RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives.

Metabolic dysfunction-associated steatotic liver disease (MASLD)-and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage-corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

Spleen stiffness measurement by vibration-controlled transient elastography at 100 Hz for non-invasive predicted diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a modelling study.

BACKGROUND: In patients with compensated advanced chronic liver disease (cACLD), risk of clinically significant portal hypertension (CSPH) can be estimated by applying non-invasive tests such as liver stiffness measurement (LSM), platelet count, and, in some cases, BMI. We aimed to assess the diagnostic utility of spleen stiffness measurement (SSM) at 100 Hz as a standalone non-invasive test for CSPH and to evaluate its incremental value compared with the ANTICIPATE±NASH model in patients with cACLD. METHODS: For this modelling study, patients were recruited from 16 expert centres in Europe. Patients who underwent characterisation by hepatic venous pressure gradient (HVPG) and non-invasive tests (ie, LSM, platelet count, and SSM at 100 Hz) at one of the participating centres between Jan 1, 2020, and Dec 31, 2023, were considered for inclusion. Only patients aged 18 years or older with Child-Pugh class A cACLD, shown by LSM 10 kPa or more or F3 or F4 fibrosis on liver histology, were included. The overall cohort was split into the derivation cohort (patients recruited between Jan 1, 2020, and Dec 31, 2022) and the temporal validation cohort (patients recruited between Jan 1, 2023, and Dec 31, 2023). The ANTICIPATE±NASH model was applied to assess individual CSPH probability and SSM was investigated as a standalone non-invasive test for CPSH; in combination with platelet count and BMI; and in a full model of SSM, LSM, platelet count, and BMI (ie, the Non-Invasive CSPH Estimated Risk [NICER] model). All models were binary logistic regression models. The primary outcome was CSPH. We evaluated the discriminative utility of the models by calculating the area under the receiver operating characteristics curve (AUC) and creating calibration plots and calibration of intercept, slope, and integrated calibration index. FINDINGS: 407 patients with cACLD were included, 202 (50%) in the derivation cohort and 205 (50%) in the validation cohort. Median age was 60·0 years (IQR 55·0-66·8); 275 (68%) of 407 patients were male and 132 (32%) were female. 164 (40%) of 407 patients had metabolic dysfunction-associated steatotic liver disease (MASLD), 133 (33%) had MASLD with increased alcohol intake or alcohol-related liver disease, 75 (18%) had viral hepatitis (61 [81%] of whom had sustained virologic response of hepatitis C virus or suppression of hepatitis B virus DNA), and 35 (9%) had other chronic liver diseases. 241 (59%) patients had CSPH. Median SSM was 45·0 kPa (32·1-65·4) and LSM was 21·4 kPa (14·1-31·6). SSM and LSM had similar AUCs for prediction of CSPH in the derivation cohort (0·779 [95% CI 0·717-0·842] vs 0·781 [0·718-0·844]; p=0·97) and in the validation cohort (0·830 [0·772-0·887] vs 0·804 [0·743-0·864]; p=0·50). The SSM-based model comprising platelet count and BMI had a similar AUC as the ANTICIPATE±NASH model in both the derivation cohort (0·849 [0·794-0·903] vs 0·849 [0·794-0·903]; p=0·999) and in the validation cohort (0·873 [0·819-0·922] vs 0·863 [0·810-0·916]; p=0·75). The NICER model had a significantly higher AUC for prediction of CSPH than the ANTICIPATE±NASH model in the derivation cohort (0·889 [0·843-0·934] vs 0·849 [0·794-0·903]; p=0·022) and in the validation cohort (0·906 [0·864-0·946] vs 0·863 [0·810-0·916]; p=0·012). INTERPRETATION: The addition of SSM to LSM, BMI, and platelet count outperformed the ANTICIPATE±NASH model for CSPH risk stratification in our cohort of contemporary patients with cACLD. SSM improves the non-invasive diagnosis of CSPH, supporting its implementation into clinical practice. FUNDING: Echosens.

Porto-sinusoidal vascular disorder in surgical candidates for liver metastases: Prevalence, non-invasive diagnosis, and burden on surgical outcomes.

BACKGROUND & AIMS: Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data is available. We aimed to i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; ii) assess whether liver (LSM) and spleen stiffness measurements (SSM) could diagnose PSVD and predict post-operative complications. METHODS: This is a prospective single center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient we evaluated previous exposure to chemotherapy, co-morbidities, elastography, type of surgery, histological features at the resection specimen, morbidity [post-hepatectomy liver failure (PHLF), major complications according to Clavien-Dindo], and 90-days survival. RESULTS: Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. SSM <21 kPa (NPV 87%) and >40 kPa (PPV 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of PHLF (22 vs 45%) and major complications (11 vs 31%). Pre-operative LSM was associated with post-operative morbidity. The cut-offs LSM <4.5 kPa and >8 kPa predicted the risk of clinically significant PHLF (0%, 11%, and 33% in LSM <4.5 kPa, 4.5-8 kPa,>8 kPa respectively) and major complications (0%, 25%, 44% in LSM <4.5 kPa, 4.5-8 kPa,>8 kPa, respectively). CONCLUSIONS: PSVD is very common among patients undergoing liver surgery for metastases and it is associated with increased morbidity. LSM and SSM can correctly identify patients with PSVD and those at risk of clinically relevant post-operative complications.

Sarcopenia evaluated by EASL/AASLD computed tomography-based criteria predicts mortality in patients with cirrhosis: A systematic review and meta-analysis.

Background & Aims: Sarcopenia is associated with increased morbidity and mortality in patients with cirrhosis, but its definition in current literature is very heterogeneous. We performed a systematic review and meta-analysis to assess the association between mortality and sarcopenia evaluated by computed tomography (CT) in patients with cirrhosis, both overall and stratified for the criteria used to define sarcopenia. Methods: Medline, Embase, Scopus, and Cochrane Library were searched up to January 2023. We included studies assessing sarcopenia presence with CT scans and providing data on the risk of mortality. Adjusted hazard ratios (HRs) and 95% CIs were pooled using a random-effects model. Results: Thirty-nine studies comprising 12,827 patients were included in the meta-analysis. The summary prevalence of sarcopenia was 44% (95% CI 38-50%). The presence of sarcopenia (any definition) was an independent predictor of mortality with an adjusted HR of 2.07 (95% CI 1.81-2.36), and the result was consistent in all subgroup analyses. The prognostic role of the EASL/AASLD criteria was confirmed for the first time with an HR of 1.86 (95% CI 1.53-2.26) (n = 14 studies). The cut-offs used to define sarcopenia based on psoas muscle parameters varied among studies, thus, a subgroup analysis was not feasible. There was no substantial heterogeneity for the main estimates and no significant risk of publication bias. Conclusions: Sarcopenia on CT is associated with a 2-fold higher risk of mortality in patients with cirrhosis. The cut-offs proposed by EASL/AASLD are prognostically relevant and should be the recommended criteria used to define sarcopenia in clinical practice. Impact and implications: Sarcopenia assessed by the reference standard (computed tomography scan) is an independent predictor of mortality in patients with cirrhosis, with a 2-fold increase in the risk of death in all sensitivity analyses. This finding is particularly valid in patients from Europe and North America, and in transplant candidates. Stratifying for the parameters and cut-offs used, we confirmed for the first time the prognostic impact of the definition proposed by EASL/AASLD, supporting their use in clinical practice. Psoas muscle assessment is promising, but data are still limited and too heterogeneous to recommend its routine use at present.

Malnutrition independently predicts mortality at 18 months in patients hospitalised for severe acute respiratory syndrome corona virus 2 (SARS-coV-2).

RATIONALE: To investigate the association between malnutrition and patient outcome following hospitalisation for Corona Virus Disease 2019 (COVID-19). METHODS: In April 2020, 268 adult patients (235 included in the follow-up) hospitalised for COVID-19 infection were evaluated for malnutrition risk and diagnosis using modified Nutritional Risk Screening 2002 and modified Global Leadership Initiative on Malnutrition criteria (GLIM), respectively. An 18-month follow-up was carried out to assess the incidence and the associated risk factors for death and re-hospitalization. RESULTS: The outcome was unknown for 33 patients. Death occurred in 39% of the 235 patients included in the follow-up. The risk of death was independently associated with malnutrition risk or diagnosis of malnutrition, whereas the male sex showed a protective association. The Kaplan-Meier survival curves showed that patients with diagnosis of malnutrition had lower survival rate. The re-hospitalization rate was 31% and was negatively associated with BMI≥25, and positively associated with length of hospitalisation for COVID-19 and with cancer comorbidity. CONCLUSIONS: In hospitalized patients for SARS-CoV-2 disease, both malnutrition risk (p = 0.050) and diagnosis of malnutrition (p = 0.047 with modified GLIM and C-reactive protein >0.5 mg/dL; p = 0.024 with modified GLIM and C-reactive protein >5 mg/dL) were predictive risk factors for mortality, whereas male sex was associated with lower risk of death. Overweight at time of hospitalization and the length of hospitalisation were respectively protective and risk factor for re-hospitalization after discharge.

Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder.

BACKGROUND AND AIMS: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension. APPROACH AND RESULTS: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value. CONCLUSIONS: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.

Evaluation of ChatGPT as a Counselling Tool for Italian-Speaking MASLD Patients: Assessment of Accuracy, Completeness and Comprehensibility.

BACKGROUND: Artificial intelligence (AI)-based chatbots have shown promise in providing counseling to patients with metabolic dysfunction-associated steatotic liver disease (MASLD). While ChatGPT3.5 has demonstrated the ability to comprehensively answer MASLD-related questions in English, its accuracy remains suboptimal. Whether language influences these results is unclear. This study aims to assess ChatGPT's performance as a counseling tool for Italian MASLD patients. METHODS: Thirteen Italian experts rated the accuracy, completeness and comprehensibility of ChatGPT3.5 in answering 15 MASLD-related questions in Italian using a six-point accuracy, three-point completeness and three-point comprehensibility Likert's scale. RESULTS: Mean scores for accuracy, completeness and comprehensibility were 4.57 ± 0.42, 2.14 ± 0.31 and 2.91 ± 0.07, respectively. The physical activity domain achieved the highest mean scores for accuracy and completeness, whereas the specialist referral domain achieved the lowest. Overall, Fleiss's coefficient of concordance for accuracy, completeness and comprehensibility across all 15 questions was 0.016, 0.075 and -0.010, respectively. Age and academic role of the evaluators did not influence the scores. The results were not significantly different from our previous study focusing on English. CONCLUSION: Language does not appear to affect ChatGPT's ability to provide comprehensible and complete counseling to MASLD patients, but accuracy remains suboptimal in certain domains.

Metformin and the Liver: Unlocking the Full Therapeutic Potential.

Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes.

Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis.

BACKGROUND AND AIMS: A simple noninvasive score, the Agile 3+ score, combining liver stiffness measurement, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for the identification of advanced fibrosis in patients with suspected NAFLD. We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease, so currently, the two terms are interchangeable. APPROACH AND RESULTS: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the April 24, 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤ 0.451) and rule-in (≥ 0.679) cutoffs. We included 6 observational studies (total of 6955 participants) with biopsy-proven NAFLD [mean age 53 (SE 4) years, mean body mass index 30.9 (SE 2.3) kg/m 2 , 54.0% men, prevalence of diabetes 59.6%]. The pooled prevalence of advanced fibrosis (≥ F3) was 42.1%. By the rule-out cutoff, the overall sensitivity and specificity were 88% (95% CI: 81-93%; I2 = 89.2%) and 65% (95% CI: 54-75%; I2 = 97.6%), respectively. By the rule-in cutoff, the overall sensitivity and specificity were 68% (95% CI: 57-78%; I2 =91.1%) and 87% (95% CI: 80%-92%; I2 =96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age ( p < 0.01), body mass index ( p < 0.01), and, although not statistically significant, sex ( p = 0.06). CONCLUSIONS: Our systematic review and meta-analysis suggests that Agile 3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Unlocking the Power of Late-Evening Snacks: Practical Ready-to-Prescribe Chart Menu for Patients with Cirrhosis.

The efficacy of the late-evening snack (LES) has been extensively studied due to the impact of the longest intermeal duration occurring at night in patients with cirrhosis. While actual clinical guidelines on nutrition in chronic liver disease recommend an LES, no specific nutritional compositions have been reported by the European Association for the Study of the Liver (EASL) and the European Society for Clinical Nutrition and Metabolism (ESPEN). Late-evening snacks vary greatly among studies, including natural foods and/or nutritional supplements, yet oral supplements still need to fully meet the LES's nutritional composition. In addition, many hepatologists need to gain experience in nutritional approaches and have access to registered dieticians who can help them manage patients with liver disease. Therefore, this review study aims to summarise evidence regarding using LESs and the mechanisms behind long starvation in patients with cirrhosis. It also provides a practical nutritional guide with several LES options based on common natural foods tailored to special patients' nutritional requirements and geographical backgrounds. In preventing accelerated starvation and related protein malnutrition and sarcopenia in patients with cirrhosis, the nutritional composition of LESs is essential. The proper and straightforward application of the LES's rational nutrition is an advantage to cirrhotic patients and should be carried out by healthcare professionals to enhance the overall liver function and nutritional status of patients with cirrhosis.

Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease.

Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47-3.41) and large (HR 3.86, 95% CI 2.34-6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39-5.05) and large (HR 4.90, 95% CI 2.49-9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16-6.74) or large (HR 5.29, 95% CI 1.96-14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Accuracy of spleen stiffness measurement for the diagnosis of clinically significant portal hypertension in patients with compensated advanced chronic liver disease: a systematic review and individual patient data meta-analysis.

BACKGROUND: The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting. METHODS: In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 109 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 109 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 109 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164. FINDINGS: Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I2<25%) for most estimates. INTERPRETATION: Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective ß-blocker treatment. FUNDING: None.

Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study.

BACKGROUND: Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). METHODS: We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. RESULTS: After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3-4.0) kPa, 2nd tertile: 5.3 (4.9-5.9) kPa and 3rd tertile: 7.9 (6.7-9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1-147) vs. 85.8 (48.3-139) vs. 111 (59.3-203) µg/L, p = 0.021; median hepcidin: 2.5 (1.1-5.2) vs. 4.4 (2.5-7.3) vs. 4.1 (1.9-6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23-3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15-3.13, p = 0.013). CONCLUSIONS: Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders.

From Listing to Recovery: A Review of Nutritional Status Assessment and Management in Liver Transplant Patients.

Liver transplantation (LT) is a complex surgical procedure requiring thorough pre- and post-operative planning and care. The nutritional status of the patient before, during, and after LT is crucial to surgical success and long-term prognosis. This review aims to assess nutritional status assessment and management before, during, and after LT, with a focus on patients who have undergone bariatric surgery. We performed a comprehensive topic search on MEDLINE, Ovid, In-Process, Cochrane Library, EMBASE, and PubMed up to March 2023. It identifies key factors influencing the nutritional status of liver transplant patients, such as pre-existing malnutrition, the type and severity of liver disease, comorbidities, and immunosuppressive medications. The review highlights the importance of pre-operative nutritional assessment and intervention, close nutritional status monitoring, individualised nutrition care plans, and ongoing nutritional support and monitoring after LT. The review concludes by examining the effect of bariatric surgery on the nutritional status of liver transplant recipients. The review offers valuable insights into the challenges and opportunities for optimising nutritional status before, during, and after LT.

Osteosarcopenia in NAFLD/MAFLD: An Underappreciated Clinical Problem in Chronic Liver Disease.

Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), affects a significant portion of the population worldwide. NAFLD is characterised by fat accumulation in the liver, while NASH is associated with inflammation and liver damage. Osteosarcopenia, which combines muscle and bone mass loss, is an emerging clinical problem in chronic liver disease that is often underappreciated. The reductions in muscle and bone mass share several common pathophysiological pathways; insulin resistance and chronic systemic inflammation are the most crucial predisposing factors and are related to the presence and gravity of NAFLD and to the worsening of the outcome of liver disease. This article explores the relationship between osteosarcopenia and NAFLD/MAFLD, focusing on the diagnosis, prevention and treatment of this condition in patients with CLD.

Individual and population screening of varices needing treatment by a simple, safe and accurate test.

BACKGROUND: Several tests have been developed to screen varices needing treatment (VNT) in different screening settings. We aimed to develop simple estimators to quantify VNT risk and spare endoscopy while missing <5% of VNT, adapted to different screenings in the main etiologies. METHODS: 2,368 patients with chronic liver disease were included. The main VNT predictors were platelets, prothrombin index (PI) and LSM. Their interactions led to score construction, LIP: (LSM*45)/(PI*platelets), and BLIP: BMI-adjusted LIP in NAFLD. Scores were categorized either for population (VNT sensitivity ≥95%) or individual (negative predictive value ≥95%) VNT screening. RESULTS: 1) Scores diagnosing VNT. AUROCs were, PLER: 0.767 Anticipate: 0.773 (p=0.059 vs previous), LIP: 0.779 (p=0.136), PLEASE: 0.789 (p=0.196). 2) Population screening performance was in increasing order (with missed VNT rate), Baveno6 criteria: 23.9% (2.5%), Anticipate: 24.5%, p=0.367 vs previous (3.3%), PLER: 27.3%, p<0.001 (3.6%), LIP: 33.4%, p<0.001 (4.2%), PLEASE: 35.2%, p=0.006 (3.6%). In NAFLD, LIP: 38.6%, BLIP: 40.8%, p=0.038. 3) Individual screening performance was, expanded Baveno6 criteria: 42.7%, LIP: 54.1%, p<0.001. In NAFLD, performance was, NAFLD-cirrhosis criteria: 66.7%, BLIP: 74.6%, p<0.001. CONCLUSION: LIP combined simplicity, performance and safety in each etiology. In NAFLD, BMI-adjusted LIP outperformed other tests.