Risk Factors For Liver Disease Research Articles

Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases: MASLD and risk of four related diseases

Introduction and ObjectivesRecently, Delphi consensus proposed an overarching term steatotic liver disease (SLD), with various subcategories such as MASLD, MetALD and ALD. Our aim was to investigate the association between MASLD/MetALD/ALD and four intrahepatic and extrahepatic diseases (liver diseases, renal diseases, cardiovascular diseases, and cancers) in the UK Biobank cohort. Patients and MethodsBy defining hepatic steatosis as image-derived phenotype (IDP)-PDFF >5.21%, we used data from the UK Biobank to diagnose MASLD/ MetALD/ALD. The odd ratio (OR) and the hazard ratio (HR) were calculated using the logistic regression modals and Cox regression models, respectively. ResultsAmong 39,230 eligible individuals, 6,865 MASLD subjects, 2,379 MetALD subjects and 884 ALD subjects were diagnosed. The last follow-up time was October 13, 2023. Consistent with the logistic analyses, MASLD/MetALD/ALD were significantly associated with a higher risk of liver diseases (HR=3.04 [95%CI:2.60∼3.56], HR = 2.69 [95% CI: 2.12∼3.42] and HR =3.99 [95%CI:2.92∼5.45], respectively). Subjects with MASLD also had an increased higher risk of renal diseases (HR = 1.40 [95%CI:1.20∼1.64]) and subjects with ALD had an increased higher risk of cancers (HR = 1.36 [95%CI:1.15∼1.60]). ConclusionIt is the first study to report the association between MASLD, MetALD, ALD and common intrahepatic and extrahepatic diseases based on magnetic resonance imaging data—PDFF. We found that MASLD, MetALD and ALD were risk factors for liver diseases. Meanwhile, MASLD was also a risk factor for renal diseases and ALD was a risk factor for cancers.

Convergence of Alcohol Consumption and Dietary Quality in US Adults Who Currently Drink Alcohol: An Analysis of Two Core Risk Factors of Liver Disease.

Alcohol consumption and poor dietary habits are on the rise in the United States, posing significant challenges to public health due to their contribution to chronic diseases such as liver failure. While associations between alcohol consumption patterns and diet quality have been explored, the relationship between specific alcoholic beverage types and diet quality remains underexamined. This study aims to compare diet quality among consumers of different alcoholic beverage types. We conducted a cross-sectional analysis of 1917 current alcohol drinkers from the National Health and Nutrition Examination Survey (NHANES) who completed a 24 h dietary recall survey. Diet quality was assessed using the Healthy Eating Index (HEI), with higher scores indicating superior diet quality. Multivariable logistic regression models were employed to assess differences in HEI between consumers of various alcoholic beverage types, using wine-only drinkers as the reference group and controlling for demographic, socioeconomic, lifestyle, and metabolic syndrome variables. Beer-only drinkers were more likely to have lower income, higher rates of cigarette smoking, and insufficient physical activity compared to other alcohol consumers. In the fully adjusted multivariable model, beer-only drinkers had an HEI score that was 3.12 points lower than wine-only drinkers. In contrast, liquor/cocktail-only and multiple-type drinkers had similar HEI scores to wine-only drinkers. Beer-only consumption is associated with poorer diet quality among alcohol drinkers. Targeted patient education and public health campaigns may be effective in addressing the combined impact of alcohol consumption and poor diet quality on chronic disease risk.

Ambient air pollution exposure is associated with liver fat and stiffness in Latino youth with a more pronounced effect in those with PNPLA3 genotype and more advanced liver disease

BackgroundExposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD). ObjectivesWe sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity. MethodsData was analyzed from 113 Latino youth (age 11–19) with obesity in Southern California. Individual exposure to particulate matter with aerodynamic diameter ≤ 2.5μm (PM2.5), ≤ 10μm (PM10), nitrogen dioxide (NO2), 8-hour maximum ozone (8hrMax-O3), 24-hr O3, and redox-weighted oxidative capacity (Oxwt) were estimated using residential address histories and United States Environmental Protection Agency air quality observations. HFF and liver stiffness were measured using magnetic resonance imaging. Linear models were used to determine associations between short-term and long-term exposure to air pollutants with HFF and liver stiffness. Modification by PNPLA3 and liver disease severity was then examined. ResultsShort-term exposure to 8hrMax-O3 was positively associated with HFF. Relationships between air pollution exposure and HFF were not impacted by PNPLA3 genotype or liver disease severity. Long-term exposure to 8hrMax-O3 and Oxwt were positively associated with liver stiffness. Associations between air pollution exposure and liver stiffness depended on PNPLA3 genotype, such that individuals with GG genotypes exhibited stronger, more positive relationships between short-term exposure to PM10, 8hrMax-O3, 24-hr O3, and Oxwt and liver stiffness than individuals with CC/CG genotypes. In addition, relationships between short-term exposure to NO2 and liver stiffness were stronger in those with severe liver disease. DiscussionAir pollution exposure may be a risk factor for liver disease among Latino youth with obesity, particularly in those with other preexisting risks for liver damage.

Hepatocellular Carcinoma in Acute Hepatic Porphyria: A Meta-Analysis of Observational Studies.

Hepatocellular carcinoma (HCC) is a long-term complication of acute hepatic porphyria (AHP) inclusive of acute intermittent porphyria [AIP], variegate porphyria [VP], or hereditary coproporphyria [HCP]. Data on HCC risk in AHP patients are limited and heterogeneous. We performed this meta-analysis with aims to (a) determine incidence of HCC in AHP and specific subtypes of AHP and (b) examine high-risk groups for HCC. Data from studies reporting HCC development in AHP patients were pooled and reported per 100 person years with 95% confidence intervals (CI). 12 observational (5 prospective) studies (11 Europe and 1 US) on 2735 patients (mean age 54.8 yrs., 62% females) with AHP (80% AIP) were analyzed. 115 HCC cases were observed with HCC incidence per 100 person years of 0.3 (0.2-0.5) in AHP, 0.4 (0.2-0.6) in AIP, 0.3 (0-0.4) in VP, and 0.2 (0.1-0.6) in HCP. The risk was 0.4 (0.2-0.6) in females, 0.3 (0.1-0.5) in males, 0.9 (0.1-1.7) in symptomatic, and 0.5 (0-1.6) in asymptomatic patients. Analyses were heterogeneous with publication bias. AHP patients with HCC were older females with a higher prevalence of cirrhosis, alcohol use, and viral hepatitis. The annual incidence of HCC in AHP patients is 0.3%, with higher risk in AIP, older females, symptomatic patients, and those with other risk factors of liver disease. Future studies pooling individual patient data and overcoming limitations of the current meta-analysis are needed as a basis for deriving a effective screening and surveillance approach for HCC in patients with AHP.

Screening for compensated advanced chronic liver disease using transient elastography in outpatient addiction clinics.

Patients with substance use disorders present with many risk factors for liver disease-including alcohol, hepatitis C virus infection, and obesity-and should thus be screened for compensated advanced chronic liver disease (cACLD). Such screening could potentially be performed by outpatient addiction clinics. In this study, we aimed to assess the feasibility, acceptability, and results of cACLD screening using transient elastography (TE) among all patients attending routine follow-up visits at addiction clinics, regardless of their liver disease risk factors. Liver fibrosis evaluation using TE was offered to every patient consulting two different addiction clinics in France, between December 2020 and September 2021, during dedicated half-day screening sessions. The screening was proposed during the patient's routine care and was performed immediately after the scheduled consultation. Patients with a liver stiffness measurement over 8 kPa were referred to a hepatology visit in the addiction clinic within 2-4 weeks. Screening was offered to 227 patients and was accepted by 116 (51%) patients. Twelve patients had a liver stiffness over 8 kPa, and nine of these patients attended the recommended specialist hepatology visit. Five patients (4.3% of those screened) were diagnosed with cACLD. Patients' acceptance of the screening was associated with older age, being on one's own or professionally inactive, and presenting with alcohol use disorder. Overall, our results demonstrated that opportunistic cACLD screening using TE in outpatient addiction clinics was feasible and acceptable, with good results.

Assessing Alcohol Genes Targets in Mouse Liver

Background: Alcohol is a risk factor for liver diseases. There is a correlation between alcohol consumption and fatty liver disease. Experiences have shown gene expression alteration in the liver following alcohol consumption. Since the molecular mechanism of connection between alcohol consumption and fatty liver disease needs a clear perspective, this study aims to explore the significant genes that are targeted by alcohol in the liver of mice.Methods: Gene expression profiles of mice livers fed with alcohol were retrieved from the Gene Expression Omnibus (GEO) database and compared with the control samples. Data are pre-evaluated with the GEO2R program, and the significant differentially expressed genes (DEGs) are analyzed via gene expression evaluations and regulatory network assessment. Results: Among the 25619 dysregulated genes, 78 significant DEGs were pointed out. Gene expression analysis showed that most extremely dysregulated genes are up-regulated and belong to the cytochrome P450 genes family. Finally, cytochrome P450 and glutathione S-transferase genes family, as well as hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4, were introduced as the critical targeted genes.Conclusion: In conclusion, detoxification of xenobiotics, cellular metabolism and homeostasis, the pathogenesis of some liver diseases, synthesis of several prostaglandins and steroid hormones, and inflammation fibrosis in the liver are possibly associated with alcohol consumption.

Population screening for cirrhosis.

In response to the growing health crisis of liver-related morbidity and mortality, screening for liver cirrhosis has emerged as a promising strategy for early detection and timely intervention. By identifying individuals with severe fibrosis or compensated cirrhosis, screening holds the promise of enhancing treatment outcomes, delaying disease progression, and ultimately improving the quality of life of affected individuals. Clinical practice guidelines from international scientific societies currently recommend targeted screening strategies, investigating high-risk populations with known risk factors of liver disease. While there is good evidence that screening increases case finding in the population, and a growing number of studies indicate that screening may motivate beneficial lifestyle changes in patients with steatotic liver disease, there are major gaps in knowledge in need of clarification before screening programs of cirrhosis are implemented. Foremost, randomized trials are needed to ensure that screening leads to improved liver-related morbidity and mortality. If not, screening for cirrhosis could be unethical due to overdiagnosis, overtreatment, increased health care costs, negative psychological consequences of screening, and futile invasive investigations. Moreover, the tests used for screening need to be optimized toward lower false positive rates than the currently used FIB-4 while retaining few false negatives. Finally, barriers to adherence to screening and implementation of screening programs need to be elucidated. This review provides a comprehensive overview of the current landscape of screening strategies for liver cirrhosis and the promises and pitfalls of current methods for early cirrhosis detection.

Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis.

Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation. To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis. Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation. Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, P < 0.001; AUC = 0.795, P < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa (P = 0.040). Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.

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...

Protocolo de valoración de la fibrosis hepática. Pruebas no invasivas para el diagnóstico de la enfermedad hepática crónica compensada

Liver fibrosis should be assessed in all cases of chronic liver disease to adjust follow-up to each individual's risk of hepatic morbidity and mortality. Non-invasive tests can identify both patients with no risk of advanced fibrosis and those with a high probability of having compensated advanced chronic liver disease (cACLD). Simple serum-based tests are accessible and their use is recommended in non-specialized care, where the prevalence of cACLD is low. They should be used to rule out cACLD and only when there are risk factors for liver disease. Elastography techniques are more specific and are used to confirm cACLD in a second stage. Vibration-controlled transient elastography is the most validated and follows the rule of 5 (10-15-20-25kPa), indicating progressively higher risks of decompensation and death. Acoustic radiation force impulse techniques are becoming more widespread as they can be performed as abdominal the same time as ultrasound.

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&amp;lt;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.

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. 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). 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 &gt; 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 &lt; 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.

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.