Risk Of Hepatocellular Cancer Research Articles

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis

BackgroundInflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive...

A critical review of diagnostic and prognostic markers of chronic hepatitis B infection.

A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the clinical importance and current issues of the major markers used in both the detection and prognosis of chronic hepatitis B. An important indicator of an ongoing and persistent infection is the hepatitis B surface antigen. Hepatitis B virus DNA quantification monitoring aids in assessing viral load and hepatic cancer risk. While limited evidence of liver damage is provided by alanine aminotransferase levels, the hepatitis B core antibody verifies acute infection. Seroconversion to the hepatitis B e antibody is linked to a lower risk of disease development, and the hepatitis B e antigen status is a critical prognostic factor. Treatment choices are guided by a biopsy of the liver or minimally invasive liver fibrosis detection. Genotypes of the hepatitis B virus and host variables influence the prognosis by adding to the disease's variability. Noninvasive techniques to evaluate the severity of the disease are provided by serum markers of fibrosis, such as the fibrosis score based on four criteria and the aspartate aminotransferase-to-platelet ratio index. The requirement for indicators that distinguish between distinct viral phases and increase specificity in evaluating liver damage is one of the challenges facing chronic hepatitis B research. Even though it is quite difficult to find reliable biomarkers for resistance especially when it comes to hepatocellular cancer risk estimation, there are advanced methods, which include imaging and omics that can help in improving the accuracy of the diagnostics and prognosis. Interventions early point that improve patient outcomes are made possible using diagnostics and prognostics as they are quite effective in managing the complicated landscape of chronic hepatitis B. Key in addressing these challenges today and improving the diagnostic and prognostic markers in thefuture, particularly those that would support the development of successful treatment plans for people living with chronic hepatitis B virus (HBV), are scientific research, technological advances and collaborations.

VEGF-2578C/A, -460T/C Polymorphisms and Gastrointestinal Tract Cancer Risk: An Updated Meta-Analysis.

Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.

Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-β pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-β family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-β based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.

THU586 Lipid Species In Non-alcoholic Fatty Liver Disease (NAFLD) In Type 1 Diabetes

Abstract Disclosure: A. Taiwo: None. H. Thakker: None. J. Maschek: None. J. Cox: None. S. Summers: Owner/Co-Owner; Self; Centaurus Therapeutics. D. Jalal: None. W. Sivitz: None. A. Dokun: None. B. Chaurasia: None. Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis at an early stage, which can progress over the years to nonalcoholic steatohepatitis (NASH) and cirrhosis. Steatosis is composed of various lipid species which is derived from influx of monounsaturated and polyunsaturated fatty acids, saturated fats, into the liver caused by peripheral lipolysis in adipocytes and de novo lipogenesis. It is estimated that 20-30% patients with NAFLD will progress to NASH. Hepatic lipotoxicity and inflammation are two key factors that drive the progression of NAFLD to NASH. The presence of NASH increases the risk of cardiovascular events, cirrhosis, hepatocellular cancer and non-liver malignancies. Objective: To determine the association of lipid species with NAFLD in individuals with Type 1 diabetes. Study Design: Thirty individuals with Type 1 diabetes were recruited from our diabetes Clinic at University of Iowa Hospital & Clinics. Participants in this cross-sectional study were categorized into two groups based on the results of a FibroScan, an elastography technique that quantifies liver fat and stiffness. Classification as cases (n = 16) or controls (n = 14) was assigned based on the presence or absence of evidence for NAFLD respectively. The participants came in for a single visit where fasting plasma was drawn for lipidomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total thirty-three lipid species belonging to four different lipid classes: sphingolipids (dihydroceramides, ceramides, dihydrosphingomyelin, sphingomyelin, hexosylceramide), diacylglycerol, phosphatidylcholine and triacylglycerols were analyzed via targeted lipidomics. Results: The BMI was significantly higher in the cases than controls (P = 0.002) and the cases used significantly higher 24 hr insulin doses than controls (P = 0.004). The cases displayed significantly higher circulating levels of total ceramides (p=0.02), diacylglycerol (P= 0.0003) and triacylglycerols (P=0.0003). The two groups displayed similar levels of hexosylceramide, dihydrosphingomyelin, sphingomyelin and phosphatidylcholine. Similar to previous findings numerous sphingolipid species, diacylglycerol and triacylglycerols were found to be positively correlated with BMI. In addition, they were found to be positively correlated with 24hrs insulin dose. Importantly, total circulating dihydroceramide, ceramide, diacylglycerol and triacylglycerols levels were significantly corelated with steatosis score (P = <0.05). None of the lipid species correlated with the fibrosis score. Conclusion: These results suggest that Type 1 diabetes individuals with NAFLD have a higher BMI and display elevated circulating levels of dihydroceramides, ceramides, diacylglycerol and triacylglycerols that are strongly associated with the development of fatty liver disease. Presentation: Thursday, June 15, 2023

Serological Evidence of Hepatitis B Virus among Secondary School Students in a Community in Plateau State, Nigeria

Hepatitis B virus is among the common viral infectious agents of global public health concern because it increases the risk of hepatocellular cancer, liver fibrosis, and mortality from liver disease. The study's objectives were to detect hepatitis B surface antigen (HBsAg) in the blood samples of students of Government Secondary School, Bet, Pankshin, Plateau State. A cross-sectional analytical study was conducted between October and November 2018. Blood samples were collected from 168 participants which were analysed for HBsAg using a One-step Rapid Strip (Royal Care) and HBeAg by Combo Test Device (Skytech USA). Data were analyzed using SPSS version 21.0 (USA). P-values < 0.05 were considered significant. An overall 7.1% of the 168 samples analysed were seropositive for HBsAg and 6.7% for HBeAg. Males had a seropositivity of 11.6%, whereas females had a seropositivity of 4.0% (p = 0.061). The distribution of HBsAg in relation to age group was higher in the age group 13-19 years with 7.3% and the lowest in the age group 6-12 years with 6.7%. Those with history of sexual exposures had a seropositivity of 14.3% (p = 0.174; OR = 0.371, those with history of exposure to sharp objects had 7.3% (p = 0.869; OR = 0.876), those with the history of blood transfusion had none (p = 0.319; OR = 1.00), participants without history of ever screened for the virus had a seropositivity of 7.4% (p = 0.529; OR = 1.00) while the alcoholics had 13.6% (p = 0.205; OR = 0.416. It is imperative to act quickly to prevent liver disease morbidity and mortality given the seropositivity of 7.1% of HBV, which is of considerable public health concern. There is need to intensify campaign awareness and vaccination against HBV among all unvaccinated age groups.

Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV. Theoretically, suppression of Treg cell functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To assess the potential benefit of adding MAF to the anti-CHB protocol, 2 μg/mL MAF was combined with the GMI-HBVac as an anti-Treg treatment in an HBV-infected animal model. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and the upregulation of IFN-gamma-producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulated T cell infiltration in HBV-infected livers. These effects may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF can act as an adjuvant with GMI-HBVac to deplete Tregs in mice with an established CHB infection. This unique therapeutic vaccine regimen produced a functional cure, as revealed by the remarkable clearance of HBsAg.

Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis

The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through2021. We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Aims: Chronic HBV infection is associated with high morbidity and mortality rate due to increased risk of hepatic cirrhosis and hepatocellular cancer. Treatment modilities and resistance is currently investigated. Several mechanisms were underlying in drug resistance. P-glycoprotein (P-gp), the product of multidrug resistance gene (MDR-1), is well-known mechanism of MDR phenotype. MDR gene C1236T polymorphism is associated with decreased p-gp function. The mutation of MDR gene can affect the clinical course of disease and response rate to treatment. It was aimed to investigate the relationship between MDR gene polymorphism and clinical course and treatment responses in chronic HBV infection in our study. Methods: A total of 90 (male/female:69/21) patients with chronic HBV infection under Lamivudine treatment was enrolled in this study. Mean ages were 49.8±12.6 (range:22-75) years. The patients were categorized as: Treatment responded (group 1: HBV-DNA is negative at 24th week) and treatment refractory (group 2: HBV-DNA is still positive after 24th week). Group 1 was consisted of 51 (M/F: 38/13) and group 2 was consisted of 39 (M/F: 31/9) patients. There was no significant difference between ages and genders of two groups. Histologic activity indexes (HAI), total bilirubin, AST and ALT levels, HBV-DNA titers were significantly higher in the patients in group 2 than group 1 (p<0.05). Results: Genotype distributions; homozygous CC genotype was in 8 (15.7%),heterozygous CT genotype was in 37 (%72.5), homozygous TT genotype wasin 6 (11.8%) in patients at group 1. Homozygous CC genotype was in 13 (33.3%), heterozygous CT genotype was in 21 (53.8%), homozygous TT genotype was in 5 (12.8%) in patients at group 2. CC genotype was more common in group 2 than group 1 (p=0.044). C and T alleles’ frequencies in the group 1 and 2 were 51.96% and 60.26%, 48.04% and 39.74%, respectively (p>0.05). The patients with YMDD mutation positive at group 2 (n:11), 5 (45%) had have CC genotype, 5 (45%) had have CT, 1 (9%) had have TT genotype.The patients with YMDD mutation negative at group 2 (n:8), 3 (37%) patients had have CC and 5 (63%) patients had have CT genotype. CC genotype was more common in the patients with YMDD mutation positive than group 1 (p=0.043). Moreover, CC genotype was more common in the patients with HBV-DNA positive at 12nd month of Lamivudine treatment than group 1 (p=0.042). Conclusion: Consequently; MDR-1 and p-gp polymorphisms are important factors in the clinical course of chronic HBV infection and may influence the treatment responses. In the current study, it was found that the CC genotype of MDR-1 gene C1236T was more common in the patients with lamivudine resistant HBV infection.

Seroprevalence and Sociodemographic Characteristics for Hepatitis C Infection in North Central Nigeria

Hepatitis C virus infection is a concern for global health because it increases the risk of hepatocellular cancer, liver fibrosis, and mortality from liver disease. No safeguarding vaccination is yet accessible. The study's objectives were to identify the sociodemographic characteristics and the seroprevalence of the hepatitis C virus in the study area. A cross-sectional study was conducted by collecting blood samples from 1511 participants which were analysed for anti-HCV using a third-generation ELISA Kit. Data were analysed using SPSS version 23.0. p-values < 0.05 were considered significant. An overall 5.2% of the 1511 samples analysed were seropositive. Males had a seroprevalence of 7.1%, whereas females had a seroprevalence of 3.9% (p=0.01). The lowest seroprevalence was among the divorced and widowed, who had no detectable anti-HCV (p=0.007). Singles had the highest seroprevalence at 7.1%. Seroprevalence was highest (5.9%) among those with tertiary education and lowest (2.7%; p=0.461) among those with primary education. The highest seroprevalence was 6.9% among unemployed people, whereas the lowest was 3.4% among farmers (p=0.414). The highest seroprevalence was seen in monogamists (6.1%), with polygamists having none (p = 0.05). The seroprevalence was highest in non-alcoholics at 5.5% and lowest in alcoholics at 4.1% (p=0.407). Smokers had the lowest seroprevalence, at 3.2%, whereas non-smokers had the highest, at 5.3% (p=0.462). It is imperative to act quickly to prevent liver disease morbidity and mortality given the seroprevalence of 5.2% of HCV, which is of considerable public health concern.

Gradual deterioration of fatty liver disease to liver cancer via inhibition of AMPK signaling pathways involved in energy-dependent disorders, cellular aging, and chronic inflammation.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer kind. According to recent research, a fatty liver increases the risk of hepatocellular cancer. Nevertheless, the AMPK signaling pathway is crucial. In addition, 5'-AMP-activated protein kinase (AMPK) is strongly linked to alterations in the tumor microenvironment, such as inflammation, hypoxia, and aging. The objective of this study is to evaluate the impact of the AMPK signaling pathway on the progression of fatty liver to HCC. In this study, we established a mouse liver cancer model using high-fat diets and nano-nitrosamines (nano-DEN). In addition, we employed a transcriptomic technique to identify all mRNAs detected in liver samples at the 25th weekexpression of proteins linked with the LKB1-AMPK-mTOR signaling pathway, inflammation, aging, and hypoxia was studied in microarrays of liver cancer tissues from mice and humans. These proteins included p-AMPK, LKB1, mTOR, COX-2, β-catenin, HMGB1, p16, and HIF-1α. Data were collected at different times in the liver as well as in cancerous and paracancerous regions and analyzed by a multispectral imaging system. The results showed that most of the genes in the AMPK signaling pathway were downregulated. Prakk1 expression was upregulated compared to control group but downregulated in the cancerous regions compared to the paracancerous regions. Stk11 expression was downregulated in the cancerous regions. Mtor expression was upregulated in the cancerous regions. During liver cancer formation, deletion of LKB1 in the LKB1-AMPK-mTOR signaling pathway reduces phosphorylation of AMPK. It contributed to the upregulation of mTOR, which further led to the upregulation of HIF1α. In addition, the expression of β-catenin, COX-2, and HMGB1 were upregulated, as well as the expression of p16 was downregulated. These findings suggest that changes in the AMPK signaling pathway exacerbate the deterioration of disrupted energy metabolism, chronic inflammation, hypoxia, and cellular aging in the tumor microenvironment, promoting the development of fatty liver into liver cancer.

Risk stratification for hepatocellular cancer among patients with cirrhosis using a hepatic fat polygenic risk score.

Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies. We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association with HCC. Discriminatory accuracy was assessed using the C-statistic. During 4,759 person-years of follow-up, 93 patients developed HCC. Mean age was 59.8 years, 68.6% were male, 27.2% Hispanic, 25.1% non-Hispanic Black, 25.7% had NAFLD, 42.1% had heavy alcohol use, and 19.5% had active HCV. HCC risk increased by 134% per unit increase in PRS (HR = 2.30; 95% CI, 1.35-3.92). Compared to cirrhosis patients in the lowest tertile of the PRS, those in the highest tertile had 2-fold higher risk of HCC (HR = 2.05; 95% CI, 1.22-3.44). The PRS alone had modest discriminatory ability (C-statistic = 0.58; 95% CI, 0.52-0.63); however, adding PRS to a predictive model with traditional HCC risk factors had a C-statistic of 0.70 (95% CI, 0.64-0.76), increasing from 0.68 without the PRS (p = 0.0012). Our findings suggest that PRS may enhance risk prediction for HCC in contemporary U.S. cirrhosis patients.

Interplay Between Fatty Acids, Stearoyl-Co-A Desaturase, Mechanistic Target of Rapamycin, and Yes-Associated Protein/Transcriptional Coactivator With PDZ-Binding Motif in Promoting Hepatocellular Carcinoma

Interplay Between Fatty Acids, Stearoyl-Co-A Desaturase, Mechanistic Target of Rapamycin, and Yes-Associated Protein/Transcriptional Coactivator With PDZ-Binding Motif in Promoting Hepatocellular Carcinoma

Nonalcoholic fatty liver disease is specifically related to the risk of hepatocellular cancer but not extrahepatic malignancies.

We performed a matched cohort study among individuals with and without nonalcoholic fatty liver disease (NAFLD) to determine: 1) the incidence of cancers (extrahepatic and liver) and their spectrum and 2) if NAFLD increases the risk of extrahepatic cancers. The NAFLD and non-NAFLD (control) cohorts were identified from electronic medical records via International Classification of Diseases (ICD) codes from a single center and followed from 2010 to 2019. Cohorts were matched 1:2 for age, sex, race, body mass index (BMI), and type 2 diabetes. A total of 1,412 subjects were included in the analyses. There were 477 individuals with NAFLD and 935 controls (median age, 52 years; women, 54%; white vs. black: 59% vs. 38%; median BMI, 30.4 kg/m2; type 2 diabetes, 34%). The cancer incidence (per 100,000 person-years) was 535 vs. 1,513 (NAFLD vs. control). Liver cancer incidence (per 100,000 person-years) was 89 in the NAFLD group vs. 0 in the control group, whereas the incidence of malignancy was higher across other types of cancer in the control group vs. in the NAFLD group. The overall extrahepatic cancer risk in NAFLD is not increased above and beyond the risk from background risk factors such as age, race, sex, BMI, and type 2 diabetes.

Biochemical predictors of hepatocellular cancer development after one year in patients who achieved HCV clearance by direct-acting antiviral treatment.

The continued risk of hepatocellular cancer (HCC) following HCV clearance by direct-acting antivirals (DAAs), even if a sustained viral response (SVR) is achieved, has been previously reported. This study's objective was to identify biochemical predictors for HCC occurrence in patients who achieved HCV clearance by DAA treatment after one year. Patients who achieved SVR at week 24 with DAA between November 2015 and January 2021 and had no evidence of HCC were evaluated retrospectively. Biochemical parameters such as serum AFP (Alpha-fetoprotein), AST (Aspartate Aminotransferase), ALT (Alanine aminotransferase), albumin, PLT (platelet) count, FIB-4 and APRI indexes (non-invasive fibrosis indexes) were analyzed before starting the DAA treatment, at the end of the treatment (EOT), and 24th-week post-treatment. Throughout a median follow-up time of 43±16.2 months, it was observed that HCC occurred in 14 (5.6%) of 248 CHC patients who reached SVR at the 24th week after DAA treatment. According to multivariate analysis, AFP levels were >7.08 ng/ml before treatment (HR, 3.8; p=0.050), >5.15 ng/ml at the EOT (HR, 6.8; p=0.019), and >5.68 ng/ml at the 24th week post-treatment (HR, 21.2; p=0.002); albumin levels were <3.75 g/dl before treatment (HR, 3.6; p=0.042), <4.05 g/dl at the EOT (HR, 6.9; p=0.005), and <4.15 g/dl at week 24 post-treatment (HR, 8.8; p=0.002); PLT counts <153.000/mm3 at the 24th week post-treatment (HR, 12.1; p=0.001) were determined to be independent biochemical predictors for the development of HCC after one year of ending DAA treatment. AFP and albumin levels before treatment, at the EOT, and post-treatment at week 24, and PLT numbers at week 24 post-treatment can be used to foresee the risk of developing HCC one year after ending of DAA treatment.

7[alpha]-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) is a novel AKR1D1 substrate driving metabolic dysfunction and hepatocellular cancer risk in patients with non-alcoholic fatty liver disease (NAFLD)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Hereditary hemochromatosis: Temporal trends, sociodemographic characteristics, and independent risk factor of hepatocellular cancer - nationwide population-based study.

BACKGROUNDHereditary hemochromatosis (HH) has an increased risk of hepatocellular cancer (HCC) both due to genetic risks and iron overload as iron overload can be carcinogenic; HH impacts the increasing risk of HCC, not only through the development of cirrhosis but concerning hepatic iron deposition, which has been studied further recently. AIMTo evaluate HH yearly trends, patient demographics, symptoms, comorbidities, and hospital outcomes. The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients, independent of liver cirrhosis complications. The study investigated HH (without cirrhosis) as an independent risk factor for HCC.METHODSWe analyzed data from National Inpatient Sample (NIS) Database, the largest national inpatient data collection in the United States, and selected HH and HCC cohorts. HH was first defined in 2011 International Classification of Disease - 9th edition (ICD-9) as a separate diagnosis; the HH cohort is extracted from January 2011 to December 2019 using 275.01 (ICD-9) and E83.110 (ICD-10) diagnosis codes of HH. Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis (alcoholic, non-alcoholic, and biliary), viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors. The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC. We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor (greedy) propensity score method using the patients' age, gender, and race. We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort. We further analyzed HH without cirrhosis (removing HH patients with a diagnosis of cirrhosis) as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model. RESULTSDuring the 2011-2019 period, a total of 18031 hospitalizations with a primary or secondary diagnosis of HH (excluding liver diseases) were recorded in the NIS database. We analyzed different patients’ characteristics, and we found increments in inpatient population trend with a Ptrend < 0.001 and total hospital cost of care trend from $42957 in 2011 to $66152 in 2019 with a Ptrend < 0.001 despite no change in Length of Stay over the last decade. The multivariate analyses showed that HH without cirrhosis (aOR, 28.8; 95%CI, 10.4–80.1; P < 0.0001), biliary cirrhosis (aOR, 19.3; 95%CI, 13.4–27.6; P < 0.0001), non-alcoholic cirrhosis (aOR, 17.4; 95%CI, 16.5–18.4; P < 0.0001), alcoholic cirrhosis (aOR, 16.9; 95%CI, 15.9–17.9; P < 0.0001), hepatitis B (aOR, 12.1; 95%CI, 10.85–13.60; P < 0.0001), hepatitis C (aOR, 8.58; 95%CI, 8.20–8.98; P < 0.0001), Wilson disease (aOR, 4.27; 95%CI, 1.18–15.41; P < 0.0001), NAFLD or NASH (aOR, 2.96; 95%CI, 2.73–3.20; P < 0.0001), alpha1-antitrypsin deficiency (aOR, 2.10; 95%CI, 1.21–3.64; P < 0.0001), diabetes mellitus without chronic complications (aOR, 1.17; 95%CI, 1.13–1.21; P < 0.0001), and blood transfusion (aOR, 1.80; 95%CI, 1.69–1.92; P < 0.0001) are independent risk factor for liver cancer.CONCLUSIONOur study showed an increasing trend of in-hospital admissions of HH patients in the last decade. These trends were likely related to advances in diagnostic approach, which can lead to increased hospital utilization and cost increments. Still, the length of stay remained the same, likely due to a big part of management being done in outpatient settings. Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors. More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.

Using quantitative immunohistochemistry in patients at high risk for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is the primary form of liver cancer and a major cause of cancer death worldwide. Early detection is key to effective treatment. Yet, early diagnosis is challenging, especially in patients with cirrhosis, who are at high risk of developing HCC. Dysfunction or loss of function of the transforming growth factor β (TGF-β) pathway is associated with HCC. Here, using quantitative immunohistochemistry analysis of samples from a multi-institutional repository, we evaluated if differences in TGF-β receptor abundance were present in tissue from patients with only cirrhosis compared with those with HCC in the context of cirrhosis. We determined that TGFBR2, not TGFBR1, was significantly reduced in HCC tissue compared with cirrhotic tissue. We developed an artificial intelligence (AI)-based process that correctly identified cirrhotic and HCC tissue and confirmed the significant reduction in TGFBR2 in HCC tissue compared with cirrhotic tissue. Thus, we propose that a reduction in TGFBR2 abundance represents a useful biomarker for detecting HCC in the context of cirrhosis and that incorporating this biomarker into an AI-based automated imaging pipeline could reduce variability in diagnosing HCC from biopsy tissue.

AKR1D1 knockdown identifies 7[alpha]-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) as a driver of metabolic dysfunction and hepatocellular cancer risk in patients with non-alcoholic fatty liver disease (NAFLD)

AKR1D1 knockdown identifies 7[alpha]-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) as a driver of metabolic dysfunction and hepatocellular cancer risk in patients with non-alcoholic fatty liver disease (NAFLD)

Clinical Outcomes of Patients With Suspicious (LI-RADS 4) Liver Observations

Hepatocellular cancer (HCC) surveillance is associated with increased curative treatment and improved survival, underscoring its importance in patients with cirrhosis.1 Surveillance is 1 step in a larger HCC screening continuum, and those with abnormal screening results must undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI).2 The Liver Imaging Reporting and Data System (LI-RADS) classifies liver observations in at-risk patients based on risk of malignancy and HCC, with LR-5 observations having a positive predictive value exceeding 95% for HCC. However, indeterminate liver nodules (ie, LR-3 or LR-4) are commonly observed in clinical practice, associated with heterogenous HCC risk, and have large variations in practice management.3,4 We previously reported the natural history of LR-3 observations in a multicenter cohort of patients with cirrhosis, demonstrating a high annual incidence for HCC development of 8.4 cases per 100 person-years;5 however, the natural history of LR-4 observations remains uncertain. Herein, we aimed to characterize clinical outcomes in patients with LR-4 observations in a multicenter cohort.