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

INTRODUCTION AND OBJECTIVES: The 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 METHODS: This 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. RESULTS: LHF 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). CONCLUSIONS: In 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.

Mildly Low Serum Sodium Levels in Chronic Liver Disease: At Risk for Sarcopenia and Portal Hypertension.

OBJECTIVE: Hyponatremia and sarcopenia in advanced chronic liver disease (ACLD) are both associated with portal hypertension (PHT) and worse prognosis. This study investigated their interrelationship. METHODS: This retrospective study analyzed 751 patients with CLD who underwent magnetic resonance elastography (MRE) at Nippon Kokan Hospital (Kawasaki, Japan). Patients were classified and studied in five groups based on serum sodium (Na) levels: <135, 135-136, 137-138, 139-140, and >140 mEq/L. PHT was assessed by thrombocytopenia, varices, and ascites, and magnetic resonance imaging (MRI) data were used to diagnose sarcopenia. RESULTS: The proportions of the five groups were 3/4/13/32/48 (%), and the mean liver stiffness (LS) was 6.6/5.7/4.2/3.2/3.2 (kPa), with significant progressive increases at Na < 139 (p< 0.01). The incidence of all PHT events and sarcopenia also increased at <139 (each p < 0.01). By contrast, the LS thresholds for predicting thrombocytopenia, varices, and ascites increased from 3.5 to 4.7 and 5.1, respectively, and were the same at 3.4 for low Na (<139) and sarcopenia (all p < 0.01). Multivariate analysis of factors associated with low Na identified LS and sarcopenia as independent factors (p < 0.05 both). In the Cox proportional hazards model, low Na was a significant prognostic factor in ACLD (hazard ratio (HR) 5.33, p < 0.01); however, the albumin-bilirubin (ALBI) score (HR 2.49) and sarcopenia (HR 4.03) were extracted in the multivariate analysis (p < 0.05 both). CONCLUSIONS: Studies using MRE imaging showed that low Na levels in CLD are associated with worse prognosis, not only due to elevated LS (i.e., PHT) but also the strong association with sarcopenia.

Liver Disease-Related Sarcopenia: A Predictor of Poor Prognosis by Accelerating Hepatic Decompensation in Advanced Chronic Liver Disease.

Background Sarcopenia is considered a prognostic factor for advanced chronic liver disease (ACLD) independent of liver function, but the underlying mechanisms are unknown. Here, we investigated whether sarcopenia contributed to hepatic decompensation and worsened prognosis. Methods This was a single-center retrospective study of 708 patients with chronic liver disease who underwent magnetic resonance elastography (MRE). Magnetic resonance imaging (MRI) was used to diagnose sarcopenia and hepatic decompensation (presence of ascites). Results The incidence of sarcopenia (29% overall) and age were significantly correlated to increased liver stiffness (LS) (p < 0.01 each), but age did not differ for LS ≥ 4 kPa. Rates of thrombocytopenia and varices increased at ≥4 kPa, and ascites (n = 52) accounted for 81% of patients with ≥6 kPa LS. Age, alcoholic liver disease, C-reactive protein, sodium level, and controlling nutritional status score were extracted as factors contributing to sarcopenia (all p < 0.05). In ACLD, sarcopenia was an independent predictor of ascites (p < 0.01), and in a follow-up analysis of 163 patients without ascites at baseline, the incidence of ascites in patients with sarcopenia was significantly higher, even after adjusting for LS and liver severity (p < 0.01). The Cox proportional hazards model indicated albumin-bilirubin score and sarcopenia as independent prognostic factors (p < 0.01 each). Conclusions In ACLD, both portal hypertension and liver disease-related sarcopenia were found to occur at ≥4 kPa. Sarcopenia was accompanied by mildly decreased sodium levels and contributed to the early development of ascites and poor prognosis, independent of liver function.

Clinical significance of hepatic fat loss in chronic liver disease: a study using MRI proton density fat fractionation.

BACKGROUND/AIMS: The liver plays a central role in the fatty acid metabolism. Therefore, cirrhosis is prone to energy malnutrition and is associated with a poor prognosis. On the other hand, proton density fat fraction (PDFF) measured by magnetic resonance imaging (MRI) is a noninvasive and highly accurate method to quantify liver fat. In this study, we aimed to investigate the relationship between hepatic fat loss (HFL) and malnutrition by PDFF measurement in chronic liver disease (CLD). METHODS: In this retrospective single-center study of 485 patients with CLD, hepatic fat content was measured by MRI-PDFF, and CT-measured body composition and CONUT (Controlling Nutritional Status) score were used as nutritional assessment methods, respectively. RESULTS: In the overall cohort, MRI-PDFF was positively correlated with body fat mass, muscle mass and respectively. The HFL defined by PDFF ≤ 2.7% is 25%, and in multivariate analysis, decreased body fat mass and Triglyceride, and increased CONUT score were independent associated factors of HFL (p < 0.05, for all). Additionally, 35% of patients with cirrhosis (n = 107) had HFL, and the Cox proportional hazards model showed that Child-Pugh score and HFL were independent prognostic factors (p < 0.01, for both). CONCLUSIONS: MRI-PDFF was shown to be a useful indicator of malnutrition in cirrhosis reflecting body composition. Preservation of liver fat content in nutritional therapy may improve the prognosis of cirrhotic patients.

Evaluation of the effects of pemafibrate on metabolic dysfunction-associated steatotic liver disease with hypertriglyceridemia using magnetic resonance elastography combined with fibrosis-4 index and the magnetic resonance imaging-aspartate aminotransferase score.

Background and Aim: In this retrospective study, we evaluated the effects of pemafibrate treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia using non-invasive stiffness-based models, including magnetic resonance elastography (MRE) combined with the fibrosis-4 (FIB-4) (MEFIB) index and the magnetic resonance imaging (MRI)-aspartate aminotransferase (AST) (MAST) score. Methods: In total, 179 patients with MASLD treated with pemafibrate were enrolled. We evaluated the effects of 48-week pemafibrate treatment using the MEFIB index, which classifies patients based on the combination of liver stiffness measurement (LSM) on MRE and FIB-4 and the MAST score, which is calculated based on LSM on MRE, MRI-proton density fat fraction (MRI-PDFF), and AST levels. Results: Pemafibrate treatment led to significant reduction in AST, alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) (P = 0.011, <0.001, and <0.001, respectively) and significant improvements in triglyceride and high-density lipoprotein cholesterol levels (P < 0.001 and <0.001, respectively). The MRI-PDFF values were not significantly altered. However, a significant decrease in LSM on MRE was detected (P = 0.003). Evaluation of fibrosis using the MEFIB index and MAST score demonstrated significant improvement (P = 0.004 and <0.001, respectively). Changes in the MAST score showed positive correlation with changes in ALT and GGT levels (r = 0.821, P < 0.001, and r = 0.808, P < 0.001, respectively). Additionally, ALT and GGT levels at baseline were significantly associated with improvements in the MAST score (P < 0.001 and <0.001, respectively). Conclusion: Pemafibrate led to improvements in the MEFIB index and MAST score, as well as liver function. It is a promising therapeutic agent for patients with MASLD and hypertriglyceridemia with the potential to reduce liver-related events.

Diagnosis and Pathogenesis of Sarcopenia in Chronic Liver Disease Using Liver Magnetic Resonance Imaging.

Background Liver magnetic resonance imaging (MRI) is rarely used to evaluate sarcopenia. This study sought to develop new diagnostic criteria for MRI in Asians and investigate the relationship between adipopenia and sarcopenia using MRI proton density fat fraction (PDFF), which is correlated with body fat mass. Methodology This study included 512 patients with chronic liver disease (CLD) who underwent magnetic resonance elastography (MRE). The following parameters were assessed: paraspinal muscle area/height index (PSMI) measured at the level of the superior mesenteric artery and PDFF. The cutoff PSMI and PDFF values for the diagnosis of sarcopenia and adipopenia, respectively, were determined using receiver operating characteristic analysis of Asians with low body mass index. Results Among patients with CLD, the prevalence rates of sarcopenia and adipopenia were 25% and 17%, respectively. We found that sarcopenia increased from stage 3 fibrosis and was inversely correlated with steatosis grade. Multivariate analysis found that MRI-PDFF was associated with sarcopenia. The Kaplan-Meier method in cirrhosis (n = 122) showed that the non-sarcopenia, sarcopenia, and sarcopenia/adipopenia groups had three-year survival rates of 97%, 55% (p < 0.01), and 23%, respectively. The Cox proportional hazards model identified the Child-Pugh score and sarcopenia/adipopenia as independent prognostic factors. Conclusions The new diagnostic criteria for sarcopenia confirmed that the prognosis of cirrhosis can be stratified. Furthermore, sarcopenia with adipopenia was shown to be a phenotype of severe sarcopenia in cirrhosis, and screening for sarcopenia should include cases in the precirrhotic stage.

A Case of Hepatitis C-Related Decompensated Cirrhosis Observed by MRI Imaging Data During Treatment With Direct-Acting Antiviral Agents.

Sofosbuvir/velpatasvir therapy can safely treat hepatitis C virus (HCV)-related decompensated cirrhosis and has been shown to improve liver function at an early stage. However, the pathophysiology of the liver during treatment remains unclear. In this case report, we analyzed hepatic morphology on magnetic resonance imaging during the treatment period and confirmed that liver function and malnutrition were greatly improved with the elimination of HCV, and that rapid hemodynamic changes were occurring in the liver.