Post Hoc Analysis of a Phase 2 Randomized Trial of Pemafibrate in Metabolic Dysfunction-associated Steatotic Liver Disease: Associations With Platelet Count, Liver Stiffness, and Spleen Volume.

Dietary fatty acids (FA) affect metabolic risk factors. The aim of this study was to explore if changes in dietary fat intake during energy restriction were associated with plasma FA composition. The study also investigated if these changes were associated with changes in liver fat, liver stiffness and plasma lipids among persons with non-alcoholic fatty liver disease. Dietary and plasma FA were investigated in patients with non-alcoholic fatty liver disease (n 48) previously enrolled in a 12-week-long open-label randomised controlled trial comparing two energy-restricted diets: a low-carbohydrate high-fat diet and intermittent fasting diet (5:2), to a control group. Self-reported 3 d food diaries were used for FA intake, and plasma FA composition was analysed using GC. Liver fat content and stiffness were measured by MRI and transient elastography. Changes in intake of total FA (r 0·41; P = 0·005), SFA (r 0·38; P = 0·011) and MUFA (r 0·42; P = 0·004) were associated with changes in liver stiffness. Changes in plasma SFA (r 0·32; P = 0·032) and C16 : 1n-7 (r 0·33; P = 0·028) were positively associated with changes in liver fat, while total n-6 PUFA (r −0·33; P = 0·028) and C20 : 4n-6 (r −0·42; P = 0·005) were inversely associated. Changes in dietary SFA, MUFA, cholesterol and C20:4 were positively associated with plasma total cholesterol and LDL-cholesterol. Modifying the composition of dietary fats during dietary interventions causes changes in the plasma FA profile in patients with non-alcoholic fatty liver disease. These changes are associated with changes in liver fat, stiffness, plasma cholesterol and TAG. Replacing SFA with PUFA may improve metabolic parameters in non-alcoholic fatty liver disease patients during weight loss treatment.

Efficacy of Ruxolitinib By Baseline Spleen Volume in Patients with Polycythemia Vera Resistant to or Intolerant of Hydroxyurea

Thrombocytopenia is often observed after yttrium-90 radioembolization (RE). Possible mechanisms include radiation toxicity to the bone marrow, consumption in the liver due to local radiation effects, and sequestration in the spleen. We sought to identify the causative factors. Patients with complete baseline and 3-month post-RE imaging and laboratory data were included in this retrospective analysis. Univariate and multivariate regression analyses were performed on clinical, procedural, and imaging data. A total of 116 patients were identified (65 male, 51 female; median age 64years). Forty-six patients were treated for primary and 70 for metastatic liver malignancy. Of these, 86 were treated with resin and 30 with glass microspheres; median activity was 1.85GBq. Eighty-three patients underwent whole-liver treatment. Maximum individual change in platelet count was -20.2% leading to new or increased grade of thrombocytopenia in 48 patients (41.4%) by National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.02 criteria. Independent risk factors for decreased platelet count included change in spleen volume (median change +17.5%; p=0.001) and whole-liver (rather than lobar or segmental) treatment (p=0.025). Administered activity and absorbed dose were not associated with change in platelet count. The change in spleen volume itself was associated with previous epidermal growth factor receptor-inhibitor treatment (p=0.002), whole-liver absorbed dose (p=0.027), and multiple-line chemotherapy (0.012) for whole-liver treatments only. Post-RE treatment increase of spleen volume is correlated with decreased peripheral platelet count suggesting a mechanism of increased portal hypertension and hypersplenism being responsible.

Systematic review with meta-analysis: Change in liver stiffness during anti-viral therapy in patients with hepatitis B

Quantitative spleen and liver volume changes predict survival of patients with primary sclerosing cholangitis

Background and Aims. Endoscopic variceal ligation (EVL) of esophageal varices alters the portal pressure. We observed the changes in 2D-shear wave elastography (2D-SWE) measurements of spleen and liver following EVL and tried to identify the predictors for rebleeding and mortality at 6 months. Methods. A prospective observational study of 202 patients who underwent EVL for bleeding esophageal varices was done. 2D-SWE measurements of liver stiffness (LS) and spleen stiffness (SS) and spleen volume (SV) were measured half an hour before, 1 hour, 2 weeks, and 6 weeks after EVL. All were followed up for 6 months for rebleeding and all-cause mortality. Results. 83 patients were in child C (41%). Difference in SV, SS, and LS at 2 and 6 weeks from baseline was noted as Delta 2 (2nd week post-EVL - pre-EVL SV, LS, and SS) and Delta 3 (6th week post EVL - pre - EVL SV, LS and SS), respectively. Mean Delta 2 VOL and Delta 3 VOL were lower in the bleeding and mortality groups. Delta 2 SS, Delta 3 SS, Delta 2 LS, and Delta 3 LS were higher in the rebleeding and mortality groups. These changes were statistically significant. AUROC in predicting rebleeding was the highest for Delta 2 VOL (0.773) and Delta 3 LS (0.764) amongst the USG parameters that performed better than MELD score (0.677). AUROC in predicting mortality was the highest for Delta 3 VOL and Delta 2 VOL-0.873 and 0.842, respectively, and higher than MELD’s (0.641). Statistically significant variables in binary logistic regression analysis for rebleeding were Delta 3 LS and Delta 3 SS and none for mortality. Conclusion. LS, SS, and SV change after EVL. Changes in liver and spleen stiffness at 6 weeks from baseline had good diagnostic accuracy for predicting rebleeding at 6 months.

Gaucher disease type 1 is characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. A safe, effective oral therapy is needed. To determine whether eliglustat, a novel oral substrate reduction therapy, safely reverses clinical manifestations in untreated adults with Gaucher disease type 1. Phase 3, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia. Of 72 patients screened, 40 were enrolled. Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg twice daily; n = 20) or placebo (n = 20) for 9 months. The primary efficacy end point was percentage change in spleen volume in multiples of normal from baseline to 9 months; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count. All patients had baseline splenomegaly and thrombocytopenia (mostly moderate or severe), most had mild or moderate hepatomegaly, and 20% had mild anemia. Least-square mean spleen volume decreased by 27.77% (95% CI, -32.57% to -22.97%) in the eliglustat group (from 13.89 to 10.17 multiples of normal) vs an increase of 2.26% (95% CI, -2.54% to 7.06%) in the placebo group (from 12.50 to 12.84 multiples of normal) for an absolute treatment difference of -30.03% (95% CI, -36.82% to -23.24%; P < .001). For the secondary end points, the least-square mean absolute differences between groups all favored eliglustat, with a 1.22-g/dL increase in hemoglobin level (95% CI, 0.57-1.88 g/dL; P < .001), 6.64% decrease in liver volume (95% CI, -11.37% to -1.91%; P = .007), and 41.06% increase in platelet count (95% CI, 23.95%-58.17%; P < .001). No serious adverse events occurred. One patient in the eliglustat group withdrew (non-treatment related); 39 of the 40 patients transitioned to an open-label extension study. Among previously untreated adults with Gaucher disease type 1, treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count. The clinical significance of these findings is uncertain, and more definitive conclusions about clinical efficacy and utility will require comparison with the standard treatment of enzyme replacement therapy as well as longer-term follow-up. clinicaltrials.gov Identifier: NCT00891202.

Background/Objectives: Endoscopic variceal ligation (EVL) is a common treatment for preventing variceal bleeding in patients with advanced chronic liver disease (ACLD). However, its acute hemodynamic impact is typically assessed using invasive methods, and there is data on short-term spleen stiffness (SS) dynamics are limited. This pilot study aimed to quantify short-interval changes in liver stiffness (LS) and SS following EVL using transient elastography (TE), and to explore their associations with clinical and laboratory parameters. Methods: This prospective observational study enrolled adults with advanced liver disease undergoing esophagogastroduodenoscopy (EGD) with or without EVL at a tertiary center. Liver and spleen TE were performed in a fasted state immediately before endoscopy and repeated within 12 h after EVL. Organ-specific probes and predefined quality criteria were used, and non-parametric methods were applied to assess within-patient changes and correlations. Results: Fifty patients were included in the study: 21 underwent EVL, while the remaining 29 underwent diagnostic endoscopies only. The most common cause was alcohol-related liver disease. Within the EVL subgroup, the median liver stiffness (LSM) increased from 27.6 kPa to 45.1 kPa, and the median spleen stiffness (SSM) increased from 59.9 kPa to 98.3 kPa, both within 12 h. While these increases showed a uniform direction, they did not reach statistical significance. A higher baseline SS predicted a greater LS increase, and stiffness measures correlated with creatinine, disease duration, Child-Pugh class, albumin and ascites. Conclusions: Short-term increases in liver and spleen stiffness following EVL are consistent with acute hemodynamic alterations, such as increased hepatic perfusion and splenic congestion, rather than structural remodeling. These findings, beyond changes in stiffness alone, support the feasibility of integrating TE, particularly the measurement of SS, into early peri-procedural hemodynamic surveillance after EVL. They also justify larger studies with serial time points and direct portal pressure validation.

Practical Measures of Clinical Benefit with Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I

BACKGROUNDLiver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases. Fibrosis progression varies markedly in patients with hepatitis C virus (HCV). Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV.AIMTo investigate changes in liver stiffness measured by transient elastography (TE) in a large, racially diverse cohort of United States patients with chronic hepatitis C (CHC).METHODSWe evaluated the differences in liver stiffness between patients treated with direct-acting antiviral (DAA) therapy and untreated patients. Patients had ≥ 2 TE measurements and no prior DAA exposure. We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment, controlling for age, sex, race, diabetes, smoking status, human immunodeficiency virus status, baseline alanine aminotransferase, and baseline liver stiffness. Separate regression models analyzed the change in liver stiffness as measured by kPa, stratified by cirrhosis status.RESULTSOf 813 patients, 419 (52%) initiated DAA treatment. Baseline liver stiffness was 12 kPa in 127 (16%). Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients, respectively. There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment (0.016 kPa/month; CI: -0.051, 0.084) or in the untreated group (0.001 kPa/mo; CI: -0.090, 0.092), controlling for covariates. A higher baseline kPa score was independently associated with decreased liver stiffness. CONCLUSIONDAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.

BackgroundUveal melanoma (UM) patients with liver metastases often undergo hepatic artery infusion therapy (HAIC). Due to diffuse metastatic spread in the liver, patients often develop hepatomegaly and secondary, portal hypertension which may lead to splenomegaly. This study aimed to compare spleen volumetry and the change of spleen volume (SV) for the evaluation of HAIC treatment response.Patients and methodsIn this study, 179 UM patients (mean age 64.8 ± 11.0y, 53% female) with liver metastases undergoing HAIC were included. Treatment response was analyzed by RECIST 1.1 and SV on CT imaging before and after first HAIC. The correlation of change in spleen and liver volume was analyzed with Spearman test. Overall survival (OS) was calculated as the time from the first HAIC to patient death using Kaplan-Meier test and multivariate analysis was performed for RECIST 1.1 and SV.ResultsIn the study population, OS was 13.8 months (95% CI 10.6-14.7 months). Change in SV before and after first HAIC was +4% (interquartile range [IQR] -4.0%–12.0%, p = 0.49) and showed a weak correlation with OS (r = -0.11, p = 0.18). UM patients with progressive disease (PD) according to RECIST 1.1 showed an increase in SV compared to patients with stable disease (SD) (p = 0.04). Compared to RECIST 1.1, SV was not significant prognostic factor that can identify a change in OS.ConclusionsIn uveal melanoma patients with liver metastases undergoing HAIC, neither the change of SV nor splenomegaly could be identified as prognostic factors for OS.

Background and AimsLiver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population.MethodsIn 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured.ResultsPost-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes.ConclusionsLiver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

A Phase Ib Dose-finding Study of Panobinostat and Ruxolitinib in Myelofibrosis.Consistent with the reports the panobinostat/ruxolitinib combination demonstrated the anticipated AEs but was considered tolerable in a small number of patients as showcased by those experiencing clinical benefits after ≥5 years of treatment

MPN-332: Clinical Benefit of Pelabresib (Cpi-0610) in Combination with Ruxolitinib in JAK Inhibitor Treatment-Naïve Myelofibrosis Patients: Interim Efficacy Subgroup Analysis from Arm 3 of the MANIFEST Phase 2 Study

An open-label, noncomparative study of miglustat in type I Gaucher disease: Efficacy and tolerability over 24 months of treatment