Cause Of Liver Disease Research Articles

Climate change and liver disease: a mini review

Climate change poses a growing threat to human health and well-being, with emerging evidence pointing to its intricate relationship with liver diseases. Indeed, climate change influences liver diseases through various direct and indirect mechanisms. Alcohol-related liver disease, Metabolic dysfunction-associated liver disease (MASLD), and viral hepatitis are the three most common causes of liver disease, and all are susceptible to the effects of climate change. Shifts in dietary habits driven by altered food availability, substance abuse exacerbated by social instability, extreme weather events affecting healthcare access, and the emergence of waterborne infections are among the factors exacerbating liver disease incidence and severity. On the flip side, healthcare systems, including liver units, significantly contribute to climate change through energy consumption, medical waste, and transportation emissions. The need for sustainable healthcare practices, telemedicine, and waste reduction strategies is becoming increasingly evident. Recognizing this intricate interplay and addressing the dual interaction between climate change and liver disease is imperative for safeguarding human health and reducing the environmental footprint of healthcare facilities. As climate change continues to unfold, understanding its implications for liver disease is critical for public health and environmental sustainability.

Outcome of MAFLD-related HCC in Egyptian patients: a single center study

BackgroundGlobally, MAFLD becomes in the top list of causes of liver disease. Its effect ranges from steatosis, metabolic steato-hepatitis to MAFLD-related cirrhosis and hepatocellular carcinoma. There is a growing evidence that MAFLD-related HCC seems to be different from HCCs of other causes pathologically, so the purpose of our study was to assess the effect of MAFLD on the prognosis of HCC regarding outcome after management of HCC and survival rate in comparison to a group of patients with HCV-related HCC.ResultsTwenty-nine patients with MAFLD related HCC were included in group A, while 58 patients with HCV related HCC were enrolled as group B. Both groups were matched regarding age and gender. The mean age in group A and B was 58.86 (±8.47) years and 60/05(± 6.83) years respectively. Comparison between both groups regarding tumor burden and characteristics of HCC, type of management, and post intervention follow-up showed no significant statistical difference between both groups except for lymph node metastases which was higher in patients with HCV related HCC with p = 0.045. Also, a significant difference between both studied groups regarding AFP was detected; the median of AFP in MAFLD-related HCC was (7.2 ng/ml) but much higher in HCV-related HCC group (129.2 ng/ml) with p = 0.001.ConclusionOur data showed no significant difference between the two studied groups regarding outcome of HCC or survival rate except for AFP level before and after management which was higher in HCV patients related HCC. Although both of inclusion and exclusion criteria were strict to the criteria, so the number of participants in the research were not large enough; to our knowledge, this is the first study on MAFLD-HCC in Egypt and Africa. More studies on prospective bases are essentially needed to stand on solid conclusion about the nature and outcome of MAFLD-related HCC.

Effects of antagonism of thromboxane-prostanoid receptor on alcohol-associated liver disease

Backgrounds: Alcohol-associated liver disease (ALD) is one of the leading causes of liver diseases. Thromboxane-prostanoid receptor (TP-R) is widely expressed in the liver and is activated by thromboxane A2 (TXA2). A previous study reported an increase in TP-R mRNA level in liver after ethanol feeding. Preclinical studies have documented that TP-R antagonists exert a protective effect against cardiovascular and liver diseases. In particular, TP-R antagonist is reported to attenuate ALD in rodents. However, the mechanism(s) by which antagonizing TP-R attenuates ALD remains unclear. Methods: Herein, we used the chronic plus binge ethanol feeding model. Briefly, male, C57BL/6 wild-type mice (8-week) were fed a Lieber-Decarli ethanol (5% v/v) diet (ET, n = 10) or isocaloric control diet (CON, n = 6) for ten days followed by a single binge administration of ethanol or maltose-dextrin via oral gavage. A cohort of ethanol-fed mice received SQ 29,548, a TP-R antagonist (ET+SQ, n = 8) by oral administration. Results: Western blot analysis showed that the protein level of thromboxane A2 synthase 1 ( P<0.05), responsible for TXA2 production, was upregulated in the mouse liver upon ethanol exposure. Of note, ethanol feeding significantly increased plasma aspartate transferase (AST) level ( P<0.05), which was abolished by SQ administration ( P<0.05). Moreover, compared with CON mice, ET mice showed an increase in liver protein levels of pro-inflammatory markers, including TNFa ( P<0.05), cluster of differentiation 68 (CD68, P<0.001), and vascular cell adhesion protein 1 ( P<0.05). In addition, the pro-fibrogenic markers including collagen type 1 alpha 1 chain (COL1A1, P<0.05) and matrix metalloproteinase 9 (MMP9, P<0.01) were also increased in ET mice. However, these alterations were not found in ET+SQ mice compared to their controls. In particular, ET+SQ mice exhibited a marked reduction in hepatic protein levels of CD68 ( P<0.001), COL1A1 ( P<0.001), and MMP9 ( P<0.01) versus ET mice. Interestingly, we noted that ethanol consumption decreases the protein level of NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), a component of mitochondrial complex I, in mouse liver ( P<0.05), which was reversed by SQ administration( P<0.05). Conclusion: These findings suggest that blockade of TP-R activity attenuates ethanol-induced liver inflammation and fibrosis possibly through improving the function of mitochondrial complex I. This study was supported by the NIH-NIAAA P50 award-Alcohol Center of Research-Nebraska (P50AA030407-5130). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protocolo diagnóstico de la alteración de las transaminasas en el paciente oncológico

The diagnostic and etiological approach to transaminase abnormalities in oncology patients is a complex process that can be difficult to interpret at times. It also has a wide potential range of severity, from a transient, asymptomatic abnormality to acute liver failure. For this reason, an exhaustive, systematic differential diagnosis must be performed that includes both the most frequent causes of liver disease in the general population as well as causes specific to oncology patients arising from the use of antitumor treatments, liver tumor involvement, or other concomitant phenomena.

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.

Surfactant protein A promotes western diet-induced hepatic steatosis and fibrosis in mice

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common cause of liver disease in the United States due to the increased incidence of metabolic dysfunction and obesity. Surfactant protein A (SPA) regulates macrophage function, strongly binds to lipids, and is implicated in renal and idiopathic pulmonary fibrosis (IPF). However, the role of SPA in lipid accumulation, inflammation, and hepatic fibrosis that characterize MASLD remains unknown. SPA deficient (SPA−/−) and age-matched wild-type (WT) control mice were fed a Western diet for 8 weeks to induce MASLD. Blood and liver samples were collected and used to analyze pathological features associated with MASLD. SPA expression was significantly upregulated in livers of mice with MASLD. SPA deficiency attenuated lipid accumulation along with downregulation of genes involved in fatty acid uptake and reduction of hepatic inflammation as evidenced by the diminished macrophage activation, decreased monocyte infiltration, and reduced production of inflammatory cytokines. Moreover, SPA−/− inhibited stellate cell activation, collagen deposit, and liver fibrosis. These results highlight the novel role of SPA in promoting fatty acid uptake into hepatocytes, causing excessive lipid accumulation, inflammation, and fibrosis implicated in the pathogenesis of MASLD.

Progression of liver disease and associated risk of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the primary liver cancer type, often seen in individuals with chronic liver disease. Once the patient progresses to the cirrhotic stage, the annual incidence of HCC is approximately 2%-4%. As it exceeds the minimum threshold of 1.0%-1.5% per year, HCC screening every 6 months through abdominal ultrasound is indicated in the cirrhotic population. While the incidence of viral hepatitis-associated HCC is decreasing, there is a notable rise of HCC associated with metabolic dysfunction-related steatotic liver disease and alcohol-related liver disease, particularly in high-income countries. The most effective approach for oncological prevention remains addressing the cause of liver disease. The indications for HCC screening in patients without cirrhosis depend on the etiology of liver disease and the stage of fibrosis, assessed by liver biopsy or noninvasive tests such as FIB-4 or transient elastography. However, clear recommendations for HCC screening in patients without cirrhosis and for the different etiologies are currently unavailable. Research efforts should focus on identifying markers, or combinations thereof, to provide a more accurate estimate of HCC occurrence. Such advancements would enable the effective targeting of populations at the highest risk of HCC and the establishment of the correct timing to start the screening.

Advances in Nanocarriers for Delivering Therapeutic Agents Against Hepatitis B Virus

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first‐line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off‐target toxicity caused by the whole‐body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti‐HBV therapeutics and discusses the opportunities and challenges for the future development of anti‐HBV nanotherapeutics.

Metabolic-associated fatty liver disease and older age

With the growing obesity epidemic around the world, metabolic associated fatty liver disease (MAFLD), formerly called non-alcoholic fatty liver disease (NAFLD), has become a common cause of liver disease, including in older age groups, the incidence of which is increasing significantly due to significant social change economic development and improvements in health care over recent years. While NAFLD primarily focuses on the accumulation of fat in the liver, MAFLD considers both the presence of fatty tissue in the liver and associated metabolic risk factors such as diabetes mellitus, dyslipidemia or obesity, providing a more detailed approach to diagnosis and treatment of steatotic liver disease. Thus, the introduction of the term MAFLD reflects a more comprehensive approach to encompass the diverse spectrum of patients affected by this disease and recognizes the complex relationship between metabolic disorders and liver health. Age-associated structural changes can significantly affect the morphology, physiology and oxidative capacity of the liver. With age, the weight of the liver decreases, the functionality of liver cells decreases, leading to a decrease in the rate of protein synthesis, its participation in fat, carbohydrate, pigment, water-electrolyte metabolism decreases, detoxification function and vitamin synthesis are inhibited. That is, the involutive effect on the structure and functional activity of the liver during the aging process, the presence of comorbidity and features of structural and functional changes in MAFLD in elderly people require a special approach in choosing tactics for managing this group of patients. The review article examines data from scientific studies on the prevalence and diagnosis of MAFLD, taking into account involutive changes in the liver in elderly people.

Article Review: The Hepatic Physiology and Pathophysiology of Different Types of Hepatitis

Globally, viral hepatitis is a frequent cause of liver disease with high morbidity and fatality rates. Since the liver produces a large number of hematopoietic factors and carries out numerous essential tasks that influence metabolism throughout the body. The purpose of this study is to identify hematological complications in patients with acute viral hepatitis. This information will be useful for treating and monitoring these patients. Also, everyone should be aware of the symptoms of hepatitis. Due of this, this article.

Protocolo diagnóstico de la hepatopatía por fármacos o tóxicos

Drug-induced liver injury (DILI) is one of the most complex liver disorders, due not only to the variety of drugs, vaccines, herbal products, and dietary supplements used in daily practice, but also to the absence of specific biomarkers of hepatotoxicity, which hinders the diagnosis of this condition. The diagnostic process requires a detailed medical history in search of possible toxins and other risk factors as well as additional tests, mainly analytical and radiological, to rule out other possible causes of liver disease and, at the same time, to evaluate the severity of the condition.

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers.

Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2-15.1 mg/dL; 0.01-0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79-260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug-drug interactions leading to hepatotoxicity. Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

Understanding the impact of non-alcoholic steatohepatitis with metabolic comorbidities on adults: a real-world qualitative study

Objective Limited real-world evidence exists to better understand the patient experience of living with symptoms and impacts of non-alcoholic steatohepatitis (NASH). This study aimed to (1) describe patient-reported perspectives of NASH symptoms and impacts on patients’ daily lives and (2) develop a patient-centered conceptual NASH model. Methods A cross-sectional study using semi-structured qualitative interviews was conducted among adults (≥18 years) in the United States living with NASH. Eligible participants were diagnosed with NASH, had mild to advanced fibrosis (F1-F3), and no other causes of liver disease. The interview guide was informed by a targeted literature review (TLR) to identify clinical signs, symptoms, impacts, and unmet treatment needs of NASH. Participants described their experiences and perspectives around NASH and the symptoms, symptom severity/bother, and impact of NASH on their daily activities. Interviews were audio-recorded and transcribed verbatim for coding and thematic analysis. Results Twenty participants (age: 42.4 years; female: 50.0%) were interviewed. Participants discussed their experience with NASH symptoms (most frequent: fatigue [75.0%]; weakness/lethargy [70.0%]) and impacts (most frequent: physical and psychological/emotional [70.0% each]; dietary [68.4%]). Participants considered most symptoms to be moderately severe or severe and moderately or highly bothersome. Findings from the TLR and qualitative interviews were incorporated into a conceptual model that describes patient-reported symptoms and impacts of NASH, clinical signs, risk factors, and unmet treatment needs. Conclusion Our study provides insights into patients’ perspectives of NASH symptoms and their impact on their daily lives. These findings may guide patient-physician conversations, supporting patient-centered treatment decisions and disease management.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Prevalence of Nonalcoholic Steatohepatitis and Associated Fibrosis Stages Among US Adults Using Imaging-Based vs Biomarker-Based Noninvasive Tests.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease worldwide. Therapies are under development for nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, such that the prevalence of NASH with liver fibrosis, which is likely to require treatment, may be of interest to healthcare decision makers. Noninvasive tests are used in initial screening for NASH, as well as in observational studies of NASH prevalence. However, existing evidence does not address how estimated prevalence varies with different noninvasive tests. This analysis estimated the prevalence of NASH among US adults and assessed variation with different noninvasive tests. Methods: A cross-sectional analysis was conducted using the 2017-March 2020 National Health and Nutrition Examination Survey cycle. Participants with presumed NAFLD (steatosis and without alternative causes of liver disease) were identified, among whom NASH was predicted based on FAST score, Fibrosis-4 (FIB-4), and AST-to-Platelet Ratio Index (APRI) cutoffs across 11 scenarios. Among NASH participants, fibrosis stages were explored based on distribution across the spectrum of liver-stiffness measurements. Results: Among participants with complete data for the analysis (N=6969), prevalence of presumed NAFLD was 25.6%. Within presumed NAFLD, prediction of NASH using imaging-based NIT cutoffs yielded estimated prevalence of 1.3%-4.8% (3.3 million-12.2 million) based on FAST score cutoffs from 0.35-0.67. Using biomarker-based NIT cutoffs yielded estimated prevalence of 0.4%-12.3% (1.0 million-14.5 million) based on FIB-4 cutoffs from 0.90-2.67, and 0.1%-1.9% (0.2-5.0 million) based on APRI cutoffs from 0.50-1.50. Conclusion: Prevalence of NASH among US adults was estimated to range from 1.3% to 4.8% when predicted using imaging-based noninvasive test values for participants with presumed NAFLD, generally aligning with estimates in the literature of prevalence of biopsy-confirmed NASH. Use of biomarker-based noninvasive test values for prediction of NASH yielded a wider range of estimates with FIB-4, and a considerably lower range of estimates with APRI.

Pathophysiological-Based Nutritional Interventions in Cirrhotic Patients with Sarcopenic Obesity: A State-of-the-Art Narrative Review.

In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition.

A case of patient with decompensated Budd-Chiari syndrome treated with T-TIPS: A case report

A 46-years old man with a recent onset of painful hepatomegaly and abdominal swelling was referred to the emergency department and hospitalized in the internal medicine ward for a diagnostic hepatological work-up. He had no clinically significant previous medical history, except for a mild long-standing polycitemia. When admitted to hospital, he was febrile but hemodynamically stable (blood pressure 100/60 mmHg, pulse rate 90/min) and had a satisfactory blood oxygen saturation levels in room air. At clinical examination, he was slightly sub-icteric; a palpable but tender hepatomegaly together with a significant abdominal effusion and a mild leg swelling were noticed. In order to evaluate different possible causes of liver disease, alcoholic, viral, autoimmune, metabolic and congenital etiologies were excluded, mainly by biochemical tests.

Liver regulatory mechanisms of noncoding variants at lipid and metabolic trait loci

Genome-wide association studies (GWASs) have identified hundreds of risk loci for liver disease and lipid-related metabolic traits, although identifying their target genes and molecular mechanisms remains challenging. We predicted target genes at GWAS signals by integrating them with molecular quantitative trait loci for liver gene expression (eQTL) and liver chromatin accessibility QTL (caQTL). We predicted specific regulatory caQTL variants at four GWAS signals located near EFHD1, LITAF, ZNF329, and GPR180. Using transcriptional reporter assays, we determined that caQTL variants rs13395911, rs11644920, rs34003091, and rs9556404 exhibit allelic differences in regulatory activity. We also performed a protein binding assay for rs13395911 and found that FOXA2 differentially interacts with the alleles of rs13395911. For variants rs13395911 and rs11644920 in putative enhancer regulatory elements, we used CRISPRi to demonstrate that repression of the enhancers altered the expression of the predicted target and/or nearby genes. Repression of the element at rs13395911 reduced the expression of EFHD1, and repression of the element at rs11644920 reduced the expression of LITAF, SNN, and TXNDC11. Finally, we showed that EFHD1 is a metabolically active gene in HepG2 cells. Together, these results provide key steps to connect genetic variants with cellular mechanisms and help elucidate the causes of liver disease.

No correlation between MASLD and poor outcome of Atezolizumab-Bevacizumab therapy in patients with advanced HCC.

It has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic-associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab-Bevacizumab (AtezoBev). We collected data from 295 AtezoBev-treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model. Risk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow-up, 10% of patients experienced immune-related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors. Our study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.

P1178 Detection of occult liver disease in patients with Inflammatory Bowel Disease

Abstract Background Investigation of liver disease is recommended in the ECCO Guidelines for Extraintestinal Manifestations in Inflammatory Bowel Disease (IBD). The aim of this study was to analyse the prevalence of liver disease in IBD patients, to examine the frequency of different aetiologies, and to investigate a possible correlation between the severity of liver disease and IBD. Methods Cross-sectional descriptive study including all patients with inflammatory bowel disease (IBD) of nine hospitals in Spain. The study of liver disease was carried out in two phases: patients with FIB-4 greater than 1.3 (greater than 2 in those aged 65 years or more), as well as those with APRI greater than 0.5 and/or elevated transaminases were selected as those at risk of liver disease. In the second phase, these patients underwent a medical history, comprehensive blood tests, abdominal ultrasound with SWE elastography and Fibroscan® (including transitional elastography (TE) and Controlled Attenuation Parameter (CAP)). Results In total, 5302 patients were enrolled and 1640 (31%) were identified as at risk for liver disease. The University Hospital of Burgos has completed the second phase of the study in patients diagnosed with IBD between 2010 and 2021 (n=151). Of these patients, 72.2% were male and the median age was 61 years. Ulcerative colitis (57%) was the most common type of IBD and 62% of the patients were overweight or obese, while 12% of the patients had high-risk alcohol consumption. Metabolic hepatic steatosis was the most frequent cause of liver disease (35%). Moderate/severe steatosis was detected in 44.3% of patients by CAP and 24% by ultrasound. The prevalence of advanced fibrosis was 10.6% and 12% when assessed by ET and SWE, respectively. Notably, 12.6% displayed ultrasound signs of chronic liver disease. A positive correlation was found between the ET and the SWE for liver fibrosis, with a correlation coefficient of ĸ = 0.663. On univariate analysis, an increased risk of significant fibrosis (p=0.011) and moderate/severe steatosis (p=0.00) was found only in those who were overweight or obese. However, no association with severity of liver disease was found for perianal disease, use of immunosuppressants or history of previous surgery. Conclusion The incidence of unrecognised liver disease in IBD patients is substantial, with metabolic hepatic steatosis being the most common cause. The severity of liver disease in these patients cannot be ignored, with one in ten patients having advanced fibrosis. In the univariate study, only obesity was found to correlate with the severity of steatosis and fibrosis, while IBD severity showed no significant association with liver disease severity.