Introduction

Liver stiffness measurements has become a "gold standard" for liver fibrosis assessment. New techniques based on the same physical principles have become available, but little is known about their comparative efficacy, especially in subjects with non-alcoholic fatty liver disease.

Aims & Methods

Aim: to compare the data of liver stiffness measurement with the use of FibroScan 502 (EchoSens, France) and iLivTouch FT200 (Wuxi Hisky Medical Technologies Co., China) devices.
Method:
Subjects with non-alcoholic fatty liver disease (per EASL guidelines) who gave informed consent were eligible for the study (NCT05224037 at clinicaltrials.gov). All participants were examined on the same day with the use of both, iLivTouch FT200 (Wuxi Hisky Medical Technologies Co., China) (data are marked as LT) with a standard sensor, and Fibroscan 502 (EchoSens, France) with M or XL sensors depending on the patient's characteristics (FS). We compared the efficacy of examination and analyzed the results obtained with both devices depending on the stage of liver fibrosis. The null hypothesis was the absence of differences between the data obtained using both devices.

Results

The data of 105 people (58 women, mean age per group 52.8±12.6 years, BMI: 32.3±9.48 kg/m²) were available. Success rate for FS was 68.7 ± 29% compared to LT: 86.9±19%; p<0.001. In 5 patients, it was impossible to conduct examination with FS, while it was possible to obtained at least 10 measurements using LT (in all cases BMI was >35 kg/m²). In 1 case, it was not possible to obtain sufficient number of measurements with LT, although FS gave successful result.
There was significant direct correlation between the data of liver stiffness measurements obtained with both devices: Spearman rank R=0.56. However, comparison revealed significant difference in values: 9.6±6.6 kPa with LT vs 6.9±4.5 kPa using FS, p<0.0001.
In patients with NAFLD with advanced stages of liver fibrosis (F2+, n=29) the values of FS and LT were similar: 11.8±5.9 kPa for FS vs 13.9±7.9 kPa for LT, p=0.2. However, the values of liver stiffness differed significantly when subjects had milder stages (F0-1, n=71,) of liver fibrosis: 4.9±1.0 kPa for FS vs 7.4±3.0 kPa, p<0.001. The agreement in liver fibrosis stage assessment (using cut-off values provided by the manufacturers) were as follows: for F0 - 56.9%, for F1-42.9%, F2-43.8%, F3-66.7%, and F4-70% of cases.

Conclusion

The results of liver stiffness obtained with Fibroscan and iLivTouch correlate closely. However, the agreement between studied techniques in subjects with non-alcoholic fatty liver disease is low.To make the measurements obtained with iLivTouch more accurate it may be necessary to develop new cut-off values that corresponds with different stages of liver fibrosis.
This work was performed with financial support of Ministry of Science and Higher Education of Russia, research grant No. FGMF-2022–0005

Introduction

Non-alcoholic fatty liver disease (NAFLD) can progress to fibrosis and cirrhosis. The evaluation of fibrosis in chronic liver disease using non-invasive methods is a current topic. Standard methods are liver stiffness measurement and serum biomarkers. Splenic elasticity measurement is a recent and interesting non-invasive approach that arouses the interest of the latest studies to evaluate fibrosis severity in NAFLD.
The aim of this study is to identify patients with NAFLD and advanced liver fibrosis, by establishing correlations between splenic and liver elasticity and fibrosis serum biomarkers.

Aims & Methods

This is a prospective study conducted in the hepato-gastroenterology department including all patients followed for hepatic steatosis during the period from July 2022 to January 2023. Patients with a family or personal history of chronic liver disease, and women with acute steatohepatitis in pregnancy or cholestasis in pregnancy were excluded. Measurement of hepatic and splenic stiffness and the degree of hepatic steatosis was done using liver elastrography (Fibroscan®) and Transient elastography with controlled attenuation parameter (CAP), respectively. NAFLD fibrosis (NFS) and Fibrosis-4 scores were calculated. Data were entered and processed using SPSS software version 22.0.

Results

We included 44 patients, divided into 28 women and 16 men (Sex-ratio F/M = 1.75), with a mean age of 61.4 years [32 to 84 years]. Three patients were smokers and four were alcoholics. Hypertension was found in 56.8%, 54.5% were diabetics and 52.3% were dyslipidemics. The mean BMI was 29.6 kg/m²±4.15 kg/m². Obesity was found in 45.5%, 36.4% were overweight and 18.2% of patients were normal weight. Hepatic steatosis was discovered following pain in the right hypochondrium in 79.5% of the cases and in front of a cytolysis in the remaining cases. All patients had diffuse steatosis without portal hypertension or degeneration signs on ultrasound.
Biological results showed cytolysis in seven patients. No patient had cholestasis. All patients had preserved liver function: normal prothrombin level and albumin. Hyperglycemia and lipid disturbance were observed in 43.2% and 36.4% of cases respectively.
Fibrosis was assessed by FIB4 score with a mean value of 1.11± 0.78; NFS score with a mean value of -1.16±1.18 and liver stiffness ranging from 2.4Kpa to 28.4Kpa (mean value 6.67Kpa). The degree of fibrosis judged by Fibroscan results was F0-F1 in 31 cases, F2 in 5 cases, F3 in 5 cases and F4 in 3 cases. Advanced fibrosis was correlated with NFS score (p=0.016), FIB-4 (p=0.001); but not associated with CAP value (p=0.51).
The mean splenic elasticity was 27.57 Kpa (ranging from 8.3 to 75 Kpa). It was significantly associated with liver elasticity (p=0.012) with an AUROC of 0.784. A threshold of 17.4 Kpa was predictive of advanced fibrosis with a specificity of 85.7% and a sensitivity of 73.5% (CI [0.029-0.404]). Similarly, splenic elasticity was correlated with CAP value (p=0.013). No association was identified with NFS and FIB4 scores.

Conclusion

Measurement of splenic elasticity is a simple and reliable non-invasive tool, comparable to liver elasticity, for the prediction of liver fibrosis during NAFLD.

Disclosure

no conflict of interest

Introduction

Currently, about 25-30% of the world population is affected by non-alcoholic fatty liver disease (NAFLD); over time, about 20% tends to develop a certain degree of inflammation in the liver tissue, defying the non-alcoholic steatohepatitis (NASH). Moreover, approximately 20% of NASH patients evolve into a high-grade liver fibrosis condition that leads to severe liver impairment (cirrhosis) (1, 2, 3).
The serial use of non-invasive fibrosis tests can refine prognosis in patients with non-alcoholic fatty liver disease (NAFLD) and evaluate the progression or improvement of liver fibrosis.

Aims & Methods

We evaluated predictors of improvement or worsening of liver stiffness measurements (LSM) in well characterized cohorts of patients with NAFLD from London (UK) and Milan (Italy).
We included two consecutive cohorts of 405 patients with at least two outpatient visits between 2014 and 2022. The minimum time interval between baseline and follow-up LSM was >6 months. LSM worsening was defined as an increase of >20% kPa if the baseline LSM was ≥5 kPa, or a follow-up LSM >6 kPa if the baseline LSM was <5 kPa. An LSM improvement was defined as an LSM decrease of >20% kPa (if the baseline LSM was >6 kPa).
A significant change in weight was defined as a >5% reduction or increase at follow-up, while a significant change in glycated hemoglobin (HbA1c) was defined as a >10% reduction or increase.
The variation between the true and expected FIB-4 index (based on the patient’s age at the follow-up visit, but using the blood tests performed at the first visit) was calculated. A significant improvement or worsening in FIB-4 was defined as a >20% variation between the actual and “expected” FIB-4.

Results

Of the 405 patients, 282 (70%) were males; mean age was 54±11 years. The median time from the first visits was 20.3 (13.9 – 28.7) months.
128 and 54 patients had an LSM >8 kPa and LSM>12 KPa at follow-up, respectively.
77 patients (19.3%) had an LSM improvement, while 67 (16.8%) had an LSM worsening; 256 patients (63.9%) maintained a stable value.
In patients with an LSM improvement, 22 had an improvement, 12 had worsening, while 37 had stable FIB-4.
In patients with an LSM worsening, 10 had an improvement, 20 had worsening, while 33 had a stable FIB-4.
In multiple logistic regression analysis, LSM worsening was independently associated with an increase in ALT and in HbA1c levels (OR 1.02 and 1.03 respectively), but also with a reduction in total cholesterol and AST levels (OR 0.98 for both). LSM improvement was independently associated with weight and ALT reduction (OR 0.93 and 0.98 respectively), but also with an increased AST level (OR 1.02).

Conclusion

More than 35% of patients with NAFLD have significant changes in their LSM measurements over a period of 20 months, with worsening or improvement at similar rates. Improvement in weight is independently associated with significant improvement in LSM measurements. On the converse, worsening in metabolic comorbidities, particularly glycemic control, could be associated with significant worsening in LSM, further supporting a multidisciplinary model of care.

References

1. Younossi Z, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018;15(1):11-20.
2. Sheka AC, et al. Nonalcoholic Steatohepatitis: A Review. JAMA 2020;323(12):1175-1183.
3. Liu J, et al. Estimating global prevalence, incidence, and outcomes of non-alcoholic fatty liver disease from 2000 to 2021: systematic review and meta-analysis. Chin Med J (Engl). 2022 Jul 20;135(14):1682-1691.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a significant health concern. Weight loss is a cornerstone of NAFLD management, yet sustainable weight loss remains challenging. Motivational interviewing (MI) has shown promise as a behaviour change technique. Effectiveness of MI in NAFLD has not been adequately studied, especially among Asians.

Aims & Methods

This randomised controlled trial (NCT06348628) evaluated whether MI improves weight loss in NAFLD patients compared to standard care (SoC). Participants aged 18–60 years with newly diagnosed NAFLD and BMI ≥25 kg/m² were recruited. The intervention group (G1) received SoC plus four MI sessions (at baseline, 1, 3, and 6 months) delivered by trained psychiatrists, incorporating strategies such as agenda setting, exploring pros and cons, and negotiating change plans. The control group (G2) received only SoC. Primary outcomes included weight change, liver biochemistry, liver imaging & stiffness. Secondary outcomes included motivation for weight loss (URICA scale), psychological status (DASS-21), and quality of life (WHO QoL BREF). The analysis evaluated changes in anthropometric and biochemical parameters, psychological aspects, and the influence of baseline factors including demographic characteristics, NAFLD severity and psychological factors on outcomes.

Results

There were 219 participants (G1-107, G2-112). All of them completed the 12-month follow-up, with similar retention observed in both groups. The two groups were comparable at baseline (mean BMI: G1-28.4 kg/m², G2-28.4 kg/m²; DASS 21 for both G1 and G2: no depression, no stress, no anxiety; URICA readiness and motivational stage for both G1 and G2 was contemplation). Only 28% (30/107) of participants attended all four MI sessions. 69.15% (74/107) attended at least three MI sessions.
At 12 months, the mean weight change (mean ± SD) was –4.6±5.5 kg in G1 compared to –4.7± 6.3 kg in G2 (mean difference –0.1 kg, 95% CI: -2.0 to 0.7; p=0.20). There were also no significant differences in other anthropometric and biochemical parameters, ultrasound grade, FIB-4 score, liver stiffness, psychological factors (URICA scores, DASS-21 scores, or WHO QoL-BREF domains) between G1 and G2 (all p>0.05).
We assessed factors associated with attending ≥3 MI sessions. Sociodemographic characteristics (age, gender, occupation, and level of education) showed no significant association with session attendance (all p>0.05). Lower baseline depression score (DASS 21) was significantly associated with ≥3 session attendance [OR 0.92, 95% CI:0.87 to 0.97; p=0.002). Additionally, higher baseline physical QoL (domain 1: pain, sleep, energy, etc) was positively associated with attending ≥3 sessions (OR 1.33, 95% CI:1.19 to 1.63; p=0.002). Baseline anxiety and stress scores (DASS 21), and the other three QoL domains (2-4: psychological, social and environment) were significant in univariate analysis but was not in multivariate analysis. Baseline readiness and motivational stages (URICA scale) were not significantly associated with attendance (p=0.17). Patient’s physical factors like baseline weight and BMI were also not predictive of MI session adherence (p=0.53 and p=0.47, respectively).

Conclusion

Our results suggests that MI was difficult to adhere to and did not produce significant improvements in weight loss in NAFLD compared to SoC. The difficulty in engaging and retaining participants underscores the challenges of MI in this population and highlights the need for alternate behavioural strategies.

Introduction

Liver fibrosis is the main prognostic driver and an independent risk factor for both hepatic and extrahepatic events and global mortality in patients with non-alcoholic fatty liver disease (NAFLD). Thus, many serum markers and scores for the assessment of fibrosis severity have been drawn up. Recently, researchers developed the easy Liver Fibrosis Test (eLIFT) and the BMI, AST/ALT ratio and Diabetes (BARD) score.

Aims & Methods

This study aimed to compare the eLIFT and the BARD scores with Transient Elastography for the assessment of liver fibrosis in obese patients with NAFLD.
We conducted a transversal study including obese patients recruited from the Department of Nutrition referred to our center for screening for liver steatosis and a non-invasive evaluation of liver fibrosis. We excluded patients who had pre-existing chronic liver disease, chronic alcohol consumers, or those with ongoing medication other than those for metabolic syndrome.
Demographic and clinical features of the participants were recorded. All participants underwent Transient Elastography (TE) and had their AST, ALT, gamma-glutamyl transferase (GGT), platelet count, and prothrombin time measured in a random blood sample, taken the same day of the TE. We calculated for each patient the eLIFT and BARD scores using standard formulas.
Liver stiffness measurements (LSM) used to define the risk for advanced fibrosis as low, indeterminate, and high, based on EASL guidelines 2021, were respectively: <8 kPa, ≥8 and < 12 kPa, and ≥12 kPa.
An eLIFT <8 indicated a low risk of advanced fibrosis, whereas a result ≥8 identified patients at risk of advanced fibrosis. The BARD score ranges from 0 to 4, considered low from 0 to 1 with a high negative predictive value (NPV) for advanced fibrosis, and considered high from 2 to 4 with a high risk of advanced fibrosis.

Results

A total of 213 obese patients with NAFLD were included, with a mean age of 49.04 ± 11.76 years, 88% were female. The mean body mass index (BMI) was 40.67 ± 10.16 kg/m² and the mean waist circumference (WC) was 115.07 ± 17.49 cm.
TE results revealed that 191 patients had a low risk of advanced fibrosis (89.7%), 13 had an indeterminate risk of advanced fibrosis (6.1%), and nine patients had a high risk of advanced fibrosis (4.2%). Using eLIFT, 195 patients were classified in the low-risk of advanced fibrosis group of which 187 had also a low risk based on TE and only 8 had a high risk of advanced fibrosis, which corresponds to a rate of sensitivity at 92.6%; specificity at 27.3%; NPV at 95.9%; and positive predictive value (PPV) at 16.7%.
The BARD score was low in 21 patients (9.9%) and high in 192 (90.1%). Among the 21 patients with a low BARD score, 19 had a low risk of advanced fibrosis based on LSM and two had a high risk of advanced fibrosis. In the group of patients with a high score, only nine had advanced fibrosis. Sensitivity was 8.5%; specificity was 90%; NPV was 94.4%; and PPV was 4.7%. Both scores had high NPV for a high risk of advanced fibrosis, but the BARD score had a lower sensibility than eLIFT, with better specificity.
AUROC were 0.515 (95% CI, 0.11-0.92) and 0.743 (95% CI, 0.49-0.99) for eLIFT and BARD scores, respectively.

Conclusion

Both eLIFT and BARD scores were useful for ruling out advanced fibrosis (NPV > 90%) in an obese population with NAFLD. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs.

Introduction

The part of NAFLD children has a progressive sub-phenotype known as nonalcoholic steatohepatitis (NASH), characterized by the ability to develop advanced fibrosis, cirrhosis, and end-stage liver disease [1]. Given the high prevalence of NAFLD and invasiveness of the liver biopsy, there is an essential need to find safe non-invasive modalities to determine liver fibrosis in children [2].

Aims & Methods

To investigate serum fibrosis markers in obese children with non-alcoholic fatty liver disease (NAFLD) depending on the presence of liver fibrosis.
94 children aged 9 to 17 years (average age 12.15 ± 2.51 years) were included in the study. According to the transient elastography data (FibroScan®502touch, Echosence, France) and body mass index, children were divided into four groups: group 1 - 27 obese NAFLD children with fibrosis ≥F1, group 2 - 35 obese NAFLD children without fibrosis, group 3 - 18 obese children without NAFLD and fibrosis. Group 4 (control) consisted of 14 children with normal weight without NAFLD and liver fibrosis. The serum levels of vascular endothelial growth factor (VEGF) (Wuhan Fine Biotech Co Ltd, China), transforming growth factor-beta 1 (TGF-β1) (IBL International, Germany), cytokeratin-18 (CK-18) (IDL Biotech AB, Sweden) were determined by enzyme-linked immunosorbent assay (ELISA). Serum content of hydroxyproline free (HPf) and hydroxyproline protein-bound (HPp/b) according to Osadchuk and glycosaminoglycans (GAG) according to Rimington were evaluated.

Results

In 1 group children, a significant increase in the median level of CK-18 (in 2.2 times, p<0.05), VEGF (in 2.4 times, p<0.05), and TGF-β1 (in 2.7 times, p<0.05) was found compared to 4 group children. Moreover, CK-18 level was significantly higher in 1 group of patients compared to 2 group (in 1.4 times, p<0.05) and 3 group (in 1.8 times, p<0.05). In all group children, an increase in the serum HPp/b content was found: in 1 group - in 1.2 times (p<0.01), in 2 group - in 1.2 times (p<0.05), in 3 group - in 1.3 times (p<0.05) compared to 4 group. The changes in the content of hydroxyproline led to an increase in the HPp/b/HPf ratio in all groups: 1.4 times (p<0.01) in 1 and 2 groups, in 1.3 times (p<0.01) in 3 group. Also, in 1 group of children median GAG level was increased by 1.3 times (p<0.001).
In children with NAFLD HPf content negatively correlated with CAP (r= - 0.408; p<0.01), CK-18 (r=-0.469; p<0.01), the ratio HPp/b/HPf positively correlated with CAP (r=0.307; p<0.05). CK-18 positively correlated with fibrosis degree (according to METAVIR) (r=0.468; p=0.008) and liver steatosis degree (r=0.357; p=0.048). A positive correlation was also found between VEGF levels and the degree of liver fibrosis (r=0.372, p=0.036).

Conclusion

Serum levels of VEGF, TGF-β1, HPp/b, and GAG were significantly elevated in children with non-alcoholic fatty liver fibrosis. Assessment of these parameters may be useful for early diagnosis of liver fibrosis in children with NAFLD.

References

1. Schwimmer JB, Johnson JS, Angeles JE, et al. Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;157(4):1109-1122. doi:10.1053/j.gastro.2019.06.028.
2. Alkhouri N. Putting it all together: Noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in adults and children. Clin Liver Dis (Hoboken). 2017;9(6):134-137. Published 2017 Jun 29. doi:10.1002/cld.636