Risk Of Chronic Liver Disease Research Articles

Effect of whole grain and fiber consumption on chronic liver diseases: a systematic review and meta-analysis.

Objective: The aim of the present study was to conduct a meta-analysis of observational studies to explore the latest evidence on the influence of whole grain and fiber consumption on total chronic liver diseases. Methods: We searched the PubMed and Web of Science online databases and reference lists of eligible articles up to June, 2024. Results: The odds ratio (OR) between whole grain intake and total chronic liver disease risk was 0.90 (95% confidence interval (CI): 0.81 to 0.99, p < 0.001) and indicated an OR of 0.65 (95% CI: 0.57 to 0.74, p < 0.001) between fiber intake and total chronic liver disease risk when comparing the highest and lowest total intake, both indicating a significant negative correlation. Furthermore, subgroup analysis revealed that the protective effect of whole grains on chronic liver diseases was the most significant in cirrhosis (OR = 0.65; 95% CI: 0.57 to 0.74) and mortality (OR = 0.37; 95% CI: 0.29 to 0.47). Conclusion: Whole grain and fiber intake has a protective effect on the risk of chronic liver diseases.

Generic sofosbuvir and daclatasvir for treatment of hepatitis C virus infection in patients with sickle cell disease

Background and purpose of the studySickle cell disease (SCD) patients are at a high risk of chronic liver disease (CLD) due to chronic viral hepatitis infection such as hepatitis C virus (HCV) infection, iron overload, and sickle cell hepatopathy. Nowadays, several oral direct-acting antiviral drugs (DAAs) have been developed and approved by the FDA for hepatitis C treatment. However, the safety and efficacy of DAAs in SCD patients remain insufficiently explored.Purpose of the studyTo evaluate the efficacy and safety of administration of generic sofosbuvir (SOF) and daclatasvir (DCV) for 12 weeks in SCD patients infected with HCV.MethodsA retrospective study included 38 SCD patients infected with HCV treated with generic SOF (400 mg) and DCV (60 mg) for 12 weeks without ribavirin. The effectiveness of the HCV treatment was assessed by the sustained virologic response (SVR) at 24 weeks after the end of the treatment (SVR24).ResultsThe SVR24 rate was 100% (38/38).There were insignificant alterations in hemoglobin and total bilirubin levels during HCV treatment or at end of treatment (EOT). The number of anemic patients who needed blood transfusion two weeks before HCV treatment, at week 4 of treatment, and at EOT was 11 (28.9%), 3 (8%), and 1 (3%) respectively. Moreover, the reductions in serum transaminase levels from baseline were statistically significant compared to the EOT.ConclusionGeneric SOF and DCV regimens appear to be safe and effective in the treatment of chronic HCV in patients with SCD.

Cross-sectional study of the prevalence of chronic liver disease risk factors and liver fibrosis in a remotely living Indigenous Australian population

ObjectivesRemotely living Indigenous Australians have a disproportionate mortality from cirrhosis and hepatocellular cancer (HCC). However, there are no local population studies examining the prevalence of chronic liver disease (CLD) in...

Frailty and risk of metabolic dysfunction–associated steatotic liver disease and other chronic liver diseases

Background & AimsFrailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction–associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. MethodsA total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. ResultsDuring a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40–1.97; frailty index: HR = 2.01, 95% CI = 1.67–2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54–4.34; frailty index: HR = 4.54, 95% CI = 3.65–5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging–derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32–2.04; frailty index: OR = 1.48, 95% CI = 1.30–1.68). ConclusionsFrailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. Impact and implicationsWhile frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA-seq to reveal sex-dependent patterns in IUGR-induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast-driven T cell conversion into an immune-adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non-immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over-expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.

Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease

BackgroundMitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored.MethodsWe extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality.Results96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e − 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15–6.85), 2.82-fold (1.69–4.72), and 4.41-fold (3.04–6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome.ConclusionsOur findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.

Early Prediction of Liver Disease

Abstract: Chronic liver disease (CLD) poses a substantial global health challenge, leading to considerable morbidity and mortality. The timely identification of CLD is imperative to enhance patient outcomes and ensure effective disease management. This research introduces an innovative machine learning framework designed to predict liver disease at an early stage, utilizing a wide range of clinical data resources. By integrating demographic information, laboratory test results, imaging findings, and patient medical history, our model aims to accurately forecast the onset and progression of CLD. Advanced classification algorithms, including Random Forest and Gradient Boosting, are employed for feature selection and model development. Performance evaluation is conducted on a comprehensive dataset comprising longitudinal patient records. The results demonstrate promising accuracy, sensitivity, and specificity, highlighting the potential of machine learning in enhancing CLD risk assessment and enabling timely interventions.

Lifestyle and genetic risk of chronic liver disease in metabolically healthy and unhealthy individuals from the general population

Background & AimsIt is unclear to what extent lifestyle and genetic factors affect incidence of chronic liver disease (CLD) in a general population and if lifestyle affects CLD independently of underlying cardiometabolic perturbations and genetic predisposition. MethodsWe examined 27,991 men and women aged 44-73 years from the Malmö Diet and Cancer Study recruited between 1991-1996 and followed until end of 2020 using registry-linkage (median follow-up time 25.1 years; 382 incident first-time CLD events). Associations between cardiometabolic factors, polygenic risk scores (PRSs), and lifestyle factors in relation to CLD were examined using multivariable Cox proportional hazards regression models. ResultsIncidence of CLD increased with number of cardiometabolic risk factors (the hazard ratio (HR) per each additional cardiometabolic risk factor was 1.33 (95% CI: 1.21-1.45; p= 5.1 x 10-10). Two novel polygenic risk scores (PRS) for metabolic dysfunction-associated steatotic liver disease (MASLD) and a PRS for liver cirrhosis associated with higher risk of CLD but provided marginal predictive utility on top of other risk factors and compared to the PNPLA3 rs738409 genetic variant. An unhealthy lifestyle (high alcohol intake, current smoking, physical inactivity and unhealthy diet) markedly increased risk of CLD (HR=3.97, 95% CI: 2.59-6.10). Observed associations between examined lifestyle factors and CLD were largely independent of cardiometabolic perturbations and polygenic risk. ConclusionsWe confirmed the importance of cardiometabolic dysfunction in relation to risk of CLD in a general population. Lifestyle risk factors were shown to independently associate with CLD and added predictive information on top of cardiometabolic risk factors. Information on the polygenic risk of liver disease does not currently add to prediction of CLD in a general population. Lay summaryIn this large longitudinal study of a general population, we found that cardiometabolic, genetic and lifestyle risk factors all contribute to the development of chronic liver disease (CLD). Our results suggest that an unhealthy lifestyle, including alcohol consumption, smoking, physical inactivity, and an unhealthy diet, substantially increase risk of CLD independently of underlying genetic risk or cardiometabolic health. This suggest that a large proportion of CLD cases are potentially preventable through adoption of healthy lifestyle changes. Impact and implicationsThis large population-based prospective study suggests largely independent roles of cardiometabolic, lifestyle, and genetic risk factors in the development of chronic liver disease. Findings strengthen the evidence base for a beneficial effect of modification of high-risk lifestyle behaviors in the primary prevention of chronic liver disease in the general population.

478 Magnetic Resonance Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease

OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.

Occult liver disease: A multinational perspective

Occult liver disease refers to the presence of unrecognized chronic liver disease and cirrhosis. Liver disease is currently the eleventh cause of death globally, representing 4% of all deaths in the world. Alcohol consumption is the leading cause of cirrhosis globally, accounting for approximately 60% of cases. The estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 32.4% and has been steadily increasing over the last years. Viral hepatitis B and C accounted for 1.3 million deaths in 2020.Several studies in populations at high risk of chronic liver disease (elevated liver enzymes, type 2 diabetes, excessive alcohol consumption) have found an elevated prevalence of occult liver disease. Attempts should be made to assess the prevalence of occult liver disease in Latin America, a region with one of the highest rates of metabolic diseases and excessive alcohol consumption.Screening for NAFLD in high-risk subjects and screening for excessive drinking and alcohol use disorders at every level of medical care is relevant. Efforts should also focus on the early treatment of occult liver disease to try to reduce liver disease burden and, in the case of occult viral hepatitis infection, prevent further spreading.

Sleep patterns, genetic predisposition, and risk of chronic liver disease: A prospective study of 408,560 UK Biobank participants

BackgroundLittle is known about the role that combined sleep behaviors play in the association with chronic liver disease (CLD) risk. MethodsWe included 408,560 participants initially free of CLD from the UK Biobank. A healthy sleep pattern was defined by early chronotype, sleep duration of 7–8 h/day, no insomnia, no snoring, and no excessive daytime sleepiness. Cox regression models were used to examine the association of healthy sleep pattern with incident CLD and their interaction with PNPLA3 genetic risk. ResultsDuring a median 12.5 years of follow-up, we documented 10,915 incident all-cause CLD cases, including 388 viral hepatitis, 4782 non-alcoholic fatty liver disease (NAFLD), 1356 cirrhosis, 973 alcoholic liver disease, and 725 liver cancer cases. Compared to participants with a healthy sleep score of 0–1, the hazard ratio (HR) (95 % confidence interval [CI]) for those with a sleep score of 5 was 0.54 (0.49, 0.60) for CLD, 0.52 (0.30, 0.90) for viral hepatitis, 0.47 (0.41, 0.55) for NAFLD, 0.57 (0.43, 0.75) for cirrhosis, 0.32 (0.23, 0.44) for alcoholic liver disease, and 0.53 (0.37, 0.77) for liver cancer. Healthy sleep pattern and PNPLA3 genetic risk exerted significant additive effects on CLD risk (relative excess risk due to the interaction: 0.05; attributable proportion due to the interaction: 13 %). LimitationsMeasurement error was unavoidable for self-reported data on sleep behaviors. ConclusionsOur analyses provide evidence that healthy sleep pattern was inversely associated with the development of CLD, and participants with higher genetic risk were more likely to develop CLD when exposed to the unhealthy sleep pattern.

Association of depressive symptoms with chronic liver disease among middle-aged and older adults in China

BackgroundThe relationship between depressive symptoms and chronic liver disease (CLD) is still unclear. We aimed to determine whether depressive symptoms are associated with CLD in a large population sample.MethodsThe data was from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing nationally representative prospective cohort study. Depressive symptoms were assessed with the catchment-area epidemiology survey-depression (CES-D). CLD was identified by the patient’s self-report about a physician’s diagnosis at each visit. Multi-adjusted logistic regression and Cox regression models were used.ResultsA total of 14,995 participants (53.1% female; mean age: 58.85 ± 9.87 years) and 13,405 participants (53.64% female; mean age: 58.58 ± 9.69 years) were included in the cross-sectional and longitudinal analyses, respectively. In the cross-sectional analysis, the odds ratio of CLD in patients with moderate and severe depressive symptoms were 1.46 [95% confidence interval (CI), 1.16–1.83] and 1.78 (95% CI, 1.23–2.56) than those with none/mild depressive symptoms, respectively. In the longitudinal analysis, compared to participants with none/mild depressive symptoms, the hazard rates of CLD in those with moderate and severe depressive symptoms were 1.65 (95%CI, 1.33–2.03) and 1.80 (95%CI, 1.24–2.60). And the 50th percentile difference of time (years) at the incidence of CLD in participants with moderate and severe depressive symptoms were − 0.83 (95%CI, −1.18, −0.49) and − 0.96 (95%CI, −1.56, −0.35), respectively.ConclusionElevated depressive symptoms were associated with an increased risk of CLD among middle-aged and older adults in China.

Risk of chronic liver disease and cirrhosis mortality among patients with digestive system cancers: a registry-based analysis.

Non-cancer deaths are now becoming a great threat to the health of cancer survivors. There are no comprehensive and systematic reports on chronic liver disease and cirrhosis mortality (CLDCM) among patients with digestive system cancers (DSCs). This research aimed to quantitatively assess the risks and patterns of CLDCM among patients with DSCs. From the surveillance, epidemiology and end results (SEER) program, we extracted the data of patients diagnosed with DSCs between 2000 and 2017. Trends in incidence-based mortality rate (IBMR) were calculated using Joinpoint software. The standardized mortality ratio (SMR) was obtained based on the reference of the general United States population. The cumulative incidence function curves were constructed by all causes of death. Independent indicators were identified using the multivariate Fine and Gray competing risk model. We included 906,292 eligible patients from the SEER program, of which 3068 (0.34%) died from chronic liver disease and cirrhosis (CLDC). The IBMR of CLDC continued to increase during the study period [average annual percent change (APC): 6.7%; 95% confidence interval (CI) 5.1-8.2] and the SMR was significantly increased (SMR: 3.19; 95% CI 3.08-3.30). The cumulative mortality of CLDC was the lowest in all causes of death. Furthermore, the age at diagnosis, race, gender, marital status, year of diagnosis, SEER stage, surgery, chemotherapy and radiotherapy were identified as independent indicators. Better screening, diagnostic and management approaches need to be implemented as a preferred method to protect the liver among patients with DSCs.

Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study

BackgroundLow diet quality, diabetes, and chronic inflammation are risk factors of liver cancer and chronic liver disease (CLD), but the extent to which insulinemic and inflammatory diets are independently associated with risk of liver cancer and CLD mortality is unknown. MethodsWe conducted a prospective cohort analysis among 78,356 postmenopausal women in the Women’s Health Initiative Observational Study. Two validated dietary indices, the empirical dietary index for hyperinsulinemia (EDIH) and the empirical dietary inflammation pattern (EDIP), were estimated from a food-frequency questionnaire. Incident cases of liver cancer and CLD mortality were adjudicated via review of medical records and linkage to National Death Index. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, adjusted for age, diabetes, body mass index, and other covariates. ResultsDuring a median 22.1 y of follow-up, we documented 176 primary liver cancer cases and 156 CLD mortality cases. EDIH was positively associated with incident liver cancer (HRQuartile 4 vs. Quartile 1 = 1.68; 95% CI: 1.00, 2.83; P-trend = 0.05) and CLD mortality (HRQ4 vs. Q1 = 2.28; 95% CI: 1.25, 4.15; P-trend = 0.02) in the multivariable model. EDIP was also positively associated with liver cancer (HRQ4 vs. Q1 = 1.88; 95% CI: 1.17, 3.03; P-trend = 0.009) and CLD mortality (HRQ4 vs. Q1 = 1.85; 95% CI: 1.09, 3.15; P-trend = 0.007). Estimates remained significant and robust in sensitivity analyses. Further analyses indicated positive associations for refined grains, processed meat, sugary beverages, and eggs, and inverse associations for coffee/tea and poultry. ConclusionsDietary insulinemic and inflammatory potentials were independently associated with higher risk of liver cancer and CLD mortality in U.S. postmenopausal women. These findings suggest a potential role for diet modification to reduce risk of liver cancer and CLD.

Maternal and Neonatal Outcomes in Intrahepatic Cholestasis of Pregnancy.

The aims of our study were to evaluate the maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP). In this observational, retrospective case-control study, we included all pregnant women who gave birth with a diagnosis of ICP between January 2010 and December 2020 at the Unit of Obstetrics and Gynecology, University Hospital of Messina. The data were compared with those from a control group of pregnant women who did not have ICP. One hundred twenty-nine and eighty-five patients were included, respectively, in the study and in the control group. There was a significant difference between the two groups in the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm delivery, which were more frequent in the ICP patients. No neonatal adverse events were recorded, although a significant difference in the meconium-stained amniotic fluid condition was noted. After a 24-month follow-up, 48/129 patients with ICP accepted to be reassessed by liver ultrasound, elastographic examination, and liver function blood tests. No patient showed signs of chronic liver disease. This study confirmed a higher probability of adverse short-term maternal outcomes in ICP pregnant patients, but a lower probability of adverse short-term fetal outcomes and the absence of a long-term maternal risk of chronic liver disease.

Metabolic dysfunction-associated fatty liver disease in people living with HIV

The prevalence of metabolic risk factors and non-alcoholic fatty liver disease (NAFLD) is high among people living with HIV (PLWH). Data on the recently proposed definition of metabolic dysfunction-associated fatty liver disease (MAFLD) in PLWH receiving antiretroviral therapy (ART) remains unknown. A total of 282 PLWH were included in this cross-sectional cohort study. Vibration-controlled transient elastography (VCTE) was used to assess hepatic steatosis and fibrosis. MAFLD and its subgroups (overweight/obese, lean/normal weight, and type 2 diabetes) were defined according to a recently published international consensus statement. The majority of this cohort was male (n = 198, 70.2%), and the median age was 51.5 years. The median BMI was 25 kg/m2, and obesity was prevalent in 16.2% (n = 44). A total of 207 (73.4%) PLWH were classified as non-MAFLD while 75 (26.6%) qualified as MAFLD. The median CAP in the MAFLD group was 320 dB/m. PLWH with MAFLD showed a higher median LSM (p < 0.008) and were older (p < 0.005) compared to the non-MAFLD group. Overall, the metabolic risk profile was comparable between MAFLD and NAFLD. The majority of PLWH and MAFLD were overweight or obese (n = 58, 77.3%). The highest median LSM values were observed in the subgroup with MAFLD and type 2 diabetes. HIV-related parameters did not differ between non-MAFLD and MAFLD. The prevalence of MAFLD in PLWH is high and comparable to NAFLD. PLWH may be characterized according to the novel MAFLD criteria and its subgroups to identify patients at risk for chronic liver disease.

Clonal haematopoiesis and risk of chronic liver disease.

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms ofliver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response.

Association of per- and polyfluoroalkyl substance exposure with fatty liver disease risk in US adults

Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants with demonstrated hepatotoxicity. Few studies have examined the association between PFAS and fatty liver disease (FLD) risk in an adult population. In this cross-sectional study of participants from the 2017-2018 National Health and Nutrition Examination Survey, serum PFAS were measured, and FLD cases were ascertained by vibration-controlled transient elastography. Logistic regression models were used to examine the association between circulating PFAS levels and FLD risk. Analyses were stratified into non-alcoholic FLD and alcoholic FLD risk groups by alcohol intake status, as well as controlling for other risk factors, including personal demographics, lifestyle factors, and related health factors. Among 1,135 eligible participants, 446 had FLD. For FLD risk, the multivariable-adjusted odds ratio per log-transformed SD increase (ORSD) in perfluorohexane sulfonate (PFHxS) was 1.13 (95% CI 1.01-1.26). The association between PFHxS and FLD appeared stronger among individuals with obesity or high-fat diets (both p interaction <0.05). When limiting the analysis to 212 heavy drinkers (≥2 drinks/day for women and ≥3 drinks/day for men), significantly higher risk of alcoholic FLD was found for higher levels of perfluorooctanoic acid (ORSD 1.79; 95% CI 1.07-2.99), PFHxS (ORSD 2.06; 95% CI 1.17-3.65), and perfluoroheptane sulfonic acid (ORSD 1.44; 95% CI 1.00-2.07), and marginally significant higher risk for total PFAS (ORSD 2.12; 95% CI 0.99-4.54). In never or light drinkers, we did not observe any significant association between PFAS and non-alcoholic FLD. Significant positive associations were found for PFAS with aspartate aminotransferase, gamma-glutamyl transaminase, total bilirubin, and albumin (β ranged from 0.008 to 0.101, all p <0.05). Higher serum PFAS was moderately associated with FLD risk and worse liver function in the general population, and among those with independent risk factors, including heavy alcohol intake, obesity, or high-fat diets, PFAS increased the risk. These results suggest synergistic effects on hepatic steatosis between PFAS exposures as measured through biomonitoring data and lifestyle risk factors in a nationally representative US population. The per- and polyfluoroalkyl substances (PFAS) may convey higher risk for chronic liver disease in humans. Among 1,135 US adults in the 2017-2018 National Health and Nutrition Examination Survey, we found that higher serum PFAS was associated with higher fatty liver disease risk and worse liver function, especially among those with liver disease risk factors, including heavy alcohol intake, obesity, or high-fat diets. Continuously monitoring PFAS in the population and examining how they potentiate risk to the liver are essential.

Effects of thiacloprid exposure on microbiota-gut-liver axis: Multiomics mechanistic analysis in Japanese quails.

Neonicotinoid insecticides (NNIs) are the most widely used class of pesticides globally. However, NNIs may cause adverse health effects, including chronic liver disease, and perturbation of the gut microbiota. Thiacloprid (THI) is one of the NNIs widely used in agriculture. Therefore, it is essential to elucidate effects of THI on the microbiota-gut-liver axis to assess the risk of chronic liver disease following exposure to NNIs. This study aimed at investigating whether THI exposure promoted liver injury by altering the gut microbiota and related metabolites. In this study, healthy male quails were exposed to 2 or 4mg/kg THI or 0.75 % (w/v) saline once daily for 6 weeks, respectively. Metabolomics, 16S rRNA sequencing, and transcriptomic methods were performed to analyze the toxic mechanisms of THI in Japanese quails. We found that THI evoked damage and disruption to intestinal barrier function, leading to increased harmful substances such as lipopolysaccharide (LPS) and phenylacetic acid entering the liver. Besides, our results showed significantly altered hepatic bile acid and cholesterol metabolism in THI-exposed quails, with abnormal liver lipid metabolism, showing severe liver injury, fibrosis, and steatosis compared with the control quails. In conclusion, THI exposure aggravates liver injury via microbiota-gut-liver axis.

Diet and Risk of Non-Alcoholic Fatty Liver Disease, Cirrhosis, and Liver Cancer: A Large Prospective Cohort Study in UK Biobank.

Background and Aims: Epidemiological evidence has shown the association between nutritional habits and liver disease. However, results remain conflicting. This study investigated the influence of dietary factors on the risk of incident non-alcoholic fatty liver disease (NAFLD), cirrhosis, and liver cancer. Methods: Data from the UK Biobank database were analyzed (n = 372,492). According to baseline data from the food frequency questionnaire, two main dietary patterns (Western and prudent) were identified using principal component analysis. We used cox proportional hazards models to explore the associations of individual food groups and dietary patterns with NAFLD, cirrhosis, and liver cancer. Results: During a median follow-up of 12 years, 3527 hospitalized NAFLD, 1643 cirrhosis, and 669 liver cancer cases were recorded among 372,492 participants without prior history of cancer or chronic liver diseases at baseline. In multivariable adjusted analysis, participants in the high tertile of Western dietary pattern score had an 18% (95%CI = 1.09−1.29), 21% (95%CI = 1.07−1.37), and 24% (95%CI = 1.02−1.50) higher risk of incident NAFLD, liver cirrhosis, and liver cancer, respectively, compared with the low tertile. Participants in the high tertile of prudent scores had a 15% (95%CI = 0.75−0.96) lower risk of cirrhosis, as compared with those in the low tertile. In addition, the higher consumption of red meat and the lower consumption of fruit, cereal, tea, and dietary fiber were significantly associated with a higher risk of NAFLD, cirrhosis, and liver cancer (ptrend < 0.05). Conclusions: This large prospective cohort study showed that an increased intake of food from the Western dietary pattern could be correlated with an increased risk of chronic liver diseases, while the prudent pattern was only correlated with a reduced liver cirrhosis risk. These data may provide new insights into lifestyle interventions for the prevention of chronical liver diseases.