Liver Stiffness Score Research Articles

An Alternative Non-Invasive Screening Model for Liver Fibrosis among US Adults at Risk of MASLD.

Background and Aims: Screening for liver fibrosis presents a clinical challenge. This study aimed to explore a useful alternative method for assessing fibrosis risk among US adults at risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A liver stiffness score (LSS) model was proposed and tested using data from 3976 participants at possible risk of MASLD, obtained from the US National Health and Nutrition Examination Survey (NHANES). Results: The LSS model was developed using liver stiffness measurements, blood biochemistry, and body measurement data from 2414 NHANES participants at risk of MASLD, sampled between 2017 and 2020: LSS = exp(0.007035 × bodyweightkg - 0.1061 × raceblack1,0 + 0.183221 × diabetes1,0 + 0.008539 × ASTIU/L - 0.0018 × plateletcount1000cell/UL - 0.21011 × albuming/dL + 2.259087). The probability (P) of having fibrosis F3 + F4 is calculated as follows: P = 0.0091 × LSS2 - 0.0791 × LSS + 0.1933. The developed LSS model was tested on 1562 at-risk participants from the 2017-2018 cycle. The results showed that the LSS model achieved AUROC values of 0.79 and 0.78 for diagnosing cirrhosis (F4) and advanced fibrosis (F3 + F4) in the US population, respectively. It outperformed existing models such as NFS, FIB-4, SAFE, and FIB-3. For screening F3 + F4 fibrosis, the LSS model's top decile outperformed the NFS and FIB-4 models by 37.7% and 42.6%, respectively. Additionally, it showed superior performance compared to the waist circumference classification method by 29.5%. Conclusions: derived from an ethnically diverse population dataset, the LSS screening model, along with its probability equation, may offer clinicians a valuable alternative method for assessing the risk of liver fibrosis in the at-risk adult population.

Liver fibrosis and liver stiffness in patients with obesity and type 1 diabetes.

To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI). In this prospective cross-sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables. The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P < .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P < .001). Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1-13.6, P < .001). Aspartate transaminase (AST), alanine transaminase, gamma-glutamyl transferase (GGT), triglycerides and the android-to-gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts. Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control.

PRECLINICAL VASCULAR ORGAN DAMAGE AND VASCULAR AGEING ASSESMENT IN NON-ALCOHOLIC FATTY LIVER DISEASE AND METABOLIC ASSOCIATED FATTY LIVER DISEASE PATIENTS

Objective: Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) are a growing health problem, with a growing prevalence due to its association with metabolic syndrome and diabetes. It is known to be a risk factor for the development of cirrhosis and hepatocarcinoma, but it is also known to be an important cardiovascular risk factor. The aim of this study is to assess the burden of preclinical vascular organ damage. Design and method: The study enrolled 80 consecutive patients (mean age 63.3±15.0) who underwent hepatological evaluation in our department, with evaluation of liver fibrosis score (APRI score, FIB-4) and liver stiffness, and quantification of cardiovascular risk according to Guidelines (2021 ESC Guidelines on cardiovascular disease prevention in clinical practice). Carotid atherosclerotic burden was evaluated by B-mode ultrasound in each segment (common, bulb, internal), bilaterally, and expressed as mean of maximum IMT (M-MAX), right common carotid artery distensibility and stiffness (CardioVascular Suite 4, Quipu, Italy). Aortic stiffness was evaluated as carotid-femoral pulse wave velocity (PWV), measured by applanation tonometry (PulsePen DiaTecne, Italy), with calculation of vascular ageing. Results: We found no significant correlation between ultrasound or tonometry parameters and liver stiffness and fibrosis scores. VPWV was significantly above upper limit of normal of 10 m/s (11.6±6.0 m/s, p=0.02), and the percentiles for age were significantly higher than 50th (61.7±25.1, p&lt;0.001), with 52,5% of patients showing increased PWV. Similarly, M-MAX was higher than the upper normality level of 0.9 mm (1.09±0.30 mm, p&lt;0.001). 70% of patients had an increased M-MAX. Vascular age based on arterial stiffness resulted significantly higher than biological age (mean difference 4.6 years, p&lt;0.001). 76.2% (71/80) of the overall cohort and 45,2% (14/31) of patients classified as low risk showed at least one type of vascular organ damage. Conclusions: Patients with NAFLD or MAFLD showed a large prevalence of arterial stiffening and increased IMT and an enhanced vascular ageing, even among those classified at low cardiovascular risk according to Guidelines. Vascular organ damage evaluation could be useful to identify preclinical organ damage in these patients

A scientifically validated combination of garcinol, curcuminoids, and piperine for mild to moderate nonalcoholic steatohepatitis patients-results from a randomized, double-blind, placebo-controlled study.

Garcinol is a naturally occurring compound from the fruit rind of the Garcinia indica, with antioxidant, anti-inflammatory, and anticancer properties. Curcuminoids are the active molecule from the rhizome of Curcuma longa, studied extensively for its health benefits as an anti-inflammatory and antioxidant activities. Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic steatohepatitis characterized by liver fat and inflammation. To evaluate the clinical efficacy and safety of Garcinol, Curcuminoids and piperine (GCP) combination in patients with mild to moderate NASH in a randomized, double-blind, placebo-controlled study. The patients received one tablet (450 mg) of GCP containing garcinol-50 mg, curcuminoids -250 mg and piperine 5 mg or a placebo (450 mg of microcrystalline cellulose) twice daily for 90 days. Changes in circulating aspartate aminotransferase (AST), alanine transaminase (ALT) levels, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) using Fibroscan were compared from baseline to day 90. Anthropometric parameters, serum levels of lipids, Interleukin (IL-6), hsCRP, and adiponectin were estimated. Safety was evaluated by laboratory parameters and by monitoring adverse events. Seventy-two patients were randomized and 63 (GCP = 32, Placebo = 31) completed the study. The mean age of the patients was 48.3 ± 8.7 years (36 males and 27 females). The mean reduction in AST (U/L) was 9.53 in GCP and 3.16 in placebo (p < 0.001) and that of ALT (U/L) was 13.47 in GCP and 7.43 in Placebo (p = 0.002). The liver stiffness and CAP scores showed a better reduction in GCP (0.56 kPa and 12.38 db/m) compared to placebo (0.064 kPa and 10.42 db/m) p < 0.05. Consequently, the noninvasive Fibroscan-AST (FAST) score reduction was also found to be significant in GCP compared to placebo. Additionally, body weight, lipid levels, hsCRP, and IL-6 in serum decreased, while adiponectin levels increased in GCP-supplemented participants compared to placebo. The combination of garcinol and curcuminoids was well tolerated with no significant changes in hematological and clinical laboratory parameters during the 90-day supplementation. Our results suggest that GCP could be a possible supplement for the management of NASH.Clinical trial registration: https://clinicaltrials.gov/, identifier CTRI/2019/11/022147.

The Steatosis-associated fibrosis estimator (SAFE) score: validation in the general US population.

Noninvasive tests are important in the initial risk stratification of people at risk of fibrosis. The recently developed steatosis-associated fibrosis estimator (SAFE) score may have such potential but awaits external validation. We analyzed 6973 participants aged 18-80 in the National Health and Nutrition Examination Survey 2017-2020 cycle with data on liver stiffness and SAFE score without prevalent heart failure. Fibrosis was defined as liver stiffness ≥8.0kPa. Accuracy was evaluated by AUC and assessment of test characteristics at the prespecified cutoffs for ruling out/ruling in fibrosis. The SAFE score categorized 14.7% of the population as high risk, 30.4% as intermediate risk, and 54.9% as low risk for fibrosis. The actual fibrosis prevalence in these groups was 28.0%, 10.9%, and 4.0%, respectively, translating into a positive predictive value of 0.28 at the high-risk cutoff and a negative predictive value of 0.96 at the low-risk cutoff. The AUC of the SAFE score (0.748) was significantly higher than the fibrosis-4 index (0.619) or NAFLD fibrosis score (0.718). However, test performance strongly depended on age categories: 90% of participants aged 18-40 years were considered at low risk for fibrosis, including 89/134 (66%) of clinically significant fibrosis cases. In the oldest group (60-80y), fibrosis could only be safely ruled out among 17%, corresponding to a high referral rate of up to 83%. The best SAFE score performance was found in the middle-aged group (40-60y). The results were consistent in target populations with metabolic dysfunction or steatosis. The SAFE score has overall good diagnostic accuracy in detecting fibrosis but was highly dependent on age. The SAFE score lacked sensitivity in younger populations and the ability to rule out fibrosis in older populations.

Selective Use of Pulmonary Vasodilators in Patients with Fontan Physiology.

Fontan-associated liver disease is a well-known sequela following the Fontan procedure for patients living with single-ventricle heart disease. Pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors, have emerged as a potential therapeutic option for lowering central venous pressures by reducing pulmonary vascular resistance. We performed a single-center retrospective review of Fontan patients who were placed on pulmonary vasodilator therapy with prehemodynamic and posthemodynamic, MR elastography, and histologic assessments. A total of 125 patients with Fontan circulation underwent surveillance with cardiac catheterization during the review period. Fifty-three (42%) patients who did not have increased end-diastolic pressures at the time of cardiac catheterization were started on phosphodiesterase type 5 inhibitor therapy. Nine patients (17%) underwent posttherapy follow-up catheterization. The mean Fontan pressure decreased from 15.4 ± 3.3 mmHg to 13.3 ± 2.5 mmHg (p=0.026), after initiation of pulmonary vasodilatory therapy. There was no change in end-diastolic pressure, transpulmonary gradient, wedge pressure, pulmonary vascular resistance, cardiac index, or saturation. Eleven patients (21%) underwent pretherapy MR elastography testing with posttherapy follow-up MR elastography. We found no improvement in liver stiffness score following the application of pulmonary vasodilators. Three patients underwent pretherapy and posttherapy liver biopsies, with variable histological changes observed within the hepatic parenchyma. These data demonstrate indeterminate results for the selective use of pulmonary vasodilators but highlight the need for large prospective randomized control trials of pulmonary vasodilator therapies to fully assess the benefit of such therapies in Fontan-associated liver disease.

S3086 New Diagnosis of Systemic Amyloidosis in a Patient With Chronic Hepatitis B and Elevated Liver Stiffness Score on MR Elastography

S3086 New Diagnosis of Systemic Amyloidosis in a Patient With Chronic Hepatitis B and Elevated Liver Stiffness Score on MR Elastography

Liver Stiffness Is Associated with the Burden of Carotid and Systemic Atherosclerosis in an Unorganized Cohort of Patients 40-64 Years Old.

Background: The aim of the study is to research the relationship between the severity of liver fibrosis and the burden of carotid and systemic atherosclerosis. Methods: The study includes 163 patients 40 to 64 years of age without atherosclerotic CVD or liver disease. All patients underwent duplex scanning of the carotid and lower limb arteries. All patients underwent transient liver elastometry using the FibroScan (Echosens, France). Results: Carotid plaque was detected in 110 (67.5%) patients. Based on the results of linear regression analysis, relationships between liver stiffness and carotid total plaque area (r = 0.21; p = 0.025) were found. Significant relationships were established between liver stiffness and atherosclerosis burden score based on the results of linear regression (r = 0.17; p = 0.029). Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis. An increase in liver stiffness >4.5 kPa was associated with an odds ratio of generalized atherosclerosis of 3.48 (95% CI 1.07–11.3; p = 0.038) after adjusting confounding factors. Conclusion: Among patients 40–64 years of age without established atherosclerotic CVD and liver disease, liver stiffness directly correlates with the burden of carotid and systemic atherosclerosis. Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis.

MR elastography-based staging of liver fibrosis in Fontan procedure associated liver disease is confounded by effects of venous congestion

To compare targeted and global liver stiffness measured by magnetic resonance elastography (MRE) with liver biopsy in patients who have undergone the Fontan procedure, and to assess the relationship between liver stiffness and fibrosis stage. Targeted and global liver stiffness was compared with a quantification of liver fibrosis measured by percentage of Sirius Red (%SR) staining of biopsy samples. MRE values were compared with three other biopsy-scoring methods: Ishak, Scheuer/Ludwig-Batts/Metavir, and congestive hepatic fibrosis score (CHFS). Additionally, in patients who had two or more MRE studies, global liver stiffness was compared for longitudinal assessment. Thirty-four patients were included in the study, with a mean age of 16.2 years. There was no statistically significant correlation between MRE-derived liver stiffness and Ishak score, Metavir score, %SR staining, and CHFS score. Twenty patients had multiple MRE studies, with a mean age of 16.5 years, and these showed a statistically significant increase in mean liver stiffness from 3.72 to 4.68 (26% increase) within an average period of 24 months. The lack of correlation of liver stiffness with fibrosis stage observed in this study indicates that the effects of venous congestion in Fontan patients can confound the use of liver stiffness as a biomarker for fibrosis as assessed by percentage of SR staining, Ishak score, Metavir score, and CHFS score. These results provide motivation for further development of magnetic resonance imaging-based biomarkers to increase the specificity in the assessment of Fontan-associated liver disease. A steady increase in liver stiffness observed in these patients may be useful for longitudinal follow-up of liver health.

Modified and alternative Baveno VI criteria based on age for ruling out high-risk varices in patients with compensated cirrhosis

BackgroundThe Baveno VI criteria (B6C) have been recommended to screen high-risk varices (HRV) in patients with liver cirrhosis to avoid the use of esophagogastroduodenoscopy (EGD). Due to conservative nature of B6C and the general unavailability of transient elastography in the medical institutions, clinical application of B6C is restricted. We aimed to optimize B6C and attempted to replace the liver stiffness (LS) score with other parameters that could help patients avoid EGD.MethodsA total of 1,188 patients with compensated cirrhosis were analyzed and divided into the training cohort (TC) and validating cohort (VC) by the split-sample method. Variables were selected to develop new criteria in the TC before verification in the VC.ResultsThe parameters of age ≥ 50 years, LS, platelet count (PLT), and spleen area (SA) were independently associated with HRV. The risk of HRV was 2.39 times greater in patients over 50 years, hence alternative B6C (AB6C) and modified B6C (MB6C) criteria were built based on age. MB6C was built by adjusting the cut-off value of LS and PLT (patients aged < 50 years with PLT > 100 × 109/L and LS < 30 kPa; patients aged ≥ 50 years with a combined PLT > 125 × 109/L and LS < 20 kPa). MB6C helped avoid EGD in 310 (51.2%) patients, whereas 7 (2.3%) cases of HRV were missed. The predicting performance HRV showed no statistical difference between PLT, SA, or LS. SA was selected to replace LS and in the built AB6C (patients aged < 50 years with PLT > 100 × 109/L and SA < 55 cm2; patients aged ≥ 50 years with a combined PLT > 125 × 109/L and SA < 44 cm2). Using AB6C avoided 297 (49.1%) EGDs with a total of 8 (2.7%) cases of HRV that were missed.ConclusionsOur novel MB6C and AB6C were stratified by age and provided excellent performance for ruling out HRV, which performed better than B6C and EB6C (expanded B6C) in helping to avoid EGD screening.Clinical trial registration numberChiCTR-DDD-17013845.

Histological regression and clinical benefits in patients with liver cirrhosis after long-term anti-HBV treatment

Objective: Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients. Methods: Treatment-naïve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis. Results: Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably (P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression (OR=0.887, 95%CI: 0.802-0.981, P=0.020). Conclusions: After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Liver stiffness and steatosis in preeclampsia as shown by transient elastography–a prospective cohort study

Preeclampsia is a multisystem disorder and the leading cause of severe morbidity and death in pregnancy. Liver involvement in preeclampsia ranges from elevated liver enzyme levels to hepatic infarction or rupture. Endothelial dysfunction leads to changes in blood flow and congestion and may be involved in the pathophysiology of preeclampsia. Changes in splanchnic blood flow and portal congestion can lead to altered liver stiffness. Transient elastography is a noninvasive, ultrasound-based technique that measures organ stiffness and steatosis and is therefore widely used in clinical hepatology. Previous studies reported elevated liver stiffness and liver steatosis, as measured by transient elastography, in women with preeclampsia. This study followed changes in liver stiffness and steatosis, as measured by transient elastography, from the antepartum period to 1-week postpartum among women with preeclampsia compared with healthy controls and evaluated the association between preeclampsia severity and transient elastography results. This prospective cohort study was conducted from 2017 through 2021. The study group comprised women with preeclampsia, and the control group comprised healthy pregnant women hospitalized for other reasons. All the participants underwent transient elastography either on diagnosis of preeclampsia (study group) or on hospital admission (control group) and again in the postpartum period. Liver stiffness measurements are expressed in kilopascals (kPa) in the range of 2.5 to 75 kPa, and liver steatosis isexpressed by controlled attenuation parameter in the range of 100 to 400 dB/m. The study group comprised 36 women and the control group 37. Liver stiffness scores were significantly elevated in the study when compared with the control group, both in the antepartum period (P<.001) and the postpartum period (P=.025). Liver stiffness scores decreased significantly after delivery in the study and control groups (P<.001 and P=.002, respectively). Liver steatosis scores were higher in the study group than in the control group both in the antepartum and postpartum periods (P<.001 and P<.02, respectively). In the multivariable analysis, the diagnosis of preeclampsia correlated with higher antepartum liver stiffness scores (P=.005). For the study group, postpartum liver stiffness and liver steatosis scores were increased among those with vs those without severe features of preeclampsia (P=.03 and P=.04, respectively) CONCLUSION: Reductions in liver stiffness and steatosis from the antepartum to the postpartum period were documented in both the preeclampsia and control groups. However, both these measures were higher in the preeclampsia group and correlated with preeclampsia severity. Larger studies may be able to determine whether transient elastography can predict the severity of preeclampsia or other related metabolic conditions that correlate with chronic hypertension.

The contribution of daytime sleepiness to impaired quality of life in NAFLD in an ethnically diverse population

Health-related quality of life (HRQoL) is lower in people with NAFLD compared to the general population. Sleep disturbance resulting in daytime sleepiness is common in patients with NAFLD, but the effect of daytime sleepiness on HRQoL in NAFLD is unclear. The prevalence and natural history of NAFLD vary in different ethnic groups, but there has been limited ethnic diversity in HrQoL studies to date. We aimed to assess whether daytime sleepiness is independently associated with reduced HRQoL in an ethnically diverse UK population. We conducted HRQoL assessments using SF-36 version 2 and Epworth Sleepiness Scale (ESS) questionnaires in 192 people with NAFLD. Multivariate linear regression was used to identify factors independently affecting HRQoL scales. People with NAFLD reported significantly reduced physical health-related SF-36 scores compared to the general UK population. South Asian NAFLD patients reported impairment in physical health, but not mental health, approximately a decade before White NAFLD patients. In multivariate linear regression, daytime sleepiness (ESS score > 10), was the most significant independent predictor of reduced physical health. Age, BMI and liver stiffness score were also significantly associated. HRQoL is impaired earlier in patients of South Asian ethnicity. ESS score > 10, indicative of excessive daytime sleepiness, is an independent predictor of reduced HRQoL in people with NAFLD regardless of ethnicity. Daytime sleepiness should be considered as a contributing factor to reduced HRQoL in clinical practice and when evaluating patient-related outcomes in clinical trials.

Feasibility of liver stiffness measured using two-dimensional shear wave elastography in assessing preoperative liver function for patients with hepatocellular carcinoma.

To evaluate the feasibility of liver stiffness (LS) measured using two-dimensional shear wave elastography (2D SWE) in assessing preoperative liver function for patients with hepatocellular carcinoma (HCC). A total of 143 patients who underwent surgical resection for HCC between August 2018 and December 2019 were enrolled prospectively. LS measurement, liver function tests including serum biochemical indicators, and indocyanine green (ICG) clearance test were performed preoperatively. Child-Pugh (CP) score, Albumin-bilirubin (ALBI) score and Model for End-Stage Liver Disease score were calculated. ICG retention rate at 15min (ICG R15) and ICG elimination rate constant (ICG K) were determined automatically. Fibrosis stage was determined based on pathological findings. The association between LS and serum biochemical indicators, liver function scores, and the ICG results were analyzed. Weak to moderate correlations were identified between LS and biochemical indicators of liver function (all p < 0.01). Weak correlation was identified between LS and CP score, and between LS and ALBI score (all p < 0.001). Moderate correlation was identified between LS and ICG R15 (Pearson r = 0.62, p < 0.001), and between LS and ICG K value (Pearson r = - 0.49, p < 0.001). The best cutoff of LS to discriminate a normal ICG R15 was 10.6kPa, with area under the curve (AUC), sensitivity, specificity of 0.874, 0.900 and 0.724, respectively. LS determined using 2D SWE could be a potential tool for the preoperative evaluation of liver function in patients with HCC.

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy.

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.

S1143 Noninvasive Assessment of NAFLD in Potential Kidney Transplant Recipients

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease among US adults. Risk factors (RF) for NAFLD including diabetes mellitus (DM) and hypertension (HTN), also increase the risk of chronic kidney disease (CKD). Our aim is to assess the prevalence of NAFLD and identify RF and predictors for NAFLD in patients listed for Kidney Transplant (KT). We also use noninvasive tests (NITs) to assess the prevalence of at least significant fibrosis in the NAFLD group. Methods: We performed a retrospective chart review on patients listed for KT. We included all adult patients listed for KT between 03/2015-08/2019. Exclusion criteria included a history of prior liver transplant, listed for simultaneous liver kidney transplant, and lack of available liver imaging in the past 5 years. We excluded patients with a history of either nonNAFLD liver disease or excessive alcohol use from the NAFLD group, but included them in the nonNAFLD analysis. We collected data on demographics, comorbidities, etiology of CKD, liver chemistries, and imaging of the liver. Most patients listed for KT after 2018 had a LE. FIB-4 score was calculated for all NAFLD patients. Results: 204 patients were included. 22.5% of patients were found to have NAFLD based on imaging describing an echogenic liver or hepatic steatosis. See table 1. On univariate analysis, a history of DM, metabolic syndrome (MS), DM as cause of CKD, and BMI were significantly associated with NAFLD (all p< 0.05). On multivariate analysis, ALT level was the only independent predictor of NAFLD (p< 0.05). The mean FIB4 score in the NAFLD group was 1.43. 67% of the NAFLD group had a FIB-4 < 1.45. 28.3% of the NAFLD group had an indeterminate FIB-4 score of >1.45 but < 3.25. 4.3% of the NAFLD group had a FIB-4 score >3.25, likely having advanced fibrosis. 56% of NAFLD patients had an available liver stiffness (LS) score. Of the NAFLD patients with LS scores, 11.5% was consistent with F2 fibrosis and 11.5% with ≥F3 fibrosis. Conclusion: NAFLD prevalence in patients listed for KT is similar to that of US adults, but this patient group may have a higher prevalence of at least significant fibrosis. Patients listed for KT who have a high BMI or history of MS or DM, especially if they have an abnormal ALT, should be evaluated for NAFLD. Potential KT recipients with NAFLD should have NITs such as a FIB-4 score or LE to assess for advanced fibrosis. Further studies are required to confirm these findings.Table 1.: Percentage of patients meeting inclusion criteria as compared by whether they were accepted for full assessment or not.

Evaluation of long-term changes of aspartate\u2014platelet ratio index, FIB4, and liver stiffness in chronic hepatitis C patients successfully treated by direct-acting antivirals

BackgroundA large number of chronic hepatitis C patients had been successfully treated by directly acting antivirals; therefore, strategies for the long-term follow-up of these patients have to be planned based on the post-treatment fibrosis stage—the main determinant of prognosis. In this study, we aim to evaluate changes in aspartate-platelet ratio index, FIB4, and liver stiffness in chronic hepatitis C patients who achieved SVR and ended treatment more than 1 year by DAAs.ResultsOne hundred chronic hepatitis C patients who achieved SVR were enrolled at a median of 16 months after the end of treatment by DAAs. According to the baseline liver stiffness, 63 and 37 patients belonged to early (F0, F1, and F2) and advanced (F3 and F4) fibrosis stages, respectively. Both groups showed a decline of the degree of liver stiffness at follow-up compared to the baseline that was statistically significant in the early fibrosis group (5.9±1.5 vs 5.4±2.2 Kpcal, p=0.04), while measurements in the advanced group were (18±8.8 vs 15.9 ± 7.8 Kpcal, p=0.07). Also, serum biomarkers of fibrosis improved in both groups, where the recorded APRI and FIB4 before and after treatment were 0.42±0.3 vs 0.24±0.1, p<0.01 and 1±0.6 vs 0.93 ±0.5, p=0.1 in the early group and 0.85 ±0.5 vs 0.4±0.2, p <0.001 and 2.9±2.3 vs 1.8±1.4, p<0.02) in the advanced group, respectively. Changes in APRI and FIB4 correlated with changes in AST and ALT, but liver stiffness changes were not affected by changes in liver enzymes.ConclusionAlthough long-term improvement of APRI, FIB4, and liver stiffness scores could be achieved in chronic HCV patients after SVR by DAAS. High measurements of liver stiffness before treatment likely persist. We recommend transient elastography as a reliable tool for fibrosis assessment post-treatment.

Non-Invasive Assessment of Liver Fibrosis and Steatosis in End-Stage Renal Disease Patients Undergoing Renal Transplant Evaluation.

BackgroundNon-alcoholic fatty liver disease (NAFLD) has an increased prevalence in end-stage renal disease (ESRD) due to similar risk factors. The aim of this study was to assess non-invasive testing including transient elastography (TE) for liver stiffness (LS), controlled attenuated parameter (CAP) for steatosis, Fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST) to platelet ratio index (APRI) and NAFLD fibrosis score (NFS), for evaluation of NAFLD along with advanced fibrosis (AF) in patients with ESRD undergoing renal transplant evaluation.MethodsData were retrospectively collected within 12 weeks of TE. Primary outcomes were AF, defined by LS ≥ 9 kPa compared to APRI > 1.5, FIB-4 > 2.67, and NFS of 0.675, and ≥ 5% steatosis by CAP ≥ 263 dB/m compared to liver histology when available.ResultsA total of 171 patients were evaluated: mean age 56, 65% male, 36% obese, 47% had diabetes, 96% hypertension, and 56% dyslipidemia. Mean LS was 6.5 kPa with 21% having AF. Mean CAP was 232 dB/m, with 25% having steatosis. Those with AF were older with higher NFS. Those with steatosis were obese and had diabetes without higher LS or fibrosis scores. Only NFS was associated with LS ≥ 9 kPa. In those with liver histology, AF was associated with LS ≥ 9 kPa but not with APRI, FIB-4, or NFS.ConclusionsDespite normal liver enzymes, non-invasive assessment via TE in ESRD patients exhibited high prevalence of AF and steatosis not detected by APRI or FIB-4 scores. This high prevalence was secondary to the common risk factors such as obesity and diabetes, among patients with NAFLD and ESRD.

Liver Stiffness Is a Predictor of Rebleeding in Patients With Hepatitis B-Related Cirrhosis: A Real-World Cohort Study.

Background: Esophageal vein rebleeding is a life-threatening complication of liver cirrhosis. However, the role of non-invasive methods that were developed to evaluate the severity of chronic liver disease, especially in rebleeding, remains unclear.Aims: To evaluate the performance of liver stiffness and non-invasive fibrosis scores in predicting esophageal vein rebleeding in hepatitis B virus (HBV) cirrhotic patients.Methods: A prospective analysis of 194 HBV patients between 2017 and 2021 was performed. Receiver operating characteristic (ROC) curves and time-dependent ROC curves were used to assess the power for predicting rebleeding with non-invasive fibrosis score and liver stiffness.Results: During the median follow-up time of 68.28 weeks, 55 patients experienced rebleeding. In the entire cohort, the area under the ROC curve for liver stiffness measurement (LSM) predicting for rebleeding was 0.837, with a cut-off value of 17.79 kPa, and the time-dependent ROC curve also showed stable prediction performance of LSM. The predictive ability of the non-invasive fibrosis score was less than that of LSM, and there were statistical differences. Moreover, patients using non-selective beta-blockers and HBV DNA-negative patients experienced significantly reduced rebleeding.Conclusions: Compared with non-invasive fibrosis scores, LSM can more simply and accurately predict rebleeding events of hepatitis B liver cirrhosis.

Non-invasive Methods in Diagnosis of Nonalcoholic Fatty Liver Disease

ABSTRACT Background: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for increased morbidity and mortality plus cardiovascular disease and malignancy. Despite all of these, most patients have good prognosis if diagnosed at early stages. Objective: The study was designed to evaluate different non-invasive methods as a diagnostic tool of non-alcoholic fatty liver disease among diabetic and non-diabetic patients. Patients and Methods: The study was done on 100 patients were divided into two groups of 50 diabetics and 50 non-diabetics with fatty liver disease on abdominal ultrasonography finding. These patients were assessed with transient elastography (TE) after lab tests and then scoring systems (Fib-4 and NAFLD fibrosis score) and liver stiffness scores were compared between the two groups. Results: There was statistically significant difference between the two groups as regard Fib-4 and NAFLD fibrosis score (p F2) than those with (F2 or less) (p < 0.001). Conclusion: A combination of Fibroscan, Fib-4 and NAFLD fibrosis score provides a valuable non-invasive method in diagnosis of NAFLD patients, and this can eliminate the need for liver biopsy in patients without clear indication, especially diabetic patients that can help in early diagnosis of NAFLD before development of fibrosis.