Metabolic dysfunction-associated steatotic liver disease (MASLD) with onset in youth may be more consequential for adverse outcomes than that detected later in adulthood. Transaminitis in the general population is a marker of the prevalence of MASLD. There are no previous community-based studies in Indian youth assessing the prevalence of transaminitis. The purpose of this study was to find out the prevalence of transaminitis, MASLD and elevated Fibrosis-4 (FIB-4) index among young South Indian adults.

This was a cross-sectional study done over a period of 1 year from January 2022 among adults aged 18-30 years. Multistage sampling was used to recruit participants with body mass index (BMI) < 30 kg/m2 and without moderate to heavy alcohol consumption from four different sociogeographic regions. Detailed history, physical examination and investigations including liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), platelet count, and metabolic workup were carried out. FIB-4 index and Nonalcoholic fatty liver disease-liver fat score (NAFLD-LFS) were calculated. LFS ≥ -0.64 was used to rule in MASLD.

A total of 2373 (1170 males) participants with a mean age of 24 ± 3.5 years were included. Transaminitis (AST or ALT≥35 IU/L) was seen in 25.9% of the cohort. MASLD by NAFLD-LFS was present in 27.4% of the population. FIB-4 index ≥1.3 was found in 54 (2.27%) participants. Neck circumference and Trivandrum Medical College adiposity index were associated with transaminitis, MASLD, and elevated FIB-4. Blood pressure, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower among participants with transaminitis, but they were not different among those with elevated FIB-4 index. BMI and waist-hip ratio were not different among participants with and those without transaminitis or MASLD.

There is a high prevalence of transaminitis and MASLD in community-dwelling young adult Indians. We recommend screening all young adult Indians for MASLD and transaminitis.

Liver fibrosis screening is recommended in at-risk groups, but a clear definition of "at risk" for entry criteria is lacking. We analyzed different combinations of established risk factors to define specific screening entry criteria with a prespecified sensitivity requirement.

Data regarding individuals aged 40-70 years from Finnish health-examination surveys (FINRISK 2002-2012 and Health 2000, n=15,057) and the UK Biobank (n=454,990) were linked with healthcare registries for liver cirrhosis-related events (LREs; liver-related hospitalizations, cancer, or death). The predictive performance of 1919 combinations of risk factors, including alcohol consumption, metabolic disturbances, abnormal liver function tests, and Chronic Liver Disease risk score, was assessed for 10-year LRE risk requiring a minimum 90% sensitivity. Validations were performed using liver stiffness measurement (LSM) >12 kPa in the NHANES 2017-2020 sample (n=3367).

Optimal entry criteria for predicting 10-year LRE risk with >90% sensitivity included any one of: hazardous alcohol use, severe obesity, metabolic syndrome, an AST-to-ALT ratio >0.8 with elevated ALT, and an intermediate-to-high Chronic Liver Disease risk score. The sensitivity and specificity for this strategy were 91% and 51% for LREs, respectively, in the Finnish cohort, and 91% and 41% for LSM >12 kPa in the US sample. In the US sample, applying these entry criteria followed by fibrosis-4 ≥1.3 for predicting LSM >12 kPa reduced the sensitivity to 45% (specificity: 85%), which was attributed to the suboptimal sensitivity of fibrosis-4.

This study identifies an inexpensive risk factor-based strategy with >90% sensitivity for predicting LRE and LSM >12 kPa, which is practical and scalable for targeted liver fibrosis screening to improve population outcomes. However, a more sensitive first-line noninvasive fibrosis test is needed.

Aminotransferases, particularly alanine aminotransferase (ALT), are commonly used in the detection, diagnosis, and management of chronic liver diseases. ALT, a sensitive and cost-effective marker of liver injury, remains pivotal in predicting clinical outcomes and guiding interventions in several chronic liver diseases including metabolic dysfunction-associated steatotic liver disease, and chronic viral hepatitis. This study aims to explore the evolving role of ALT as a biomarker. A comprehensive review of evidence was conducted, focusing on studies evaluating ALT thresholds, diagnostic accuracy, and integration with non-invasive liver assessment tools. Special emphasis was given to novel approaches, including artificial intelligence-driven algorithms. Expert opinions from hepatology care perspectives were considered to assess the practical implications of refining ALT-based diagnostic strategies. ALT levels are influenced by diverse factors such as age, gender, and metabolic risks, challenging the use of specific thresholds as biomarker of disease and prognosis. Emerging evidence suggests redefining ALT ranges to enhance sensitivity and accuracy in detecting liver abnormalities. The integration of ALT with advanced non-invasive diagnostic tools, artificial intelligence, and comprehensive patient assessments can optimize early detection of liver disease, thus reducing underdiagnosis, particularly in asymptomatic or vulnerable populations. This work highlights the urgency to tailor the diagnostic approaches in primary and specialized care, ensuring timely and targeted intervention to effectively address the global burden of liver diseases.

Cardiovascular health (CVH) has been associated with various systemic diseases. However, the relationship between CVH, as measured by Life's Essential 8 (LE8), and liver function markers in the general population remains poorly understood.

This study analyzed data from 21,156 participants (aged ≥ 20) from the NHANES 2005-2018 to investigate the associations between CVH and liver function markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin and AST/ALT ratio]. Linear regression models were used, along with a restricted cubic spline (RCS) to assess dose-response. Weighted quantile sum (WQS) regression and quantile g-computation (QGC) analyses were employed to evaluate the association between CVH and liver function markers.

Linear regression analysis showed that each 1-point increase in CVH score was significantly associated with decreased levels of liver enzymes [ALT: -0.200 U/L (95% CI: -0.223, -0.176), AST: -0.043 U/L (-0.062, -0.024), GGT: -0.453 U/L (-0.509, -0.397), ALP: -0.310 U/L (-0.340, -0.281)] and increased levels of albumin [0.040 g/dL (0.036, 0.045)] and AST/ALT ratio [0.0056 (0.0051, 0.0061)]. Notably, CVH score demonstrated non-linear dose-response relationships with ALT, ALP, and AST/ALT ratio. Age significantly modified these associations, while nicotine exposure, BMI, and blood lipids were identified as primary contributors through WQS and QGC analyses. E-value analysis suggested robustness to unmeasured confounding.

This study demonstrates robust associations between CVH and liver function markers in United States adults, with nicotine exposure, BMI, and blood lipids identified as significant contributors. These findings suggest that maintaining optimal cardiovascular health may have beneficial effects on liver function, highlighting potential targets for integrated prevention strategies.

Iron overload has been proposed as a risk factor for atherosclerosis, but the available data are controversial. Here, we investigated whether iron status shows sex-specific associations with peripheral arterial disease (PAD).

Using two different analytical approaches (machine-learning and logistic regression), we studied the association between blood iron biomarkers and PAD in 368 individuals from the Heidelberg Study on Diabetes and Complications (HEIST-DiC) and in 5101 individuals from the National Health and Nutrition Examination Survey (NHANES 1999-2004). Additionally, by analysing data from the UK Biobank, we investigated the odds of PAD in individuals with hemochromatosis genotypes (n = 448,575).

We found that iron biomarkers were among the top predictors of PAD in the machine-learning classification in both cohorts. In the HEIST-DiC cohort, ferritin, iron, and transferrin were ranked among the top predictive markers, while in the NHANES cohort, ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT) and iron showed high predictive power. In the regression analysis, ferritin showed a positive interaction among females in the HEIST-DiC (OR 2.68, 95% CI 0.94-7.61, P = 0.057) and NHANES cohorts (OR 1.76, 95% CI 1.16-2.67, P = 0.008). The multivariable regression analysis of the NHANES cohort detected a nonlinear relationship between ferritin and PAD, in that, certain ferritin ranges (48-97 ng/mL: OR 14.59, 95% CI 1.6-135.93, P = 0.019; 98-169 ng/mL: OR 171.07, 95% CI 1.27-23404, P = 0.039) in females were positively associated with PAD. Nevertheless, we did not detect significant associations between hemochromatosis genotypes and PAD in the UK Biobank.

Taken together, our data show that iron biomarkers, importantly, elevated ferritin within physiological limits are associated with clinically apparent PAD in females. These findings add to the body of evidence suggesting sex differences in PAD and highlight a possible role of iron (directly or indirectly) in this relationship.

Liver biopsy contribution in patients with unexplained elevation of transaminases is not clearly established. The aim was to study liver biopsy contribution in patients with unexplained elevated transaminases strictly defined according to the current guidelines, reflecting the present clinical practice.

In a retrospective study, we identified all the liver biopsies performed in patients with elevated transaminases for at least six months. Patients with a particular context, or with an identified cause of liver disease were excluded. The biopsies were classified according to the 4 following injury patterns: hepatitic, biliary, steatotic, vascular.

87 patients were included. Liver biopsy showed minimal changes or a normal histology in 48%, a steatotic pattern in 21%, a hepatitic pattern in 13%, a vascular pattern in 8%, a biliary pattern in 1%, and a mixed pattern in 8%. A cause could be determined in 21% of patients with normal histology, 85% with steatosis, 56% with hepatitis, 75% with biliary, but in none with isolated vascular pattern. Liver biopsy had important clinical and therapeutic implications in 15% of patients, with a diagnosis of autoimmune hepatitis, primary biliary cholangitis or metabolic dysfunction-associated steatohepatitis. Elevation of transaminases > 10 upper normal limit was present in all the patients with confirmed autoimmune hepatitis, but in only 7% of others.

Liver biopsy had important clinical and therapeutic implications in 15% of patients. However, the majority of patients had minimal changes without a cause, or minor vascular lesions of uncertain significance.

Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.

To describe the proportion of patients with liver fibrosis in at-risk populations in primary care (PC). To know the agreement between FIB-4 and transitional elastography (TE), interobserver agreement between PC and hospital care (HC) in TE, and associated risk Factors (RF).

Observational, descriptive, cross-sectional study in ≥16 years of age with RF for chronic liver disease. Sex and age, RF (alteration of liver tests [LT], metabolic syndrome, diabetes, obesity, alcohol consumption, hepatic steatosis), and FIB-4, controlled attenuation parameter and TE in PC and in HC, were collected. According to a consensus algorithm, vibration-controlled TE was performed in PC in patients with FIB-4≥1,3, and those with measurement ≥8kPa were referred to HC.

326 patients were studied. 71% were not referred to HC, due to liver stiffness <8kPa. 83 of the 95 derivations did TE in HC. 45 (54%) had TE ≥8, and 25 (30%) ≥12. The proportion of patients with stiffness ≥8kPa was 13,8% (45/326) and ≥12kPa, 7,6% (25/326). The predictive values of the FIB-4 were low. The interobserver correlation coefficient between TE in PC and HC was 0,433. Variables associated with TE ≥8 in PC: LT alteration, diabetes and steatosis. With TE ≥12: LT alteration, diabetes and obesity.

LT alteration and obesity.

The study supports the sequential performance of serum indices and TE as a screening for fibrosis in the at-risk population in PC, which allows a reduction in the percentage of patients referred to AH, and a better stratification of risk patients.

Hypophosphatasia (HPP) is a rare genetic metabolic bone disorder that is underdiagnosed. Although there are many forms of this disease, based on age of onset, symptoms, and severity, HPP is characterized by low serum alkaline phosphatase levels, bone fractures, and dental complications. Diagnosis of HPP is made from clinical, laboratory, and radiologic findings. Genetic testing for an ALPL gene variant responsible for causing HPP confirms a molecular diagnosis. Distinguishing HPP from other more common bone disorders, such as osteoporosis, is important as the treatment for these diseases differs greatly. Although there is no known cure for HPP, treatment should be holistic and multidisciplinary.

The Ryukyu archipelago is located southwest of the Japanese islands, and people originally from this region, the Ryukyu population, have a unique genetic background distinct from that of other populations, including people from mainland Japan. However, few genetic studies have focused on the Ryukyu population. In this study, we performed genome-wide association studies (GWAS) on the serum levels of alanine aminotransferase (ALT, n = 15,224), aspartate aminotransferase (AST, n = 15,203), and gamma-glutamyl transferase (GGT, n = 14,496) in the Ryukyu population. We found 13 loci with a genome-wide significant association (P < 5 × 10-8), three for ALT, four for AST, and six for GGT, including one novel locus associated with ALT: rs117595134-A in HMMR/HMMR-AS1, ß =  - 0.131, standard error = 0.024, P = 4.90 × 10-8. Rs117595134-A is common in the Japanese population but is not observed in other ethnic populations in the 1000 genomes database. Additionally, 77 of 80 loci derived from Korean GWAS and 541 of 716 loci from European GWAS showed the same directions of effect (P = 1.41 × 10-19, P = 2.50 × 10-44, binomial test), indicating that most of susceptibility loci are shared between the Ryukyu population and other ethnic populations.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

Background and Objectives: As a key mechanism of metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, inflammation triggered by chronic liver injury and immune cells with macrophages enables MASLD to progress to an advanced stage with irreversible processes such as fibrosis, cell necrosis, and cancer in the liver. The complexity of MASLD, including crosstalk between multiple organs and the liver, makes developing a new drug for MASLD challenging, especially in single-drug therapy. It was reported that upregulation of Notch1 is closely associated with the function of pro-inflammatory macrophages. To leverage this signaling pathway in treating MASLD, we developed a combination therapy. Materials and Methods: We chose Notch1 siRNA (siNotch1) to block the Notch pathway so that phenotypic regulation and functional recovery can be achieved in macrophages, combining with small molecule drug AMD3100. AMD3100 can cut off the migration of inflammatory cells to the liver to impede the development of inflammation and inhibit the CXCL12/CXCR4 biological axis in liver fibrosis to protect against the activation of HSCs. Then, we investigated the efficacy of the combination therapy on resolving inflammation and MASLD. Results: We demonstrated that in liver cells, siNotch1 combined with AMD3100 not only directly modulated macrophages by downregulating multiple pathways downstream of Notch, exerting anti-inflammatory, anti-migration, and switch of macrophage phenotype, but also modulated macrophage phenotypes through inhibiting NET release. The restored macrophages further regulate HSC and neutrophils. In in vivo pharmacodynamic studies, combination therapy exhibits a superior therapeutical effect over monotherapy in MASLD models. Conclusions: These results constitute an siRNA therapeutical approach combined with a small molecule drug against inflammation and liver injury in MASLD, offering a promising therapeutic intervention for MASLD.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) affects up to 70 000 people in the UK and the most common inherited cause of end-stage kidney disease (ESKD). It is generally a late-onset multisystem disorder characterised by bilateral kidney cysts, liver cysts and an increased risk of intracranial aneurysms. Approximately 50% of people with ADPKD reach ESKD by age 60. Disease-associated pain, discomfort, fatigue, emotional distress and, impaired mobility can impact health-related quality of life. The approval of tolvaptan, a vasopressin V2 receptor antagonist, has greatly advanced the care for people with ADPKD, shifting the focus from general chronic kidney disease management to targeted therapeutic approaches. While guidance from NICE and SMC provides a foundational framework, this is not clear or comprehensive enough to offer practical guidance for healthcare professionals in real-world settings. This commentary expands on the previous United Kingdom Kidney Association (UKKA) commentary in 2016 with an updated evidence base, the incorporation of real-world data and expert opinion to provide practical guidance to healthcare professionals. Through co-development with people affected by ADPKD, it now incorporates valuable patient perspectives and offers practical recommendations for the UK kidney community seeking to harmonise the quality of care of all people with ADPKD.

The liver is vital for metabolism, detoxification, storage, and secretion. Cholestasis, in which bile flow is hindered, can cause serious harm to the liver. This study examines the potential of ellagic acid to prevent cholestasis in male rats that has been caused by alpha-naphthyl isothiocyanate (ANIT).

Male rats were divided into four groups for an 8-day study. The control group received 5 % dimethyl sulfoxide (DMSO) orally for eight days and maize oil (1 mL/kg, orally) 48 h before sacrifice. The ANIT Group received 5 % DMSO orally for 8 days, the ANIT (100 mg/kg, orally) administered on the 6th day, 48 h before sacrifice. The low-Dose Ellagic Acid + ANIT Group was given ellagic acid (5 mg/kg, orally) for eight days, with ANIT (100 mg/kg, orally) on the 6th day, 48 h prior to sacrifice. The high-Dose Ellagic Acid + ANIT Group received ellagic acid (10 mg/kg, orally) for eight days, the ANIT (100 mg/kg, orally) on the 6th day, 48 h before sacrifice. Different biochemical and histopathological analyses were conducted to assess the protective effects of ellagic acid on ANIT-induced liver injury.

ANIT significantly elevated serum of liver enzymes. It caused severe bile duct inflammation and reduced bile salt export pump (BSEP) and Na+-taurocholate cotransporting polypeptide (NTCP) expression, indicating liver injury. Ellagic acid treatment mitigated these changes, improving biochemical parameters and reducing liver damage. ANIT-induced cholestasis results in bile acid accumulation due to decreased BSEP and NTCP expression linked to impaired farnesoid X receptor (FXR) signaling. Ellagic acid restored BSEP and NTCP levels via FXR activation, reducing bile acids and inflammatory markers IL-1β and TNF-α. Ellagic acid also enhanced SIRT1 activity, further improving FXR function and bile acid homeostasis.

Ellagic acid exhibits protective effects against cholestasis by enhancing the FXR signaling and ntcp and bsep expression with mitigating liver damage and inflammation.

BackgroundSince 2009, European guidelines recommend individuals with hepatitis B virus (HBV) and HIV be tested for hepatitis D virus (HDV).AimTo analyse HDV testing in individuals with HBV/HIV during routine practice in the Netherlands.MethodsWe assessed data from the ATHENA cohort of people with HIV who were ever HBV surface antigen-positive, aged ≥ 18 years and attended one of 24 HIV treatment centres in the Netherlands during 2000-22. Using longitudinal analysis, we estimated the percentage of individuals ever tested for HDV (antibody or RNA test) over time. In cross-sectional analysis, determinants for ever being tested by end of follow-up were assessed using relative risk regression.ResultsWe identified 1,715 individuals with HBV/HIV; 1,460 (85.1%) and 255 (14.9%) were male and female at birth, respectively (median age: 52 years; IQR: 42-59). Only 249 (14.5%) had an HDV test. The percentage tested increased from 5.0% (95% CI: 3.4-7.3) in 2000 to 17.0% (95% CI: 14.9-19.3) in 2022. In 2022, 16.2% (95% CI: 13.7-19.1) of men who have sex with men, 25.0% (95% CI: 9.7-50.9) of persons who inject(ed) drugs and 18.1% (95% CI: 14.6-22.3) of heterosexual/others were tested. In multivariable analysis, ever having an HDV test was associated with detectable HBV DNA viral load (p < 0.001), ever presenting with elevated alanine aminotransferase (ALT) levels (p = 0.023), advanced fibrosis/cirrhosis (p = 0.001) and being overweight/obese (p = 0.043).ConclusionsHDV testing coverage in the Netherlands is low for individuals with HBV/HIV. Although testing was more common in those with advanced liver disease, a considerable proportion at risk of HDV still need testing.

Whether and how sex plays differential roles in aging-related multimorbidity among people with HIV (PWH) is poorly characterized.

We included 2479 PWH and 5376 people without HIV from the baseline assessment of the CHART cohort (Comparative HIV and Aging Research in Taizhou). Ten non-AIDS comorbidities were investigated. Multiple logistic regression was used to assess the correlates of multimorbidity, defined as the coexistence of ≥2 non-AIDS comorbidities. Multimorbidity patterns were identified through hierarchical cluster analysis.

The prevalence of multimorbidity was higher in PWH than in people without HIV (74.6% vs 66.9%, P < .001). This difference was particularly pronounced in women in each age group from 18 through 59 years and among men in each age group from 18 through 49 years. A significant interaction between sex and HIV on multimorbidity was identified (P < .001), with the strength of the association between HIV infection and multimorbidity being stronger in women than in men. Women with HIV presented a unique aggregation pattern of multimorbidity, where neuropsychiatric disorders (depression, neurocognitive impairment) clustered with cardiometabolic diseases. In contrast, all men and women without HIV manifested a similar multimorbidity pattern, where depression and neurocognitive impairment were clustered with hematologic abnormalities but not with cardiometabolic diseases.

Earlier onset and higher burden of multimorbidity in PWH, as well as disproportionate vulnerability to and a unique multimorbidity pattern among women with HIV, underscore the urgent need for early and sexually oriented integrative interventions and health services targeting multimorbidity in PWH.

Chronic liver diseases (CLD) are a leading cause of death worldwide, with alcohol consumption and metabolic risk factors as the two reasons accounting for the majority of cases of CLD in many developed countries. Currently there is a lack of specific strategies for early diagnosis of CLD and consequently most cases are diagnosed in advanced stages of the disease, which is associated with negative consequences for disease management and prognosis. Screening for CLD is based on either detection of chronic viral hepatitis B and C, or detection of liver fibrosis in patients with steatotic liver disease related to alcohol or metabolic dysfunction. There are non-invasive tools available for detection of liver fibrosis, including serological and imaging-based tests. Clinical practice guidelines recommend screening for liver fibrosis using algorithms that combine different non-invasive tests, with widely available but low accuracy tests such as FIB-4 for a first screening step in primary care setting, and other tests with less availability but higher accuracy, such as Transient Elastography or Enhanced Liver Fibrosis Test as a second step. There are different pathways for early detection of patients with CLD from primary to specialized care, where primary care providers are key for early detection, management and referral of patients. In addition, intervention on metabolic risk factors and alcohol consumption should be carried out in collaboration between specialized therapy and primary care. This review describes liver fibrosis from the community perspective, highlighting gaps in knowledge on how to define the optimal combination of tests, target population, the ideal pathway of care for CLD, and how to increase implementation of programs for early diagnosis of liver diseases in clinical practice.

Liver disease is an increasing cause of premature mortality. Early detection of liver disease in primary care gives opportunity to intervene and change outcomes. Engagement in liver disease care by NHS bodies responsible for primary care pathway development could drive improvements. The formation of integrated care systems (ICS) in England provides an opportunity to reassess engagement with liver disease nationally.

To update the level of engagement with community chronic liver disease management among ICSs and health authorities across the UK.

A cross-sectional follow-up survey to ICS and UK health boards.

Questions used for a previous survey in 2020 were adapted and sent electronically to NHS bodies responsible for health care across the UK, using a freedom of information request. Quantitative analysis was undertaken using Microsoft Excel.

There were 67 responses from 68 possible ICS and health board areas, representing 99% UK coverage. Twenty-seven per cent had a named individual responsible for liver disease. Monitoring of local liver disease health statistics happened in 34% of all UK areas. Comprehensive care pathways were available in n = 24/67 (36%) of areas, an increase from 26% in the 2020 survey. Areas with no liver pathways in place fell from 58% to 36% between the two surveys. Regional variations persist, with Wales and Scotland moving towards comprehensive coverage. Almost double the number of areas were making use of transient elastography within community pathways of care, up from 25% to 46%.

The results of this re-survey highlight improvements, but emphasise the need to build on regional success to further reduce inequality in care commissioning.

Golgi protein 73 (GP73) is implicated in key pathogenic processes, particularly those related to inflammation and fibrogenesis. In the last years, its measurement has emerged as a promising biomarker for detection of liver fibrosis (LF), a common consequence of chronic liver disease that can progress to cirrhosis and eventually hepatocellular carcinoma. GP73 concentrations in blood appear significantly increased in LF patients, correlating with disease severity, making this biomarker a possible non-invasive alternative for detecting and monitoring this condition regardless of etiology. Understanding the molecular mechanisms involving GP73 expression could also lead to new therapeutic strategies aimed at modulating its synthesis or function to prevent or reverse LF. Despite its clinical potential, GP73 as a LF biomarker faces several challenges. The lack of demonstrated comparability among different assays as well as the lack of knowledge of individual variability can make difficult the result interpretation. Further research is therefore needed focusing on robust clinical validation of GP73 as a LF biomarker. Addressing analytical, biological, and clinical limitations will be critical to exploiting its potential for improving detection and monitoring of advanced LF.

The prevalence of obesity, along with that of its associated health conditions, including cardiovascular diseases, diabetes mellitus, and liver diseases, such as non-alcoholic fatty liver disease (NAFLD), is increasing annually. Bariatric surgery is indicated for the treatment of obesity if conservative treatment fails. While various liver fibrosis scores have been proposed for assessing liver function, they are typically used prior to bariatric surgery. This study aimed to determine whether fibrosis scores calculated from non-invasive parameters are effective in monitoring liver function after bariatric surgery.

This study analyzed data from 151 patients who underwent sleeve gastrectomy (SG) and were followed up at 3, 6, 9, 12, 24, and 36 months postoperatively. From the routinely collected parameters, liver fibrosis scores (APRI, Fib-4, BARD, Forns index [FORNS], Lok score [LOK], and NAFLD scores) were calculated retrospectively and compared to diabetes status % excess weight loss (%EWL) and % total weight loss (%TWL) over a 3-year follow-up period.

After SG, APRI, FORNS, and NAFLD scores showed significant improvements, whereas Fib-4, BARD, and LOK scores did not improve. Similarly, body mass index, %EWL, %TWL, and diabetes status also improved significantly. Throughout the 3-year follow-up period, only the APRI and NAFLD scores showed significant improvement.

Only APRI and NAFLD scores changed significantly after SG. Thus, these two scores may be used to reflect and monitor liver function in patients who have undergone SG.

Phthalates are the emerging environmental toxicants derived from phthalic acid and its constituents, which are moderately present in plastics and many personal care products. Phthalate exposure occurs through various environmental factors, including air, water, and soil, with absorption facilitated via ingestion, inhalation, and dermal contact. Upon exposure, phthalates become bioavailable within the biological systems and undergo biotransformation and detoxification processes in the liver. The physicochemical properties of phthalates indicate their lipophilicity, environmental persistence, and bioaccumulation potential, influencing their absorption, distribution, and hepatic biotransformation. The prolonged exposure to phthalates adversely influences the biological redox system by altering the levels of the enzymatic and non-enzymatic antioxidants, molecular signaling pathways, and causing hepatic pathogenesis. The strategies to combat phthalate-induced toxicity include avoiding exposure to these compounds and using plant-based bioactive molecules such as polyphenols, which possess therapeutic potential as antioxidants, suppress inflammatory cascades, prevent oxidative damage, and stabilize cellular integrity. This review presents a comprehensive and updated account of the chemical, biochemical, immunological, and toxicological properties of phthalates, along with novel plant-based therapeutic strategies to mitigate the phthalate-induced adverse effects on living systems.

Routine liver function tests capture information about the metabolic and inflammatory condition of the liver, but we lack sensitive biomarkers of early hepatocyte stress. In humans, soluble CD46 (sCD46) levels in blood were recently identified as an accurate biomarker of hepatic steatosis. Here, we explore the diagnostic utility of sCD46 in other liver diseases.

We developed, optimised and validated an ELISA that facilitates measurements of human sCD46 in plasma, serum and culture supernatants. Then, we analysed mechanisms that lead to the release of sCD46 and identified its role in various hepatic stress conditions.

We discovered that prostaglandin E2 (PGE2) drives upregulation of matrix metalloproteinase (MMP)-1 in fat-loaded hepatocytes, leading to proteolytic shedding of CD46. We further found that sCD46 release was increased by viral, toxic and hypoxic stresses.

sCD46 appears to be a promising biomarker with potential applications in the detection of early liver diseases or monitoring therapeutic responses, which could complement established diagnostic algorithms because sCD46 release is uniquely responsive to hepatocyte stress.

Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on steatotic liver disease limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver outcomes, and effect modification by folic acid (FA) supplementation in mother-child pairs.

We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with 43 MDCs measured during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. Outcomes included elevated liver enzymes in children and established clinical scores for steatosis and fibrosis in mothers (i.e.

ALT, FLI, HSI, FIB-4). Bayesian-weighted quantile sum regression assessed MDC-mixture associations with liver outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation.

In children, many MDC-mixtures were associated with liver injury. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95% CI 1.67%, 19.4%) and AST by 5.27% (95% CI 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations (p-interactions <0.05). In mothers, only the LMWP-mixture was associated with odds for steatosis (odds ratio = 1.53, 95% CI 1.01-2.28 for HSI >36, and odds ratio 1.62, 95% CI 1.05-2.49 for AST:ALT <1). In mothers and children, most associations were attenuated (null) at FA supplementation ≥600 μg/day (p-interactions <0.05).

Pregnancy MDC exposures may increase risk of liver injury and steatosis, particularly in children. Adequate FA supplementation and maternal cobalt levels may attenuate these associations.

The effects of environmental chemical exposures on steatotic liver diseases are not well understood. In a parallel investigation of mothers and children, we found that pregnancy exposures to metabolism-disrupting chemicals may increase the risk of liver injury and steatosis, especially in the child, and that these associations could be attenuated by higher folic acid and/or cobalt levels. These findings can inform policies to decrease environmental chemical pollution and contribute to the design of clinical interventions addressing the metabolic dysfunction-associated steatotic liver disease epidemic.

The objective of this study was to evaluate the diagnostic accuracy of the lactate dehydrogenase-to-albumin ratio (LAR) in adult-onset Still's disease (AOSD) and compare it with other inflammatory indices, using patients with fever of unknown origin (FUO) as a control group due to their overlapping clinical features with AOSD. The study also compared LAR's diagnostic performance with other inflammatory indices like the serum immune-inflammatory index (SII), ferritin/erythrocyte sedimentation rate (FER), CRP/albumin ratio (CAR), platelet/lymphocyte ratio (PLR), and neutrophil/lymphocyte ratio (NLR), as well as its combinations with FER, PLR, and ferritin (LAR + FER, LAR + PLR, LAR + ferritin).

A retrospective evaluation was conducted on 70 patients with fever of unknown cause and 78 patients with AOSD, admitted between January 2000 and December 2023 in a tertiary care hospital. Demographic, clinical, and laboratory characteristics were compared between the groups. ROC analysis provided cutoff values, sensitivity, and specificity for each inflammatory index.

ROC analysis showed significant p-values (p < 0.05) for indices other than LAR (p = 0.090) LAR + PLR (p = 0.806), and PLR (p = 0.634) in diagnosing AOSD. The highest specificity was found in LAR + ferritin (92.90%), and the highest sensitivity in CAR (100.0%). NLR, SII, FER, and LAR + FER were the indices with both sensitivity and specificity above 50%. LAR had a sensitivity of 76.90% and a specificity of 48.60%. The cutoff values were 3978.0 µg/L for ferritin and 70.98 for LAR. Significant statistical differences between AOSD and non-AOSD groups were observed for all indices except CAR (p = 0.133).

LAR can differentiate AOSD patients from FUO, but its specificity is lower than most other indices. The diagnostic utility of these indices in clinical practice remains controversial.

Individuals with genetic polymorphisms in UGT1A1 exhibit bilirubin levels that belie their risk of liver disease (Gilbert's syndrome) but it is not known if this phenomenon extends to other common liver blood tests (LBTs).

A genome-wide association analysis of 10 LBTs was conducted using the UK biobank. Polygenic scores (PGS) were created from discordant loci (e.g. loci associated with the LBT but not associated with cirrhosis morbidity risk). Participants were assigned to a low, intermediate or high PGS for each LBT. A high PGS approximates Gilbert's syndrome (i.e. elevated LBT without an analogous increase in disease risk). The prognostic significance of an 'elevated' LBT-and how this differs by PGS-was assessed through competing risk survival analysis.

This study included 157 005 and 166 871 participants for the discovery and validation phases, respectively. Elevated LBTs were more prevalent in the high versus low PGS group, yet the 10-year risk of cirrhosis morbidity was comparable. For example, in the low PGS group, 4.3% had an elevated gamma-glutamyltransferase (GGT) and the 10-year risk of cirrhosis morbidity was .45%. Conversely, in the high PGS group, 21.2% had an elevated GGT and the 10-year risk was .38%. Accordingly, the 10-year risk of cirrhosis morbidity for individuals with an elevated GGT was markedly different in the low vs. high group (4.2% vs. 1.2%; p < .001). Similar results were apparent for Fibrosis-4 index, total bilirubin, and platelet count.

Variability in LBTs is influenced by genetic polymorphisms that have a neutral effect on disease risk. These findings have implications for interpreting elevated LBTs in clinical practice.

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high-grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow-up. Alkaline phosphatase (AP), gamma-GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02-1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43-0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver-directed therapies.

Acute liver injury (ALI) is an injury to liver tissue caused by viruses, drugs, alcohol, and oxygen deprivation, and is one of the most common and serious clinical disorders. Hydroxytyrosol (HT) is a naturally occurring polyphenolic compound isolated from forsythia and has excellent anti-inflammatory properties. However, the effect and mechanisms of HT in ALI remain unclear. We used the LPS/D-GalN induced experimental ALI mouse model and AML12 cells to reveal the efficacy and potential mechanisms of HT in ALI, and HE staining was used for the evaluation of pathologies. A biochemical assay was used to detect changes in liver function, RNA-seq was conducted to reveal the underlying mechanisms of HT for ALI, and WB, RT-qPCR, and IF were used to assess the effects of HT action. Furthermore, an in vitro ALI model against HT in AML12 cells induced by LPS/D-GalN was used to assess the HT protection mechanism. HT significant alleviated LPS/D-GalN-induced ALI in the mice by suppressing inflammatory. In terms of RNA-seq, HT improved the TNF, ECM-receptor interaction, and PI3K/AKT signaling pathway, and it downregulated the mRNA levels of VCAM-1, CXCL5, TNF-α and IL-6 in the liver. Mechanically, HT alleviated LPS/D-GalN in the mice by targeting TNF-α, thereby inhibiting the TNF-α/PI3K/AKT signaling pathway.

Background: Emerging studies demonstrate that exposure to brominated flame retardants (BFRs) can have harmful effects on human health. Our study focused on the relationship between exposure to various BFRs and markers of liver function. Methods: To further explore the association between BFR exposure and liver function impairment, we used data from the National Health and Nutrition Examination Surveys (NHANES) for three cycles from 2009 to 2014, leaving 4206 participants (≥20 years of age) after screening. Nine BFRs and eight liver function tests (LFTs) were measured in the participants' serum to represent BFRs and liver function impairment in vivo. To investigate whether there is a relationship between BFRs and health outcome, statistical research methods such as the weighted linear regression model, restricted cubic spline (RCS), weighted quantile sum (WQS), quantile-based g computing (QGC), and the Bayesian Kernel Machine Regression (BKMR) were used to evaluate the correlation between serum BFRs and LFTs. Results: The studies reveals that exposure to BFRs is associated with liver function biomarkers. In a weighted linear regression model, we found that PBB153, PBDE99, PBDE154, PBDE209, PBDE85 exposure was positively correlated with AST, ALT, GGT, ALP, TP, and SL risk. In RCS model, the nonlinear relationships between PBB153 and AST, ALT, and GGT and PBDE209 and ALT and TP are the most significant. The exposure to combined BFRs was positively correlated with AST, ALT, and GGT in WQS and QGC models. BKMR analysis showed that BFR exposure was positively correlated with AST, ALT, ALP, and GGT. Conclusions: Exposure to BFRs is associated with liver function impairment, suggesting that BFR exposure is potentially toxic to the human liver, but more in-depth studies are needed to explore this correlation.

Steatotic liver disease is the overarching term for conditions characterised by abnormal lipid accumulation in the liver (liver or hepatic steatosis). Steatotic liver disease encompasses what was previously termed non-alcoholic fatty liver disease (NAFLD), which is now called metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, steatotic liver disease includes alcohol-related liver disease (ALD) and MetALD, the new classification for the overlap between MASLD and ALD, and rare causes of liver steatosis. Cirrhosis is globally the 11th leading cause of death, and steatotic liver disease has become the leading cause of cirrhosis in the EU and USA. Steatotic liver disease affects around 30% of the global population and is mainly driven by obesity, type 2 diabetes, and alcohol intake, but only a minor proportion with steatotic liver disease progress to cirrhosis. The presence and progression of liver fibrosis led by hepatic inflammation is the main predictor of liver-related death across the entire spectrum of steatotic liver diseases. A combination of recent advancements of widely available biomarkers for early detection of liver fibrosis together with considerable advancements in therapeutic interventions offer the possibility to reduce morbidity and mortality in patients with steatotic liver disease. This Seminar covers the recent reclassification of steatotic liver disease and how it reflects clinical practice and prognosis. For early detection of liver fibrosis, we propose a collaborative diagnostic framework between primary care and liver specialists. Lastly, we discuss current best practices for managing steatotic liver disease, we explore therapeutic targets across the spectrum of steatotic liver diseases, and we review the pipeline of drugs in development for MASLD.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults are understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥70 years) and assess for associations with mortality.

Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality.

Of the 11 853 participants with ALT and AST levels, 1 054 (8.9%) deaths were recorded over a median of 6.4 (interquartile range [IQR] 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 and 5-13 U/L, respectively; for AST, the lowest quintiles were 8-18 and 7-17 U/L, respectively. On both univariate and models adjusted for covariates including age, body mass index, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% confidence interval {CI} 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88], respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers.

Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only affected older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered.

As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this.

Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes.

Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results.

The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required.

Background and aims Compensated advanced chronic liver disease (cACLD) refers to asymptomatic patients with advanced fibrosis who do not yet exhibit clinical or radiological signs of portal hypertension. Early detection of cACLD is essential for effective risk stratification and timely management, potentially preventing progression to more severe and irreversible stages of liver disease. Transient elastography (TE) is the primary diagnostic method for cACLD, with several diagnostic thresholds commonly used. Ultrasonography (USG) is widely used as an initial diagnostic tool for liver disease, but its effectiveness in diagnosing cACLD is not well established. To the best of our knowledge, this study is the first to systematically evaluate the diagnostic accuracy of USG in detecting cACLD, using TE as a reference standard based on validated diagnostic thresholds. We also examined whether combining USG findings with platelet count and serum albumin could enhance diagnostic utility. Additionally, we discuss the strengths and limitations of established non-invasive scoring systems, including the Enhanced Liver Fibrosis (ELF) test, Fibrosis-4 (Fib-4) index, and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS), to determine if our approach offers a more accessible and practical solution in clinical settings Methods This retrospective cross-sectional study was conducted at the Royal Wolverhampton NHS Trust, Wolverhampton, England, including patients with suspected liver disease who underwent USG, TE, and blood tests. Valid TE readings followed manufacturer guidelines, and patients with USG-detected portal hypertension or confounding conditions (e.g., acute hepatitis, heart failure) were excluded. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of USG against TE, with TE values >15 kPa confirming and <10 kPa excluding cACLD. Results Among 1,528 patients (mean age 51 years, range 16-89), 982 were male (64.3%) and 546 were female (35.7%). The cohort predominantly comprised Caucasian (n=1,087, 71.1%) and South-East Asian (n=256, 16.8%) patients. USG showed a sensitivity of 64.6% (95%CI: 58.3-70.6%) and specificity of 78.2% (95%CI: 75.6-80.6%) for cACLD, with a PPV of 40.2% (95%CI: 36.7-43.7%) and an NPV of 90.7% (95%CI: 89.2-92.1%). High NPV was consistent across all etiologies. In patients with a normal liver on USG, NPV improved to 92.7% (95%CI: 90.9-94.6%) when serum albumin >35 g/L and platelet count >150 x 109/L were present. In patients with sonographic signs of liver disease, PPV increased to 84.1% (95%CI: 73.3-94.9%) when platelet count and albumin were low but dropped to 20.8% (95%CI: 15.4-26.3%) when both were normal. Conclusions USG alone has limited reliability in diagnosing cACLD but is valuable for ruling out advanced fibrosis in asymptomatic patients due to its high NPV. Adding platelet and albumin levels improves diagnostic accuracy, though TE remains essential for definitive diagnosis. This approach may streamline screening and optimize resource use, particularly in settings with limited TE access. USG combined with platelet count and serum albumin offers a cost-effective, accessible, and practical solution for the initial assessment of cACLD. Further studies are needed to validate these findings in broader populations.

Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.

Jaundice and hyperbilirubinemia are common clinical problems characterized by the presence of bile pigments in the blood and their deposition in body tissues. This clinical condition can be associated with a broad spectrum of potential benign and malignant causes, including hepatic inflammation, biliary obstruction, impaired bilirubin conjugation and bilirubin overproduction Therefore, the hyperbilirubinemia diagnostic work-up sometimes can be highly challenging and its therapeutic management can require a multidisciplinary approach.

We report on a unique case of life-threatening jaundice and hepatic failure in a 20-year-old female who presented to the emergency room with complaints of fever, constant left abdominal pain and generalized profuse fatigue. A complete and detailed medical history, multiple tests for various infection, radiologic investigations and histological tests were performed in order to clarify the etiology of that rapidly progressive clinical condition. Based on the results, the patient jaundice was caused by an Epstein-Barr virus (EBV) infection and secondary cold agglutinin syndrome. Given the rare and complex diagnosis, multiple clinical specialists were asked to carry out the best patient management.

This rare case highlights how challenging the differential diagnosis and treatment of hyperbilirubinemia can be, presenting a unique case of life-threatening multifactorial hepatic failure treated successfully with rituximab.

The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma.

This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level.

This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021.

A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively.

In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.

Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) are both facets of the metabolic syndrome, associated with obesity and insulin resistance. MASLD, a term that replaces non-alcoholic fatty liver disease (NAFLD), occurs in up to 70% of people with T2D. Not only do T2D and MASLD commonly co-occur, but there is a synergistic, bidirectional relationship between these conditions, meaning that each affects the natural disease course of the other. As such, it is important for those caring for people with T2D to recognize the importance of this co-diagnosis. In this summary, we detail the synergistic relationship between T2D and MASLD, explain the current challenges in recognizing this common co-diagnosis and suggest practical approaches for those caring for people with T2D to improve the diagnosis and treatment of MASLD.