Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern linked to increased risks of cardiovascular disease, chronic kidney disease (CKD), and premature mortality. Ginkgo biloba has shown potential therapeutic benefits in conditions characterized by metabolic dysfunction. This study aimed to evaluate the potential protective effects of Ginkgo biloba supplementation on overall survival (OS) and the incidence of cardiovascular and renal outcomes specifically in MASLD patients.

This cohort study included 402,476 participants from the UK Biobank, categorized into MASLD and No steatotic liver disease (SLD) cohorts. Ginkgo biloba users and non-users were compared using inverse probability of treatment weighting to balance baseline characteristics. Clinical outcomes were assessed using Cox proportional hazards models, with subgroup analyses.

Ginkgo biloba supplementation was associated with significantly improved OS [hazard ratio (HR) = 0.79, 95 % confidence interval (CI): 0.64-0.98, p = 0.034) and reduced risks of cardiovascular events (HR = 0.82, 95 % CI: 0.66-1.00, p = 0.012) and CKD (HR = 0.73, 95 % CI: 0.56-0.96, p = 0.012) in the MASLD cohort, while no significant benefits were observed in the No SLD cohort. Subgroup analyses indicated enhanced benefits in older adults, males, individuals with BMI ≥ 25 kg/m², and diabetic patients. The beneficial effects were pronounced in patients with advanced fibrosis.

Ginkgo biloba supplementation is associated with improved survival and reduced cardiovascular and renal risks in MASLD patients, particularly in high-risk subgroups. These findings highlight the potential of Ginkgo biloba as an adjunctive therapy in MASLD management. This is the first large-scale study to examine the potential impact of Ginkgo biloba supplementation on clinical outcomes in MASLD, with fibrosis-stratified analyses providing insights into its differential effects across disease severity.

This study aimed to compare 3-min delayed phase images with 5-min delayed phase images for quantifying hepatic extracellular volume fraction (ECV) using dual-energy CT.

Between January 2020 and July 2022, 80 consecutive patients with chronic liver disease (45 men and 35 women, mean age: 69.3 ± 10.4 years) were included in this study cohort. All patients underwent both 3- and 5-min delayed phase CT scans for assessing focal liver lesions. Extracellular volume fraction value was calculated by the iodine densities of the hepatic parenchyma and aorta and compared between in each phase. Correlations between ECV values in each phase with the albumin-bilirubin (ALBI) score and grade, fibrosis-4 index (Fib-4), and clinical fibrosis stage were statistically analysed.

No significant difference was found in ECV values between the 3- and 5-min delayed phase images (P = 0.056). The ratio of ECV values for 3- to 5-min delayed phase images was 0.984 ± 0.078, ranging from 0.85 to 1.16. The ECV calculated on 3- and 5-min delayed phase images showed strong and moderate correlations with ALBI grade (Spearman's ρ; 0.763 and 0.724, respectively) and ALBI score (Spearman's ρ; 0.707 and 0.668, respectively) and also showed moderate correlations with Fib-4 (Spearman's ρ; 0.548 and 0.543, respectively) and clinical fibrosis stage (Spearman's ρ; 0.468 and 0.435, respectively).

Three-minute delayed phase images were found to be equivalent to 5-min delayed phase images for the calculation of ECV.

Three-minute delayed phase images were found to be equivalent to 5-min delayed phase images for calculating ECV in the same patients, and both 3- and 5-min delayed phase CT scans showed strong and moderate correlation with serum fibrous makers, including ALBI score and grade and fibrosis-4 index. This could facilitate the clinical use of hepatic ECV in daily practice.

The LiverRisk score (LRS) has recently been proposed to predict liver fibrosis and future development of liver-related outcomes in the general population. Here, we performed an external validation of this score.

We used data from National Health and Nutrition Examination Survey 2017-2020, a United States population-based cohort to assess the diagnostic accuracy of the LRS to detect a liver stiffness measurement (LSM) ≥8 and ≥12 kPa. Performance was tested among the entire general population and clinically relevant subgroups.

The cohort comprised 7,025 participants (aged 49 [33-63], 49% male), and 9.7% had an LSM ≥8 and 3.2% had an LSM ≥12 kPa. The area under the receiver characteristic operator curve (AUC) in the overall population was 0.73 (95% confidence interval [CI] :0.71-0.75) and 0.78 (95% CI: 0.74-0.81) to detect an LSM ≥8 and ≥ 12 kPa, respectively, significantly outperforming the fibrosis 4 index (FIB-4) but not the nonalcoholic fatty liver disease fibrosis score, steatosis-associated fibrosis estimator (SAFE), or metabolic dysfunction-associated fibrosis 5 (MAF-5). Performance was consistent among most subgroups, but AUC levels to detect an LSM ≥8 kPa decreased to <0.70 among participants aged 18-40 or 60-80 years, blacks, and individuals with diabetes or liver steatosis. The LRS categorized 80.5% as very low risk, 17.7% as low risk, and 1.8% as at risk, prevalence of an LSM ≥8 in these groups was 6.3%, 20.8%, and 50.5%, respectively. The sensitivity to detect an LSM ≥8 kPa was 47.3% in the overall population (but dropped to 21.3% for individuals aged 18-40 years) despite applying the lowest cut-off, which should yield the highest sensitivity.

The LRS score is a promising new tool to predict liver fibrosis; however, its diagnostic accuracy attenuates especially among patients aged 18-40 or 60-80 years. The overall sensitivity was only 47.3% at the lowest LRS cut-off. Further studies assessing cost-benefit ratios according to the LRS compared to FIB-4 and other risk scores such as MAF-5 and SAFE are required to determine its usefulness in referral strategies.

Invasive right heart catheterization plays a central role in identifying pulmonary hypertension (PH) disorders. However, non-invasive biomarkers of portopulmonary hypertension (PoPH) are required. Liver stiffness evaluated by FibroScan® is useful for the assessment of liver fibrosis in patients with chronic liver diseases. This study sought to investigate the utility of liver stiffness for the classification of PoPH among precapillary PH patients.

A total of 46 patients [38 females, median (interquartile range) age 63.0 (50.8-72.0) years old] with precapillary PH were divided into a PoPH group (N = 6) and a non-PoPH group (N = 40) based on the presence of portosystemic shunts and/or portal hypertension with hepatic venous pressure gradient >5 mmHg.

The PoPH group showed higher cardiac index and lower pulmonary vascular resistance than the non-PoPH group. Other hemodynamic variables and liver fibrosis biomarkers such as fibrosis-4 index and albumin-bilirubin score were comparable between the 2 groups. Liver stiffness measurements in the PoPH group were significantly higher than those in the non-PoPH group [12.8 kPa (9.4-17.3 kPa) vs 4.15 kPa (3.30-5.50 kPa), p < 0.001]. The cut-off value for the classification of PoPH was 8.50 kPa from the receiver operating characteristic curve (area under curve 0.979, 95 % Confidence interval 8.50 kPa - 11.00 kPa).

Liver stiffness evaluated by transient elastography may be a non-invasive biomarker to detect the liver status that caused PoPH among precapillary PH patients.

Predicting the risk of hepatic decompensation guides prognostication and therapy; however, it is challenging in patients with cirrhosis due to metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to improve a previously developed predictive tool of hepatic decompensation in MASLD cirrhosis (ABIDE) by incorporating liver stiffness measurement (LSM).

A multi-centre retrospective cohort of patients with compensated cirrhosis due to MASLD was identified, with decompensation incidence assessed using competing risk regression. The prognostic accuracy of a modified ABIDE model incorporating LSM (ABID-LSM) was assessed using time-dependent AUC (tAUC) and compared with other predictive models.

Out of 388 patients, 273 (70.4%) had available LSM. Hepatic decompensation occurred in 54 (20%) patients during follow-up (median 31 months, range: 20-60). The predictive accuracy at 5 years of ABID-LSM (tAUC 0.80) was better than ABIDE (tAUC 0.75, p = 0.03) and LSM (tAUC 0.63, p < 0.001). The ABID-LSM model calibrated well (slope 0.99) with excellent overall performance (Integrated Brier Score 0.15). A cut-off of 8.1 separated those at high and low risk of hepatic decompensation at 5 years (24% vs. 5%, respectively, sHR = 4.8, p < 0.001). The ABID-LSM model had better predictive ability at 5 years than ALBI, FIB-4, NAFLD Decompensation Risk Score and ANTICIPATE models (all p < 0.001) as well as hepatic vein pressure gradient measurement (tAUC 0.78 vs. 0.71, p < 0.001, n = 60).

The ABID-LSM model has greater accuracy in predicting hepatic decompensation in patients with cirrhosis due to MASLD than existing predictive models. If externally validated, ABID-LSM may identify those who benefit from pharmacotherapy and close monitoring.

Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking.

Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed.

A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x103/mm3, respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log10 IU/ml and 3.8 (3.4-4.1) log10 IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation).

BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low.

Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period.

Phenoconversion, a genotype-phenotype mismatch, challenges a successful implementation of personalized medicine. The aim of this study was to detect and determine phenoconversion using the solanidine metabolites 3,4-seco-solanidine-3,4-dioic acid (SSDA) and 4-OH-solanidine as diet-derived cytochrome P450 2D6 (CYP2D6) biomarkers in a geriatric, multimorbid cohort with high levels of polypharmacy.

Blood samples and data of geriatric, multimedicated patients were collected during physician counsel (CT: NCT05247814). Solanidine and its metabolites were determined via liquid chromatography/tandem mass spectrometry and used for CYP2D6 phenotyping. CYP2D6 genotyping was performed and activity scores (AS) were assigned. Complete medication intake was assessed. A shift of the AS predicted via genotyping as measured by phenotyping was calculated.

Solanidine and its metabolites were measured in 88 patients with complete documentation of drug use. Patients had a median age of 83 years (interquartile range [IQR] 77-87) and the majority (70.5%, n = 62) were female. Patients took a median of 15 (IQR 12-17) medications. The SSDA/solanidine metabolic ratio correlated significantly with the genotyping-derived AS (P < .001) and clearly detected poor metabolizers. In the model adjusted for age, sex, Charlson Comorbidity Index and estimated glomerular filtration rate each additional CYP2D6 substrate/inhibitor significantly lowered the expected AS by 0.53 (95% confidence interval 0.85-0.21) points in patients encoding functional CYP2D6 variants (R2 = 0.242).

Phenotyping of CYP2D6 activity by measurement of diet-derived biomarkers elucidates phenoconversion in geriatric patients. These results might serve as a prerequisite for the validation and establishment of a bedside method to measure CYP2D6 activity in multimorbid patients for successful application of personalized drug prescribing.

Cirrhosis-related inpatient hospitalizations have increased dramatically over the past decade. We used a longitudinal dataset capturing a large metropolitan area in the United States from 2011 to 2021 to evaluate contemporary hospitalization rates and risk factors among frail patients with cirrhosis.

We conducted a retrospective, longitudinal cohort study using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) database, an electronic health record repository that aggregates de-duplicated data across 7 health care systems in the Chicago metropolitan area, from 2011 to 2021. The primary outcome of our study was the rate of hospitalization encounters. Frailty was defined by the Hospital Frailty Risk Score. Hospitalization rates were reported per 100 patients per year, and a multivariable logistic regression analysis identified predictors of annual hospitalization probability.

During the study period, of 36,971 patients, 16,265 patients (44%) were hospitalized (compensated, 18.4%; decompensated, 81.6%). Hospitalization rates were highest in patients with decompensated cirrhosis, reaching nearly 77.3 hospitalizations/100 patients per year. Hospitalization rates among patients with compensated cirrhosis were also high (14.2 vs 77.3 hospitalization/100 patients per year), with odds of annual hospitalization 3 times (odds ratio, 3.1; 95% confidence interval, 2.9-3.4) as high among compensated patients with intermediate frailty and 5 times (odds ratio, 5.2; 95% confidence interval, 4.5-6.0) as high among those with severe frailty (compared with compensated patients with low frailty).

Compensated and decompensated cirrhosis patients with intermediate to severe frailty face a substantially increased odds of annual hospitalizations compared with those with low frailty. Future work should focus on targeted interventions to incorporate routine frailty screenings into cirrhosis care and to ultimately minimize high hospitalization rates.

An association between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and the development of extrahepatic malignancies has been demonstrated. However, the association of fibrosis with extrahepatic cancer is unclear. Our study aimed to test the long-term association between liver fibrosis marker and the incidence of hepatic and extrahepatic malignancies.

A retrospective cohort study of a nationally representative sample, following 763 752 adult Clalit health services members without pre-existing liver-related diagnoses or malignancies for 14.67 years. The adjusted association between baseline liver Fibrosis-4 score (FIB-4; FIB-4 ≥ 2.67 indicated presumed advanced fibrosis), assessed from routine laboratory measurements, and incident cancer was assessed through multivariable Cox regression models.

The study included 763 752 people (mean age 54.3 ± 8.2 years, 43.9% males). Presumed advanced fibrosis was associated with a 16% greater risk for malignancy compared to the risk of those with no fibrosis (hazard ratio (HR) = 1.16; 95% CI, 1.10-1.22), adjusting for age, sex, ethnicity, socioeconomic status, peripherality index, baseline smoking, and obesity. The association of advanced fibrosis with malignancy was stronger when the age-specific FIB-4 cutoff was applied (HR = 1.40; 1.34-1.46) and in a subsample of subjects with MASLD diagnosis at baseline (HR = 1.43; 1.12-1.83). The association remained robust across sex, age, and ethnic groups. Both inconclusive fibrosis and fibrosis were strongly associated with malignancy of the liver or bile ducts [(HR = 1.41; 1.21-1.66) and (HR = 5.66; 4.19-7.64), respectively].

Liver fibrosis score is independently associated with malignancy occurrence and certain types of malignancies, and may serve as an indicator of high-risk cancer in the general population.

Noninvasive and cost-effective markers are needed to replace esophagogastroduodenoscopy in the screening for severe esophagogastric varices (EGVs) and portal hypertensive gastropathy (PHG).

This study evaluated the performances of several commonly used fibrosis markers in assessing EGVs and PHG in cirrhosis patients.

Retrospective cohort study.

A series of 323 patients with cirrhosis were consecutively enrolled and endoscopically followed up until variceal eradication was achieved. The Fibrosis-4 (FIB-4) score, albumin-bilirubin (ALBI) index, aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and Lok score were calculated for each patient upon first admission. The performances of these markers in assessing EGVs and PHG were determined.

In the screening for clinically relevant esophageal varices (CREVs), none of the markers showed a significant ability to differentiate CREVs from non-CREVs (P > .05). The AAR (area under the curve (AUC): 0.581, sensitivity: 52.0%, specificity: 66.1%, P = .033) and the GPR (AUC = 0.596, sensitivity: 64.0%, specificity: 50.0%, P = .033) fairly differentiated clinically relevant gastric varices (CRGVs) from non-CRGVs patients. Moreover, no correlation was noted between PHG and CREVs (r = .016, P = .778) or between PHG and CRGVs (r = -.024, P = .666). Furthermore, no difference in the severity of PHG before and after variceal eradication was detected (P = .224).

The studied markers revealed poor to no ability to assess EGVs or PHG. Hence, they cannot be used to substitute EGD in the screening for EGVs. Furthermore, endoscopic eradication of EGVs did not affect the severity of PHG.

This study aimed to develop and validate a non-invasive model for screening advanced liver fibrosis and predicting liver-related outcomes in patients with type 2 diabetes mellitus (T2DM).

This study included patients with T2DM from five tertiary hospitals for the development and internal validation of a non-invasive model. Advanced liver fibrosis was defined as a liver stiffness measurement ≥12 kPa. An external validation cohort was obtained from the National Health and Nutrition Examination Survey (NHANES), and the model's predictive performance for hepatocellular carcinoma (HCC) and liver-related mortality was assessed in the UK Biobank.

In total, 28,197 patients with T2DM were enrolled. In the derivation cohort (n = 1,129), waist circumference, alanine aminotransferase, aspartate aminotransferase, platelet count, and albumin were identified as independent risk factors for advanced fibrosis and were fit to develop the "DiabetesLiver score." The area under the curve (AUC) was 0.835 (95% confidence interval [CI]: 0.781-0.890), significantly higher than the AUCs of non-invasive tests (all p < 0.01). It maintained high AUCs of 0.870 and 0.823 in the internal validation (n = 1,000), and NHANES cross-sectional (n = 1,432) cohorts, respectively. A dual cutoff of 2.39 and 3.99 with sensitivity ≥90% and specificity ≥90%, respectively, was used to classify patients into low-, middle-, and high-risk groups. In the UK Biobank cohort (n = 24,636), the high-risk group had an elevated risk of liver-related outcomes.

The DiabetesLiver score demonstrated good performance in identifying advanced liver fibrosis and the development of liver-related events in the T2DM population.

National Natural Science Foundation.

The close interplay between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes supports the need to identify beneficial combination therapies of antidiabetic medications targeted for the treatment of MASLD. This study aimed to investigate the complementary effects of combination therapy with pioglitazone (PIO) and empagliflozin (EMPA) on MASLD in individuals with type 2 diabetes.

In a randomized, open-label trial, 50 participants with type 2 diabetes and MASLD were assigned 1:1:1 to receive PIO 15 mg, EMPA 10 mg, or a combination (PIO 15 mg plus EMPA 10 mg) daily for 24 weeks. Liver fat fraction and stiffness were evaluated using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE), respectively.

Combination therapy resulted in the largest reduction in liver fat and stiffness among treatment groups. Participants experiencing a relative reduction ≥ 30% or an absolute reduction ≥ 5% in liver fat were the most prevalent in the combination group (100.0% vs. 57.1% in PIO and 87.5% in EMPA, p = 0.010). In addition, the combination group showed the highest proportion of individuals with a relative reduction ≥ 30% in liver fat and ≥ 20% in liver stiffness than the monotherapy groups (50.0% vs. 21.4% in PIO and 6.3% in EMPA, p = 0.029). Combination therapy did not induce the changes in subcutaneous fat deposition observed in the monotherapy groups, but it did show the most substantial reduction in visceral fat, concurrently showing the largest increase in adiponectin level across the three groups (p = 0.036).

Combination therapy of PIO with EMPA showed synergistic benefits for MASLD in individuals with type 2 diabetes, compensating for the inadequate or unfavorable effects of monotherapies; ClincialTrials.gov number, NCT03646292.

The trial was registered at ClinicalTrials.gov (registration number: NCT03646292).

To assess the performance of fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS) and aspartate aminotransferase to platelet ratio index (APRI) for advanced fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD) subgroups categorized by concomitant liver conditions.

We conducted a multicentered study comprising inpatients with type 2 diabetes mellitus and MAFLD. Participants were categorized into 2 groups: MAFLD with pure metabolic etiologies (MAFLD-P) and MAFLD with mixed etiologies (MAFLD-M). Diagnostic performance of FIB-4, NFS, and APRI was assessed by area under the curve (AUC), sensitivity, and specificity.

This study comprised a total of 1475 participants, with a mean (SD) age of 58.4 (13) years and 835 (56.6%) males. FIB-4 and APRI had higher AUCs for advanced fibrosis in the MAFLD-M group than in the MAFLD-P group (MAFLD-M vs MAFLD-P: FIB-4 0.680 vs 0.591, P = .0442; APRI 0.723 vs 0.631, P = .0363). No significant difference was observed in the AUC of NFS between the 2 subgroups (MAFLD-M 0.572 vs MAFLD-P 0.617; P = .3237). Besides, the sensitivity of FIB-4 (69.6% vs 54.0%; P = .019) and APRI (43.5% vs 26.1%; P = .005) was higher in the MAFLD-M group. However, no significant difference in sensitivity of NFS and specificity of FIB-4, NFS, and APRI was observed between subgroups.

In this diagnostic study of the type 2 diabetes mellitus population, FIB-4 and APRI showed better performance for identifying advanced fibrosis in MAFLD with mixed etiologies.

To determine the impact of hepatic dysfunction on the motor manifestations of Parkinson's disease.

We conducted a retrospective cohort study using data from the Parkinson's Progression Markers Initiative. Liver fibrosis was defined using the Fibrosis-4 score. Our primary outcome was the association of baseline Fibrosis-4 score with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score. Additional outcomes were MDS-UPDRS part II, MDS-UPDRS part IV, Hoehn and Yahr stage, and levodopa equivalent daily dose. We used linear regression models to evaluate associations at baseline and 5 years after enrollment. We used linear mixed models to evaluate the association of liver fibrosis with the progression of motor dysfunction. Models were adjusted for demographics, comorbidities, alcohol use, time since Parkinson's disease diagnosis, levodopa equivalent daily dose, and genetic predisposition.

We included 360 people with Parkinson's disease with a mean age of 61.8 years (standard deviation 9.7) and 41.1 % women. There was a significant association between liver fibrosis and baseline MDS-UPDRS part III score (β=2.3, 95 % CI: 0.2, 4.5). Liver fibrosis was also correlated with higher interhemispheric signal asymmetry on DAT-SPECT scans in the anterior putamen (p < 0.05 by Wilcoxon rank sum test). There was no correlation with Fibrosis-4 score and any other motor assessment at baseline or after 5 years. Patients with elevated Fibrosis-4 scores had a slower rate of progression in MDS-UPDRS part III scores.

In people with Parkinson's disease, the presence of comorbid liver fibrosis was associated with more severe motor dysfunction early, but not later, within their disease course.

Objective To evaluate the effect of pemafibrate (PEM) on metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We retrospectively evaluated 43 patients with hyperlipidemia and MASLD to determine changes in clinical factors between the start of PEM treatment and 0.5 years later. Using FibroScan, 39 of 43 patients were evaluated for liver stiffness (LS; kPa) and controlled attenuation parameter (CAP; dB/m). None of the patients had decompensated cirrhosis. Results Thirty patients were women, the median age was 66 years old, the median fibrosis-4 (FIB-4) score was 2.52, the median LS was 8.05 kPa, and the median CAP was 280.5 dB/m at the start of PEM treatment. AST, ALT, ALP, γGTP, and triglyceride levels decreased 0.5 years after starting PEM treatment, but FIB-4, LS, and CAP values did not decrease. However, LS decreased in patients with a FIB-4 index ≥1.3 at the start of PEM treatment, whereas it did not change in patients with a FIB-4 index <1.3. Similarly, LS decreased in patients with a value ≥8 kPa at the start of treatment and did not change in those with <8 kPa. The decreased LS group had higher baseline ALT and LS levels and lower ALT levels during 0.5 years of follow-up than the increased LS group. Conclusion At the initiation of PEM treatment, the LS decreased in patients with MASLD complicated by hyperlipidemia and moderate LS (FIB-4>1.3 or LS >8 kPa). Although there is currently no approved treatment for MASLD, PEM may be a viable treatment option for MASLD with mild LS.

Statins may lower the risk of hepatocellular carcinoma (HCC) by mitigating liver fibrosis progression.

To evaluate the association between statin use and the risk of HCC and hepatic decompensation, with an emphasis on liver fibrosis progression, among adult patients with chronic liver disease (CLD).

This cohort study used data from the Research Patient Data Registry from 2000 to 2023 on patients 40 years or older with CLD and a baseline Fibrosis-4 (FIB-4) score of 1.3 or higher. Participants were grouped into statin users and nonusers. Data analysis was conducted from August 5, 2024, to January 3, 2025.

Statin use.

Outcomes included 10-year cumulative incidence of HCC and hepatic decompensation as well as transitions in liver fibrosis risk categories based on FIB-4 scores. Statin use was defined as exposure to a cumulative defined daily dose (cDDD) of 30 or more. Fibrosis progression was assessed through FIB-4 group transitions (low, intermediate, and high) over time. Outcomes were analyzed using adjusted subhazard ratio (aSHR) and trends in serial FIB-4 scores.

The analysis included 16 501 participants (mean [SD] age, 59.7 [11.0] years; 6750 females [40.9%] and 9751 males [59.1%]) with CLD, including 3610 statin users and 12 891 nonusers. Statin users exhibited a significantly lower 10-year cumulative incidence of HCC (3.8% vs 8.0.%; risk difference, -4.2%; 95% CI, -5.3 to -3.1%) and hepatic decompensation (10.6% vs 19.5%; risk difference, -9.0%; 95% CI, -10.6 to -7.3) compared with nonusers. The aSHR was 0.67 (95% CI, 0.59 to 0.76) for HCC and 0.78 (95% CI, 0.67 to 0.91) for hepatic decompensation. Exposure to lipophilic statins and duration of statin use (≥600 cDDDs) were associated with further reductions in HCC and hepatic decompensation risks. Among 7038 patients with serial FIB-4 data, patients with intermediate baseline FIB-4 scores, 14.7% (95% CI, 13.0% to 16.6%) of statin users transitioned to the high group compared with 20.0% (95% CI, 18.6% to 21.5%) of nonusers. For patients with high baseline FIB-4 scores, 31.8% (95% CI, 28.0% to 35.9%) of statin users transitioned to the intermediate group and 7.0% (95% CI, 5.2% to 9.6%) transitioned to the low-risk group, compared to 18.8% (95% CI, 17.2% to 20.6%) and 4.3% (95% CI, 3.5% to 5.2%) of nonusers, respectively (P < .001).

This cohort study found that statin use was associated with a reduced risk of HCC and hepatic decompensation in patients with CLD, as well as improved FIB-4 group transitions over time. These findings provide support for the potential role of statins in prevention of HCC and liver disease progression.

Many studies have shown a close relationship between type 2 diabetes mellitus and obesity. Glucagon-like peptide-1 (GLP-1) agonists are particularly preferred as antidiabetic medications for obese patients with type 2 diabetes because they not only help with glycemic control but also promote weight loss by slowing gastric emptying. Fatty liver disease, a significant complication of obesity, can progress to hepatic fibrosis and cirrhosis in later stages. Platelets ratio index (APRI), fibrosis-4 index (FIB-4), indices are two of the most studied indirect markers of hepatic fibrosis. Our study aimed to investigate the effect of exenatide, a GLP-1 agonist, on the APRI and FIB-4 indices in obese patients with type 2 diabetes mellitus. We included obese patients with type 2 diabetes treated with exenatide at the endocrinology and metabolism outpatient clinics of Bakırköy Dr. Sadi Konuk Training and Research Hospital between January 2015 and May 2018. We calculated the APRI and FIB-4 indexes retrospectively using data on aspartate aminotransferase, alanine aminotransferase, platelet counts, and ages. The study included 170 patients, with an average age of 48.27 ± 11 years. We compared the APRI and FIB-4 indices at the third and sixth months after the onset of exenatide and before the treatment. While there was no significant change in the FIB-4 index with treatment, the APRI index showed a significant decrease. In conclusion, our study observed a significant decrease in the APRI index with exenatide treatment, while the FIB-4 index remained unchanged. More research is needed on liver fibrosis indices in the obese population.

Background: The triglyceride-glucose (TyG) index has emerged as a novel surrogate marker of insulin resistance, but its changes after hepatitis C virus (HCV) eradication remain unclear. This study aimed to evaluate changes in the TyG index following direct-acting antiviral (DAA) treatment. Methods: HCV-infected patients achieving sustained virological response 12 weeks post-treatment (SVR12) were prospectively enrolled from May 2015 to June 2023. Exclusion criteria included the following: (1) failure to achieve SVR12; (2) use of anti-diabetes or anti-hyperlipidemia medications; and (3) hepatitis B virus or human immunodeficiency virus co-infection. Changes in lipid profiles, TyG index, and homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated from baseline to SVR12. Insulin resistance was defined as HOMA-IR ≥ 2.5. The optimal TyG index cut-off for predicting insulin resistance was determined using the Youden Index. Results: A total of 111 patients (median age: 61.0 years; 45.9% male) were included. The TyG index correlated positively with HOMA-IR (Pearson's r = 0.32, p < 0.001). Among patients with pre-existing insulin resistance, significant improvements were observed at SVR12 in both HOMA-IR (4.0 [IQR: 3.1-5.4] vs. 2.5 [IQR: 2.0-3.9]; p < 0.001) and TyG index (8.47 [IQR: 8.08-8.68] vs. 8.36 [IQR: 8.00-8.71]; p = 0.028). Using 8.27 as the optimal TyG index cut-off, similar improvements were noted in HOMA-IR (2.8 [IQR: 2.0-4.3] vs. 2.3 [IQR: 1.5-3.8]; p = 0.031) and TyG index (8.62 [IQR: 8.46-8.83] vs. 8.52 [IQR: 8.27-8.89]; p = 0.003). Conclusions: The TyG index is a valuable tool for monitoring changes in insulin resistance after HCV eradication, particularly in patients with baseline insulin resistance.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.

Objective The progression of liver fibrosis and a male sex are risk factors for hepatocarcinogenesis under nucleos(t)ide analog (NA) therapy. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for hepatocarcinogenesis. This study aimed to investigate the factors involved in hepatocarcinogenesis during NAs therapy, including MAFLD. Methods This study is a retrospective study [observation period: median 9.4 years (2.1-19.6 years)]. The subjects were 164 patients taking NAs for more than 2 years and were hepatitis B envelope antigen (HBeAg)-negative with undetectable hepatitis B virus (HBV)-DNA. The patient had no history of hepatocellular carcinoma (HCC). We investigated the profile of HCC onset after NAs therapy using a decision tree analysis Results HCC developed in 20.7% (34/164) of the patients during the observation period. The prevalence of MAFLD was significantly higher in the HCC group than in the non-HCC group (64.7% vs. 43.9%, p=0.03). In particular, in the low-medium risk group classified by PAGE-B, MAFLD increased the risk of HCC development. According to a multivariate analysis, fibrosis-4 (FIB-4) index≥2.67, a male sex, and MAFLD (OR 2.4, 95%CI 1.0-6.0, p=0.04) were independent factors associated with the onset of HCC. In a decision tree analysis, MAFLD was the second classifier for the onset of HCC, next to the FIB-4 index (MAFLD 62.5%, non-MAFLD 28.5%). Conclusions We found that MAFLD was an independent risk factor for HCC in HBeAg-negative patients with undetectable HBV-DNA after NAs therapy. We further revealed that MAFLD was the second-best classifier for hepatocarcinogenesis, next to the FIB-4 index. MAFLD therefore appears to have a synergistic effect on hepatocarcinogenesis with hepatic fibrosis.

Chronic hepatitis B (CHB) patients who have sustained virological suppression (SVS) still develop hepatocellular carcinoma(HCC), and the risk factors for developing HCC in these patients are not fully understood. This study included a total of 5234 patients who achieved SVS. After SVS, the incidence rate of HCC was 1.9% in 1-8 years and 1.33% in 9-16 years. There was a significant difference between the two periods (P < 0.001). After 1-8 years and 9-16 years of SVS, after multivariate analysis and IPTW adjustment, the factors related to the occurrence of HCC were men, hypertensive patients, diabetes patients and high FIB-4 scores. In summary, patients with CHB who have achieved SVS may still develop HCC. Among them, men, hypertensive patients, diabetes patients and high FIB-4 scores should be listed as the key monitoring objects of HCC. Clinical trial number: Not applicable.

This study investigates the link between inflammatory markers and liver fibrosis in type 2 diabetes mellitus (T2DM) patients with metabolic dysfunction-associated fatty liver disease (MAFLD).

From Oct 2020 to Oct 2024, 769 hospitalized T2DM patients were studied. They were split into Control (n=389) and Experimental groups (T2DM with MAFLD, n=380). The Experimental group was further divided based on FIB-4 scores into non-fibrosis (FIB-4< 1.3, n=267), suspected fibrosis (1.3 ≤ FIB-4 ≤ 2.67, n=99), and advanced fibrosis (FIB-4 > 2.67, n=14). Logistic regression identified factors affecting liver fibrosis, while ROC analysis assessed the predictive value of NLR, SIRI, PLR, and PHR for liver fibrosis in T2DM-MAFLD patients.

The Experimental group showed higher BMI, FPG, TG, TC, LDL-C, ALT, AST, ALB, GGT, and SUA, but lower age, diabetes duration, MPV, and HDL-C (P< 0.05). Compared to non-fibrosis, suspected fibrosis had higher age, diabetes duration, MPV, AST, and NLR, and lower LY, PLR, PHR. Advanced fibrosis featured higher age, AST, NLR, FPG, HbA1c, SIRI, and lower LY, RBC, LDL-C, PLR, PHR, Hb, PLT, and ALB (P< 0.05). Logistic regression identified NLR, SIRI, PLR, and PHR as significant factors for liver fibrosis. ROC analysis showed AUCs of 0.712 (NLR), 0.757 (SIRI), 0.703 (PLR), and 0.806 (PHR) with sensitivities and specificities varying among markers. Optimal cut-offs were 1.573 (NLR), 1.465 (SIRI), 110.819 (PLR), and 185.379 (PHR).

NLR, SIRI, PLR, and PHR significantly influence liver fibrosis in T2DM patients with MAFLD, aiding in its diagnosis and management.

Current treatments for chronic hepatitis B (CHB) virus involve nucleos(t)ide analogs and pegylated interferon-alpha (PEG-IFNα). This study compares the efficacy and safety of PEG-IFNα monotherapy with its combinations with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in managing CHB. We included 147 treatment-naïve patients divided into three groups: Group A (PEG-IFNα-2b with ETV), Group B (PEG-IFNα-2b with TDF), and Group C (PEG-IFNα-2b monotherapy). Evaluations occurred every 12 weeks up to 48 weeks. The Kaplan-Meier method showed no significant differences in cumulative HBsAg loss, but HBV DNA clearance rates were higher in the TDF group than in the ETV group (P = 0.01). Higher incidences of elevated alanine aminotransferase (ALT), aspartate aminotransferase, and thrombocytopenia were observed in the TDF group compared to other groups. After propensity score matching, the TDF group had a higher undetectable HBV DNA rate than the IFN group, but no significant differences in HBsAg clearance rates. Both TDF and ETV groups achieved more significant HBsAg reductions from baseline to week 48 than the IFN group (P < 0.05). ETV showed a lower HBeAg clearance rate (30.00% vs 87.50%, P < 0.05) but higher ALT normalization (76.92% vs 45.45%, P < 0.05). In the TDF group, patients with lower baseline HBsAg levels, high ALT levels, and lower aspartate aminotransferase-to-platelet ratio index (APRI) scores were more likely to achieve HBsAg loss. These findings suggest that TDF and ETV are effective for viral suppression, with TDF showing superior HBV DNA clearance but more adverse events.

This study investigates how different treatments for chronic hepatitis B (CHB), a widespread liver infection, compare in effectiveness and safety. By evaluating the use of pegylated interferon-alpha alone and in combination with two other drugs, entecavir and tenofovir disoproxil fumarate (TDF), researchers found that TDF offers better viral suppression but also comes with more side effects. For patients receiving TDF combined with PEG-IFN therapy, low HBsAg levels, elevated alanine aminotransferase levels, and lower APRI scores were associated with a higher likelihood of achieving HBsAg loss. Consistent with previous findings, this study confirms the benefits of nucleos(t)ide analog plus PEG-IFN therapy for CHB treatment and further explores which patients are more likely to benefit from combination therapy. Furthermore, this study underscores the importance of further monitoring adverse events in patients receiving combination therapy.

Extrahepatic manifestations of chronic hepatitis B virus (HBV) infection include development of kidney disease (KD). While anti-HBV treatment reduces the risk of liver-related events, the impact of HBV treatment on KD remains unclear. Using a large US-based electronic medical record (EMR) database, we examined whether patients with HBV are at higher risk of developing KD, whether the development of KD is associated with HBV-related liver disease, and whether anti-HBV treatment mitigates these risks.

Data were queried from the IQVIA Ambulatory EMR database from 2006 to 2020. Propensity score matching was performed to better ensure balance across analyses. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs for onset of KD between groups.

Among patients with and without HBV (n = 11,772 each), those with HBV were more than twice as likely to develop KD vs. matched controls without HBV infection (HR, 2.18 [95% CI, 1.90-2.50]; p < 0.001); most events occurred after age 55 years. Patients with HBV and concomitant hypertension, diabetes, or obesity had a greater likelihood for development of KD by age 75 years (19% with HBV vs. 6% without HBV); the cumulative probability of developing KD among patients with HBV along with concomitant comorbidities surpassed the additive risk of developing KD among those who had the comorbidities without HBV or only had HBV. Among patients with HBV, advanced liver disease was not significantly associated with KD. Patients treated with antivirals had a lower risk for KD compared with untreated HBV patients (HR, 0.61 [95% CI, 0.42-0.87]; p < 0.01).

HBV infection contributes to the development of KD, and anti-HBV treatment can lower KD risk. As such, clinicians should consider screening patients for HBV infection or initiating treatment early, particularly in patients with risk factors for KD.

Introduction Hepatitis C virus (HCV) infection is still a worldwide health issue, leading to progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma. Detection at early stages of advanced liver fibrosis is critical for early treatment and appropriate management. Liver biopsy, though still considered the gold standard for fibrosis staging, is invasive and costly and poses possible risks and complications. The application of non-invasive biomarkers such as the platelet-to-lymphocyte ratio (PLR) as substitute tools for fibrosis staging is on the rise. This study aimed to determine the utility of PLR in predicting advanced liver fibrosis in HCV infection. Methodology This retrospective observational study was carried out at the department of hepatogastroenterology, Sindh Institute of Urology and Transplantation (SIUT), Pakistan, in patients aged ≥18 years old who had established chronic infection of HCV and had undergone liver biopsy and shear wave elastography (SWE) in the period between January 2018 and December 2023. Exclusion criteria consisted of coexisting liver and hematological disorders and incomplete patient clinical records. Laboratory parameters, demographic variables, and fibrosis scores were compared. The ratio of PLR was calculated. Area under the receiver operating characteristic (AUROC) curve analysis was done for PLR, and at an optimal cutoff, diagnostic accuracy was obtained for PLR and was compared to aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4). Results A total of 107 HCV-infected patients, who had a mean age of 49.1 ± 8.9 years, were enrolled in the study. Liver biopsy confirmed significant fibrosis (meta-analysis of histological data in viral hepatitis (METAVIR) score ≥ 2) in 56 (52.3%) patients. The PLR was significantly lower in patients with advanced fibrosis (4.17 ± 1.44 vs. 6.8 ± 1.99, p ≤ 0.001). The AUROC for PLR was 0.879 (p ≤ 0.001). At an optimal cutoff of ≤5.41, PLR showed a high sensitivity of 85.71%, specificity of 86.27%, and an excellent diagnostic accuracy of 85.98%. The diagnostic accuracy of PLR was far superior to APRI (37%) and FIB-4 (40%) in predicting advanced liver fibrosis in HCV patients. Conclusion PLR is a simple, cost-effective, highly sensitive, non-invasive marker for advanced liver fibrosis in chronic infection with HCV. It is superior to currently established non-invasive markers such as APRI and FIB-4 and can be utilized as a good screening tool for fibrosis in resource-limited situations.

This study examines the impact of glucosamine on the progression and outcomes of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction and alcohol-associated liver disease (MetALD) using a large scale cohort.

Present study utilized inverse probability of treatment weighting (IPTW) to adjust for confounders in this cohort study. Participants were classified based on glucosamine use, and primary and secondary outcomes included all-cause mortality, liver cirrhosis, cardiovascular disease, cerebrovascular disease, and chronic kidney disease (CKD) incidences. Cox proportional hazards models were used to assess hazard ratios and 95 % confidence intervals.

We found that glucosamine significantly reduces all-cause mortality in MASLD and MetALD cohorts after IPTW adjustment (P < 0.001). Additionally, glucosamine use was associated with lower liver cirrhosis incidence in MASLD both before (P = 0.003) and after IPTW adjustment (P = 0.046). Glucosamine also decreased cardiovascular disease risk in MASLD (P < 0.001) and MetALD (P = 0.037) cohorts, though it showed no significant impact on cerebrovascular disease incidence. Furthermore, glucosamine use was associated with a significantly lower incidence of CKD in the MASLD cohort (P = 0.034) and the entire cohort (P = 0.030), but not in the No steatotic liver disease cohort or MetALD cohort.

The findings suggest that glucosamine could be a beneficial supplementary therapy for managing steatotic liver diseases, particularly for patients at high risk for cardiovascular and renal complications. Further clinical trials are required to validate these potential benefits.

This study aims to identify the most accurate and useful non-invasive method to replace liver biopsy for the diagnosis of non-alcoholic fatty liver disease (NAFLD) before bariatric surgery and postoperative follow-up in morbidly obese patients.

This single-center study is a retrospective analysis of prospectively collected data from 68 morbidly obese patients who underwent laparoscopic sleeve gastrectomy with intraoperative liver biopsy. Preoperative non-invasive diagnostic methods, including fatty liver index, NAFLD fibrosis score, enhanced liver fibrosis score, FibroScan, magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS)-PDFF, and magnetic resonance elastography (MRE) were compared against liver biopsy results. Diagnostic performance was assessed using Spearman's correlation and receiver operating characteristic (ROC) curve analysis.

Liver biopsy confirmed the presence of steatosis in 92.7% of patients, Nonalcoholic Steatohepatitis (NASH) in 64.7%, and liver fibrosis (≥F1) in 72.0%. MRI-PDFF and MRS-PDFF demonstrated the highest diagnostic accuracy for NASH, with the strongest correlation with histological findings. For liver fibrosis, MRE showed the strongest correlation with histological fibrosis stage, while FibroScan-Liver Stiffness Measurement (LSM) demonstrated better diagnostic performance in ROC analysis. However, the overall diagnostic quality of non-invasive methods for fibrosis assessment remained modest, with no method achieving a quality value above 0.6.

MRI-PDFF and MRS-PDFF were the most accurate noninvasive methods for diagnosing NASH in morbidly obese patients. For liver fibrosis, FibroScan-LSM may be more suitable for detection, while MRE may better reflect fibrosis severity. Further studies are needed to assess the cost-effectiveness and clinical applicability of these methods.

More accurate stratification of patients with chronic hepatitis C after permanent hepatitis C virus (HCV) clearance by direct-acting antivirals (DAAs) is important for improving long-term surveillance and treatment. The aim of this study was to stratify patients with chronic hepatitis C who are at risk of developing hepatocellular carcinoma (HCC) after HCV cure.

This multicenter, retrospective cohort study included 3177 consecutive adult chronic hepatitis C patients without decompensated cirrhosis who were treated with all-oral DAAs. The primary study endpoints were long-term cumulative de novo HCC incidence, HCC recurrence rates, and survival. Additionally, we analyzed the development of HCC by patients without cirrhosis, stratified by age and fibrosis status according to the FIB-4 index.

After exclusions, data from 3024 patients were available for analysis. The overall median follow-up period was 6.5 years. None of the patients with non-cirrhosis/FIB-4 < 1.45 (n = 475) developed HCC regardless of background factors. For patients with non-cirrhosis/FIB-4 ≥ 3.25, older age had a greater impact on HCC incidence (log-rank test: p = 0.038). In addition, metabolic factors, including body mass index and diabetes mellitus, were not related to HCC incidence. HCC recurrence commonly occurred within 5 years after HCV cure; nevertheless, HCV cure contributed to an improvement of survival rates.

Age is a pivotal factor in predicting de novo HCC development following HCV cure in patients with moderate to advanced fibrosis. Conversely, patients with mild fibrosis (FIB-4 < 1.45) may be eligible for discharge from specialized care after achieving HCV elimination.

Triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophages and systemic levels of soluble TREM2 (sTREM2) appear critical in the development of chronic liver disease (CLD) and seem relevant in its detection. The aim of this study was to examine sTREM2 as a marker for early CLD and its potential to predict posthepatectomy liver failure (PHLF) in patients undergoing partial hepatectomy.

sTREM2 was assessed in the plasma of 108 patients undergoing liver resection. Blood was drawn prior to surgery (preop) and on the first and fifth postoperative day.

Preop sTREM2 levels were similar across different indications for resection (p = 0.091). Higher preop sTREM2 levels were associated with advanced hepatic fibrosis (p = 0.030) and PHLF (p = 0.007). Fibrosis-4 index (FIB-4) (p = 0.619) and model for end-stage liver disease (MELD) (p = 0.590) did not show a difference between patients grouped by their CLD. Comparing the AUC from receiver-operating characteristic analysis, sTREM2 (AUC = 0.708) outperformed FIB-4 (AUC = 0.529), MELD (AUC = 0.587), Child-Pugh grading (AUC = 0.570) and LiMAx (liver maximum capacity test) (AUC = 0.516) in predicting PHLF. Similarly, in uni- and multivariate analysis, only sTREM2 proved predictive for PHLF (p = 0.023). High-risk (p = 0.003) and low-risk (p = 0.011) cut-offs for systemic sTREM2 levels could identify patients at risk for adverse outcomes after surgery. Finally, high sTREM2 was associated with decreased overall survival after liver surgery (p <0.001).

Circulating sTREM2 shows sensitivity for early-stage, asymptomatic liver disease, irrespective of the underlying indication for liver surgery. Assessment of CLD via sTREM2 monitoring could improve early detection of CLD and improve outcomes after liver surgery.

Soluble TREM2 (sTREM2) has previously been shown to correlate with the degree of chronic liver disease. We found that even in patients undergoing liver resection, who generally do not suffer from end-stage liver disease, sTREM2 reflects liver fibrosis status and predicts postoperative development of liver dysfunction. This is especially relevant for liver surgeons and patients, as postoperative liver dysfunction is the main reason for postoperative mortality. Our findings are also important for hepatologists, as early detection of liver fibrosis and cirrhosis is paramount for overall patient survival and we can show that even in a cohort with a median model for end-stage liver disease score of 6, sTREM2 is able to distinguish patients based on their liver fibrosis status.