Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). New nomenclature and distinction of metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. We assessed the impact of different levels of alcohol consumption on SLD severity and its interaction with metabolic comorbidities. METHODS: Population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation) and U.S. (validation) cohorts. Controlled attenuation parameter (CAP≥275 dB/m) identified SLD. At least one cardiometabolic risk factor was required to define MASLD. Among MASLD patients, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as LSM≥8 kPa and at-risk MASH as FAST score≥0.35. RESULTS: The derivation cohort included 2,227 subjects with MASLD (9% reported low, 14% moderate alcohol consumption), and 76 cases with MetALD. Overall prevalence of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (OR=1.69 [95%CI 1.06-2.71]). CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease, in a similar magnitude to MetALD spectrum. IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently co-exist, but their joint effects on liver fibrosis remain uncertain. This study analyzes subjects form the general population with metabolic dysfunction-associated steatotic liver disease (MASLD) enrolled in Spain and U.S. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that patients with unhealthy metabolic status and MASLD have no safe limits of daily alcohol intake.

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD. METHODS: This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: 340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Phenotypes of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

Point-of-Care Noninvasive Prediction of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Individual risk prediction of liver-related events (LRE) is needed for clinical assessment of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) patients. We aimed to provide point-of-care validated liver stiffness measurement (LSM)-based risk prediction models for the development of LRE in patients with NAFLD, focusing on selecting patients for clinical trials at risk of clinical events. METHODS: Two large multicenter cohorts were evaluated, 2638 NAFLD patients covering all LSM values as the derivation cohort and 679 more advanced patients as the validation cohort. We used Cox regression to develop and validate risk prediction models based on LSM alone, and the ANTICIPATE and ANTICIPATE-NASH models for clinically significant portal hypertension. The main outcome of the study was the rate of LRE in the first 3 years after initial assessment. RESULTS: The 3 predictive models had similar performance in the derivation cohort with a very high discriminative value (c-statistic, 0.87-0.91). In the validation cohort, the LSM-LRE alone model had a significant inferior discrimination (c-statistic, 0.75) compared with the other 2 models, whereas the ANTICIPATE-NASH-LRE model (0.81) was significantly better than the ANTICIPATE-LRE model (0.79). In addition, the ANTICIPATE-NASH-LRE model presented very good calibration in the validation cohort (integrated calibration index, 0.016), and was better than the ANTICIPATE-LRE model. CONCLUSIONS: The ANTICIPATE-LRE models, and especially the ANTICIPATE-NASH-LRE model, could be valuable validated clinical tools to individually assess the risk of LRE at 3 years in patients with NAFLD/NASH.

Enterohepatic Shunt-Driven Cholemia Predisposes to Liver Cancer.

BACKGROUND & AIMS: Pathogenesis of hepatocellular carcinoma (HCC), which kills millions annually, is poorly understood. Identification of risk factors and modifiable determinants and mechanistic understanding of how they impact HCC are urgently needed. METHODS: We sought early prognostic indicators of HCC in C57BL/6 mice, which we found were prone to developing this disease when fed a fermentable fiber-enriched diet. Such markers were used to phenotype and interrogate stages of HCC development. Their human relevance was tested using serum collected prospectively from an HCC/case-control cohort. RESULTS: HCC proneness in mice was dictated by the presence of congenitally present portosystemic shunt (PSS), which resulted in markedly elevated serum bile acids (BAs). Approximately 10% of mice from various sources exhibited PSS/cholemia, but lacked an overt phenotype when fed standard chow. However, PSS/cholemic mice fed compositionally defined diets, developed BA- and cyclooxygenase-dependent liver injury, which was exacerbated and uniformly progressed to HCC when diets were enriched with the fermentable fiber inulin. Such progression to cholestatic HCC associated with exacerbated cholemia and an immunosuppressive milieu, both of which were required in that HCC was prevented by impeding BA biosynthesis or neutralizing interleukin-10 or programmed death protein 1. Analysis of human sera revealed that elevated BA was associated with future development of HCC. CONCLUSIONS: PSS is relatively common in C57BL/6 mice and causes silent cholemia, which predisposes to liver injury and HCC, particularly when fed a fermentable fiber-enriched diet. Incidence of silent PSS/cholemia in humans awaits investigation. Regardless, measuring serum BA may aid HCC risk assessment, potentially alerting select individuals to consider dietary or BA interventions.

Weil syndrome coincident with upper gastrointestinal bleeding.

A 48 year old male was referred to our center due to a gastrointestinal bleeding with melena secondary to a Forrest IIb gastric ulcer treated endoscopically. Physical examination revealed bilateral conjunctival suffusion, bradypsychia, and asterixis. Epidemiological history included a trip to Dominican Republic two weeks before, presenting later a flu-like syndrome. He had no history of NSAID use. Laboratory tests showed a normocytic anemia, leukocytosis with neutrophilia, acute renal failure, severe hyponatremia, a predominant direct hyperbilirubinemia, hyperamylasemia, and mild coagulopathy (Table 1). An abdominal ultrasound was performed, with no pathological findings, and a chest-abdominal computed tomography (CT), bilateral diffuse ground glass pulmonary opacities and pleural effusion, mild hepatomegaly, and peritoneal and gastrohepatic ligament lymphadenopathy, with no signs of acute pancreatitis. A second look upper endoscopy revealed a Forrest III gastric ulcer. Gastric biopsies results ruled out malignancy and Helicobacter pylori infection. Due to his recent travel history combined with his characteristic signs and symptoms a clinical diagnosis of leptospirosis was made and empirical antibiotic therapy with meropenem was started. The serology for Leptospira was positive (IgG 1/1600) and antibiotic therapy was de-escalated to ceftriaxone with clinical and analytical remission on day five of his hospital stay with complete radiological resolution at 6 months.

Prediction of clinical events by liver stiffness and chronic kidney disease by NAFLD in patients with type-2 diabetes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with poorer glycemic control and a higher risk of type-2 diabetes (T2D) complications, extrahepatic and cardiovascular disease (CVD). Our study aim was to evaluate the association between NAFLD, T2D complications, and the development of overall clinical events (OCE) (CV, liver-related, and mortality) in patients with T2D. METHODS: Prospective single-center study comprising T2D subjects with no history of CVD and non-T2D matched controls. Patients were selected from the Outpatient Diabetes Clinic of Vall d'Hebron Hospital and related primary care centers. RESULTS: 186 diabetics and 57 controls were included. Amongst T2D, 124/186 subjects had NAFLD (66.6%). T2D-NAFLD subjects showed a heavier metabolic burden and higher median liver stiffness (5.6kPa [4.5-7.3] vs 4.8 [4.2-5.8]; p=0.004) compared to non-NAFLD diabetics. During a median follow-up of 5.6 years, 33 (17.7%) T2D patients developed OCE vs 4 (7.0%) controls (p=0.049). No differences were found for OCE between NAFLD and non-NAFLD diabetics (16.9% vs 19.4%; p=0.68). CV was the most reported outcome and only one liver event occurred. NAFLD diabetics showed more often chronic kidney disease (CKD), whereas T2D complications and subclinical CVD rates were similar. A higher liver stiffness, older age, and male gender were independently associated with OCE amongst the entire T2D population and NAFLD diabetics. CONCLUSIONS: NAFLD and liver stiffness were associated with CKD and clinical outcomes in diabetics, respectively. A hepatic evaluation is recommended to identify high-risk T2D patients that would benefit from early referral to specialized care.

[Metabolic morbidity in the prison population of Catalonia, Spain]. / Morbilidad metabólica en la población penitenciaria de Cataluña.

OBJECTIVE: To investigate the prevalence of metabolic morbidity (MM) amongst prison inmates. DESIGN: Multicentric, cross-sectional observational study. SETTING: All (nine) prisons in Catalonia. PARTICIPANTS: Convicted inmates that are not in an «open regime¼, whose healthcare relies on the Prison Primary Care Teams. INTERVENTIONS: MM was defined as the presence of at least one component of the metabolic syndrome, i.e., obesity, arterial hypertension, type2 diabetes, and/or dyslipidemia. The variables collected included anthropometric measurements, medical history and laboratory values related to MM. The source of information was the Catalan Primary Healthcare Services Information System (SISAP). MAIN MEASUREMENTS: The prevalence of MM, overall and by several participant subcategories, was calculated. To investigate the risk factors associated to a higher prevalence of MM, a multivariable logistic regression analysis was carried out and expressed as adjusted odds ratios and 95% confidence intervals. RESULTS: 4338 inmates were studied, of whom 93.9% were male. Mean age was 38.4years, 51.7% were born in European Union countries, and 6.7% were infected by HIV. The variables associated with a significantly increased risk of presenting MM were older age and HIV infection, whereas certain geographical origins (i.e., non-UE European countries, Maghreb and Sub-Saharan Africa) were associated with lower risk of MM. CONCLUSIONS: In spite of being an overall young population, prison inmates present high rates of MM. Older age, HIV infection and geographic origin appear as the most strongly associated factors with MM in the prison population. MM should be detected early in order to prevent complications. Prevention, screening and treatment of MM ought to be considered a priority in the clinical routine of prison healthcare professionals.

Prevalence estimation of significant fibrosis because of NASH in Spain combining transient elastography and histology.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non-alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. METHODS: This was an observational, retrospective, cross-sectional, population-based study with merged data from two Spanish datasets: a large (N = 12 246) population-based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi-centric biopsy-proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy-proven cohort. RESULTS: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53-11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13-8.75). In the biopsy-proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2-4). The estimated prevalence of NASH F2-3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29-5.98) and 0.70% (95% CI 0.10-4.95) respectively. CONCLUSIONS: These estimations provide an accurate picture of the current prevalence of NASH-related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.

Outcomes and potential surrogate markers for future clinical trials of non-alcoholic steatohepatitis cirrhosis.

Non-alcoholic steatohepatitis has emerged as a major public health problem, and the burden of non-alcoholic steatohepatitis cirrhosis is projected to increase by 64%-156% by 2030. The threat is aggravated by the fact that are currently no approved drugs for the treatment of non-alcoholic steatohepatitis. In this paper, we review the main challenges to drug development in patients with non-alcoholic steatohepatitis cirrhosis, and describe the opportunities brought by the advances in the understanding of the clinical and pathophysiological nuances of cirrhosis. The design of therapeutic regimens for non-alcoholic steatohepatitis cirrhosis will vary according to the specific cirrhosis substage (compensated vs decompensated), and the specific mechanistic basis of therapy, targeted either at improving aetiology-specific pathways and/or at more general aetiology-agnostic processes. The understanding of the probabilistic expectations for the whole range of potential outcomes, rooted at different mechanistic drivers at each specific substage, will be essential in order to choose adequate estimands and therapeutic strategies for clinical trials and individual patients with non-alcoholic steatohepatitis cirrhosis. Finally, we provide a summary of the main pitfalls and uncertainties in the design of clinical trials for non-alcoholic steatohepatitis cirrhosis and discuss potential biomarkers for use in trials and practice for these patients.

Metabolic-associated fatty liver voxel-based quantification on CT images using a contrast adapted automatic tool.

BACKGROUND & AIMS: Metabolic-dysfunction associated fatty liver disease (MAFLD) is highly prevalent and can lead to liver complications and comorbidities, with non-invasive tests such as vibration-controlled transient elastography (VCTE) and invasive liver biopsies being used for diagnosis The aim of the present study was to develop a new fully automatized method for quantifying the percentage of fat in the liver based on a voxel analysis on computed tomography (CT) images to solve previously unconcluded diagnostic deficiencies either in contrast (CE) or non-contrast enhanced (NCE) assessments. METHODS: Liver and spleen were segmented using nn-UNet on CE- and NCE-CT images. Radiodensity values were obtained for both organs for defining the key benchmarks for fatty liver assessment: liver mean, liver-to-spleen ratio, liver-spleen difference, and their average. VCTE was used for validation. A classification task method was developed for detection of suitable patients to fulfill maximum reproducibility across cohorts and highlight subjects with other potential radiodensity-related diseases. RESULTS: Best accuracy was attained using the average of all proposed benchmarks being the liver-to-spleen ratio highly useful for CE and the liver-to-spleen difference for NCE. The proposed whole-organ automatic segmentation displayed superior potential when compared to the typically used manual region-of-interest drawing as it allows to accurately obtain the percent of fat in liver, among other improvements. Atypical patients were successfully stratified through a function based on biochemical data. CONCLUSIONS: The developed method tackles the current drawbacks including biopsy invasiveness, and CT-related weaknesses such as lack of automaticity, dependency on contrast agent, no quantification of the percentage of fat in liver, and limited information on region-to-organ affectation. We propose this tool as an alternative for individualized MAFLD evaluation by an early detection of abnormal CT patterns based in radiodensity whilst abording detection of non-suitable patients to avoid unnecessary exposure to CT radiation. Furthermore, this work presents a surrogate aid for assessing fatty liver at a primary assessment of MAFLD using elastography data.

Fibroblast growth factor 21 is a hepatokine involved in MASLD progression.

AIM: We aimed to assess the role of FGF21 in metabolic dysfunction-associated steatotic liver disease (MASLD) at a multi-scale level. METHODS: We used human MASLD pathology samples for FGF21 gene expression analyses (qPCR and RNAseq), serum to measure circulating FGF21 levels and DNA for genotyping the FGF21 rs838133 variant in both estimation and validation cohorts. A hepatocyte-derived cell line was exposed to free fatty acids at different timepoints. Finally, C57BL/6J mice were fed a high-fat and choline-deficient diet (CDA-HFD) for 16 weeks to assess hepatic FGF21 protein expression and FGF21 levels by ELISA. RESULTS: A significant upregulation in FGF21 mRNA expression was observed in the liver analysed by both qPCR (fold change 5.32 ± 5.25 vs. 0.59 ± 0.66; p = 0.017) and RNA-Seq (3.5 fold; FDR: 0.006; p < 0.0001) in MASLD patients vs. controls. Circulating levels of FGF21 were increased in patients with steatohepatitis vs. bland steatosis (386.6 ± 328.9 vs. 297.9 ± 231.5 pg/mL; p = 0.009). Besides, sex, age, A-allele from FGF21, GG genotype from PNPLA3, ALT, type 2 diabetes mellitus and BMI were independently associated with MASH and significant fibrosis in both estimation and validation cohorts. In vitro exposure of Huh7.5 cells to high concentrations of free fatty acids (FFAs) resulted in overexpression of FGF21 (p < 0.001). Finally, Circulating FGF21 levels and hepatic FGF21 expression were found to be significantly increased (p < 0.001) in animals under CDA-HFD. CONCLUSIONS: Hepatic and circulating FGF21 expression was increased in MASH patients, in Huh7.5 cells under FFAs and in CDA-HFD animals. The A-allele from the rs838133 variant was also associated with an increased risk of steatohepatitis and significant and advanced fibrosis in MASLD patients.

Non-Alcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: The metabolic effects of polycystic ovary syndrome (PCOS) may increase the risk of non-alcoholic fatty liver disease (NAFLD). However, the burden of NAFLD in PCOS has not been unequivocally defined. This systematic review (SR), meta-analysis (MA) assessed NAFLD's prevalence, and risk factors in patients with PCOS. METHODS: A literature search was performed in MEDLINE, Scopus, and Scielo. First, we performed a MA of proportions to estimate the prevalence of NAFLD in PCOS. Second, we performed meta-analyses of precalculated adjusted odds ratios to examine NAFLD risk factors. Finally, we performed a meta-regression to model how the estimated prevalence changed with changes in prespecified variables. RESULTS: We identified 817 articles from the database searches. Thirty-six were included. MA of proportions found a pooled NAFLD prevalence of 43% (95% CI, 35-52%) with high heterogeneity (I2 = 97.2%). BMI, waist circumference, ALT values, HOMA-IR values, free androgen index levels, hyperandrogenism, and triglycerides were associated with significantly higher risk-adjusted odds of NAFLD among patients with PCOS. Meta-regression showed that rises in NAFLD prevalence were mediated through increases in metabolic syndrome prevalence and higher levels of HOMA-IR, free androgen index, and total testosterone. CONCLUSION: The prevalence of NAFLD (43%) among PCOS patients is high despite their average young age, with several metabolic and PCOS-specific factors influencing its occurrence. Screening programs may aid in detecting metabolic-associated fatty liver disease and prevent its consequences. Further work is required to establish the burden of liver-related outcomes once NAFLD has progressed in the PCOS population.

Outcomes of Patients with Severe Obesity and Cirrhosis with Portal Hypertension Undergoing Bariatric Surgery: a Systematic Review.

PURPOSE: Thus far, little attention has been paid to bariatric surgery (BS) in patients with severe obesity (SO) and cirrhosis with portal hypertension (PH). To address this knowledge gap, we systematically reviewed the available literature and evidence about BS in patients with SO and cirrhosis with PH. We inform on the perioperative and long-term outcomes of this intervention. MATERIALS AND METHODS: Articles were identified in MEDLINE, SCOPUS, LILACS, and SCIELO, and included if they analyzed SO patients with clinically significant PH and reported the characteristics and outcomes of BS. RESULTS: Six articles, including 32 patients, were included. The most frequent type of BS was sleeve gastrectomy performed in 27 patients. Perioperative transfusions were often not required, with only one case report describing the use of 1 unit of packed red blood cells post-operatively. Neither intraoperative nor post-op deaths were reported. All patients reported significant weight loss with improvements in comorbidities during the follow-up periods. Overall, 27 out of 29 patients had T2DM resolution, and 13 out of 23 had arterial hypertension resolution. One study reported improvements in the parameters of fibroscan. CONCLUSION: This systematic review described the outcomes of BS among patients with SO with cirrhosis and PH. Performing this kind of surgery among these patients appears safe and associated with acceptable perioperative and long-term outcomes. However, further studies are required to provide evidence-based, strong recommendations.

Uncovering the NAFLD burden in people living with HIV from high- and middle-income nations: a meta-analysis with a data gap from Subsaharan Africa.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become a significant concern among people living with HIV (PLHIV), albeit its burden remains unclear. The primary objective of this systematic review (SR) and meta-analysis (MA) was to estimate the prevalence of NAFLD and significant fibrosis in PLHIV. The secondary objective was to determine the risk factors for NAFLD among PLHIV. METHODS: We searched MEDLINE and Scopus from inception to 30 December 2022 for peer-reviewed studies that included PLHIV and reported the prevalence of NAFLD. MA of proportions was used to estimate the pooled prevalence of NAFLD and significant fibrosis. MA of pre-calculated effect estimates examined risk factors for NAFLD in PLHIV. RESULTS: We included 24 articles published between 2009 and 2022, encompassing 6326 PLHIV. The pooled prevalence of NAFLD was 38% (95% CI: 31-45%) with high heterogeneity (I2 = 96.3%). The pooled prevalence of significant fibrosis was 13% (95% CI: 8-18%) with high heterogeneity (I2 = 92.09%). Subgroup analyses showed a NAFLD prevalence of 40% (95% CI: 24-57%) in the United States, 33% (95% CI: 31-36) in Asia, 42% (95% CI: 24-61%) in Europe and 33% (95% CI: 29-37) in South America. When stratifying by income level, NAFLD was 39% (95% CI: 31-48) prevalent in PLHIV from high-income economies and 34% in both upper-middle-income (95% CI: 31-37%) and lower-middle-income economies (95% CI: 28-41%). Higher body mass index (BMI) (OR = 1.32, 95% CI: 1.13-1.55; I2 = 89.9%), increasing triglycerides (OR = 1.48, 95% CI: 1.22-2.79; I2 = 27.2%) and dyslipidaemia (OR = 1.89, 95% CI: 1.32-2.71; I2 = 15.5%) were all associated with higher risk-adjusted odds of NAFLD in PLHIV. DISCUSSION: The burden of NAFLD and significant fibrosis in PLHIV is significant. Therefore, targeted efforts to screen and diagnose NAFLD in this population are needed. Health services for PLHIV could include ways to target NAFLD risk factors, screen for liver disease and implement interventions to treat those with significant fibrosis or more advanced stages of liver disease. Taking no action to address NAFLD in PLHIV should not be an option. CONCLUSIONS: This SR and MA found a 38% NAFLD and 13% significant fibrosis prevalence in PLHIV. Increasing triglyceride levels, higher BMI values and dyslipidaemia were associated with higher risk-adjusted odds of NAFLD among PLHIV.

Accuracy of a sequential algorithm based on FIB-4 and ELF to identify high-risk advanced liver fibrosis at the primary care level.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, and liver fibrosis is the strongest predictor of morbimortality. We aimed to assess the performance of a sequential algorithm encompassing the Fibrosis 4 (FIB-4) and Enhanced Liver Fibrosis (ELF) scores for identifying patients at risk of advanced fibrosis. This cross-sectional study included one hospital-based cohort with biopsy-proven NAFLD (n = 140) and two primary care cohorts from different clinical settings: Type 2 Diabetes (T2D) follow-up (n = 141) and chronic liver disease (CLD) initial study (n = 138). Logistic regression analysis was performed to assess liver fibrosis diagnosis models based on FIB-4 and ELF biomarkers. The sequential algorithm retrieved the following accuracy parameters in predicting stages F3-4 in the biopsy-confirmed cohort: sensitivity (85%), specificity (73%), negative predictive value (79%) and positive predictive value (81%). In both T2D and CLD cohorts, a total of 28% of patients were classified as stages F3-4. Furthermore, of all F3-4 classified patients in the T2D cohort, 80% had a diagnosis of liver disease and 44% were referred to secondary care. Likewise, of all F3-4 classified patients in the CLD cohort, 71% had a diagnosis of liver disease and 44% were referred to secondary care. These results suggest the potential utility of this algorithm as a liver fibrosis stratifying tool in primary care, where updating referral protocols to detect high-risk F3-4 is needed. FIB-4 and ELF sequential measurement is an efficient strategy to prioritize patients with high risk of F3-4 in populations with metabolic risk factors.

Review article: The need for more efficient and patient-oriented drug development pathways in NASH-setting the scene for platform trials.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. METHODS: Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. RESULTS: Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design (trial Phase and type of population, e.g., Phase 2b for non-cirrhotic NASH patients); the operational requirements such as the scope of the clinical network, the use of concurrent versus non-concurrent control arms, or the re-allocation of participants upon trial adaptations; the methodological appraisal (i.e. Bayesian vs. frequentist approach); patients' needs and patient-centred outcomes; main regulatory considerations and the funding and sustainability scenarios. CONCLUSIONS: PT represent a promising avenue in NASH but there are a number of conundrums that need addressing. It is likely that before a global NASH PT becomes a reality, 'proof-of-platform' at a smaller scale needs to be provided.

Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study.

BACKGROUND AND AIMS: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. METHOD: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. RESULTS: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. CONCLUSIONS: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.