Steatotic liver disease and HIV: an agenda for 2030.

People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV.

Needs assessment for creation of a platform trial network in metabolic-dysfunction associated steatohepatitis.

BACKGROUND: The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project (IMI2-853966) aimed to develop tools to establish integrated research platforms (IRP) for conducting adaptive-design trials in various diseases, including metabolic-dysfunction associated steatohepatitis (MASH). One essential component of a successful MASH IRP is a robust and reliable Clinical Research Network (CRN). Herein, we outline the required elements and anticipated steps to set-up such a CRN. METHODS: We identified European clinical research sites that could potentially serve as the foundation for MASH IRP and a CRN. A survey was sent to sites to assess their interest in joining a CRN, their familiarity with platform trials, and their capacity to participate in a future MASH IRP. RESULTS: A total of 141 investigators were invited to participate in the survey, and 40% responded. More than half of the answers (52%) identify MASH with advanced fibrosis (F3-4) as the subpopulation with the greatest unmet need. Regarding the difficulty in identifying candidates for trials, 65% find it is moderately difficult and 30% very difficult. Most respondents (94%) believe that a platform trial could offer substantial benefits to patients. Nearly all researchers express interest in participating in a platform trial (78%), with 22% indicating their interest would be contingent on initial industry funding. CONCLUSION: While preliminary, our findings on responding sites are encouraging for the potential establishment of a CRN for a MASH IRP. However, funding schemes and sustainability strategies to provide proof-of-platform in MASH seem key in the short-term scenario.

Metabolic dysfunction-associated steatohepatitis (MASH) occurs when the liver becomes damaged due to the build up of fat, which is often related to obesity and diabetes. There is a lack of effective drug treatments for MASH, so strategies to strengthen clinical research in this area are needed. Here, we survey key European experts on MASH to assess their interest in joining a network of MASH researchers and their interest in participating in a new type of clinical trial called a platform trial, where multiple drugs can be tested simultaneously. Researchers largely agree that these are promising approaches to boost drug development in the field, although have concerns regarding funding and sustainability strategies. Our findings may inform the creation of a network of MASH researchers capable of running a platform trial, which in turn may speed up research into treatments for MASH.

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.

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.

Unlocking the potential of TIPS placement as a bridge to elective and emergency surgery in cirrhotic patients: a meta-analysis and future directions for endovascular resuscitation in acute care surgery.

BACKGROUND: In this systematic review and meta-analysis, we examined the evidence on transjugular intrahepatic portosystemic shunt (TIPS) as a bridge to elective and emergency surgery in cirrhotic patients. We aimed to assess the perioperative characteristics, management approaches, and outcomes of this intervention, which is used to achieve portal decompression and enable the safe performance of elective and emergent surgery. METHODS: MEDLINE and Scopus were searched for studies reporting the outcomes of cirrhotic patients undergoing elective and emergency surgery with preoperative TIPS. The risk of bias was evaluated using the methodological index for non-randomized studies of interventions, and the JBI critical appraisal tool for case reports. The outcomes of interest were: 1. Surgery after TIPS; 2. Mortality; 3. Perioperative transfusions; and 4. Postoperative liver-related events. A DerSimonian and Laird (random-effects) model was used to perform the meta-analyses in which the overall (combined) effect estimate was presented in the form of an odds ratio (summary statistic). RESULTS: Of 426 patients (from 27 articles), 256 (60.1%) underwent preoperative TIPS. Random effects MA showed significantly lower odds of postoperative ascites with preoperative TIPS (OR = 0.40, 95% CI 0.22-0.72; I2 = 0%). There were no significant differences in 90-day mortality (3 studies: OR = 0.76, 95% CI 0.33-1.77; I2 = 18.2%), perioperative transfusion requirement (3 studies: OR = 0.89, 95% CI 0.28-2,84; I2 = 70.1%), postoperative hepatic encephalopathy (2 studies: OR = 0.97, 95% CI 0.35-2.69; I2 = 0%), and postoperative ACLF (3 studies: OR = 1.02, 95% CI 0.15-6.8, I2 = 78.9%). CONCLUSIONS: Preoperative TIPS appears safe in cirrhotic patients who undergo elective and emergency surgery and may have a potential role in postoperative ascites control. Future randomized clinical trials should test these preliminary results.

Underlying etiology associated with the diagnosis of absent contractility on high resolution esophageal manometry / Etiologías subyacentes asociadas al diagnóstico de contractilidad ausente en la manometría esofágica de alta resolución

Background/Aims: Absent contractility is considered a disorder of peristalsis. The literature about the etiology and clinical characteristics is scarce and the evidence on systemic diseases associated with this esophageal disorder is limited. Therefore, we aimed to determine the etiology of absent contractility in our population using the clinical algorithm recently described in the literature. Methods: We conducted a retrospective, descriptive study at a single tertiary hospital of all patients diagnosed of absent contractility between May 2018 and February 2020. Data on demographic characteristics, medication, comorbidities, and laboratory and paraclinical tests were recorded from clinical records. Results: A total of 72 patients with absent contractility were included for analysis. There was a predominance of female sex (n=43, 59.7%), with a mean age of 55.4 (±15.0) years. We identified a systemic disorder associated with absent contractility in 64 (88.9%) patients. From these, 31 (43.1%) patients were diagnosed with a systemic autoimmune disease, 26 (36.1%) patients were considered to have absent contractility secondary to pathological exposure to acid-reflux and 15 (20.8%) patients were diagnosed with other non-autoimmune systemic disorders. In the remaining eight (11.1%) patients, there were no underlying systemic disorders that could justify the diagnosis of absent contractility. Conclusions: A systematic approach to search for an underlying cause in patients diagnosed with absent contractility is warranted. Up to 90% of patients with absent contractility have a systemic disorder associated with this condition.(AU)

Antecedentes: La contractilidad ausente se considera un trastorno de la peristalsis esofágica. La literatura que existe sobre la etiología y las características clínicas es escasa y la evidencia sobre enfermedades sistémicas asociadas a este trastorno esofágico es limitada. Nuestro objetivo fue determinar la etiología de la contractilidad ausente en nuestra población utilizando el algoritmo clínico recientemente descrito en la literatura. Métodos: Se realizó un estudio descriptivo retrospectivo en un hospital terciario de todos los pacientes diagnosticados de ausencia de contractilidad entre mayo de 2018 y febrero de 2020. Se recogieron datos de características demográficas, medicación, comorbilidades y pruebas de laboratorio y estudios paraclínicos. Resultados: Se incluyeron para el análisis un total de 72 pacientes con ausencia de contractilidad. Predominó el sexo femenino (n=43, 59,7%), con una edad media de 55,4 (±15,0) años. Identificamos un trastorno sistémico asociado con la ausencia de contractilidad en 64 (88,9%) pacientes. De estos 31 (43,1%) pacientes fueron diagnosticados de una enfermedad autoinmune sistémica, 26 (36,1%) pacientes se consideraron con ausencia de contractilidad secundaria a exposición patológica al reflujo ácido y 15 (20,8%) fueron diagnosticados con otras enfermedades no autoinmunes sistémicas. En los 8 pacientes restantes (11,1%) no hubo trastornos sistémicos subyacentes que pudieran justificar el diagnóstico de contractilidad ausente. Conclusiones: Un enfoque sistemático está justificado para investigar una causa subyacente en pacientes diagnosticados de contractilidad ausente. Hasta el 90% de los pacientes con contractilidad ausente tienen un trastorno sistémico asociado con esta afectación de la motilidad esofágica.(AU)

Underlying etiology associated with the diagnosis of absent contractility on high resolution esophageal manometry.

BACKGROUND/AIMS: Absent contractility is considered a disorder of peristalsis. The literature about the etiology and clinical characteristics is scarce and the evidence on systemic diseases associated with this esophageal disorder is limited. Therefore, we aimed to determine the etiology of absent contractility in our population using the clinical algorithm recently described in the literature. METHODS: We conducted a retrospective, descriptive study at a single tertiary hospital of all patients diagnosed of absent contractility between May 2018 and February 2020. Data on demographic characteristics, medication, comorbidities, and laboratory and paraclinical tests were recorded from clinical records. RESULTS: A total of 72 patients with absent contractility were included for analysis. There was a predominance of female sex (n=43, 59.7%), with a mean age of 55.4 (±15.0) years. We identified a systemic disorder associated with absent contractility in 64 (88.9%) patients. From these, 31 (43.1%) patients were diagnosed with a systemic autoimmune disease, 26 (36.1%) patients were considered to have absent contractility secondary to pathological exposure to acid-reflux and 15 (20.8%) patients were diagnosed with other non-autoimmune systemic disorders. In the remaining eight (11.1%) patients, there were no underlying systemic disorders that could justify the diagnosis of absent contractility. CONCLUSIONS: A systematic approach to search for an underlying cause in patients diagnosed with absent contractility is warranted. Up to 90% of patients with absent contractility have a systemic disorder associated with this condition.

Opioid-induced esophageal dysfunctio — Prevalence and manometric findings

Background: prescription opioid use is on the rise. There has been an increasing recognition that chronic opioid consumption can result in esophageal motility disorders, and this association has been named opioid-induced esophageal dysfunction (OIED).Aims: to analyze the prevalence of chronic opioid consumption in patients referred for esophageal motility testing in a European center; to describe the clinical characteristics and the association of opioid consumption with esophageal motility disorders.Methods: a retrospective, descriptive study in patients who had undergone an HRM in a single center. The clinical history in the electronic medical records was reviewed. Results: the prevalence of opioid prescription in patients referred to our institution was 10.1 %, and 4.8 % of themwere chronic active opioid users. There was a 32 % prevalence of OIED. Comparing chronic active opioid users(CAOU) with OIED and CAOU patients without OIED, there was a higher prevalence of males (43.8 % vs 8.8 %; p-value = 0.007). Converting the different opioid medications to morphine milligram equivalent daily dose (MMED), CAOU patients with OIED had a higher MMED than CAOU patients without OIED (125.2 ± 31.3 vs 33.4 ± 5.7 MME; p = 0.041). Dysphagia was the most common indication for performing an HRM in 60.0 % of CAOU patients. Furthermore, dysphagia was more frequent in CAOU patients with OIED (87.5 % vs 47.0 %; p = 0.019).Conclusions: chronic opioid users with OIED complained mostly of dysphagia. There was an association of male sex and a higher dose of opioids in CAOU patients with esophageal motility disorders. (AU)

Opioid-induced esophageal dysfunction - Prevalence and manometric findings.

BACKGROUND: prescription opioid use is on the rise. There has been an increasing recognition that chronic opioid consumption can result in esophageal motility disorders, and this association has been named opioid-induced esophageal dysfunction (OIED). AIMS: to analyze the prevalence of chronic opioid consumption in patients referred for esophageal motility testing in a European center; to describe the clinical characteristics and the association of opioid consumption with esophageal motility disorders. METHODS: a retrospective, descriptive study in patients who had undergone an HRM in a single center. The clinical history in the electronic medical records was reviewed. RESULTS: the prevalence of opioid prescription in patients referred to our institution was 10.1 %, and 4.8 % of them were chronic active opioid users. There was a 32 % prevalence of OIED. Comparing chronic active opioid users (CAOU) with OIED and CAOU patients without OIED, there was a higher prevalence of males (43.8 % vs 8.8 %; p-value = 0.007). Converting the different opioid medications to morphine milligram equivalent daily dose (MMED), CAOU patients with OIED had a higher MMED than CAOU patients without OIED (125.2 ± 31.3 vs 33.4 ± 5.7 MME; p = 0.041). Dysphagia was the most common indication for performing an HRM in 60.0 % of CAOU patients. Furthermore, dysphagia was more frequent in CAOU patients with OIED (87.5 % vs 47.0 %; p = 0.019). CONCLUSIONS: chronic opioid users with OIED complained mostly of dysphagia. There was an association of male sex and a higher dose of opioids in CAOU patients with esophageal motility disorders.