Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: a retrospective cohort study
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SUBMITTER: Lin M
PROVIDER: S-EPMC10886697 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveChronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) are the leading causes of hepatocellular carcinoma (HCC). This study aimed to explore the impact of baseline MASLD on the risk of HCC development in patients with CHB receiving antiviral treatment.MethodsWe consecutively recruited 535 patients with CHB who initiated antiviral treatment between January 2007 and January 2023. The exclusion criteria included coexisting HDV, HCV, or HIV infection; other chronic liver diseases; extrahepatic malignancies; prior HCC; and HCC development within one year. A baseline liver biopsy was performed in 467 patients (87 %). MASLD was defined as hepatic steatosis diagnosed histologically or by imaging, combined with one cardiometabolic risk factor. The cumulative incidence of HCC and its associated factors was analyzed in patients with CHB, with and without MASLD.ResultsIn total, 535 treatment-naïve patients with CHB were included, with a median follow-up of 6.05 years. MASLD was not associated with an increased incidence of HCC in patients with CHB (HR: 1.17; 95 % CI: 0.77-1.79; p = 0.466). The cumulative incidence of HCC increased with the number of fulfilled cardiometabolic criteria (0-2 criteria vs. ≥ 3 criteria) (HR: 3.93; 95 % CI: 1.89-8.19; p < 0.001).Age (HR: 1.03, 95 % CI 1.01-1.06, p = 0.010), male sex (HR: 3.17; 95 % CI 1.34-7.53, p = 0.009), diabetes (HR: 2.81; 95 % CI 1.54-5.12, p < 0.001), and cirrhosis (HR:3.03; 95 % CI 1.57-5.5.86, p < 0.001) were independently associated with HCC development.ConclusionsIt was not MASLD, but rather the presence of multiple cardiometabolic risk factors in patients with CHB that was associated with the risk of HCC in those receiving antiviral treatment. Furthermore, older age, male sex, diabetes, and cirrhosis aggravated the risk of HCC in patients with CHB.
| S-EPMC11425165 | biostudies-literature
Project description:ImportanceIn the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC.ObjectiveTo develop a prediction model for HCC incidence in a cohort of patients with MASLD.Design, setting, and participantsThis prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024.ExposureData were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD.Main outcome and measuresThe cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk.ResultsA total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241.Conclusions and relevanceThis prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.
| S-EPMC11240192 | biostudies-literature
Project description:The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.
| S-EPMC11294468 | biostudies-literature
Project description:Background and aimThis study aimed to compare the determinants and impact of hepatocellular carcinoma (HCC) surveillance rates for people with metabolic dysfunction-associated steatotic liver disease (MASLD) versus other chronic liver diseases.MethodsA dataset of HCC patients from a UK hospital (2007-2022) was analyzed. The Mann-Whitney U-test compared continuous variables. The χ2 and two-tailed Fisher exact tests compared categorical data. Regression modeling analyzed the impact of MASLD on the size and number of HCC nodules and curative treatment. The Cox proportional hazards model assessed the influence of MASLD on overall survival.ResultsA total of 176 of 687 (25.6%) HCC patients had MASLD. Fewer people with MASLD HCC were enrolled in HCC surveillance compared to non-MASLD HCC (38 [21.6%] vs 215 [42.1%], P < 0.001). Patients with MASLD HCC were less likely to have been under secondary care (n = 57 [32.4%] vs 259 [50.7%], P < 0.001) and less likely to have cirrhosis (n = 113 [64.2%] vs 417 [81.6%], P < 0.001). MASLD was associated with a 12.3-mm (95% confidence interval [CI] 10.8-14.0 mm) greater tumor diameter compared to people without MASLD (P = 0.002). Patients with MASLD HCC had 0.62 reduced odds (95% CI 0.43-0.91) of receiving curative treatment compared to non-MASLD HCC (P = 0.014). Overall survival was similar for patients with MASLD HCC versus non-MASLD HCC (hazard ratio 1.03, 95% CI 0.85-1.25, P = 0.748).ConclusionPatients with MASLD are less likely to have been enrolled in HCC surveillance due to undiagnosed cirrhosis or presenting with non-cirrhotic HCC. Patients with MASLD HCC present with larger tumors and are less likely to receive curative treatment.
| S-EPMC11660197 | biostudies-literature
Project description:BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays a crucial role in maintaining healthy. However, the impact of early-life gut microbiota dysbiosis on the advancement of MASLD-HCC remains inadequately understood.MethodsIn the present study, we investigated the role of early-life gut microbiota in the development of MASLD-HCC in streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded the body weight and lifespan, and dynamically monitored the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (T-CHO) and blood glucose in the serum monthly. In addition, we examined various immune cells present in the liver, such as T cells, B cells, NK cells, NKT cells, αβT cells, γδT cells, macrophage and MDSC cells by flow cytometry and conducted liquid chromatography mass spectrometry (LC-MS) based analysis on liver tissue from control and early-life antibiotic exposure mice (early-Abx) MASLD-HCC mice.ResultsWe found that early-Abx mice suffered from more severe tumor burden and further confirmed that hepatocytes and immune cells were all disturbed. Importantly, early-life antibiotic exposure alters the liver metabolic profiling especially glycerophospholipids and lipid accumulation. Furthermore, mice exposed to antibiotics in early-life showed disturbances in glucose metabolism and developed insulin resistance.ConclusionsCollectively, our findings revealed that early-life antibiotic exposure accelerated the progression of MASLD-HCC by impairing the hepatocytes, immune homeostasis and metabolites persistently, highlighting the importance of the early-life microbiota in the development of MASLD-HCC.
| S-EPMC11539558 | biostudies-literature
Project description:The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is closely linked with a heightened risk of hepatocellular carcinoma (HCC), the fourth leading cause of cancer-related deaths worldwide. Despite the elevated risk of HCC in patients with MASLD, the existing surveillance guidelines are inadequate, particularly for those without cirrhosis. This review evaluates current HCC surveillance practices in patients with MASLD and their shortcomings. It also highlights the critical need for enhanced HCC risk stratification and diagnostic accuracy through new techniques. In this review article, we performed a comprehensive literature review of studies focusing on HCC risk factors in MASLD/MASH patients from 2000 to 2023. We discussed that demographics, comorbidities, liver fibrosis, and genetic markers play critical roles in HCC risk stratification. Additionally, non-invasive tests (NITs) for fibrosis may improve the accuracy for HCC risk stratification and diagnosis. More recently, innovative approaches, such as machine learning techniques and liquid biopsy utilizing extracellular vesicles, cell-free DNA, and circulating tumor cells show promise in redefining early HCC detection. Thus, integrating these various risk factors could optimize early detection of HCC for the growing MASLD/MASH patient population. However, further research is needed to confirm their effectiveness and practical implementation in clinical settings.
| S-EPMC11535805 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-06-16 | GSE246223 | GEO
Project description:Background and aimsMetabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of liver-related events in patients with chronic hepatitis B (CHB), possibly by accelerating fibrosis progression. Therefore, we studied the influence of MASLD on liver stiffness measurement (LSM) kinetics in CHB patients.MethodsWe conducted a multicenter retrospective cohort study of CHB patients with at least two LSM with FibroScan. We studied the absolute change in LSM and the change in LSM stage from the first LSM to the most recent LSM among CHB patients with MASLD compared to patients without MASLD.ResultsWe analysed 1055 CHB patients; 259 (28.0%) had MASLD. Patients with MASLD had a higher first and last LSM (6.1 vs. 5.2 kPa and 5.6 vs. 4.7 kPa, p < 0.001), were significantly less likely to achieve a decrease in LSM stage (52.8% vs. 74% p < 0.001) and were more likely to experience an increase in LSM stage (19.3% vs. 13.6%, p = 0.035) during follow-up. 417 (39.5%) patients initiated antiviral therapy (AVT) which was associated with a decline in LSM (p < 0.001). However, patients with MASLD who were treated were less likely to decrease in LSM stage (52.4% vs. 77.0%, p < 0.001) and were more likely to experience an increase in LSM stage (23.5% vs. 12.8%, p = 0.021) despite AVT.ConclusionPresence of MASLD was independently associated with higher LSM in untreated CHB patients and with less decline in LSM after initiation of AVT. Furthermore, CHB patients with MASLD were more likely to experience an increase in LSM despite AVT.
| S-EPMC11855902 | biostudies-literature
Project description:Although a robust association between metabolic dysfunction-associated fatty liver disease (MASLD) and cardiovascular disease (CVD) has been established, the impact of MASLD on CVD risk in young adults has not been fully evaluated. This population-based study included adults aged 20-39 years who underwent health screening examinations from 2009 to 2012 based on Korean National Health Insurance Service database. MASLD was defined as a fatty liver index ≥ 30 without any other cause of steatosis, and presence of one or more cardiometabolic risk factors. The primary outcome was newly developed CVD, including myocardial infarction, ischemic stroke, and congestive heart failure. During the median 10.6 years of follow-up, MASLD was observed in 1,435,659 (25.3%) of the 5,666,728 participants. Cumulative incidence of major adverse cardiovascular events was significantly higher in individuals with MASLD compared those without steatosis (P < 0.001). The adjusted hazard ratio (HR) for myocardial infarction was 1.23 [95% CI (confidence interval): 1.18-1.27] in individuals with MASLD compared to those without steatosis. The HR for ischemic stroke and congestive heart failure were higher in individuals with MASLD compared to those without steatosis (HR, 1.12; 95% CI, 1.07-1.17 and HR, 1.18; 95% CI, 1.15-1.21, respectively]. In the subgroup analysis, the elevated HR for CVD in the MASLD group was prominent among individuals who were female and obese. MASLD was associated with an increased risk of CVD in young adults. These findings highlight the need for early intervention in patients with MASLD before they reach middle to reduce the risk of CVD, particularly among young adults in South Korea.
| S-EPMC11832902 | biostudies-literature
Project description:IntroductionThis study aimed to investigate the liver-related outcomes of newly suggested metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD), as well as alcohol-associated liver disease (ALD).MethodsFrom a National Health Insurance Service Health Screening Cohort, we included 369,094 participants who underwent health checkups between 2009 and 2010 in South Korea. Steatotic liver disease (SLD) was defined as a fatty liver index ≥60. The risk of primary liver cancer (PLCa), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), incident cirrhosis, and decompensated cirrhosis was compared with no SLD. The subdistribution hazard ratio (SHR) was calculated using the Fine-Gray model regarding competing risks.ResultsA total of 3,232 participants (0.9%) developed PLCa during the median follow-up of 3,227,176 person-years: 0.5% with no SLD, 1.1% with MASLD, 1.3% with MetALD, and 1.9% with ALD. Competing risk analysis revealed that compared with no SLD, MASLD (SHR: 1.65; 95% CI: 1.44-1.88), MetALD (SHR: 1.87; 95% CI: 1.52-2.29), and ALD (SHR: 1.86; 95% CI: 1.39-2.49) were associated with an increased risk of PLCa. MASLD (SHR: 1.96; 95% CI: 1.67-2.31), MetALD (SHR: 2.23; 95% CI: 1.75-2.84), and ALD (SHR: 2.34; 95% CI: 1.67-3.29) were associated with a higher risk of HCC. No significant difference was observed in the risk of iCCA. The risk of incident cirrhosis and decompensated cirrhosis increased in the order of no SLD, MASLD, MetALD, and ALD.ConclusionMASLD, MetALD, and ALD have an increased risk of PLCa, HCC, incident cirrhosis, and decompensated cirrhosis but not iCCA. These findings may serve as a robust ground for the prognostic value of the newly suggested MASLD and MetALD.
| S-EPMC11305668 | biostudies-literature