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OBJECTIVE: Infections cause considerable morbidity after liver transplantation (LT). Acute liver failure is a rapidly progressing life-threatening condition where pretransplant dental evaluation is not always possible. We investigated how missing pretransplant dental treatment in acute or subacute liver failure correlates with post-transplant infectious complications. SUBJECTS AND METHODS: Medical and dental data came from hospital records and infection data from the Finnish LT registry. The follow-up was until February 2011. Of 51 patients (LT during 2000-2006), 16 had and 35 did not have dental treatment pretransplant. RESULTS: Univariate Cox regression analysis demonstrated a 2.46-fold (95% Cl 1.06-5.69) infection risk among the patients omitted from dental treatment. After adjustment for either pretransplant factors alone or both pre- and post-transplant factors, the corresponding infection risk increased, respectively, to 8.17-fold (95% Cl 2.19-30.6) and 8.54-fold (95% Cl 1.82-40.1). This increased risk involved a variety of bacterial, viral, and fungal infections of various sources both < 6 and > 6 months after transplantation. CONCLUSION: High risk of infections was noticed in acute liver failure patients without pretransplant dental treatment, but a more severe medical condition might have influenced the results. We encourage eradication of dental infection foci whenever clinical condition allows. [ABSTRACT FROM AUTHOR]

Background and Aims: The enhanced liver fibrosis (ELF) test has good discrimination performance in detecting advanced liver fibrosis. The chronic liver disease (CLivD) risk score based on clinical data accurately predicts risk for future severe liver disease. Considering the ELF test as a surrogate marker for liver fibrosis, we analyzed predictors of elevated ELF (eELF) and its change., Methods: The study cohort consisted of Finnish general population-based health surveys Health2000 and a follow-up study 10 years later Health2011 with 6084 and 2937 individuals, respectively with phenotype and ELF data. eELF was defined as ELF ≥ 9.8, and clinically relevant fibrosis progression as an ELF change ≥0.6. CLivD risk score was calculated at baseline. Analyses were age-adjusted., Results: Obesity measures and diabetes predicted eELF at baseline. Only waist-hip ratio (WHR) could predict clinically relevant fibrosis progression over the follow-up consistently among men and women (OR 1.35 and 1.41, respectively). High-risk alcohol use was a significant risk factor for eELF only among men (OR 1.72, p  = 0.049), and it did not predict fibrosis progression in either sex. Although elevated transaminases were associated with eELF, in most individuals with eELF they were within reference limits. Increased CLivD scores correlated with baseline and the change of ELF values over the 10-year follow-up independent of baseline ELF ( p  < 0.001)., Conclusions: Liver fibrosis progression is difficult to predict based on single risk factors or liver enzymes. ELF had limited value to predict fibrosis progression. The CLivD score, based on multiple risk factors, predicted both occurrence of baseline eELF and its progression over a 10-year follow-up.

Background: Prevalent manifestation of metabolic dysfunction, metabolic dysfunction-associated steatotic liver disease (MASLD), has been associated with poorer cognitive performance and greater decline in cognitive functions., Aim: The aim of this study was to analyze whether MASLD, measured by fatty-liver-index (FLI), predicts decline in cognitive performance during 11 years., Methods: This study was based on the Finnish nationwide, population-based Health 2000 Health Examination Survey and its follow-up, Health 2011 Survey. Cognitive performance was assessed with verbal fluency, word-list learning (WLL), delayed word-list recall (both at baseline and at follow-up), and with simple reaction time and visual choice reaction time tests (only at baseline). Statistical analyses were performed using multivariate linear regression adjusted for age, sex, education, APOE ε4 genotype, hypercholesterolemia, diabetes mellitus, hypertension, depressive symptoms, physical activity smoking status, C-reactive protein and HOMA of insulin resistance., Results: Cross-sectionally, 5,139 (mean age 52.3 years) and longitudinally, 3,143 (mean age 49.3 years) participants were examined. Cross-sectionally, no associations between FLI and cognitive performance were found in the adjusted models. Longitudinally, baseline FLI > 60 predicted poorer WLL (p < 0.005) and a decline in WLL from baseline to follow-up (p < 0.04)., Conclusions: Our results suggest that MASLD is an independent predictor of decline in a test measuring working memory and learning., Competing Interests: Conflicts of interest No conflicts of interest., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD., Competing Interests: Declaration of competing interest Christos S. Mantzoros has recused himself as EIC from handling this manuscript, reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. Christopher D Byrne has received an independent research grant from Echosens. France. W. Kim received honoraria for lectures from GSK, Hanmi, KOBIOLABS, and Novo Nordisk; consulting fees from Boehringer-Ingelheim, GSK, Novo Nordisk, Ildong, YUHAN, Hanmi, HK Inoen, Standigm, PharmaKing, Olix Pharma, TSD Life Sciences, Daewoong, QUEST, Therasid Bioscience, and Korea United Pharm; grants from GSK, Gilead, Novartis, Pfizer, Roche, Springbank, Ildong, BMS, DaeWoong, Hanmi, Novo Nordisk, Galmed, Enyo, and KOBIOLABS; stock options from KOBIOLABS and Lepidyne; and founded Remedygen outside the submitted work. Anoop Misra has received honorarium for lectures from Astra Zendeca, Boehringer Ingelgheim, Janssen, Lupin, Novo Nordisk and US Vitamins. Yusuf Yilmaz has served as a consultant or advisory board member for Zydus and Novo Nordisk. Boehringer Ingelheim. Wah Kheong Chan has served as a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Ming-Lung Yu has received research support (grant) from Abbvie, BMS, Gilead, Merck and Roche diagnostics, served as a consultant of Abbott, Abbvie, BMS, Gilead, Roche and Roche diagnostics, and speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. Vincent Wong has served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, Novo Nordisk, and Unilab. He has received a research grant from Gilead Sciences, and is a co-founder of Illuminatio Medical Technology. Giada Sebastiani has acted as speaker for Merck, Gilead, Abbvie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. Jacob George has served on advisory Boards and receives honoraria for talks from Novo Nordisk, Astra Zeneca, Roche, BMS, Pfizer, Cincera, Pharmaxis, Boehringer Mannheim, CSL, Gilead, Eisai. Carolyn Newberry serves as a consultant for Nestle Nutrition Sciences. The other authors declare no conflict of interest related to the preparation of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alcohol-associated liver disease (ALD), as highlighted in this narrative review, is a major public health concern, increasingly impacting global disease burden and premature mortality. In 2019, ALD accounted for the loss of 11 million life-years worldwide. The rising number of deaths and disability-adjusted life-years attributed to ALD, particularly pronounced in the United States, are alarming. Projections suggest that the economic impact of ALD, as seen in the United States, could potentially double by 2040. ALD is increasingly prevalent among younger adults (20-45 y) and has become the leading cause of liver transplantation in both United States and Europe. During the COVID-19 pandemic, the existing trend was further amplified as high-risk drinking patterns coincided with a rise in hospital admissions for alcohol-associated hepatitis and increased ALD-related mortality. The prevalence of ALD is estimated at 3.5% in the general population, 26.0% among hazardous drinkers, and 55.1% among those with alcohol use disorders. Alarmingly, 5-year mortality rates for patients with ALD exceed 50%, with even higher rates in more advanced disease stages. Methodological challenges, such as underreporting, diagnostic difficulties, and variability in registry data quality, complicate the accurate assessment of the impact of ALD. Additionally, the contribution of alcohol to the progression of other liver diseases is often under acknowledged in health care registries, leading to a significant underestimation of its broader implications for liver health. Addressing the growing ALD concern requires robust public health initiatives, heightened awareness, refined diagnostic techniques, and comprehensive epidemiological studies. These measures are vital to tackle the increasing prevalence of ALD and mitigate its extensive impact on individuals and health care systems., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The optimal calcineurin inhibitor after liver transplantation (LT) for primary biliary cholangitis (PBC) remains debated. We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis from the Scientific Registry of Transplant Recipients. We included adults with PBC who underwent primary LT from 1995 to 2022. Patients with initial cyclosporine treatment were 1:3 matched with those with initial tacrolimus treatment, ensuring exact calendar-period match. Primary outcomes were patient and graft survival. After matching, 579 patients with PBC and initial cyclosporine and 1348 with tacrolimus were well balanced for baseline characteristics. During a median follow-up of 11.1 years, 1044 (54%) deaths and 124 (6%) re-LTs occurred. In the overall matched sample, no significant survival difference emerged between cyclosporine and tacrolimus. However, tacrolimus conferred a survival advantage in some secondary analysis, such as LT after year 2000 and women, and in a 6-month landmark analysis excluding early postoperative events and calcineurin inhibitor switches. Cyclosporine did not reduce graft loss from PBC recurrence or affect laboratory markers of recurrence. In conclusion, we found no benefit of starting immunosuppression with cyclosporine after LT for PBC., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11., Methods: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members., Results: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%)., Conclusions: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background & Aims: A new nomenclature and subclassification for steatotic liver disease (SLD) was recently introduced. We validated the prognostic value of SLD subclasses in a Finnish population-based cohort and explored the impact of metabolic risk factors and alcohol consumption on liver-related outcomes and death., Methods: The study included 23,910 individuals (47% men, mean age 50.5 ± 14.0 years, BMI 27.0 ± 4.7 kg/m 2 ) from the FINRISK and Health 2000 health examination surveys with healthcare registry linkage for severe liver-related outcomes and deaths. SLD was identified by alanine aminotransferase (ALT) levels >20 U/L in women and >30 U/L in men (primary analysis) or fatty liver index (FLI) ≥60 (sensitivity analysis)., Results: The prevalence of ALT-defined SLD was 43% (n = 10,380), with subclass rates of 34.5% for metabolic dysfunction-associated steatotic liver disease (MASLD), 4.2% for coexistent MASLD and alcohol-related liver disease (ALD) (i.e., MetALD), and 1.8% for ALD. During a median 13.3-year follow-up, we observed 129 liver-related events. MetALD and ALD increased the age- and sex-adjusted liver-related outcome risk by fourfold (HR 3.83, 95% CI 2.51-5.84, p <0.001) and eightfold (HR 7.90, 95% CI 5.16-12.30, p <0.001), respectively, compared with patients with MASLD. ALD was also associated with the highest risk for non-liver mortality. Metabolic risk factors were present in 93% and 96% of individuals with ALT-defined SLD and ALD, respectively. Alcohol use amplified the risk of liver-related outcomes in individuals with MASLD. Sensitivity analyses by the FLI were similar., Conclusion: SLD is a significant public health concern. Nearly all ALD cases exhibit metabolic risk factors. Among ALT-defined SLD subclasses, ALD presents the highest risk for both liver-related and non-liver-related outcomes. Alcohol use increases the risk of liver-related outcomes in individuals with MASLD., Impact and Implications: This study provides important information for physicians, researchers, and patients, demonstrating that the new classification of steatotic liver disease (SLD) has prognostic relevance at the population level. Evaluating the SLD subclass for a patient helps in understanding the magnitude of the risk for liver- and non-liver-related outcomes. In particular, the risks are highest in those with alcohol-related liver disease (ALD), but also increased in individuals with coexisting metabolic dysfunction-associated steatotic liver disease (MASLD) and ALD (MetALD) when compared with those with MASLD. However, alcohol use increased the risk of liver-related outcomes also in individuals with MASLD, highlighting the importance of evaluating alcohol use in every patient with SLD. Nearly all individuals with ALD have metabolic risk factors, and it is important to treat these factors to improve the survival of these patients., (© 2024 The Authors.)

Background & Aims: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis (PSC) are lacking. We evaluated the predictive value of serum and biliary biochemistry for the progression of bile duct disease in PSC using repeated endoscopic retrograde cholangiopancreatography (ERCP) examinations to identify surrogate markers for more personalized surveillance., Methods: We conducted a prospective analysis including patients with PSC who underwent ERCP for confirmation of diagnosis, monitoring of disease progression, or dysplasia surveillance. ERCP findings were scored, and dilatation was performed if a dominant stricture was diagnosed or if a cytology brush could not be passed. Bile samples were aspirated for biliary IL8 and calprotectin. We analysed optimal cut-off values and AUCs for 20 laboratory markers and evaluated their association with the time to an ERCP score increase of ≥2 points or first dilatation, whichever came first. Of the 1,002 patients, 653 had ≥2 ERCP examinations and ≥3 years of follow-up. After excluding patients with PSC-overlap syndrome or initial dilatation, 398 patients were included., Results: Of the patients included, 62% had mild or moderate and 38% had advanced bile duct disease. During follow-up, 41% of patients demonstrated progression of disease. Biliary calprotectin (AUC 0.76; 95% CI 0.69 to 0.82) and IL8 (AUC 0.76; 95% CI 0.69 to 0.84) were the only variables that demonstrated predictive value for disease progression and/or need for dilatation., Conclusions: Biliary calprotectin and IL8 are promising surrogate markers for identifying patients with PSC at risk of progression and determining the timing for subsequent imaging. Conventional liver function tests may not be sensitive or specific enough to monitor PSC progression, particularly in the short term., Impact and Implications: Validated prognostic tools for estimating short-term bile duct disease progression in primary sclerosing cholangitis are lacking. In this prospective study, based on sequential endoscopic retrograde cholangiopancreatography examinations, biliary calprotectin and IL8 levels turned out to be more sensitive for predicting bile duct progression than traditional liver function tests, such as alkaline phosphatase, in the short term. These findings could lead to more personalized patient surveillance and improve clinical practice by providing a more accurate method for monitoring disease progression and treatment responses. Additionally, these markers have potential as surrogate endpoints in clinical drug trials. The limitation is that measurement of biliary IL8 and calprotectin requires endoscopic retrograde cholangiopancreatography with bile sampling., (© 2024 The Authors.)

Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: A need exists for effective and practical tools to identify individuals at increased risk of liver-related outcomes (LROs) within the general population., Approach and Results: We externally validated the chronic liver disease (CLivD) score for LROs in the UK Biobank cohort. We also investigated the sequential combined use of CLivD and fibrosis-4 (FIB-4) scores. Our analysis included 369,832 adults without baseline liver disease and with available data for CLivD and FIB-4 computation. LROs reflecting compensated or decompensated liver cirrhosis or HCC were ascertained through linkages with electronic health care registries. Discriminatory performance and cumulative incidence were evaluated with competing-risk methodologies. Over a 10-year follow-up, time-dependent AUC values for LRO prediction were 0.80 for CLivD lab (including gamma-glutamyltransferase), 0.72 for CLivD non-lab (excluding laboratory values), and 0.75 for FIB-4. CLivD lab demonstrated AUC values exceeding 0.85 for liver-related death and severe alcohol-associated liver outcomes. The predictive performance of FIB-4 increased with rising CLivD scores; 10-year FIB-4 AUC values ranged from 0.60 within the minimal-risk CLivD subgroup to 0.81 within the high-risk CLivD subgroup. Moreover, in the minimal-risk CLivD subgroup, the cumulative incidence of LRO varied from 0.05% to 0.3% across low-to-high FIB-4 strata. In contrast, within the high-risk CLivD subgroup, the corresponding incidence ranged from 1.7% to 21.1% (up to 33% in individuals with FIB-4 >3.25)., Conclusions: The CLivD score is a valid tool for LRO risk assessment and improves the predictive performance of FIB-4. The combined use of CLivD and FIB-4 identified a subgroup where 1 in 3 individuals developed LROs within 10 years., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene., Methods: The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m 2 ). The effects of HFE variants on these associations were also evaluated., Results: Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes ( n  = 92) and severe liver-related outcomes ( n  = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02-1.21]; p  = 0.012 and HR 1.11 [95% CI 1.02-1.21]; p  = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes., Conclusion: Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia.

Background: Kidney disease is common after liver transplantation (LT), but postoperative kidney failure is difficult to predict. Current guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with pre-LT estimated glomerular filtration rate (eGFR) below 30-40 mL/min, which might be too liberal. The aim of this study was to evaluate the risk of kidney failure after LT. We also assessed the predictive ability of pretransplantation eGFR using various equations., Methods: This single-center study included patients undergoing primary LT 2006-2020. Patients undergoing simultaneous liver-kidney transplantations or on dialysis before LT were analysed separately. We calculated 5 different eGFR equations measured just before LT and assessed their predictive ability using Kaplan-Meier cumulative incidence estimates., Results: Among 556 LT patients with a median follow-up of 5.0 years (IQR 2.0-8.5), 20 developed kidney failure during follow-up, 7 of them within 1-year post LT. Six of these 7 suffered from major perioperative complications. Depending on the eGFR equation used, the incidence of kidney failure within 1-year was 3.9-6.7% at pre-LT eGFR-values <30 mL/min, 1.2-3.1% at eGFR 30-60 mL/min, and 0.6-0.9% at eGFR >60 mL/min., Conclusions: Kidney failure within 1-year post-LT could not be reliably predicted by pre-LT eGFR. However, kidney failure was uncommon even in patients with severely reduced pre-LT glomerular filtration rate (eGFR <30 mL/min), and extremely rare in patients unaffected by major perioperative complications. Our data prompts further consideration regarding the guidelines for SLKT in patients with a reduced preoperative eGFR.

Competing Interests: I declare no competing interests.

Background: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy., Methods: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries., Results: Consensus ranged from 88.8% to 96.9% (mean = 92.3%)., Conclusions: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background & Aims: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US., Methods: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates., Results: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant., Conclusions: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC., Impact and Implications: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: Steatotic liver disease (SLD) is a growing global concern. The Chronic Liver Disease (CLivD) risk score predicts liver-related outcomes in the general population using easily accessible variables with or without laboratory tests (CLivD lab and CLivD non-lab ). We assessed CLivD's associations with liver steatosis, fibrosis and its combined performance with fibrosis-4 (FIB-4) for advanced fibrosis detection., Methods: Using the National Health and Nutrition Examination Survey data (2017-2020), 3603 participants aged 40-70 years with valid liver stiffness measurements (LSMs) were included. Advanced fibrosis was defined as LSM ≥12 kPa, and SLD as controlled attenuation parameter ≥288 dB/m., Results: Significant associations were found between CLivD and SLD and advanced fibrosis. CLivD lab had an area under the curve (AUC) for advanced fibrosis of 0.72 (95% CI 0.68 to 0.77), while CLivD non-lab had an AUC of 0.68 (95% CI 0.64 to 0.72), both slightly higher than FIB-4 (AUC 0.66, 95% CI 0.60 to 0.72). Among participants without obesity, AUC of CLivD lab was 0.82 (95% CI 0.76 to 0.88) and AUC of CLivD non-lab was 0.72 (95% CI 0.65 to 0.79). The CLivD score improved FIB-4's AUC for advanced fibrosis detection from <0.5 at minimal CLivD scores to >0.8 at high CLivD scores. A sequential CLivD→FIB-4 strategy outperformed universal FIB-4 testing, enhancing specificity from 72% to 83%, with sensitivity at 51%-53%. This strategy identified a subgroup with a 55% prevalence of advanced fibrosis, while 47% had minimal-risk CLivD scores, eliminating the need for FIB-4 testing., Conclusions: The CLivD score, designed for predicting liver-related outcomes, effectively identifies liver steatosis and advanced fibrosis in the general population. Combining CLivD with FIB-4 enhances advanced fibrosis detection accuracy. The CLivD score could enhance population-based liver fibrosis screening, optimising resource allocation., Competing Interests: FÅ is an Associate Editor for eGastroenterology., (Copyright © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Few studies have investigated mortality rates in patients with Wilson's disease and compared these to the general population. Here, we examined several clinical outcomes (including cardiovascular, psychiatric, neurologic conditions) in a population-based study of patients with Wilson's disease., Method: We used nationwide registers to identify all patients with a first diagnosis of Wilson's disease between 2002 and 2020 in Sweden. Each patient was matched by age, sex, and municipality with up to 10 reference individuals from the general population. Validated registers were used to investigate outcomes up to 19 years after baseline in patients and reference individuals., Results: We identified 151 patients with Wilson's disease matched with 1441 reference individuals. Median age at baseline was 26 years (IQR 17-42) and 50% were males. During a median follow-up of 6.6 years (IQR 2.9-12.9), 10 (6.6%) patients with Wilson's disease died compared with 31 (2.2%) reference individuals. This translated to a hazard ratio (HR) of 3.8 (95%CI = 1.8-8.1). Mortality was higher among Wilson's disease patients with baseline neuropsychiatric diagnoses (HR 7.9, 95%CI = 2.9-21.8). Cumulative mortality over 10 years was 9.3% (95%CI = 5.0-16.8) in Wilson's disease, compared to 2.4% (95%CI = 1.6-3.6) in reference individuals. We observed significantly elevated risks in the Wilson's disease group for incident cardiovascular disease, and incident psychiatric and neurological conditions when considering liver transplantation or death from other causes as competing events., Conclusion: In this large population-based cohort study, patients with Wilson's disease had an almost four-fold increased mortality rate compared with matched individuals from the general population., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease., Methods: This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression., Results: Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04-0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05-0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21-2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07-2.68, p < 0.05 respectively)., Conclusions: Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)