibrosis more accurately than two-dimensional shear-wave elastography and helped assess fibrosis regardless of inflammation. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Barr in this issue.

Novel Liver Stiffness-Based Nomogram for Predicting Hepatocellular Carcinoma Risk in Patients with Chronic Hepatitis B Virus Infection Initiating Antiviral Therapy.

Simple SummaryWe developed a novel risk-scoring model for hepatocellular carcinoma development in treatment-naïve patients with chronic hepatitis B virus infection who are starting antiviral therapy with entecavir or tenofovir. The model reflects age, platelet count, hepatitis B e antigen positivity, serum albumin and total bilirubin levels, cirrhosis development, and liver stiffness values measured by transient elastography. Our new model showed better performance for predicting hepatocellular carcinoma development (Harrell’s c-index: 0.799) than the PAGE-B, modified PAGE-B, and modified REACH-B models in Asian patients with chronic hepatitis B receiving potent antiviral therapy.Hepatocellular carcinoma (HCC) risk prediction is important to developing individualized surveillance approaches. We designed a novel HCC prediction model using liver stiffness on transient elastography for patients receiving antiviral therapy against hepatitis B virus (HBV) infection. We recruited 2037 patients receiving entecavir or tenofovir as first-line antivirals and used the Cox regression analysis to determine key variables for model construction. Within 58.1 months (median), HCC developed in 182 (8.9%) patients. Patients with HCC showed a higher prevalence of cirrhosis (90.7% vs. 45.9%) and higher liver stiffness values (median 13.9 vs. 7.2 kPa) than those without. A novel nomogram (score 0–304) was established using age, platelet count, cirrhosis development, and liver stiffness values, which were independently associated with increased HCC risk, along with hepatitis B e antigen positivity and serum albumin and total bilirubin levels. Cumulative HCC probabilities were 0.7%, 5.0%, and 22.7% in the low- (score ≤87), intermediate- (88–222), and high-risk (≥223) groups, respectively. The c-index value was 0.799 (internal validity: 0.805), higher than that of the PAGE-B (0.726), modified PAGE-B (0.756), and modified REACH-B (0.761) models (all p < 0.05). Our nomogram showed acceptable performance in predicting HCC in Asian HBV-infected patients receiving potent antiviral therapy.

No influence of hepatic steatosis on the 3-year outcomes of patients with quiescent chronic hepatitis B.

The influence of hepatic steatosis on the natural history of chronic hepatitis B (CHB) virus is unclear. Therefore, we investigated whether concurrent steatosis in patients with CHB influences the probability of hepatitis B surface antigen (HBsAg) loss, fibrosis progression and hepatocellular carcinoma (HCC) development. This study enrolled treatment-naïve patients with virologically (HBV DNA <2,000IU/ml) and biochemically (alanine aminotransferase level <40IU/L) quiescent CHB who underwent transient elastography between January 2004 and December 2015 and completed 3years of follow-up. RESULTS: The mean age of the study population (n=720) was 52.0years, and there were more men than women (n=419, 58.2%). The mean HBV DNA level was 321.6IU/ml. During the 3-year period, 74 (10.3%) patients achieved HBsAg seroclearance. Lower HBV DNA levels (hazard ratio=0.995, p<.05) were independently associated with HBsAg seroclearance, while hepatic steatosis was not (p>.05). Fibrosis progressed in 89 (12.4%) patients. Male gender (odds ratio [OR]=1.720) and higher body mass index (OR=1.083) were independently associated with an increased probability of fibrosis progression (all p<.05), while higher total cholesterol levels (OR=0.991) and higher liver stiffness values (OR=0.862) were independently associated with a decreased probability of fibrosis progression (all p<.05). HCC developed in 46 (6.4%) patients. Male gender (OR=3.917) and higher AST levels (OR=1.036) were independently associated with an increased probability of HCC development (p<.05). Hepatic steatosis was not associated with the probability of HBsAg seroclearance, fibrosis progression or HCC development in patients quiescent CHB in our study. Further studies with longer follow-up periods are required to validate our findings.

High liver stiffness values by transient elastography related to metabolic syndrome and harmful alcohol use in a large Spanish cohort.

Background and AimsTransient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort.MethodNested study within the PREVHEP‐ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population‐based, cross‐sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained.ResultsData from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP‐III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02–1.04; p < 0.001]), sex (OR 0.8 [0.6–0.95; p = 0.02]), AST (OR 1.01 [1.01–1.02; p < 0.001]), GGT (OR 1.005 [1.003–1.006; p < 0.001]) and metabolic syndrome (OR 2.1 [1.7–2.6; p < 0.001]); risk factors associated with suggestive cACLD were age (OR 1.04 [1.02–1.05; p < 0.001]), AST (OR 1.01 [1.01–1.02; p < 0.001]), GGT (OR 1.006 [1.004–1.008; p < 0.001]), low platelets (OR 0.997 [0.994–0.999; p = 0.02]) and metabolic syndrome (OR 2.2 [1.6–2.9; p < 0.001]); and risk factors associated with highly suggestive cACLD were age (OR 1.04 [1.02–1.06; p = 0.001]), AST (OR 1.02 [1.01–1.03; p < 0.001]), GGT (OR 1.005 [1.003–1.007; p < 0.001]), low platelets (OR 0.993 [0.989–0.997; p < 0.001]), metabolic syndrome (OR 2.1 [1.4–3.3; p = 0.001]) and alcohol consumption (OR 1.8 [1.05–3.1; p = 0.03]). A non‐negligible proportion of patients with normal transaminase levels, even with healthy transaminase levels, showed significant fibrosis and suggestive and highly suggestive cACLD 4.6% (95% CI 2.4–3.0), 2.1% (95% CI 1.9–2.5) and 1% (95% CI 0.7–1.1), respectively.ConclusionWe found high proportion of significant fibrosis and cACLD measured by TE. The most relevant factor associated with significant fibrosis was metabolic syndrome, however TE is still an imperfect method since it overestimated the fibrosis stage in 50% of the histologically analyzed subjects.

Higher liver stiffness in patients with chronic congestive heart failure: data from NHANES with liver ultrasound transient elastography.

Liver stiffness in patients with chronic congestive heart failure (CCHF) is poorly understood and liver ultrasound transient elastography (LUTE) is a new non-invasive method to detect this condition. In this cross-sectional study we explored liver stiffness and secondary congestive hepatopathy in patients with CCHF detected by LUTE. Data from the National Health and Nutrition Examination Survey (NHANES 2017-2018) were analyzed. All participants undergoing LUTE and without liver disease were included, among whom, 110 participants were diagnosed with CCHF. The cut-off values of stiffness for fibrosis and cirrhosis were above 7.65 and 13.01 kPa, respectively. Data regarding liver stiffness were compared between the participants with and without CCHF. Among patients with CCHF, the median liver stiffness was 6.0 kPa, above 7.65 kPa in 32.7% of patients, and above 13.01 kPa in 14.6% of patients. The mean liver stiffness was 5.0 kPa in the control group and was significantly lower than that of patients with CCHF (P<0.001). The ratio of serum albumin/globulin (A/G) gradually decreased according to the liver stiffness of patients with CCHF (P=0.03). Patients with CCHF had higher liver stiffness values than controls, nearly one-third had substantial fibrosis, and more than one in seven patients progressed to cirrhosis. The A/G ratio may be a potential biomarker for liver stiffness caused by CCHF.

Risk of Liver Fibrosis According to TSH Levels in Euthyroid Subjects.

Alterations in thyroid function may contribute to the development of liver fibrosis especially in subjects with non-alcoholic fatty liver disease. This study aimed to investigate the risk of liver fibrosis according to low-normal thyroid function in the general population. We performed a descriptive cross-sectional study in subjects from 18–75 years randomly selected from 16 primary health care centers from 2017–2019. Each subject underwent clinical evaluation, physical examination, blood analysis and transient hepatic elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with fibrosis. We included 1096 subjects (60 ± 11 years; 61% women); 70% had strict-normal thyroid function and 30% had low-normal thyroid function. Low-normal thyroid function was associated with a higher liver stiffness (LS) values: 5.2 vs. 4.8 kPa (p = 0.001) and a greater prevalence of fibrosis: 6.1 vs. 3% (p = 0.016) and 4.3 vs. 2.1% (p = 0.044) for the cut-off points of ≥8.0 kPa and ≥9.2 kPa, respectively. After adjustment for potential confounding factors, the risk of fibrosis in subjects with low-normal thyroid function was OR 1.54 (p = 0.213). In conclusion, low-normal thyroid function is associated with higher LS values and a greater risk of liver fibrosis in the general population, being dependent on other metabolic factors.

Liver and spleen elastography of dogs affected by brachycephalic obstructive airway syndrome and its correlation with clinical biomarkers

The purpose of this study is to determine whether the brachycephalic obstructive airway syndrome (BOAS) is correlated to alterations in liver and spleen elasticity. Forty-eight brachycephalic and 22 mesocephalic dogs were submitted to a BOAS functional assessment, laboratory tests, abdominal ultrasound and liver and spleen Acoustic Radiation Force Impulse (ARFI) elastography. Dogs clinically affected by BOAS had higher values of liver stiffness (p < 0.001) than healthy dogs: medial lobes (1.57 ± 0.37 m/s), left and right lateral lobes (1.54 ± 0.50 m/s, 1.23 ± 0.28 m/s, respectively) and caudate lobe (1.28 ± 0.42 m/s). Compared to the mesocephalic group, the brachycephalic group (BOAS clinically affected and unaffected dogs) had higher spleen (2.51 ± 0.45 m/s; p < 0.001) and liver stiffness (p < 0.001): medial lobes (1.53 ± 0.37 m/s), left and right lateral lobes (1.47 ± 0.47 m/s, 1.20 ± 0.30 m/s, respectively) and caudate lobe (1.23 ± 0.40 m/s). Principal component analysis explained 70% of the variances composed by liver stiffness increase, erythrocytes and alanine aminotransferase reduction. Brachycephalic dogs had higher spleen and liver stiffness and a subacute inflammatory state, which represent another BOAS systemic effect. Consequently, these dogs can be at higher risk of hepatic disorders compared with mesocephalic dogs, similarly to humans affected by sleep apnea syndrome.

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics.

Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.

Comparison of hepatic and splenic stiffness in chronic hepatitis C infection with and without schistosomal infection; correlation with hepatic histopathological changes.

Aim of the studyTo assess the degree of liver and spleen stiffness in chronic hepatitis C virus (HCV) patients co-infected with schistosomiasis, and chronic HCV mono-infected patients.Material and methodsThe present study was conducted on 50 Egyptian chronic HCV patients, categorized into two groups: group A (25 patients with chronic HCV mono-infection) and group B (25 patients with chronic HCV and schistosomiasis coinfection). Also, 25 age- and sex-matched healthy subjects with no evidence of liver disease were included in the study as a control group. Stage of fibrosis was assessed invasively by histopathological examination of liver biopsies (patients only) and non-invasively by acoustic radiation force impulse imaging (ARFI) (all subjects).ResultsARFI of liver (ARFI L) and ARFI of spleen (ARFI S) in group A patients who had significant fibrosis were 1.82 ±0.24 and 2.72 ±0.26, respectively, while in group B, ARFI L and ARFI S in patients with significant fibrosis was 1.99 ±0.53 and 3.10 ±0.57, respectively.ConclusionsThe current study demonstrated insignificantly higher values of liver stiffness and significantly higher values of spleen stiffness assessed by ARFI in patients co-infected with HCV and schistosomiasis than mono-infected with HCV.

The assessment of liver fibrosis in children with obesity on two methods: transient and two dimensional shear wave elastography

The aim of this study was to assess the liver stiffness values in children with obesity versus healthy children on 2D-SWE and TE taking into account different laboratory parameters. We performed a case-control study on 287 children aged between 3 to 18 years, admitted in a Romanian Pediatric Tertiary Hospital, which we divided according to the body mass index (BMI) into two groups: the study group-77 children with obesity, and control group-210 children with normal weight. All children underwent anamnesis, clinical exam, laboratory parameters, ultrasound exam, and elastography. Children with obesity presented higher values of platelets, AST, ALT, and AAR as compared to control group (p = 0.0005/p = 0.0065/p < 0.0001/p < 0.0001). We found no significant differences for APRI between the two groups (p = 0.9827), although the values were higher in children with obesity. Significantly higher values of liver stiffness in children with obesity on both 2D-SWE and TE (p = 0.0314/p < 0.0001) were obtained. Similarly, the velocity values measured by 2D-SWE were also significantly higher in the study group (p < 0.0001). Our findings revealed significantly higher levels of platelets, transaminases, AAR, and liver stiffness values on both TE and 2D-SWE in children with obesity. 2D-SWE and TE might represent useful non-invasive methods for predicting liver impairment associated to pediatric obesity.

Spleen stiffness to liver stiffness ratio significantly differs between ALD and HCV and predicts disease-specific complications.

Background & AimsBoth liver stiffness (LS) and spleen stiffness (SS) are widely used to non-invasively assess liver fibrosis and portal hypertension, respectively. We aimed to identify the impact of disease etiology, namely the localization of inflammation (portal vs. lobular), on the SS/LS ratio.MethodsIn this multicenter study, LS and SS were prospectively assessed in 411 patients with alcohol-related liver disease (ALD) or hepatitis C virus (HCV) using FibroScan® (Echosens, Paris); changes in these parameters were also studied in response to treatment (alcohol withdrawal, HCV therapy). LS and spleen length (SL) were further analyzed in a retrospective cohort of 449 patients with long-term data on decompensation/death.ResultsBoth, SS and SL were significantly higher in HCV compared to ALD (42.0 vs. 32.6 kPa, p≪0.0001, 15.6 vs. 11.9 cm, p≪0.0001) despite a lower mean LS in HCV. Consequently, the SS to LS ratio and the SL to LS ratio were significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, p≪0.0001) through all fibrosis stages. Notably, SL linearly increased with SS and the relation between SS and SL was identical in HCV and ALD. In contrast, livers were much larger in ALD at comparable LS. After treatment, LS significantly decreased in both diseases without significant changes to the SS/LS ratio. In the prognostic cohort, patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%); liver failure was the major cause of death (p≪0.01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (p≪0.001).ConclusionBoth SS/LS and SL/LS ratios are significantly higher in patients with portal HCV compared to lobular ALD. Thus, combined LS and SS or SL measurements provide additional information about disease etiology and disease-specific complications.Lay summaryHerein, we show that patients with hepatitis C virus infection (HCV) have higher spleen stiffness and portal pressure than patients with alcohol-related liver disease (ALD), within the same fibrosis stage and matched to liver stiffness. Thus, the spleen stiffness to liver stiffness ratio is significantly higher in patients with HCV compared to ALD. Additionally, patients with HCV more commonly progress to portal hypertension-related complications (e.g. variceal bleeding), while patients with ALD more commonly progress to liver failure (e.g. jaundice). The spleen stiffness to liver stiffness ratio is a useful tool to confirm disease etiology and predict disease-specific complications.

Hepatic Changes in the Fontan Circulation: Identification of Liver Dysfunction and an Attempt to Streamline Follow-up Screening.

We tried to identify structural and functional liver aberrances in a palliated Fontan population and sought to determine useful screening modalities, in order to propose a screening protocol to detect patients at risk. Twenty nine patients, median age 23.7years (interquartile range (IQR) 20.5-27.2) and median Fontan interval 19.7years (IQR 4.5-21.4), were prospectively studied with echocardiography, blood analysis (including serum fibrosis scores Forns, APRI and FIB4), liver imaging (ultrasound (US), Doppler), and shear wave elastography to determine liver stiffness (LS). Laboratory tests predominantly showed abnormal values for gamma-glutamyltransferase. Forns index indicated moderate fibrosis in 29% of patients and correlated with Fontan interval (p = 0.034). US liver morphology was deviant in 46% of patients, with surface nodularity in 21% and nodular hyperplasia in 29%. Doppler assessment of flow velocities was within normal ranges for most patients. LS (mean 10.4±3.7kPa) was elevated in 96% of our population and higher LS values were significantly related to longer Fontan interval (p = 0.018). Adolescent and adult Fontan patients show moderate signs of liver dysfunction. Usefulness of serum parameters and fibrosis scores in post-Fontan screening remains ambiguous. The high percentage of morphologic liver changes in palliated patients supports the use of US in periodic follow-up. LS likely overestimates fibrosis due to liver congestion, arguing for the need of validation through sequential measurements. Screening should minimally encompass US assessment in combination with selective liver fibrosis scores. The role of LS measurement in Fontan follow-up and liver screening needs to be further elucidated.

Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis

The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness. We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis. Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79-0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82-0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86-0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83-0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (p<0·0001), and with significantly higher cutoff values for diagnosis of all fibrosis stages but F≥1. The presence of histological features of asymptomatic and non-severe alcoholic hepatitis was associated with increased liver stiffness (p<0·0001). In a multivariate analysis, AST (p<0·0001) and bilirubin (p=0·0002) concentrations, and prothrombin activity (p=0·01), were independently associated with the presence of histological features of asymptomatic and non-severe alcoholic hepatitis. Lastly, specific liver stiffness cutoffs were determined on the basis of concentrations of AST and bilirubin. Liver stiffness cutoff values increased in patients with increased AST concentrations, bilirubin concentrations, or both. This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs. None.

Prediction of major complications after hepatectomy using liver stiffness values determined by magnetic resonance elastography.

Liver fibrosis is a risk factor for hepatectomy but cannot be determined accurately before hepatectomy because diagnostic procedures are too invasive. Magnetic resonance elastography (MRE) can determine liver stiffness (LS), a surrogate marker for assessing liver fibrosis, non-invasively. The aim of this study was to investigate whether the LS value determined by MRE is predictive of major complications after hepatectomy. This prospective study enrolled consecutive patients who underwent hepatic resection between April 2013 and August 2016. LS values were measured by imaging shear waves by MRE in the liver before hepatectomy. The primary endpoint was major complications, defined as Clavien-Dindo grade IIIa or above. Logistic regression analysis identified independent predictive factors, from which a logistic model to estimate the probability of major complications was constructed. A total of 96 patients were included in the study. Major complications were observed in 15 patients (16 per cent). Multivariable logistic analysis confirmed that higher LS value (P = 0·021) and serum albumin level (P = 0·009) were independent predictive factors for major complications after hepatectomy. Receiver operating characteristic (ROC) analysis showed that the best LS cut-off value was 4·3 kPa for detecting major complications, comparable to liver fibrosis grade F4, with a sensitivity of 80 per cent and specificity of 82 per cent. A logistic model using the LS value and serum albumin level to estimate the probability of major complications was constructed; the area under the ROC curve for predicting major complications was 0·84. The LS value determined by MRE in patients undergoing hepatectomy was an independent predictive factor for major complications.

A case of severe stenosis of hepatic veins and inferior vena cava with stomal variceal bleeding induced by oxaliplatin-based chemotherapy

A 27-year-old woman with colon cancer and liver metastasis was referred to our hospital. Colectomy and colostomy were performed to improve her ileus. Following 13 sessions of oxaliplatin-based chemotherapy (OC) with mFOLFOX6+bevacizumab, thrombocytopenia and frequent peristomal bleeding occurred. Computed tomography showed severe ascites, splenomegaly, significant collateral veins around the stoma, and severe stenosis of the hepatic veins (HV) and inferior vena cava (IVC). Ultrasound elastography showed high liver (and spleen) stiffness values. Repeated OC appeared to cause IVC stenosis as a result of worsening sinusoidal obstruction syndrome (SOS), and peristomal variceal bleeding. After ultrasound-guided percutaneous embolization, bleeding did not recur. Unfortunately, the patient died of liver dysfunction caused by severe SOS. The incidence of OC-induced SOS is reported to be about 50%; however, there is apparently no report of OC-induced HV and IVC stenosis, and in most cases, portal hypertension is improved after OC cessation. This is the first report of OC-induced severe HV and IVC stenosis resulting in refractory peristomal variceal bleeding and eventual death.

Liver stiffness measurement predicts hepatocellular carcinoma development in patients treated with direct-acting antivirals.

Background and AimPredictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct‐acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA.MethodsIn this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC.ResultsThe median LS value according to ARFI measurements was 1.34 m/s (range: 0.67–4.35). During the follow‐up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13–27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63–13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66–10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62–43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC.ConclusionThe LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.

Improvement of Liver Fibrosis after Long-Term Antiviral Therapy Assessed by Fibroscan in Chronic Hepatitis B Patients With Advanced Fibrosis

Performing repeated liver biopsies to assess the improvement of liver fibrosis is impractical. The purpose of this prospective cohort study was to assess the improvement of liver fibrosis during antiviral treatment by serial liver stiffness (LS) measurement using Fibroscan in chronic hepatitis B (CHB) patients with advanced fibrosis. Nucleos(t)ide analog-naive CHB patients with advanced fibrosis in histological findings (stage ≥F3), high viral load (hepatitis B virus DNA ≥2,000 IU/ml), and normal liver enzyme levels (<2 × upper normal limit) before starting antiviral treatment were included in this study. LS measurement was performed at baseline and annually for 5 years during antiviral treatment. Five-year fibrosis improvement was defined as LS value <7.2 kPa (<F3) at year 5. The mean LS value of 120 patients significantly decreased over time (14.5 kPa at baseline; 11.3 kPa at year 1; 9.6 kPa at year 2; 9.3 kPa at year 3; 8.6 kPa at year 4; and 8.3 kPa at year 5). Multivariate analysis showed that baseline LS value was the only predictor of 5-year fibrosis improvement (odds ratio, 0.907; 95% confidence interval, 0.838-0.980; P=0.014). Patients with low baseline LS values (<12.0 kPa) had a greater probability of experiencing significant fibrosis improvement than those with high baseline LS values (≥12.0 kPa) (81.5% vs. 29.0%, P<0.001). In CHB patients with advanced fibrosis receiving antiviral treatment, annual LS measurement revealed that fibrosis improvement slows but continues during treatment. Low LS value (<12.0 kPa) at baseline was a significant predictor for 5-year fibrosis improvement.