Risk Factors For Liver Disease Research Articles

Vitamin D Deficiency Is Associated with Advanced Liver Fibrosis and Impaired Fasting Glucose in Alcohol Use Disorder.

Vitamin D deficiency is a risk factor for liver disease, insulin resistance, and beta cell dysfunction. Individuals with alcohol use disorder (AUD) have many comorbidities, with a heavy burden of liver disease and metabolic complications, including type 2 diabetes mellitus (T2DM). We aimed to analyze the prevalence and associations of vitamin D deficiency in patients admitted for in-hospital treatment of AUD. A cross-sectional study was conducted in patients consecutively admitted for the treatment of AUD between January 2017 and October 2023. Sociodemographic data, substance use characteristics, and blood parameters were available at admission. Vitamin D status was assessed through the serum concentrations of 25-hydroxyvitamin D [25(OH)D] levels using a direct competitive chemiluminescent immunoassay method. Deficiency of vitamin D was defined as a concentration less than 20 ng/mL; impaired fasting glucose (IFG) was defined by fasting blood glucose >100 mg/dL (5.6 mmol/L), and advanced liver fibrosis by an FIB-4 index >3.25. Two hundred and forty-three patients were included (75% male) with a mean age of 49 ± 10 years, mean BMI of 26.4 ± 7.3, mean alcohol consumption of 163 ± 81 g/day, and a mean duration of AUD of 18.1 ± 11.2 years. Mean 25(OH)D, fasting blood glucose, AST, ALT, and platelets were 14.4 ± 10.2 ng/mL, 103.4 ± 40.9 mg/dL, 55.1 ± 75.8 U/L, 44.8 ± 76.6 U/L, and 206.3 ± 84.8 × 109/L, respectively. The prevalence of vitamin D deficiency was 80.6%, and 41.1% of patients had levels less than 10 ng/mL. IFG was present in 32.3% of patients, and 20.5% had FIB-4 values >3.25. In the multivariable analysis, IFG (OR, 2.51; 95% CI: 1.02-6.17, p = 0.04) and advanced liver fibrosis (OR, 4.27; 95% CI: 1.21-15.0, p = 0.02) were the only factors associated with vitamin D deficiency. Vitamin D deficiency was very prevalent in this series of patients with AUD and was associated with impaired fasting glucose and advanced liver fibrosis.

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

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

Difference in the Mechanism of Iron Overload-Enhanced Acute Hepatotoxicity Induced by Thioacetamide and Carbon Tetrachloride in Rats.

Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl4). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl4, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl4 was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl4 model. The data showed that dietary iron overload exacerbates TAA- and CCl4-induced acute liver injury with different mechanisms.

Abstract C104: Addressing health disparities: Enhancing knowledge and screening practices for liver disease risk factors among African Americans

Abstract Background: Liver cancer poses a significant health burden globally, with racial and ethnic disparities in its incidence. Among these disparities, the Black population in the United States faces a heightened risk of liver cancer due to the higher prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. This study aimed to evaluate the effectiveness of a culturally tailored educational intervention designed to enhance awareness of liver cancer prevention and screening among at-risk populations. Methods: Descriptive statistics were used to characterize participant demographics and clinical factors. Paired t-tests assessed the difference in knowledge scores before and after the intervention. Poisson regression with robust variance estimation determined the association between physicians' recommendations for testing and patients receiving blood tests. Results: The study included 137 African American participants. Prior to the intervention, the majority were aware that casual contact does not transmit HBV or HCV (79.6%) and that sharing needles for tattoos or drug injection can transmit the viruses (77.4%). The mean knowledge score increased significantly from 6.61 pre-intervention to 8.44 post-intervention (p-value<0.001). Poisson regression analysis showed that African American adults were less likely to receive physician recommendations for blood tests for HBV (RR=0.95, 95%CI:0.87,1.04) and HCV (RR=0.91, 95%CI:0.83,1.00) compared to other racial/ethnic groups. Conclusions: The culturally tailored educational intervention effectively improved knowledge of HBV and HCV among African American participants, indicating the importance of culturally sensitive programs in reducing liver cancer disparities. Efforts to increase awareness of liver disease and promote testing within the healthcare system are crucial for reducing the morbidity and mortality associated with HBV and HCV infections among African Americans. Character count (with spaces): 1,963 Acknowledgment: This study was supported by TUFCCC/HC Regional Comprehensive Cancer Health Disparity Partnership, Award Number U54 CA221704(5) from the National Cancer Institute of National Institutes of Health (NCI/NIH) and by NIGMS/NIH award # 1SC3GM131949[GXM1] . The author team would like to thank Community Advisory Board members, leaders, and staff members for collaborating with community/faith-based organization partners. We also acknowledge the research team staff of Planning Evaluation Core under TUFCCC/HC Regional Comprehensive Cancer Health Disparity Partnership for their support and contribution for their support and contributions to Community Outreach Core's data management. Its contents are solely the authors' responsibility and do not necessarily represent the official views of the NCI/NIH or the NIGMS/NIH.   Citation Format: Jade A. Truehart, Thoin F. Begum, Keshanti Bruce, Lin Zhu, Ming-Chin Yeh, Evelyn Gonzalez, Marilyn A. Fraser, Ada Wong, Steven Zhu, Nathaly Rubio-Torio, Grace X. Ma, Yin Tan. Addressing health disparities: Enhancing knowledge and screening practices for liver disease risk factors among African Americans [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C104.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors

Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. Approach and Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12–54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8–21.3, p < 0.001). Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

Current practice and recommendations for management of hepatitis B virus in people living with HIV in Asia.

The prevalence of HIV and hepatitis B virus (HBV) co-infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. Important routes of transmission of both these infections include high-risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV-induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV. This article describes the prevalence of co-infection, current clinical practice, and recommendations for the management of people living with HIV-HBV co-infection in Asia. Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV-HBV co-infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co-infection rates. Mother-to-child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.

Incidentally Discovered Cryptogenic Cirrhosis in a Patient with Untreated Celiac Disease

Celiac disease is a common gastrointestinal disorder that primarily manifests its effects on the small bowel. However, the systemic nature of this condition, especially regarding the liver, has been gaining some recognition in the literature. Mild liver disease is common, but few cases progress to cirrhosis. We present a case of an asymptomatic 78-year-old male with a past medical history of longstanding celiac disease, atrial fibrillation, heart failure with preserved ejection fraction, type 2 diabetes mellitus (DM), and chronic kidney disease stage III who underwent a computed tomography (CT) scan for thoracic aortic aneurysm surveillance. Incidentally, on a CT scan, cirrhotic liver morphology was discovered. Right upper quadrant ultrasound confirmed heterogenous echotexture of the liver, consistent with a diagnosis of cirrhosis. Laboratory work-up demonstrated elevated alkaline phosphatase of 171, tissue transglutaminase (TTG) significantly elevated at > 100, and a negative panel of other chronic liver disease labs, including negative anti-smooth muscle antibody, antimitochondrial antibody, liver kidney microsomal antibody, HFE gene, ceruloplasmin, alpha-1-antitrypsin, and alpha-fetoprotein < 2 ng/mL. The patient was not taking any hepatotoxic medications. Although the patient did have type 2 DM, his hemoglobin A1c was well-controlled at 5.9%, and he had no hyperlipidemia and a normal body mass index, making a metabolic etiology of liver disease less likely. The patient had no significant alcohol use, either. The only patient’s major risk factor for liver disease was his untreated celiac disease, diagnosed in infancy. The patient was instructed to avoid any gluten, alcohol, and other hepatotoxic substances and was subsequently followed by a gastroenterologist. The following case report explores the pathogenesis of celiac-associated liver disease and the effect a gluten-free diet can have on the small bowel and the liver.

Population genetic testing and SERPINA1 sequencing identifies unidentified alpha-1 antitrypsin deficiency alleles and gene-environment interaction with hepatitis C infection.

Alpha-1 antitrypsin deficiency (AATD), a relatively common autosomal recessive genetic disorder, is underdiagnosed in symptomatic individuals. We sought to compare the risk of liver transplantation associated with hepatitis C infection with AATD heterozygotes and homozygotes and determine if SERPINA1 sequencing would identify undiagnosed AATD. We performed a retrospective cohort study in a deidentified Electronic Health Record (EHR)-linked DNA biobank with 72,027 individuals genotyped for the M, Z, and S alleles in SERPINA1. We investigated liver transplantation frequency by genotype group and compared with hepatitis C infection. We performed SERPINA1 sequencing in carriers of pathogenic AATD alleles who underwent liver transplantation. Liver transplantation was associated with the Z allele (ZZ: odds ratio [OR] = 1.31, p<2e-16; MZ: OR = 1.02, p = 1.2e-13) and with hepatitis C (OR = 1.20, p<2e-16). For liver transplantation, there was a significant interaction between genotype and hepatitis C (ZZ: interaction OR = 1.23, p = 4.7e-4; MZ: interaction OR = 1.11, p = 6.9e-13). Sequencing uncovered a second, rare, pathogenic SERPINA1 variant in six of 133 individuals with liver transplants and without hepatitis C. Liver transplantation was more common in individuals with AATD risk alleles (including heterozygotes), and AATD and hepatitis C demonstrated evidence of a gene-environment interaction in relation to liver transplantation. The current AATD screening strategy may miss diagnoses whereas SERPINA1 sequencing may increase diagnostic yield for AATD, stratify risk for liver disease, and inform clinical management for individuals with AATD risk alleles and liver disease risk factors.

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma.

Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.

Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China

This study aimed to estimate the prevalence of liver steatosis and fibrosis in the general population and populations with potential risk factors in China, so as to inform policies for the screening and management of fatty liver disease and liver fibrosis in general and high-risk populations. This cross-sectional, population-based, nationwide study was based on the database of the largest health check-up chain in China. Adults from 30 provinces who underwent a check-up between 2017 and 2022 were included. Steatosis and fibrosis were assessed and graded by transient elastography. Overall and stratified prevalence was estimated among the general population and various subpopulations with demographic, cardiovascular, and chronic liver disease risk factors. A mixed effect regression model was used to examine predictors independently associated with steatosis and fibrosis. In 5,757,335 participants, the prevalence of steatosis, severe steatosis, advanced fibrosis, and cirrhosis was 44.39%, 10.57%, 2.85%, and 0.87%, respectively. Participants who were male, with obesity, diabetes, hypertension, dyslipidemia, metabolic syndrome, or elevated alanine aminotransferase or aspartate aminotransferase had a significantly higher prevalence of all grades of steatosis and fibrosis, and those with fatty liver, decreased albumin or platelet count, and hepatitis B virus infection also had a significantly higher prevalence of fibrosis than their healthy counterparts. Most cardiovascular and chronic liver disease risk factors were independent predictors for steatosis and fibrosis, except for dyslipidemia for fibrosis. Asubstantial burden of liver steatosis and fibrosis was found in China. Our study provides evidence for shaping future pathways for screening and risk stratification of liver steatosis and fibrosis in the general population. The findings of this study highlight that fatty liver and liver fibrosis should be included in disease management programs as targets for screening and regular monitoring in high-risk populations, especially in those with diabetes.

SAT-415 - Patients with risk factors for liver diseases associated with hepatic steatosis constitute the target population for liver fibrosis assessment in primary care

SAT-415 - Patients with risk factors for liver diseases associated with hepatic steatosis constitute the target population for liver fibrosis assessment in primary care

P68 Liver fibrosis is independent of methotrexate use in patients with moderate-to-severe psoriasis

Abstract Methotrexate has been implicated for liver disease in patients with psoriasis for many years. Liver fibrosis (LF) has various established risk factors, but data on the impact of methotrexate on LF in patients with psoriasis are lacking. This cross-sectional cohort study aimed to determine the prevalence of LF using noninvasive LF markers in patients with psoriasis, and to evaluate the relationship between LF and the cumulative dose of methotrexate and other liver disease risk factors. Adults with moderate-to-severe chronic plaque psoriasis diagnosed by a dermatologist, who were selected for a LF assessment, were recruited from dermatology clinics in a tertiary centre between June 2020 and March 2021. Data were recorded as part of standard clinical care and at the time of recruitment. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were used, indicating ≥ mild LF (≥ 7 kPa), ≥ moderate LF (≥ 7.9 kPa) and ≥ advanced LF (≥ 9.5 kPa). Both continuous and categorical LSM values were used for evaluation. A total of 225 patients were included [median age 48, interquartile range (IQR) 37–57, 51% female]. Fifty-six per cent had a body mass index (BMI) ≥ 30 kg m−2, and the median alcohol use disorders identification test (AUDIT) score was 4 (IQR 1–7, 23% score ≥ 8). Ninety-one per cent had received methotrexate for a median duration of 36 months (IQR 14–78). Prevalence rates of LF were 31%, 21% and 13% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between methotrexate and continuous LSM values [unadjusted coefficient 0.16, 95% confidence interval (CI) 0.49–0.82; P = 0.63] or using the categorical LSM cutoff values: 7 kPa (unadjusted coefficient 1.06, 95% CI 0.98–1.15; P = 0.19), 7.9 kPa (unadjusted coefficient 1.03, 95% CI 0.94–1.12; P = 0.58) and 9.5 kPa (unadjusted coefficient 1.01, 95% CI 0.91–1.12; P = 0.84). Similarly, no significant relationship was found when adjusting for other risk factors for LF. The following risk factors were associated with higher LSM values: BMI (P &amp;lt; 0.001), waist circumference (P &amp;lt; 0.001), metabolic syndrome (P &amp;lt; 0.001), AUDIT score (P = 0.020) and Fib-4 score (P = 0.03). This study confirms a high prevalence of significant LF in patients with moderate-to-severe psoriasis. More importantly, it shows that cumulative methotrexate was not associated with LF, and other risk factors including BMI, waist circumference, metabolic syndrome, alcohol intake and Fib-4 score are important predictors for LF. The findings suggest that these risk factors should be assessed in this group of patients to identify patients requiring regular liver health monitoring. Further research is needed to determine whether methotrexate contributes to the progression of LF in the context of pre-existing LF.

Liver Involvement in Patients with Systemic Sclerosis: Role of Transient Elastography in the Assessment of Hepatic Fibrosis and Steatosis.

Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of the study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients fulfilling the 2013 ACR/EULAR classification criteria were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), activity index, videocapillaroscopy, echocardiography, and lung function data were analyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis. In addition, hepatic steatosis was evaluated by means of controlled attenuation parameter (CAP) findings. Specifically, CAP values ≥ 238 ≤ 259 dB/m were considered consistent with mild steatosis (S1), values ≥ 260 ≤ 290 dB/m were compatible with moderate steatosis (S2), and values ≥ 291 dB/m were indicative of severe steatosis (S3). Results The median age of patients was 51 years, with a median disease duration of 6 years. The median LS was 4.5 (2.9-8.3) kPa; 69.5% of patients had no evidence of fibrosis (F0); 27.1% displayed LS values between 5.2 and 7 kPa; and only 3.4% of patients had LS values > 7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164-343). Overall, 66.1% of patients did not show evidence of steatosis (CAP values < 238 dB/m); 15.2% showed values consistent with mild (S1) steatosis (CAP value ≥ 238 ≤ 259 dB/m); 13.5% had moderate (S2) steatosis (CAP value ≥ 260 ≤ 290 dB/m); and 5.1% were deemed to have severe steatosis (S3) due to CAP values ≥ 291 dB/m. Conclusions Although systemic sclerosis is associated with fibrosis of the skin and several organs, only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Therefore, fibrosis of the liver did not appear to be a significant concern in SSc patients, albeit moderate fibrosis could still be detected in a significant proportion of subjects. A prolonged follow-up may clarify whether liver fibrosis in SSc patients may still progress. Likewise, the prevalence of significant steatosis was low (5.1%) and depended on the same variables associated with fatty liver disease in the general population. TE was shown to be an easy and valuable method for detection and screening of hepatic fibrosis in SSc patients with no additional risk factors for liver disease and may be useful to assess the potential progression of liver fibrosis over time.

Hepatocellular carcinoma in a large cohort of type 2 diabetes patients

AimsTo elucidate the current burden of hepatocellular carcinoma (HCC) in type 2 diabetes (DM2) with a focus on the associated clinical determinants. MethodsIncidence of HCC between 2009 and 2019 in the diabetic and general population was calculated from regional administrative and hospital databases. Potential determinants of the disease were evaluated with a follow-up study. ResultsIn the DM2 population, the incidence resulted in 8.05 cases per 10,000 yearly. This rate was three times higher than that of the general population. 137,158 patients with DM2 and 902 HCC were found for the cohort study. The survival of HCC patients was 1/3 of that of cancer-free diabetic controls. Age, male sex, alcohol abuse, previous viral hepatitis B and C, cirrhosis, low platelet count, elevated GGT/ALT, higher BMI and HbA1c levels were associated with HCC occurrence. Diabetes therapy was not adversely associated with HCC development. ConclusionIncidence of HCC in DM2 is more than tripled compared to the general population with high mortality. These figures are higher than those expected from the previous evidence. In parallel with known risk factors for liver disease, such as viruses and alcohol, insulin-resistance characteristics are associated with a higher probability of HCC.

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.

Liver Involvement in Individuals with Obesity: A Cross-sectional Study from Western India.

Obesity is a largely neglected health problem in developing countries which leads to additional morbidities including nonalcoholic fatty liver disease (NAFLD), one of the most important causes of chronic liver disease. Central obesity is intricately related to the pathogenesis of the NAFLD, which over time could result in a fiogenic response and end-stage liver disease. We have attempted to study the association of various risk factors and laboratory investigations with the incidence of liver involvement in obese individuals. A cross-sectional study of 210 patients was carried out in a tertiary care center in Western India. Patients above 18 years of age with either general or abdominal obesity were included and their history taking and general and systemic examination was done along with laboratory investigations and ultrasonography for visualize any liver involvement. Age &gt;50 years, female gender, postmenopausal state, sedentary lifestyle, high body mass index (BMI), waist circumference (WC), and neck circumference were all risk factors for liver involvement in obese individuals. Raised C-reactive protein (CRP), serum glutamic-oxaloacetic transaminase (SGOT), triglycerides, low density lipoprotein (LDL), cholesterol, fasting blood sugar (FBS), 2-hour postprandial blood sugar (PP2BS), and low high density lipoprotein (HDL), serum protein, and albumin were significantly associated with liver disease. Patients having high NAFLD fiosis and BMI, aminotransferace ratio and diabetes (BARD) scores, or Metabolic syndrome (MS) was at a higher risk for liver disease. Advancing age, postmenopausal females, and lack of physical activity are risk factors for liver disease in obesity. Raised CRP and SGOT along with impaired lipid profile and glycemic control could be used as markers for fatty liver in obese individuals. MS greatly increases the risk of liver involvement in obese individuals.

Stratification Of LIver Disease (SOLID): protocol for a prospective observational cohort study to determine the optimum biomarker strategies for the detection of advanced liver disease at the primary–secondary care interface

IntroductionUndiagnosed fatty liver disease is prevalent in the community, due to high rates of harmful alcohol consumption and/or obesity. Fatty liver disease can progress to cirrhosis and its complications. Early...

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9kPa (adjusted odds ratio= 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio= 1.76; 95% CI 1.20-2.56; p= 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

Specific aspects of social significant liver diseases, risk factors, and food safety: A comprehensive review

In the contemporary landscape of scientific inquiry, the study and assessment of risk factors for chronic liver diseases have expanded substantially. This surge in research is driven by the heightened prevalence of common risk factors and the consequential socio-economic impact of chronic liver diseases. Beyond their medical implications, these diseases pose significant economic challenges. Recent scientific investigations affirm that chronic hepatitis (CH) and liver cirrhosis (LC) are predominantly shaped by identifiable risk factors. In this article, synthesizes current research, providing compelling evidence that underscores the societal importance of chronic liver diseases and their association with risk factors. The prevalence of these diseases and their directly linked risk factors is notably high in diverse populations. Moreover, the economic implications of chronic liver diseases extend beyond healthcare, highlighting the need for a multidimensional approach in understanding and addressing these health challenges. As the scientific community unravels the multifaceted nature of chronic liver diseases, this review contributes to the growing body of evidence supporting the assertion that a comprehensive understanding of risk factors is crucial. Furthermore, the abstract advocates for an integrated approach, exploring the intersectionality between risk factors for liver diseases and the critical issue of food safety. By recognizing and addressing this complex interplay, policymakers, healthcare professionals, and researchers can develop targeted interventions that encompass both medical and socio-economic dimensions, fostering a more resilient and healthier society.

PS-B07-10: SUPEROXIDE DISMUTASE PROFILE OF LIVER TISSUE IN HYPERURICEMIA RATS AFTER DAILY CONSUMPTION OF COFFEE

Background: The elevation of serum uric acid may cause metabolic syndrome and increase systemic inflammation also oxidative stress which are the risk factors for liver disease. Recently, coffee as the most popular drink worldwide could promote antioxidant activity due to some anti-inflammatory effects of some polyphenolic compounds such as cafestol, kahweol, and diterpenes. This study aimed to analyze the profile of liver tissue superoxide dismutase (SOD) in hyperuricemia rats after daily consumption of coffee. Method: Four groups, each consisting of 6 rats (Rattus norvegicus), respectively were observed as 1) negative control group; 2) positive control group; 3) caffeinated coffee group; 4) decaffeinated coffee group. Hyperuricemia was conditioned by administering high purine intake into the 2nd until 4th group as much as 140 mg/200gr of weight. Coffee, which is caffeinated and decaffeinated was given to the third and the fourth group respectively with doses 144 mg/200gr of weight. SOD of liver tissue was measured after 30 days of treatment. Result: In hyperuricemia rats, daily consumption of coffee shows higher liver SOD levels compared to a positive control group. The average (+SD) of liver SOD each group respectively 79.51(+3.06); 32.24(+3.53); 53.28(+4.49); and 68.03(+4.72). Numeric comparative hypothetic test using one-way ANOVA shows the difference mean between each group was statistically significant (95%CI; p &lt; 0.05). Conclusion: Daily consumption of both caffeinated and decaffeinated coffee may reduce oxidative stress in liver tissue of hyperuricemia rats.