Acute liver failure in pregnancy.

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.

New and emerging treatments for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Real-world efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.

Comprehensive study of the interplay between immunological and metabolic factors in hepatic steatosis.

The pathophysiology of hepatic steatosis is thoroughly reviewed in this comprehensive report, with particular attention to the complex interactions between inflammatory pathways, insulin resistance, lipid metabolism, metabolic dysregulation, and immunological responses in the liver including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). The study highlights the role of immune cell regulation in disease progression and explores the potential of immune cell-specific treatments for treating hepatic disorders. The development of liver disorders is significantly influenced by immune cells, including dendritic cells, T cells, and natural killer cells. Clinical investigations show that immune cell-specific treatments can effectively reduce liver fibrosis and inflammation. Future research should focus on finding new immunological targets for therapeutic interventions, as well as addressing the management challenges associated with NAFLD/NASH. Hepatic immune microorganisms also impact liver homeostasis and disorders. Improvements in immune cell regulation and liver transplantation methods give patients hope for better prognoses. Important phases include optimizing the selection of donors for malignancy of the liver, using machine perfusion for organ preservation, and fine-tuning immunosuppressive strategies. For focused treatments in hepatic steatosis, it is imperative to understand the intricate interactions between immune and metabolic variables. Understanding the liver's heterogeneous immune profile, encompassing a range of immune cell subpopulations, is crucial for formulating focused therapeutic interventions. To improve patient care and outcomes in hepatic illnesses, there is an urgent need for further research and innovation. Therefore, to effectively treat hepatic steatosis, it is important to enhance therapeutic techniques and maximize liver transplantation strategies.

The Relationship between Pathogenesis and Possible Treatments for the MASLD-Cirrhosis Spectrum.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that entails a broad spectrum of conditions that vary in severity. Its development is influenced by multiple factors such as environment, microbiome, comorbidities, and genetic factors. MASLD is closely related to metabolic syndrome as it is caused by an alteration in the metabolism of fatty acids due to the accumulation of lipids because of an imbalance between its absorption and elimination in the liver. Its progression to fibrosis is due to a constant flow of fatty acids through the mitochondria and the inability of the liver to slow down this metabolic load, which generates oxidative stress and lipid peroxidation, triggering cell death. The development and progression of MASLD are closely related to unhealthy lifestyle habits, and nutritional epigenetic and genetic mechanisms have also been implicated. Currently, lifestyle modification is the first-line treatment for MASLD and nonalcoholic steatohepatitis; weight loss of ≥10% produces resolution of steatohepatitis and fibrosis regression. In many patients, body weight reduction cannot be achieved; therefore, pharmacological treatment should be offered in particular populations.

Analysis on acupoint selection rules in the treatment of metabolism-associated fatty liver disease based on data mining. / åŸºäºŽæ•°æ®æŒ–æŽ˜æŠ€æœ¯åˆ†æžé’ˆç¸æ²»ç–—ä»£è°¢ç›¸å ³è„‚è‚ªæ€§è‚ç— çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To explore the rules of acupoint selection in the treatment of metabolic-associated fatty liver disease (MAFLD) with acupuncture and moxibustion by using data mining technology. METHODS: The clinical research literature on acupuncture treatment of MAFLD was collected from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine from their inception to November 20, 2022. According to our inclusion and exclusion criteria, the literature was independently screened and re-screened by two research members, and the screened results were checked, followed by establishing an acupoint prescription database using Excel 2019. Descriptive statistics of acupoints applied frequency, involved meridians, locations and specific acupoints were perpormed. Then, SPSS Modeler18.0 software was used to conduct analysis about association rules, and the SPSS Statistics 26.0 software was used to perform cluster analysis on high-frequency acupoints, exploring the characteristics and rules of acupoint selection and combination in the treatment of MAFLD. RESULTS: Totally, 178 papers were collected, containing 130 acupoints, with a total application frequency of 1 305. The top five acupoints are Zusanli (ST36), Fenglong (ST40), Ganshu (BL18), Taichong (LR3) and Sanyinjiao (SP6). The commonly involved meridians are the Stomach Meridian of Foot Yangming, Bladder Meridian of Foot Taiyang, and Spleen Meridian of Foot Taiyin. The employed acupoints are mostly located in the lower limbs and abdomen, and the five Shu acupoints and crossing acupoints are in the majority. The association rule analysis of high frequency acupoints indicated that of the 16 qualified acupoint groups, the top 5 with close correlation degrees are ST36 and ST40, ST36 and LR3, ST36 and SP6, ST40 and LR3 and ST36, ST36 and SP6 and ST40. Further, 3 effective clusters were obtained by cluster analysis. CONCLUSIONS: Acupuncture and moxibustion treatment of MAFLD follows the therapeutic principles of soothing the liver, invigorating the spleen, tonifying the kidney, and resolving phlegm and removing dampness. The core acupoint group is ST36, ST40 and LR3, and the combination of acupoints is based on syndrome differentiation. These results may provide a useful reference for clinical practice.

Health information in short videos about metabolic dysfunction-associated steatotic liver disease: Analysing quality and reliability.

BACKGROUND & AIMS: Short videos, crucial for disseminating health information on metabolic dysfunction-associated steatotic liver disease (MASLD), lack a clear evaluation of quality and reliability. This study aimed to assess the quality and reliability of MASLD-related videos on Chinese platforms. METHODS: Video samples were collected from three platforms (TikTok, Kwai and Bilibili) during the period from November 2019 to July 2023. Two independent reviewers evaluated the integrity of the information contained therein by scoring six key aspects of its content: definition, epidemiology, risk factors, outcomes, diagnosis and treatment. The quality and reliability of the videos were assessed using the Journal of the American Medical Association (JAMA) criteria, the Global Quality Score (GQS) and the modified DISCERN score. RESULTS: A total of 198 videos were included. The video content exhibited an overall unsatisfactory quality, with a primary emphasis on risk factors and treatment, while diagnosis and epidemiology were seldom addressed. Regarding the sources of the videos, the GQS and modified DISCERN scores varied significantly between the platforms (p = .003), although they had generally similar JAMA scores (p = .251). Videos created by medical professionals differed significantly in terms of JAMA scores (p = .046) compared to those created by nonmedical professionals, but there were no statistically significant differences in GQS (p = .923) or modified DISCERN scores (p = .317). CONCLUSIONS: The overall quality and reliability of the videos were poor and varied between platforms and uploaders. Platforms and healthcare professionals should strive to provide more reliable health-related information regarding MASLD.

Guideline-based management of metabolic dysfunction-associated steatotic liver disease in the primary care setting.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. Primary care providers play a critical role in the screening, diagnosis, and management of MASLD and/or metabolic dysfunction-associated steatohepatitis (MASH), though they can face challenges in this setting, particularly where healthcare resources are limited and barriers to care exist. To address these challenges, several guidelines have been developed to provide evidence-based recommendations for the clinical assessment and management of patients with MASLD/MASH. AIMS: To provide a unified, simple-to-understand, practical guide for MASLD screening, diagnosis, and management based on current guideline recommendations, for use by primary care providers in daily practice. METHODS: Evidence-based recommendations from several international guidelines were summarized, focusing on the similarities and differences between them. RESULTS: Recommendations are broadly aligned across the guidelines, but several key differences are evident. Practical guidance is provided on screening, identifying target populations for risk stratification, initial evaluation of individuals with suspected MASLD, surveillance, risk stratification and referral, as well as approaches to the management of MASLD and associated comorbidities, with specific considerations for the primary care setting. CONCLUSIONS: Primary care providers are ideally placed to identify at-risk individuals, implement evidence-based interventions to prevent the development of fibrosis and cirrhosis, and effectively manage comorbidities. Equipping primary care providers with the necessary knowledge and tools to effectively manage MASLD/MASH may help to improve patient outcomes and reduce the burden of liver disease.

Intermittent fasting regimens for metabolic dysfunction-associated steatotic liver disease: a systematic review and network meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive hepatic fat accumulation. Intermittent fasting (IF) has emerged as a potential therapeutic strategy with the ability to induce weight loss, improve insulin sensitivity and reduce hepatic steatosis. We aim to compare the efficacy of different IF regimens for MASLD management. A systematic review and network meta-analysis of randomized controlled trials investigating different IF regimens for MASLD. PubMed , EMBASE , WOS , SCOPUS and Cochrane Central Register of Controlled Trials were searched until 10 April 2023. Analysis was performed using R software with the meta and netmeta packages. Mean difference (MD) was used to pool continuous outcomes with 95% confidence intervals (CIs). Our meta-analysis was registered in PROSPERO (CRD42023418467). Our meta-analysis included eight randomized controlled trials with a total of 635 participants. The 5 : 2 diet significantly improved liver stiffness (MD, -0.32; 95% CI, -0.55 to -0.09; P  < 0.01). Time-restricted feeding significantly improved liver steatosis (controlled attenuation parameter score) (MD, -39.83; 95% CI, -64.78 to -14.87; P  < 0.01). No significant changes were observed in asparate aminotransferase, gamma-glutamyl transpeptidase, low-density lipoproteins cholesterol, total cholesterol, triglyceride levels, basal metabolic index, blood pressure, Homeostatic Model Assessment of Insulin Resistance, fasting blood sugar, lean body mass or waist circumference across all IF regimens. However, alternate-day fasting showed positive results in anthropometric measures, including significant improvements in lean body mass, waist circumference, fat mass and weight reduction ( P  < 0.05). IF regimens showed various positive effects on clinical outcomes in MASLD patients; however, these effects were not consistent. Therefore, a patient-tailored IF regimen should be considered.

Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis.

Fatty liver grafts are susceptible to ischemia reperfusion injury (IRI), increasing the risk of biliary complications after liver transplantation (LT). Ferroptosis, a newly recognized programmed cell death, is expected to be a novel therapeutic target for IRI. We investigated whether exosomes derived from heme oxygenase 1-modified bone marrow mesenchymal stem cells (HExos) relieve ferroptosis and protect biliary tracts from IRI in a rat fatty liver transplantation model. Rats were fed with a methionine choline deficient (MCD) diet for 2 weeks to induce severe hepatic steatosis. Steatotic grafts were implanted and HExos were administered after liver transplantation. A series of functional assays and pathological analysis were performed to assess ferroptosis and biliary IRI. The HExos attenuated IRI following liver transplantation, as demonstrated by less ferroptosis, improved liver function, less Kupffer and T cell activation, and less long-term biliary fibrosis. MicroRNA (miR)-204-5p delivered by HExos negatively regulated ferroptosis by targeting a key pro-ferroptosis enzyme, ACSL4. Ferroptosis contributes to biliary IRI in fatty liver transplantation. HExos protect steatotic grafts by inhibiting ferroptosis, and may become a promising strategy to prevent biliary IRI and expand the donor pool.

Low Health Literacy, Lack of Knowledge, and Self-Control Hinder Healthy Lifestyles in Diverse Patients with Steatotic Liver Disease.

INTRODUCTION: In parallel with the obesity and diabetes epidemics, steatotic liver disease (SLD) has emerged as a major global public health concern. The mainstay of therapy is counseling on weight loss and increased exercise. However, such lifestyle modifications infrequently lead to success. We aimed to identify barriers to diet and lifestyle modification in patients with SLD. METHODS: Patients with SLD completed a 14-item questionnaire that assigned barriers to healthy eating to three categories: lack of knowledge, lack of self-control, and lack of time, with a higher summary score indicating more perceived barriers. We administered assessments of health literacy and physical activity. We analyzed the data using descriptive statistics and ordinal regression analysis. RESULTS: We included 151 participants with a median age of 64; 54% were female and 68.2% were Hispanic. Median BMI was 31.9 kg/m2. Most respondents, 68.2%, had low health literacy and were either underactive, 29.1% or sedentary, 23.2%. Lack of self-control was the strongest barrier to achieving a healthy lifestyle, followed by lack of knowledge. Lack of time was not significant barrier. Patients with the most significant barriers were more likely to have obesity, low health literacy, and be sedentary. DISCUSSION: Lack of self-control and knowledge are the greatest barriers to adopting a healthy lifestyle in patients with SLD. Future clinical interventions should integrate education that targets various health literacy levels with behavioral approaches to improve a sense of agency.

[Acute Fatty Liver of Pregnancy - Case Series]. / Akute Schwangerschaftsfettleber ­ Fallserie einer seltenen Schwangerschaftskomplikation.

With a prevalence of 0,01-0,03%, acute fatty liver in pregnancy (AFLP) is a rare and dangerous complication of pregnancy and is difficult to distinguish from other, sometimes more common, pregnancy diseases such as HELLP syndrome, aHUS and TTP because of its mostly non-specific symptoms. Due to its rarity, AFLP is often not obvious to the obstetrician as a possible differential diagnosis. Yet early diagnosis and the fastest possible delivery is the only causal therapy and is important for the mortality rate. In the present manuscript, the pathophysiology, diagnosis and therapy of acute fatty liver in pregnancy are highlighted for the clinical routine based on case descriptions from three university hospitals, and reference is made to possible findings that are helpful in establishing the diagnosis. The angiogenic preeclampsia marker sFlt-1 plays a role and provides new opportunities to consider pathophysiological approaches.

Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar / Common Approach to Metabolic-Associated Fatty Liver Disease in Patients With Psoriasis: Consensus-Based Recommendations From a Multidisciplinary Group of Experts

En los últimos años se están haciendo notables esfuerzos para entender la relación existente entre la psoriasis y la esteatosis hepática metabólica (EHmet). No solo se presenta este trastorno en pacientes psoriásicos con una mayor prevalencia, sino que además se acompaña de una mayor gravedad. Con este precedente, se evidencia la necesidad de establecer un protocolo de abordaje precoz de la enfermedad hepática en los pacientes con psoriasis. Asimismo, es de especial relevancia la evaluación de riesgo y beneficio en referencia al uso de tratamientos con potencial hepatotóxico. En el presente manuscrito se exponen las recomendaciones de un panel de expertos en dermatología y hepatología para el cribado, diagnóstico, monitorización y criterios de derivación en pacientes con psoriasis, en caso de sospecha de esteatosis hepática metabólica (AU)

Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease (MAFLD). Not only is MALFD diagnosed more often in patients with psoriasis, but its clinical course is also more aggressive. A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis. Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments. This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected (AU)

[Translated article] Common Approach to Metabolic-Associated Fatty Liver Disease in Patients With Psoriasis: Consensus-Based Recommendations From a Multidisciplinary Group of Experts / Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar

Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease (MAFLD). Not only is MALFD diagnosed more often in patients with psoriasis, but its clinical course is also more aggressive. A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis. Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments. This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected (AU)

En los últimos años se están haciendo notables esfuerzos para entender la relación existente entre la psoriasis y la esteatosis hepática metabólica (EHmet). No solo se presenta este trastorno en pacientes psoriásicos con una mayor prevalencia, sino que además se acompaña de una mayor gravedad. Con este precedente, se evidencia la necesidad de establecer un protocolo de abordaje precoz de la enfermedad hepática en los pacientes con psoriasis. Asimismo, es de especial relevancia la evaluación de riesgo y beneficio en referencia al uso de tratamientos con potencial hepatotóxico. En el presente manuscrito se exponen las recomendaciones de un panel de expertos en dermatología y hepatología para el cribado, diagnóstico, monitorización y criterios de derivación en pacientes con psoriasis, en caso de sospecha de esteatosis hepática metabólica (AU)