Higher Liver Stiffness Measurement Research Articles

Vibration-Controlled Transient Elastography–Based Parameters Predict Clinical Outcomes in Liver Transplant Recipients

Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk stratify liver transplant (LT) recipients, however, there is currently little data demonstrating the relationship between VCTE and clinical outcomes. 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5kPa and hepatic steatosis as controlled attenuation parameter (CAP)≥ 270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. The LSM was elevated in 64 (18%) and CAP in 163 (45%) of LT recipients. The baseline LSM values were similar in patients with elevated vs. normal CAP values. After a median follow up of 65 (IQR 20, 140) months from LT to baseline VCTE, 66 (18%) of patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (HR 1.97, 95% CI 1.11, 3.50, p=0.02) and new onset cirrhosis (HR 6.74, 95% CI 2.08, 21.79, p<0.01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow up with HR 4.14 [95% CI 1.29, 13.27, p=0.017]. The VCTE based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk stratification strategies to improve outcomes among LT recipients.

Association of Aortic Stiffness and Pressure Pulsatility With Noninvasive Estimates of Hepatic Steatosis and Fibrosis: The Framingham Heart Study.

Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community. Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression. In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated β per SD, 0.05 [95% CI, 0.01-0.09]; P=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (β=0.11 [95% CI, 0.07-0.15]; P<0.001), forward pressure wave amplitude (β=0.05 [95% CI, 0.01-0.09]; P=0.01), and central pulse pressure (β=0.05 [95% CI, 0.01-0.09]; P=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P<0.001). Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity. A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis. The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03. Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.

Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis

BackgroundHepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use.MethodRisk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis.ResultsDuring the median follow-up period of 61.00 (57.00–66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02–1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10–5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86–1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01–1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram’s 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80–0.88), 0.83 (95% CI 0.79–0.87), and 0.81 (95% CI 0.77–0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05).ConclusionsOlder age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.

Previous hepatitis E virus infection is associated with increased liver stiffness in patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a chronic, progressive liver disease that, in most cases, may require lifelong immunosuppression. Hepatitis E virus (HEV) is a leading cause of acute, typically self‑limited hepatitis worldwide, although immunocompromised patients may develop chronic hepatitis. We aimed to evaluate the impact of HEV seropositivity on the clinical course of AIH. The study involved a group of 374 adult patients with AIH (68% women; median [interquartile range] age, 34 [18-83] years; 38% with liver cirrhosis). Serum HEV immunoglobulin (Ig) G and IgM antibodies were measured by enzyme‑linked immunosorbent assay, liver fibrosis was assessed by liver stiffness measurement (LSM), and liver cirrhosis was confirmed with liver histology or LSM. Fifty‑five patients (15%) with AIH were HEV IgG‑positive. These patients were older (P <0.001), had higher body mass index, and higher value of LSM (both P <0.05). In a multivariable model including the levels of alanine aminotransferase and IgG, the HEV seropositive status was associated with an increased risk of advanced liver fibrosis with odds ratio of 3.69 (95% CI, 1.26-10.77; P = 0.02), as reflected by liver stiffness equal to or above 10.5 kPa. HEV IgG seropositivity was, however, not linked with the type of treatment or worse AIH outcome. Seroprevalence of HEV in the patients with AIH was lower than in the general population of Polish blood donors (43%). Patients with AIH and HEV IgG‑positive status seem to be at risk of more advanced liver fibrosis. However, the overall seroprevalence of HEV IgG is lower in patients with AIH than in blood donors in Poland.

Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study

BackgroundPersons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances.MethodsData was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI).ResultsAt baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement.ConclusionsMore than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

The associations between fibrosis changes and liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with liver fibrosis. We investigated the associations between changes in liver stiffness measurement (LSM) over 3-year period and the development of cirrhosis or hepatocellular carcinoma (HCC) in patients with MASLD. This study involved patients with MASLD who underwent transient elastography at baseline and 3 years after baseline from 2012 to 2020. Low (L), indeterminate (I) and high (H) LSM values were classified as <8 kPa, 8-12 kPa and >12 kPa respectively. Among 1738 patients, 150 (8.6%) were diagnosed with cirrhosis or HCC. The proportions of patients with L, I and H risk were 69.7%, 19.9% and 10.5% at baseline, and 78.8%, 12.8% and 8.4% at 3 years after baseline, respectively. The incidence rates of cirrhosis or HCC per 1000 person-years were 3.7 (95% confidence interval [CI], 2.4-5.5) in the L → L + I group, 23.9 (95% CI, 17.1-32.6) in the I → L + I group, 38.3 (95% CI, 22.3-61.3) in the H → L + I group, 62.5 (95% CI, 32.3-109.2) in the I → H group, 67.8 (95% CI, 18.5-173.6) in the L → H group and 93.9 (95% CI 70.1-123.1) in the H → H group. Two risk factors for the development of cirrhosis or HCC were LSM changes and low platelet counts. LSM changes could predict clinical outcomes in patients with MASLD. Thus, it is important to monitor changes in the fibrotic burden by regular assessment of LSM values.

Dissociation in hepatic vein pressure gradient, liver stiffness measurement and complications in histological subtypes of porto-sinusoidal vascular disease

Background and aimsPortosinusoidal vascular disease (PSVD) is a broad term encompassing varied histological patterns with changes in portal tracts and sinusoids without cirrhosis. We aimed to assess whether there is...

Prognostic value of liver stiffness in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis.

Liver stiffness measurement, assessed by vibration-controlled transient elastography, has been recognized as a powerful tool for liver fibrosis assessment. The potential of liver stiffness measurement to predict clinically relevant outcomes in fatty liver disease has received considerable attention. This study aimed to investigate the prediction of liver-related events in metabolic dysfunction-associated steatotic liver disease patients by liver stiffness measurement value on transient elastography. We systematically searched the Electronic databases including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov until 6 September 2023. The hazard ratios adjusted for confounders were extracted and pooled by random-effects model analysis. A total of 20587 individuals from 7 studies were included. The pooled HRs were 18.65 (95% CI 9.95-34.95, P < 0.01, I2 = 0%) in the stratification analysis of the highest versus lowest liver stiffness measurement categories. In 1-kPa analysis, the risk of liver-related events was increased with 1 kPa increment (HR 1.05, 95% CI 1.03-1.07, P < 0.01, I2 = 74.47%). Metabolic dysfunction-associated steatotic liver disease patients with high liver stiffness measurement values were at an increased risk of liver-related events. Liver stiffness measurement can be used as a prognostic tool to achieve risk stratification in fatty liver patients.

Prediction of Sinusoidal Obstructive Syndrome after Allogeneic Stem Cell Transplantation Using Liver Stiffness Measurement By Fibroscan

Background: Sinusoidal Obstructive Syndrome/ Veno-Occlusive Disease (SOS/VOD) is a potentially life-threatening complication post allogeneic transplantation (HSCT) with an incidence of ~ 10% in adults. The sensitivity of SOS symptoms (hyperbilirubinemia ≥2 mg/dl, weight gain&amp;gt;5%, painful hepatomegaly and ascites) is good, but the specificity is relatively low because other conditions such as infections, GvHD, and exacerbation of previous liver disease may cause similar symptoms. Transient elastography (TE) using FibroScan has been implemented as a non-invasive assessment of post-sinusoidal portal hypertension (PHTN) one of the hallmarks of SOS. We aimed to assess TE's applicability in predicting and diagnosis of SOS. Methods: This single-center study was conducted between January 2021 and June 2023. Twenty-seven patients (pts) underwent TE, 11 before HSCT (group 1) due to high risk of developing SOS in order to guide subsequent treatment, and 17 after HSCT (group 2) (1 pt was in both groups) due to an elevation of bilirubin ≥2 mg/dl. SOS was defined using the EBMT criteria. Results: Eleven pts were included in the 1 st group (M 5, F 6). The median age was 43 (22-65) years. 7 pts had acute myelogenous leukemia (AML) -4/7 secondary AML (sAML), and 4 pts had myelofibrosis (MF). 5/7 AML pts received a median of 4 (2-5) lines of chemotherapy before HSCT; 2/4 sAML pts got azacytidine/ venetoclax and all 4 MF pts received Ruxolitinib before HSCT. Two pts had chemotherapy for antecedent malignancy. Donors were HLA-matched siblings (n=5), matched unrelated (n=2), or haploidentical (n=4). Risk factors for developing VOD included: active disease (n=9), multiple lines of chemotherapy (n=7), elevated serum ferritin (n=5), splenomegaly (n=5 including 1 pt with overt PHTN), severe liver toxicity during previous treatment (n=4), age ≥60 (n=3), second transplantation (n=3), pre-existing liver disease including fatty liver (n=3, including 1 pt with liver cirrhosis), severe obesity (n=2), prior treatment with GO (n=2), baseline liver enzymes elevation (n=2), and alcohol abuse(n=1). The conditioning regimen included total body irradiation (n=1), busulphan (BU) alone (n=5), or double alkylating agents (DAC, n=5), respectively. Four patients had myeloablative conditioning (MAC). Most pts had several risk factors for VOD median 5 (3-8). This group had a median liver stiffness measurement (LSM) of 10.1 kPa (range, 3.3-28.3). In 6/11 pts with LSM ≥7.2 kPa, the conditioning was modified; Treosulfan was given instead of BU (n=3), non-DAC instead of DAC protocol (n=3), reduced intensity instead of MAC (n=4), methotrexate was omitted (n=2). One pt received Defibrotide prophylaxis. With these modifications only 2 pts developed SOS (1 died). The second group included 17 pts (M 10, F 7), median age 49 (32-62) years with AML/myelodysplastic syndrome (n=7), acute lymphoblastic leukemia (n=5), MF (n=4), and lymphoma (n=1). Ten had MAC, and 5 had DAC. Five had active disease at HSCT. Three had prior liver disease. All pts had bilirubin elevation ≥2 mg/dl after HSCT but only 10 fulfilled additional criteria for the diagnosis of SOS based on the EBMT criteria. Pts who developed SOS had significantly higher LSM compared to those who did not; 10.7 kPa (IQR, 7.5-25.2) versus 5.9 kPa (IQR, 5.1-7.4), respectively (p=0.007) (Figure 1A). There was a positive correlation between the diagnosis of SOS and LSM levels, with a correlation coefficient of 0.6 (p= 0.04) as determined by the Spearman correlation test. LSM was able to diagnose SOS with an AUC of 0.89 (p=0.008) (Figure 1B). The cut-off value for SOS diagnosis was 7.5 kPa, with a sensitivity of 80% and specificity of 88%. Pts with severe VOD were treated with defibrotide and none of them died .of VOD. Conclusions: Pts with a high risk for VOD may have a high baseline LSM. In these pts, modifying the planned conditioning and GVHD prophylaxis regimens to less hepato-toxic ones may reduce the incidence of subsequent VOD. LSM elevation after HSCT should increase awareness of SOS, while pts with hyperbilirubinemia and low LSM usually suffered from other causes of liver toxicity. High LSM could support the diagnosis of VOD in borderline cases. Therefore, LSM may be an additional diagnostic tool in diagnosing SOS after HSCT, but more studies are needed to confirm these findings.

Relationships between education and non-alcoholic fatty liver disease

IntroductionIndividuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES). MethodsThis cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done. ResultsIn the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education. ConclusionThe study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.

Food Insecurity Is Associated With Chronic Liver Disease Among US Adults.

Food insecurity is associated with many poor health outcomes. Most contemporary liver disease is metabolic and impacted by nutritional status. Data regarding the association between food insecurity and chronic liver disease are limited. We evaluated the linkage between food insecurity and liver stiffness measurements (LSMs), a key measure of liver health. A cross-sectional analysis of 3502 subjects aged 20 years and older from the 2017 to 2018 National Health and Nutrition Examination Survey. Food security was measured using the US Department of Agriculture's Core Food Security Module. Models were adjusted using age, sex, race/ethnicity, education, poverty-income ratio, smoking, physical activity, alcohol intake, sugary beverage intake, Healthy Eating Index-2015 score. All subjects underwent vibration-controlled transient elastography, which provides LSMs (kPa) and a measure of hepatic steatosis (controlled attenuation parameter, dB/m). LSM was stratified: <7, 7 to 9.49, 9.5 to 12.49 (advanced fibrosis), and ≥12.5 (cirrhosis) in the whole-study population and stratified by age (20 to 49y and 50y and older). There were no significant differences in mean controlled attenuation parameter, alanine aminotransferase, or aspartate aminotransferase values by food security status. However, food insecurity was associated with a higher mean LSM (6.89±0.40 kPa vs. 5.77±0.14 kPa, P=0.02) for adults 50 years and older. After multivariate adjustment, food insecurity was associated with higher LSMs across all risk stratifications for adults 50 years and older: LSM≥7 kPa [odds ratio (OR): 2.06, 95% CI, 1.06 to 4.02]; LSM≥9.5 kPa (OR: 2.50, 95% CI, 1.11 to 5.64); LSM≥12.5 kPa (OR: 3.07, 95% CI, 1.21 to 7.80). Food insecurity is associated with liver fibrosis and an increased risk of advanced fibrosis and cirrhosis in older adults.

Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also associated with chronic liver diseases. The aim of this study was to identify semaphorins associated with NAFLD and their relationship with steatosis and fibrosis stages. In this prospective, case-control study, serum semaphorin concentrations (SEMA3A, -3C, -4A, -4D, -5A and -7A) were measured in 95 NAFLD patients and 35 healthy controls. Significantly higher concentrations of SEMA3A, -3C and -4D and lower concentrations of SEAMA5A and -7A were found in NAFLD. While there was no difference according to steatosis grades, SEMA3C and SEMA4D significantly increased and SEMA3A significantly decreased with fibrosis stages and had better accuracy in predicting fibrosis compared to the FIB-4 score. Immunohistochemistry confirmed higher expression of SEMA4D in hepatocytes, endothelial cells and lymphocytes in NAFLD livers. The SEMA5A rs1319222 TT genotype was more frequent in the NAFLD group and was associated with higher liver stiffness measurements. In conclusion, we provide the first evidence of the association of semaphorins with fibrosis in patients with NAFLD.

Frequent detection of functional hyposplenism via assessment of pitted erythrocytes in patients with advanced liver cirrhosis.

Asplenia or functional hyposplenism are risk factors for severe infections, and vaccinations against encapsulated bacteria are advised. There are only limited data regarding the spleen function of cirrhotic patients. We evaluated spleen function in patients with liver cirrhosis, who were prospectively enrolled in this study. Spleen function was evaluated by the measurement of pitted erythrocytes. Functional hyposplenism was defined as a percentage of PE of >15%. 117 patients, mean age 58.4 years and 61.5% (n = 72) male with liver cirrhosis were included. Functional hyposplenism was diagnosed in 28/117 patients (23.9%). Pitted erythrocytes correlated with albumin (p = 0.024), bilirubin (p<0.001), international normalized ratio (INR; p = 0.004), model of end-stage liver disease (MELD) score (p<0.001) and liver stiffness (p = 0.011). Patients with functional hyposplenism had higher MELD scores (median 13 vs. 10; p = 0.021), liver stiffness (46.4 kPa vs. 26.3 kPa; p = 0.011), INR (1.3 vs. 1.2; p = 0.008) and a higher Child-Pugh stage (Child C in 32.1% vs. 11.2%; p = 0.019) as compared to patients without functional hyposplenism. Functional hyposplenism was not associated with the etiology of cirrhosis. Importantly, 9/19 patients with Child C cirrhosis had functional hyposplenism. A quarter of patients with liver cirrhosis and almost 50% of patients with Child C cirrhosis have functional hyposplenism. Functional hyposplenism is associated with poor liver function and the degree of portal hypertension, which is characterized by higher liver stiffness measurements in transient elastography.

HIGH VALUES OF LIVER STIFFNESS PLAY AN IMPORTANT ROLE IN STRATIFYING THE RISK OF HEPATOCELLULAR CARCINOMA IN CIRRHOTIC HEPATITIS C PATIENTS.

Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.

Prediction of post-hepatectomy liver failure and long-term prognosis after curative resection of hepatocellular carcinoma using liver stiffness measurement

Background and study aimsPost-hepatectomy liver failure (PHLF) is the main cause of perioperative death after hepatocellular carcinoma (HCC) resection. PHLF occurrence is related to both the hepatectomy volume and the degree of cirrhosis. Accurate preoperative assessment of the degree of cirrhosis may aid in reducing the incidence of PHLF. Several studies have shown that the liver stiffness measurement (LSM) is well correlated with cirrhosis. This study explored the relationship between LSM and PHLF occurrence after radical HCC resection and the effect on long-term prognosis. Patients and methodsWe retrospectively analyzed the clinical data of 164 patients who underwent radical HCC resection at our center from January 2017 to January 2020. The related postoperative PHLF factors were analyzed. The LSM threshold in postoperative PHLF was calculated through receiver operating characteristic (ROC) curve analysis. Patients were grouped according to different LSM thresholds and survival analysis was performed. ResultsForty-six patients experienced PHLF, of whom 19, 21, and 6 were classified as grades A, B, and C, respectively. Multivariate analysis indicated that LSM was an independent risk factor for PHLF after HCC surgery (OR = 1.174, P < 0.000). LSM (OR = 1.219, P < 0.000) and intraoperative bleeding (OR = 1.001, P = 0.047) were risk factors for grade B-C PHLF. The LSM threshold that predicted PHLF occurrence was 17.9 kPa (AUC = 0.831, P < 0.000) and 24.5 kPa (AUC = 0.867, P < 0.000) for grade B-C PHLF. LSM was correlated with PHLF severity (r = 0.439, P < 0.001). The median survival times were 32 vs 26 months (P = 0.016) for patients with LSM ≤ 17.9 kPa vs those with LSM > 17.9 kPa and 28 vs 24 months (P = 0.004) for patients with LSM ≤ 24.5 kPa vs those with LSM > 24.5 kPa. ConclusionLSM is related to PHLF occurrence in patients undergoing HCC resection; a higher LSM is associated with the occurrence of more severe PHLF after surgery. In addition, LSM may aid in predicting long-term survival after liver resection in patients with HCC.

2D-shear wave elastography: number of acquisitions can be reduced according to clinical setting

BackgroundThe factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM).MethodsAt least three LSM were performed in 452 patients who underwent LSM by 2D-SWE (supersonic shear imaging) out of an initial database of 1650 patients. The mean value of the three LSM was our best measurement method. Bland–Altman plots were used to evaluate intra-operator variability when considering only one, or the first two measurements. Variability was assessed by taking the absolute value of the difference between the first LSM and the mean of the three LSM. Logistic regression was used to assess the factors associated with the highest tertile of variability.ResultsThe limit of agreement was narrower with the mean of the first and second measurements than with each measurement taken separately (− 2.83 to 2.99 kPa vs. − 5.86 to 6.21 kPa and − 5.77 to 5.73 kPa for the first and second measurement, respectively). A BMI ≥ 25 kg/m2 and a first LSM by 2D-SWE ≥ 7.1 kPa increased the odds of higher variability by 3.4 and 3.9, respectively. Adding a second LSM didn’t change the variability in patients with BMI < 25 and a first LSM by 2D-SWE < 7.1 kPa.ConclusionsIntra-operator variability of LSM by 2D-SWE increases with both a high BMI and high LSM value. In patients with BMI < 25 kg/m2 and a first LSM < 7.1 kPa we recommend performing only one LSM.

Different Risk Factors for Early and Late Recurrence After Curative Resection of Hepatocellular Carcinoma.

Factors of early and late recurrence after curative resection of hepatocellular carcinoma (HCC) may be different. The aim of this study was to identify clinical factors, including liver stiffness measurement (LSM), which are associated with HCC recurrence after curative resection. Patients who underwent preoperative LSM and primary curative resection for HCC between October 2015 and May 2018 were retrospectively reviewed, with 1year as the cut-off between early and late recurrence. Recurrence was observed in 42/149 (28.2%) patients over a median follow-up of 38.3months (early recurrence: 10 [6.7%] patients; late recurrence: 32 [21.5%] patients). Multivariate analysis identified LSM (P = 0.026) and tumor size (P = 0.010) as the only factors that were significantly associated with recurrence-free survival. Compared with patients without recurrence, those with early recurrence had larger tumor size (P = 0.035) and those with late recurrence had higher LSM (P = 0.024). Receiver-operating characteristic analysis indicated that the optimal LSM cut-off value for predicting HCC recurrence was 7.4kPa. Tumor size was associated with early HCC recurrence after curative resection and LSM was associated with late recurrence. LSM cut-off of 7.4kPa is recommended in predicting recurrence.

Prediction of high-risk esophageal varices in patients with compensated cirrhosis using albumin-bilirubin-platelet score.

Despite the fact that endoscopy is the gold standard for screening of high-risk varices (HRVs) in patients with compensated cirrhosis, it is invasive, costly and not necessary for all patients. So, noninvasive tests can replace endoscopy. We aimed at evaluating the albumin-bilirubin-platelet (ALBL-PLT) score as a noninvasive test in predicting HRVs in compensated cirrhotic patients versus Baveno VI and extended Baveno VI criteria. patients with compensated cirrhosis (n = 204) were included. Laboratory parameters, esophagogastroduodenoscopy (EGD) and liver stiffness measurement by transient elastography were done. Classification of patients according to the status of HRVs was done. We compared both groups on the basis of ALBL-PLT score, Baveno VI and extended Baveno VI criteria. Among the total patients, 96/204 (47%) patients had HRVs. They have higher liver stiffness measurement than those without HRVs (33 ± 13.1 versus 19.3 ± 8.25, CI, -19.94, -7.31, P value <0.001). Also, all HRVs patients have an ALBL-PLT score of more than 3. The area under the receiver operating characteristic curve for the ALBL-PLT score is higher than that for Baveno VI and extended Baveno VI criteria (0.894 versus 0.722 and 0.792, respectively). ALBL-PLT score of more than three has a good predictive value in predicting HRVs among compensated cirrhotic patients.

PNPLA3 is the dominant SNP linked to liver disease severity at time of first referral to a tertiary center

BackgroundSingle nucleotide polymorphisms (SNPs) in genes including PNPLA3, TM6SF2, HSD17B13 and SERPINA1 have been identified as risk modifiers of progression in chronic liver disease (CLD). However, it is unclear whether genotyping for these risk variants is useful in clinical routine. MethodsLiver disease severity was assessed by liver stiffness measurement (LSM) and by presence of clinical manifestations of advanced-chronic liver disease (ACLD) in 779 consecutive CLD patients at the time of referral to a tertiary center. The associations of risk variants with CLD severity were calculated individually and in a combined model using a polygenic risk-score. ResultsNon-alcoholic fatty liver disease (NAFLD) was the most common etiology (n = 511, 65.6%), and ACLD was present in 217 (27.9%) patients. The PNPLA3-G-allele remained independently associated with higher LSM (adjusted-B: 2.508 [95%CI: 0.887–4.130], P = 0.002) or the presence of ACLD (aOR: 1.562 [95%CI: 1.097–2.226], P = 0.013). SERPINA1-Z-allele was also independently associated with LSM (adjusted-B: 4.558 [95%CI: 1.182–7.934], P = 0.008), while the other risk alleles did not attain statistical significance. Combining these risk alleles into a polygenic risk-score was significantly associated with LSM (adjusted-B: 0.948 [95%CI: 0.153–1.743], P = 0.020). ConclusionPNPLA3 risk-variants are linked to liver disease severity at the time of first referral to an outpatient hepatology clinic.