Advanced Chronic Liver Disease Research Articles

Diagnostic and Prognostic Value of Serum Leptin in Critically Ill Patients with Acute versus Acute-on-Chronic Liver Failure

Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.

Increases and decreases in liver stiffness measurements are independently associated with the risk of liver-related events in NAFLD.

The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with NAFLD is not well-understood. We prospectively defined rates of progression to and regression from LSM-defined compensated advanced chronic liver disease (cACLD) and their associations with liver-related events (LRE). Participants in the NASH Clinical Research Network NAFLD Database 2 and 3 studies were included. Progression to cACLD was defined as reaching LSM ≥10 kPa in participants with LSM < 10 kPa on initial VCTE; regression from cACLD was defined as reaching LSM < 10 kPa in participants with baseline LSM ≥ 10 kPa. LRE was defined ≥1 of the following: liver-related death, liver transplant, hepatocellular carcinoma, MELD>15, development of varices, or hepatic decompensation. Univariate and multivariable interval-censored Cox regression analyses were used to compare the cumulative LRE probability by LSM progression and regression status. In 1,403 participants, 89 LRE developed over a mean follow-up of 4.4 years with an LRE annual incidence rate of 1.5 (95% CI: 1.2-1.8). In participants at risk, progression to LSM ≥10 or ≥15 kPa occurred in 29% and 17%, whereas regression to LSM <10 or <15 Kpa occurred in 44% and 49%. Progressors to cACLD (≥10 kPa) experienced a higher cumulative LRE rate versus non-progressors [16% vs 4%, Adj.HR: 3.8, 95% CI [2.3-6.5], P < 0.01]. Regressors from cACLD (to LSM <10 kPA) experienced a lower LRE rate than non-regressors [7% vs 32%%, Adj.HR: 0.25, 95% CI [0.10-0.61], P < 0.01] CONCLUSIONS: Change in LSM over time is independently and bi-directionally associated with risk of LRE and is a non-invasive surrogate for clinical outcomes in patients with NAFLD. (Word count: 275) IMPACT AND IMPLICATIONS: The prognostic value of change in LSM in patients with NAFLD is not well understood. In this large prospective study of patients with NAFLD and serial VCTE exams, baseline and dynamic changes in LSM were associated with the risk of developing liver-related events. LSM is a useful non-invasive surrogate of clinical outcomes in patients with NAFLD.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10mmHg. A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15kPa and platelet count ≥ 150 × 109/L] OR SSM < 21kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25kPa OR SSM ≥ 50kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Hypercalcemia caused by advanced chronic liver disease without malignancy: a rare entity

Hypercalcemia caused by advanced chronic liver disease without malignancy: a rare entity

Assessment of the liver with two‐dimensional shear wave elastography following COVID‐19 infection: A pilot study

AbstractIntroduction/PurposeThe coronavirus disease (COVID‐19) is a widely spread viral infectious disease, which can impact multiple organs, including the liver. Elevated liver enzymes have been reported in COVID‐19 patients; however, potential changes in liver stiffness following the viral infection remain uncertain. The main aim of this pilot study was to determine if there is a significant difference in liver stiffness between individuals who have never been infected with COVID‐19 and those who had been infected with COVID‐19 &lt;6 months, experiencing only mild symptoms. The secondary aim was to compare the liver stiffness between participants infected with COVID‐19 depending on the elapsed time since infection.MethodsTwo‐dimensional shear wave elastography (2D‐SWE) was performed prospectively on 68 participants. Thirty‐four participants had been infected with COVID‐19 (all for &lt;6 months) (COVID‐19 group), and another 34 had never been infected with COVID‐19 (control group). The mean 2D‐SWE measurements of both the COVID‐19 group and the control group were compared using an independent t‐test. The mean 2D‐SWE measurements of the COVID‐19 subgroups A (&lt;2 months), B (2 to &lt;4 months) and C (4 to &lt;6 months) were compared using a one‐way ANOVA test (P &lt; 0.05).ResultsThe (mean ± standard deviation) liver stiffness (kPa) of the COVID‐19 group (5.26 ± 1.63 kPa) was significantly higher than the control group (4.30 ± 0.96 kPa) (P = 0.005). There was no significant difference in liver stiffness among subgroups A (5.20 ± 1.79 kPa), B (4.70 ± 1.53 kPa) and C (5.96 ± 1.48 kPa) (P = 0.143) respectively.DiscussionThe mean liver stiffness of 4.30 ± 0.96k Pa in the control group showed a high probability of being normal as per guidelines. Conversely, the mean liver stiffness of 5.26 ± 1.63 kPa in the COVID‐19 group exhibited a statistically significant increase compared to the control group. However, compensated advanced chronic liver disease was ruled out without other known clinical signs, as per guidelines.ConclusionA statistically significant increase in liver stiffness value was observed in the post‐COVID‐19 infection group compared to the group who had never been infected. This highlights the potential for short‐term impact on liver stiffness associated with COVID‐19 infection. However, it is unclear if these changes in liver stiffness are associated with liver injury. Further study is warranted to investigate the effects of COVID‐19 infection and its long‐term impact on the liver.

Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country

BackgroundThe Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. MethodsRetrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). ResultsWe evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. ConclusionWe found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

Prognostic significance of low hepatic fat content in advanced chronic liver disease: MRI-PDFF insights

Introduction and ObjectivesThe mechanisms of hepatic fat loss in late-stage metabolic dysfunction-associated fatty liver disease (MASLD) are enigmatic and the prognostic significance of low hepatic fat content (LHF) in chronic liver disease (CLD) is unknown. Proton density fat fraction (PDFF), measured by magnetic resonance imaging (MRI), is considered the most accurate noninvasive method for quantifying hepatic fat content. This study aimed to address these issues by evaluating PDFF. Patients and MethodsThis is a single-center, retrospective study involving 762 patients with CLD, measuring liver stiffness (LS) using MR elastography and PDFF using MRI. LHF was defined as a PDFF ≤ 2.7 % and hepatic reserve function was assessed using the albumin-bilirubin (ALBI) score. Multivariate analysis explored associations between variables. ResultsLHF was 27 % in the entire cohort, and PDFF was significantly decreased with LS ≥ 5.5 kPa (p < 0.05). On the multivariate analysis, low body mass index and ALBI score were independently associated with LHF (p < 0.05). In advanced CLD (n = 288), ALBI score and PDFF showed a significant negative correlation regardless of etiology (MASLD/non-MASLD: r= -0.613/-0.233), and the prevalence of LHF increased with progression of ALBI grade (p < 0.01 each). In addition, lower PDFF was associated with increased liver-related and all-cause mortality (p < 0.01), and Cox proportional hazards models extracted LHF as an independent prognostic factor, along with ALBI score and hepatocellular carcinoma (p < 0.05 each). ConclusionsIn ACLD, hepatic reserve dysfunction contributed to hepatic fat loss independent of nutritional status, suggesting that LHF may be a poor prognostic factor in all etiologies.

Distribution of Normative Percentiles of Liver Stiffness Measurement Using Ultrasound Shear Wave Elastography in an Adult Asian Indian Population

Abstract Objective The aim of this study was to determine the normative percentiles for liver stiffness measurement (LSM) using shear wave elastography in an adult Asian Indian population as part of the preventive radiology initiative of the Indian Radiological and Imaging Association (IRIA). Methods LSMs were ascertained by two-dimensional (2D) shear wave elastography using the Mindray Resona series of ultrasound machines. The image quality was assessed using the motion stability index (M-STB) and reliability (RLB) map. Ten acquisitions were documented, and an interquartile range-to-median (IQR/M) ratio ≤30% kilopascal (kPa) units was considered a good-quality measurement. A subgroup of the study population without comorbidities was chosen to derive the normative percentile distribution of LSM using a generalized least squares multivariable fractional polynomial regression model that adjusted for sex and body mass index (BMI). The effectiveness of the estimated percentiles was assessed on the entire study population using the greater than 90th percentile value of the LSM as the cutoff for abnormality. Results The study included 852 people who underwent shear wave elastography from June 2022 to July 2023. The magnitude of compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) was 6.81% (95% confidence interval [CI]: 5.30–8.7) and 4.91% (95% CI: 3.67–6.60), respectively. The normative percentiles were estimated from 282 persons without associated comorbidity and risk factors. The mean age (standard deviation [SD]) of the normal individuals was 40.90 ± 12.92 years, and 210 (71.47%) were males. The mean age (SD) of the 570 persons excluded from the normative percentiles analysis was 47.94 (12.49) years and 72.11% were males. The sex- and BMI-adjusted age-specific 90th percentiles of LSM were 8.76, 8.78, 8.96, 8.97, 9.25, and 9.45 kPa for 18 to 20, 21 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years, respectively. Conclusion The sex- and BMI-adjusted age-specific 90th percentiles for LSM using shear wave elastography in Asian Indian adults are almost similar to the greater than 9 kPa cutoff proposed by the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement guidelines to discriminate cACLD and CSPH from normal individuals.

Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous–portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.

Evaluation of spleen stiffness by 2D shear wave elastography for ruling out high risk varices in patients with chronic advanced liver disease. A systematic review and meta-analysis

ObjectivesTo systematically review the accuracy of spleen stiffness measurement (SSM) by 2D- Shear Wave Elastography (2D-SWE) in predicting high risk for bleeding varices (HRV) in cirrhotic patients. MethodsPubMed, Embase, Web of Science, Medline, Cochrane, and Google Scholar databases were searched up to 31/05/2023 for all human studies using 2D-SWE to estimate SSM and endoscopy to detect HRV. Meta-analysis was performed using a generalized linear mixed model. Publication bias was evaluated using the funnel plot asymmetry test. The Area Under the Summarized Receiver Operating Characteristic curve (AUSROC) was estimated using the “mada” package. ResultsA total of 13 studies and 1970 patients were included. Of them, 27.8 % had HRV. The pooled sensitivity and polled specificity of SSM in detecting HRV were 90 % (95 %CI:87–92 %) and 68 % (95 %CI:58–77 %), respectively, with an AUSROC at 0.86 (95 %CI:0.82–0.90). The median cutoff value of SSM in detecting HRV was 34.2 kPa. In studies including exclusively HBV cirrhotic patients, SSM's polled sensitivity and specificity in predicting HRV was 88 % (95 %CI:82–92 %) and 73 % (95 %CI:68–78 %), respectively. The AUSROC was 0.84 (95 %CI:0.81–0.87). The number of repeated measurements per patient (<5 or ≥ 5) did not affect the method’s capability. Using Aixplorer to evaluate SSM had a higher sensitivity in ruling out HRV than other 2D-SWE devices. ConclusionsOur meta-analysis supports that SSM by 2D-SWE has a good diagnostic performance for ruling out HRV in cirrhosis.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients

Non-invasive tests for alcohol-associated liver disease.

Alcohol consumption is a global phenomenon and a major contributor to alcohol-associated liver disease (ALD). Detecting individuals at risk of ALD has been challenging, with only a small fraction of patients being identified at early stages compared to other chronic liver diseases. In response to this challenge, non-invasive tests (NITs) have become essential tools for the detection of ALD, offering opportunities for early identification and intervention to mitigate the disease burden. Non-invasive alcohol consumption biomarkers are crucial in estimating individuals' recent alcohol intake, providing valuable insights into their drinking patterns. Various NITs have been investigated for the initial screening of asymptomatic individuals at risk of ALD, as well as for identifying specific stages of the disease. These NITs are applied in two main clinical scenarios: population-based stratification for identifying and predicting liver-related symptoms, and diagnosing and prognosticating compensated cirrhosis or advanced chronic liver disease in secondary or tertiary care settings. Moreover, NITs play a significant role in the prognostic assessment of patients with various manifestations of ALD, including alcohol-associated hepatitis, decompensated cirrhosis, and metabolic and alcohol-associated liver disease. These tests guide appropriate treatment decisions and predict outcomes. In this review, various NITs for the early detection and monitoring of alcohol consumption were discussed. Additionally, the evaluation of NITs for screening and predicting ALD and liver complications was addressed comprehensively. Future perspectives of NITs for ALD were explored, alongside a thorough discussion of the opportunities and challenges associated with NITs for ALD screening.

Validation and Comparison of Non-Invasive Tests for the Exclusion of High-Risk Varices in Compensated Advanced Chronic Liver Disease

Non-invasive tests (NITs) are a potential alternative to screening oesophagogastroduodenoscopy (OGD) for ruling out high-risk varices (HRVs) in patients with compensated advanced chronic liver disease (cACLD). This retrospective study aimed to externally validate and compare various NITs in a multi-centre Australian cohort. Patients with cACLD were enrolled between January 2013 and December 2022. Liver stiffness measurements (LSMs), clinicopathological data, and OGD results were collected. A total of 210 patients were included. The median age was 57 years and 65.7% were male. The main aetiology of cACLD was hepatitis C (41.9%), and 91.9% of patients were Child–Pugh A. HRV prevalence was 12.4%. The Baveno VI criteria (B6C) was the only NIT that could safely reduce the need for OGDs across all aetiologies of cACLD, with a negative predictive value of 98.6 and spared OGD in 33.8%. The FIB-4 would have avoided the most OGDs (71%); however, the HRV miss rate was 6%. The results suggest that the B6C is the best performing NIT in our cohort and reliably excludes HRVs in cACLD patients, regardless of aetiology. This study confirms that the Baveno VI criteria can be applied in an Australian, mixed aetiology cohort to avoid unnecessary screening OGD.

Serum proteomic profiling of patients with compensated advanced chronic liver disease with and without clinically significant portal hypertension.

Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD). Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups. We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH. We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.

Carcinoma hepatocelular

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. Between 80% and 90% of cases occur in patients with advanced chronic liver disease, traditionally of viral etiology. Its clinical manifestations are very nonspecific and, in most cases, it is asymptomatic. Early diagnosis of HCC is essential, hence the screening strategies based on periodic abdominal ultrasound in patients with chronic liver disease. A peculiarity of this tumor is the possibility of making a non-invasive radiological diagnosis based on dynamic imaging tests (computed tomography or magnetic resonance imaging), reserving a histological study for cases with inconclusive results. The prognosis of HCC depends on the tumor stage as well as characteristics of the underlying liver disease and the patient's functional status, which will determine the different treatment options.

Improved Applicability and Diagnostic Accuracy of the Novel Spleen-Dedicated Transient Elastography Device for High-Risk Esophageal Varices.

Spleen stiffness measurement (SSM) by transient elastography (TE) has been repeatedly demonstrated as the reliable way to rule out the presence of high-risk esophageal varices (HRV). We aimed to evaluate and compare novel vs. standard TE-SSM module performance in diagnosing HRV in patients with compensated advanced chronic liver disease (cACLD). This retrospective study included patients with cACLD; blood data, upper digestive endoscopy performed within 3 months of TE, SSM@50Hz and SSM@100Hz were collected. Overall, 112 patients with cACLD were analyzed (75.9% males, average age of 66, 43.7% alcohol-related chronic liver disease, 22.3% metabolic-associated steatotic liver disease, 6.2% viral hepatitis). Reliable SSM was possible in 80.3% and 93.8% of patients by using SSM@50Hz and SSM@100Hz probe, respectively. At the cut-off 41.8 kPa and 40.9 kPa (Youden), SSM@50Hz and SSM@100Hz had AUROCs of 0.746 and 0.752, respectively, for diagnosing HRV (p = 0.71). At the respective cut-offs, sensitivities for HRV were 92.9% and 100%, resulting in misclassification rates of 7.1% and 0% by using SSM@50Hz and SSM@100Hz. SSM reliably excludes HRV in cACLD patients, with measurements below 41 kPa potentially avoiding EGD in around 50% of cases, with minimal risk of HRV omission. SSM@100Hz demonstrated less measurement failures and no HRV misclassification.

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.

Liver Stiffness Determined by Transient Elastography Is a Simple and Highly Accurate Predictor for Presence of Liver Cirrhosis in Clinical Routine

Introduction: Early detection of patients with advanced chronic liver disease is critical for the prevention of complications and inclusion in surveillance programs for hepatocellular carcinoma. In daily clinical care, it remains challenging to differentiate early cirrhosis from lower fibrosis grades without performing a liver biopsy. The aim of the present study was to assess the performance of different non-invasive detection tools to differentiate cirrhosis from lower fibrosis grades. Methods: Data of 116 patients (51 male, 65 female) with chronic liver disease of various origins undergoing liver biopsy was analyzed. Routine laboratory values, liver stiffness measurement (LSM) by transient elastography, and histological liver assessment were collected. Results: Robust and significant correlations with the histological fibrosis stage were identified for LSM (r = 0.65), the FAST score (0.64), the FIB-4 (0.48), serum aspartate aminotransferase (AST) concentration (0.41), NFS (0.33), international normalized ratio (INR; 0.30), methacetin breath test results (−0.40), and serum albumin concentration (−0.29) by spearman rank correlation. Receiver operating characteristic curves were built for these parameters to separate patients with cirrhosis from those with any other fibrosis stage. The highest AUC was achieved by LSM (0.9130), followed by the FAST score (0.8842), the FIB-4 (0.8644), the NFS (0.8227), INR (0.8142), serum albumin (0.7710), and serum AST (0.7620). The most promising clinical applicability would be an LSM value of 12.2 kPa, achieving 95.7% sensitivity and 75.3% specificity. Conclusion: LSM and FAST score seem to be robust non-invasive measurements for liver fibrosis. LSM and FAST scores may have the potential to reliably detect patients with liver cirrhosis in clinical routine settings.

Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile. This is a retrospective study of a prospectively collected registry of patients with MASLD and compensated advanced chronic liver disease (cACLD) who underwent EGR. Patients were categorized as (1) monotherapy: EGR alone and (2) combination therapy: GLP-1RA prescribed within 6months prior to or after EGR. Outcomes included changes in noninvasive tests of hepatic fibrosis, weight profile, and insulin resistance status at 12months. Thirty patients (body mass index 40.7 ± 9.3kg/m2) were included. Of these, 12 patients (40%) underwent EGR monotherapy, and 18 patients (60%) underwent EGR + GLP-1RA combination therapy. Combination therapy group experienced greater improvements in fibrosis compared to monotherapy group (alanine aminotransferase: reduction by 55 ± 23% vs 29 ± 22% (p = 0.008), NAFLD fibrosis score: reduction by 181 ± 182% vs 30 ± 83% (p = 0.04), liver stiffness measurement on transient elastography: reduction by 54 ± 12% vs 14 ± 45% (p = 0.05)). There were greater reductions in hemoglobin A1c and homeostatic model assessment for insulin resistance in combination therapy compared to monotherapy (p < 0.05). At 12months, the combination therapy group experienced 18.2 ± 6.6% TWL, while monotherapy group experienced 9.6 ± 3.3% TWL (p = 0.004). In patients with MASLD and cACLD, combination of EGR with GLP-1RA is associated with greater improvements in hepatic fibrosis, weight profile, and insulin resistance compared to EGR alone.

Spleen Stiffness-Based Algorithms Are Superior to Baveno VI Criteria to Rule Out Varices Needing Treatment in Patients With Advanced Chronic Liver Disease.

The Baveno VI criteria have set the stage for noninvasive assessment of compensated advanced chronic liver disease (ACLD). The algorithm combining liver stiffness measurement (LSM, <20 kPa) and platelet count (>150,000/μL) safely avoids screening endoscopy for varices needing treatment (VNT) but identifies only a relatively low number of patients. We aimed to evaluate the value of spleen stiffness measurement (SSM) using spleen-dedicated elastography in ruling out VNT. In this real-life multicenter retrospective derivation-validation cohort, all consecutive patients with ACLD (defined by LSM ≥10 kPa) with available upper endoscopy, laboratory results, spleen diameter, LSM, and SSM measured with spleen-dedicated transient elastography were included. VNT were defined as medium-to-large varices or small varices with red spots. In the derivation cohort (n = 201, 11.9% VNT), SSM demonstrated excellent capability at identifying VNT (area under the receiver operating characteristic curve [AUROC] 0.88), outperforming LSM (AUROC 0.77, P = 0.03) and platelets (AUROC 0.73, P = 0.002). In comparison with Baveno VI criteria (33.8% spared endoscopies), the sequential Baveno VI plus SSM and a novel spleen size and stiffness model were able to increase the number of patients avoiding endoscopy (66.2% and 71.1%, respectively) without missing more than 5% of VNT. These findings were confirmed in an external validation cohort of patients with more advanced liver disease (n = 176, 34.7% VNT) in which the number of spared endoscopies tripled (27.3% and 31.3% for SSM-based algorithms) compared with Baveno VI criteria (8.5%). Spleen stiffness-based algorithms are superior to Baveno VI criteria in ruling out VNT in patients with ACLD and double the number of patients avoiding screening endoscopy.